The Impact of ESBLs-Positive Escherichia coli’s Resistance to Cefepime and Its Guidance for Clinical Treatment

Abstract

Background

Escherichia coli (E. coli) is a common pathogen in bloodstream infections (BSI), and the production of extended-spectrum beta-lactamases (ESBLs) is its main mechanism of resistance. However, the impact of different ESBL genotypes of E. coli on the resistance to Cefepime (FEP) remains unclear.

Methods

A total of 2356 cases of BSI patients were collected. The experimental group included 188 ESBL-positive E. coli strains that were resistant to FEP but sensitive to ceftazidime (CAZ). Antibiotic usage and resistance rates were evaluated through antimicrobial susceptibility testing and antibiotic usage records. The ESBL genotypes were identified, and the minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) of FEP were determined.

Results

In ESBL-positive E. coli, three ESBL genotypes were identified: 188 strains of CTX-M, 130 strains of TEM-1, and 26 strains of OXA-10. Among them, 124 strains carried both CTX-M-9 and TEM-1 genotypes, 22 strains carried two CTX-M genotypes (CTX-M-1 and CTX-M-2), 20 strains carried both CTX-M-9 and OXA-10, and 6 strains carried three genotypes (CTX-M-9, CTX-TEM-1, and OXA-10). The MIC50, MIC90, MPC50, and MPC90 of the 188 ESBL-positive E. coli were 64, 256, 128, and 528, respectively. The MIC values ranged from 32 to 256, while the MPC values ranged from 64 to 528. The MIC50, MIC90, MPC50, and MPC90 of the 40 ESBL-negative E. coli were 0.5, 1, 64, and 128, respectively; the MIC values ranged from 0.25 to 4, while the MPC values ranged from 32 to 256, respectively.

Conclusion

ESBL-positive E. coli induces an increase in the MIC value of FEP, leading to an increase in FEP resistance. The inoculation effect also causes a significant increase in the MPC value of FEP, especially the increase in selection index value, indicating selective enrichment and amplification of drug-resistant mutants, resulting in clinical treatment failure.

Keywords:

• Escherichia coli
• cefepime
• ESBLs
• mutant prevention concentration

Abbreviations

BSI, bloodstream infections; CAZ, ceftazidime; CZO, cefazolin; CXM, cefuroxime sodium; CTX, cefotaxime; CZ ceftizoxime; E. coli, Escherichia coli; ESBLs, extended-spectrum β-lactamases; FEP, Cefepime; IMP, imipenem; IS, selection index; MEM, meropenem; MIC, Minimum inhibitory concentration; MPC, Mutant prevention concentration; PTA, piperacillin/tazobactam; TZP, piperacillin sodium and tazobactam sodium; TGC, tigecycline.

Ethics Approval

This study was approved by the ethics committee of The Second Affiliated Hospital of Chongqing Medical University (No. 202308V1). The study completely followed the guiding principles in the Declaration of Helsinki.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare that they have no competing interests.

Additional information

Funding

This work was supported by the Joint general project of the Chongqing Science and Technology Bureau and the Chongqing Municipal Health Commission (2023MSXM117).