Trends in antimicrobial susceptibility for azithromycin and ceftriaxone in Neisseria gonorrhoeae isolates in Amsterdam, the Netherlands, between 2012 and 2015

摘要

Resistance of Neisseria gonorrhoeae to azithromycin and ceftriaxone has been increasing in the past years. This is of concern since the combination of these antimicrobials is recommended as the first-line treatment option in most guidelines. To analyse trends in antimicrobial resistance, we retrospectively selected all consultations with a positive N. gonorrhoeae culture at the sexually transmitted infection clinic, Amsterdam, the Netherlands, from January 2012 through September 2015. Minimum inhibitory concentrations (MICs) for azithromycin and ceftriaxone were analysed per year, and determinants associated with decreased susceptibility to azithromycin (MIC?>?0.25 mg/L) or ceftriaxone (MIC?>?0.032 mg/L) were assessed. Between 2012 and 2015 azithromycin resistance (MIC?>?0.5 mg/L) was around 1.2%, the percentage of isolates with intermediate MICs (>?0.25 and?≤?0.5 mg/L) increased from 3.7% in 2012, to 8.6% in 2015. Determinants associated with decreased azithromycin susceptibility were, for men who have sex with men (MSM), infections diagnosed in the year 2014, two infected sites, and HIV status (HIV; associated with less decreased susceptibility); for heterosexuals this was?having ≥?10 sex partners (in previous six months). Although no ceftriaxone resistance (MIC?>?0.125 mg/L) was observed during the study period, the proportion of isolates with decreased ceftriaxone susceptibility increased from 3.6% in 2012, to 8.4% in 2015. Determinants associated with decreased ceftriaxone susceptibility were, for MSM, infections diagnosed in 2014, and pharyngeal infections; and for heterosexuals, infections diagnosed in 2014 or 2015, being of female sex, and having?≥?10 sex partners. Continued decrease of azithromycin and ceftriaxone susceptibility will threaten future treatment of gonorrhoea. Therefore, new treatment strategies are warranted. Keywords: Neisseria gonorrhoeae , antimicrobial resistance, susceptibility, azithromycin, ceftriaxoneIntroductionSince penicillin became available in the 1940s, Neisseria gonorrhoeae infection has become a treatable sexually transmitted infection (STI) [1]. Yet successful eradication is hampered by emerging resistance to all first-line antibiotics used so far. Latest in this trend are resistance and treatment failures to extended-spectrum cephalosporins (ESC) [1,2]. We reported an increase in ESC-resistant N. gonorrhoeae among men who have sex with men (MSM) in Amsterdam, the Netherlands, between 2006 and 2008 [3]. To halt the development and spread of resistance, international gonorrhoea guidelines recommend dual therapy consisting of ceftriaxone (an ESC) and azithromycin [4-6]. Dual therapy is also effective against Chlamydia trachomatis , which frequently coincides with gonorrhoea [4]. However, resistance and treatment failures have been documented for both drugs [7-13]. Taking the historical course of emerging antimicrobial-resistant gonorrhoea strains into account, without additional measures, a further decrease in ceftriaxone and azithromycin susceptibility is to be expected [1]. Moreover, high level azithromycin-resistant gonorrhoea has been reported in the United Kingdom (UK) since 2015 [9]. In addition, the first treatment failure on dual therapy of azithromycin and ceftriaxone was reported in 2016 [14]. The World Health Organization (WHO) recommends abandoning an antibiotic as first-line treatment once the prevalence of resistant strains in the population exceeds 5% [15]. Surveillance is essential to monitor this development. Therefore, we analysed the susceptibility to azithromycin and ceftriaxone of N. gonorrhoeae isolates among attendees of the STI Outpatient Clinic in Amsterdam, the Netherlands, between 2012 and 2015. We also assessed which determinants were associated with decreased susceptibility.MethodsStudy populationThe STI Outpatient Clinic in Amsterdam, is the largest centre for STI care in the Netherlands, with up to 40,000 consultations each year [16]. We test and treat (free of charge) patients who: are younger than 25 years-old, commercial sex workers, clients of commercial sex workers, MSM, have?≥?3 sex partners in the previous six months, were notified of an STI by a sex partner, have STI-related complaints, are of non-West-European origin, or are of non-North-American origin.Dual therapy for gonorrhoea is not recommended in the Netherlands, instead ceftriaxone 500 mg is used, and azithromycin is added only in case of a suspected or proven coinfection with C. trachomatis [17]. This single treatment alternative is supported by the 2016 WHO gonorrhoea treatment guideline [6].For this study, we included consultations from January 2012 through September 2015, with a positive N. gonorrhoeae culture, and available minimum inhibitory concentrations (MICs) for azithromycin and ceftriaxone. Per consultation, defined as all visits that are part of a new request for healthcare, a patient could be infected at up to four anatomical sites (cervix/vagina, pharynx, r