Evidence map›Paper›PMID 39614972›Full record

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

Ceftazidime-avibactam tolerance and persistence among difficult-to-treat KPC-producing Klebsiella pneumoniae clinical isolates from bloodstream infections.

N Abichabki, G G Gaspar, L R Bortolato, D A F S Lima, L N Silva, R H C Pocente, J C Ferreira, T C Ogasawara, D Pereira, R R Guerra and 11 more

Abstract read
PubMed Publisher
In one paragraph

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 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. CombatingFrontiers in cellular and infection microbiology · 2025
    Review
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

21 authors.

N AbichabkiFaculdade de Ciências Farmacêuticas de Ribeirão Preto - Universidade de São Paulo, Ribeirão Preto, Brazil.
G G GasparFaculdade de Medicina de Ribeirão Preto - Universidade de São Paulo, Ribeirão Preto, Brazil.
L R BortolatoFaculdade de Ciências Farmacêuticas de Ribeirão Preto - Universidade de São Paulo, Ribeirão Preto, Brazil.
D A F S LimaHospital das Clínicas da Faculdade de Medicina de Ribeirão Preto - Universidade de São Paulo, Ribeirão Preto, Brazil.
L N SilvaHospital das Clínicas da Faculdade de Medicina de Ribeirão Preto - Universidade de São Paulo, Ribeirão Preto, Brazil.
R H C PocenteHospital das Clínicas da Faculdade de Medicina de Ribeirão Preto - Universidade de São Paulo, Ribeirão Preto, Brazil.
J C FerreiraFaculdade de Ciências Farmacêuticas de Ribeirão Preto - Universidade de São Paulo, Ribeirão Preto, Brazil.
T C OgasawaraFaculdade de Ciências Farmacêuticas de Ribeirão Preto - Universidade de São Paulo, Ribeirão Preto, Brazil.
D PereiraHospital de Clínicas de Porto Alegre - Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
R R GuerraHospital de Clínicas de Porto Alegre - Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
C WilhelmHospital de Clínicas de Porto Alegre - Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
P BarthHospital de Clínicas de Porto Alegre - Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
A F MartinsHospital de Clínicas de Porto Alegre - Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
A BarthHospital de Clínicas de Porto Alegre - Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
G U L BragaFaculdade de Ciências Farmacêuticas de Ribeirão Preto - Universidade de São Paulo, Ribeirão Preto, Brazil.
E C P De MartinisFaculdade de Ciências Farmacêuticas de Ribeirão Preto - Universidade de São Paulo, Ribeirão Preto, Brazil.
J Bengtsson-PalmeDivision of Systems and Synthetic Biology, Department of Life Sciences, SciLifeLab, Chalmers University of Technology, Gothenburg, Sweden.
F Bellissimo-RodriguesFaculdade de Medicina de Ribeirão Preto - Universidade de São Paulo, Ribeirão Preto, Brazil.
V R BollelaFaculdade de Medicina de Ribeirão Preto - Universidade de São Paulo, Ribeirão Preto, Brazil.
A L C DariniFaculdade de Ciências Farmacêuticas de Ribeirão Preto - Universidade de São Paulo, Ribeirão Preto, Brazil.
L N AndradeFaculdade de Ciências Farmacêuticas de Ribeirão Preto - Universidade de São Paulo, Ribeirão Preto, Brazil. leonardo@fcfrp.usp.br.

Funding

Conselho Nacional de Desenvolvimento Científico e Tecnológico 140875/2024-7Conselho Nacional de Desenvolvimento Científico e Tecnológico CNPq- Projeto Universal 406192/2023-5Coordenação de Aperfeiçoamento de Pessoal de Nível Superior 88887.670254/2022-0 (PROEX)Instituto Nacional de Pesquisa em Resistência Antimicrobiana INCT- MCTI/CNPq/CAPES/FAPs nº 16/2014Knut och Alice Wallenbergs Stiftelse KAW 2020.0239Stiftelsen för Strategisk Forskning FFL21-0174Vetenskapsrådet 2020-00120
6 · The paper itself

Abstract

purposeTolerance and persistence occur "silently" in bacteria categorized as susceptible by antimicrobial susceptibility testing in clinical microbiology laboratories. They are different from resistance phenomena, not well-studied, and often remain unnoticeable. We aimed to investigate and characterize ceftazidime-avibactam (CZA) tolerance/persistence in 80 Klebsiella pneumoniae isolates from bloodstream infections.

methodsWe used the Tolerance Disk Test (TDtest) to detect CZA tolerance/persistence and investigate the avibactam (AVI) influence on them, and time-kill assays with minimal duration for killing (MDK) determination to characterize/differentiate CZA tolerance from persistence, for selected isolates. Whole genome sequencing was performed for 49/80 selected isolates to investigate genes related to beta-lactam tolerance/persistence and resistance as well as phylogeny studies.

resultsTolerance/persistence to CZA was detected in 48/80 (60%) isolates, all extensively drug-resistant (XDR) or multidrug-resistant, carbapenem-resistant K. pneumoniae (CRKp), KPC producers, and previously categorized as susceptible (not resistant) to CZA. No heteroresistance was detected. CZA tolerance/persistence occurred due to ceftazidime tolerance/persistence and was not related to AVI in the CZA combination. 5/11 isolates were characterized as CZA-tolerant and 5/11 as CZA-persistent. The single (1/11) XDR and CRKp non-KPC producer was truly susceptible. All the CZA-tolerant/persistent isolates (ST11, ST258, ST340, ST437, ST16, ST17, and ST307) harbored the carbapenemase-encoding gene bla

conclusionAmong the K. pneumoniae bloodstream isolates studied, 60%, previously categorized as susceptible to CZA, were, actually, tolerant/persistent to this antibiotic, all these KPC producers.

Indexed as

Anti-Bacterial AgentsAzabicyclo CompoundsBacteremiabeta-LactamasesCeftazidimeKlebsiella InfectionsKlebsiella pneumoniaeBacterial ProteinsDrug CombinationsDrug Resistance, Multiple, BacterialHumansMicrobial Sensitivity TestsWhole Genome SequencingAnti-Bacterial Agentsavibactam, ceftazidime drug combinationAzabicyclo CompoundsBacterial Proteinsbeta-LactamasesCeftazidimeDrug CombinationsAntibiotic resistant bacteriaMinimal duration for killing (MDK)Time-kill assaysTolerance disk test (TDtest)

Identifiers

PMID39614972

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.