(P64) High background level of a reduced susceptible phenotype to extended-spectrum cephalosporins in oropharyngeal Neisseria species in a setting without ceftriaxone resistant Neisseria gonorrhoeae

Background
Over the past century, antimicrobial resistance (AMR) has emerged for essentially all antibiotics (AB) that have been introduced to treat Neisseria gonorrhoeae (NG). Meanwhile, AMR determinants are known to exist in the commensal Neisseria population. Neisseria species are ubiquitously and abundantly present in all humans and are more often subjected to AB for a broader range of indications than gonorrhea. Given the natural competence of NG and its shared niche with commensal Neisseria in the oropharynx, AMR surveillance in commensals has been suggested as a way of gaining insight in AMR emergence in NG.

Method
Ninety-two unique Neisseria isolates representing 6 species were cultured from 16 oropharyngeal samples (6 NG culture-positive ESwabs^® and 10 rinse samples from healthy subjects). Each isolate was analyzed with respect to their phenotypic susceptibility to beta-lactam antibiotics, in particular extended-spectrum cephalosporins (ESCs), in conjunction with sequencing of the penA gene (penicillin-binding protein 2).

Results
Decreased susceptibility (DS) or resistance to ESCs was observed in 48/92 Neisseria strains (52%) and two extensive drug resistant (XDR) Neisseria subflava isolates were identified in NG positive swabs (penicillin, cefixime, ceftriaxone, ciprofloxacin and azithromycin resistant). Segments of NG mosaic penA were recognized in penA alleles obtained from commensal Neisseria in each oropharyngeal sample. DNA uptake sequences (DUS) were confirmed in the adjacent regions of the penA gene in all Neisseria species.

Conclusion
Despite the high background level of decreased susceptibility to ESCs in the oropharyngeal commensal Neisseria population, ceftriaxone resistant NG has not yet been detected in the Netherlands. Although we have tested a limited number of samples, the ample availability of mosaic penA sequence blocks in the oropharyngeal Neisseria species, their reduced susceptibility to ESCs, the shared niche with oropharyngeal NG and the natural competence of NG, raises questions on the long-term implications of these findings. Even if horizontal gene transfer (HGT) with subsequent penA mosaicism in NG would occur very sporadically, increasing background levels of XDR commensals may still become a cause of concern. Given the extraordinary capacity of NG to develop resistance, identifying potential threats and increasing our understanding of AMR emergence in NG is imperative.