Gonorrhoea treatment failures to cefixime and azithromycin in England, 2010

Abstract

Successful treatment of gonorrhoea is the mainstay of public health control. Cefixime and ceftriaxone, highly active third generation cephalosporins, are today the recommended first-line agents in most countries and azithromycin is a second-line agent. However, there is increasing evidence of decreasing susceptibility and emergence of therapeutic failures. In this report two cases of clinical failure to cefixime are described, one of which additionally shows failure to azithromycin and selection of a less susceptible strain during treatment.

Sexually Transmitted Infections Treatment Guidelines, 2021

“…Cephalosporin treatment failure is the persistence of N. gonorrhoeae infection despite recommended cephalosporin treatment; such failure is indicative of infection with cephalosporin-resistant gonorrhea among persons whose partners were treated and whose risk for reinfection is low. Suspected treatment failure has been reported among persons receiving oral and injectable cephalosporins (852)(853)(854)(855)857,859,861,863,864,867,875,894). Treatment failure should be considered for persons whose symptoms do not resolve within 3-5 days after recommended treatment and report no sexual contact during the posttreatment follow-up period and persons with a positive test of cure (i.e., positive culture >72 hours or positive NAAT >7 days after receiving recommended treatment) when no sexual contact is reported during the posttreatment follow-up period (874).…”

“…Monotherapy with azithromycin 2 g orally as a single dose has been demonstrated to be 99.2% effective against uncomplicated urogenital gonorrhea (95% CI: 97.3%–99.9%) ( 883 ). However, monotherapy is not recommended because of concerns about the ease with which N. gonorrhoeae can develop resistance to macrolides, the high proportion of isolates with azithromycin decreased susceptibility, and documented azithromycin treatment failures ( 859 ). Strains of N. gonorrhoeae circulating in the United States are not adequately susceptible to penicillin, tetracycline, and older macrolides (e.g., erythromycin), and thus use of these antimicrobials cannot be recommended.…”

Neisseria gonorrhoeae Treatment Failure and Susceptibility to Cefixime in Toronto, Canada

“…10,11 Reports from Asia and Europe indicate cefixime treatment failures of N gonorrhoeae infections in urethral and pharyngeal sites due to isolates with cefixime MICs of 0.12 g/mL or greater. [12][13][14][15][16][17] However, clinical studies on cefixime efficacy given increasing MICs are lacking.…”

“…18 Reduced susceptibility to cefixime was defined as an MIC of 0.12 g/mL or greater based on pharmacokinetic/pharmacodynamic data and reports of cefixime failure in Japan and Europe. 10,13,19 Molecular analysis of N gonorrhoeae isolates with reduced susceptibility to cefixime included the genes of penicillin binding proteins PBP1 (ponA) and PBP2 (penA), outer membrane porin PIB (porB), and the efflux system regulated by MtrR and the mtrR gene promoter. [20][21][22][23][24][25][26] Mosaic PBP2s are novel gene cassettes that suggest an admixture of genetic material from both wild-type N gonorrhoeae and other commensal Neisseria species.…”

“…12,19,36 Since then, there have been case reports from the United Kingdom, Austria, France, and Norway and reports of failures of cefixime to treat gonococcal urethritis with MICs 0.19 g/mL or greater. [13][14][15][16][17] The routine identification of N gonorrhoeae treatment failures due to reduced susceptibility is problematic because of the increasing use of NAAT (nucleic acid amplification test), which is not able to provide antibiotic susceptibility results. In 2007, a web-based survey of US public health laboratories showed that only 4.9% of all testing for N gonorrhoeae was performed by culture.…”