Decreased susceptibility of Neisseria gonorrhoeae isolates from Switzerland to cefixime and ceftriaxone: Antimicrobial susceptibility

203 words) Background Neisseria gonorrhoeae can rapidly develop resistance to antimicrobial agents. Over the last years, decreased gonococcal susceptibility to third-generation cephalosporins, especially cefixime, emerged worldwide. Therefore, current international guidelines recommend dual therapy for gonorrhoea with ceftriaxone plus either azithromycin or doxycycline. Gonococcal susceptibility data in Switzerland are sparse. Methods We investigated the prevalence of antibiotic susceptibility of N. gonorrhoeae in specimens collected between 1990 and 2012 at the University of Zurich, Switzerland. Minimum inhibitory concentrations (MICs) for cefixime, ceftriaxone, ciprofloxacin, and penicillin were determined by Etests. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints were used to define reduced susceptibility. Results A total of 320 isolates were tested. Between 1990 and 2006 all tested samples were susceptible to both cephalosporins. Subsequently, the prevalence of elevated MICs for cefixime increased to 10.4% (2007/2008), 11.5% (2009/2010), and 11.4% (2011/2012); and for ceftriaxone to 2.4% (2007/2008), 4.7% (2009/2010), and 0% (2011/2012), respectively. The prevalence of resistance to ciprofloxacin (72.7%) and penicillin (22.7%) was high in 2011/2012. Conclusions Decreasing susceptibility of N. gonorrhoeae to third-generation cephalosporins in Switzerland supports treatment recommendations with ceftriaxone plus azithromycin or doxycycline. Health-care providers need to be aware of possible treatment failures with cephalosporins. Continued surveillance of gonococcal antimicrobial resistance is essential. Background (1773 words) Infections with Neisseria gonorrhoeae may cause serious complications, including pelvic inflammatory disease, infertility, peritonitis, and chronic pain, and it enhances HIV transmission [1, 2]. Effective treatment of gonorrhoea is mandatory to control disease transmission and prevent sequelae. However, N. gonorrhoeae rapidly developed antimicrobial resistance to all previously recommended first-line drugs, including penicillins, tetracyclines, and fluoroquinolones. Third-generation cephalosporins, such as cefixime and ceftriaxone, remain the only readily available active antimicrobial class. In recent years, however, gonococcal strains with reduced susceptibility to cefixime emerged and spread worldwide [3]. Clinical treatment failures with cefixime have been reported in Japan, several European countries, Canada, and South Africa [4-10]. In 2009, the first treatment failures to ceftriaxone were observed in Australia [11] and 2010 in Sweden [12]. Currently, the identification of extensively drug-resistant (XDR) N. gonorrhoeae strains with high-level ceftriaxone resistance in Japan [13], France [14], and Spain [15], are of major concern. In addition to high ceftriaxone minimum inhibitory concentrations (MICs), these XDR strains are typically multidrug-resistant, exhibiting additional resistance to fluoroquinolones as well as to older drugs. Consequently, most treatment guidelines now recommend combination therapy with the injectable agent ceftriaxone plus either azithromycin or doxycycline instead of oral monotherapy with cefixime [16, 17]. In Switzerland, a strong rise in N. gonorrhoeae infections was observed during the past decade. Notifications have increased nearly threefold, with 521 reported cases in 2003, and 1569 cases in 2012, of which 77% occurred in men [18]. Reporting gonorrhoea to public health authorities has been mandatory in Switzerland since 1988. However, gonococcal susceptibility data in Switzerland are sparse [19]. Due to the current N. gonorrhoeae resistance problem, improving gonococcal antimicrobial resistance surveillance is of utmost importance and high on the agenda of the WHO’s “Global action plan to control the spread and impact of antimicrobial resistance in Neisseria gonorrhoeae, 2012” [20]. Local antimicrobial surveillance is essential for evidence-based treatment recommendations. Given the lack of data, we investigated the distribution of antibiotic susceptibility of N. gonorrhoeae in specimens collected between 1990 and 2012. Methods All isolates were obtained in the northeastern part of Switzerland and the region of Zurich between January 1990 and December 2012. Specimens were cultured from symptomatic gonorrhoea patients with only one isolate taken per patient in case they were infected at multiple sites. Species confirmation and susceptibility testing was performed at the Institute of Medical Microbiology, University of Zurich. Specimens were cultured on selective media, i.e. until 2009 on Thayer Martin agar (Difco; Becton, Dickinson and Company, Basel, Switzerland), supplemented with IsoVitalex, and after 2009 on VCA3 agar (BioMérieux, Marcy-l’Etoile, France). The commercial biochemical gallery Api NH (BioMérieux) was used for the identification. Minimum inhibitory concentrations (MICs) for cefixime, ceftriaxone, ciprofloxacin and penicillin were determined by the Etest method (BioMérieux, Marcy l’Etoile, France) on Difco GC agar until 2004 (Becton Dickinson, Cockeyswille, MD, USA) and after 2005 on chocolate agar with PolyViteX (BioMérieux) or on MH-horse blood agar (BioMérieux). In order to demonstrate the comparability of the different methods, we tested 9 isolates (199