淋病奈瑟菌对庆大霉素的敏感性及 25 年来马拉维持续使用庆大霉素治疗泌尿生殖道淋病的疗效结果。
Gentamicin Susceptibility in Neisseria gonorrhoeae and Treatment Outcomes for Urogenital Gonorrhea After 25 Years of Sustained Gentamicin Use in Malawi.
机构信息
From the UNC Project Malawi, Lilongwe, Malawi.
Institute for Global Health and Infectious Diseases, University of North Carolina, Chapel Hill, NC.
出版信息
Sex Transm Dis. 2022 Apr 1;49(4):251-256. doi: 10.1097/OLQ.0000000000001580.
BACKGROUND
Gentamicin has been used for the treatment of gonorrhea in Malawi since 1993. However, declining clinical cure rates have been suspected. We evaluated current Neisseria gonorrhoeae susceptibility to gentamicin in vitro and clinically.
METHODS
Men with acute urethritis were recruited at the Bwaila District Hospital STI Clinic in Lilongwe, Malawi, between January 2017 and August 2019. All men provided urethral swabs for etiological testing at enrollment and test of cure (TOC), 1 week later, using Gram-stained microscopy and culture. We used Etest to determine minimum inhibitory concentrations (MICs) of gentamicin, azithromycin, cefixime, ceftriaxone, ciprofloxacin, and spectinomycin; disc diffusion for tetracycline susceptibility; and whole-genome sequencing (WGS) to verify/refute treatment failure.
RESULTS
Among 183 N. gonorrhoeae culture-positive men enrolled, 151 (82.5%) had a swab taken for TOC. Of these 151 men, 16 (10.6%) had a positive culture at TOC. One hundred forty-one baseline isolates were tested for gentamicin susceptibility using Etest: 2 (1.4%), MIC = 2 μg/mL; 111 (78.7%), MIC = 4 μg/mL; and 28 (19.9%), MIC = 8 μg/mL. All isolates were susceptible to azithromycin, cefixime, ceftriaxone, and spectinomycin, whereas 63.1% had intermediate susceptibility or resistance to ciprofloxacin. Almost all (96.1%) isolates were resistant to tetracycline. All examined isolates cultured at TOC (n = 13) had gentamicin MICs ≤8 μg/mL. Ten men had pretreatment and posttreatment isolates examined by whole-genome sequencing; 2 (20%) were verified new infections (4119 and 1272 single-nucleotide polymorphisms), whereas 8 (80%) were confirmed treatment failures (0-1 single-nucleotide polymorphism).
CONCLUSIONS
Gentamicin MICs poorly predict gonorrhea treatment outcome with gentamicin, and treatment failures are verified with gonococcal strains with in vitro susceptibility to gentamicin. The first-line treatment of gonorrhea in Malawi should be reassessed.
背景
自 1993 年以来，庆大霉素一直在马拉维用于治疗淋病。然而，临床治愈率的下降已经引起了怀疑。我们评估了目前淋病奈瑟菌对庆大霉素的体外和临床敏感性。
方法
2017 年 1 月至 2019 年 8 月期间，在马拉维利隆圭的 Bwaila 区医院性传播感染诊所招募了患有急性尿道炎的男性。所有男性在入组时和 1 周后的治疗结束时（TOC）均提供尿道拭子进行病因学检测，采用革兰氏染色显微镜检查和培养。我们使用 Etest 确定庆大霉素、阿奇霉素、头孢克肟、头孢曲松、环丙沙星和壮观霉素的最小抑菌浓度（MIC）；使用纸片扩散法检测四环素的敏感性；并进行全基因组测序（WGS）以验证/反驳治疗失败。
结果
在 183 例淋病奈瑟菌培养阳性的男性中，有 151 例（82.5%）进行了 TOC 拭子检测。在这 151 名男性中，有 16 名（10.6%）在 TOC 时培养阳性。用 Etest 检测了 141 例基线分离株对庆大霉素的敏感性：2 株（1.4%），MIC=2μg/ml；111 株（78.7%），MIC=4μg/ml；28 株（19.9%），MIC=8μg/ml。所有分离株均对阿奇霉素、头孢克肟、头孢曲松和壮观霉素敏感，而 63.1%的分离株对环丙沙星表现出中介或耐药性。几乎所有（96.1%）分离株对四环素耐药。在 TOC 培养的所有分离株（n=13）的庆大霉素 MICs≤8μg/ml。10 名男性的预处理和治疗后分离株进行了全基因组测序；2 名（20%）被证实为新感染（4119 和 1272 个单核苷酸多态性），而 8 名（80%）被证实为治疗失败（0-1 个单核苷酸多态性）。
结论
庆大霉素 MIC 不能很好地预测庆大霉素治疗淋病的效果，而治疗失败则通过体外对庆大霉素敏感的淋病奈瑟菌株得到证实。马拉维淋病的一线治疗方法应重新评估。
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