Susceptibility of endometrial isolates recovered from women with clinical pelvic inflammatory disease or histological endometritis to antimicrobial agents.

The CDC recommended outpatient treatment of pelvic inflammatory disease (PID) is an intramuscular dose of ceftriaxone plus 14 days of doxycycline, with or without metronidazole. European guidelines (2017) include moxifloxacin plus ceftriaxone as a first line regimen, particularly for women with Mycoplasma genitalium-associated PID. However, the susceptibility of bacteria recovered from the endometrium of women with PID to moxifloxacin is unknown. The in vitro antibiotic susceptibility of facultative and anaerobic bacteria recovered from endometrial biopsy samples were evaluated from 105 women having symptomatic PID and/or histologically confirmed endometritis. A total of 342 endometrial isolates from enrollment visits were identified using a combination of biochemical tests and sequencing. Isolates were tested for antimicrobial susceptibility using agar dilution against ceftriaxone, clindamycin, doxycycline, metronidazole and moxifloxacin according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. Neisseria gonorrhoeae was susceptible to ceftriaxone with all isolates having an MIC of 0.03 µg/mL. All the other endometrial isolates were susceptible to ceftriaxone, except for Prevotella species, only half of which were susceptible. The in vitro susceptibility profile for BV-associated bacteria (Gardnerella vaginalis, Atopobium vaginae, Prevotella species, Porphyromonas species and anaerobic gram-positive cocci) revealed greater susceptibility to moxifloxacin compared to doxycycline. Moxifloxacin was superior to metronidazole for G. vaginalis and A. vaginae, and either metronidazole or moxifloxacin was needed to cover Prevotella species. Based on in vitro susceptibility testing, the combination of ceftriaxone plus moxifloxacin provides similar coverage of facultative and anaerobic pathogens compared to the combination of ceftriaxone, metronidazole and doxycycline. Head to head clinical studies of these treatment regimens are needed to evaluate clinical efficacy and eradication of endometrial pathogens following treatment.

Susceptibility of bacterial vaginosis (BV)-associated bacteria to secnidazole compared to metronidazole, tinidazole and clindamycin.

Secnidazole, a 5-nitroimidazole with a longer half-life, is structurally related to metronidazole and tinidazole. For treatment of bacterial vaginosis (BV), secnidazole is a suitable single-dose oral drug having a longer serum half-life than metronidazole. The objective of this study was to evaluate the antimicrobial susceptibility of vaginal isolates of facultative and anaerobic bacteria to secnidazole, metronidazole, tinidazole and clindamycin. A total of 605 unique BV-related bacteria and 108 isolates of lactobacilli recovered from the human vagina of US women during the years 2009-2015 were tested for antimicrobial susceptibility by the agar dilution CLSI reference method to determine the minimal inhibitory concentration (MIC). The MIC90 (µg/mL) for secnidazole was similar to metronidazole and tinidazole for Anaerococcus tetradius (secnidazole: MIC90 2; metronidazole: MIC90 2; tinidazole: MIC90 4), Atopobium vaginae (32; >128; 128), Bacteroides species (2; 2; 2), Finegoldia magna (2; 2; 4), Gardnerella vaginalis (128; 64; 32), Mageeibacillus indolicus (2; 2; 2), Megasphaera-like bacteria (0.5; 0.25; 0.5), Mobiluncus curtisii (128; >128; >128) and Mobiluncus mulieris (>128; >128; >128), Peptoniphilus lacrimalis (4; 4; 4) and Peptoniphilus harei (2; 2; 4), Porphyromonas species (0.25; 0.5; 0.25), Prevotella bivia (8; 8; 8), Prevotella amnii (2; 1; 2) and Prevotella timonensis (2; 2; 2). In this evaluation, 14 (40%) of 35 P. bivia, 5 (14%) of 35 P. amnii and 21 (58%) of 36 P. timonensis isolates were resistant to clindamycin with MIC values of >128 µg/mL. Secnidazole, like metronidazole, was superior to clindamycin for Prevotella spp., Bacteroides spp., Peptoniphilus spp., Anaerococcus tetradius and Finegoldia magna. Clindamycin had greater activity against Atopobium vaginae, Gardnerella vaginalis and Mobiluncus spp. compared to the nitroimidazoles. All 27 Lactobacillus crispatus, 26 (96%) of 27 L. jensenii, 5 (19%) of 27 L. gasseri and 18 (67%) of 27 L. iners isolates were susceptible to clindamycin (MIC ≤2) while the MIC90 for all lactobacilli tested was >128 µg/mL for secnidazole, metronidazole and tinidazole. Secnidazole has similar in vitro activity against the range of microorganisms associated with BV compared to metronidazole or tinidazole. Further, secnidazole spares lactobacilli, a characteristic which is desirable in drugs used to treat bacterial vaginosis.