Next Article in Journal
Antibiotic Susceptibility of Aerobic and Facultative Anaerobic Gram-Negative Rods in Hong Kong and Implications on Usefulness of Ceftazidime-Avibactam and Ceftolozane-Tazobactam
Previous Article in Journal
Bacteriophage Therapy on an In Vitro Wound Model and Synergistic Effects in Combination with Beta-Lactam Antibiotics
Previous Article in Special Issue
Translational PK/PD for the Development of Novel Antibiotics—A Drug Developer’s Perspective
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Antibiotics
Volume 13
Issue 9
10.3390/antibiotics13090801
antibiotics-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Systematic Review

Risk Factors Associated with Antibiotic Exposure Variability in Critically Ill Patients: A Systematic Review

by
Laura Gras-Martín
1,2,3,
Adrián Plaza-Diaz
1,2,
Borja Zarate-Tamames
1,2,
Paula Vera-Artazcoz
2,3,4,
Olga H. Torres
2,3,5,
Carla Bastida
6,7,
Dolors Soy
6,7 and
Jesús Ruiz-Ramos
1,2,3,*
1
Pharmacy Department, Hospital de la Santa Creu i Sant Pau, Sant Antoni Maria Claret 167, 08025 Barcelona, Spain
2
Institut de Recerca Sant Pau (IR SANT PAU), Sat Quintí 77-79, 08041 Barcelona, Spain
3
Department of Medicine, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain
4
Intensive Care Department, Hospital de la Santa Creu i Sant Pau, Sant Antoni Maria Claret 167, 08025 Barcelona, Spain
5
Geriatric Unit, Internal Medicine Department, Hospital de la Santa Creu i Sant Pau, Sant Antoni Maria Claret 167, 08025 Barcelona, Spain
6
Pharmacy Department, Division of Medicines, Hospital Clinic of Barcelona, Villarroel 170, 08036 Barcelona, Spain
7
Department of Pharmacology, Toxicology and Therapeutical Chemistry, Faculty of Pharmacy, Universitat de Barcelona, Campus Diagonal, Av. de Joan XXIII, 27-31, 08028 Barcelona, Spain
*
Author to whom correspondence should be addressed.
Antibiotics 2024, 13(9), 801; https://doi.org/10.3390/antibiotics13090801
Submission received: 19 July 2024 / Revised: 15 August 2024 / Accepted: 22 August 2024 / Published: 24 August 2024
(This article belongs to the Special Issue Featured Reviews in Pharmacokinetics and Pharmacodynamics of Antibiotics)
Browse Figures
Versions Notes

Abstract

:
(1) Background: Knowledge about the behavior of antibiotics in critically ill patients has been increasing in recent years. Some studies have concluded that a high percentage may be outside the therapeutic range. The most likely cause of this is the pharmacokinetic variability of critically ill patients, but it is not clear which factors have the greatest impact. The aim of this systematic review is to identify risk factors among critically ill patients that may exhibit significant pharmacokinetic alterations, compromising treatment efficacy and safety. (2) Methods: The search included the PubMed, Web of Science, and Embase databases. (3) Results: We identified 246 observational studies and ten clinical trials. The most studied risk factors in the literature were renal function, weight, age, sex, and renal replacement therapy. Risk factors with the greatest impact included renal function, weight, renal replacement therapy, age, protein or albumin levels, and APACHE or SAPS scores. (4) Conclusions: The review allows us to identify which critically ill patients are at a higher risk of not reaching therapeutic targets and helps us to recognize the extensive number of risk factors that have been studied, guiding their inclusion in future studies. It is essential to continue researching, especially in real clinical practice and with clinical outcomes.

1. Introduction

Sepsis is a life-threatening organ dysfunction, impacting millions of people around the world each year and killing one in three to one in six of those it affects. Early administration of appropriate antimicrobial treatment is one of the most effective interventions to reduce mortality in patients with sepsis. Therefore, it is essential to carry out effective and safe anti-infective treatment [1].
Knowing the optimal dosage of these drugs is very complex because, unlike other treatments, the pharmacological effect cannot be evaluated immediately. It is known that the behavior of drugs depends on the relationship between their pharmacokinetics and pharmacodynamics (PK/PD). In the case of antimicrobial agents, pharmacodynamics refers to the minimum inhibitory concentration (MIC) of the microorganism to be treated. This relationship has been extensively studied in recent years, especially in critically ill patients [2,3,4,5,6,7]. This knowledge, along with the increase in resistance, has led to the discovery that the initially assumed PK/PD targets are not sufficient to resolve the infection. Studies conducted on the PK/PD of antibiotics in critically ill patients have made it possible to define specific therapeutic targets for these patients [8,9,10,11,12,13,14].
The pharmacokinetics of the anti-infective agents are crucial for attaining their optimal effect, and we know that they are highly variable in critically ill patients [15,16,17,18,19,20,21]. When a patient is admitted to the intensive care unit (ICU), significant physiological changes occur that are generally not considered in the design of dosing regimens. The factors influencing changes in pharmacokinetics vary across different sources, and there is a lack of consistent data on the true impact and magnitude of each factor. Some of these factors include renal replacement therapy (RRT), extracorporeal membrane oxygenation (ECMO), obesity, aging, or comorbidities, which are also increasing in these units [22,23,24,25,26,27,28,29,30,31,32]. In fact, several studies have concluded that high percentages of critically ill patients on antibiotic treatment have plasma concentrations outside the therapeutic range, including several groups of antibiotics [33,34,35,36,37,38].
Despite this information, standard doses are still frequently used for these patients, with little consensus on the appropriate dosing [39,40]. The only way to ensure that patients achieve adequate antibiotic exposure and thus avoid therapeutic failures and side effects is through the determination of plasma concentration. However, this practice is not available for all patients in most centers due to costs and lack of evidence on clinical outcomes [10,41,42,43,44,45,46,47,48,49,50,51,52,53]. Most of these studies exhibit considerable variability in terms of the drugs studied, infections, causative microorganisms, and patient characteristics. In ICUs, we find very heterogeneous patients, and it is likely that pharmacokinetic variability will not be the same in all of them, nor will the impact on dosing, antibiotic exposure, and clinical outcomes.
The aim of this systematic review is to identify risk factors in critically ill patients who may present relevant pharmacokinetic alterations that compromise the efficacy and safety of the treatment.

2. Results

A total of 4895 articles were identified through computer searches in the selected databases, with 1141 duplicates removed through electronic or manual methods. A total of 3754 studies were screened by title and abstract and 489 were assessed for eligibility by full-text assessment. A total of 256 studies were finally included in the systematic review (Figure 1). Detailed reporting quality and risk-of-bias assessments are presented in Figures S1 and S2 (Supplementary Materials; File S3).
Most of the studies found were prospective, observational, and single-center studies. Different types of studies could be distinguished based on whether the outcome was to evaluate pharmacokinetic variability (evaluate alterations in the clearance and/or volume of distribution), develop a population pharmacokinetic model (PKPOP) (develop pharmacokinetic models tailored to critically ill patients using specialized software such as Nonmem®), or assess antibiotic exposure variability (evaluate variations in antimicrobial concentrations without assessing pharmacokinetic parameters). Only nine studies (3.50%) also evaluated clinical outcomes. The average number of patients per study was 85.3, ranging from three to 7220 patients. These studies were conducted practically worldwide, although the numbers varied widely by region. They included studies on many different antibiotics, with studies on beta-lactams being prominent (n = 136), followed by vancomycin (n = 42). The remaining characteristics of the analyzed studies are presented in Table 1.
The most studied risk factors in the publications were renal function, weight, age, sex, and renal replacement. The risk factors that were found to have the most impact were renal function, weight, renal replacement, age, and protein or albumin levels, in that order. Looking at the risk factors by the percentage of studies that concluded differences versus the studies analyzed, the risk factors with the most impact were renal function, burns, acid–base parameters, trauma, and renal replacement. The risk factors studied in each study, the number of articles that analyzed them, and the number of articles that established them as determinants, classified by antibiotic group and for each outcome type (pharmacokinetic parameters or population model and exposure), are included in Table 2. The percentage of risk factors that had the greatest influence, represented by drug group, and the effect of each risk factor by drug group can be observed in Figure 2. Some studies do not conclude statistically significant differences but do determine that there is considerable variability.
Some of the risk factors include different characteristics. Sepsis or septic shock was assessed based on the presence of these conditions, the use of vasopressors, or mean arterial pressure, while acute phase reactants were evaluated using C-reactive protein, fever, procalcitonin, or leukocyte count. Leukocyte count was the only factor among them that was not found to be relevant in any study. From studies concluding that blood protein levels were relevant, 86.67% included only albumin. Diabetes mellitus, congestive heart failure, cancer, chronic obstructive pulmonary disease (COPD), and neutropenia were the relevant associated comorbidities, all for beta-lactams except COPD, which was associated with vancomycin. The only two diagnoses associated with different outcomes were acute respiratory distress syndrome in one study and neurocritical in another. Midazolam was the determining comedication for daptomycin, and drug interactions with quinolones were significant. Types of infections showing differences were abdominal focus sepsis for aminoglycosides and beta-lactams, the Pitt bacteremia score for beta-lactams, and respiratory infections for linezolid and beta-lactams (one study for each). The details of the relevant risk factors that include more different variables can be seen in Figure 2 and Figure 3.
Other risk factors associated with inadequate exposure (evaluated in only one study) were lower protein binding beta-lactams, CYP1A2 polymorphism for ciprofloxacin, heart failure, McCabe score, infusion duration, and high drainage fluid production for beta-lactams. There were also other risk factors related to relevant pharmacokinetic changes: serum sodium, brain glucose concentration, uric acid, cardiac index, and ICU-onset infection. The review identified several other variables that, despite being analyzed, did not significantly impact achieving adequate antimicrobial concentrations or the pharmacokinetic models developed. A comprehensive list of these variables is available in the Supplementary Materials (File S4).
Some risk factors have been studied much more extensively than others. The relationship between the number of publications that analyzed a risk factor (and the number of patients) versus the number of publications that concluded that risk factors were determinants can be observed in Figure 4.

3. Discussion

To the best of our knowledge, this is the first systematic review to identify risk factors in critically ill patients that may compromise the efficacy and safety of antibiotic treatments which included more than just population kinetics. Recently, a very comprehensive systematic review was published, but it included only studies developing population kinetics and focused solely on beta-lactams [54]. Population kinetics can be very helpful in determining the variability of exposure to a treatment, but what we are really interested in is whether these changes will have a clinical impact. Unfortunately, we found very few studies that directly link risk factors to antimicrobial underexposure and clinical outcomes. However, considering the strong correlation between appropriate antibiotic exposure and clinical outcomes [55], analyzing clinical and demographic variables that might influence antibiotic exposure is highly relevant. Various scientific societies and international consensus groups have emphasized the importance of PK/PD objectives in improving clinical outcomes for critically ill patients [10]. Currently, we have information about the desired therapeutic targets, and these have indeed been directly related to significant clinical variables [8,9,10,11,12,13,14]. Including other antibiotics has also helped identify risk factors that may be relevant to therapeutic groups other than beta-lactams, such as liver function in the case of linezolid.
Numerous narrative reviews have explored optimizing antimicrobial dosing in critically ill patients, emphasizing strategies such as extended infusions and higher dosages based on variations in drug clearance and volume of distribution [2,5]. Our review seeks to advance this discussion by identifying less commonly considered parameters that may also influence antimicrobial concentrations in this patient group. We analyzed all the risk factors examined in the studies and highlighted the most significant ones. Our approach not only considers the number of studies that reviewed each factor but also the percentage of studies that found each factor relevant. This method helps us discern which factors have been extensively studied and which have not, particularly when statistical significance is challenging to achieve due to the limited number of studies or small patient populations.
While previous reviews on pharmacokinetics in critically ill patients have predominantly addressed differences from a theoretical perspective—focusing on variations in the volume of distribution, renal function, antimicrobial penetration challenges, and the lipophilicity of these drugs [56], our review takes a more practical approach. We evaluate multiple pharmacokinetic models specifically developed for critically ill patients, allowing us to group and quantify the significance of several less commonly discussed variables in antimicrobial pharmacokinetics.
We concur with the recently published population pharmacokinetics review of beta-lactams [54] that renal function, weight, and renal replacement have the greatest impact on antibiotic exposure, in that order. While it seems clear that these three risk factors affect antibiotic exposure in critically ill patients, dosing regimens used in these settings for most antibiotics are not weight-adjusted. With the increasing prevalence of obesity in both the general population and among patients in critical care units, weight and body surface area have become increasingly important factors in justifying antimicrobial monitoring in critically ill patients. Critically ill obese patients may require higher-than-standard doses of β-lactams, linezolid, and quinolones [57]. Conversely, dosing should be based on total body weight for certain antibiotics such as amikacin, vancomycin, or daptomycin, while adjusted body weight should be used for others. Given the limited availability of pharmacokinetic studies in this patient population and the significant variability in pharmacokinetics among critically ill patients, therapeutic drug monitoring of all administered antibiotics, when possible, is highly recommended.
Regarding beta-lactam drugs, the therapeutic group most commonly used in critically ill patients, our review identified multiple variables associated with variations in plasma concentrations, with weight, renal function, renal replacement therapy (RRT), and age being the most significant. The DALI study [38] revealed that with the doses typically used, about 26% of patients did not reach the minimum target concentration of fT > 50%, and nearly 40% of patients did not achieve fT > 100%. This study also correlated these variables with the clinical outcomes of the patients, highlighting the importance of considering different patient covariates to achieve adequate plasma concentrations. In a narrative review, Stašek J et al. [12] explained the main factors associated with variations in beta-lactam antibiotics in critically ill patients, focusing on renal function, inflammation, hypoalbuminemia, and renal replacement therapy. Our study complements the information provided by other authors, adding data to the number of patients and published articles that consider each variable and introducing new variables such as sex, acid–base disorders, diagnosis at admission, and the site of infections.
The information obtained on vancomycin was the second most abundant in terms of the number of studies, following beta-lactams. Compared to previous reviews [58], which primarily focused on age, weight, and renal function, our study has identified additional variables, such as severity scales, trauma diagnosis on admission, and hypoalbuminemia, as potential factors to consider for optimizing the dose of this drug.
Although there are recommendations for different renal functions and RRT for most antibiotics, the literature often lacks consensus on the most appropriate doses. Additionally, crucial characteristics such as the type and dosage of RRT, which have been shown to be relevant in several studies, are often not considered. The other risk factors described as most relevant in the beta-lactam review and in our work are also similar. Some of these include age, serum albumin, and disease severity, and in no case is dose adjustment considered for these patients.
Both this work and the analyzed studies have limitations. The recommended methodology has been used, and the articles and the document with all the data have been reviewed by several people, but even so, the entire process remains very manual. As a result, we found significant heterogeneity in published population pharmacokinetic studies, which limited the feasibility of meaningfully pooling quantitative parameters. Critically ill patients is a term that includes a clinical heterogeneity of situations across eligible studies that enrolled different populations. We included studies that involved critically ill patients who underwent antimicrobial drug monitoring. However, it is unclear whether all patients had confirmed infections or were necessarily septic. The inclusion of patients who were not septic would increase the likelihood of finding no variables associated with subtherapeutic antibiotic concentrations. Additionally, although we have analyzed studies of all antibiotics without exclusion, a large number of studies are on beta-lactams. Moreover, beta-lactams are a very heterogeneous group of antibiotics, and it would be more appropriate to assess the risk factors affecting each of them separately. The studies that examine exposure do so at the described doses, which may differ from those used in each center. To be able to extrapolate the results from such a large number of articles, we had to combine studies that examine specific subgroups with studies that analyzed risk factors individually, which were not usually the main objective. Studies that reviewed risk factors as a secondary objective did not take this objective into account when calculating the sample size to determine statistical significance. We found that some risk factors are very under-studied, and some are studied in very few patients. There is a lack of studies in routine clinical practice that consider all associated factors and have a sufficient sample size to reach valuable conclusions. Based on the authors’ linguistic expertise, only studies published in English and Spanish were included, which may have led to the exclusion of some studies that could have identified additional variables influencing the pharmacokinetics of antimicrobials in critically ill patients. However, the large number of studies incorporated ensures that the primary variables have been thoroughly considered.
Therefore, we align with the conclusions of many of the analyzed studies: variability in critically ill patients is very high, and the best way to ensure therapeutic target attainment in these patients is to perform Therapeutic Drug Monitoring (TDM). ICU patients are also highly variable among themselves, due to patient characteristics, the reason for admission, the need for vasoactive drugs or fluid replacement, comorbidities, concomitant treatments, lab abnormalities, or the need for extracorporeal supports, among other factors. The effect of the analyzed risk factors can be crucial in determining which patients, among the critically ill, may be at even greater risk of incorrect dosing, and this can be a criterion for prioritizing TDM if it cannot be performed in all patients.

4. Materials and Methods

This systematic review was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO), identification code CRD42024570977. The protocol adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [59].
In order to achieve the objective of this systematic review and identify risk factors among critically ill patients, we conducted a search aimed at finding studies evaluating the effect of risk factors that could significantly influence antibiotic treatments in the ICU.
We searched for all published studies involving adult patients admitted to the ICU and receiving antibiotic treatment, investigating potential risk factors that could affect antibiotic exposure in these patients. Any variable examined in the included studies for its effect on plasma concentrations of antimicrobials was considered as a risk factor. The details of the search strategy can be found in the Supplementary Materials.
All studies meeting these criteria were included, regardless of whether they focused on these factors as primary objectives or not, analyzed risk factors or directly assessed a population subgroup (e.g., obese patients, those undergoing continuous RRT, ECMO, etc.), studied antibiotic exposure (typically through plasma concentrations), or examined the impact on pharmacokinetic parameters. We categorized covariates using a preplanned, custom classification based on patterns commonly identified in a preliminary literature review conducted by the authors. Given the nature of this review, no formal sensitivity or subgroup analyses were prespecified to assess heterogenicity. Studies not in English or Spanish, retrospective studies, reviews, and abstracts were excluded. Other exclusion criteria were studies that did not assess pharmacokinetic variability or exposure, those that exclusively focused on non-antibiotic agents such as antivirals or antifungals, and those for which full-text access was unavailable.
The search was conducted on 21 March 2024 on the following bibliographic databases: PubMed, Web of Science, and Embase, according to the eligibility criteria and with no time restrictions. The data from searches in each database were exported to an Excel document, and an initial phase for the detection of duplicates was performed. A subsequent duplication detection phase was conducted in the resulting database using a DOI identifier and manual assessment. The results of the refined database were screened (title/abstract) by two independent investigators, with disagreements resolved by a third researcher. This method was replicated for the following full-text assessment and final inclusion of articles. Once selected, data were collected and validated by two independent investigators for each report. Finally, all data were processed in the Excel document, including the most important characteristics of each study.
We assessed the risk of bias in all included randomized clinical trials using Risk of Bias 2 (RoB2). Each study report was assessed by two authors independently, with any disagreements resolved by a third author. For clinical pharmacokinetics studies, the 24-item ClinPK checklist from the Reporting Guidelines for Clinical Pharmacokinetic Studies [60] was used to evaluate the quality of the manuscripts.

5. Conclusions

This review allows us to identify which critically ill patients are at a higher risk of not reaching therapeutic targets. This review also helps us recognize the extensive number of variables that have been studied, guiding their inclusion in future studies. It is essential to continue researching, especially in real clinical practice and with clinical outcomes.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/antibiotics13090801/s1, File S1: Search strategy; File S2: Excluded and Included studies; File S3: Risk of bias analysis; File S4: Risk factors that were studied without finding any impact; File S5: Main characteristics of studies. References [28,32,33,34,36,49,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,125,126,127,128,129,130,131,132,133,134,135,136,137,138,139,140,141,142,143,144,145,146,147,148,149,150,151,152,153,154,155,156,157,158,159,160,161,162,163,164,165,166,167,168,169,170,171,172,173,174,175,176,177,178,179,180,181,182,183,184,185,186,187,188,189,190,191,192,193,194,195,196,197,198,199,200,201,202,203,204,205,206,207,208,209,210,211,212,213,214,215,216,217,218,219,220,221,222,223,224,225,226,227,228,229,230,231,232,233,234,235,236,237,238,239,240,241,242,243,244,245,246,247,248,249,250,251,252,253,254,255,256,257,258,259,260,261,262,263,264,265,266,267,268,269,270,271,272,273,274,275,276,277,278,279,280,281,282,283,284,285,286,287,288,289,290,291,292,293,294,295,296,297,298,299,300,301,302,303,304,305,306,307,308,309] are the studies included in the review, that are cited in the Supplementary Materials.

Author Contributions

Conceptualization, L.G.-M.; methodology, L.G.-M.; formal analysis, A.P.-D., B.Z.-T. and J.R.-R.; data curation, L.G.-M.; writing—original draft preparation, L.G.-M., B.Z.-T., P.V.-A. and J.R.-R.; writing—review and editing, C.B. and D.S.; visualization, D.S., O.H.T. and P.V.-A.; supervision, D.S. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

This study was conducted in accordance with the Declaration of Helsinki and approved by the Hospital Sant Pau Ethical Committee (ID: Reference No: - IIBSP-TER-2024-26).

Informed Consent Statement

Not applicable.

Data Availability Statement

Data are available under reasonable request.

Conflicts of Interest

The authors declare no conflicts of interest.

References

  1. Evans, L.; Rhodes, A.; Alhazzani, W.; Antonelli, M.; Coopersmith, C.M.; French, C.; Machado, F.R.; Mcintyre, L.; Ostermann, M.; Prescott, H.C.; et al. Surviving sepsis campaign: International guidelines for management of sepsis and septic shock 2021. Intensive Care Med. 2021, 47, 1181–1247. [Google Scholar] [CrossRef] [PubMed]
  2. Abdul-Aziz, M.H.; Lipman, J.; Mouton, J.W.; Hope, W.W.; Roberts, J.A. Applying Pharmacokinetic/Pharmacodynamic Principles in Critically Ill Patients: Optimizing Efficacy and Reducing Resistance Development. Semin. Respir. Crit. Care Med. 2015, 36, 136–153. [Google Scholar] [CrossRef] [PubMed]
  3. Dhaese, S.; Van Vooren, S.; Boelens, J.; De Waele, J. Therapeutic drug monitoring of β-lactam antibiotics in the ICU. Expert Rev. Anti-infective Ther. 2020, 18, 1155–1164. [Google Scholar] [CrossRef] [PubMed]
  4. Blasco, A.C.; Alfaro, L.A.; Reinoso, J.C.; Mestre, M.J.G.; Rodríguez-Gascón, A. Análisis Farmacocinético-Farmacodinámico en Microbiología: Herramienta para Evaluar el Tratamiento Antimicrobiano Enfermedades Infecciosas y Microbiologia Clinica; Elsevier Doyma: Amsterdam, The Netherlands, 2015; Volume 33, pp. 48–57. [Google Scholar]
  5. Rizk, M.L.; Bhavnani, S.M.; Drusano, G.; Dane, A.; Eakin, A.E.; Guina, T.; Jang, S.H.; Tomayko, J.F.; Wang, J.; Zhuang, L.; et al. Considerations for Dose Selection and Clinical Pharmacokinetics/Pharmacodynamics for the Development of Antibacterial Agents. Antimicrob. Agents Chemother. 2019, 63. [Google Scholar] [CrossRef]
  6. Scaglione, F.; Paraboni, L. Influence of pharmacokinetics/pharmacodynamics of antibacterials in their dosing regimen selection. Expert Rev. Anti-infective Ther. 2006, 4, 479–490. [Google Scholar] [CrossRef]
  7. Ambrose, P.G.; Bhavnani, S.M.; Rubino, C.M.; Louie, A.; Gumbo, T.; Forrest, A.; Drusano, G.L. Antimicrobial Resistance: Pharmacokinetics-Pharmacodynamics of Antimicrobial Therapy: It’s Not Just for Mice Anymore. Clin. Infect. Dis. 2007, 44, 79–86. [Google Scholar] [CrossRef]
  8. Scharf, C.; Liebchen, U.; Paal, M.; Taubert, M.; Vogeser, M.; Irlbeck, M.; Zoller, M.; Schroeder, I. The higher the better? Defining the optimal beta-lactam target for critically ill patients to reach infection resolution and improve outcome. J. Intensive Care 2020, 8, 86. [Google Scholar] [CrossRef]
  9. Tängdén, T.; Martín, V.R.; Felton, T.W.; Nielsen, E.I.; Marchand, S.; Brüggemann, R.J.; Bulitta, J.B.; Bassetti, M.; Theuretzbacher, U.; Tsuji, B.T.; et al. The role of infection models and PK/PD modelling for optimising care of critically ill patients with severe infections. Intensive Care Med. 2017, 43, 1021–1032. [Google Scholar] [CrossRef]
  10. Abdul-Aziz, M.-H.; Alffenaar, J.-W.C.; Bassetti, M.; Bracht, H.; Dimopoulos, G.; Marriott, D.; Neely, M.N.; Paiva, J.-A.; Pea, F.; Sjovall, F.; et al. Antimicrobial therapeutic drug monitoring in critically ill adult patients: A Position Paper#. Intensive Care Med. 2020, 46, 1127–1153. [Google Scholar] [CrossRef]
  11. Guilhaumou, R.; Benaboud, S.; Bennis, Y.; Dahyot-Fizelier, C.; Dailly, E.; Gandia, P.; Goutelle, S.; Lefeuvre, S.; Mongardon, N.; Roger, C.; et al. Optimization of the treatment with be-ta-lactam antibiotics in critically ill patients—Guidelines from the French Society of Pharmacology and Therapeutics (Société Fran-çaise de Pharmacologie et Thérapeutique—SFPT) and the French Society of Anaesthesia and Intensive Care Medicine (Société Française d’Anesthésie et Réanimation—SFAR). Crit. Care 2019, 23, 1–20. [Google Scholar]
  12. Stašek, J.; Keller, F.; Kočí, V.; Klučka, J.; Klabusayová, E.; Wiewiorka, O.; Strašilová, Z.; Beňovská, M.; Škardová, M.; Maláska, J. Update on Therapeutic Drug Monitoring of Beta-Lactam Antibiotics in Critically Ill Patients—A Narrative Review. Antibiotics 2023, 12, 568. [Google Scholar] [CrossRef]
  13. Lin, B.; Hu, Y.; Xu, P.; Xu, T.; Chen, C.; He, L.; Zhou, M.; Chen, Z.; Zhang, C.; Yu, X.; et al. Expert consensus statement on therapeutic drug monitoring and individuali-zation of linezolid. Front. Public Health 2022, 10, 967311. [Google Scholar] [CrossRef]
  14. Wong, G.; Taccone, F.; Villois, P.; Scheetz, M.H.; Rhodes, N.J.; Briscoe, S.; McWhinney, B.; Nunez-Nunez, M.; Ungerer, J.; Lipman, J.; et al. β-Lactam pharmacodynamics in Gram-negative bloodstream infections in the critically ill. J. Antimicrob. Chemother. 2019, 75, 429–433. [Google Scholar] [CrossRef] [PubMed]
  15. Pea, F.; Viale, P.; Furlanut, M. Antimicrobial Therapy in Critically Ill Patients A Review of Pathophysiological Conditions Responsible for Altered Disposition and Pharmacokinetic Variability. Clin. Pharmacokinet. 2005, 44, 1009–1034. [Google Scholar] [CrossRef] [PubMed]
  16. Scaglione, F.; Paraboni, L. Pharmacokinetics/pharmacodynamics of antibacterials in the Intensive Care Unit: Setting appropriate dosing regimens. Int. J. Antimicrob. Agents 2008, 32, 294–301.e7. [Google Scholar] [CrossRef]
  17. Veiga, R.P.; Paiva, J.-A. Pharmacokinetics–pharmacodynamics issues relevant for the clinical use of beta-lactam antibiotics in critically ill patients. Crit. Care 2018, 22, 233. [Google Scholar] [CrossRef] [PubMed]
  18. Ulldemolins, M.; Nuvials, X.; Palomar, M.; Masclans, J.R.; Rello, J. Appropriateness is Critical. Crit. Care Clin. 2011, 27, 35–51. [Google Scholar] [CrossRef]
  19. Blot, S.I.; Pea, F.; Lipman, J. The effect of pathophysiology on pharmacokinetics in the critically ill patient — Concepts appraised by the example of antimicrobial agents. Adv. Drug Deliv. Rev. 2014, 77, 3–11. [Google Scholar] [CrossRef]
  20. Cotta, M.O.; Roberts, J.A.; Lipman, J. Antibiotic Dose Optimization in Critically Ill Patients. Med. Intensive 2015, 39, 563–572. [Google Scholar] [CrossRef]
  21. Roberts, J.A.; Abdul-Aziz, M.-H.; Lipman, J.; Mouton, J.W.; Vinks, A.A.; Felton, T.W.; Hope, W.W.; Farkas, A.; Neely, M.N.; Schentag, J.J.; et al. Individualised antibiotic dosing for patients who are critically ill: Challenges and potential solutions. Lancet Infect. Dis. 2014, 14, 498–509. [Google Scholar] [CrossRef]
  22. Ulldemolins, M.; Roberts, J.A.; Rello, J.; Paterson, D.L.; Lipman, J. The Effects of Hypoalbuminaemia on Optimizing Antibacterial Dosing in Critically Ill Patients. Clin. Pharmacokinet. 2011, 50, 99–110. [Google Scholar] [CrossRef]
  23. Contejean, A.; Maillard, A.; Canouï, E.; Kernéis, S.; Fantin, B.; Bouscary, D.; Parize, P.; Garcia-Vidal, C.; Charlier, C. Advances in antibacterial treatment of adults with high-risk febrile neutropenia. J. Antimicrob. Chemother. 2023, 78, 2109–2120. [Google Scholar] [CrossRef] [PubMed]
  24. Alobaid, A.S.; Hites, M.; Lipman, J.; Taccone, F.S.; Roberts, J.A. Effect of obesity on the pharmacokinetics of antimicrobials in critically ill patients: A structured review. Int. J. Antimicrob. Agents 2016, 47, 259–268. [Google Scholar] [CrossRef]
  25. Miglis, C.; Rhodes, N.J.; Kuti, J.L.; Nicolau, D.P.; Van Wart, S.A.; Scheetz, M.H. Defining the impact of severity of illness on time above the MIC threshold for cefepime in Gram-negative bacteraemia: A ‘Goldilocks’ window. Int. J. Antimicrob. Agents 2017, 50, 487–490. [Google Scholar] [CrossRef]
  26. Ewoldt, T.M.; Abdulla, A.; Hunfeld, N.; Li, L.; Smeets, T.J.; Gommers, D.; Koch, B.C.; Endeman, H. The impact of sepsis on hepatic drug metabolism in critically ill patients: A narrative review. Expert Opin. Drug Metab. Toxicol. 2022, 18, 413–421. [Google Scholar] [CrossRef]
  27. Pistolesi, V.; Morabito, S.; Mario, F.; Di Regolisti, G.; Cantarelli, C.; Fiaccadori, E. A Guide to Understanding Antimicrobial Drug Dosing in Critically Ill Patients on Renal Replacement Therapy [Internet]. 2019. Available online: http://aac.asm.org/ (accessed on 18 July 2024).
  28. Li, Z.; Bai, J.; Wen, A.; Shen, S.; Duan, M.; Li, X. Pharmacokinetic and Pharmacodynamic Analysis of Critically Ill Patients Under-going Continuous Renal Replacement Therapy with Imipenem. Clin. Ther. 2020, 42, 1564–1577.e8. [Google Scholar] [CrossRef] [PubMed]
  29. Fiore, M.; Peluso, L.; Taccone, F.S.; Hites, M. The impact of continuous renal replacement therapy on antibiotic pharmacokinetics in critically ill patients. Expert Opin. Drug Metab. Toxicol. 2021, 17, 543–554. [Google Scholar] [CrossRef] [PubMed]
  30. Gatti, M.; Pea, F. Antimicrobial Dose Reduction in Continuous Renal Replacement Therapy: Myth or Real Need? A Practical Ap-proach for Guiding Dose Optimization of Novel Antibiotics. Clin. Pharmacokinet. 2021, 60, 1271–1289. [Google Scholar]
  31. Jang, S.M.; Lewis, S.J.; Rhie, S.J. Optimal antipseudomonal β-lactam drug dosing recommendations in critically-ill Asian patients receiving CRRT. J. Crit. Care 2022, 72, 154172. [Google Scholar] [CrossRef]
  32. Zheng, J.; Sun, Z.; Sun, L.; Zhang, X.; Hou, G.; Han, Q.; Li, X.; Liu, G.; Gao, Y.; Ye, M.; et al. Pharmacokinetics and Pharmacodynamics of Linezolid in Patients With Sepsis Receiving Continuous Venovenous Hemofiltration and Extended Daily Hemofiltration. J. Infect. Dis. 2020, 221, S279–S287. [Google Scholar] [CrossRef]
  33. Wong, G.; Briscoe, S.; McWhinney, B.; Ally, M.; Ungerer, J.; Lipman, J.; Roberts, J.A. Therapeutic drug monitoring of beta-lactam antibiotics in the critically ill: Direct measurement of unbound drug concentrations to achieve appropriate drug exposures. J. Antimicrob. Chemother. 2018, 73, 3087–3094. [Google Scholar] [CrossRef] [PubMed]
  34. Taccone, F.S.; Laterre, P.-F.; Dugernier, T.; Spapen, H.; Delattre, I.; Witebolle, X.; De Backer, D.; Layeux, B.; Wallemacq, P.; Vincent, J.-L.; et al. Insufficient β-lactam concentrations in the early phase of severe sepsis and septic shock. Crit. Care 2010, 14, R126. [Google Scholar] [CrossRef]
  35. Luyt, C.-E.; Bréchot, N.; Trouillet, J.-L.; Chastre, J. Antibiotic stewardship in the intensive care unit. Crit. Care 2014, 18, 480. [Google Scholar] [CrossRef] [PubMed]
  36. Abdulla, A.; Dijkstra, A.; Hunfeld, N.G.M.; Endeman, H.; Bahmany, S.; Ewoldt, T.M.J.; Muller, A.E.; van Gelder, T.; Gommers, D.; Koch, B.C.P. Failure of target attainment of beta-lactam antibiotics in critically ill patients and associated risk factors: A two-center prospective study (EXPAT). Crit. Care 2020, 24, 558. [Google Scholar] [CrossRef] [PubMed]
  37. De Waele, J.J.; Lipman, J.; Akova, M.; Bassetti, M.; Dimopoulos, G.; Kaukonen, M.; Koulenti, D.; Martin, C.; Montravers, P.; Rello, J.; et al. Risk factors for target non-attainment during empirical treatment with β-lactam antibiotics in critically ill patients. Intensive Care Med. 2014, 40, 1340–1351. [Google Scholar] [CrossRef] [PubMed]
  38. Roberts, J.A.; Paul, S.K.; Akova, M.; Bassetti, M.; De Waele, J.J.; Dimopoulos, G.; Kaukonen, K.M.; Koulenti, D.; Martin, C.; Montravers, P.; et al. DALI: Defining antibiotic levels in intensive care unit patients: Are current ß-lactam antibiotic doses sufficient for critically ill patients? Clin. Infect. Dis. 2014, 58, 1072–1083. [Google Scholar] [CrossRef] [PubMed]
  39. Charmillon, A.; Novy, E.; Agrinier, N.; Leone, M.; Kimmoun, A.; Levy, B.; Demoré, B.; Dellamonica, J.; Pulcini, C. The ANTIBIOPERF study: A nationwide cross-sectional survey about practices for β-lactam administration and therapeutic drug monitoring among critically ill patients in France. Clin. Microbiol. Infect. 2016, 22, 625–631. [Google Scholar] [CrossRef]
  40. Williams, P.G.; Tabah, A.; Cotta, M.O.; Sandaradura, I.; Kanji, S.; Scheetz, M.H.; Imani, S.; Elhadi, M.; Luque-Pardos, S.; Schellack, N.; et al. International survey of antibiotic dosing and monitoring in adult intensive care units. Crit. Care 2023, 27, 241. [Google Scholar] [CrossRef]
  41. Rao, G.G.; Konicki, R.; Cattaneo, D.; Alffenaar, J.-W.; Marriott, D.J.E.; Neely, M.; On behalf of the IATDMCT Antimicrobial Scientific Committee. Therapeutic Drug Monitoring Can Improve Linezolid Dosing Regimens in Current Clinical Practice: A Review of Linezolid Pharmacokinetics and Pharmacodynamics. Ther. Drug Monit. 2020, 42, 83–92. [Google Scholar] [CrossRef]
  42. De Waele, J.J.; Carrette, S.; Carlier, M.; Stove, V.; Boelens, J.; Claeys, G.; Leroux-Roels, I.; Hoste, E.; Depuydt, P.; Decruyenaere, J.; et al. Therapeutic drug monitoring-based dose optimisation of piperacillin and meropenem: A randomised controlled trial. Intensive Care Med. 2013, 40, 380–387. [Google Scholar] [CrossRef]
  43. Steffens, N.A.; Zimmermann, E.S.; Nichelle, S.M.; Brucker, N. Meropenem use and therapeutic drug monitoring in clinical practice: A literature review. J. Clin. Pharm. Ther. 2021, 46, 610–621. [Google Scholar] [CrossRef] [PubMed]
  44. Wicha, S.G.; Märtson, A.; Nielsen, E.I.; Koch, B.C.; Friberg, L.E.; Alffenaar, J.; Minichmayr, I.K. The International Society of Anti-Infective Pharmacology (ISAP), the PK/PD study group of the European Society of Clinical Microbiology, Infectious Diseases (EPASG) From Therapeutic Drug Monitoring to Model-Informed Precision Dosing for Antibiotics. Clin. Pharmacol. Ther. 2021, 109, 928–941. [Google Scholar] [CrossRef]
  45. Osorio, C.; Garzón, L.; Jaimes, D.; Silva, E.; Bustos, R.-H. Impact on Antibiotic Resistance, Therapeutic Success, and Control of Side Effects in Therapeutic Drug Monitoring (TDM) of Daptomycin: A Scoping Review. Antibiotics 2021, 10, 263. [Google Scholar] [CrossRef] [PubMed]
  46. Falcone, M.; Russo, A.; Cassetta, M.I.; Lappa, A.; Tritapepe, L.; D'Ettorre, G.; Fallani, S.; Novelli, A.; Venditti, M. Variability of pharmacokinetic parameters in patients receiving different dosages of daptomycin: Is therapeutic drug monitoring necessary? J. Infect. Chemother. 2013, 19, 732–739. [Google Scholar] [CrossRef]
  47. Galar, A.; Valerio, M.; Muñoz, P.; Alcalá, L.; García-González, X.; Burillo, A.; Sanjurjo, M.; Grau, S.; Bouza, E. Systematic Therapeutic Drug Monitoring for Linezolid: Variability and Clinical Impact. Antimicrob. Agents Chemother. 2017, 61, e00687-17. [Google Scholar] [CrossRef] [PubMed]
  48. Galar, A.; Muñoz, P.; Valerio, M.; Cercenado, E.; García-González, X.; Burillo, A.; Sánchez-Somolinos, M.; Juárez, M.; Verde, E.; Bouza, E. Current use of daptomycin and systematic therapeutic drug monitoring: Clinical experience in a tertiary care institution. Int. J. Antimicrob. Agents 2018, 53, 40–48. [Google Scholar] [CrossRef]
  49. Takahashi, N.; Kondo, Y.; Kubo, K.; Egi, M.; Kano, K.-I.; Ohshima, Y.; Nakada, T.-A. Efficacy of therapeutic drug monitoring-based antibiotic regimen in critically ill patients: A systematic review and meta-analysis of randomized controlled trials. J. Intensive Care 2023, 11, 48. [Google Scholar] [CrossRef]
  50. Mangalore, R.P.; Ashok, A.; Lee, S.J.; Romero, L.; Peel, T.N.; A Udy, A.; Peleg, A.Y. Beta-Lactam Antibiotic Therapeutic Drug Monitoring in Critically Ill Patients: A Systematic Review and Meta-Analysis. Clin. Infect. Dis. 2022, 75, 1848–1860. [Google Scholar] [CrossRef]
  51. Al-Shaer, M.H.; Rubido, E.; Cherabuddi, K.; Venugopalan, V.; Klinker, K.; Peloquin, C. Early therapeutic monitoring of β-lactams and associated therapy outcomes in critically ill patients. J. Antimicrob. Chemother. 2020, 75, 3644–3651. [Google Scholar] [CrossRef]
  52. Ewoldt, T.M.J.; Abdulla, A.; Rietdijk, W.J.R.; Muller, A.E.; de Winter, B.C.M.; Hunfeld, N.G.M.; Purmer, I.M.; van Vliet, P.; Wils, E.-J.; Haringman, J.; et al. Model-informed precision dosing of beta-lactam antibiotics and ciprofloxacin in critically ill patients: A multicentre randomised clinical trial. Intensive Care Med. 2022, 48, 1760–1771. [Google Scholar] [CrossRef]
  53. on behalf of the TARGET Study Group; Hagel, S.; Fiedler, S.; Hohn, A.; Brinkmann, A.; Frey, O.R.; Hoyer, H.; Schlattmann, P.; Kiehntopf, M.; Roberts, J.A.; et al. Therapeutic drug monitoring-based dose optimisation of piperacillin/tazobactam to improve outcome in patients with sepsis (TARGET): A prospective, multi-centre, randomised controlled trial. Trials 2019, 20, 330. [Google Scholar] [CrossRef]
  54. Hansel, J.; Mannan, F.; Robey, R.; Kumarendran, M.; Bladon, S.; Mathioudakis, A.G.; Ogungbenro, K.; Dark, P.; Felton, T.W. Covariates in population pharmacokinetic studies of critically ill adults receiving β-lactam antimicrobials: A systematic review and narrative synthesis. JAC-Antimicrobial Resist. 2023, 6, dlae030. [Google Scholar] [CrossRef] [PubMed]
  55. Gatti, M.; Cojutti, P.G.; Pea, F. Impact of attaining aggressive vs. conservative PK/PD target on the clinical efficacy of beta-lactams for the treatment of Gram-negative infections in the critically ill patients: A systematic review and meta-analysis. Crit. Care 2024, 28, 123. [Google Scholar] [CrossRef] [PubMed]
  56. Varghese, J.M.; Roberts, J.A.; Lipman, J. Antimicrobial Pharmacokinetic and Pharmacodynamic Issues in the Critically Ill with Severe Sepsis and Septic Shock. Crit. Care Clin. 2011, 27, 19–34. [Google Scholar] [CrossRef] [PubMed]
  57. Hites, M.; Taccone, F.S. Optimization of antibiotic therapy in the obese, critically ill patient. Reanim. 2015, 24, 278–294. [Google Scholar] [CrossRef]
  58. Pea, F.; Furlanut, M.; Negri, C.; Pavan, F.; Crapis, M.; Cristini, F.; Viale, P. Prospectively Validated Dosing Nomograms for Maximizing the Pharmacodynamics of Vancomycin Administered by Continuous Infusion in Critically Ill Patients. Antimicrob. Agents Chemother. 2009, 53, 1863–1867. [Google Scholar] [CrossRef]
  59. Page, M.J.; McKenzie, J.E.; Bossuyt, P.M.; Boutron, I.; Hoffmann, T.C.; Mulrow, C.D.; Shamseer, L.; Tetzlaff, J.M.; Akl, E.A.; Brennan, S.E.; et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ 2021, 372, n71. [Google Scholar] [CrossRef]
  60. Kanji, S.; Hayes, M.; Ling, A.; Shamseer, L.; Chant, C.; Edwards, D.J.; Edwards, S.; Ensom, M.H.H.; Foster, D.R.; Hardy, B.; et al. Reporting Guidelines for Clinical Pharmacokinetic Studies: The ClinPK Statement. Clin. Pharmacokinet. 2015, 54, 783–795. [Google Scholar] [CrossRef] [PubMed]
  61. Whitehouse, T.; Cepeda, J.A.; Shulman, R.; Aarons, L.; Nalda-Molina, R.; Tobin, C.; MacGowan, A.; Shaw, S.; Kibbler, C.; Singer, M.; et al. Pharmacokinetic studies of linezolid and teicoplanin in the critically ill. J. Antimicrob. Chemother. 2005, 55, 333–340. [Google Scholar] [CrossRef] [PubMed]
  62. Burkhardt, O.; Kumar, V.; Katterwe, D.; Majcher-Peszynska, J.; Drewelow, B.; Derendorf, H.; Welte, T. Ertapenem in critically ill patients with early-onset ventilator-associated pneumonia: Pharmacokinetics with special consideration of free-drug concentration. J. Antimicrob. Chemother. 2006, 59, 277–284. [Google Scholar] [CrossRef]
  63. Roos, J.F.; Lipman, J.; Kirkpatrick, C.M.J. Population pharmacokinetics and pharmacodynamics of cefpirome in critically ill patients against Gram-negative bacteria. Intensive Care Med. 2007, 33, 781–788. [Google Scholar] [CrossRef] [PubMed]
  64. Roberts, J.A.; Field, J.; Visser, A.; Whitbread, R.; Tallot, M.; Lipman, J.; Kirkpatrick, C.M.J. Using Population Pharmacokinetics To Determine Gentamicin Dosing during Extended Daily Diafiltration in Critically Ill Patients with Acute Kidney Injury. Antimicrob. Agents Chemother. 2010, 54, 3635–3640. [Google Scholar] [CrossRef]
  65. Asin-Prieto, E.; Rodriguez-Gascon, A.; Troconiz, I.F.; Soraluce, A.; Maynar, J.; Sanchez-Izquierdo, J.A.; Isla, A. Population pharmacokinetics of piperacillin and tazobactam in critically ill patients undergoing continuous renal replacement therapy: Application to pharmacokinetic/pharmacodynamic analysis. J. Antimicrob. Chemother. 2013, 69, 180–189. [Google Scholar] [CrossRef]
  66. Escobar, L.; Andresen, M.; Downey, P.; Gai, M.N.; Regueira, T.; Bórquez, T.; Lipman, J.; Roberts, J.A. Population pharmacokinetics and dose simulation of vancomycin in critically ill patients during high-volume haemofiltration. Int. J. Antimicrob. Agents 2014, 44, 163–167. [Google Scholar] [CrossRef]
  67. Couffignal, C.; Pajot, O.; Laouénan, C.; Burdet, C.; Foucrier, A.; Wolff, M.; Armand-Lefevre, L.; Mentré, F.; Massias, L. Population pharmacokinetics of imipenem in critically ill patients with suspected ventilator-associated pneumonia and evaluation of dosage regimens. Br. J. Clin. Pharmacol. 2014, 78, 1022–1034. [Google Scholar] [CrossRef] [PubMed]
  68. Carlier, M.; Noe, M.; Roberts, J.A.; Stove, V.; Verstraete, A.G.; Lipman, J.; De Waele, J.J. Population pharmacokinetics and dosing simulations of cefuroxime in critically ill patients: Non-standard dosing approaches are required to achieve therapeutic exposures. J. Antimicrob. Chemother. 2014, 69, 2797–2803. [Google Scholar] [CrossRef] [PubMed]
  69. Zoller, M.; Maier, B.; Hornuss, C.; Neugebauer, C.; Döbbeler, G.; Nagel, D.; Holdt, L.M.; Bruegel, M.; Weig, T.; Grabein, B.; et al. Variability of linezolid concentrations after standard dosing in critically ill patients: A prospective observational study. Crit. Care 2014, 18, R148. [Google Scholar] [CrossRef]
  70. Luque, S.; Grau, S.; Alvarez-Lerma, F.; Ferrández, O.; Campillo, N.; Horcajada, J.; Basas, M.; Lipman, J.; Roberts, J. Plasma and cerebrospinal fluid concentrations of linezolid in neurosurgical critically ill patients with proven or suspected central nervous system infections. Int. J. Antimicrob. Agents 2014, 44, 409–415. [Google Scholar] [CrossRef]
  71. Ulldemolins, M.; Soy, D.; Llaurado-Serra, M.; Vaquer, S.; Castro, P.; Rodríguez, A.H.; Pontes, C.; Calvo, G.; Torres, A.; Martín-Loeches, I. Meropenem Population Pharmacokinetics in Critically Ill Patients with Septic Shock and Continuous Renal Replacement Therapy: Influence of Residual Diuresis on Dose Requirements. Antimicrob. Agents Chemother. 2015, 59, 5520–5528. [Google Scholar] [CrossRef]
  72. Kees, M.G.; Minichmayr, I.K.; Moritz, S.; Beck, S.; Wicha, S.G.; Kees, F.; Kloft, C.; Steinke, T. Population pharmacokinetics of meropenem during continuous infusion in surgical ICU patients. J. Clin. Pharmacol. 2015, 56, 307–315. [Google Scholar] [CrossRef]
  73. Abdul-Aziz, M.H.; Rahman, A.N.A.; Mat-Nor, M.-B.; Sulaiman, H.; Wallis, S.C.; Lipman, J.; Roberts, J.A.; Staatz, C.E. Population Pharmacokinetics of Doripenem in Critically Ill Patients with Sepsis in a Malaysian Intensive Care Unit. Antimicrob. Agents Chemother. 2016, 60, 206–214. [Google Scholar] [CrossRef]
  74. Roger, C.; Muller, L.; Wallis, S.C.; Louart, B.; Saissi, G.; Lipman, J.; Lefrant, J.Y.; Roberts, J.A. Population pharmacokinetics of linezolid in critically ill patients on renal replacement therapy: Comparison of equal doses in continuous venovenous haemofiltration and continuous venovenous haemodiafiltration. J. Antimicrob. Chemother. 2015, 71, 464–470. [Google Scholar] [CrossRef] [PubMed]
  75. Roberts, J.A.; Cotta, M.O.; Cojutti, P.; Lugano, M.; Della Rocca, G.; Pea, F. Does Critical Illness Change Levofloxacin Pharmacokinetics? Antimicrob. Agents Chemother. 2016, 60, 1459–1463. [Google Scholar] [CrossRef] [PubMed]
  76. Ulldemolins, M.; Martín-Loeches, I.; Llauradó-Serra, M.; Fernández, J.; Vaquer, S.; Rodríguez, A.; Pontes, C.; Calvo, G.; Torres, A.; Soy, D. Piperacillin population pharmacokinetics in critically ill patients with multiple organ dysfunction syndrome receiving continuous venovenous haemodiafiltration: Effect of type of dialysis membrane on dosing requirements. J. Antimicrob. Chemother. 2016, 71, 1651–1659. [Google Scholar] [CrossRef]
  77. Roger, C.; Wallis, S.C.; Louart, B.; Lefrant, J.-Y.; Lipman, J.; Muller, L.; Roberts, J.A. Comparison of equal doses of continuous venovenous haemofiltration and haemodiafiltration on ciprofloxacin population pharmacokinetics in critically ill patients. J. Antimicrob. Chemother. 2016, 71, 1643–1650. [Google Scholar] [CrossRef]
  78. Alobaid, A.S.; Wallis, S.C.; Jarrett, P.; Starr, T.; Stuart, J.; Lassig-Smith, M.; Mejia, J.L.O.; Roberts, M.S.; Lipman, J.; Roberts, J.A. Effect of Obesity on the Population Pharmacokinetics of Meropenem in Critically Ill Patients. Antimicrob. Agents Chemother. 2016, 60, 4577–4584. [Google Scholar] [CrossRef] [PubMed]
  79. Taubert, M.; Zoller, M.; Maier, B.; Frechen, S.; Scharf, C.; Holdt, L.-M.; Frey, L.; Vogeser, M.; Fuhr, U.; Zander, J. Predictors of Inadequate Linezolid Concentrations after Standard Dosing in Critically Ill Patients. Antimicrob. Agents Chemother. 2016, 60, 5254–5261. [Google Scholar] [CrossRef]
  80. Tsai, D.; Stewart, P.; Goud, R.; Gourley, S.; Hewagama, S.; Krishnaswamy, S.; Wallis, S.C.; Lipman, J.; Roberts, J.A. Optimising meropenem dosing in critically ill Australian Indigenous patients with severe sepsis. Int. J. Antimicrob. Agents 2016, 48, 542–546. [Google Scholar] [CrossRef]
  81. Blassmann, U.; Roehr, A.C.; Frey, O.R.; Vetter-Kerkhoff, C.; Thon, N.; Hope, W.; Briegel, J.; Huge, V. Cerebrospinal fluid penetration of meropenem in neurocritical care patients with proven or suspected ventriculitis: A prospective observational study. Crit. Care 2016, 20, 343. [Google Scholar] [CrossRef]
  82. Rahbar, A.J.; Lodise, T.P.; Abraham, P.; Lockwood, A.; Pai, M.P.; Patka, J.; Rabinovich, M.; Curzio, K.; Chester, K.; Williams, B.; et al. Pharmacokinetic and Pharmacodynamic Evaluation of Doripenem in Critically Ill Trauma Patients with Sepsis. Surg. Infect. 2016, 17, 675–682. [Google Scholar] [CrossRef]
  83. Naik, B.I.; Roger, C.; Ikeda, K.; Todorovic, M.S.; Wallis, S.C.; Lipman, J.; Roberts, J.A. Comparative total and unbound pharmacokinetics of cefazolin administered by bolus versus continuous infusion in patients undergoing major surgery: A randomized controlled trial. Br. J. Anaesth. 2017, 118, 876–882. [Google Scholar] [CrossRef]
  84. Xie, J.; Roberts, J.A.; Alobaid, A.S.; Roger, C.; Wang, Y.; Yang, Q.; Sun, J.; Dong, H.; Wang, X.; Xing, J.; et al. Population Pharmacokinetics of Tigecycline in Critically Ill Patients with Severe Infections. Antimicrob. Agents Chemother. 2017, 61, e00345-17. [Google Scholar] [CrossRef] [PubMed]
  85. Wicha, S.G.; Frey, O.R.; Roehr, A.C.; Pratschke, J.; Stockmann, M.; Alraish, R.; Wuensch, T.; Kaffarnik, M. Linezolid in liver failure: Exploring the value of the maximal liver function capacity (LiMAx) test in a pharmacokinetic pilot study. Int. J. Antimicrob. Agents 2017, 50, 557–563. [Google Scholar] [CrossRef]
  86. Sime, F.B.; Hahn, U.; Warner, M.S.; Tiong, I.S.; Roberts, M.S.; Lipman, J.; Peake, S.L.; Roberts, J.A. Using Population Pharmacokinetic Modeling and Monte Carlo Simulations To Determine whether Standard Doses of Piperacillin in Piperacillin-Tazobactam Regimens Are Adequate for the Management of Febrile Neutropenia. Antimicrob. Agents Chemother. 2017, 61. [Google Scholar] [CrossRef] [PubMed]
  87. Sjövall, F.; Alobaid, A.S.; Wallis, S.C.; Perner, A.; Lipman, J.; A Roberts, J. Maximally effective dosing regimens of meropenem in patients with septic shock. J. Antimicrob. Chemother. 2017, 73, 191–198. [Google Scholar] [CrossRef] [PubMed]
  88. Moor, A.B.-D.; Rypulak, E.; Potręć, B.; Piwowarczyk, P.; Borys, M.; Sysiak, J.; Onichimowski, D.; Raszewski, G.; Czuczwar, M.; Wiczling, P. Population Pharmacokinetics of High-Dose Tigecycline in Patients with Sepsis or Septic Shock. Antimicrob. Agents Chemother. 2018, 62. [Google Scholar] [CrossRef]
  89. Braune, S.; König, C.; Roberts, J.A.; Nierhaus, A.; Steinmetz, O.; Baehr, M.; Kluge, S.; Langebrake, C. Pharmacokinetics of meropenem in septic patients on sustained low-efficiency dialysis: A population pharmacokinetic study. Crit. Care 2018, 22, 25. [Google Scholar] [CrossRef]
  90. Bos, J.C.; Prins, J.M.; Mistício, M.C.; Nunguiane, G.; Lang, C.N.; Beirão, J.C.; A A Mathôt, R.; van Hest, R.M. Pharmacokinetics and pharmacodynamic target attainment of ceftriaxone in adult severely ill sub-Saharan African patients: A population pharmacokinetic modelling study. J. Antimicrob. Chemother. 2018, 73, 1620–1629. [Google Scholar] [CrossRef]
  91. Hanberg, P.; Öbrink-Hansen, K.; Thorsted, A.; Bue, M.; Tøttrup, M.; Friberg, L.E.; Hardlei, T.F.; Søballe, K.; Gjedsted, J. Population Pharmacokinetics of Meropenem in Plasma and Subcutis from Patients on Extracorporeal Membrane Oxygenation Treatment. Antimicrob. Agents Chemother. 2018, 62. [Google Scholar] [CrossRef]
  92. Soraluce, A.; Asín-Prieto, E.; Rodríguez-Gascón, A.; Barrasa, H.; Maynar, J.; Carcelero, E.; Soy, D.; Isla, A. Population pharmacokinetics of daptomycin in critically ill patients. Int. J. Antimicrob. Agents 2018, 52, 158–165. [Google Scholar] [CrossRef]
  93. Kanji, S.; Roberts, J.A.; Xie, J.; Alobaid, A.; Zelenitsky, S.; Hiremath, S.; Zhang, G.; Watpool, I.; Porteous, R.; Patel, R. Piperacillin Population Pharmacokinetics in Critically Ill Adults During Sustained Low-Efficiency Dialysis. Ann. Pharmacother. 2018, 52, 965–973. [Google Scholar] [CrossRef]
  94. Fournier, A.; Goutelle, S.; Que, Y.-A.; Eggimann, P.; Pantet, O.; Sadeghipour, F.; Voirol, P.; Csajka, C. Population Pharmacokinetic Study of Amoxicillin-Treated Burn Patients Hospitalized at a Swiss Tertiary-Care Center. Antimicrob. Agents Chemother. 2018, 62. [Google Scholar] [CrossRef]
  95. Tsai, D.; Stewart, P.C.; Hewagama, S.; Krishnaswamy, S.; Wallis, S.C.; Lipman, J.; Roberts, J.A. Optimised dosing of vancomycin in critically ill Indigenous Australian patients with severe sepsis. Anaesth. Intensive Care 2018, 46, 374–380. [Google Scholar] [CrossRef]
  96. Turner, R.B.; Kojiro, K.; Won, R.; Chang, E.; Chan, D.; Elbarbry, F. Prospective evaluation of vancomycin pharmacokinetics in a heterogeneous critically ill population. Diagn. Microbiol. Infect. Dis. 2018, 92, 346–351. [Google Scholar] [CrossRef] [PubMed]
  97. Stein, G.E.; Smith, C.L.; Scharmen, A.; Kidd, J.M.; Cooper, C.; Kuti, J.; Mitra, S.; Nicolau, D.P.; Havlichek, D.H. Pharmacokinetic and Pharmacodynamic Analysis of Ceftazidime/Avibactam in Critically Ill Patients. Surg. Infect. 2019, 20, 55–61. [Google Scholar] [CrossRef] [PubMed]
  98. Leuppi-Taegtmeyer, A.B.; Decosterd, L.; Osthoff, M.; Mueller, N.J.; Buclin, T.; Corti, N. Multicenter Population Pharmacokinetic Study of Colistimethate Sodium and Colistin Dosed as in Normal Renal Function in Patients on Continuous Renal Replacement Therapy. Antimicrob. Agents Chemother. 2019, 63. [Google Scholar] [CrossRef] [PubMed]
  99. Sukarnjanaset, W.; Jaruratanasirikul, S.; Wattanavijitkul, T. Population pharmacokinetics and pharmacodynamics of piperacillin in critically ill patients during the early phase of sepsis. J. Pharmacokinet. Pharmacodyn. 2019, 46, 251–261. [Google Scholar] [CrossRef]
  100. Zamora, A.P.; Roig, R.J.; Badosa, E.L.; Riera, J.S.; Fernández, X.L.P.; Campos, P.C.; Bonin, R.R.; Ramos, P.A.; Quintano, F.T.; Martinez, E.S.; et al. Optimized meropenem dosage regimens using a pharmacokinetic/pharmacodynamic population approach in patients undergoing continuous venovenous haemodiafiltration with high-adsorbent membrane. J. Antimicrob. Chemother. 2019, 74, 2979–2983. [Google Scholar] [CrossRef] [PubMed]
  101. Sime, F.B.; Lassig-Smith, M.; Starr, T.; Stuart, J.; Pandey, S.; Parker, S.L.; Wallis, S.C.; Lipman, J.; Roberts, J.A. Population Pharmacokinetics of Unbound Ceftolozane and Tazobactam in Critically Ill Patients without Renal Dysfunction. Antimicrob. Agents Chemother. 2019, 63. [Google Scholar] [CrossRef]
  102. Kanji, S.; Roberts, J.A.; Xie, J.; Zelenitsky, S.; Hiremath, S.; Zhang, G.; Watpool, I.; Porteous, R.; Patel, R. Vancomycin Population Pharmacokinetics in Critically Ill Adults During Sustained Low-Efficiency Dialysis. Clin. Pharmacokinet. 2020, 59, 327–334. [Google Scholar] [CrossRef]
  103. Sime, F.B.; Lassig-Smith, M.; Starr, T.; Stuart, J.; Pandey, S.; Parker, S.L.; Wallis, S.C.; Lipman, J.; Roberts, J.A. A Population Pharmacokinetic Model-Guided Evaluation of Ceftolozane-Tazobactam Dosing in Critically Ill Patients Undergoing Continuous Venovenous Hemodiafiltration. Antimicrob. Agents Chemother. 2019, 64. [Google Scholar] [CrossRef]
  104. Kovacevic, T.; Miljkovic, B.; Kovacevic, P.; Dragic, S.; Momcicevic, D.; Avram, S.; Jovanovic, M.; Vucicevic, K. Population pharmacokinetic model of Vancomycin based on therapeutic drug monitoring data in critically ill septic patients. J. Crit. Care 2019, 55, 116–121. [Google Scholar] [CrossRef]
  105. Kalaria, S.N.; Gopalakrishnan, M.; Heil, E.L. A Population Pharmacokinetics and Pharmacodynamic Approach To Optimize Tazobactam Activity in Critically Ill Patients. Antimicrob. Agents Chemother. 2020, 64. [Google Scholar] [CrossRef] [PubMed]
  106. Masich, A.M.; Kalaria, S.N.; Gonzales, J.P.; Heil, E.L.; Tata, A.L.; Claeys, K.C.; Patel, D.; Gopalakrishnan, M. Vancomycin Pharmacokinetics in Obese Patients with Sepsis or Septic Shock. Pharmacother. J. Hum. Pharmacol. Drug Ther. 2020, 40, 211–220. [Google Scholar] [CrossRef]
  107. Bue, M.; Sou, T.; Okkels, A.S.L.; Hanberg, P.; Thorsted, A.; Friberg, L.E.; Andersson, T.L.; Öbrink-Hansen, K.; Christensen, S. Population pharmacokinetics of piperacillin in plasma and subcutaneous tissue in patients on continuous renal replacement therapy. Int. J. Infect. Dis. 2020, 92, 133–140. [Google Scholar] [CrossRef] [PubMed]
  108. Niibe, Y.B.; Suzuki, T.B.; Yamazaki, S.M.; Suzuki, T.; Takahashi, N.; Hattori, N.; Nakada, T.-A.; Oda, S.; Ishii, I. Population Pharmacokinetic Analysis of Meropenem in Critically Ill Patients With Acute Kidney Injury Treated With Continuous Hemodiafiltration. Ther. Drug Monit. 2020, 42, 588–594. [Google Scholar] [CrossRef] [PubMed]
  109. Onichimowski, D.; Będźkowska, A.; Ziółkowski, H.; Jaroszewski, J.; Borys, M.; Czuczwar, M.; Wiczling, P. Population pharmacokinetics of standard-dose meropenem in critically ill patients on continuous renal replacement therapy: A prospective observational trial. Pharmacol. Rep. 2020, 72, 719–729. [Google Scholar] [CrossRef]
  110. Smit, C.; van Schip, A.M.; A van Dongen, E.P.; Brüggemann, R.J.M.; Becker, M.L.; Knibbe, C.A.J. Dose recommendations for gentamicin in the real-world obese population with varying body weight and renal (dys)function. J. Antimicrob. Chemother. 2020, 75, 3286–3292. [Google Scholar] [CrossRef]
  111. Blackman, A.L.; Jarugula, P.; Nicolau, D.P.; Chui, S.H.; Joshi, M.; Heil, E.L.; Gopalakrishnan, M. Evaluation of Linezolid Pharmacokinetics in Critically Ill Obese Patients with Severe Skin and Soft Tissue Infections. Antimicrob. Agents Chemother. 2021, 65. [Google Scholar] [CrossRef]
  112. Ulldemolins, M.; Bastida, C.; Llauradó-Serra, M.; Csajka, C.; Rodríguez, A.; Badia, J.R.; Martín-Loeches, I.; Soy, D. Once-daily 1 g ceftriaxone optimizes exposure in patients with septic shock and hypoalbuminemia receiving continuous veno-venous hemodiafiltration. Eur. J. Clin. Pharmacol. 2021, 77, 1169–1180. [Google Scholar] [CrossRef]
  113. Wang, X.; Wang, Y.; Yao, F.; Chen, S.; Hou, Y.; Zheng, Z.; Luo, J.; Qiu, B.; Li, Z.; Wang, Y.; et al. Pharmacokinetics of Linezolid Dose Adjustment for Creatinine Clearance in Critically Ill Patients: A Multicenter, Prospective, Open-Label, Observational Study. Drug Des. Dev. Ther. 2021, ume 15, 2129–2141. [Google Scholar] [CrossRef]
  114. De Winter, S.; van Hest, R.; Dreesen, E.; Annaert, P.; Wauters, J.; Meersseman, W.; Eede, N.V.D.; Desmet, S.; Verelst, S.; Vanbrabant, P.; et al. Quantification and Explanation of the Variability of First-Dose Amikacin Concentrations in Critically Ill Patients Admitted to the Emergency Department: A Population Pharmacokinetic Analysis. Eur. J. Drug Metab. Pharmacokinet. 2021, 46, 653–663. [Google Scholar] [CrossRef]
  115. Cheng, V.; Abdul-Aziz, M.H.; Burrows, F.; Buscher, H.; Corley, A.; Diehl, A.; Jakob, S.M.; Levkovich, B.J.; Pellegrino, V.; Que, Y.-A.; et al. Population pharmacokinetics of cefepime in critically ill patients receiving extracorporeal membrane oxygenation (an ASAP ECMO study). Int. J. Antimicrob. Agents 2021, 58, 106466. [Google Scholar] [CrossRef]
  116. Lan, J.; Wu, Z.; Wang, X.; Wang, Y.; Yao, F.; Zhao, B.-X.; Wang, Y.; Chen, J.; Chen, C. Population Pharmacokinetics Analysis and Dosing Simulations Of Meropenem in Critically Ill Patients with Pulmonary Infection. J. Pharm. Sci. 2022, 111, 1833–1842. [Google Scholar] [CrossRef]
  117. Dreesen, E.; Gijsen, M.; Elkayal, O.; Annaert, P.; Debaveye, Y.; Wauters, J.; O Karlsson, M.; Spriet, I. Ceftriaxone dosing based on the predicted probability of augmented renal clearance in critically ill patients with pneumonia. J. Antimicrob. Chemother. 2022, 77, 2479–2488. [Google Scholar] [CrossRef] [PubMed]
  118. Meenks, S.D.; le Noble, J.L.; Foudraine, N.A.; de Vries, F.; Neef, K.N.; Janssen, P.K. Population pharmacokinetics of unbound ceftriaxone in a critically ill population. Int. J. Clin. Pharmacol. Ther. 2022, 60, 373–383. [Google Scholar] [CrossRef] [PubMed]
  119. Alshaer, M.H.; Barlow, B.; Maranchick, N.; Moser, M.; Gramss, L.; Burgmann, H.; Al Jalali, V.; Wölfl-Duchek, M.; Jäger, W.; Poschner, S.; et al. Meropenem Population Pharmacokinetics and Simulations in Plasma, Cerebrospinal Fluid, and Brain Tissue. Antimicrob. Agents Chemother. 2022, 66, e0043822. [Google Scholar] [CrossRef] [PubMed]
  120. Kumta, N.; Heffernan, A.J.; Cotta, M.O.; Wallis, S.C.; Livermore, A.; Starr, T.; Wong, W.T.; Joynt, G.M.; Lipman, J.; Roberts, J.A. Plasma and Cerebrospinal Fluid Population Pharmacokinetics of Meropenem in Neurocritical Care Patients: A Prospective Two-Center Study. Antimicrob. Agents Chemother. 2022, 66, e0014222. [Google Scholar] [CrossRef] [PubMed]
  121. Fukumoto, S.B.; Ohbayashi, M.; Okada, A.; Kohyama, N.; Tamatsukuri, T.; Inoue, H.; Kato, A.; Kotani, T.; Sagara, H.; Dohi, K.; et al. Population Pharmacokinetic Model and Dosing Simulation of Meropenem Using Measured Creatinine Clearance for Patients with Sepsis. Ther. Drug Monit. 2022, 45, 392–399. [Google Scholar] [CrossRef]
  122. Meenks, S.D.; Punt, N.; le Noble, J.L.M.L.; Foudraine, N.A.; Neef, K.; Janssen, P.K.C. Target attainment and population pharmacokinetics of flucloxacillin in critically ill patients: A multicenter study. Crit. Care 2023, 27, 82. [Google Scholar] [CrossRef]
  123. Tang, T.; Li, Y.; Xu, P.; Zhong, Y.; Yang, M.; Ma, W.; Xiang, D.; Zhang, B.; Zhou, Y. Optimization of polymyxin B regimens for the treatment of carbapenem-resistant organism nosocomial pneumonia: A real-world prospective study. Crit. Care 2023, 27, 164. [Google Scholar] [CrossRef]
  124. Wang, Y.; Yao, F.; Chen, S.; Ouyang, X.; Lan, J.; Wu, Z.; Wang, Y.; Chen, J.; Wang, X.; Chen, C. Optimal Teicoplanin Dosage Regimens in Critically Ill Patients: Population Pharmacokinetics and Dosing Simulations Based on Renal Function and Infection Type. Drug Des. Dev. Ther. 2023, ume 17, 2259–2271. [Google Scholar] [CrossRef]
  125. Barreto, E.F.; Chang, J.; Rule, A.D.; Mara, K.C.; Meade, L.A.; Paul, J.; Jannetto, P.J.; Athreya, A.P.; Scheetz, M.H.; for the BLOOM Study Group. Population pharmacokinetic model of cefepime for critically ill adults: A comparative assessment of eGFR equations. Antimicrob. Agents Chemother. 2023, 67, e0081023. [Google Scholar] [CrossRef] [PubMed]
  126. Facca, B.; Frame, B.; Triesenberg, S. Population Pharmacokinetics of Ceftizoxime Administered by Continuous Infusion in Clinically Ill Adult Patients. Antimicrob. Agents Chemother. 1998, 42, 1783–1787. [Google Scholar] [CrossRef] [PubMed]
  127. Frame, B.C.; Facca, B.F.; Nicolau, D.P.; Triesenberg, S.N. Population Pharmacokinetics of Continuous Infusion Ceftazidime. Clin. Pharmacokinet. 1999, 37, 343–350. [Google Scholar] [CrossRef]
  128. Dailly, E.; Arnould, J.; Fraissinet, F.; Naux, E.; de la Bouralière, M.L.; Bouquié, R.; Deslandes, G.; Jolliet, P.; Le Floch, R. Pharmacokinetics of ertapenem in burns patients. Int. J. Antimicrob. Agents 2013, 42, 48–52. [Google Scholar] [CrossRef]
  129. Beumier, M.; Roberts, J.A.; Kabtouri, H.; Hites, M.; Cotton, F.; Wolff, F.; Lipman, J.; Jacobs, F.; Vincent, J.-L.; Taccone, F.S. A new regimen for continuous infusion of vancomycin during continuous renal replacement therapy. J. Antimicrob. Chemother. 2013, 68, 2859–2865. [Google Scholar] [CrossRef] [PubMed]
  130. Öbrink-Hansen, K.; Juul, R.V.; Storgaard, M.; Thomsen, M.K.; Hardlei, T.F.; Brock, B.; Kreilgaard, M.; Gjedsted, J. Population Pharmacokinetics of Piperacillin in the Early Phase of Septic Shock: Does Standard Dosing Result in Therapeutic Plasma Concentrations? Antimicrob. Agents Chemother. 2015, 59, 7018–7026. [Google Scholar] [CrossRef]
  131. Lin, W.-W.; Wu, W.; Jiao, Z.; Lin, R.-F.; Jiang, C.-Z.; Huang, P.-F.; Liu, Y.-W.; Wang, C.-L. Population pharmacokinetics of vancomycin in adult Chinese patients with post-craniotomy meningitis and its application in individualised dosage regimens. Eur. J. Clin. Pharmacol. 2015, 72, 29–37. [Google Scholar] [CrossRef]
  132. Ide, T.; Takesue, Y.; Ikawa, K.; Morikawa, N.; Ueda, T.; Takahashi, Y.; Nakajima, K.; Takeda, K.; Nishi, S. Population pharmacokinetics/pharmacodynamics of linezolid in sepsis patients with and without continuous renal replacement therapy. Int. J. Antimicrob. Agents 2018, 51, 745–751. [Google Scholar] [CrossRef]
  133. Kang, S.; Jang, J.Y.; Hahn, J.; Kim, D.; Lee, J.Y.; Min, K.L.; Yang, S.; Wi, J.; Chang, M.J. Dose Optimization of Cefpirome Based on Population Pharmacokinetics and Target Attainment during Extracorporeal Membrane Oxygenation. Antimicrob. Agents Chemother. 2020, 64. [Google Scholar] [CrossRef]
  134. Grensemann, J.; Busse, D.; König, C.; Roedl, K.; Jäger, W.; Jarczak, D.; Iwersen-Bergmann, S.; Manthey, C.; Kluge, S.; Kloft, C.; et al. Acute-on-chronic liver failure alters meropenem pharmacokinetics in critically ill patients with continuous hemodialysis: An observational study. Ann. Intensive Care 2020, 10, 48. [Google Scholar] [CrossRef]
  135. Liu, D.; Chen, W.; Wang, Q.; Li, M.; Zhang, Z.; Cui, G.; Li, P.; Zhang, X.; Ma, Y.; Zhan, Q.; et al. Influence of venovenous extracorporeal membrane oxygenation on pharmacokinetics of vancomycin in lung transplant recipients. J. Clin. Pharm. Ther. 2020, 45, 1066–1075. [Google Scholar] [CrossRef]
  136. Ruiz, J.; Ramirez, P.; Villarreal, E.; Gordon, M.; Sánchez, M.; Martín, M.; Castellanos-Ortega. Effect of pharmacokinetic/pharmacodynamic ratio on tigecycline clinical response and toxicity in critically ill patients with multidrug-resistant Gram-negative infections. SAGE Open Med. 2020, 8. [Google Scholar] [CrossRef]
  137. Lin, Z.; Chen, D.-Y.; Zhu, Y.-W.; Jiang, Z.-L.; Cui, K.; Zhang, S.; Chen, L.-H. Population pharmacokinetic modeling and clinical application of vancomycin in Chinese patients hospitalized in intensive care units. Sci. Rep. 2021, 11, 2670. [Google Scholar] [CrossRef]
  138. Šíma, M.; Michaličková, D.; Ryšánek, P.; Cihlářová, P.; Kuchař, M.; Lžičařová, D.; Beroušek, J.; Hartinger, J.M.; Vymazal, T.; Slanař, O. No Time Dependence of Ciprofloxacin Pharmacokinetics in Critically Ill Adults: Comparison of Individual and Population Analyses. Pharmaceutics 2021, 13, 1156. [Google Scholar] [CrossRef] [PubMed]
  139. Zhao, Y.-C.; Zou, Y.; Xiao, Y.-W.; Wang, F.; Zhang, B.-K.; Xiang, D.-X.; Yu, F.; Luo, H.; Sandaradura, I.; Yan, M. Does Prolonged Infusion Time Really Improve the Efficacy of Meropenem Therapy? A Prospective Study in Critically Ill Patients. Infect. Dis. Ther. 2021, 11, 201–216. [Google Scholar] [CrossRef] [PubMed]
  140. Alsultan, A.; Dasuqi, S.A.; Aljamaan, F.; Omran, R.A.; Syed, S.A.; AlJaloud, T.; AlAhmadi, A.; Alqahtani, S.; Hamad, M.A. Pharmacokinetics of meropenem in critically ill patients in Saudi Arabia. Saudi Pharm. J. 2021, 29, 1272–1277. [Google Scholar] [CrossRef]
  141. Wang, C.; Zhang, C.; Li, X.; Zhao, S.; He, N.; Zhai, S.; Ge, Q. Dose Optimization of Vancomycin for Critically Ill Patients Undergoing CVVH: A Prospective Population PK/PD Analysis. Antibiotics 2021, 10, 1392. [Google Scholar] [CrossRef]
  142. Busse, D.; Simon, P.; Schmitt, L.; Petroff, D.; Dorn, C.; Dietrich, A.; Zeitlinger, M.; Huisinga, W.; Michelet, R.; Wrigge, H.; et al. Comparative Plasma and Interstitial Tissue Fluid Pharmacokinetics of Meropenem Demonstrate the Need for Increasing Dose and Infusion Duration in Obese and Non-obese Patients. Clin. Pharmacokinet. 2021, 61, 655–672. [Google Scholar] [CrossRef]
  143. Farkas, A.; Oikonomou, K.; Ghanbar, M.; Villasurda, P.; Varghese, J.; Lipman, J.; Sassine, J.; Ranganathan, D.; Roberts, J.A. Population Pharmacokinetics of Intraperitoneal Gentamicin and the Impact of Varying Dwell Times on Pharmacodynamic Target Attainment in Patients with Acute Peritonitis Undergoing Peritoneal Dialysis. Antimicrob. Agents Chemother. 2022, 66, e0167921. [Google Scholar] [CrossRef]
  144. Hahn, J.; Min, K.L.; Kang, S.; Yang, S.; Park, M.S.; Wi, J.; Chang, M.J. Population Pharmacokinetics and Dosing Optimization of Piperacillin-Tazobactam in Critically Ill Patients on Extracorporeal Membrane Oxygenation and the Influence of Concomitant Renal Replacement Therapy. Microbiol. Spectr. 2021, 9, e0063321. [Google Scholar] [CrossRef] [PubMed]
  145. Gijsen, M.; Elkayal, O.; Annaert, P.; Van Daele, R.; Meersseman, P.; Debaveye, Y.; Wauters, J.; Dreesen, E.; Spriet, I. Meropenem Target Attainment and Population Pharmacokinetics in Critically Ill Septic Patients with Preserved or Increased Renal Function. Infect. Drug Resist. 2022, 15, 53–62. [Google Scholar] [CrossRef] [PubMed]
  146. Pressiat, C.; Kudela, A.; De Roux, Q.; Khoudour, N.; Alessandri, C.; Haouache, H.; Vodovar, D.; Woerther, P.-L.; Hutin, A.; Ghaleh, B.; et al. Population Pharmacokinetics of Amikacin in Patients on Veno-Arterial Extracorporeal Membrane Oxygenation. Pharmaceutics 2022, 14, 289. [Google Scholar] [CrossRef]
  147. Alihodzic, D.; Wicha, S.G.; Frey, O.R.; König, C.; Baehr, M.; Jarczak, D.; Kluge, S.; Langebrake, C. Ciprofloxacin in Patients Undergoing Extracorporeal Membrane Oxygenation (ECMO): A Population Pharmacokinetic Study. Pharmaceutics 2022, 14, 965. [Google Scholar] [CrossRef]
  148. Šíma, M.; Bobek, D.; Cihlářová, P.; Ryšánek, P.; Roušarová, J.; Beroušek, J.; Kuchař, M.; Vymazal, T.; Slanař, O. Factors Affecting the Metabolic Conversion of Ciprofloxacin and Exposure to Its Main Active Metabolites in Critically Ill Patients: Population Pharmacokinetic Analysis of Desethylene Ciprofloxacin. Pharmaceutics 2022, 14, 1627. [Google Scholar] [CrossRef]
  149. Kang, S.; Yang, S.; Hahn, J.; Jang, J.Y.; Min, K.L.; Wi, J.; Chang, M.J. Dose Optimization of Meropenem in Patients on Veno-Arterial Extracorporeal Membrane Oxygenation in Critically Ill Cardiac Patients: Pharmacokinetic/Pharmacodynamic Modeling. J. Clin. Med. 2022, 11, 6621. [Google Scholar] [CrossRef] [PubMed]
  150. An, G.; Creech, C.B.; Wu, N.; Nation, R.L.; Gu, K.; Nalbant, D.; Jimenez-Truque, N.; Fissell, W.; Rolsma, S.; Patel, P.C.; et al. Evaluation of Empirical Dosing Regimens for Meropenem in Intensive Care Unit Patients Using Population Pharmacokinetic Modeling and Target Attainment Analysis. Antimicrob. Agents Chemother. 2023, 67, e0131222. [Google Scholar] [CrossRef]
  151. Bai, J.; Wen, A.; Li, Z.; Li, X.; Duan, M. Population pharmacokinetics and dosing optimisation of imipenem in critically ill patients. Eur. J. Hosp. Pharm. 2023. [Google Scholar] [CrossRef]
  152. Martínez-Casanova, J.; Esteve-Pitarch, E.; Colom-Codina, H.; Gumucio-Sanguino, V.D.; Cobo-Sacristán, S.; Shaw, E.; Maisterra-Santos, K.; Sabater-Riera, J.; Pérez-Fernandez, X.L.; Rigo-Bonnin, R.; et al. Predictive Factors of Piperacillin Exposure and the Impact on Target Attainment after Continuous Infusion Administration to Critically Ill Patients. Antibiotics 2023, 12, 531. [Google Scholar] [CrossRef]
  153. An, G.; Creech, C.B.; Wu, N.; Nation, R.L.; Gu, K.; Nalbant, D.; Jimenez-Truque, N.; Fissell, W.; Patel, P.C.; Fishbane, N.; et al. Population pharmacokinetics and target attainment analyses to identify a rational empirical dosing strategy for cefepime in critically ill patients. J. Antimicrob. Chemother. 2023, 78, 1460–1470. [Google Scholar] [CrossRef] [PubMed]
  154. Bilal, M.; Zoller, M.; Fuhr, U.; Jaehde, U.; Ullah, S.; Liebchen, U.; Büsker, S.; Zander, J.; Flury, B.B.; Taubert, M. Cefepime Population Pharmacokinetics, Antibacterial Target Attainment, and Estimated Probability of Neurotoxicity in Critically Ill Patients. Antimicrob. Agents Chemother. 2023, 67, e0030923. [Google Scholar] [CrossRef]
  155. Ehmann, L.; Zoller, M.; Minichmayr, I.K.; Scharf, C.; Huisinga, W.; Zander, J.; Kloft, C. Development of a dosing algorithm for meropenem in critically ill patients based on a population pharmacokinetic/pharmacodynamic analysis. Int. J. Antimicrob. Agents 2019, 54, 309–317. [Google Scholar] [CrossRef] [PubMed]
  156. Soraluce, A.; Barrasa, H.; Asín-Prieto, E.; Sánchez-Izquierdo, J.; Maynar, J.; Isla, A.; Rodríguez-Gascón, A. Novel Population Pharmacokinetic Model for Linezolid in Critically Ill Patients and Evaluation of the Adequacy of the Current Dosing Recommendation. Pharmaceutics 2020, 12, 54. [Google Scholar] [CrossRef]
  157. Lee, J.H.; Lee, D.-H.; Kim, J.S.; Jung, W.-B.; Heo, W.; Kim, Y.K.; Kim, S.H.; No, T.-H.; Jo, K.M.; Ko, J.; et al. Pharmacokinetics and Monte Carlo Simulation of Meropenem in Critically Ill Adult Patients Receiving Extracorporeal Membrane Oxygenation. Front. Pharmacol. 2021, 12. [Google Scholar] [CrossRef] [PubMed]
  158. Dedkaew, T.; Cressey, T.R.; Punyawudho, B.; Lucksiri, A. Pharmacokinetics of vancomycin in critically ill patients in Thailand. Int. J. Pharm. Pharm. Sci. 2015, 7, 232–237. [Google Scholar]
  159. Seo, H.; Kim, Y.K.; Park, S.; Kim, H.-I.; Lee, D.-H. Population Pharmacokinetics and Monte Carlo Simulation of Cefepime in Critically Ill Patients with Hospital-Acquired/Ventilator-Associated Pneumonia. Infect. Chemother. 2023, 55, 29–41. [Google Scholar] [CrossRef]
  160. Mattioli, F.; Fucile, C.; Del Bono, V.; Marini, V.; Parisini, A.; Molin, A.; Zuccoli, M.L.; Milano, G.; Danesi, R.; Marchese, A.; et al. Population pharmacokinetics and probability of target attainment of meropenem in critically ill patients. Eur. J. Clin. Pharmacol. 2016, 72, 839–848. [Google Scholar] [CrossRef]
  161. Abdulla, A.; Rogouti, O.; Hunfeld, N.G.M.; Endeman, H.; Dijkstra, A.; van Gelder, T.; Muller, A.E.; de Winter, B.C.M.; Koch, B.C.P. Population pharmacokinetics and target attainment of ciprofloxacin in critically ill patients. Eur. J. Clin. Pharmacol. 2020, 76, 957–967. [Google Scholar] [CrossRef] [PubMed]
  162. Cheng, V.; Abdul-Aziz, M.H.; Burrows, F.; Buscher, H.; Corley, A.; Diehl, A.; Levkovich, B.J.; Pellegrino, V.; Reynolds, C.; Rudham, S.; et al. Population pharmacokinetics of ciprofloxacin in critically ill patients receiving extracorporeal membrane oxygenation (an ASAP ECMO study). Anaesth. Crit. Care Pain Med. 2022, 41, 101080. [Google Scholar] [CrossRef]
  163. Isla, A.; Rodríguez-Gascón, A.; Trocóniz, I.F.; Bueno, L.; Solinís, M.; Maynar, J.; Sánchez-Izquierdo, J.; Pedraz, J.L. Population Pharmacokinetics of Meropenem in Critically Ill Patients Undergoing Continuous Renal Replacement Therapy. Clin. Pharmacokinet. 2008, 47, 173–180. [Google Scholar] [CrossRef]
  164. Alobaid, A.S.; Wallis, S.C.; Jarrett, P.; Starr, T.; Stuart, J.; Lassig-Smith, M.; Mejia, J.L.O.; Roberts, M.S.; Roger, C.; Udy, A.A.; et al. Population Pharmacokinetics of Piperacillin in Nonobese, Obese, and Morbidly Obese Critically Ill Patients. Antimicrob. Agents Chemother. 2017, 61, e01276-16. [Google Scholar] [CrossRef] [PubMed]
  165. Kim, Y.K.; Kim, H.S.; Park, S.; Kim, H.-I.; Lee, S.H.; Lee, D.-H. Population pharmacokinetics of piperacillin/tazobactam in critically ill Korean patients and the effects of extracorporeal membrane oxygenation. J. Antimicrob. Chemother. 2022, 77, 1353–1364. [Google Scholar] [CrossRef] [PubMed]
  166. Ernest, D.; Cutler, D.J. Gentamicin clearance during continuous arteriovenous hemodiafiltration. Crit. Care Med. 1992, 20, 586–589. [Google Scholar] [CrossRef] [PubMed]
  167. Shikuma, L.R.; Ackerman, B.H.; Weaver, R.H.; Solem, L.D.; Strate, R.G.; Cerra, F.B.; Zaske, D.E. Effects of treatment and the metabolic response to injury on drug clearance: A prospective study with piperacillin. Crit Care Med. 1990, 18, 37–41. [Google Scholar] [CrossRef]
  168. Cornwell, E.E.; Belzberg, H.; Berne, T.V.; Gill, M.A.; Theodorou, D.; Kern, J.W.; Yu, W.; Asensio, J.; Demetriades, D. Pharmacokinetics of aztreonam in critically ill surgical patients. Am. J. Heal. Pharm. 1997, 54, 537–540. [Google Scholar] [CrossRef]
  169. Giles, L.J.; Jennings, A.C.; Thomson, A.H.; Creed, G.; Beale, R.J.; McLuckie, A. Pharmacokinetics of meropenem in intensive care unit patients receiving continuous veno-venous hemofiltration or hemodiafiltration. Crit. Care Med. 2000, 28, 632–637. [Google Scholar] [CrossRef]
  170. Barletta, J.F.; Johnson, S.B.; Nix, D.E.; Nix, L.C.; Erstad, B.L. Population Pharmacokinetics of Aminoglycosides in Critically Ill Trauma Patients on Once-Daily Regimens. J. Trauma: Inj. Infect. Crit. Care 2000, 49, 869–872. [Google Scholar] [CrossRef]
  171. Malone, R.S.; Fish, D.N.; Abraham, E.; Teitelbaum, I. Pharmacokinetics of Cefepime during Continuous Renal Replacement Therapy in Critically Ill Patients. Antimicrob. Agents Chemother. 2001, 45, 3148–3155. [Google Scholar] [CrossRef]
  172. Traunmüller, F.; Schenk, P.; Mittermeyer, C.; Thalhammer-Scherrer, R.; Ratheiser, K.; Thalhammer, F. Clearance of ceftazidime during continuous venovenous haemofiltration in critically ill patients. J. Antimicrob. Chemother. 2002, 49, 129–134. [Google Scholar] [CrossRef]
  173. Uchino, S.; Cole, L.; Morimatsu, H.; Goldsmith, D.; Bellomo, R. Clearance of vancomycin during high-volume haemofiltration: Impact of pre-dilution. Intensive Care Med. 2002, 28, 1664–1667. [Google Scholar] [CrossRef]
  174. Fiaccadori, E.; Maggiore, U.; Rotelli, C.; Giacosa, R.; Parenti, E.; Picetti, E.; Sagripanti, S.; Manini, P.; Andreoli, R.; Cabassi, A. Removal of linezolid by conventional intermittent hemodialysis, sustained low-efficiency dialysis, or continuous venovenous hemofiltration in patients with acute renal failure. Crit. Care Med. 2004, 32, 2437–2442. [Google Scholar] [CrossRef]
  175. Meyer, B.; Kornek, G.V.; Nikfardjam, M.; Karth, G.D.; Heinz, G.; Locker, G.J.; Jaeger, W.; Thalhammer, F. Multiple-dose pharmacokinetics of linezolid during continuous venovenous haemofiltration. J. Antimicrob. Chemother. 2005, 56, 172–179. [Google Scholar] [CrossRef]
  176. Fish, D.N.; Teitelbaum, I.; Abraham, E. Pharmacokinetics and Pharmacodynamics of Imipenem during Continuous Renal Replacement Therapy in Critically Ill Patients. Antimicrob. Agents Chemother. 2005, 49, 2421–2428. [Google Scholar] [CrossRef] [PubMed]
  177. Kielstein, J.T.; Czock, D.; Schöpke, T.; Hafer, C.; Bode-Böger, S.M.; Kuse, E.; Keller, F.; Fliser, D. Pharmacokinetics and total elimination of meropenem and vancomycin in intensive care unit patients undergoing extended daily dialysis*. Crit. Care Med. 2006, 34, 51–56. [Google Scholar] [CrossRef] [PubMed]
  178. Klansuwan, N.; Ratanajamit, C.; Kasiwong, S.; Wangsiripaisan, A. Clearance of vancomycin during high-efficiency hemodialysis. J. Med. Assoc. Thail. 2006, 89, 986–991. [Google Scholar] [PubMed]
  179. Bracco, D.; Landry, C.; Dubois, M.-J.; Eggimann, P. Pharmacokinetic variability of extended interval tobramycin in burn patients. Burns 2008, 34, 791–796. [Google Scholar] [CrossRef] [PubMed]
  180. Burkhardt, O.; Hafer, C.; Langhoff, A.; Kaever, V.; Kumar, V.; Welte, T.; Haller, H.; Fliser, D.; Kielstein, J.T. Pharmacokinetics of ertapenem in critically ill patients with acute renal failure undergoing extended daily dialysis. Nephrol. Dial. Transplant. 2008, 24, 267–271. [Google Scholar] [CrossRef]
  181. Golestaneh, L.; Gofran, A.; Mokrzycki, M.; Chen, J. Removal of vancomycin in sustained low-efficiency dialysis (SLED): A need for better surveillance and dosing. Clin. Nephrol. 2009, 72, 286–291. [Google Scholar] [CrossRef]
  182. Deshpande, P.; Chen, J.; Gofran, A.; Murea, M.; Golestaneh, L. Meropenem removal in critically ill patients undergoing sustained low-efficiency dialysis (SLED). Nephrol. Dial. Transplant. 2010, 25, 2632–2636. [Google Scholar] [CrossRef]
  183. Bilgrami, I.; Roberts, J.A.; Wallis, S.C.; Thomas, J.; Davis, J.; Fowler, S.; Goldrick, P.B.; Lipman, J. Meropenem Dosing in Critically Ill Patients with Sepsis Receiving High-Volume Continuous Venovenous Hemofiltration. Antimicrob. Agents Chemother. 2010, 54, 2974–2978. [Google Scholar] [CrossRef]
  184. Seyler, L.; Cotton, F.; Taccone, F.S.; De Backer, D.; Macours, P.; Vincent, J.-L.; Jacobs, F. Recommended β-lactam regimens are inadequate in septic patients treated with continuous renal replacement therapy. Crit. Care 2011, 15, R137. [Google Scholar] [CrossRef] [PubMed]
  185. Baptista, J.P.; Sousa, E.; Martins, P.J.; Pimentel, J.M. Augmented renal clearance in septic patients and implications for vancomycin optimisation. Int. J. Antimicrob. Agents 2012, 39, 420–423. [Google Scholar] [CrossRef] [PubMed]
  186. Roberts, D.M.; Roberts, J.A.; Roberts, M.S.; Liu, X.; Nair, P.; Cole, L.; Lipman, J.; Bellomo, R. Variability of antibiotic concentrations in critically ill patients receiving continuous renal replacement therapy. Crit. Care Med. 2012, 40, 1523–1528. [Google Scholar] [CrossRef]
  187. Petejova, N.; Martinek, A.; Zahalkova, J.; Duricova, J.; Brozmannova, H.; Urbanek, K.; Grundmann, M.; Plasek, J.; Kacirova, I. Vancomycin pharmacokinetics during high-volume continuous venovenous hemofiltration in critically ill septic patients. Biomed. Pap. 2014, 158, 065–072. [Google Scholar] [CrossRef]
  188. D’arcy, D.M.; Casey, E.; Gowing, C.M.; Donnelly, M.B.; I Corrigan, O. An open prospective study of amikacin pharmacokinetics in critically ill patients during treatment with continuous venovenous haemodiafiltration. BMC Pharmacol. Toxicol. 2012, 13, 14. [Google Scholar] [CrossRef]
  189. Binder, L.; Schwörer, H.; Hoppe, S.; Streit, F.; Neumann, S.; Beckmann, A.; Wachter, R.; Oellerich, M.; Walson, P.D. Pharmacokinetics of Meropenem in Critically Ill Patients With Severe Infections. Ther. Drug Monit. 2013, 35, 63–70. [Google Scholar] [CrossRef] [PubMed]
  190. Adnan, S.; Li, J.X.; Wallis, S.C.; Rudd, M.; Jarrett, P.; Paterson, D.L.; Lipman, J.; Udy, A.A.; Roberts, J.A. Pharmacokinetics of meropenem and piperacillin in critically ill patients with indwelling surgical drains. Int. J. Antimicrob. Agents 2013, 42, 90–93. [Google Scholar] [CrossRef]
  191. Carlier, M.; Carrette, S.; Roberts, J.A.; Stove, V.; Verstraete, A.; Hoste, E.; Depuydt, P.; Decruyenaere, J.; Lipman, J.; Wallis, S.C.; et al. Meropenem and piperacillin/tazobactam prescribing in critically ill patients: Does augmented renal clearance affect pharmacokinetic/pharmacodynamic target attainment when extended infusions are used? Crit. Care 2013, 17, R84. [Google Scholar] [CrossRef]
  192. Sturm, A.W.; Allen, N.; Rafferty, K.D.; Fish, D.N.; Toschlog, E.; Newell, M.; Waibel, B. Pharmacokinetic Analysis of Piperacillin Administered with Tazobactam in Critically Ill, Morbidly Obese Surgical Patients. Pharmacother. J. Hum. Pharmacol. Drug Ther. 2013, 34, 28–35. [Google Scholar] [CrossRef]
  193. Carlier, M.; Carrette, S.; Stove, V.; Verstraete, A.G.; De Waele, J.J. Does consistent piperacillin dosing result in consistent therapeutic concentrations in critically ill patients? A longitudinal study over an entire antibiotic course. Int. J. Antimicrob. Agents 2014, 43, 470–473. [Google Scholar] [CrossRef]
  194. Huttner, A.; Von Dach, E.; Renzoni, A.; Huttner, B.D.; Affaticati, M.; Pagani, L.; Daali, Y.; Pugin, J.; Karmime, A.; Fathi, M.; et al. Augmented renal clearance, low beta-lactam concentrations and clinical outcomes in the critically ill: An observational prospective cohort study. Int. J. Antimicrob. Agents 2015, 45, 385–392. [Google Scholar] [CrossRef] [PubMed]
  195. Sime, F.B.; Roberts, M.S.; Tiong, I.S.; Gardner, J.H.; Lehman, S.; Peake, S.L.; Hahn, U.; Warner, M.S.; Roberts, J.A. Can therapeutic drug monitoring optimize exposure to piperacillin in febrile neutropenic patients with haematological malignancies? A randomized controlled trial. J. Antimicrob. Chemother. 2015, 70, 2369–2375. [Google Scholar] [CrossRef] [PubMed]
  196. Awissi, D.; Beauchamp, A.; Hébert, E.; Lavigne, V.; Munoz, D.L.; Lebrun, G.; Savoie, M.; Fagnan, M.; Amyot, J.; Tétreault, N.; et al. Pharmacokinetics of an Extended 4-hour Infusion of Piperacillin-Tazobactam in Critically Ill Patients Undergoing Continuous Renal Replacement Therapy. Pharmacother. J. Hum. Pharmacol. Drug Ther. 2015, 35, 600–607. [Google Scholar] [CrossRef]
  197. Villa, G.; Cassetta, M.I.; Tofani, L.; Valente, S.; Chelazzi, C.; Falsini, S.; De Gaudio, A.R.; Novelli, A.; Ronco, C.; Adembri, C. Linezolid extracorporeal removal during haemodialysis with high cut-off membrane in critically ill patients. Int. J. Antimicrob. Agents 2015, 46, 465–468. [Google Scholar] [CrossRef] [PubMed]
  198. Wen, A.; Li, Z.; Yu, J.; Li, R.; Cheng, S.; Duan, M.; Bai, J. Clinical Validation of Therapeutic Drug Monitoring of Imipenem in Spent Effluent in Critically Ill Patients Receiving Continuous Renal Replacement Therapy: A Pilot Study. PLOS ONE 2016, 11, e0153927. [Google Scholar] [CrossRef]
  199. Boucher, B.A.; Hudson, J.Q.; Hill, D.M.; Swanson, J.M.; Wood, G.C.; Laizure, S.C.; Arnold-Ross, A.; Hu, Z.-Y.; Hickerson, W.L. Pharmacokinetics of Imipenem/Cilastatin Burn Intensive Care Unit Patients Undergoing High-Dose Continuous Venovenous Hemofiltration. Pharmacother. J. Hum. Pharmacol. Drug Ther. 2016, 36, 1229–1237. [Google Scholar] [CrossRef] [PubMed]
  200. Jung, B.; Mahul, M.; Breilh, D.; Legeron, R.; Signe, J.; Jean-Pierre, H.; Uhlemann, A.-C.; Molinari, N.; Jaber, S. Repeated Piperacillin-Tazobactam Plasma Concentration Measurements in Severely Obese Versus Nonobese Critically Ill Septic Patients and the Risk of Under– and Overdosing*. Crit. Care Med. 2017, 45, e470–e478. [Google Scholar] [CrossRef]
  201. Roger, C.; Cotta, M.O.; Muller, L.; Wallis, S.C.; Lipman, J.; Lefrant, J.-Y.; Roberts, J.A. Impact of renal replacement modalities on the clearance of piperacillin-tazobactam administered via continuous infusion in critically ill patients. Int. J. Antimicrob. Agents 2017, 50, 227–231. [Google Scholar] [CrossRef]
  202. Carrié, C.; Petit, L.; D'Houdain, N.; Sauvage, N.; Cottenceau, V.; Lafitte, M.; Foumenteze, C.; Hisz, Q.; Menu, D.; Legeron, R.; et al. Association between augmented renal clearance, antibiotic exposure and clinical outcome in critically ill septic patients receiving high doses of β-lactams administered by continuous infusion: A prospective observational study. Int. J. Antimicrob. Agents 2018, 51, 443–449. [Google Scholar] [CrossRef]
  203. Ruiz-Ramos, J.; Villarreal, E.; Gordon, M.; Martin-Cerezula, M.; Broch, M.J.; Marqués, M.R.; Poveda, J.L.; Castellanos-Ortega; Ramírez, P. Implication of Haemodiafiltration Flow Rate on Amikacin Pharmacokinetic Parameters in Critically Ill Patients. Blood Purif. 2017, 45, 88–94. [Google Scholar] [CrossRef] [PubMed]
  204. Fournier, A.; Eggimann, P.; Pantet, O.; Pagani, J.L.; Dupuis-Lozeron, E.; Pannatier, A.; Sadeghipour, F.; Voirol, P.; Que, Y.-A. Impact of Real-Time Therapeutic Drug Monitoring on the Prescription of Antibiotics in Burn Patients Requiring Admission to the Intensive Care Unit. Antimicrob. Agents Chemother. 2018, 62. [Google Scholar] [CrossRef] [PubMed]
  205. Sinnollareddy, M.G.; Roberts, M.S.; Lipman, J.; Peake, S.L.; A Roberts, J. Pharmacokinetics of piperacillin in critically ill patients with acute kidney injury receiving sustained low-efficiency diafiltration. J. Antimicrob. Chemother. 2018, 73, 1647–1650. [Google Scholar] [CrossRef]
  206. Wang, S.; Lin, F.; Ruan, J.; Ye, H.; Wang, L. Pharmacokinetics of multiple doses of teicoplanin in Chinese elderly critical patients. Expert Rev. Clin. Pharmacol. 2018, 11, 537–541. [Google Scholar] [CrossRef] [PubMed]
  207. Kassel, L.E.; Van Matre, E.T.; Foster, C.J.; Fish, D.N.; Mueller, S.W.; Sherman, D.S.; Wempe, M.F.; MacLaren, R.; Neumann, R.T.; Kiser, T.H. A Randomized Pharmacokinetic and Pharmacodynamic Evaluation of Every 8-Hour and 12-Hour Dosing Strategies of Vancomycin and Cefepime in Neurocritically ill Patients. Pharmacother. J. Hum. Pharmacol. Drug Ther. 2018, 38, 921–934. [Google Scholar] [CrossRef] [PubMed]
  208. Olbrisch, K.; Kisch, T.; Thern, J.; Kramme, E.; Rupp, J.; Graf, T.; Wicha, S.G.; Mailänder, P.; Raasch, W. After standard dosage of piperacillin plasma concentrations of drug are subtherapeutic in burn patients. Naunyn-Schmiedeberg's Arch. Pharmacol. 2018, 392, 229–241. [Google Scholar] [CrossRef]
  209. Barrasa, H.; Soraluce, A.; Isla, A.; Martín, A.; Maynar, J.; Canut, A.; Sánchez-Izquierdo, J.A.; Rodríguez-Gascón, A. Pharmacokinetics of linezolid in critically ill patients on continuous renal replacement therapy: Influence of residual renal function on PK/PD target attainment. J. Crit. Care 2019, 50, 69–76. [Google Scholar] [CrossRef]
  210. Schmidt, J.J.; Strunk, A.-K.; David, S.; Bode-Böger, S.M.; Martens-Lobenhoffer, J.; Knitsch, W.; Scherneck, S.; Welte, T.; Kielstein, J.T. Single- and multiple-dose pharmacokinetics and total removal of colistin in critically ill patients with acute kidney injury undergoing prolonged intermittent renal replacement therapy. J. Antimicrob. Chemother. 2019, 74, 997–1002. [Google Scholar] [CrossRef]
  211. Singhan, W.; Vadcharavivad, S.; Areepium, N.; Wittayalertpanya, S.; Chaijamorn, W.; Srisawat, N. The effect of direct hemoperfusion with polymyxin B immobilized cartridge on meropenem in critically ill patients requiring renal support. J. Crit. Care 2019, 51, 71–76. [Google Scholar] [CrossRef]
  212. Bouglé, A.; Dujardin, O.; Lepère, V.; Hamou, N.A.; Vidal, C.; Lebreton, G.; Salem, J.-E.; El-Helali, N.; Petijean, G.; Amour, J. PHARMECMO: Therapeutic drug monitoring and adequacy of current dosing regimens of antibiotics in patients on Extracorporeal Life Support. Anaesth. Crit. Care Pain Med. 2019, 38, 493–497. [Google Scholar] [CrossRef]
  213. Dhaese, S.A.; Thooft, A.D.; Farkas, A.; Lipman, J.; Verstraete, A.G.; Stove, V.; Roberts, J.A.; De Waele, J.J. Early target attainment of continuous infusion piperacillin/tazobactam and meropenem in critically ill patients: A prospective observational study. J. Crit. Care 2019, 52, 75–79. [Google Scholar] [CrossRef] [PubMed]
  214. Leon, L.; Guerci, P.; Pape, E.; Thilly, N.; Luc, A.; Germain, A.; Butin-Druoton, A.-L.; Losser, M.-R.; Birckener, J.; Scala-Bertola, J.; et al. Serum and peritoneal exudate concentrations after high doses of β-lactams in critically ill patients with severe intra-abdominal infections: An observational prospective study. J. Antimicrob. Chemother. 2019, 75, 156–161. [Google Scholar] [CrossRef]
  215. A Roberts, J.; Joynt, G.M.; Lee, A.; Choi, G.; Bellomo, R.; Kanji, S.; Mudaliar, M.Y.; Peake, S.L.; Stephens, D.; Taccone, F.S.; et al. The Effect of Renal Replacement Therapy and Antibiotic Dose on Antibiotic Concentrations in Critically Ill Patients: Data From the Multinational Sampling Antibiotics in Renal Replacement Therapy Study. Clin. Infect. Dis. 2020, 72, 1369–1378. [Google Scholar] [CrossRef]
  216. Gieling, E.M.; Wallenburg, E.; Frenzel, T.; de Lange, D.W.; Schouten, J.A.; Oever, J.T.; Kolwijck, E.; Burger, D.M.; Pickkers, P.; ter Heine, R.; et al. Higher Dosage of Ciprofloxacin Necessary in Critically Ill Patients: A New Dosing Algorithm Based on Renal Function and Pathogen Susceptibility. Clin. Pharmacol. Ther. 2020, 108, 770–774. [Google Scholar] [CrossRef]
  217. Moni, M.; Sudhir, A.S.; Dipu, T.S.; Mohamed, Z.; Prabhu, B.P.; Edathadathil, F.; Balachandran, S.; Singh, S.K.; Prasanna, P.; Menon, V.P.; et al. Clinical efficacy and pharmacokinetics of colistimethate sodium and colistin in critically ill patients in an Indian hospital with high endemic rates of multidrug-resistant Gram-negative bacterial infections: A prospective observational study. Int. J. Infect. Dis. 2020, 100, 497–506. [Google Scholar] [CrossRef] [PubMed]
  218. Lin, S.-Y.; Shen, L.-J.; Wu, V.-C.; Ko, W.-J.; Wu, C.-C.; Wu, F.-L.L. Pharmacokinetics and dosing of vancomycin in patients undergoing sustained low efficiency daily diafiltration (SLEDD-f): A prospective study. J. Formos. Med Assoc. 2021, 120, 737–743. [Google Scholar] [CrossRef] [PubMed]
  219. de Freitas, F.M.; Zamoner, W.; dos Reis, P.F.; Balbi, A.L.; Ponce, D. Vancomycin for Dialytic Therapy in Critically Ill Patients: Analysis of Its Reduction and the Factors Associated with Subtherapeutic Concentrations. Int. J. Environ. Res. Public Heal. 2020, 17, 6861. [Google Scholar] [CrossRef]
  220. Kühn, D.; Metz, C.; Seiler, F.; Wehrfritz, H.; Roth, S.; Alqudrah, M.; Becker, A.; Bracht, H.; Wagenpfeil, S.; Hoffmann, M.; et al. Antibiotic therapeutic drug monitoring in intensive care patients treated with different modalities of extracorporeal membrane oxygenation (ECMO) and renal replacement therapy: A prospective, observational single-center study. Crit. Care 2020, 24, 664. [Google Scholar] [CrossRef]
  221. Corcione, S.; De Nicolò, A.; Lupia, T.; Segala, F.V.; Pensa, A.; Loia, R.C.; Romeo, M.R.; Di Perri, G.; Stella, M.; D’avolio, A.; et al. Observed concentrations of amikacin and gentamycin in the setting of burn patients with gram-negative bacterial infections: Preliminary data from a prospective study. Therapies 2020, 76, 409–414. [Google Scholar] [CrossRef]
  222. Petersson, J.; Giske, C.G.; Eliasson, E. Poor Correlation between Meropenem and Piperacillin Plasma Concentrations and Delivered Dose of Continuous Renal Replacement Therapy. Antimicrob. Agents Chemother. 2021, 65. [Google Scholar] [CrossRef]
  223. Nicolau, D.P.; De Waele, J.; Kuti, J.L.; Caro, L.; Larson, K.B.; Yu, B.; Gadzicki, E.; Zeng, Z.; Rhee, E.G.; Rizk, M.L. Pharmacokinetics and Pharmacodynamics of Ceftolozane/Tazobactam in Critically Ill Patients With Augmented Renal Clearance. Int. J. Antimicrob. Agents 2021, 57, 106299. [Google Scholar] [CrossRef] [PubMed]
  224. Fillâtre, P.; Lemaitre, F.; Nesseler, N.; Schmidt, M.; Besset, S.; Launey, Y.; Maamar, A.; Daufresne, P.; Flecher, E.; Le Tulzo, Y.; et al. Impact of extracorporeal membrane oxygenation (ECMO) support on piperacillin exposure in septic patients: A case–control study. J. Antimicrob. Chemother. 2021, 76, 1242–1249. [Google Scholar] [CrossRef] [PubMed]
  225. Moser, S.; Rehm, S.; Guertler, N.; Hinic, V.; Dräger, S.; Bassetti, S.; Rentsch, K.M.; Sendi, P.; Osthoff, M. Probability of pharmacological target attainment with flucloxacillin in Staphylococcus aureus bloodstream infection: A prospective cohort study of unbound plasma and individual MICs. J. Antimicrob. Chemother. 2021, 76, 1845–1854. [Google Scholar] [CrossRef]
  226. Esteve-Pitarch, E.; Gumucio-Sanguino, V.D.; Cobo-Sacristán, S.; Shaw, E.; Maisterra-Santos, K.; Sabater-Riera, J.; Pérez-Fernandez, X.L.; Rigo-Bonnin, R.; Tubau-Quintano, F.; Carratalà, J.; et al. Continuous Infusion of Piperacillin/Tazobactam and Meropenem in ICU Patients Without Renal Dysfunction: Are Patients at Risk of Underexposure? Eur. J. Drug Metab. Pharmacokinet. 2021, 46, 527–538. [Google Scholar] [CrossRef] [PubMed]
  227. Pařízková, R.; Martínková, J.; Havel, E.; Šafránek, P.; Kaška, M.; Astapenko, D.; Bezouška, J.; Chládek, J.; Černý, V. Additional File 1 of Impact of Cumulative Fluid Balance on the Pharmacokinetics of Extended Infusion Meropenem in Critically Ill Patients with Sepsis. Available online: https://pubmed.ncbi.nlm.nih.gov/34274013/ (accessed on 18 July 2024). [CrossRef]
  228. Liebchen, U.; Paal, M.; Bucher, V.; Vogeser, M.; Irlbeck, M.; Schroeder, I.; Zoller, M.; Scharf, C. Trough concentrations of meropenem and piperacillin during slow extended dialysis in critically ill patients with intermittent and continuous infusion: A prospective observational study. J. Crit. Care 2021, 67, 26–32. [Google Scholar] [CrossRef]
  229. Messiano, C.G.; Junior, R.M.; Pereira, G.O.; Junior, E.M.d.S.; Gomez, D.D.S.; Santos, S.R.C.J. Therapeutic Target Attainment of 3-Hour Extended Infusion of Meropenem in Patients With Septic Burns. Clin. Ther. 2022. [Google Scholar] [CrossRef]
  230. Zoller, M.; Paal, M.; Greimel, A.; Kallee, S.; Vogeser, M.; Irlbeck, M.; Schroeder, I.; Liebchen, U.; Scharf, C. Serum linezolid concentrations are reduced in critically ill patients with pulmonary infections: A prospective observational study. J. Crit. Care 2022, 71, 154100. [Google Scholar] [CrossRef]
  231. Shekar, K.; Abdul-Aziz, M.H.; Cheng, V.; Burrows, F.; Buscher, H.; Cho, Y.-J.; Corley, A.; Diehl, A.; Gilder, E.; Jakob, S.M.; et al. Antimicrobial Exposures in Critically Ill Patients Receiving Extracorporeal Membrane Oxygenation. Am. J. Respir. Crit. Care Med. 2023, 207, 704–720. [Google Scholar] [CrossRef] [PubMed]
  232. Smeets, T.J.; de Geus, H.R.; Rietveld, A.; Rietdijk, W.J.; Koch, B.C.; Endeman, H.; Hunfeld, N.G. Pursuing the Real Vancomycin Clearance during Continuous Renal Replacement Therapy in Intensive Care Unit Patients: Is There Adequate Target Attainment? Blood Purif. 2023, 52, 652–659. [Google Scholar] [CrossRef]
  233. Correia, P.; Launay, M.; Balluet, R.; Gergele, L.; Gauthier, V.; Morel, J.; Beuret, P.; Mariat, C.; Thiery, G.; Ragey, S.P. Towards optimization of ceftazidime dosing in obese ICU patients: The end of the ‘one-size-fits-all’ approach? J. Antimicrob. Chemother. 2023, 78, 2968–2975. [Google Scholar] [CrossRef]
  234. Martin, C.; Lambert, D.; Bruguerolle, B.; Saux, P.; Freney, J.; Fleurette, J.; Meugnier, H.; Gouin, F. Ofloxacin pharmacokinetics in mechanically ventilated patients. Antimicrob. Agents Chemother. 1991, 35, 1582–1585. [Google Scholar] [CrossRef]
  235. Akers, K.S.; Niece, K.L.; Chung, K.K.; Cannon, J.W.; Cota, J.M.; Murray, C.K. Modified Augmented Renal Clearance score predicts rapid piperacillin and tazobactam clearance in critically ill surgery and trauma patients. J. Trauma: Inj. Infect. Crit. Care 2014, 77, S163–S170. [Google Scholar] [CrossRef] [PubMed]
  236. Gomez, D.S.; Sanches-Giraud, C.; Silva, C.V.; Oliveira, A.M.R.R.; da Silva, J.M.; Gemperli, R.; Santos, S.R. Imipenem in burn patients: Pharmacokinetic profile and PK/PD target attainment. J. Antibiot. 2014, 68, 143–147. [Google Scholar] [CrossRef]
  237. Ko, A.; Harada, M.Y.; Barmparas, G.; Jay, J.; Sun, B.J.; Chen, E.; Mehrzadi, D.; Patel, B.; Mason, R.; Ley, E.J. Reducing acute kidney injury due to vancomycin in trauma patients. J. Trauma: Inj. Infect. Crit. Care 2016, 81, 352–357. [Google Scholar] [CrossRef] [PubMed]
  238. Mokline, A.; Gharsallah, L.; Rahmani, I.; Gaies, E.; Tabelsi, S.; A Messadi, A. Pharmacokinetics and pharmacodynamics of Linezolid in burn patients. Ann. Burn. Fire Disasters 2018, 31, 118–121. [Google Scholar]
  239. Lim, S.K.; Lee, S.A.; Kim, C.; Kang, E.; Choi, Y.H.; Park, I. High variability of teicoplanin concentration in patients with continuous venovenous hemodiafiltration. Hemodial. Int. 2019, 23, 69–76. [Google Scholar] [CrossRef] [PubMed]
  240. Kovacevic, T.; Miljkovic, B.; Mikov, M.; Satara, S.S.; Dragic, S.; Momcicevic, D.; Kovacevic, P. The Effect of Hypoalbuminemia on the Therapeutic Concentration and Dosage of Vancomycin in Critically Ill Septic Patients in Low-Resource Countries. Dose-Response 2019, 17. [Google Scholar] [CrossRef]
  241. Wu, C.-C.; Tai, C.H.; Liao, W.-Y.; Wang, C.-C.; Kuo, C.-H.; Lin, S.-W.; Ku, S.-C. Augmented renal clearance is associated with inadequate antibiotic pharmacokinetic/pharmacodynamic target in Asian ICU population: A prospective observational study. Infect. Drug Resist. 2019, ume 12, 2531–2541. [Google Scholar] [CrossRef]
  242. Morbitzer, K.A.; Rhoney, D.H.; Dehne, K.A.; Jordan, J.D. Enhanced renal clearance and impact on vancomycin pharmacokinetic parameters in patients with hemorrhagic stroke. J. Intensive Care 2019, 7, 51. [Google Scholar] [CrossRef]
  243. Breilh, D.; Honore, P.M.; De Bels, D.; Roberts, J.A.; Gordien, J.B.; Fleureau, C.; Dewitte, A.; Coquin, J.; Rozé, H.; Perez, P.; et al. Pharmacokinetics and pharmacodynamics of anti-infective agents during continuous veno-venous hemofiltration in critically ill patients: Lessons learned from an ancillary study of the IVOIRE trial. J. Transl. Intern. Med. 2019, 7, 155–169. [Google Scholar] [CrossRef]
  244. Oliveira, M.S.; Machado, A.S.; Mendes, E.T.; Chaves, L.; Neto, L.V.P.; da Silva, C.V.; Santos, S.R.C.J.; Sanches, C.; Macedo, E.; Levin, A.S. Pharmacokinetic and Pharmacodynamic Characteristics of Vancomycin and Meropenem in Critically Ill Patients Receiving Sustained Low-efficiency Dialysis. Clin. Ther. 2020, 42, 625–633. [Google Scholar] [CrossRef]
  245. Mahmoud, A.A.; Avedissian, S.N.; Al-Qamari, A.; Bohling, T.; Pham, M.; Scheetz, M.H. Pharmacokinetic Assessment of Pre- and Post-Oxygenator Vancomycin Concentrations in Extracorporeal Membrane Oxygenation: A Prospective Observational Study. Clin. Pharmacokinet. 2020, 59, 1575–1587. [Google Scholar] [CrossRef] [PubMed]
  246. Veillette, J.J.; Winans, S.A.; Maskiewicz, V.K.; Truong, J.; Jones, R.N.; Forland, S.C. Pharmacokinetics and Pharmacodynamics of High-Dose Piperacillin–Tazobactam in Obese Patients. Eur. J. Drug Metab. Pharmacokinet. 2021, 46, 385–394. [Google Scholar] [CrossRef] [PubMed]
  247. Gijsen, M.; Dreesen, E.; Van Daele, R.; Annaert, P.; Debaveye, Y.; Wauters, J.; Spriet, I. Pharmacokinetic/Pharmacodynamic Target Attainment Based on Measured versus Predicted Unbound Ceftriaxone Concentrations in Critically Ill Patients with Pneumonia: An Observational Cohort Study. Antibiotics 2021, 10, 557. [Google Scholar] [CrossRef]
  248. Shi, L.; Zhuang, Z.; Duan, L.; Zhu, C.; Xue, H.; Wang, X.; Xu, X.; Yuan, Y.; Shi, L.; Li, J.; et al. Dose Optimization of Teicoplanin for Critically Ill Patients With Renal Dysfunction and Continuous Renal Replacement Therapy: Experience From a Prospective Interventional Study. Front. Pharmacol. 2022, 13, 817401. [Google Scholar] [CrossRef]
  249. Zhao, J.; Fan, Y.; Yang, M.; Liang, X.; Wu, J.; Chen, Y.; Guo, B.; Zhang, H.; Wang, R.; Zhang, F.; et al. Association between Augmented Renal Clearance and Inadequate Vancomycin Pharmacokinetic/Pharmacodynamic Targets in Chinese Adult Patients: A Prospective Observational Study. Antibiotics 2022, 11, 837. [Google Scholar] [CrossRef]
  250. Calov, S.; Munzel, F.; Roehr, A.C.; Frey, O.; Higuita, L.M.S.; Wied, P.; Rosenberger, P.; Haeberle, H.A.; Ngamsri, K.-C. Daptomycin Pharmacokinetics in Blood and Wound Fluid in Critical Ill Patients with Left Ventricle Assist Devices. Antibiotics 2023, 12, 904. [Google Scholar] [CrossRef]
  251. Tikiso, T.; Fuhrmann, V.; König, C.; Jarczak, D.; Iwersen-Bergmann, S.; Kluge, S.; Wicha, S.G.; Grensemann, J. Acute-on-chronic liver failure alters linezolid pharmacokinetics in critically ill patients with continuous hemodialysis: An observational study. Ann. Intensive Care 2023, 13, 83. [Google Scholar] [CrossRef] [PubMed]
  252. Roberts, D.M.; Liu, X.; A Roberts, J.; Nair, P.; Cole, L.; Roberts, M.S.; Lipman, J.; Bellomo, R. Additional File 1 of A multicenter Study on the Effect of Continuous Hemodiafiltration Intensity on Antibiotic Pharmacokinetics. Available online: https://pubmed.ncbi.nlm.nih.gov/25881576/ (accessed on 18 July 2024). [CrossRef]
  253. Scharf, C.; Weinelt, F.; Schroeder, I.; Paal, M.; Weigand, M.; Zoller, M.; Irlbeck, M.; Kloft, C.; Briegel, J.; Liebchen, U. Does the cytokine adsorber CytoSorb® reduce vancomycin exposure in critically ill patients with sepsis or septic shock? a prospective observational study. Ann. Intensive Care 2022, 12, 44. [Google Scholar] [CrossRef]
  254. Wulkersdorfer, B.; Bergmann, F.; Amann, L.; Fochtmann-Frana, A.; Al Jalali, V.; Kurdina, E.; Lackner, E.; Wicha, S.G.; Dorn, C.; Schäfer, B.; et al. Effect of albumin substitution on pharmacokinetics of piperacillin/tazobactam in patients with severe burn injury admitted to the ICU. J. Antimicrob. Chemother. 2023, 79, 262–270. [Google Scholar] [CrossRef]
  255. Shahrami, B.; Najmeddin, F.; Rouini, M.R.; Najafi, A.; Sadeghi, K.; Amini, S.; Khezrnia, S.S.; Sharifnia, H.R.; Mojtahedzadeh, M. Evaluation of Amikacin Pharmacokinetics in Critically Ill Patients with Intra-abdominal Sepsis. Adv. Pharm. Bull. 2019, 10, 114–118. [Google Scholar] [CrossRef] [PubMed]
  256. Simon, P.; Busse, D.; Petroff, D.; Dorn, C.; Ehmann, L.; Hochstädt, S.; Girrbach, F.; Dietrich, A.; Zeitlinger, M.; Kees, F.; et al. Linezolid Concentrations in Plasma and Subcutaneous Tissue are Reduced in Obese Patients, Resulting in a Higher Risk of Underdosing in Critically Ill Patients: A Controlled Clinical Pharmacokinetic Study. J. Clin. Med. 2020, 9, 1067. [Google Scholar] [CrossRef]
  257. Del Bono, V.; Giacobbe, D.R.; Marchese, A.; Parisini, A.; Fucile, C.; Coppo, E.; Marini, V.; Arena, A.; Molin, A.; Martelli, A.; et al. Meropenem for treating KPC-producing Klebsiella pneumoniae bloodstream infections: Should we get to the PK/PD root of the paradox? Virulence 2016, 8, 66–73. [Google Scholar] [CrossRef] [PubMed]
  258. Wu, C.; Zhang, X.; Xie, J.; Li, Q.; He, J.; Hu, L.; Wang, H.; Liu, A.; Xu, J.; Yang, C.; et al. Pharmacokinetic/Pharmacodynamic Parameters of Linezolid in the Epithelial Lining Fluid of Patients With Sepsis. J. Clin. Pharmacol. 2022, 62, 891–897. [Google Scholar] [CrossRef]
  259. Corti, N.; Rudiger, A.; Chiesa, A.; Marti, I.; Jetter, A.; Rentsch, K.; Müller, D.; Béchir, M.; Maggiorini, M. Pharmacokinetics of Daily Daptomycin in Critically Ill Patients Undergoing Continuous Renal Replacement Therapy. Chemotherapy 2013, 59, 143–151. [Google Scholar] [CrossRef] [PubMed]
  260. Corcione, S.; D’avolio, A.; Loia, R.C.; Pensa, A.; Segala, F.V.; De Nicolò, A.; Fatiguso, G.; Romeo, M.; Di Perri, G.; Stella, M.; et al. Pharmacokinetics of meropenem in burn patients with infections caused by Gram-negative bacteria: Are we getting close to the right treatment? J. Glob. Antimicrob. Resist. 2020, 20, 22–27. [Google Scholar] [CrossRef]
  261. Lyu, Y.; Yang, Y.; Li, X.; Peng, M.; He, X.; Zhang, P.; Dong, S.; Wang, W.; Wang, D. Selection of piperacillin/tazobactam infusion mode guided by SOFA score in cancer patients with hospital-acquired pneumonia: A randomized controlled study. Ther. Clin. Risk Manag. 2018, 14, 31–37. [Google Scholar] [CrossRef]
  262. van der Starre, P.J.; Kolz, M.; Lemmens, H.J.; Faix, J.D.; Mitchell, S.; Miller, C. Vancomycin plasma concentrations in cardiac surgery with the use of profound hypothermic circulatory arrest. Eur. J. Cardio-Thoracic Surg. 2010, 38, 741–744. [Google Scholar] [CrossRef]
  263. Triginer, C.; Izquierdo, I.; Fernández, R.; Rello, J.; Torrent, J.; Benito, S.; Net, A. Gentamicin volume of distribution in critically ill septic patients. Intensive Care Med. 1990, 16, 303–306. [Google Scholar] [CrossRef]
  264. Tang, G.J.; Tang, J.J.; Lin, B.S.; Kong, C.W.; Lee, T.Y. Factors affecting gentamicin pharmacokinetics in septic patients. Acta Anaesthesiol. Scand. 1999, 43, 726–730. [Google Scholar] [CrossRef]
  265. Rebuck, J.A.; Fish, D.N.; Abraham, E. Pharmacokinetics of Intravenous and Oral Levofloxacin in Critically Ill Adults in a Medical Intensive Care Unit. Pharmacother. J. Hum. Pharmacol. Drug Ther. 2002, 22, 1216–1225. [Google Scholar] [CrossRef]
  266. Belzberg, H.; Zhu, J.; Cornwell, E.E.; Murray, J.A.; Sava, J.; Salim, A.; Velmahos, G.C.; Gill, M.A. Imipenem Levels Are Not Predictable in the Critically Ill Patient. J. Trauma: Inj. Infect. Crit. Care 2004, 56, 111–117. [Google Scholar] [CrossRef] [PubMed]
  267. Navarro, A.S.; Gandarillas, C.-I.C.; Lerma, F.A.; Menacho, Y.A.; Domínguez-Gil, A. Pharmacokinetics and Pharmacodynamics of Levofloxacin in Intensive Care Patients. Clin. Pharmacokinet. 2005, 44, 627–635. [Google Scholar] [CrossRef]
  268. van Zanten, A.R.; Polderman, K.H.; van Geijlswijk, I.M.; van der Meer, G.Y.; Schouten, M.A.; Girbes, A.R. Ciprofloxacin pharmacokinetics in critically ill patients: A prospective cohort study. J. Crit. Care 2008, 23, 422–430. [Google Scholar] [CrossRef]
  269. Brink, A.; Richards, G.; Schillack, V.; Kiem, S.; Schentag, J. Pharmacokinetics of once-daily dosing of ertapenem in critically ill patients with severe sepsis. Int. J. Antimicrob. Agents 2008, 33, 432–436. [Google Scholar] [CrossRef]
  270. Chapuis, T.M.; Giannoni, E.; A Majcherczyk, P.; Chioléro, R.; Schaller, M.-D.; Berger, M.M.; Bolay, S.; A Décosterd, L.; Bugnon, D.; Moreillon, P. Prospective monitoring of cefepime in intensive care unit adult patients. Crit. Care 2010, 14, R51. [Google Scholar] [CrossRef] [PubMed]
  271. Aubron, C.; Corallo, C.E.; Nunn, M.O.; Dooley, M.J.; Cheng, A.C. Evaluation of the Accuracy of a Pharmacokinetic Dosing Program in Predicting Serum Vancomycin Concentrations in Critically Ill Patients. Ann. Pharmacother. 2011, 45, 1193–1198. [Google Scholar] [CrossRef]
  272. Chung, J.; Oh, J.M.; Cho, E.M.; Jang, H.J.; Hong, S.B.; Lim, C.M.; Koh, Y.S. Optimal Dose of Vancomycin for Treating Methicillin-Resistant Staphylococcus Aureus Pneumonia in Critically Ill Patients. Anaesth. Intensive Care 2011, 39, 1030–1037. [Google Scholar] [CrossRef]
  273. Karnik, N.D.; Sridharan, K.; Jadhav, S.P.; Kadam, P.P.; Naidu, R.K.; Namjoshi, R.D.; Gupta, V.; Gore, M.S.; Surase, P.V.; Mehta, P.R.; et al. Pharmacokinetics of colistin in critically ill patients with multidrug-resistant Gram-negative bacilli infection. Eur. J. Clin. Pharmacol. 2013, 69, 1429–1436. [Google Scholar] [CrossRef] [PubMed]
  274. Koegelenberg, C.F.N.; Nortje, A.; Lalla, U.; Enslin, A.; Irusen, E.M.; Rosenkranz, B.; I Seifart, H.; Bolliger, C.T. The pharmacokinetics of enteral antituberculosis drugs in patients requiring intensive care. South Afr. Med. J. 2013, 103, 394–398. [Google Scholar] [CrossRef]
  275. de Montmollin, E.; Bouadma, L.; Gault, N.; Mourvillier, B.; Mariotte, E.; Chemam, S.; Massias, L.; Papy, E.; Tubach, F.; Wolff, M.; et al. Predictors of insufficient amikacin peak concentration in critically ill patients receiving a 25 mg/kg total body weight regimen. Intensive Care Med. 2014, 40, 998–1005. [Google Scholar] [CrossRef] [PubMed]
  276. Nakamura, A.; Takasu, O.; Sakai, Y.; Sakamoto, T.; Yamashita, N.; Mori, S.; Morita, T.; Nabeta, M.; Hirayu, N.; Yoshiyama, N.; et al. Development of a teicoplanin loading regimen that rapidly achieves target serum concentrations in critically ill patients with severe infections. J. Infect. Chemother. 2015, 21, 449–455. [Google Scholar] [CrossRef] [PubMed]
  277. Abdul-Aziz, M.H.; Lipman, J.; Akova, M.; Bassetti, M.; De Waele, J.J.; Dimopoulos, G.; Dulhunty, J.; Kaukonen, K.-M.; Koulenti, D.; Martin, C.; et al. Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill patients associated with improved pharmacokinetic/pharmacodynamic and patient outcomes? An observation from the Defining Antibiotic Levels in Intensive care unit patients (DALI) cohort. J. Antimicrob. Chemother. 2015, 71, 196–207. [Google Scholar] [CrossRef] [PubMed]
  278. Zander, J.; Döbbeler, G.; Nagel, D.; Maier, B.; Scharf, C.; Huseyn-Zada, M.; Jung, J.; Frey, L.; Vogeser, M.; Zoller, M. Piperacillin concentration in relation to therapeutic range in critically ill patients—A prospective observational study. Crit. Care 2016, 20, 79. [Google Scholar] [CrossRef]
  279. Allou, N.; Charifou, Y.; Augustin, P.; Galas, T.; Valance, D.; Corradi, L.; Martinet, O.; Vandroux, D.; Allyn, J. A study to evaluate the first dose of gentamicin needed to achieve a peak plasma concentration of 30 mg/l in patients hospitalized for severe sepsis. Eur. J. Clin. Microbiol. Infect. Dis. 2016, 35, 1187–1193. [Google Scholar] [CrossRef]
  280. Obara, V.Y.; Zacas, C.P.; Carrilho, C.M.D.d.M.; Delfino, V.D.A. Currently used dosage regimens of vancomycin fail to achieve therapeutic levels in approximately 40% of intensive care unit patients. Rev. Bras. Ter. Intensive 2016, 28, 380–386. [Google Scholar] [CrossRef]
  281. Bakke, V.; Sporsem, H.; Von der Lippe, E.; Nordøy, I.; Lao, Y.; Nyrerød, H.C.; Sandvik, L.; Hårvig, K.R.; Bugge, J.F.; Helset, E. Vancomycin levels are frequently subtherapeutic in critically ill patients: A prospective observational study. Acta Anaesthesiol. Scand. 2017, 61, 627–635. [Google Scholar] [CrossRef]
  282. Ruiz, J.; Ramirez, P.; Company, M.J.; Gordon, M.; Villarreal, E.; Concha, P.; Aroca, M.; Frasquet, J.; Remedios-Marqués, M.; Castellanos-Ortega. Impact of amikacin pharmacokinetic/pharmacodynamic index on treatment response in critically ill patients. J. Glob. Antimicrob. Resist. 2018, 12, 90–95. [Google Scholar] [CrossRef]
  283. Burger, R.; Guidi, M.; Calpini, V.; Lamoth, F.; Decosterd, L.; Robatel, C.; Buclin, T.; Csajka, C.; Marchetti, O. Effect of renal clearance and continuous renal replacement therapy on appropriateness of recommended meropenem dosing regimens in critically ill patients with susceptible life-threatening infections. J. Antimicrob. Chemother. 2018, 73, 3413–3422. [Google Scholar] [CrossRef]
  284. Huang, Y.; Yang, J.; Xie, J.; Liu, L.; Liu, S.; Guo, F.; Qiu, H.; Yang, Y. Association Between Pathophysiology and Volume of Distribution Among Patients With Sepsis or Septic Shock Treated With Imipenem: A Prospective Cohort Study. J. Infect. Dis. 2020, 221, S272–S278. [Google Scholar] [CrossRef]
  285. Helset, E.; Nordøy, I.; Sporsem, H.; Bakke, V.D.; Bugge, J.F.; Gammelsrud, K.W.; Zucknick, M.; Lippe, E.; von der Lippe, E. Factors increasing the risk of inappropriate vancomycin therapy in ICU patients: A prospective observational study. Acta Anaesthesiol. Scand. 2020, 64, 1295–1304. [Google Scholar] [CrossRef]
  286. Ram, K.; Sheikh, S.; Bhati, R.K.; Tripathi, C.D.; Suri, J.C.; Meshram, G.G. Steady-state pharmacokinetic and pharmacodynamic profiling of colistin in critically ill patients with multi-drug-resistant gram-negative bacterial infections, along with differences in clinical, microbiological and safety outcome. Basic Clin. Pharmacol. Toxicol. 2021, 128, 128–140. [Google Scholar] [CrossRef] [PubMed]
  287. Ren, J.; Hou, Y.; Li, J.; Gao, Y.; Li, R.; Jin, X.; Zhang, J.; Wang, X.; Wang, G. An evaluation on the association of vancomycin trough concentration with mortality in critically ill patients: A multicenter retrospective study. Clin. Transl. Sci. 2021, 14, 1780–1790. [Google Scholar] [CrossRef]
  288. Niibe, Y.; Suzuki, T.; Yamazaki, S.; Uchida, M.; Suzuki, T.; Takahashi, N.; Hattori, N.; Nakada, T.-A.; Ishii, I. Identification of factors affecting meropenem pharmacokinetics in critically ill patients: Impact of inflammation on clearance. J. Infect. Chemother. 2022, 28, 532–538. [Google Scholar] [CrossRef] [PubMed]
  289. Mitton, B.; Paruk, F.; Gous, A.; Chausse, J.; Milne, M.; Becker, P.; Said, M. Evaluating the usefulness of the estimated glomerular filtration rate for determination of imipenem dosage in critically ill patients. South Afr. Med J. 2022, 112, 765–768. [Google Scholar] [CrossRef]
  290. Helset, E.; Cheng, V.; Sporsem, H.; Thorstensen, C.; Nordøy, I.; Gammelsrud, K.W.; Hanssen, G.; Ponzi, E.; Lipman, J.; von der Lippe, E. Meropenem pharmacokinetic/pharmacodynamic target attainment and clinical response in ICU patients: A prospective observational study. Acta Anaesthesiol. Scand. 2024, 68, 502–511. [Google Scholar] [CrossRef]
  291. Lejbman, I.A.; Torisson, G.; Resman, F.; Sjövall, F. Beta-lactam antibiotic concentrations in critically ill patients with standard and adjusted dosages: A prospective observational study. Acta Anaesthesiol. Scand. 2024, 68, 530–537. [Google Scholar] [CrossRef]
  292. Beckhouse, M.J.; Whyte, I.M.; Byth, P.L.; Napier, J.C.; Smith, A.J. Altered Aminoglycoside Pharmacokinetics in the Critically Ill. Anaesth. Intensive Care 1988, 16, 418–422. [Google Scholar] [CrossRef] [PubMed]
  293. Zeitlinger, B.S.; Zeitlinger, M.; Leitner, I.; Müller, M.; Joukhadar, C. Clinical Scoring System for the Prediction of Target Site Penetration of Antimicrobials in Patients with Sepsis. Clin. Pharmacokinet. 2007, 46, 75–83. [Google Scholar] [CrossRef]
  294. Cristallini, S.; Hites, M.; Kabtouri, H.; Roberts, J.A.; Beumier, M.; Cotton, F.; Lipman, J.; Jacobs, F.; Vincent, J.-L.; Creteur, J.; et al. New Regimen for Continuous Infusion of Vancomycin in Critically Ill Patients. Antimicrob. Agents Chemother. 2016, 60, 4750–4756. [Google Scholar] [CrossRef]
  295. Ehmann, L.; Zoller, M.; Minichmayr, I.K.; Scharf, C.; Maier, B.; Schmitt, M.V.; Hartung, N.; Huisinga, W.; Vogeser, M.; Frey, L.; et al. Role of renal function in risk assessment of target non-attainment after standard dosing of meropenem in critically ill patients: A prospective observational study. Crit. Care 2017, 21, 263. [Google Scholar] [CrossRef] [PubMed]
  296. Coste, A.; Deslandes, G.; Jalin, L.; Corvec, S.; Caillon, J.; Boutoille, D.; Grégoire, M.; Bretonnière, C. PK/PD targets of amikacin and gentamicin in ICU patients. Med. Et Mal. Infect. 2019, 50, 709–714. [Google Scholar] [CrossRef]
  297. Logre, E.; Enser, M.; Tanaka, S.; Dubert, M.; Claudinon, A.; Grall, N.; Mentec, H.; Montravers, P.; Pajot, O. Amikacin pharmacokinetic/pharmacodynamic in intensive care unit: A prospective database. Ann. Intensive Care 2020, 10, 75. [Google Scholar] [CrossRef]
  298. De Corte, T.; Verhaeghe, J.; Dhaese, S.; Van Vooren, S.; Boelens, J.; Verstraete, A.G.; Stove, V.; Ongenae, F.; De Bus, L.; Depuydt, P.; et al. Pathogen-based target attainment of optimized continuous infusion dosing regimens of piperacillin-tazobactam and meropenem in surgical ICU patients: A prospective single center observational study. Ann. Intensive Care 2023, 13, 35. [Google Scholar] [CrossRef]
  299. Guilhaumou, R.; Chevrier, C.; Setti, J.L.; Jouve, E.; Marsot, A.; Julian, N.; Blin, O.; Simeone, P.; Lagier, D.; Mokart, D.; et al. β-Lactam Pharmacokinetic/Pharmacodynamic Target Attainment in Intensive Care Unit Patients: A Prospective, Observational, Cohort Study. Antibiotics 2023, 12, 1289. [Google Scholar] [CrossRef]
  300. El-Haffaf, I.; Marsot, A.; Hachemi, D.; Pesout, T.; Williams, V.; Smith, M.-A.; Albert, M.; Williamson, D. Exposure levels and target attainment of piperacillin/tazobactam in adult patients admitted to the intensive care unit: A prospective observational study. Can. J. Anaesth. 2024, 71, 511–522. [Google Scholar] [CrossRef]
  301. Campassi, M.L.; Gonzalez, M.C.; Masevicius, F.D.; Vazquez, A.R.; Moseinco, M.; Navarro, N.C.; Previgliano, L.; Rubatto, N.P.; Benites, M.H.; Estenssoro, E.; et al. Augmented renal clearance in critically ill patients: Incidence, associated factors and effects on vancomycin treatment. Rev. Bras. Ter. Intensive 2014, 26, 13–20. [Google Scholar] [CrossRef]
  302. Zeng, J.; Leng, B.; Guan, X.; Jiang, S.; Xie, M.; Zhu, W.; Tang, Y.; Zhang, L.; Sha, J.; Wang, T.; et al. Comparative pharmacokinetics of polymyxin B in critically ill elderly patients with extensively drug-resistant gram-negative bacteria infections. Front. Pharmacol. 2024, 15, 1347130. [Google Scholar] [CrossRef] [PubMed]
  303. Frazee, E.; Rule, A.D.; Lieske, J.C.; Kashani, K.B.; Barreto, J.N.; Virk, A.; Kuper, P.J.; Dierkhising, R.A.; Leung, N. Cystatin C–Guided Vancomycin Dosing in Critically Ill Patients: A Quality Improvement Project. Am. J. Kidney Dis. 2017, 69, 658–666. [Google Scholar] [CrossRef]
  304. You, X.; Dai, Q.; Hu, J.; Yu, M.; Wang, X.; Weng, B.; Cheng, L.; Sun, F. Therapeutic drug monitoring of imipenem/cilastatin and meropenem in critically ill adult patients. J. Glob. Antimicrob. Resist. 2024, 36, 252–259. [Google Scholar] [CrossRef]
  305. Huang, F.; Cao, W.-X.; Yan, Y.-Y.; Mao, T.-T.; Wang, X.-W.; Huang, D.; Qiu, Y.-S.; Lu, W.-J.; Li, D.-J.; Zhuang, Y.-G. Influence of continuous renal replacement therapy on the plasma concentration of tigecycline in patients with septic shock: A prospective observational study. Front. Pharmacol. 2023, 14, 1118788. [Google Scholar] [CrossRef]
  306. Poli, E.C.; Simoni, C.; André, P.; Buclin, T.; Longchamp, D.; Perez, M.-H.; Ferry, T.; Schneider, A.G. Clindamycin clearance during Cytosorb® hemoadsorption: A case report and pharmacokinetic study. Int. J. Artif. Organs 2019, 42, 258–262. [Google Scholar] [CrossRef] [PubMed]
  307. Dimski, T.; Brandenburger, T.; MacKenzie, C.; Kindgen-Milles, D. Elimination of glycopeptide antibiotics by cytokine hemoadsorption in patients with septic shock: A study of three cases. Int. J. Artif. Organs 2020, 43, 753–757. [Google Scholar] [CrossRef] [PubMed]
  308. Köhler, T.; Schwier, E.; Kirchner, C.; Winde, G.; Henzler, D.; Eickmeyer, C. Hemoadsorption with CytoSorb® and the early course of linezolid plasma concentration during septic shock. J. Artif. Organs 2021, 25, 86–90. [Google Scholar] [CrossRef]
  309. Liebchen, U.; Scharf, C.; Zoller, M.; Weinelt, F.; Kloft, C.; the CytoMero Collaboration Team; Michelet, R.; Schroeder, I.; Paal, M.; Vogeser, M.; et al. No clinically relevant removal of meropenem by cytokine adsorber CytoSorb® in critically ill patients with sepsis or septic shock. Intensive Care Med. 2021, 47, 1332–1333. [Google Scholar] [CrossRef]
Antibiotics 13 00801 g001
Figure 1. Search results. PRISMA Flow Diagram.
Figure 1. Search results. PRISMA Flow Diagram.
Antibiotics 13 00801 g001
Antibiotics 13 00801 g002
Figure 2. Number of studies with the ten most relevant risk factors. (a) For risk factors. (b) For antibiotics.
Figure 2. Number of studies with the ten most relevant risk factors. (a) For risk factors. (b) For antibiotics.
Antibiotics 13 00801 g002
Antibiotics 13 00801 g003
Figure 3. Details of variables included renal function, hepatic function, weight, and renal replacement therapy as risk factors. AKI: Acute kidney injury, ARC: Augmented renal clearance, BMI: body mass index, BSA: body surface area, CRRT: continuous renal replacement therapy, SLED: sustained low-efficiency dialysis.
Figure 3. Details of variables included renal function, hepatic function, weight, and renal replacement therapy as risk factors. AKI: Acute kidney injury, ARC: Augmented renal clearance, BMI: body mass index, BSA: body surface area, CRRT: continuous renal replacement therapy, SLED: sustained low-efficiency dialysis.
Antibiotics 13 00801 g003
Antibiotics 13 00801 g004
Figure 4. Risk factors with different relevance versus those analyzed, represented on two different scales. The size of the ball indicates the number of patients analyzed. ECMO: Extracorporeal Membrane Oxygenation; Hb: Hemoglobin; Ht Hematocrit.
Figure 4. Risk factors with different relevance versus those analyzed, represented on two different scales. The size of the ball indicates the number of patients analyzed. ECMO: Extracorporeal Membrane Oxygenation; Hb: Hemoglobin; Ht Hematocrit.
Antibiotics 13 00801 g004
Table 1. Characteristics of the studies.
Table 1. Characteristics of the studies.
Number of StudiesNumber of Patients
Number of CentersUnicentric22211,342
Multicentric3410,157
Study DesignProspective observational24621,089
RCT10411
Outcome typeExposure11315,702
PKPOP1014628
PK421170
Type of analysisSubgroup1024827
Subgroup and PKPOP622093
Risk factor, no PKPOP5312,045
Risk factor and PKPOP392535
Distribution of studies by areaEurope1257036
North America399303
East Asia392707
Oceania21700
South Asia9335
South America8689
Africa5187
More than one area5493
Middle East143
Publication year1988–1996 (9 years)5117
1997–2005 (9 years)16445
2006–2014 (9 years)431997
2015–2024 (9.2 years)19218,941
Antibiotic group evaluatedMore than two antibiotic groups6256
Aminoglycosides201767
Antituberculous110
Beta lactams1377395
Daptomycin4101
Linezolid23643
Polimyxins7207
Quinolones11258
Teicoplanin7416
Tigecycline489
Vancomycin4210,602
PK: Refers to studies that have investigated how risk factors affect pharmacokinetic variables; PKPOP: Refers to studies that have investigated the impact of risk factors as covariates in a population model.
Table 2. Number and Percentage of Studies that Concluded a Risk Factor as a Determinant, and the number and percentage that Analyzed Each Risk factor, Classified by Antibiotic Group and Outcome.
Table 2. Number and Percentage of Studies that Concluded a Risk Factor as a Determinant, and the number and percentage that Analyzed Each Risk factor, Classified by Antibiotic Group and Outcome.
Antibiotic GroupTotal
Risk Factor/Primary OutcomeAmino-GlycosidesB-Lactams 2B-Lactams VancomycinDaptomycinLinezolid 2PolymyxinsQuinoloneTeicoplaninTigecyclineVancomycinOther 1Number of Studies
Age1/10 (10.0)9/80 (11.3)0/1 (0)0/2 (0)0/11 (0)1/4 (25.0)2/9 (22.2)1/4 (25.0)0/3(0)3/16 (18.8)017/139 (12.2)
Exposure1/5 (20.0)3/20 (15.0)0/1 (0)0/1 (0)0/1 (0)1/3 (33.3)1/2 (50.0)1/2(50.0)01/6 (16.7)08/41 (19.5)
PK/PKPOP0/5 (0)6/60 (10.0)00/1 (0)0/10 (0)0/1 (0)1/7 (14.3)0/2 (0)0/3(0)2/10 (20.0)09/98 (9.2)
Sex0/8 (0)4/68 (5.9)00/2 (0)0/8 (0)0/3 (0)2/6 (33.3)0/3 (0)0/3 (0)0/15 (0)06/115 (5.2)
Exposure0/4 (0)1/15 (6.7)00/1 (0)00/2 (0)2/2 (100)0/1 (0)00/6 (0)03/31 (9.7)
PK/PKPOP0/4 (0)3/53 (5.7)00/1 (0)0/8 (0)0/1 (0)0/4 (0)0/2 (0)0/3 (0)0/9 (0)03/84 (3.6)
Weight5/7 (71.4)30/88 (34.1)0/10/2 (0)6/12 (50.0)2/6 (33.3)4/8 (50.0)1/3 (33.3)2/3 (66.7)8/17 (47.1)057/146 (39.0)
Exposure1/2 (50.0)6/22 (27.3)0/10/1 (0)1/2 (50.0)2/4 (50.0)1/2 (50.0)0/1 (0)03/5 (60.0)014/40 (35.0)
PK/PKPOP4/5 (80.0)24/66 (36.4)00/1 (0)5/10 (50.0)0/2 (0)3/6 (50.0)1/2 (50.0)2/3 (66.7)5/12 (41.7)043/106 (40.6)
Renal function8/11 (72.7)74/98 (75.5)2/2 (100)1/2 (50.0)8/13 (61.5)3/5 (60.0)6/8 (75.0)3/4 (75.0)0/2 (0)18/24 (75.0)2/2 (100)125/170 (73.5)
Exposure4/5 (80.0)24/30 (80.0)2/2 (100)0/1 (0)1/2 (50.0)2/3 (66.7)2/3 (66.7)1/1 (100)010/12 (83.3)2/2 (100)48/61 (78.7)
PK/PKPOP4/6 (66.7)50/68 (73.5)01/1 (100)7/11 (63.6)1/2 (50.0)4/5 (80.0)2/3 (66.7)0/2 (0)8/12 (66.7)077/109 (70.6)
Renal replacement3/7 (42.9)22/50 (44.0)2/3 (66.7)3/3 (100)5/14 (35.7)2/2 (100)0/5 (0)3/5 (60.0)1/3 (33.3)13/17 (76.5)3/3 (100)57/110 (51.8)
Exposure1/4 (25.0)9/21 (42.9)1/2 (50.0)1/1 (100)2/4 (50.0)1/1 (100)02/2 (100)1/1 (100)7/9 (77.8)1/1 (100)26/45 (57.8)
PK/PKPOP2/3 (66.7)13/29 (44.8)1/1 (100)2/2 (100)3/10 (30.0)1/1 (100)0/5 (0)1/3 (33.3)0/2 (0)6/8 (75.0)2/2 (100)31/65 (47.7)
Protein or albumin1/4 (25.0)10/49 (20.4)0/1 (0)0/1 (0)0/2 (0)1/4 (25.0)0/1 (0)1/2 (50.0)0/2 (0)2/4 (50.0)015/70 (21.4)
Exposure0/2 (0)1/10 (10.0)0/1 (0)001/2 (50.0)01/1 (100)01/1 (100)04/17 (23.5)
PK/PKPOP1/2 (50.0)9/39 (23.1)00/1 (0)0/2 (0)0/2 (0)0/1 (0)0/1 (0)0/2 (0)1/3 (33.3)011/53 (20.8)
APACHE or SAPS2/6 (33.3)5/46 (10.9)0/1 (0)0/1 (0)0/6 (0)0/2 (0)1/3 (33.3)1/2 (50.0)0/1 (0)1/11 (9.1)1/2 (50.0)11/81 (13.6)
Exposure2/4 (50.0)3/14 (21.4)0/1 (0)00/1 (0)0/1 (0)01/1 (100)01/6 (16.7)1/2 (50.0)8/30 (26.7)
PK/PKPOP0/2 (0)2/32 (6.3)00/1 (0)0/5 (0)0/1 (0)1/3 (33.3)0/1 (0)0/1 (0)0/5 (0)03/51 (5.9)
SOFA score2/5 (40.0)5/46 (10.9)1/1 (100)01/5 (20.0)0/2 (0)1/3 (33.3)00/1 (0)1/10 (10.0)0/1 (0)11/74 (14.9)
Exposure2/3 (66.7)4/13 (30.8)1/1 (100)000/2 (0)1/1 (100)000/4 (0)0/1 (0)8/25 (32.0)
PK/PKPOP0/2 (0)1/33 (3.0)001/5 (20.0)00/2 (0)00/1 (0)1/6 (16.7)03/49 (6.1)
Hepatic function1/3 (33.3)1/23 (4.3)00/1 (0)5/8 (62.5)0/3 (0)2/6 (33.3)01/1 (100)0/3 (0)1/1 (100)11/49 (22.4)
Exposure1/2 (50.0)1/3 (33.3)0000/2 (0)0/2 (0)000/1 (0)1/1 (100)3/11 (27.3)
PK/PKPOP0/1 (0)0/20 (0)00/1 (0)5/8 (62.5)0/1 (0)2/4 (50.0)01/1 (100)0/2 (0)08/38 (21.1)
Sepsis/shock1/6 (16.7)7/39 (17.9)001/2 (50.0)00/3 (0)002/11 (18.2)1/2 (50.0)12/63 (19.0)
Exposure0/3 (0)3/13 (23.1)001/1 (100)00/1 (0)002/7 (28.6)1/2 (50.0)7/27 (25.9)
PK/PKPOP1/3 (33.3)4/26 (15.4)000/1 (0)00/2 (0)000/4 (0)05/36 (13.9)
Admission
Diagnosis		0/1 (0)1/17 (5.9)0/1 (0)0/1 (0)1/2 (50.0)000/1 (0)00/7 (0)02/30 (6.7)
Exposure0/1 (0)1/6 (16.7)0/1 (0)0/1 (0)0/1 (0)000/1 (0)00/4 (0)01/15 (6.7)
PK/PKPOP00/11 (0)001/1 (100)00000/3 (0)01/15 (6.7)
Trauma1/1 (100)3/5 (60.0)00000001/3 (33.3)05/9 (55.6)
Exposure1/1 (100)0/2 (0)00000001/3 (33.3)02/6 (33.3)
PK/PKPOP03/3 (100)0000000003/3 (100)
Burn2/2 (100)6/9 (66.7)000/1 (0)00000/1 (0)08/13 (61.5)
Exposure1/1 (100)5/6 (83.3)000/1 (0)0000006/8 (75.0)
PK/PKPOP1/1 (100)1/3 (33.3)00000000/1 (0)02/5 (40.0)
ECMO1/2 (50.0)6/14 (42.9)00/1 (0)2/2 (100)00/2 (0)00/1 (0)1/2 (50.0)2/2 (100)11/25 (44.0)
Exposure0/1 (0)1/5 (20.0)00/1 (0)2/2 (100)00001/1 (100)2/2 (100)5/11 (45.5)
PK/PKPOP1/1 (100)5/9 (55.6)00000/2 (0)00/1 (0)0/1 (0)06/14 (42.9)
Mechanical
ventilation		0/4 (0)1/14 (7.1)00001/1 (100)001/5 (20.0)03/24 (12.5)
Exposure0/3 (0)0/4 (0)00000001/4 (25.0)01/11 (9.1)
PK/PKPOP0/1 (0)1/10 (10.0)00001/1 (100)000/1 (0)02/13 (15.4)
pH parameters01/3 (33.3)001/1 (100)01/1 (100)0/1 (0)001/1 (100)4/7 (57.1)
Exposure00000000/1 (0)001/1 (100)1/2 (50.0)
PK/PKPOP01/3 (33.3)001/1 (100)01/1 (100)00003/5 (60.0)
Acute reactants1/3 (33.3)3/19 (15.8)00/1 (0)0/1 (0)000/1 (0)0/1 (0)0/2 (0)04/28 (14.3)
Exposure1/2 (50.0)1/4 (25.0)000000/1 (0)00/1 (0)02/8 (25.0)
PK/PKPOP0/1 (0)2/15 (13.3)00/1 (0)0/1 (0)0000/1 (0)0/1 (0)02/20 (10.0)
Hemoglobin/hematocrit0/2 (0)1/7 (14.3)00/2 (0)0/1 (0)1/1 (100)0000/1 (0)02/14 (14.3)
Exposure0/1 (0)0/1 (0)00/1 (0)00000000/3 (0)
PK/PKPOP0/1 (0)1/6 (16.7)00/1 (0)0/1 (0)1/1 (100)0000/1 (0)02/11 (18.2)
Fluid balance1/4 (25.0)2/15 (13.3)0/1 (0)0000/2 (0)00/2 (0)0/2 (0)03/26 (11.5)
Exposure0/3 (0)1/3 (33.3)0/1 (0)0000/1 (0)000/1 (0)01/9 (11.1)
PK/PKPOP1/1 (100)1/12 (8.3)00000/1 (0)00/2 (0)0/1 (0)02/17 (11.8)
Comorbidities0/4 (0)3/14 (21.4)00/1 (0)0/1 (0)0/1 (0)0/2 (0)001/6 (16.7)0/1 (0)4/29 (13.8)
Exposure0/4 (0)1/6 (16.7)00/1 (0)00/1 (0)0001/2 (50.0)0/1 (0)2/15 (13.3)
PK/PKPOP02/8 (25.0)000/1 (0)00/2 (0)000/4 (0)02/14 (14.3)
Comedication0/1 (0)0/10 (0)01/1 (100)00/2 (0)1/2 (50.0)000/3 (0)0/1 (0)2/20 (10.0)
Exposure0/1 (0)0/7 (0)01/1 (100)00/1 (0)0000/1 (0)0/1 (0)1/12 (8.3)
PK/PKPOP00/3 (0)0000/1 (0)1/2 (50.0)000/2 (0)01/8 (12.5)
Site of infection1/3 (33.3)3/21 (14.3)00/1 (0)1/4 (25.0)0/2 (0)0/2 (0)0/1 (0)00/3 (0)05/37 (13.5)
Exposure0/1 (0)3/9 (33.3)00/1 (0)1/2 (50.0)0/1 (0)0/1 (0)0/1 (0)00/1 (0)04/17 (23.5)
PK/PKPOP1/2 (50.0)0/12 (0)000/2 (0)0/1 (0)0/1 (0)000/2 (0)01/20 (5.0)
ECMO: Extracorporeal membrane oxygenation. PK: Studies that have investigated how risk factors affect pharmacokinetic variables; PKPOP: Studies that have investigated the impact of risk factors as covariates in a population model. 1 Other includes studies with more than two groups of antibiotics and one study on antitubercular agents. 2 A study that evaluated linezolid and beta-lactams together, this has been counted as two studies.
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Gras-Martín, L.; Plaza-Diaz, A.; Zarate-Tamames, B.; Vera-Artazcoz, P.; Torres, O.H.; Bastida, C.; Soy, D.; Ruiz-Ramos, J. Risk Factors Associated with Antibiotic Exposure Variability in Critically Ill Patients: A Systematic Review. Antibiotics 2024, 13, 801. https://doi.org/10.3390/antibiotics13090801

AMA Style

Gras-Martín L, Plaza-Diaz A, Zarate-Tamames B, Vera-Artazcoz P, Torres OH, Bastida C, Soy D, Ruiz-Ramos J. Risk Factors Associated with Antibiotic Exposure Variability in Critically Ill Patients: A Systematic Review. Antibiotics. 2024; 13(9):801. https://doi.org/10.3390/antibiotics13090801

Chicago/Turabian Style

Gras-Martín, Laura, Adrián Plaza-Diaz, Borja Zarate-Tamames, Paula Vera-Artazcoz, Olga H. Torres, Carla Bastida, Dolors Soy, and Jesús Ruiz-Ramos. 2024. "Risk Factors Associated with Antibiotic Exposure Variability in Critically Ill Patients: A Systematic Review" Antibiotics 13, no. 9: 801. https://doi.org/10.3390/antibiotics13090801

APA Style

Gras-Martín, L., Plaza-Diaz, A., Zarate-Tamames, B., Vera-Artazcoz, P., Torres, O. H., Bastida, C., Soy, D., & Ruiz-Ramos, J. (2024). Risk Factors Associated with Antibiotic Exposure Variability in Critically Ill Patients: A Systematic Review. Antibiotics, 13(9), 801. https://doi.org/10.3390/antibiotics13090801

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop