Evidence map›Paper›PMID 39546100›Full record

ArticleEuropean journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology2025

Dose optimization of piperacillin/tazobactam, cefepime, and ceftazidime for carbapenem-resistant Pseudomonas aeruginosa isolates in Türkiye.

Ecem Buyukyanbolu, Christian M Gill, Leyla Genc, Mehmet Karakus, Fusun Comert, Baris Otlu, Elif Aktas, David P Nicolau

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Article in European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Ecem BuyukyanboluDepartment of Medical Microbiology, University of Health Sciences Hamidiye Etfal Training and Research Hospital, Istanbul, Turkey. nallarecem@gmail.com.
Christian M GillCenter for Anti-Infective Research & Development, Hartford Hospital, 80 Seymour Street, Hartford, CT, 06102, USA.
Leyla GencDepartment of Medical Microbiology, University of Health Sciences Hamidiye Etfal Training and Research Hospital, Istanbul, Turkey.
Mehmet KarakusDepartment of Medical Microbiology, University of Health Sciences, Istanbul, Turkey.
Fusun ComertFaculty of Medicine, Department of Medical Microbiology, Bulent Ecevit University, Zonguldak, Turkey.
Baris OtluFaculty of Medicine, Department of Medical Microbiology, Inonu University, Malatya, Turkey.
Elif AktasDepartment of Medical Microbiology, University of Health Sciences Hamidiye Etfal Training and Research Hospital, Istanbul, Turkey.
David P NicolauCenter for Anti-Infective Research & Development, Hartford Hospital, 80 Seymour Street, Hartford, CT, 06102, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionAlthough CRPA may test susceptible to other β-lactams such as ceftazidime (CAZ), cefepime (FEP), and piperacillin/tazobactam (TZP), reduced potency has been observed. We assessed the adequacy of EUCAST Susceptible (S) or Susceptible Increased Exposure (SIE)/(I) doses for CAZ, FEP, and TZP against CRPA clinical isolates.

methodsCRPA isolates were collected from patients at three Turkish hospitals. CAZ, FEP, and TZP MICs were determined using broth microdilution. Monte Carlo simulations were performed to determine the probability of target attainment (PTA) for a free time above the MIC (fT > MIC) targets for various doses of each agent against isolates defined as susceptible. fT > MIC targets were 70% for CAZ or FEP and 50% for TZP. Cumulative fraction of response (CFR) was calculated. Optimal PTA and CFR was 90% target achievement.

resultsThe percentages of isolates SIE/I to CAZ, FEP, and TZP were 49,8%, 47%, and 31,8% respectively. Reduced potency was noted with 54,1% of CAZ-S isolates having MICs of 4 or 8 mg/L. Of the FEP and TZP-S isolates, MICs at the breakpoint (8 and 16 mg/L, respectively) were the mode with 45,2 and 53,9% of isolates for each, respectively. At an MIC of 8 mg/L for CAZ, the EUCAST standard dose was insufficient (CFR of 85%). 3 h infusions of EUCAST SIE doses were required for 90% PTA at MIC of 8 mg/L and an optimized CFR of 100%. For FEP, the SIE dose of 2 g q8h 0.5 h infusion of was effective (CFR 96%), utilization of an extended 3 h infusion further optimized the PTA at 8 mg/L (CFR 99%). For TZP, the standard dose of 4.5 q6h administered as a 0.5 h infusion was inadequate (CFR 86%). A standard TZP dose with an extended infusion (4.5 g q8h over 4 h) and the SIE dose 4.5 g q6h 3 h infusion resulted in CFRs > 95%.

conclusionThese data support the EUCAST SIE breakpoints for FEP and TZP. To optimize PTA at the SIE breakpoint for CAZ, prolonged infusion is required.

Indexed as

Anti-Bacterial AgentsCarbapenemsCeftazidimeCephalosporinsDrug Resistance, Multiple, BacterialPseudomonas aeruginosaPseudomonas InfectionsCefepimeHumansMicrobial Sensitivity TestsMonte Carlo MethodPenicillanic AcidPiperacillinPiperacillin, Tazobactam Drug CombinationTurkeyAnti-Bacterial AgentsCarbapenemsCefepimeCeftazidimeCephalosporinsPenicillanic AcidPiperacillinPiperacillin, Tazobactam Drug CombinationCarbapenem resistanceCephalosporinDose optimizationP. aeruginosaPK/PD

Identifiers

PMID39546100

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.