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Background: The US system for gonococcal antimicrobial susceptibility surveillance monitors trends exclusively among men with urethral infection, the population from whom the yield of gonococcal culture is highest. Little is known about the susceptibility of female urogenital isolates, and it is unclear whether gonococcal susceptibility among men who report sex exclusively with women (MSW) is representative of susceptibility among women., Methods: Using isolates collected during a recent treatment trial in 5 US cities, we performed a secondary analysis to compare antimicrobial susceptibilities of Neisseria gonorrhoeae urogenital isolates obtained from women, MSW, and men who have sex with men (MSM). Pretreatment isolates were collected from trial participants; minimum inhibitory concentrations (MICs) were determined by agar dilution. Geometric mean MICs were adjusted for geographic location using general linear models., Results: Susceptibility data for urogenital isolates from 56 women, 252 MSW, and 170 MSM were studied. The adjusted geometric mean ceftriaxone MIC was similar among women (0.0067 μg/mL; 95% confidence interval [CI], 0.0049-0.0092 μg/mL) and MSW (0.0060 μg/mL; 95% CI, 0.0053-0.0066 μg/mL). In contrast, the adjusted geometric mean ceftriaxone MIC was higher among MSM (0.0098 μg/mL; 95% CI, 0.0082-0.0119 μg/mL) than among MSW. This same pattern was observed for other antimicrobials, including cefixime and azithromycin, Conclusions: Ceftriaxone, cefixime, and azithromycin MICs were higher among MSM than among MSW, but were similar among women and MSW. These findings suggest that gonococcal antimicrobial susceptibility surveillance based on urethral isolates from MSW may adequately represent susceptibility of urogenital N. gonorrhoeae in women.

Antimicrobial-resistant Neisseria gonorrhoeae (NG) infection is a global public health threat, and there is a critical need to monitor patterns of resistance and risk factors. In collaboration with the World Health Organization (WHO), the U.S. Centers for Disease Control and Prevention (CDC), and the Thailand Department of Disease Control (DDC), Ministry of Public Health (MoPH) implemented the first Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP) in November 2015. Men presenting with urethritis at two clinical settings in Bangkok, Thailand (Bangrak Hospital [BH] and Silom Community Clinic @TropMed [SCC @TropMed]) provided demographic and behavioral information and had a urethral swab for Gram’s stain and NG culture collected. The NG isolates were evaluated for antimicrobial susceptibility by the Epsilometer test (Etest) to determine minimum inhibitory concentrations (MICs) for cefixime (CFM), ceftriaxone (CRO), azithromycin (AZI), gentamicin (GEN), and ciprofloxacin (CIP). From November 2015 –October 2016, 1,102 specimens were collected from 1,026 symptomatic men; 861 (78.1%) specimens were from BH and 241 (21.9%) specimens were from SCC @TropMed. Among the 1,102 specimens, 582 (52.8%) had intracellular Gram-negative diplococci and 591 (53.6%) had NG growth (i.e., NG infection); antimicrobial susceptibility testing (AST) was performed on 590 (99.8%) NG isolates. Among all symptomatic men, 293 (28.6%) had sex with men only, 430 (41.9%) were ages 18–29 years, 349 (34.0%) had antibiotic use in the last 2 weeks, and 564 (55.0%) had NG infection. Among 23 men with repeat NG infection during this first year of surveillance, 20 (87.0%) were infected twice, 2 (8.7%) were infected three times, and 1 (4.3%) was infected more than four times. All NG isolates were susceptible to CFM and CRO, and had MICs below 2 μg/mL for AZI and below 16 μg/mL for GEN. Overall, 545 (92.4%) isolates were resistant to CIP. This surveillance activity assessed individual patients, and included demographic and behavioral data linked to laboratory data. The inclusion of both individual and laboratory information in EGASP could help identify possible persistent infection and NG treatment failures. Expansion of EGASP to additional global settings is critical to assess trends and risk factors for NG, and to monitor for the emergence of resistance. [ABSTRACT FROM AUTHOR]

Monitoring trends in antimicrobial drug-resistant Neisseria gonorrhoeae is a critical public health and global health security activity because the number of antimicrobial drugs available to treat gonorrhea effectively is rapidly diminishing. Current global surveillance methods for antimicrobial drug-resistant N. gonorrhoeae have many limitations, especially in countries with the greatest burden of disease. The Enhanced Gonococcal Antimicrobial Surveillance Program is a collaboration between the World Health Organization and the Centers for Disease Control and Prevention. The program aims to monitor trends in antimicrobial drug susceptibilities in N. gonorrhoeae by using standardized sampling and laboratory protocols; to improve the quality, comparability, and timeliness of gonococcal antimicrobial drug resistance data across multiple countries; and to assess resistance patterns in key populations at highest risk for antimicrobial drug-resistant gonorrhea so country-specific treatment guidelines can be informed. [ABSTRACT FROM AUTHOR]

We investigated whether outpatient antimicrobial drug prescribing is associated with Neisseria gonorrhoeae antimicrobial drug susceptibility in the United States. Using susceptibility data from the Gonococcal Isolate Surveillance Project during 2005-2013 and QuintilesIMS data on outpatient cephalosporin, macrolide, and fluoroquinolone prescribing, we constructed multivariable linear mixed models for each antimicrobial agent with 1-year lagged annual prescribing per 1,000 persons as the exposure and geometric mean MIC as the outcome of interest. Multivariable models did not demonstrate associations between antimicrobial drug prescribing and N. gonorrhoeae susceptibility for any of the studied antimicrobial drugs during 2005-2013. Elucidation of epidemiologic factors contributing to resistance, including further investigation of the potential role of antimicrobial drug use, is needed. [ABSTRACT FROM AUTHOR]

Background. The Centers for Disease Control and Prevention (CDC) currently recommends dual therapy with ceftriaxone and azithromycin for gonorrhea to ensure effective treatment and slow emergence of antimicrobial resistance. Since 2013, the prevalence of reduced azithromycin susceptibility increased in the United States; however, these strains were highly susceptible to cephalosporins. We identified a cluster of Neisseria gonorrhoeae isolates with high-level azithromycin resistance, several of which also demonstrated decreased ceftriaxone susceptibility. Methods. Eight N. gonorrhoeae isolates collected from 7 patients on Oahu, Hawaii, seen 21 April 2016 through 10 May 2016 underwent routine Etest antimicrobial susceptibility testing by the Hawaii Department of Health. All demonstrated elevated azithromycin minimum inhibitory concentrations (MICs) >256 μg/mL and elevated ceftriaxone MICs (≥0.125 μg/mL). Isolates were sent to the University of Washington and CDC for confirmatory agar dilution testing; sequence data were sent to CDC for analysis. All patients were interviewed and treated, and when possible, partners were interviewed, tested, and treated. Results. All isolates had azithromycin MICs >16 μg/mL and 5 had ceftriaxone MICs = 0.125 μg/mL by agar dilution. All isolates were β-lactamase positive and were resistant to penicillin, tetracycline, and ciprofloxacin. Genomic analysis revealed genetic relatedness. No patients reported recent travel or antibiotic use, and no male patients reported male sex partners. All patients were successfully treated. Conclusions. This cluster of genetically related gonococcal isolates with decreased ceftriaxone susceptibility and high-level azithromycin resistance may bring the threat of treatment failure in the United States with the current recommended dual therapy one step closer. [ABSTRACT FROM AUTHOR]

Background: We assessed the validity of testing for antimicrobial susceptibility of clinical and mutant Neisseria gonorrhoeae (GC) isolates by disk diffusion in comparison to agar dilution, and Etest® (bioMerieux, France), respectively, for three third generation extended spectrum cephalosporins (ESC): ceftriaxone (CRO), cefixime (CFX), and cefpodoxime (CPD). Methods: One hundred and five clinical isolates and ten laboratory-mutants were tested following Clinical Laboratory Standard Institute (CLSI) and manufacturer's standards for each of the three methods. The measured diameters by the disk diffusion method were tested for correlation with the MIC values by agar dilution. In addition, comparisons with the Etest® were made. Categorical results for concordance, based on standard CLSI cutoffs, between the disk diffusion and the other two methods, respectively, were tested using the Chi-square statistics. Reproducibility was tested for CFX across a 6-month interval by repeated disk tests. Results: Across all 115 specimens, the disk diffusion tests produced good categorical agreements, exhibiting concordance of 93.1%, 92.1%, and 90.4% with agar dilution and 93.0%, 92.1%, and 90.4% with Etest®, for CRO, CFX, and CPD, respectively. Pearson correlations between disk-diffusion diameters and agar dilution MIC's were -0.59, -0. 67, and -0.81 for CRO, CFX, and CPD, respectively. The correlations between disk diffusion and Etest® were -0.58, -0. 73, and -0.49. Pearson correlation between the CFX disk readings over a 6-month interval was 91%. Conclusions: Disk diffusion tests remain to be a useful, reliable and fast screening method for qualitative antimicrobial susceptibility testing for ceftriaxone, cefixime, and cefpodoxime. [ABSTRACT FROM AUTHOR]

Background Neisseria gonorrhoeae has progressively developed resistance to sulfonamides, penicillin, tetracycline and fluoroquinolones, and gonococcal susceptibility to cephalosporins has been declining worldwide. Methods We described trends in gonococcal antimicrobial susceptibility in the USA from January 2006 through June 2012. Susceptibility data for cefixime, ceftriaxone, azithromycin, penicillin, tetracycline and ciprofloxacin were obtained from the Gonococcal Isolate Surveillance Project (GISP), a sentinel surveillance system that monitors antimicrobial susceptibility in urethral gonococcal isolates collected from symptomatic men at 25-30 sexually transmitted disease clinics throughout the USA. Results The percentage of isolates with elevated cefixime minimum inhibitory concentrations (MICs) (=0.25 μg/mL) increased from 0.1% in 2006 to 1.4% in 2010-2011 and was 1.1% in the first 6 months of 2012. The percentage with elevated ceftriaxone MICs (=0.125 μg/mL) increased from 0.1% in 2006 to 0.3%-0.4% during 2009 through the first 6 months of 2012. There were no temporal trends in the prevalence of elevated azithromycin MICs (=2 μg/mL) (0.2%- 0.5%). The prevalence of resistance remained high for penicillin (11.2%-13.2%), tetracycline (16.7%-22.8%) and ciprofloxacin (9.6%-14.8%). Conclusions The proportion of gonococcal isolates with elevated cephalosporin MICs increased from 2006 to 2010, but plateaued during 2011 and the first 6 months of 2012. Resistance to previously recommended antimicrobials has persisted. As the number of antimicrobials available for gonorrhoea treatment dwindles, surveillance systems such as GISP will be critical to detect emerging resistance trends and guide treatment decisions. [ABSTRACT FROM AUTHOR]

Background: Gonorrhea treatment has been complicated by antimicrobial resistance in Neisseria gonorrhoeae. Gonococcal fluoroquinolone resistance emerged more rapidly among men who have sex with men (MSM) than men who have sex exclusively with women (MSW). Objective: To determine whether N. gonorrhoeae urethral isolates from MSM were more likely than isolates from MSW to exhibit resistance to or elevated minimum inhibitory concentrations (MICs) of antimicrobials used to treat gonorrhea. Design: 6 years of surveillance data from the Gonococcal Isolate Surveillance Project. Setting: Publicly funded sexually transmitted disease clinics in 30 U.S. cities. Patients: Men with a total of 34 600 episodes of symptomatic urethral gonorrhea. Measurements: Percentage of isolates exhibiting resistance or elevated MICs and adjusted odds ratios for resistance or elevated MICs among isolates from MSM compared with isolates from MSW. Results: In all U.S. regions except the West, isolates from MSM were significantly more likely to exhibit elevated MICs of ceftriaxone and azithromycin than isolates from MSW (P < 0.050). Isolates from MSM had a high prevalence of resistance to ciprofloxacin, penicillin, and tetracycline and were significantly more likely to exhibit antimicrobial resistance than isolates from MSW (P < 0.001). Limitations: Sentinel surveillance may not be representative of all patients with gonorrhea. HIV status, travel history, and antimicrobial use data were missing for some patients. Conclusion: Men who have sex with men are vulnerable to the emerging threat of antimicrobial-resistant N. gonorrhoeae. Because antimicrobial susceptibility testing is not routinely done in clinical practice, clinicians should monitor for treatment failures among MSM diagnosed with gonorrhea. Strengthened prevention strategies for MSM and new antimicrobial treatment options are needed. Primary Funding Source: Centers for Disease Control and Prevention. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance in Neisseria gonorrhoeae has severely limited the number of treatment options, and the emergence of extended-spectrum cephalosporin resistance threatens the effectiveness of the last remaining recommended treatment regimen. This study assessed the in vitro susceptibility of N. gonorrhoeae to ETX0914, a novel spiropyrimidinetrione that inhibits DNA biosynthesis. In vitro activity was determined by agar dilution against 100 N. gonorrhoeae isolates collected from men presenting with urethritis in the USA during 2012–2013 through the Gonococcal Isolate Surveillance Project. The minimum inhibitory concentration (MIC) that inhibited growth in 50% (MIC 50 ) and 90% (MIC 90 ) of isolates was calculated for each antimicrobial agent. ETX0914 demonstrated a high level of antimicrobial activity against N. gonorrhoeae , including isolates with decreased susceptibility or resistance to currently available agents. The ability of ETX0914 to inhibit the growth of N. gonorrhoeae was similar to ceftriaxone, which is currently recommended in combination with azithromycin to treat gonorrhoea. The data presented in this study strongly suggest that ETX0914 should be evaluated in a clinical trial for the treatment of N. gonorrhoeae . [ABSTRACT FROM AUTHOR]