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Antibiotics
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Optimizing Antibiotics’ Pharmacokinetic/Pharmacodynamic (PK/PD) and Tissue Concentrations
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Optimizing Antibiotics’ Pharmacokinetic/Pharmacodynamic (PK/PD) and Tissue Concentrations

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 (20 February 2024) | Viewed by 41402

Special Issue Editors

Dr. Mehran Monchi

E-Mail Website
Guest Editor
Department of Intensive Care Medicine, Centre Hospitalier de Melun-Senart, Melun, France
Interests: infection control in the critically ill; multi-resistant bacteria; rapid detection; antibiotic therapy
Dr. Sylvain Diamantis

E-Mail Website
Guest Editor
Department of Infectious Diseases, Centre Hospitalier de Melun-Senart, Melun, France
Interests: pharmacokinetic/pharmacodynamis of antibiotics; pneumonia; sepsis; Lyme disease; impact of antibiotics on the intestinal flora microbiota

Special Issue Information

Dear Colleagues,

Low target tissue concentrations of antibiotics are associated with incomplete clinical response and the emergence of multi-drug-resistant (MDR) pathogenic bacteria. Treating increasingly resistant bacteria cannot be based only on the development of new drugs. Optimization of dosage regimen of old drugs and drug combinations offer interesting alternatives to costly new drugs. Pharmacokinetic/pharmacodynamic (PK/PD) parameters can optimize tissue concentrations and predict the clinical antibacterial efficacy. Conceptually, the appropriate application of PK/PD principles has potential to improve the outcomes, extending the usage life of available antibiotics.

Some infected tissues are studied today with more specific methods of measurement of tissue concentrations such as microdialysis, and the blood–brain barrier is intensively investigated to optimize central nervous system concentration of antibiotics.

Authors are invited to submit manuscripts of narrative and systematic reviews/meta-analysis within their area of interest including (but not limited to) the topics highlighted below:

  • Betalactam optimization using pharmacokinetic/pharmacodynamic (PK/PD) properties. 
  • Aminoglycosides optimization using pharmacokinetic/pharmacodynamic (PK/PD) properties. 
  • Pharmacokinetic/pharmacodynamic (PK/PD) of antibiotics in obese patients.
  • Pharmacokinetics of antibiotics in subjects with renal impairment. 
  • Pharmacokinetics of antimicrobial therapy in elderly patients.
  • Optimizing antibiotics pharmacokinetic-pharmacodynamic parameters in pediatric patients. 
  • Measurement of Free Plasma Concentrations of antibiotics.
  • Measuring tissue antibiotic concentrations using microdialysis.
  • Blood–brain barrier and pharmacokinetic/pharmacodynamic optimization of antibiotics.  
  • Pharmacokinetics and Tissue Penetration of antibiotics in diabetic patients.
  • Nebulized antibiotics (aminoglycosides and colistin) in respiratory infections.

Dr. Mehran Monchi
Dr. Sylvain Diamantis
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

  • antimicrobial therapy
  • pharmacokinetic/pharmacodynamic (PK/PD)
  • free plasma concentrations
  • microdialysis
  • blood-brain barrier
  • renal impairment
  • nebulized antibiotics

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Published Papers (6 papers)

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Research

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13 pages, 1627 KiB  
Article
Selective and Concentrative Enteropancreatic Recirculation of Antibiotics by Pigs
by Karyl K. Buddington, Stefan G. Pierzynowski, William E. Holmes and Randal K. Buddington
Antibiotics 2024, 13(1), 12; https://doi.org/10.3390/antibiotics13010012 - 21 Dec 2023
Viewed by 1222
Abstract
Antibiotics that are efficacious for infectious pancreatitis are present in pancreatic exocrine secretion (PES) after intravenous administration and above minimal inhibitory concentrations. We measured concentrations of four antibiotics by tandem liquid chromatography–mass spectroscopy in plasma and PES after enteral administration to juvenile pigs [...] Read more.
Antibiotics that are efficacious for infectious pancreatitis are present in pancreatic exocrine secretion (PES) after intravenous administration and above minimal inhibitory concentrations. We measured concentrations of four antibiotics by tandem liquid chromatography–mass spectroscopy in plasma and PES after enteral administration to juvenile pigs with jugular catheters and re-entrant pancreatic-duodenal catheters. Nystatin, which is not absorbed by the intestine nor used for infectious pancreatitis (negative control), was not detected in plasma or PES. Concentrations of amoxicillin increased in plasma after administration (p = 0.035), but not in PES (p = 0.51). Metronidazole and enrofloxacin that are used for infectious pancreatitis increased in plasma after enteral administration and even more so in PES, with concentrations in PES averaging 3.1 (±0.5)- and 2.3 (±0.6)-fold higher than in plasma, respectively (p′s < 0.001). The increase in enrofloxacin in PES relative to plasma was lower after intramuscular administration (1.8 ± 0.5; p = 0.001). The present results demonstrate the presence of a selective and concentrative enteropancreatic pathway of secretion for some antibiotics. Unlike the regulated secretion of bile, the constitutive secretion of PES and intestinal reabsorption may provide a continuous exposure of pancreas tissue and the small intestine to recirculated antibiotics and potentially other therapeutic molecules. There is a need to better understand the enteropancreatic recirculation of antibiotics and the associated mechanisms. Full article
(This article belongs to the Special Issue Optimizing Antibiotics’ Pharmacokinetic/Pharmacodynamic (PK/PD) and Tissue Concentrations)
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Review

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21 pages, 1749 KiB  
Review
SWOT and Root Cause Analyses of Antimicrobial Resistance to Oral Antimicrobial Treatment of Cystitis
by Pradeep Tyagi, Shachi Tyagi, Laurence Stewart and Scott Glickman
Antibiotics 2024, 13(4), 328; https://doi.org/10.3390/antibiotics13040328 - 4 Apr 2024
Cited by 2 | Viewed by 1562
Abstract
Nearly 150 million cases of urinary tract infections (UTIs) are reported each year, of which uncomplicated cystitis triggers > 25% of outpatient prescriptions of oral antimicrobial treatment (OAT). OAT aids immune cells infiltrating the urothelium in eliminating uropathogens capable of invading the urothelium [...] Read more.
Nearly 150 million cases of urinary tract infections (UTIs) are reported each year, of which uncomplicated cystitis triggers > 25% of outpatient prescriptions of oral antimicrobial treatment (OAT). OAT aids immune cells infiltrating the urothelium in eliminating uropathogens capable of invading the urothelium and surviving hyperosmotic urine. This self-evident adaptability of uropathogens and the short interval between the introduction of Penicillin and the first report of antimicrobial resistance (AMR) implicate AMR as an evolutionary conserved heritable trait of mutant strains selected by the Darwinian principle to survive environmental threats through exponential proliferation. Therefore, AMR can only be countered by antimicrobial stewardship (AMS) following the principle of the five Ds—drug, dose, duration, drug route, and de-escalation. While convenient to administer, the onset of the minimum inhibitory concentration (MIC) for OAT in urine leaves a window of opportunity for uropathogens to survive the first contact with an antimicrobial and arm their descendant colonies with AMR for surviving subsequent higher urine antimicrobial levels. Meanwhile, the initial dose of intravesical antimicrobial treatment (IAT) may be well above the MIC. Therefore, the widespread clinical use of OAT for cystitis warrants an analysis of the strengths, weaknesses, opportunity, and threats (SWOTs) and a root cause analysis of the AMR associated with OAT and IAT. Full article
(This article belongs to the Special Issue Optimizing Antibiotics’ Pharmacokinetic/Pharmacodynamic (PK/PD) and Tissue Concentrations)
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15 pages, 569 KiB  
Review
Alternative Antimicrobial Irrigation Strategies for the Treatment of Infections in Children: A Review of the Existing Literature
by Costanza Di Chiara, Matteo Ponzoni, Pierre-Philippe Piché-Renaud, Daniele Mengato, Carlo Giaquinto, Shaun K. Morris and Daniele Donà
Antibiotics 2023, 12(8), 1271; https://doi.org/10.3390/antibiotics12081271 - 1 Aug 2023
Viewed by 3193
Abstract
As a synergistic treatment approach with systemic antimicrobial therapy or a systemic antibiotic-sparing strategy, the local administration of antimicrobial agents has been proposed as an alternative route for complicated infections. With the rationale of concentrating the active principle in the desired target site, [...] Read more.
As a synergistic treatment approach with systemic antimicrobial therapy or a systemic antibiotic-sparing strategy, the local administration of antimicrobial agents has been proposed as an alternative route for complicated infections. With the rationale of concentrating the active principle in the desired target site, avoiding potentially toxic systemic levels and bypassing anatomical and physiological barriers, local irrigation or infusion of antibiotics may effectively shorten the antimicrobial therapy course and reduce both infection-related and systemic therapy-related complications. Although evidence from the adult population supports its use in selected patients with an acceptable safety profile, data specifically focused on the pediatric population are limited. To provide a rapid and easily accessible tool for clinical practice, we synthesized the most relevant evidence on the use of local antimicrobial agents in common severe infections in children: meningitis, mediastinitis, pleural infections, recurrent urinary infections, and peritonitis. A literature search was performed using predefined combined keywords through an electronic research database (PubMed). Described molecules, dosages, routes, treated age groups, and related efficacy have been summarized for prompt application to clinical practice. It should, however, be noted that the evidence for the pediatric population remains limited, and the local administration of several molecules remains off-label. A careful multidisciplinary and patient-tailored evaluation, as well as a rational use of available guidelines, should always be the basis of clinical decision making in settings where local administration of antibiotics may be considered. Full article
(This article belongs to the Special Issue Optimizing Antibiotics’ Pharmacokinetic/Pharmacodynamic (PK/PD) and Tissue Concentrations)
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12 pages, 434 KiB  
Review
Optimizing Betalactam Clinical Response by Using a Continuous Infusion: A Comprehensive Review
by Sylvain Diamantis, Catherine Chakvetadze, Astrid de Pontfarcy and Matta Matta
Antibiotics 2023, 12(6), 1052; https://doi.org/10.3390/antibiotics12061052 - 15 Jun 2023
Cited by 1 | Viewed by 1774
Abstract
Introduction: Antimicrobial resistance is a major healthcare issue responsible for a large number of deaths. Many reviews identified that PKPD data are in favor of the use of continuous infusion, and we wanted to review clinical data results in order to optimize our [...] Read more.
Introduction: Antimicrobial resistance is a major healthcare issue responsible for a large number of deaths. Many reviews identified that PKPD data are in favor of the use of continuous infusion, and we wanted to review clinical data results in order to optimize our clinical practice. Methodology: We reviewed Medline for existing literature comparing continuous or extended infusion to intermittent infusion of betalactams. Results: In clinical studies, continuous infusion is as good as intermittent infusion. In the subset group of critically ill patients or those with an infection due to an organism with high MIC, a continuous infusion was associated with better clinical response. Conclusions: Clinical data appear to confirm those of PK/PD to use a continuous infusion in severely ill patients or those infected by an organism with an elevated MIC, as it is associated with higher survival rates. In other cases, it may allow for a decrease in antibiotic daily dosage, thereby contributing to a decrease in overall costs. Full article
(This article belongs to the Special Issue Optimizing Antibiotics’ Pharmacokinetic/Pharmacodynamic (PK/PD) and Tissue Concentrations)
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13 pages, 693 KiB  
Review
How to Use Nebulized Antibiotics in Severe Respiratory Infections
by Julie Gorham, Fabio S. Taccone and Maya Hites
Antibiotics 2023, 12(2), 267; https://doi.org/10.3390/antibiotics12020267 - 28 Jan 2023
Cited by 7 | Viewed by 8882
Abstract
Difficult-to-treat pulmonary infections caused by multidrug-resistant (MDR) pathogens are of great concern because their incidence continues to increase worldwide and they are associated with high morbidity and mortality. Nebulized antibiotics are increasingly being used in this context. The advantages of the administration of [...] Read more.
Difficult-to-treat pulmonary infections caused by multidrug-resistant (MDR) pathogens are of great concern because their incidence continues to increase worldwide and they are associated with high morbidity and mortality. Nebulized antibiotics are increasingly being used in this context. The advantages of the administration of a nebulized antibiotic in respiratory tract infections due to MDR include the potential to deliver higher drug concentrations to the site of infection, thus minimizing the systemic adverse effects observed with the use of parenteral or oral antibiotic agents. However, there is an inconsistency between the large amount of experimental evidence supporting the administration of nebulized antibiotics and the paucity of clinical studies confirming the efficacy and safety of these drugs. In this narrative review, we describe the current evidence on the use of nebulized antibiotics for the treatment of severe respiratory infections. Full article
(This article belongs to the Special Issue Optimizing Antibiotics’ Pharmacokinetic/Pharmacodynamic (PK/PD) and Tissue Concentrations)
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37 pages, 1659 KiB  
Review
The Blood–Brain Barrier and Pharmacokinetic/Pharmacodynamic Optimization of Antibiotics for the Treatment of Central Nervous System Infections in Adults
by Nicholas Haddad, Maddie Carr, Steve Balian, James Lannin, Yuri Kim, Courtney Toth and Jennifer Jarvis
Antibiotics 2022, 11(12), 1843; https://doi.org/10.3390/antibiotics11121843 - 19 Dec 2022
Cited by 15 | Viewed by 23305
Abstract
Bacterial central nervous system (CNS) infections are serious and carry significant morbidity and mortality. They encompass many syndromes, the most common being meningitis, which may occur spontaneously or as a consequence of neurosurgical procedures. Many classes of antimicrobials are in clinical use for [...] Read more.
Bacterial central nervous system (CNS) infections are serious and carry significant morbidity and mortality. They encompass many syndromes, the most common being meningitis, which may occur spontaneously or as a consequence of neurosurgical procedures. Many classes of antimicrobials are in clinical use for therapy of CNS infections, some with established roles and indications, others with experimental reporting based on case studies or small series. This review delves into the specifics of the commonly utilized antibacterial agents, updating their therapeutic use in CNS infections from the pharmacokinetic and pharmacodynamic perspectives, with a focus on the optimization of dosing and route of administration that have been described to achieve good clinical outcomes. We also provide a concise synopsis regarding the most focused, clinically relevant information as pertains to each class and subclass of antimicrobial therapeutics. CNS infection morbidity and mortality remain high, and aggressive management is critical in ensuring favorable patient outcomes while averting toxicity and upholding patient safety. Full article
(This article belongs to the Special Issue Optimizing Antibiotics’ Pharmacokinetic/Pharmacodynamic (PK/PD) and Tissue Concentrations)
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