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Antibiotics
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Antibiotic Usage in Acute Situations
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Antibiotic Usage in Acute Situations

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Pharmacokinetics and Pharmacodynamics of Drugs".

Deadline for manuscript submissions: closed (28 February 2022) | Viewed by 55527

Special Issue Editors

Prof. Dr. Jeffrey Lipman

grade E-Mail Website
Guest Editor
1. Jamieson Trauma Institute, Royal Brisbane and Women’s Hospital, Brisbane, QLD 4029, Australia
2. The University of Queensland Centre for Clinical Research, Brisbane, QLD 4029, Australia
Interests: antibiotic administration (particularly pharmacokinetics); pharmacodynamics; clinical trials
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Jason Roberts

E-Mail Website
Guest Editor
UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, QLD 4102, Australia
Interests: critical care; communicable diseases

Special Issue Information

Dear Colleagues,

Antibiotics kill bacteria, depending on how much of the drug reaches and eliminates the susceptible bacteria.

Whenever I prescribe an antibiotic, two issues come to mind.

Firstly, the “O’Neil report”, which suggested that by 2050, 10 million lives a year and a cumulative 100 trillion USD of economic output will be at risk due to the rise of drug-resistant infections if proactive solutions are not found to slow down the rise of drug resistance. It proposed that, by then, more patients will die from resistant infections than from cancer.

The other statement that I am often cognisant of is that attributed to Einstein: doing the same thing over and over and expecting different results is the definition of insanity.

Putting these thoughts into context, we should be using antibiotics when appropriate, at the appropriate dose. The unnecessary use of antibiotics not only subjects patients to drug side-effects, it drives bacterial resistance. Inappropriate dosing allows for bacterial growth, with concomitant poor outcomes. 

Keeping these issues in mind, within the acute setting of the Intensive Care Unit, each day, we grapple with various decisions: firstly, when to start antibiotics, i.e., most of our patients will have a temperature and raised white blood cell count, and secondly, how to dose each patient appropriately. 

The syndromes of inflammation in ICU are often difficult to differentiate from infections. In this edition of Antibiotics, a number of manuscripts will describe these differences and shed light on not only when to use antibiotics, but when not to use such important drugs unnecessarily. The second section of the edition concentrates on the appropriate dosing of antibiotics in acute settings, getting enough of the drug to the site of the proposed infection.

Prof. Dr. Jeffrey Lipman
Prof. Dr. Jason Roberts
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • antibiotics
  • pharmacokinetics
  • pharmacodynamics
  • infection
  • critical care

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Published Papers (10 papers)

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Research

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8 pages, 495 KiB  
Article
Predictor of Early Administration of Antibiotics and a Volume Resuscitation for Young Infants with Septic Shock
by Osamu Nomura, Takateru Ihara, Yoshihiko Morikawa, Hiroshi Sakakibara, Yuho Horikoshi and Nobuaki Inoue
Antibiotics 2021, 10(11), 1414; https://doi.org/10.3390/antibiotics10111414 - 19 Nov 2021
Cited by 3 | Viewed by 2295
Abstract
(1) Background: It is critical to administer antibiotics and fluid bolus within 1 h of recognizing sepsis in pediatric patients. This study aimed to identify the predictor of the successful completion of a 1-h sepsis bundle for infants with suspected sepsis. (2) Methods: [...] Read more.
(1) Background: It is critical to administer antibiotics and fluid bolus within 1 h of recognizing sepsis in pediatric patients. This study aimed to identify the predictor of the successful completion of a 1-h sepsis bundle for infants with suspected sepsis. (2) Methods: This is an observational study using a prospective registry including febrile young infants (aged < 90 days) who visited a pediatric emergency department with a core body temperature of 38.0 °C or higher and 36.0 °C or lower. Univariate and logistic regression analyses were conducted to determine the predictor (s) of successful sepsis bundle completion. (3) Results: Of the 323 registered patients, 118 patients with suspected sepsis were analyzed, and 38 patients (32.2%) received a bundle-compliant treatment. Among potential variables, such as age, sex, and vital sign parameters, the logistic regression analysis showed that heart rate (odds ratio: OR 1.02; 95% confidence interval: 1.00–1.04) is a significant predictor of the completion of a 1-h sepsis bundle. (4) Conclusions: We found that tachycardia facilitated the sepsis recognition and promoted the successful completion of a 1-h sepsis bundle for young infants with suspected septic shock and a possible indicator for improving the quality of the team-based sepsis management. Full article
(This article belongs to the Special Issue Antibiotic Usage in Acute Situations)
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12 pages, 985 KiB  
Article
The Utility of Bedside Assessment Tools and Associated Factors to Avoid Antibiotic Overuse in an Urban PICU of a Diarrheal Disease Hospital in Bangladesh
by Farzana Afroze, Md. Tanveer Faruk, Mehnaz Kamal, Farhad Kabir, Monira Sarmin, Sharifuzzaman, Mithun Chakraborty, Md. Rezaul Hossain, Shamima Sharmin Shikha, Visnu Pritom Chowdhury, Md. Zahidul Islam, Tahmeed Ahmed and Mohammod Jobayer Chisti
Antibiotics 2021, 10(10), 1255; https://doi.org/10.3390/antibiotics10101255 - 15 Oct 2021
Cited by 1 | Viewed by 3270
Abstract
Background: Antibiotic exposure in the pediatric intensive care unit (PICU) is very high, although 50% of all antibiotics may be unnecessary. We aimed to determine the utility of simple bedside screening tools and predicting factors to avoid antibiotic overuse in the ICU among [...] Read more.
Background: Antibiotic exposure in the pediatric intensive care unit (PICU) is very high, although 50% of all antibiotics may be unnecessary. We aimed to determine the utility of simple bedside screening tools and predicting factors to avoid antibiotic overuse in the ICU among children with diarrhea and critical illness. Methods: We conducted a retrospective, single-center, case-control study that included children aged 2–59 months who were admitted to PICU with diarrhea and critical illness between 2017 and 2020. Results: We compared young children who did not receive antibiotics (cases, n = 164) during ICU stay to those treated with antibiotics (controls, n = 346). For predicting the ‘no antibiotic approach’, the sensitivity of a negative quick Sequential Organ Failure Assessment (qSOFA) was similar to quick Pediatric Logistic Organ Dysfunction-2 (qPELOD-2) and higher than Systemic Inflammatory Response Syndrome (SIRS). A negative qSOFA or qPELOD-2 score calculated during PICU admission is superior to SIRS to avoid antibiotic overuse in under-five children. The logistic regression analysis revealed that cases were more often older and independently associated with hypernatremia. Cases less often had severe underweight, altered mentation, age-specific fast breathing, lower chest wall in-drawing, adventitious sound on lung auscultation, abdominal distension, developmental delay, hyponatremia, hypocalcemia, and microscopic evidence of invasive diarrhea (for all, p < 0.05). Conclusion: Antibiotic overuse could be evaded in PICU using simple bedside screening tools and clinical characteristics, particularly in poor resource settings among children with diarrhea. Full article
(This article belongs to the Special Issue Antibiotic Usage in Acute Situations)
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14 pages, 1656 KiB  
Article
Therapeutic Approach of Chronic Pseudomonas Infection in Cystic Fibrosis—A Network Meta-Analysis
by Orsolya Varannai, Noémi Gede, Márk Félix Juhász, Zsolt Szakács, Fanni Dembrovszky, Dávid Németh, Péter Hegyi and Andrea Párniczky
Antibiotics 2021, 10(8), 936; https://doi.org/10.3390/antibiotics10080936 - 3 Aug 2021
Cited by 4 | Viewed by 2806
Abstract
Pseudomonas infection is a major determinant of morbidity and mortality in cystic fibrosis (CF). Maintaining optimal lung function in CF patients carrying Pseudomonas remains a challenge. Our study aims to investigate the efficacy of antipseudomonal inhaled antibiotics in CF patients with chronic Pseudomonas [...] Read more.
Pseudomonas infection is a major determinant of morbidity and mortality in cystic fibrosis (CF). Maintaining optimal lung function in CF patients carrying Pseudomonas remains a challenge. Our study aims to investigate the efficacy of antipseudomonal inhaled antibiotics in CF patients with chronic Pseudomonas infection. A Bayesian network meta-analysis of randomized controlled trials was conducted. The main outcomes were changes in: (a) forced respiratory volume (FEV1), (b) Pseudomonas aeruginosa sputum density, and (c) CF Questionnaire Revised Respiratory Symptom Score (CFQR-RSS) at 4 weeks follow-up. Eighteen trials which reported on treatment with aztreonam lysine, tobramycin, colistin, levofloxacin, fosfomycin/tobramycin, and amikacin in various dosages were eligible for inclusion. In terms of change in FEV1%, aztreonam lysine (t.i.d., 75 mg) with a 28-day run in the tobramycin phase, aztreonam lysine (b.i.d., 75 mg) with a 28-day run in the tobramycin phase had the highest probability of being the most effective treatment (SUCRAs were 77, 76%, respectively). Regarding change in Pseudomonas sputum density, aztreonam lysine (b.i.d., 75 mg) with a 28-day run in the tobramycin phase, aztreonam lysine (t.i.d., 75 mg) with a 28-day run in the tobramycin phase had the highest probability of being the most effective treatment (SUCRAs were 90, 86%, respectively). Regarding change in CFQR-RSS, aztreonam lysine (t.i.d., 75 mg) and aztreonam lysine (b.i.d., 75 mg) with a 28-day run in the tobramycin inhalation solution phase had the highest probability of being the most effective treatments (SUCRA:74% and 72%, respectively). Regarding changes in FEV1% and Pseudomonas sputum density, aztreonam lysine with a run in tobramycin phase may be the best treatment option in treating chronic Pseudomonas in CF. According to CFQR-RSS no significant differences were found. Given the limitations of the studies included, validation trials are called for. Full article
(This article belongs to the Special Issue Antibiotic Usage in Acute Situations)
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8 pages, 1136 KiB  
Communication
Pharmacodynamic Evaluation of a Single Dose versus a 24-Hour Course of Multiple Doses of Cefazolin for Surgical Prophylaxis
by Aaron Heffernan, Jowana Alawie, Steven C Wallis, Saiyuri Naicker, Santosh Adiraju, Jason A. Roberts and Fekade Bruck Sime
Antibiotics 2021, 10(5), 602; https://doi.org/10.3390/antibiotics10050602 - 19 May 2021
Cited by 2 | Viewed by 3621
Abstract
The optimal perioperative duration for the administration of cefazolin and other prophylactic antibiotics remains unclear. This study aimed to describe the pharmacodynamics of cefazolin for a single 2 g dose versus a 24 h course of a 2 g single dose plus a [...] Read more.
The optimal perioperative duration for the administration of cefazolin and other prophylactic antibiotics remains unclear. This study aimed to describe the pharmacodynamics of cefazolin for a single 2 g dose versus a 24 h course of a 2 g single dose plus a 1 g eight-hourly regimen against methicillin-susceptible Staphylococcus aureus. Static concentration time–kill assay and a dynamic in vitro hollow-fibre infection model simulating humanised plasma and interstitial fluid exposures of cefazolin were used to characterise the pharmacodynamics of prophylactic cefazolin regimens against methicillin-sensitive Staphylococcus aureus clinical isolates. The initial inoculum was 1 × 105 CFU/mL to mimic a high skin flora inoculum. The static time–kill study showed that increasing the cefazolin concentration above 1 mg/L (the MIC) did not increase the rate or the extent of bacterial killing. In the dynamic hollow-fibre model, both dosing regimens achieved similar bacterial killing (~3-log CFU/mL within 24 h). A single 2 g dose may be adequate when low bacterial burdens (~104 CFU/mL) are anticipated in an immunocompetent patient with normal pharmacokinetics. Full article
(This article belongs to the Special Issue Antibiotic Usage in Acute Situations)
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Review

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9 pages, 530 KiB  
Review
The Role of Abdominal Drain Cultures in Managing Abdominal Infections
by Jan J. De Waele, Jerina Boelens, Dirk Van De Putte, Diana Huis In ‘t Veld and Tom Coenye
Antibiotics 2022, 11(5), 697; https://doi.org/10.3390/antibiotics11050697 - 20 May 2022
Cited by 8 | Viewed by 4679
Abstract
Intra-abdominal infections (IAI) are common in hospitalized patients, both in and outside of the intensive care unit. Management principles include antimicrobial therapy and source control. Typically, these infections are polymicrobial, and intra-operative samples will guide the targeted antimicrobial therapy. Although the use of [...] Read more.
Intra-abdominal infections (IAI) are common in hospitalized patients, both in and outside of the intensive care unit. Management principles include antimicrobial therapy and source control. Typically, these infections are polymicrobial, and intra-operative samples will guide the targeted antimicrobial therapy. Although the use of prophylactic abdominal drains in patients undergoing abdominal surgery is decreasing, the use of drains to treat IAI, both in surgical and non-surgical strategies for abdominal infection, is increasing. In this context, samples from abdominal drains are often used to assist in antimicrobial decision making. In this narrative review, we provide an overview of the current role of abdominal drains in surgery, discuss the importance of biofilm formation in abdominal drains and the mechanisms involved, and review the clinical data on the use of sampling these drains for diagnostic purposes. We conclude that biofilm formation and the colonization of abdominal drains is common, which precludes the use of abdominal fluid to reliably diagnose IAI and identify the pathogens involved. We recommend limiting the use of drains and, when present, avoiding routine microbiological sampling. Full article
(This article belongs to the Special Issue Antibiotic Usage in Acute Situations)
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12 pages, 494 KiB  
Review
Drug Regimens of Novel Antibiotics in Critically Ill Patients with Varying Renal Functions: A Rapid Review
by Julie Gorham, Fabio Silvio Taccone and Maya Hites
Antibiotics 2022, 11(5), 546; https://doi.org/10.3390/antibiotics11050546 - 20 Apr 2022
Cited by 15 | Viewed by 5672
Abstract
There is currently an increase in the emergence of multidrug-resistant bacteria (MDR) worldwide, requiring the development of novel antibiotics. However, it is not only the choice of antibiotic that is important in treating an infection; the drug regimen also deserves special attention to [...] Read more.
There is currently an increase in the emergence of multidrug-resistant bacteria (MDR) worldwide, requiring the development of novel antibiotics. However, it is not only the choice of antibiotic that is important in treating an infection; the drug regimen also deserves special attention to avoid underdosing and excessive concentrations. Critically ill patients often have marked variation in renal function, ranging from augmented renal clearance (ARC), defined as a measured creatinine clearance (CrCL) ≥ 130 mL/min*1.73 m2, to acute kidney injury (AKI), eventually requiring renal replacement therapy (RRT), which can affect antibiotic exposure. All novel beta-lactam (BLs) and/or beta-lactam/beta-lactamases inhibitors (BL/BLIs) antibiotics have specific pharmacokinetic properties, such as hydrophilicity, low plasma–protein binding, small volume of distribution, low molecular weight, and predominant renal clearance, which require adaptation of dosage regimens in the presence of abnormal renal function or RRT. However, there are limited data on the topic. The aim of this review was therefore to summarize available PK studies on these novel antibiotics performed in patients with ARC or AKI, or requiring RRT, in order to provide a practical approach to guide clinicians in the choice of the best dosage regimens in critically ill patients. Full article
(This article belongs to the Special Issue Antibiotic Usage in Acute Situations)
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13 pages, 1093 KiB  
Review
A Narrative Review on the Approach to Antimicrobial Use in Ventilated Patients with Multidrug Resistant Organisms in Respiratory Samples—To Treat or Not to Treat? That Is the Question
by Lowell Ling, Wai-Tat Wong, Jeffrey Lipman and Gavin Matthew Joynt
Antibiotics 2022, 11(4), 452; https://doi.org/10.3390/antibiotics11040452 - 27 Mar 2022
Cited by 3 | Viewed by 13336
Abstract
Multidrug resistant organisms (MDRO) are commonly isolated in respiratory specimens taken from mechanically ventilated patients. The purpose of this narrative review is to discuss the approach to antimicrobial prescription in ventilated patients who have grown a new MDRO isolate in their respiratory specimen. [...] Read more.
Multidrug resistant organisms (MDRO) are commonly isolated in respiratory specimens taken from mechanically ventilated patients. The purpose of this narrative review is to discuss the approach to antimicrobial prescription in ventilated patients who have grown a new MDRO isolate in their respiratory specimen. A MEDLINE and PubMed literature search using keywords “multidrug resistant organisms”, “ventilator-associated pneumonia” and “decision making”, “treatment” or “strategy” was used to identify 329 references as background for this review. Lack of universally accepted diagnostic criteria for ventilator-associated pneumonia, or ventilator-associated tracheobronchitis complicates treatment decisions. Consideration of the clinical context including signs of respiratory infection or deterioration in respiratory or other organ function is essential. The higher the quality of respiratory specimens or the presence of bacteremia would suggest the MDRO is a true pathogen, rather than colonization, and warrants antimicrobial therapy. A patient with higher severity of illness has lower safety margins and may require initiation of antimicrobial therapy until an alternative diagnosis is established. A structured approach to the decision to treat with antimicrobial therapy is proposed. Full article
(This article belongs to the Special Issue Antibiotic Usage in Acute Situations)
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11 pages, 285 KiB  
Review
Ventriculitis: Infection or Inflammation
by Mahesh Ramanan, Andrew Shorr and Jeffrey Lipman
Antibiotics 2021, 10(10), 1246; https://doi.org/10.3390/antibiotics10101246 - 14 Oct 2021
Cited by 8 | Viewed by 5509
Abstract
Ventriculitis, or infection of the cerebrospinal fluid, in the presence of external ventricular drains (EVD), is an important complication and associated with substantial mortality, morbidity, and healthcare costs. Further, the conditions that require the insertion of an EVD, such as neurotrauma and subarachnoid [...] Read more.
Ventriculitis, or infection of the cerebrospinal fluid, in the presence of external ventricular drains (EVD), is an important complication and associated with substantial mortality, morbidity, and healthcare costs. Further, the conditions that require the insertion of an EVD, such as neurotrauma and subarachnoid hemorrhage, are themselves associated with inflammation of the cerebrospinal fluid. Phenotypically, patients with inflammation of the cerebrospinal fluid can present with very similar symptoms, signs, and laboratory findings to those with infection. This review examines various controversies relating to the definitions, diagnosis, challenges of differentiating infection from inflammation, prevention, and treatment of ventriculitis in patients with EVDs. Full article
(This article belongs to the Special Issue Antibiotic Usage in Acute Situations)
14 pages, 319 KiB  
Review
Beta-Lactams Dosing in Critically Ill Patients with Gram-Negative Bacterial Infections: A PK/PD Approach
by Kelly L. Maguigan, Mohammad H. Al-Shaer and Charles A. Peloquin
Antibiotics 2021, 10(10), 1154; https://doi.org/10.3390/antibiotics10101154 - 24 Sep 2021
Cited by 18 | Viewed by 5217
Abstract
Beta-lactam antibiotics are often the backbone of treatment for Gram-negative infections in the critically ill. Beta-lactams exhibit time-dependent killing, and their efficacy depends on the percentage of dosing interval that the concentration remains above the minimum inhibitory concentration. The Gram-negative resistance rates of [...] Read more.
Beta-lactam antibiotics are often the backbone of treatment for Gram-negative infections in the critically ill. Beta-lactams exhibit time-dependent killing, and their efficacy depends on the percentage of dosing interval that the concentration remains above the minimum inhibitory concentration. The Gram-negative resistance rates of pathogens are increasing in the intensive care unit (ICU), and critically ill patients often possess physiology that makes dosing more challenging. The volume of distribution is usually increased, and drug clearance is variable. Augmented renal clearance and hypermetabolic states increase the clearance of beta-lactams, while acute kidney injury reduces the clearance. To overcome the factors affecting ICU patients and decreasing susceptibilities, dosing strategies involving higher doses, and extended or continuous infusions may be required. In this review, we specifically examined pharmacokinetic models in ICU patients, to determine the desired beta-lactam regimens for clinical breakpoints of Enterobacterales and Pseudomonas aeruginosa, as determined by the European Committee on Antimicrobial Susceptibility Testing. The beta-lactams evaluated included penicillins, cephalosporins, carbapenems, and monobactams. We found that when treating less-susceptible pathogens, especially P. aeruginosa, continuous infusions are frequently needed to achieve the desired pharmacokinetic/pharmacodynamic targets. More studies are needed to determine optimal dosing strategies in the novel beta-lactams. Full article
(This article belongs to the Special Issue Antibiotic Usage in Acute Situations)
19 pages, 1047 KiB  
Review
Antibiotics in Necrotizing Soft Tissue Infections
by Tomas Urbina, Keyvan Razazi, Clément Ourghanlian, Paul-Louis Woerther, Olivier Chosidow, Raphaël Lepeule and Nicolas de Prost
Antibiotics 2021, 10(9), 1104; https://doi.org/10.3390/antibiotics10091104 - 13 Sep 2021
Cited by 26 | Viewed by 7734
Abstract
Necrotizing soft tissue infections (NSTIs) are rare life-threatening bacterial infections characterized by an extensive necrosis of skin and subcutaneous tissues. Initial urgent management of NSTIs relies on broad-spectrum antibiotic therapy, rapid surgical debridement of all infected tissues and, when present, treatment of associated [...] Read more.
Necrotizing soft tissue infections (NSTIs) are rare life-threatening bacterial infections characterized by an extensive necrosis of skin and subcutaneous tissues. Initial urgent management of NSTIs relies on broad-spectrum antibiotic therapy, rapid surgical debridement of all infected tissues and, when present, treatment of associated organ failures in the intensive care unit. Antibiotic therapy for NSTI patients faces several challenges and should (1) carry broad-spectrum activity against gram-positive and gram-negative pathogens because of frequent polymicrobial infections, considering extended coverage for multidrug resistance in selected cases. In practice, a broad-spectrum beta-lactam antibiotic (e.g., piperacillin-tazobactam) is the mainstay of empirical therapy; (2) decrease toxin production, typically using a clindamycin combination, mainly in proven or suspected group A streptococcus infections; and (3) achieve the best possible tissue diffusion with regards to impaired regional perfusion, tissue necrosis, and pharmacokinetic and pharmacodynamic alterations. The best duration of antibiotic treatment has not been well established and is generally comprised between 7 and 15 days. This article reviews the currently available knowledge regarding antibiotic use in NSTIs. Full article
(This article belongs to the Special Issue Antibiotic Usage in Acute Situations)
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