“Seesaw effect” between daptomycin and ceftobiprole in daptomycin-resistant methicillin-resistant staphylococcus aureus isolates

IF 4.9 2区医学 Q1 INFECTIOUS DISEASES

International Journal of Antimicrobial Agents Pub Date : 2025-02-21 DOI:10.1016/j.ijantimicag.2025.107469

Mengzhen Chen , Shengnan Jiang , Lu Sun , Haiping Wang , Lingfang Di , Yeqiong Liu , Ying Zhang , Hemu Zhuang , Yueqin Hong , Zhengan Wang , Feiteng Zhu , Yiyi Chen , Shujuan Ji , Yunsong Yu , Yan Chen , Xiaoxing Du

{"title":"“Seesaw effect” between daptomycin and ceftobiprole in daptomycin-resistant methicillin-resistant staphylococcus aureus isolates","authors":"Mengzhen Chen , Shengnan Jiang , Lu Sun , Haiping Wang , Lingfang Di , Yeqiong Liu , Ying Zhang , Hemu Zhuang , Yueqin Hong , Zhengan Wang , Feiteng Zhu , Yiyi Chen , Shujuan Ji , Yunsong Yu , Yan Chen , Xiaoxing Du","doi":"10.1016/j.ijantimicag.2025.107469","DOIUrl":null,"url":null,"abstract":"<div><h3>Objectives</h3><div>This study aimed to investigate the “seesaw effect” of daptomycin (DAP) and ceftobiprole (BPR) on DAP-resistant (DAP-R) methicillin-resistant <em>Staphylococcus aureus</em> (MRSA) isolates.</div></div><div><h3>Methods</h3><div>Broth microdilution minimum inhibitory concentrations (MICs) of DAP and BPR were tested for laboratory-derived and clinical DAP-R MRSA isolates to estimate the “seesaw effect.” Time-kill curves for seven representative DAP-R isolates were obtained using DAP and BPR to validate their synergistic activity <em>in vitro</em>. Whole genome sequencing as well as deletion and complementation of the <em>mprF</em> gene were performed to investigate the mechanisms of the “seesaw effect.”</div></div><div><h3>Results</h3><div>The BPR MICs decreased by half-fold in DAP-R MRSA isolates. The synergistic effect of DAP and BPR against representative clinical and community-associated MRSA (CA-MRSA) isolates was demonstrated in time-kill analyses, showing that synergistic activity was preferred in CA-MRSA compared with hospital-associated MRSA. The <em>mprF</em> mutations were identified in isolates exhibiting the “seesaw effect.” These mutations increased the DAP MIC while decreasing the BPR MIC.</div></div><div><h3>Conclusions</h3><div>The “seesaw effect” between DAP and BPR was prevalent among DAP-R MRSA isolates. This phenomenon was associated with the <em>mprF</em> mutations of MRSA.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 5","pages":"Article 107469"},"PeriodicalIF":4.9000,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Antimicrobial Agents","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0924857925000275","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}

引用次数: 0

Abstract

Objectives

This study aimed to investigate the “seesaw effect” of daptomycin (DAP) and ceftobiprole (BPR) on DAP-resistant (DAP-R) methicillin-resistant Staphylococcus aureus (MRSA) isolates.

Methods

Broth microdilution minimum inhibitory concentrations (MICs) of DAP and BPR were tested for laboratory-derived and clinical DAP-R MRSA isolates to estimate the “seesaw effect.” Time-kill curves for seven representative DAP-R isolates were obtained using DAP and BPR to validate their synergistic activity in vitro. Whole genome sequencing as well as deletion and complementation of the mprF gene were performed to investigate the mechanisms of the “seesaw effect.”

Results

The BPR MICs decreased by half-fold in DAP-R MRSA isolates. The synergistic effect of DAP and BPR against representative clinical and community-associated MRSA (CA-MRSA) isolates was demonstrated in time-kill analyses, showing that synergistic activity was preferred in CA-MRSA compared with hospital-associated MRSA. The mprF mutations were identified in isolates exhibiting the “seesaw effect.” These mutations increased the DAP MIC while decreasing the BPR MIC.

Conclusions

The “seesaw effect” between DAP and BPR was prevalent among DAP-R MRSA isolates. This phenomenon was associated with the mprF mutations of MRSA.

Abstract Image

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

International Journal of Antimicrobial Agents 医学-传染病学

CiteScore

21.60

自引率

0.90%

发文量

176

审稿时长

36 days

期刊介绍： The International Journal of Antimicrobial Agents is a peer-reviewed publication offering comprehensive and current reference information on the physical, pharmacological, in vitro, and clinical properties of individual antimicrobial agents, covering antiviral, antiparasitic, antibacterial, and antifungal agents. The journal not only communicates new trends and developments through authoritative review articles but also addresses the critical issue of antimicrobial resistance, both in hospital and community settings. Published content includes solicited reviews by leading experts and high-quality original research papers in the specified fields.