Reply to Laumen et al

To the Editor—In their letter, Laumen et al report decreased susceptibility to azithromycin and ceftriaxone among commensal Neisseria species obtained from men who have sex with men (MSM) at a sexually transmitted infection clinic in Belgium [1]. The findings of decreased susceptibility to ceftriaxone among commensal Neisseria species are similar to our report from MSM in Hanoi, Vietnam [2]. Those findings are important, as commensal Neisseria in the oropharynx are an important reservoir for antimicrobial resistance in Neisseria gonorrhoeae [3]. Genomic analysis indicates that antimicrobial use drives gonococcal evolution to specific drug-resistant lineages [4]; however, data on the impact of antibiotics on the resistome of commensal Neisseria species remain sparse.

There is a paucity of data on the prevalence and distribution of commensal Neisseria species among different populations. Approximately half of the Neisseria sp. identified in our report were N. flavescens (47%; 125/207), whereas these were not identified by Laumen et al. In that report, the most commonly identified species was N. subflava (37%; 10/27), which was the second most common species in our report (21.2%; 57/207). We both identified N. meningitidis in approximately 5% of isolates. Those variations highlight different distributions between 2 populations, although interpretation of differences is limited by low numbers of participants.

Laumen et al reported high median minimum inhibitory concentrations (MICs) to azithromycin and ceftriaxone for N. subflava and N. macacae. While not reported in our previous study, we now share median MIC data for ceftriaxone, stratified by self-reported antibiotic use within the past 6 months, for each of the 4 Neisseria species identified in their letter and N. flavescens (Table 1). Participants with antibiotic use had higher median MICs, which we used to compare with Laumen’s report. For N. subflava, we found a median MIC to ceftriaxone of 0.094 (interquartile range [IQR], 0.047–0.110), which is lower than that reported by Laumen et al (0.38), although higher than Furuya et al (0.03) [5]. For N. meningitidis, median MIC = 0.064 (IQR, 0.002–0.094), higher than that of Laumen et al (0.016). The MICs for both N. macacae and N. oralis in our report were lower than their reported MICs. N. flavescens, the most commonly isolated strain in our study, had a median MIC of 0.047 (IQR, 0.032–0.094). Given the variations in MICs, it is likely that particular strains are harboring genetic determinants of antibiotic resistance, which might increase the risk of transferring antibiotic resistance to N. gonorrhoeae.

Table 1.

Minimum Inhibitory Concentrations to Ceftriaxone for 5 Commensal Oropharyngeal Neisseria Species From Men Who Have Sex With Men in Hanoi, Vietnam, Stratified by Antibiotic Exposure in the Past 6 Months

Species and Antibiotic Usea	Ceftriaxone MIC
	n	Median	IQR
N. flavescens
No	76	0.047	0.032–0.094
Yes	49	0.064	0.032–0.125
N. macacae
No	7	0.047	0.023–0.064
Yes	5	0.064	0.047–0.064
N. meningitidis
No	10	0.002	0.002–0.094
Yes	3	0.064	0.002–0.094
N. oralis
No	2	0.056	0.047–0.064
Yes	2	0.034	0.004–0.064
N. subflava
No	33	0.064	0.032–0.094
Yes	24	0.094	0.047–0.110

Abbreviations: IQR, interquartile range; MIC, minimum inhibitory concentration determined by Etest.

^aSelf-reported use antibiotics (of any class) within the past 6 months.

We concur that using matrix-assisted laser desorption/ionization time-of-flight mass-spectrometer represents a limitation to fully characterize the prevalence of different commensal Neisseria species, particularly given that genomic tools such as ribosomal multilocus sequence typing have shown significantly higher resolution when speciating less well-studied bacterial species [6].

We agree with Laumen et al on the need for additional research on commensal Neisseria species, given their contribution to antimicrobial resistance in N. gonorrhoeae. Further research should focus on understanding the drivers of interspecies transfer of antimicrobial resistance elements and evaluating potential public health interventions, such as surveillance of antimicrobial resistance within commensal Neisseria in populations at increased risk for developing drug-resistant infections.

Notes

Financial support. This work was supported by the GloCal Global Health Fellowship, a Partnership of the Fogarty International Center and The University of California Global Health Institute [NIH Research Training Grant # R25 TW009343] and National Center for Advancing Translational Sciences and National Institutes of Health for use of REDCap software [#UL1TR001881]. Supported in part by Team Klausner Saving Lives, an educational and research training program of the University of California Los Angeles, Division of Infectious Diseases.

Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.