Mycoplasma genitalium's Antibiotic Resistance in Sexually Transmitted Infections Clinics in Israel.

OBJECTIVES: To determine the prevalence of antibiotic resistance rate in Mycoplasma genitalium, and distribution of mutations associated with this resistance, among patients that attended sexually transmitted infections (STI) investigation clinics. MATERIALS AND METHODS: This cross-sectional study included M. genitalium-positive samples (urine, vaginal, rectal, and pharyngeal swabs) collected from 170 patients attending two STI investigation clinics, which were subjected to macrolide and quinolone resistance mutations analyses. Data regarding patient age, sex, and material/anatomical site of testing were collected. RESULTS: Macrolide-resistance mutations were identified in 48.8% of samples and were more common among males (p < .0001) and in rectal samples (p < .05). A2059C was the most prevalent macrolide-resistance mutation (18.2%). Quinolone resistance was detected in 23% of the samples, with S83I being the most common (17.1%) mutation. Rate of co-resistance to macrolides and quinolones was 21.2%. CONCLUSIONS: The high rate of antibiotic resistance found in the current study, especially to macrolides, underscores the importance of antibiotic resistance monitoring in M. genitalium isolates in cases of persistent or recurrent urethritis/cervicitis, in cases of treatment failure and among specific populations. Such surveillance will improve treatment regimens and cure rates.

Sexually Transmitted Diseases in Northern Israel: Insights From a Large Referral Laboratory.

OBJECTIVES: The aims of the study are to investigate the distribution and frequency of different sexually transmitted diseases (STDs) among a large study population of individuals undergoing STD investigation both in inpatient and STD clinic settings and to evaluate influence of test anonymity on the positivity rate of pathogens. MATERIAL AND METHODS: A retrospective study retrieved epidemiologic data from the following 3 sources: a secondary referral hospital and 2 STD clinics in Northern Israel. Positivity rate of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Mycoplasma genitalium , and Trichomonas vaginalis (TV) was assessed and stratified based on age, sex, site of sampling, and anonymity of test. Adjusted odds ratios (ORs) were calculated by multivariable logistic regression. RESULTS: Overall, 3,753 assays were performed on 2,407 patients who were screened for STD. Chlamydia trachomatis (4.8%) was the most frequently detected STD, followed by NG (2.1%), MG (1.9%), and TV (0.6%). Mycoplasma genitalium (OR, 4.32; 95% CI, 1.70-10.97; p = .001) and NG (OR, 6.08; 95% CI, 2.18-16.96; p < .001) were significantly associated with male sex, while TV was more frequently encountered among female individuals (OR, 4.34; 95% CI, 1.49-12.50; p = .003). Mycoplasma genitalium infection was detected most commonly by urine samples, while rectal swabs were the leading source of positive tests for CT. Compared with fully identified patients, those tested anonymously were 6-fold more likely to be tested positive for TV (adjusted OR, 6.49; 95% CI, 2.06-20.42; p = .001). CONCLUSIONS: Chlamydia trachomatis and NG are the leading non-HIV STDs in Northern Israel. Anonymous tests predict higher positivity of TV. Rectal sampling should be increasingly used because of its efficacy in detecting CT infections.

Insights into RNA unwinding and ATP hydrolysis by the flavivirus NS3 protein.

Together with the NS5 polymerase, the NS3 helicase has a pivotal function in flavivirus RNA replication and constitutes an important drug target. We captured the dengue virus NS3 helicase at several stages along the catalytic pathway including bound to single-stranded (ss) RNA, to an ATP analogue, to a transition-state analogue and to ATP hydrolysis products. RNA recognition appears largely sequence independent in a way remarkably similar to eukaryotic DEAD box proteins Vasa and eIF4AIII. On ssRNA binding, the NS3 enzyme switches to a catalytic-competent state imparted by an inward movement of the P-loop, interdomain closure and a change in the divalent metal coordination shell, providing a structural basis for RNA-stimulated ATP hydrolysis. These structures demonstrate for the first time large quaternary changes in the flaviviridae helicase, identify the catalytic water molecule and point to a beta-hairpin that protrudes from subdomain 2, as a critical element for dsRNA unwinding. They also suggest how NS3 could exert an effect as an RNA-anchoring device and thus participate both in flavivirus RNA replication and assembly.