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

Public Health Ontario Laboratories, 81 Resources Rd, Toronto, ON M9P 3T1, Canada.
JAMA The Journal of the American Medical Association (Impact Factor: 35.29). 01/2013; 309(2):163-70. DOI: 10.1001/jama.2012.176575
Source: PubMed


Although cephalosporins are the cornerstone of treatment of Neisseria gonorrhoeae infections, cefixime is the only oral antimicrobial option. Increased minimum inhibitory concentrations (MICs) to cefixime have been identified worldwide and have been associated with reports of clinical failure.
To assess the risk of clinical treatment failure of N. gonorrhoeae infections associated with the use of cefixime.
A retrospective cohort study of culture-positive N. gonorrhoeae infections at a single sexual health clinic in Toronto, Canada, that routinely performs test of cure. The cohort comprised N. gonorrhoeae culture-positive individuals identified between May 1, 2010, and April 30, 2011, treated with cefixime as recommended by Public Health Agency of Canada guidelines.
Cefixime treatment failure, defined as the repeat isolation of N. gonorrhoeae at the test-of-cure visit identical to the pretreatment isolate by molecular typing and explicit denial of reexposure.
There were 291 N. gonorrhoeae culture-positive individuals identified. Of 133 who returned for test of cure, 13 were culture positive; 9 patients were determined to have experienced cefixime treatment failure, involving urethral (n = 4), pharyngeal (n = 2), and rectal (n = 3) sites. The overall rate of clinical treatment failure among those who had a test of cure was 6.77% (95% CI, 3.14%-12.45%; 9/133). The rate of clinical failure associated with a cefixime MIC of 0.12 μg/mL or greater was 25.0% (95% CI, 10.69%-44.87%; 7/28) compared with 1.90% (95% CI, 0.23%-6.71%; 2/105) of infections with cefixime MICs less than 0.12 μg/mL, with a relative risk of 13.13 (95% CI, 2.88-59.72; P < .001). CONCLUSION AND RELEVANCE: The rate of clinical failure following treatment of N. gonorrhoeae infections with cefixime was relatively high at a Toronto clinic and was associated with elevated MICs.

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Available from: Roberto G Melano, Oct 20, 2014
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    • "G1407 has also decreased susceptibility to CFX and, to a lesser extent, to CRO [4,21,28]. In this context, we note that most of the previously reported CFX or CRO treatment failures were due to Ng isolates of G1407 [4,11,12,39]. "
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    ABSTRACT: The spread of Neisseria gonorrhoeae (Ng) isolates resistant to the clinically implemented antibiotics is challenging the efficacy of treatments. Unfortunately, phenotypic and molecular data regarding Ng detected in Switzerland are scarce. We compared the characteristics of Ng detected during 1998-2001 (n = 26) to those detected during 2009-2012 (n = 34). MICs were obtained with the Etest and interpreted as non-susceptible (non-S) according to EUCAST. Sequence type (ST) was achieved implementing the NG-MAST. BlaTEM, ponA, penA, mtrR, penB, tet(M), gyrA, parC, mefA, ermA/B/C/F, rplD, rplV, and 23S rRNA genes were analyzed. The following susceptibility results were obtained (period:% of non-S, MIC90 in mg/L): penicillin (1998-2001: 42.3%, 3; 2009-2012: 85.3%, 16), cefixime (1998-2001: 0%, <=0.016; 2009-2012: 8.8%, 0.125), ceftriaxone (1998-2001: 0%, 0.004; 2009-2012: 0%, 0.047), ciprofloxacin (1998-2001: 7.7%, 0.006; 2009-2012: 73.5%, >=32), azithromycin (1998-2001: 11.5%, 0.25; 2009-2012: 23.6%, 0.38), tetracycline (1998-2001: 65.4%, 12; 2009-2012: 88.2%, 24), spectinomycin (1998-2001: 0%, 12; 2009-2012: 0%, 8). The prevalence of multidrug-resistant (MDR) isolates increased from 7.7% in 1998-2001 to 70.6% in 2009-2012. International STs and genogroups (G) emerged during 2009-2012 (G1407, 29.4%; G2992, 11.7%; G225, 8.8%). These isolates possessed distinctive mechanisms of resistance (e.g., G1407: PBP1 with L421, PBP2 pattern XXXIV, GyrA with S91F and D95G, ParC with S87R, PorB with G120K and A121N, mtrR promoter with A deletion). The prevalence of penicillin- ciprofloxacin- and tetracycline-resistant Ng has reached dramatic levels, whereas cefixime and ceftriaxone show MICs that tend to increase during time. International MDR clones less susceptible to cephalosporins are rapidly emerging indicating that the era of untreatable gonococcal infections is close.
    Full-text · Article · Feb 2014 · BMC Infectious Diseases
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    • "Extended-spectrum cephalosporins (ESCs) are the only remaining options for first-line empiric antimicrobial monotherapy in many countries worldwide [3-6]. However, verified treatment failures with particularly cefixime [7-13] but also rarely with ceftriaxone have been reported from several countries [14-18]. The first extensively-drug resistant (XDR) [3] gonococcal strains with high-level ESC resistance were also described recently [9,17,19]. "
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    ABSTRACT: In Poland, gonorrhoea has been a mandatorily reported infection since 1948, however, the reported incidences are likely underestimated. No antimicrobial resistance (AMR) data for Neisseria gonorrhoeae has been internationally reported in nearly four decades, and data concerning genetic characteristics of N. gonorrhoeae are totally lacking. The aims of this study were to investigate the AMR to previously and currently recommended gonorrhoea treatment options, the main genetic resistance determinant (penA) for extended-spectrum cephalosporins (ESCs), and genotypic distribution of N. gonorrhoeae isolates in Poland in 2010-2012. N. gonorrhoeae isolates cultured in 2010 (n = 28), 2011 (n = 92) and 2012 (n = 108) in Warsaw and Bialystok, Poland, were examined using antimicrobial susceptibility testing (Etest), pyrosequencing of penA and N. gonorrhoeae multi-antigen sequence typing (NG-MAST). The proportions of N. gonorrhoeae isolates showing resistance were as follows: ciprofloxacin 61%, tetracycline 43%, penicillin G 22%, and azithromycin 8.8%. No isolates resistant to ceftriaxone, cefixime or spectinomycin were found. However, the proportion of isolates with an ESC MIC = 0.125 mg/L, i.e. at the resistance breakpoint, increased significantly from none in 2010 to 9.3% and 19% in 2012 for ceftriaxone and cefixime, respectively. Furthermore, 3.1% of the isolates showed multidrug resistance, i.e., resistance to ciprofloxacin, penicillin G, azithromycin, and decreased susceptibility to cefixime (MIC = 0.125 mg/L). Seventy-six isolates (33%) possessed a penA mosaic allele and 14 isolates (6.1%) contained an A501V/T alteration in penicillin-binding protein 2. NG-MAST ST1407 (n = 58, 25% of isolates) was the most prevalent ST, which significantly increased from 2010 (n = 0) to 2012 (n = 46; 43%). In Poland, the diversified gonococcal population displayed a high resistance to most antimicrobials internationally previously recommended for gonorrhoea treatment and decreasing susceptibility to the currently recommended ESCs. The decreasing susceptibility to ESCs was mostly due to the introduction of the internationally spread multidrug-resistant NG-MAST ST1407 in 2011. It is essential to promptly revise the gonorrhoea treatment guidelines, improve the gonorrhoea laboratory diagnostics, and implement quality assured surveillance of gonococcal AMR (ideally also treatment failures) in Poland.
    Full-text · Article · Feb 2014 · BMC Infectious Diseases
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