Impact of Beta-Lactam Target Attainment on Resistance Development in Patients with Gram-Negative Infections

Author:

Maranchick Nicole F.12,Webber Jessica3,Alshaer Mohammad H.12ORCID,Felton Timothy W.45,Peloquin Charles A.12ORCID

Affiliation:

1. Infectious Disease Pharmacokinetics Lab, Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA

2. Emerging Pathogens Institute, University of Florida, Gainesville, FL 32610, USA

3. College of Pharmacy, University of Florida, Gainesville, FL 32610, USA

4. North West Ventilation Unit, Manchester University NHS Foundation Trust, Manchester M23 9LT, UK

5. Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9NT, UK

Abstract

Background: The objective was to identify associations between beta-lactam pharmacokinetic/pharmacodynamic (PK/PD) targets and Gram-negative bacteria resistance emergence in patients. Methods: Retrospective data were collected between 2016 to 2019 at the University of Florida Health-Shands Hospital in Gainesville, FL. Adult patients with two Gram-negative isolates receiving cefepime, meropenem, or piperacillin-tazobactam and who had plasma beta-lactam concentrations were included. Beta-lactam exposures and time free drug concentrations that exceeded minimum inhibitory concentrations (ƒT > MIC), four multiples of MIC (ƒT > 4× MIC), and free area under the time concentration curve to MIC (ƒAUC/MIC) were generated. Resistance emergence was defined as any increase in MIC or two-fold increase in MIC. Multiple regression analysis assessed the PK/PD parameter impact on resistance emergence. Results: Two hundred fifty-six patients with 628 isolates were included. The median age was 58 years, and 59% were males. Cefepime was the most common beta-lactam (65%) and Pseudomonas aeruginosa the most common isolate (43%). The mean daily ƒAUC/MIC ≥ 494 was associated with any increase in MIC (p = 0.002) and two-fold increase in MIC (p = 0.004). The daily ƒAUC/MIC ≥ 494 was associated with decreased time on antibiotics (p = 0.008). P. aeruginosa was associated with any increase in MIC (OR: 6.41, 95% CI [3.34–12.28]) or 2× increase in MIC (7.08, 95% CI [3.56–14.07]). Conclusions: ƒAUC/MIC ≥ 494 may be associated with decreased Gram-negative resistance emergence.

Publisher

MDPI AG

Subject

Pharmacology (medical),Infectious Diseases,Microbiology (medical),General Pharmacology, Toxicology and Pharmaceutics,Biochemistry,Microbiology

Reference36 articles.

1. Centers for Disease Control and Prevention (2023, March 23). About Antimicrobial Resistance, Available online: https://www.cdc.gov/drugresistance/about.html.

2. World Health Organization (2023, March 23). Antimicrobial Resistance: Global Report on Surveillance. 1 April 2014. Available online: https://www.who.int/publications/i/item/9789241564748.

3. Global burden of bacterial antimicrobial resistance in 2019: A systematic analysis;Murray;Lancet,2022

4. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: An international expert proposal for interim standard definitions for acquired resistance;Magiorakos;Clin. Microbiol. Infect.,2012

5. Antibacterial discovery and development—The failure of success?;Fernandes;Nat. Biotechnol.,2006

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