Expansion of the WHO GASP facilitated enhanced AMR surveillance to meet the ongoing challenges of control of gonococcal AMR. The results highlight that the emergence of decreased susceptibility to ceftriaxone and resistance to spectinomycin and azithromycin will unavoidably lead to loss of therapeutic options, and a search for new effective agents needs to be initiated to respond to the emergence of resistant isolates.

BackgroundRecent WHO guidelines recommend dual therapy with ceftriaxone or cefixime plus azithromycin for gonorrhea. Azithromycin in combination with gentamicin or spectinomycin has been recommended in treatment failure cases. Due to emergence of multi-drug resistant (MDR) and extensively-drug resistant (XDR) Neisseria gonorrhoeae strains, it is important to look for efficacy of these combinations and also of others that might be used in future. Therefore, we aimed to evaluate in vitro synergy of 21 dual combinations including current and alternative WHO recommended treatment regimens and other dual combinations.Methods and findingsThe potential utility of in-vitro interactions of 21 combinations was investigated against 95 N. gonorrhoeae strains including 79 MDR and one XDR strain collected during March 2013 to July 2017 and fractional inhibitory concentration index (FICI) was calculated. These 21 combinations comprised of two WHO currently recommended (cefixime+azithromycin, ceftriaxone+azithromycin); two WHO recommended in treatment failure cases (azithromycin+gentamicin, spectinomycin+azithromycin) and other 17 combinations.ResultsFICI of the four WHO recommended antimicrobial combinations were higher (>1.0) than the five novel combinationbreeds (FICI range 0.603–0.951) in the study i.e. gentamicin+ertapenem, moxifloxacin+ertapenem, spectinomycin+ertapenem, azithromycin+ moxifloxacin, cefixime+gentamicin. No antagonistic effect of the above four WHO recommended combinations except spectinomycin+azithromycin (FICI = 4.25) was observed for the XDR strain. Out of above five novel combinations, four combinations produced high synergistic effects in overall 95 strains and also for the XDR strain with FICI of 0.13 to 0.38. Antagonistic effects varying from 3.2 to 12.6% were observed for 10 out of 21 tested combinations (azithromycin in combination with gentamicin and spectinomycin; ceftriaxone with moxifloxacin, gentamicin, spectinomycin and ertapenem; spectinomycin with moxifloxacin and gentamicin; cefixime and gentamicin combination with moxifloxacin).ConclusionWHO recommended cefixime+azithromycin, ceftriaxone+azithromycin combinations having no antagonism indicates their continuing clinical utility. Highest antagonism without any synergistic effect for the WHO recommended spectinomycin+azithromycin in treatment failure cases suggests that this combination should be evaluated further both in vitro and in vivo. Highest synergistic or additive effect without any antagonistic effect of the above five novel combinations suggests that these may be recommended for treatment in future.

Background and Objectives:Biological false positive (BFP) reactivity by the Venereal Disease Research Laboratory (VDRL) test used for diagnosis of syphilis is a cause for concern. The use of the VDRL as a screening procedure is challenged by some studies. The aim of this study is to determine the prevalence of BFP reactions in different subject groups and to assess the usefulness of Treponema pallidum hemagglutination (TPHA) test in low titre VDRL reactive sera.Materials and Methods:A total of 5785 sera from sexually transmitted diseases (STD) clinic attendees, antenatal clinic attendees, husbands of antenatal cases, peripheral health centres attendees (representing community population) and from patients referred from different OPDs/wards were screened for BFP reactions by the VDRL test. Sera reactive in the VDRL test were confirmed by the TPHA test.Results:Out of 80 qualitative VDRL reactive sera, 68 had <1:8 titre on quantitation and TPHA was positive in 59 samples, indicating BFP reactivity in 0.2% in all the subject groups. BFP was nil in the community population. The male-to-female ratio of BFP reactions was 2:1. VDRL and TPHA positivity was highest (76%) in the age group of 20-29 years. The seroprevalence of syphilis varied from 0.4% to 3.5% in different patient groups.Conclusions:The results of this study highlight that the TPHA positivity was high (86.8%) in sera with VDRL titre less than 1:8. Therefore, for the diagnosis of syphilis, it is recommended that a confirmatory test such as TPHA should be performed on all sera with a reactive VDRL regardless of its titre.

bAntimicrobial susceptibility testing of 258 Neisseria gonorrhoeae isolates by Etest determined that 60.1% were multidrug resistant (MDR), while 5% of the strains had decreased susceptibility to currently recommended extended-spectrum cephalosporins (ESCs). Among these, 84.5% of MDR strains and 76.9% of strains that had decreased susceptibility to ESCs were susceptible to gentamicin. No MDR isolate was resistant to gentamicin. These in vitro results suggest that gentamicin might be an effective treatment option for the MDR strains and in dual therapy for gonorrhea. However, further research regarding the clinical treatment outcomes is essential. N eisseria gonorrhoeae clinical isolates resistant to extendedspectrum cephalosporins (ESCs), the last remaining options for empirical therapy, and most other antimicrobials have been reported worldwide in recent years (1-4). Organizations such as the World Health Organization (WHO), the U.S. Centers for Disease Control and Prevention (CDC), and the European Centre for Disease Prevention and Control (ECDC) are considering infections caused by multidrug-resistant (MDR) and extensively drugresistant (XDR) N. gonorrhoeae major public health problems (5-7). With the increasing prevalence of drug resistance, there is an urgent need for new and effective treatment options. Gentamicin has been used for the past 2 decades in the management of gonorrhea in Malawi (8, 9). Gentamicin has been considered an option for the treatment of infections due to the MDR and XDR strains and for future treatment of gonorrhea particularly in dual therapy in other geographic regions (10-12).Earlier studies focused on the in vitro susceptibility of N. gonorrhoeae to gentamicin (8,(13)(14)(15)(16)(17). Some of these studies were on a limited number of isolates (13,17). To the best of our knowledge, no study has analyzed the in vitro susceptibility of gentamicin against MDR strains. Therefore, this study was aimed at determining the (i) trend of in vitro susceptibility of N. gonorrhoeae isolates to gentamicin during 2010 to 2015, (ii) status of gentamicin susceptibility for MDR strains and strains with decreased susceptibility to ESCs, and (iii) profile of gentamicin-less-susceptible (LS) strains for eight other antimicrobials recommended currently and in the past for treatment of gonorrhea.A total of 258 N. gonorrhoeae isolates obtained from consecutive patients attending a sexually transmitted disease (STD) clinic from August 2010 to December 2015 were identified on the basis of colony morphology, Gram staining, and oxidase, superoxol, and carbohydrate utilization tests (18). Susceptibility testing for gentamicin and other antimicrobials, such as ESCs (ceftriaxone, cefpodoxime, cefixime), penicillin, tetracycline, ciprofloxacin, spectinomycin, and azithromycin, was performed using the Etest strip per manufacturer instructions (bioMérieux SA, France) on GC agar (Becton, Dickinson and Company [BD], Sparks, MD) containing 1% vitamin growth supplement (HiMedia, India) or Isovitalex (BD). Susceptibilit...