In vitro activity of the first-in-class triazaacenaphthylene gepotidacin alone and in combination with doxycycline against drug-resistant and -susceptible Mycoplasma genitalium.

Mycoplasma genitalium has developed resistance to first-line azithromycin and second-line moxifloxacin. Third-line pristinamycin is only 75% effective. Gepotidacin, a novel triazaacenaphthylene topoisomerase II inhibitor, blocks bacterial DNA replication. We determined the in vitro activity of gepotidacin alone and in combination with doxycycline against a diverse collection of Mycoplasma genitalium isolates (n = 54). Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were determined by a Vero-cell culture method. Macrolide resistance was present in 31 (57%) isolates, fluoroquinolone resistance in 18 (33%) isolates, and 17 (31%) had dual resistance. Synergy testing was performed for gepotidacin and doxycycline by checkerboard analysis for two macrolide- and two dual-resistant isolates. Gepotidacin was active against all 54 M. genitalium isolates with median and modal MICs of 0.125 mg/L and MIC90 of 0.25 mg/L (range ≤0.016-0.5 mg/L). No difference in gepotidacin MIC between macrolide-resistant and -susceptible isolates (p = 0.24) or between fluoroquinolone-, dual-resistant and -susceptible isolates (p = 0.2) was demonstrated. Gepotidacin MBCs were available for 44 M. genitalium isolates with median MIC of 0.064 mg/L and median MBC of 0.125 mg/L. All isolates had ≤4-fold difference between MIC and MBC, suggesting bactericidal effect for gepotidacin. Checkerboard analysis indicated synergistic effect for gepotidacin in combination with doxycycline [fractional inhibitory concentration index (ΣFICI) of 0.5] for two isolates and additive/indifference (ΣFICI at 0.62 and 0.75) for two isolates. Gepotidacin warrants further evaluation in clinical treatment trials for M. genitalium. Combination therapy with doxycycline should be clinically studied to assess effect and potential protection against development and/or spread of gepotidacin resistance.

Rapid spread of Neisseria gonorrhoeae ciprofloxacin resistance due to a newly introduced resistant strain in Nuuk, Greenland, 2012-2015: a community-based prospective cohort study.

OBJECTIVES: To determine the antimicrobial susceptibility and genotype distribution of Neisseria gonorrhoeae strains isolated from a cohort of patients in Nuuk, Greenland in order to assess the risk of rapid spread in the event of introduction of new strains. METHODS: Gonococcal isolates (n=102) obtained from a prospective cohort study of ciprofloxacin resistance were collected between March 2012 and February 2013. Etest minimal inhibitory concentrations (MICs) were determined for ciprofloxacin, azithromycin, ceftriaxone, penicillin, tetracycline, spectinomycin and gentamicin. All isolates were subjected to molecular typing using N. gonorrhoeae multiantigen sequence typing (NG-MAST). After the introduction of a ciprofloxacin-resistant strain in early 2014, an additional 18 isolates were characterised. RESULTS: During the study period, all 102 isolates were fully susceptible to ciprofloxacin (≤0.03 mg/L), azithromycin, spectinomycin, gentamicin and ceftriaxone. 10 different NG-MAST types circulated in Nuuk but 7 were found as single isolates, and 3 of the 7 belonged to 1 of the 3 major genogroups (G210, G9816 and G9817) together comprising 96% of the 102 isolates. ST210 accounted for 55% of the 102 strains. The newly introduced ciprofloxacin resistant strain belonged to ST2400 and dominated the population with 59% resistant strains within 6 months after its introduction. All G2400 strains had MICs≥2 mg/L. CONCLUSIONS: Introduction of a ciprofloxacin-resistant strain into a very homogeneous N. gonorrhoeae population led to an explosive spread of the resistant clone, probably as a result of large sexual networks suggested by the strain homogeneity. Careful surveillance of antimicrobial susceptibility is essential to avoid widespread treatment failure in closed populations.

[Diagnosis of meningococcal sepsis by real-time polymerase chain reaction]. / Meningokoksepsis diagnosticeret ved realtids-polymerasekaedereaktion.

Approximately 100 cases of meningococcal disease are reported annually in Denmark; 90% of these cases are confirmed by culture and serological methods. Real-time PCR was introduced in Denmark in 2005 as a diagnostic tool for meningococcal disease. We hereby report the first notified case of meningococcal sepsis in Denmark where real-time PCR was the primary positive microbiological result.