دورية أكاديمية
In Vitro Susceptibility and Resistance of Mycoplasma genitalium to Nitroimidazoles.
| العنوان: | In Vitro Susceptibility and Resistance of Mycoplasma genitalium to Nitroimidazoles. |
|---|---|
| المؤلفون: | Wood GE; Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA., Kim CM; Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA., Aguila LKT; Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA., Cichewicz RH; Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma, USA.; Natural Products Discovery Group, University of Oklahoma, Norman, Oklahoma, USA.; Institute for Natural Products Applications and Research Technologies, University of Oklahoma, Norman, Oklahoma, USA. |
| المصدر: | Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2023 Apr 18; Vol. 67 (4), pp. e0000623. Date of Electronic Publication: 2023 Mar 09. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 0315061 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1098-6596 (Electronic) Linking ISSN: 00664804 NLM ISO Abbreviation: Antimicrob Agents Chemother Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, American Society for Microbiology |
| مواضيع طبية MeSH: | Nitroimidazoles*/pharmacology , Nitroimidazoles*/therapeutic use , Mycoplasma genitalium*/genetics , Mycoplasma Infections*/drug therapy, Male ; Female ; Humans ; Doxycycline/pharmacology ; Doxycycline/therapeutic use ; Metronidazole/pharmacology ; Metronidazole/therapeutic use ; Tinidazole/pharmacology ; Tinidazole/therapeutic use ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Drug Resistance, Bacterial/genetics |
| مستخلص: | Mycoplasma genitalium is a sexually transmitted reproductive tract pathogen of men and women. M. genitalium infections are increasingly difficult to treat due to poor efficacy of doxycycline and acquired resistance to azithromycin and moxifloxacin. A recent clinical trial suggested that metronidazole may improve cure rates for women with pelvic inflammatory disease and reduced the detection of M. genitalium when included with standard doxycycline plus ceftriaxone treatment. As data regarding susceptibility of mycoplasmas to nitroimidazoles are lacking in the scientific literature, we determined the in vitro susceptibility of 10 M. genitalium strains to metronidazole, secnidazole, and tinidazole. MICs ranged from 1.6 to 12.5 μg/mL for metronidazole, 3.1 to 12.5 μg/mL for secnidazole, and 0.8 to 6.3 μg/mL for tinidazole. None of these agents was synergistic with doxycycline in checkerboard broth microdilution assays. Tinidazole was superior to metronidazole and secnidazole in terms of MIC and time-kill kinetics and was bactericidal (>99.9% killing) at concentrations below reported serum concentrations. Mutations associated with nitroimidazole resistance were identified by whole-genome sequencing of spontaneous resistant mutants, suggesting a mechanism for reductive activation of the nitroimidazole prodrug by a predicted NAD(P)H-dependent flavin mononucleotide (FMN) oxidoreductase. The presence of oxygen did not affect MICs of wild-type M. genitalium, but a nitroimidazole-resistant mutant was defective for growth under anaerobic conditions, suggesting that resistant mutants may have a fitness disadvantage in anaerobic genital sites. Clinical studies are needed to determine if nitroimidazoles, especially tinidazole, are effective for eradicating M. genitalium infections in men and women. |
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| معلومات مُعتمدة: | R21 AI153863 United States AI NIAID NIH HHS |
| فهرسة مساهمة: | Keywords: Mycoplasma genitalium; antibiotic resistance; metronidazole; nitroimidazole; secnidazole; tinidazole |
| المشرفين على المادة: | 0 (Nitroimidazoles) N12000U13O (Doxycycline) R3459K699K (secnidazole) 140QMO216E (Metronidazole) 033KF7V46H (Tinidazole) 0 (Anti-Bacterial Agents) |
| تواريخ الأحداث: | Date Created: 20230418 Date Completed: 20230420 Latest Revision: 20230421 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC10112249 |
| DOI: | 10.1128/aac.00006-23 |
| PMID: | 37070857 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1098-6596 |
|---|---|
| DOI: | 10.1128/aac.00006-23 |