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Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed. more...

Background: Tracking the spread of antimicrobial-resistant Neisseria gonorrhoeae is a major priority for national surveillance programmes., Objectives: We investigate whether WGS and simultaneous analysis of multiple resistance determinants can be used to predict antimicrobial susceptibilities to the level of MICs in N. gonorrhoeae., Methods: WGS was used to identify previously reported potential resistance determinants in 681 N. gonorrhoeae isolates, from England, the USA and Canada, with phenotypes for cefixime, penicillin, azithromycin, ciprofloxacin and tetracycline determined as part of national surveillance programmes. Multivariate linear regression models were used to identify genetic predictors of MIC. Model performance was assessed using leave-one-out cross-validation., Results: Overall 1785/3380 (53%) MIC values were predicted to the nearest doubling dilution and 3147 (93%) within ±1 doubling dilution and 3314 (98%) within ±2 doubling dilutions. MIC prediction performance was similar across the five antimicrobials tested. Prediction models included the majority of previously reported resistance determinants. Applying EUCAST breakpoints to MIC predictions, the overall very major error (VME; phenotypically resistant, WGS-prediction susceptible) rate was 21/1577 (1.3%, 95% CI 0.8%-2.0%) and the major error (ME; phenotypically susceptible, WGS-prediction resistant) rate was 20/1186 (1.7%, 1.0%-2.6%). VME rates met regulatory thresholds for all antimicrobials except cefixime and ME rates for all antimicrobials except tetracycline. Country of testing was a strongly significant predictor of MIC for all five antimicrobials., Conclusions: We demonstrate a WGS-based MIC prediction approach that allows reliable MIC prediction for five gonorrhoea antimicrobials. Our approach should allow reasonably precise prediction of MICs for a range of bacterial species., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.) more...

Gonorrhea is a major cause of serious reproductive complications in women and can facilitate human immunodeficiency virus (HIV) transmission. Effective treatment is a cornerstone of U.S. gonorrhea control efforts, but treatment of gonorrhea has been complicated by the ability of Neisseria gonorrhoeae to develop antimicrobial resistance. This report, using data from CDC's Gonococcal Isolate Surveillance Project (GISP), describes laboratory evidence of declining cefixime susceptibility among urethral N. gonorrhoeae isolates collected in the United States during 2006-2011 and updates CDC's current recommendations for treatment of gonorrhea. Based on GISP data, CDC recommends combination therapy with ceftriaxone 250 mg intramuscularly and either azithromycin 1 g orally as a single dose or doxycycline 100 mg orally twice daily for 7 days as the most reliably effective treatment for uncomplicated gonorrhea. CDC no longer recommends cefixime at any dose as a first-line regimen for treatment of gonococcal infections. If cefixime is used as an alternative agent, then the patient should return in 1 week for a test-of-cure at the site of infection. more...

Neisseria gonorrhoeae is a major cause of pelvic inflammatory disease, ectopic pregnancy, and infertility, and it can facilitate human immunodeficiency virus (HIV) transmission. Emergence of gonococcal resistance to penicillin and tetracycline occurred during the 1970s and became widespread during the early 1980s. More recently, resistance to fluoroquinolones developed. Resistance was documented first in Asia, then emerged in the United States in Hawaii followed by other western states. It then became prevalent in all other regions of the United States. In Hawaii, fluoroquinolone resistance was first noted among heterosexuals; however, resistance in the United States initially became prevalent among men who have sex with men (MSM) before generalizing to heterosexuals. This emergence of resistance led CDC, in 2007, to discontinue recommending any fluoroquinolone regimens for the treatment of gonorrhea. CDC now recommends dual therapy for gonorrhea with a cephalosporin (ceftriaxone 250 mg) plus either azithromycin or doxycycline. This report summarizes trends in cephalosporin susceptibility among N. gonorrhoeae isolates in the United States during 2000-2010 using data from the Gonococcal Isolate Surveillance Project (GISP). During that period, the percentage of isolates with elevated minimum inhibitory concentrations (MICs) to cephalosporins (≥0.25 µg/mL for cefixime and ≥0.125 µg/mL for ceftriaxone) increased from 0.2% in 2000 to 1.4% in 2010 for cefixime and from 0.1% in 2000 to 0.3% in 2010 for ceftriaxone. Although cephalosporins remain an effective treatment for gonococcal infections, health-care providers should be vigilant for treatment failure and are requested to report its occurrence to state and local health departments. State and local public health departments should promote maintenance of laboratory capability to culture N. gonorrhoeae to allow testing of isolates for cephalosporin resistance. They also should develop enhanced surveillance and response protocols for gonorrhea treatment failures and report gonococcal treatment failures to CDC. more...