In vitro activity of mecillinam and nitroxoline against Neisseria gonorrhoeae - re-purposing old antibiotics in the multi-drug resistance era
In vitro activity of mecillinam and nitroxoline against Neisseria gonorrhoeae - re-purposing old antibiotics in the multi-drug resistance era
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DOI：
10.1099/jmm.0.001014
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发表时间：
2019-07-01
影响因子：
3
通讯作者：
Higgins, Paul G.
中科院分区：
文献类型：
--
作者：
Fuchs, Frieder;Wille, Julia;Higgins, Paul G.
2018年，欧洲疾病预防和控制中心报告了欧洲首例广泛耐药淋病奈瑟菌感染病例。为了寻找新的抗菌治疗方案，我们调查了淋病奈瑟菌对硝唑啉(NIT)和甲氧西林(MCM)的敏感性，这两种药物目前都只被用于治疗无并发症的尿路感染。纳入来自两个德国医学中心的对青霉素不敏感的淋病奈瑟菌临床分离株(n=27)。大多数分离株对其他一系列抗淋球菌抗菌药(头孢噻肟、环丙沙星、阿奇霉素、四环素)也不敏感。进一步对所有分离株进行多位点序列分型。采用琼脂梯度扩散法测定青霉素和头孢噻肟的MIC值。头孢菌素酶纸片法检测青霉素酶的产生。琼脂稀释法测定MCM的敏感性，琼脂稀释法和纸片扩散法检测NIT。青霉素MIC为0.125~mg L(-1)，头孢噻肟MIC为0.016~1 mg L(-1)。其中5株为青霉素酶产生菌。MCM的MIC为16~128mgL(-1)，NIT的MICs为0.125~2mgL(-1)。NIT圆盘扩散(中位区直径32 mm)与琼脂稀释法结果有很好的相关性。我们证明了NIT对淋球菌标准抗生素不敏感的临床分离株具有良好的体外活性。MCM活性不理想。琼脂稀释法和纸片扩散法在NIT药敏试验中的相关性是一个具有潜在临床意义的重要方面。
In 2018, the European Centre for Disease Prevention and Control reported the first cases of extensively drug-resistant Neisseria gonorrhoeae infections in Europe. Seeking new options for antimicrobial therapy we investigated the susceptibility of N. gonorrhoeae to nitroxoline (NIT) and mecillinam (MCM), both of which are currently only indicated to treat uncomplicated urinary tract infections. Clinical N. gonorrhoeae isolates with non-susceptibility to penicillin from two German medical centres were included (n = 27). Most isolates were also non-susceptible to a range of other anti-gonococcal antimicrobials (cefotaxime, ciprofloxacin, azithromycin, tetracycline). All isolates were further characterized by multi-locus sequence typing. MICs of penicillin and cefotaxime were determined by agar gradient diffusion. Production of penicillinase was tested by cefinase disk test. Susceptibility of MCM was investigated by agar dilution, NIT by agar dilution and disk diffusion. Penicillin MICs ranged from 0.125 to 64 mg l(-1) and MICs of cefotaxime ranged from < 0.016 to 1 mg l(-1). Five isolates were penicillinase-producers. MICs of MCM ranged from 16 to > 128 mg l(-1) whereas MICs of NIT ranged from 0.125 to 2 mg l(-1). NIT disk diffusion (median zone diameter 32 mm) correlated well with results from agar dilution. We demonstrated excellent in vitro activity of NIT against clinical N. gonorrhoeae isolates with non-susceptibility to standard anti-gonococcal antibiotics. MCM activity was unsatisfactory. Correlation of agar dilution and disk diffusion in NIT susceptibility testing is an important aspect with potential clinical implications.