生殖支原体的表型抗生素耐药性及其在不同大环内酯类耐药相关突变之间的差异。

Phenotypic antibiotic resistance of Mycoplasma genitalium and its variation between different macrolide resistance-associated mutations.

作者信息

Doelman T A, Adriaens N, Westerhuis B M, Bruisten S M, Vergunst C E, Bouwman F M, van Dam A P

机构信息

Department of Medical Microbiology, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands.

Infectious Diseases, Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam, The Netherlands.

出版信息

J Antimicrob Chemother. 2025 Feb 3;80(2):465-471. doi: 10.1093/jac/dkae430.

DOI:10.1093/jac/dkae430

PMID:39656801

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11787896/

Abstract

OBJECTIVES

Mycoplasma genitalium, a sexually transmitted bacterium, faces increasing antibiotic resistance, particularly to azithromycin. However, presence of macrolide resistance-associated mutations (MRAMs) does not evidently implicate azithromycin treatment failure. This study aimed to establish an in vitro co-culture system of M. genitalium isolates and perform phenotypic susceptibility testing for different antibiotics, focusing on azithromycin to evaluate genotypic and phenotypic resistance across MRAMs.

METHODS

Urine specimens testing positive for M. genitalium via nucleic acid amplification were co-cultured with Vero cells. Phenotypic susceptibility testing was performed for eight antibiotics. Growth inhibition and MIC of M. genitalium by azithromycin were compared across different MRAMs.

RESULTS

M. genitalium was cultured from 20/40 (50.0%) positive urine samples, with phenotypic susceptibility tested in a subset. MICs ranged as follows: azithromycin (0.008->32 mg/L), levofloxacin (1-4 mg/L), moxifloxacin (<0.25-1 mg/L), sitafloxacin (<0.032-0.25 mg/L), minocycline (<0.25-1 mg/L), doxycycline (<0.125-2 mg/L), spectinomycin (<2.5->25 mg/L) and lefamulin (<0.004-0.063 mg/L). Isolates with A2058T demonstrated 24-, 7-, 15- and 12-fold increases in growth inhibition compared with A2058G at azithromycin concentrations of 4, 8, 16 and 32 mg/L, respectively (P < 0.01). MRAMs ranked from low to high impact on MIC range were as follows: wildtype (0.008-0.016), A2058T (8-32), A2059G (≥32) and A2058G (>32).

CONCLUSIONS

This study revealed that M. genitalium isolates vary in azithromycin-induced growth inhibition across MRAMs, potentially explaining differences in clinical treatment efficacy. Phenotypic susceptibility testing for other antibiotics demonstrated relatively low MICs. Future studies should incorporate clinical treatment efficacy and symptom severity to optimize treatment for M. genitalium.

摘要

目的

生殖支原体是一种性传播细菌，面临着日益增加的抗生素耐药性，尤其是对阿奇霉素的耐药性。然而，大环内酯类耐药相关突变（MRAMs）的存在并不明显意味着阿奇霉素治疗失败。本研究旨在建立生殖支原体分离株的体外共培养系统，并对不同抗生素进行表型药敏试验，重点是阿奇霉素，以评估跨MRAMs的基因型和表型耐药性。

方法

通过核酸扩增检测出生殖支原体呈阳性的尿液标本与Vero细胞共培养。对八种抗生素进行表型药敏试验。比较不同MRAMs条件下阿奇霉素对生殖支原体的生长抑制作用和最低抑菌浓度（MIC）。

结果

从20/40（50.0%）份阳性尿液样本中培养出了生殖支原体，并对其中一部分进行了表型药敏试验。MIC范围如下：阿奇霉素（0.008->32mg/L）、左氧氟沙星（1-4mg/L）、莫西沙星（<0.25-1mg/L）、司帕沙星（<0.032-0.25mg/L）、米诺环素（<0.25-1mg/L）、多西环素（<0.125-2mg/L）、壮观霉素（<2.5->25mg/L）和 lefamulin（<0.004-0.063mg/L）。在阿奇霉素浓度分别为4、8、16和32mg/L时，携带A2058T突变的分离株与携带A2058G突变的分离株相比，生长抑制分别增加了24倍、7倍、15倍和12倍（P<0.01）。对MIC范围影响由低到高的MRAMs排序如下：野生型（0.008-0.016）、A2058T（8-32）、A2059G（≥32）和A2058G（>32）。