Decreased Cephalosporin Susceptibility of Oropharyngeal Neisseria Species in Antibiotic-using Men Who Have Sex With Men in Hanoi, Vietnam

Abstract

Background: Neisseria gonorrhoeae (NG) infections are a global health burden. NG resistance to cephalosporins, which is increasingly reported, is an imminent threat to public health. Many hypothesize that commensal Neisseria species are an important reservoir for genetic material conferring antimicrobial resistance in NG; however, clinical data are lacking.

Methods: Men who have sex with men (MSM) in Hanoi, Vietnam, completed a questionnaire regarding antibiotic use. We collected pharyngeal specimens, cultured Neisseria species, and measured minimum inhibitory concentrations (MICs) to ciprofloxacin, cefixime, ceftriaxone, and cefpodoxime. Using MIC criteria for antimicrobial susceptibility in NG, we categorized the Neisseria species and compared mean MIC levels between different antibiotic user groups.

Results: Of 207 participants, 38% used at least 1 antibiotic in the past 6 months; 52% without a prescription. A median of 1 Neisseria species was cultured from each participant (range, 1-4) with 10 different Neisseria species identified overall. The proportion of Neisseria with reduced susceptibility to ciprofloxacin was 93%, cefpodoxime 84%, cefixime 31%, and ceftriaxone 28%. Antibiotic use within the past month was strongly associated with Neisseria species having increased MICs to cefixime, ceftriaxone, and cefpodoxime (mean MIC ratios of 6.27, 4.11, and 7.70, respectively), compared with those who used antibiotics between 1 and 6 months prior (P < .05, all comparisons).

Conclusions: MSM in our study often used antibiotics without a prescription. At least 1 commensal Neisseria species colonized all men. Recent use of any antibiotics may select for oropharyngeal Neisseria species with antimicrobial resistance. The normal flora of the oropharynx may be an important source of antimicrobial resistance in Neisseria gonorrhoeae.

Keywords: Neisseria; cephalosporins; gonorrhea; microbiome; resistance.

Figure 1.

Antimicrobial susceptibility profiles of oropharyngeal Neisseria species among men who have sex with men, Hanoi, Vietnam, 2016–2017 (N = 265). For all Neisseria (excluding N. meningitidis), resistance was defined as a minimum inhibitory concentration (MIC) ≥1.0 for ciprofloxacin [21]; reduced susceptibility was defined as MIC >0.6 for ciprofloxacin, MIC ≥0.12 for cefixime [22], MIC ≥0.125 for ceftriaxone [23], and MIC ≥0.25 for cefpodoxime [24]. For N. meningitidis, suspected resistance was defined as MIC >0.03 for ciprofloxacin and MIC >0.125 for ceftriaxone [25].

Figure 2.

Ratio of mean minimum inhibitory concentrations of commensal Neisseria species by antibiotic use subgroups among men who have sex with men, Hanoi, Vietnam (2016–2017). Boxes indicate value of ratio of 2 means; bars indicate 95% confidence interval of ratio of means. ^†Two-sided P value of t test for the difference in log-transformed mean of minimum inhibitory concentrations (MICs). ^‡Cephalosporins include self-reported use of ceftriaxone, cefixime, cefdinir, cefuroxime, or cephalexin.

Figure 3.

Conceptual model for the “resistant commensal reservoir” hypothesis in antibiotic-resistant Neisseria gonorrhoeae research. Double-headed arrow indicates the area of research relevant to current findings.