Exceedingly high levels of tetracycline resistance in Neisseria gonorrhoeae in eight WHO Enhanced Gonococcal Antimicrobial Surveillance Programme countries in three WHO regions, 2021-2024-doxycycline post-exposure prophylaxis will unlikely impact gonorrhoea burdens

Abstract

Objectives: Doxycycline post-exposure prophylaxis (doxycycline-PEP) can reduce incident cases of syphilis, chlamydia and possibly gonorrhoea especially among men who have sex with men with recent bacterial sexually transmitted infections (STIs). Owing to potential implementation of doxycycline-PEP internationally, global tetracycline/doxycycline resistance data for contemporary Neisseria gonorrhoeae isolates has become imperative. We report tetracycline resistance data for gonococcal isolates (n = 2993) from eight WHO Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP) countries in three WHO regions in 2021-2024, i.e. to estimate potential impact of doxycycline-PEP on the incident gonorrhoea cases in these WHO EGASP countries.

Methods: WHO EGASP isolates cultured from men with urethral discharge in Cambodia (n = 482), Indonesia (n = 101), Malawi (n = 121), The Philippines (n = 843), South Africa (n = 597), Thailand (n = 250), Uganda (n = 350) and Vietnam (n = 249) in 2021-2024 were examined. MICs (mg/L) of tetracycline were determined using Etest.

Results: The tetracycline resistance (range) using the current EUCAST (MIC > 0.5 mg/L) and CLSI (MIC > 1 mg/L) clinical resistance breakpoints in the eight WHO EGASP countries was 92.2% (83.5%-99.6%) and 80.6% (66.3%-98.6%), respectively. Using a previous minocycline-PEP resistance breakpoint (MIC > 2 mg/L) and breakpoint for high-level plasmid (tetM)-mediated tetracycline resistance (MIC > 8 mg/L), the tetracycline resistance (range) was 77.3% (47.4%-98.6%) and 74.3% (31.3%-98.6%), respectively.

Conclusions: The exceedingly high levels of gonococcal tetracycline resistance (independent of resistance breakpoint used) in the eight WHO EGASP countries elucidate that doxycycline-PEP will unlikely significantly reduce the gonorrhoea cases in these countries. Furthermore, doxycycline-PEP might rapidly select for additional gonococcal strains with tetracycline resistance (low- and high-level) and MDR/XDR strains, i.e. because these strains are mostly resistant to tetracycline.