Evidence map›Paper›PMID 40515804›Full record

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

Emergence of ceftazidime-avibactam resistance in clinical Klebsiella pneumoniae during therapy.

Siquan Shen, Xiren Deng, Lu Guo, Li Yang, Hua Yu, Fupin Hu, Xiangning Huang

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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 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
–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, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
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

7 authors.

Siquan Shen *Institute of Antibiotics, Huashan Hospital, Fudan University, 12 M. Wulumuqi Road, Shanghai, 200040, China.
Xiren Deng *Department of Laboratory Medicine and Sichuan Provincial Key Laboratory for Human Disease Gene Study, University of Electronic Science and Technology of China, Chengdu, 610072, China.
Lu Guo *Department of Pulmonary and Critical Care Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Li YangChengfei Hospital, Chengdu, China.
Hua YuDepartment of Laboratory Medicine and Sichuan Provincial Key Laboratory for Human Disease Gene Study, University of Electronic Science and Technology of China, Chengdu, 610072, China.
Fupin HuInstitute of Antibiotics, Huashan Hospital, Fudan University, 12 M. Wulumuqi Road, Shanghai, 200040, China. hufupin@fudan.edu.cn.
Xiangning HuangDepartment of Laboratory Medicine and Sichuan Provincial Key Laboratory for Human Disease Gene Study, University of Electronic Science and Technology of China, Chengdu, 610072, China. feifei52199@163.com.

Funding

National Natural Science Foundation of China 32141002 and 82172311Research Fund of Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital 2022QN55
6 · The paper itself

Abstract

backgroundThe emergence of ceftazidime-avibactam resistance in Klebsiella pneumoniae poses a significant public health threat, driven by mutations in the bla . This study investigates the evolution of KPC variants (KPC-33, KPC-84, KPC-190) during therapy, highlighting their impact on resistance profiles and treatment challenges. Understanding these mechanisms is critical for guiding clinical interventions.

methodsFour K. pneumoniae strains were isolated from a patient undergoing ceftazidime-avibactam therapy. Antimicrobial susceptibility testing and bioinformatics tools were used to characterize genetic mutations and their phenotypic effects. Whole genome sequencing, cloning, and enzymatic kinetic assays were performed to analyze resistance mechanisms.

resultsThe study identified mutations in the Ω-loop and 240-loop of KPC-2, leading to reduced avibactam affinity and increased ceftazidime hydrolysis. KPC-33 restored carbapenem susceptibility, while KPC-84 and KPC-190 conferred dual resistance. Enzymatic assays confirmed altered kinetic parameters, correlating with clinical resistance patterns.

conclusionsKPC variants exhibit complex evolutionary pathways under antibiotic pressure, complicating treatment. Enhanced surveillance and optimized dosing regimens, including higher avibactam concentrations, are recommended to mitigate resistance. This study underscores the need for global monitoring of KPC variants to inform therapeutic strategies.

Indexed as

Anti-Bacterial AgentsAzabicyclo CompoundsCeftazidimeDrug Resistance, Multiple, BacterialKlebsiella InfectionsKlebsiella pneumoniaeBacterial Proteinsbeta-LactamasesDrug CombinationsHumansMicrobial Sensitivity TestsMutationWhole Genome SequencingAnti-Bacterial Agentsavibactam, ceftazidime drug combinationAzabicyclo CompoundsBacterial Proteinsbeta-LactamasesCeftazidimeDrug CombinationsCarbapenem-resistanceCeftazidime-avibactamKlebsiella pneumoniaeKPC variants

Identifiers

PMID40515804

What OpenQuestion holds

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Registered trials

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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.