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Antibiotics
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Pharmacodinamic and Pharmacokinetics of Antibiotics in the Critically Ill
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Pharmacodinamic and Pharmacokinetics of Antibiotics in the Critically Ill

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 (31 October 2022) | Viewed by 36535

Special Issue Editor

Prof. Dr. Alberto Corona

E-Mail Website
Guest Editor
Department of Accident & Emergency and Intensive Care Medicine ASST Valcamonica, Esine & Edolo Hospital, Brescia, Italy
Interests: sepsis/infection in the critically ills; adjunctive therapies in sepsis; antimicrobial resistance; antibiotic therapy in the critically ill

Special Issue Information

Dear Colleagues, 

Patients both in wards and in intensive care units (ICU) often develop severe infections which are associated with significant mortality rates. Recent and novel technologies for the microbiological diagnosis of these infections have been developed and significantly assist in ensuring the adequacy of antibiotic treatments.

Unfortunately, treatment of bacterial infections may be complicated by alterations in the pharmacokinetics (PK) and pharmacodinamics (PD) of antimicrobial agents.

Several tools have been developed or are in development for the quantification of antimicrobial concentrations even within a few hours after sample collection.

Antibiotic efficacy may be affected by specific and single antibiotics as well as patient covariate data; therefore, therapeutic drug monitoring (TDM), when available and fast provided, gives the clinicians bedside help to improve antibiotic treatment quality and adequacy.

This Special Issue will focus on how PK and PD can be of assistance in daily clinician practice.

Prof. Dr. Alberto Corona
Guest Editor

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
  • pharmacodinamics
  • drug monitoring
  • interaction
  • CRRT
  • preterm infants
  • ECMO
  • MDR bacterial infections

Published Papers (8 papers)

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Research

Jump to: Review, Other

17 pages, 1592 KiB  
Article
“CATCH” Study: Correct Antibiotic Therapy in Continuous Hemofiltration in the Critically Ill in Continuous Renal Replacement Therapy: A Prospective Observational Study
by Alberto Corona, Alice Veronese, Silvia Santini and Dario Cattaneo
Antibiotics 2022, 11(12), 1811; https://doi.org/10.3390/antibiotics11121811 - 13 Dec 2022
Cited by 3 | Viewed by 1378
Abstract
The proper posology of antibiotics in the critically ill in CRRT is difficult to assess. We therefore performed a prospective observational cohort study to make clear hints in this topic. Our results reveal a high Sieving Coefficient for all antibiotics, equal to or [...] Read more.
The proper posology of antibiotics in the critically ill in CRRT is difficult to assess. We therefore performed a prospective observational cohort study to make clear hints in this topic. Our results reveal a high Sieving Coefficient for all antibiotics, equal to or higher than those described in previous papers. CVVH clearance in relation to total body clearance was significant, (i.e., >than 25% for all classes). A strong correlation between the antibiotic concentrations obtained in plasma and ultrafiltrate was found both at the peak and in the valley, with the determination of two equations that allow a new method for calculating the amount of antibiotic lost in CVVH both for trough levels and peak. Based on the results of our study and considering the limitations we believe that we can extrapolate the following final considerations: (1) it is likely to carry out a loading dose for the main antibiotics (2) subsequent administrations must take into account the daily loss identified by the linear regression equation. This angular coefficient gives the idea that the average daily loss of given antibiotic is about 25%; this implies that on the basis of the linear regression equation that correlates ultrafiltered/plasma antibiotic concentration, the dosage should be increased by 25% every day, while still ensuring a daily plasma TDM of the drug. Full article
(This article belongs to the Special Issue Pharmacodinamic and Pharmacokinetics of Antibiotics in the Critically Ill)
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12 pages, 1343 KiB  
Article
Population Pharmacokinetic and Pharmacodynamic Analysis of Dalbavancin for Long-Term Treatment of Subacute and/or Chronic Infectious Diseases: The Major Role of Therapeutic Drug Monitoring
by Pier Giorgio Cojutti, Sara Tedeschi, Milo Gatti, Eleonora Zamparini, Marianna Meschiari, Paola Della Siega, Maria Mazzitelli, Laura Soavi, Raffaella Binazzi, Elke Maria Erne, Marco Rizzi, Anna Maria Cattelan, Carlo Tascini, Cristina Mussini, Pierluigi Viale and Federico Pea
Antibiotics 2022, 11(8), 996; https://doi.org/10.3390/antibiotics11080996 - 24 Jul 2022
Cited by 21 | Viewed by 2811
Abstract
A population pharmacokinetic analysis of dalbavancin was conducted in patients with different infection sites. Non-linear mixed effect modeling was used for pharmacokinetic analysis and covariate evaluation. Monte Carlo simulations assessed the probability of target attainment (PTA) of total dalbavancin concentration ≥ 8.04 mg/L [...] Read more.
A population pharmacokinetic analysis of dalbavancin was conducted in patients with different infection sites. Non-linear mixed effect modeling was used for pharmacokinetic analysis and covariate evaluation. Monte Carlo simulations assessed the probability of target attainment (PTA) of total dalbavancin concentration ≥ 8.04 mg/L over time (associated with ≥90% probability of optimal pharmacodynamic target attainment of fAUC24h/MIC > 111.1 against S. aureus) associated with a single or double dosage, one week apart, of 1000 or 1500 mg in patients with different classes of renal function. Sixty-nine patients with 289 concentrations were included. Most of them (53/69, 76.8%) had bone and joint infections. A two-compartment model adequately fitted dalbavancin concentration–time data. Creatinine clearance (CLCR) was the only covariate associated with dalbavancin clearance. Monte Carlo simulations showed that, in patients with severe renal dysfunction, the 1000 mg single or double one week apart dosage may ensure optimal PTAs of 2 and 5 weeks, respectively. In patients with preserved renal function, the 1500 mg single or double one-week apart dosage may ensure optimal PTAs of 2 and 4 to 6 weeks, respectively. Therapeutic drug monitoring should be considered mandatory for managing inter-individual variability and for supporting clinicians in long-term treatments of subacute and chronic infections. Full article
(This article belongs to the Special Issue Pharmacodinamic and Pharmacokinetics of Antibiotics in the Critically Ill)
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Review

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25 pages, 375 KiB  
Review
Antibiotic Therapy in the Critically Ill with Acute Renal Failure and Renal Replacement Therapy: A Narrative Review
by Alberto Corona, Dario Cattaneo and Nicola Latronico
Antibiotics 2022, 11(12), 1769; https://doi.org/10.3390/antibiotics11121769 - 07 Dec 2022
Cited by 1 | Viewed by 3273
Abstract
The outcome for critically ill patients is burdened by a double mortality rate and a longer hospital stay in the case of sepsis or septic shock. The adequate use of antibiotics may impact on the outcome since they may affect the pharmacokinetics (Pk) [...] Read more.
The outcome for critically ill patients is burdened by a double mortality rate and a longer hospital stay in the case of sepsis or septic shock. The adequate use of antibiotics may impact on the outcome since they may affect the pharmacokinetics (Pk) and pharmacodynamics (Pd) of antibiotics in such patients. Acute renal failure (ARF) occurs in about 50% of septic patients, and the consequent need for continuous renal replacement therapy (CRRT) makes the renal elimination rate of most antibiotics highly variable. Antibiotics doses should be reduced in patients experiencing ARF, in accordance with the glomerular filtration rate (GFR), whereas posology should be increased in the case of CRRT. Since different settings of CRRT may be used, identifying a standard dosage of antibiotics is very difficult, because there is a risk of both oversimplification and failing the therapeutic efficacy. Indeed, it has been seen that, in over 25% of cases, the antibiotic therapy does not reach the necessary concentration target mainly due to lack of the proper minimal inhibitory concentration (MIC) achievement. The aim of this narrative review is to clarify whether shared algorithms exist, allowing them to inform the daily practice in the proper antibiotics posology for critically ill patients undergoing CRRT. Full article
(This article belongs to the Special Issue Pharmacodinamic and Pharmacokinetics of Antibiotics in the Critically Ill)
17 pages, 654 KiB  
Review
The Issue of Pharmacokinetic-Driven Drug-Drug Interactions of Antibiotics: A Narrative Review
by Dario Cattaneo, Cristina Gervasoni and Alberto Corona
Antibiotics 2022, 11(10), 1410; https://doi.org/10.3390/antibiotics11101410 - 13 Oct 2022
Cited by 6 | Viewed by 2608
Abstract
Patients in intensive care units (ICU) are at high risk to experience potential drug-drug interactions (pDDIs) because of the complexity of their drug regimens. Such pDDIs may be driven by pharmacokinetic or pharmacodynamic mechanisms with clinically relevant consequences in terms of treatment failure [...] Read more.
Patients in intensive care units (ICU) are at high risk to experience potential drug-drug interactions (pDDIs) because of the complexity of their drug regimens. Such pDDIs may be driven by pharmacokinetic or pharmacodynamic mechanisms with clinically relevant consequences in terms of treatment failure or development of drug-related adverse events. The aim of this paper is to review the pharmacokinetic-driven pDDIs involving antibiotics in ICU adult patients. A MEDLINE Pubmed search for articles published from January 2000 to June 2022 was completed matching the terms “drug-drug interactions” with “pharmacokinetics”, “antibiotics”, and “ICU” or “critically-ill patients”. Moreover, additional studies were identified from the reference list of retrieved articles. Some important pharmacokinetic pDDIs involving antibiotics as victims or perpetrators have been identified, although not specifically in the ICU settings. Remarkably, most of them relate to the older antibiotics whereas novel molecules seem to be associated with a low potential for pDDIs with the exceptions of oritavancin as potential perpetrator, and eravacicline that may be a victim of strong CYP3A inducers. Personalized therapeutic drug regimens by means of available web-based pDDI checkers, eventually combined with therapeutic drug monitoring, when available, have the potential to improve the response of ICU patients to antibiotic therapies. Full article
(This article belongs to the Special Issue Pharmacodinamic and Pharmacokinetics of Antibiotics in the Critically Ill)
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40 pages, 562 KiB  
Review
Use of Antibiotics in Preterm Newborns
by Raffaele Simeoli, Sara Cairoli, Nunzia Decembrino, Francesca Campi, Carlo Dionisi Vici, Alberto Corona and Bianca Maria Goffredo
Antibiotics 2022, 11(9), 1142; https://doi.org/10.3390/antibiotics11091142 - 23 Aug 2022
Cited by 5 | Viewed by 3229
Abstract
Due to complex maturational and physiological changes that characterize neonates and affect their response to pharmacological treatments, neonatal pharmacology is different from children and adults and deserves particular attention. Although preterms are usually considered part of the neonatal population, they have physiological and [...] Read more.
Due to complex maturational and physiological changes that characterize neonates and affect their response to pharmacological treatments, neonatal pharmacology is different from children and adults and deserves particular attention. Although preterms are usually considered part of the neonatal population, they have physiological and pharmacological hallmarks different from full-terms and, therefore, need specific considerations. Antibiotics are widely used among preterms. In fact, during their stay in neonatal intensive care units (NICUs), invasive procedures, including central catheters for parental nutrition and ventilators for respiratory support, are often sources of microbes and require antimicrobial treatments. Unfortunately, the majority of drugs administered to neonates are off-label due to the lack of clinical studies conducted on this special population. In fact, physiological and ethical concerns represent a huge limit in performing pharmacokinetic (PK) studies on these subjects, since they limit the number and volume of blood sampling. Therapeutic drug monitoring (TDM) is a useful tool that allows dose adjustments aiming to fit plasma concentrations within the therapeutic range and to reach specific drug target attainment. In this review of the last ten years’ literature, we performed Pubmed research aiming to summarize the PK aspects for the most used antibiotics in preterms. Full article
(This article belongs to the Special Issue Pharmacodinamic and Pharmacokinetics of Antibiotics in the Critically Ill)

Other

Jump to: Research, Review

21 pages, 607 KiB  
Systematic Review
Tissue Penetration of Antimicrobials in Intensive Care Unit Patients: A Systematic Review—Part II
by Bruno Viaggi, Alice Cangialosi, Martin Langer, Carlo Olivieri, Andrea Gori, Alberto Corona, Stefano Finazzi and Antonello Di Paolo
Antibiotics 2022, 11(9), 1193; https://doi.org/10.3390/antibiotics11091193 - 03 Sep 2022
Cited by 10 | Viewed by 10488
Abstract
In patients that are admitted to intensive care units (ICUs), the clinical outcome of severe infections depends on several factors, as well as the early administration of chemotherapies and comorbidities. Antimicrobials may be used in off-label regimens to maximize the probability of therapeutic [...] Read more.
In patients that are admitted to intensive care units (ICUs), the clinical outcome of severe infections depends on several factors, as well as the early administration of chemotherapies and comorbidities. Antimicrobials may be used in off-label regimens to maximize the probability of therapeutic concentrations within infected tissues and to prevent the selection of resistant clones. Interestingly, the literature clearly shows that the rate of tissue penetration is variable among antibacterial drugs, and the correlation between plasma and tissue concentrations may be inconstant. The present review harvests data about tissue penetration of antibacterial drugs in ICU patients, limiting the search to those drugs that mainly act as protein synthesis inhibitors and disrupting DNA structure and function. As expected, fluoroquinolones, macrolides, linezolid, and tigecycline have an excellent diffusion into epithelial lining fluid. That high penetration is fundamental for the therapy of ventilator and healthcare-associated pneumonia. Some drugs also display a high penetration rate within cerebrospinal fluid, while other agents diffuse into the skin and soft tissues. Further studies are needed to improve our knowledge about drug tissue penetration, especially in the presence of factors that may affect drug pharmacokinetics. Full article
(This article belongs to the Special Issue Pharmacodinamic and Pharmacokinetics of Antibiotics in the Critically Ill)
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21 pages, 575 KiB  
Systematic Review
Tissue Penetration of Antimicrobials in Intensive Care Unit Patients: A Systematic Review—Part I
by Stefano Finazzi, Giacomo Luci, Carlo Olivieri, Martin Langer, Giulia Mandelli, Alberto Corona, Bruno Viaggi and Antonello Di Paolo
Antibiotics 2022, 11(9), 1164; https://doi.org/10.3390/antibiotics11091164 - 29 Aug 2022
Cited by 11 | Viewed by 9173
Abstract
The challenging severity of some infections, especially in critically ill patients, makes the diffusion of antimicrobial drugs within tissues one of the cornerstones of chemotherapy. The knowledge of how antibacterial agents penetrate tissues may come from different sources: preclinical studies in animal models, [...] Read more.
The challenging severity of some infections, especially in critically ill patients, makes the diffusion of antimicrobial drugs within tissues one of the cornerstones of chemotherapy. The knowledge of how antibacterial agents penetrate tissues may come from different sources: preclinical studies in animal models, phase I–III clinical trials and post-registration studies. However, the particular physiopathology of critically ill patients may significantly alter drug pharmacokinetics. Indeed, changes in interstitial volumes (the third space) and/or in glomerular filtration ratio may influence the achievement of bactericidal concentrations in peripheral compartments, while inflammation can alter the systemic distribution of some drugs. On the contrary, other antibacterial agents may reach high and effective concentrations thanks to the increased tissue accumulation of macrophages and neutrophils. Therefore, the present review explores the tissue distribution of beta-lactams and other antimicrobials acting on the cell wall and cytoplasmic membrane of bacteria in critically ill patients. A systematic search of articles was performed according to PRISMA guidelines, and tissue/plasma penetration ratios were collected. Results showed a highly variable passage of drugs within tissues, while large interindividual variability may represent a hurdle which must be overcome to achieve therapeutic concentrations in some compartments. To solve that issue, off-label dosing regimens could represent an effective solution in particular conditions. Full article
(This article belongs to the Special Issue Pharmacodinamic and Pharmacokinetics of Antibiotics in the Critically Ill)
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15 pages, 638 KiB  
Systematic Review
Linezolid Administration to Critically Ill Patients: Intermittent or Continuous Infusion? A Systematic Literature Search and Review
by Ligia-Ancuta Hui, Constantin Bodolea, Laurian Vlase, Elisabeta Ioana Hiriscau and Adina Popa
Antibiotics 2022, 11(4), 436; https://doi.org/10.3390/antibiotics11040436 - 24 Mar 2022
Cited by 10 | Viewed by 2646
Abstract
A judicious antibiotic therapy is one of the challenges in the therapy of critically ill patients with sepsis and septic shock. The pathophysiological changes in these patients significantly alter the antibiotic pharmacokinetics (PK) and pharmacodynamics (PD) with important consequences in reaching the therapeutic [...] Read more.
A judicious antibiotic therapy is one of the challenges in the therapy of critically ill patients with sepsis and septic shock. The pathophysiological changes in these patients significantly alter the antibiotic pharmacokinetics (PK) and pharmacodynamics (PD) with important consequences in reaching the therapeutic targets or the risk of side effects. The use of linezolid, an oxazolidinone antibiotic, in intensive care is such an example. The optimization of its therapeutic effects, administration in intermittent (II) or continuous infusion (CI) is gaining increased interest. In a systematic review of the main databases, we propose a detailed analysis of the main PK/PD determinants, their relationship with the clinical therapeutic response and the occurrence of adverse effects following II or CI of linezolid to different classes of critically ill patients or in Monte Carlo simulations. Full article
(This article belongs to the Special Issue Pharmacodinamic and Pharmacokinetics of Antibiotics in the Critically Ill)
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