Background In the last two decades, there have been numerous reports worldwide of Neisseria gonorrhoeae (NG) infections with clinical treatment failure to cefixime. Mutation in multiple NG genes including penA, mtrR, pilQ, penB, and ponA, have been associated with cefixime decreased susceptibility and resistance, however, no single mutation has been identified as necessary or sufficient.
Methods We performed a systematic review of all PubMed-published articles from 01/01/1995 to 11/01/2018 that reported molecular characteristics of decreased susceptibility of NG to cefixime. We summarized the findings and made suggestions for the development of a molecular-based NG assay to predict cefixime susceptibility. Based on clinical outcome data, we defined a minimum inhibitory concentration (MIC) ≥ 0.12ug/mL as the cutoff for decreased susceptibility to cefixime. For a wild-type (non-mutated) sequence comparison, we used the penA peptide sequence of NG reference strain M32091.
Results We found 74 articles, of which we excluded 49 due to incomplete information. Among the 25 articles included, there were 415 reported NG strains with reduced susceptibility to cefixime from 22 countries. Two types of penA alterations accounted for 99.5% (413/415) of strains with decreased susceptibility to cefixime: (1) mosaic penA, which can be identified by mutations at amino acid position 375–377 or (2) non-mosaic penA but with at least one critical amino acid substation at position 501, 542, or 551. The other two strains with MIC ≥ 0.125 μg/mL were found in Spain in 2013 with a non-mosaic penA sequence but no alteration at amino acid position 501, 542 or 551.
Conclusion We conducted a systematic review of published reports of over 400 NG strains with decreased susceptibility to cefixime. We identified a combination of sequences in the mosaic and non-mosaic regions of the penA gene that if wild-type (non-mutated) may serve as reliable and sensitive markers to predict cefixime susceptibility globally.
Disclosure No significant relationships.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.