BACKGROUND: Tolerance enables bacteria to survive intermittent antibiotic exposure without an increase in antimicrobial susceptibility. In this study, we investigated the presence of tolerance to three antimicrobials, ceftriaxone, azithromycin and ciprofloxacin, in clinical isolates and the WHO (World Health Organization) reference panel of Neisseria gonorrhoeae.
METHODS: We used the modified tolerance disk (TD test) to assess for tolerance to ceftriaxone, azithromycin and ciprofloxacin in 14 WHO reference strains and 62 N. gonorrhoeae clinical isolates-evenly divided between anorectal and urogenital infections. The isolates underwent a three-step incubation process wherein the isolates were exposed to an antibiotic disk for 20 h of incubation (Step I), followed by the replacement of the antibiotic disk with a nutrient disk for overnight incubation (Step II) and additional overnight incubation with extra nutrients (Step III).
RESULTS: A total of 4 of the 62 clinical anorectal isolates and none of the urogenital isolates exhibited tolerance to azithromycin (p = 0.033). Tolerance to ceftriaxone and ciprofloxacin was observed in eight and four isolates, respectively, with no difference between infection sites. Tolerance was also detected in 8 (K, M, N, O, P, U, V, W) out of the 14 WHO reference strains, with varying patterns of tolerance to ceftriaxone (n = 8), ciprofloxacin (n = 2) and azithromycin (n = 1).
CONCLUSIONS: This study identified ceftriaxone, azithromycin and ciprofloxacin tolerance in clinical and WHO reference N. gonorrhoeae isolates. Azithromycin tolerance was more common in anorectal than urogenital infections.

BACKGROUND: The association between sodium-glucose cotransporter-2 (SGLT2) inhibitors and the risk of urogenital infections remains controversial. This study aimed to investigate the association between SGLT2 inhibitors and the incidence of perineal soft tissue infections, including Fournier\'s gangrene (FG), genital bacterial infections, and urinary tract infections (UTIs), using administrative claims data in Japan.
METHODS: In this retrospective cohort study, we utilized the JMDC Claims Database. The study included patients aged 18 years or older diagnosed with type 2 diabetes mellitus, identified by a diagnostic code, who received new prescriptions for SGLT2 inhibitors or dipeptidyl peptidase 4 (DPP-4) inhibitors between April 2014 and August 2020. Using one-to-one propensity score (PS) matching, we compared the incidence of perineal soft tissue infections, including FG, genital bacterial infection, and UTIs between groups treated with SGLT2 and DPP-4 inhibitors. Hazard ratios (HR) and their 95% confidence intervals (CI) were estimated using the Cox proportional hazards model.
RESULTS: We identified 34,897 patients in the SGLT2 inhibitor group and 135,311 patients in the DPP-4 inhibitor group. After one-to-one PS matching, 31,665 pairs were generated. The mean age of the patients was 51 years, with approximately 70% being male. The use of SGLT2 inhibitors was associated with a decreased risk of UTI (HR 0.90, 95% CI 0.83-0.98) and an increased risk of genital bacterial infection (HR 1.23, 95% CI 1.03-1.46) compared to DPP-4 inhibitors. However, no significant association was observed with perineal soft tissue infection (HR 1.05, 95% CI 0.61-1.81).
CONCLUSIONS: SGLT2 inhibitors were associated with a reduced risk of UTI and an increased risk of genital bacterial infection. They showed no significant association with perineal soft tissue infection when compared to DPP-4 inhibitors. Future research should explore broader demographics, focusing on the elderly and achieving gender balance, to gain a comprehensive understanding of infection risks.

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have been shown to reduce adverse cardiovascular events in patients with type 2 diabetes mellitus, all-cause mortality, and heart failure hospitalization in patients with heart failure, as well as adverse renal outcomes. However, concerns regarding the heightened risk of genitourinary (GU) infections, particularly urinary tract infections, remain a significant barrier to their wider adoption. Addressing these misconceptions using existing evidence is needed to ensure proper risk-benefit assessment and optimal utilization of this efficacious therapy. This review aims to provide a balanced perspective on the evidence-based cardiovascular and renal benefits of SGLT2is and the associated risk of GU infections. We also summarize and propose clinical practice considerations for SGLT2i-associated GU infections focusing on patients with cardiovascular disease.

The development of new approaches and drugs for effective control of the chronic and complicated forms of urogenital chlamydia caused by Chlamydia trachomatis, which is suspected to be one of the main causes of infertility in both women and men, is an urgent task. We used the technology of single-domain antibody (nanobody) generation both for the production of targeting anti-chlamydia molecules and for the subsequent acquisition of anti-idiotypic nanobodies (ai-Nbs) mimicking the structure of a given epitope of the pathogen (the epitope of the Chlamydial Type III Secretion System Needle Protein). In a mouse model, we have shown that the obtained ai-Nbs are able to induce a narrowly specific humoral immune response in the host, leading to the generation of intrinsic anti-Chlamydia antibodies, potentially therapeutic, specifically recognizing a given antigenic epitope of Chlamydia. The immune sera derived from mice immunized with ai-Nbs are able to suppress chlamydial infection in vitro. We hypothesize that the proposed method of the creation and use of ai-Nbs, which mimic and present to the host immune system exactly the desired region of the antigen, create a fundamentally new universal approach to generating molecular structures as a part of specific vaccine for the targeted induction of immune response, especially useful in cases where it is difficult to prepare an antigen preserving the desired epitope in its native conformation.

[This corrects the article DOI: 10.3389/fcimb.2018.00415.].

Testicular tuberculosis (TB) is a rare disease, and it tends to mimic other testicular diseases which are more common. We highlight the case of a 37-year-old male who presented to the emergency department with testicular torsion. Further investigations revealed evidence of TB.

This study evaluated the distribution of macrolide-resistant Mycoplasma genitalium in multiple urogenital specimens collected from women enrolled in a prospective multicenter US clinical study.
Four female urogenital specimens (vaginal swab, urine, endocervical swab, ectocervical brush/spatula) collected from each subject were tested using a transcription-mediated amplification (TMA) assay for M. genitalium. TMA-positive specimens were evaluated by reverse transcription-polymerase chain reaction and bidirectional Sanger sequencing of M. genitalium 23S rRNA to identify the presence of macrolide-resistance-mediating mutations (MRMs) at base positions 2058/2059.
Of 140 women with ≥1 TMA-positive specimens, 128 (91.4%) yielded M. genitalium 23S rRNA sequence. MRMs were found in 52% of vaginal specimens, 46.3% of urine specimens, 37.8% of endocervical specimens, and 46% of ectocervical specimens. There were 44 unique specimen type/sequence phenotype combinations of M. genitalium infection. Most (81; 63.3%) women had single specimen-sequence phenotype (macrolide-susceptible, MRM, or both) infections, while 24 (18.8%) women had multiple specimen-sequence phenotype concordant infections, and 23 (17.9%) women had multiple specimen-sequence phenotype discordant infections. The sensitivity for any single specimen type to detect overall urogenital tract macrolide-resistant M. genitalium infection status was 96.3% for vaginal swab samples, 82.6% for urine samples, 70.8% for endocervical swab samples, and 82.1% for ectocervical brush/spatula liquid Pap samples.
The distribution of M. genitalium infections in female urogenital tract specimens is highly complex, with multiple phenotypic combinations of the organism infecting a significant proportion of women at different anatomic specimen collection sites. Vaginal swab sampling yielded the highest sensitivity for identifying women with macrolide-resistant M. genitalium urogenital tract infections.

Urinary tract infection (UTI) is one of the most prevalent bacterial infections, particularly in women, children, and the elderly. Uropathogenic Escherichia coli (UPEC) is the predominant etiological agent of UTI. Uropathogens are directly instilled in the urinary bladder, bypassing the lower urogenital tract, in the widely used murine model of UTI. We assessed whether vaginal inoculation of UPEC led to UTI and how stages of the estrous cycle would impact bacterial colonization in mice. Mice in proestrus, estrus, metestrus, and diestrus were identified by vaginal cytology and inoculated with UPEC in the vaginal tract. Mice were euthanized 1 day after infection, and bacterial loads in the urogenital tract, liver, and spleen were enumerated. Mice in estrus exhibited the highest and most consistent UPEC burdens in all organs, except the bladder. Vaginal inoculation resulted in bladder colonization in a UPEC strain-specific manner. In contrast, transurethral inoculation of UPEC led to bladder colonization. Importantly, inoculation by both routes led to vaginal and uterine colonization and concomitant systemic dissemination to the spleen and liver. The kinetics of bacterial colonization over 2 weeks following vaginal inoculation was comparable in the urogenital tract. Tissue sections revealed the induction of vaginitis and cystitis upon the vaginal instillation of UPEC. In summary, vaginal inoculation of UPEC in mice during estrus represents a novel approach to investigate infection of the kidneys and genital tract and systemic dissemination from the urogenital tract. Our findings suggest that estrogen primes the urogenital tract to create a conducive milieu for UPEC colonization.

BACKGROUND: Type 2 diabetes mellitus (T2DM) in postmenopausal women is associated with a high incidence of urogenital infections, which negatively impact the quality of life and increase morbidity, mortality, and health-care costs. Glucosuria is a known risk factor for these infections; therefore, it is of interest to determine if increased glucosuria secondary to sodium-glucose cotransporter-2 inhibitors (SGLT2in) impacts the incidence and severity of urogenital infections in postmenopausal women with T2DM.
METHODS: The study was conducted at Gaffrée Guinle University Hospital on two groups of postmenopausal women with T2DM: with and without SGLT2in therapy (n = 80 in each group). Medical records and laboratory parameters (urinary dipstick test and culture; blood glucose, glycosylated hemoglobin, and creatinine; cervical cytologic study) of all subjects were carefully assessed at baseline and thrice during the 12-month study period.
RESULTS: We observed a significant incidence of vulvovaginitis (relative risk [RR], 2.37; 95% confidence interval [CI], 1.10-5.10; P = 0.03) and asymptomatic bacteriuria (RR, 2.47; 95% CI, 1.09-5.60; P = 0.03), but not of urinary tract infections (RR, 2.08; 95% CI, 0.74-5.81; P = 0.16), secondary to SGLT2in therapy. Genital infection was severe enough to warrant treatment discontinuation in 57.89% of patients in group 1. All urinary tract infections were of mild intensity with a good response to antibiotic therapy.
CONCLUSIONS: Glucosuria induced by SGLT2in therapy may lead to a high incidence of urogenital infections in postmenopausal women with T2DM and can be considered a risk factor for these infections.

We performed in vitro susceptibility testing for eravacycline in comparison to 4 other antimicrobials against 10 Mycoplasma genitalium, 40 Mycoplasma hominis, 44 Mycoplasma pneumoniae, 20 Ureaplasma parvum, and 20 Ureaplasma urealyticum isolates. All eravacycline MICs were ≤0.25 μg/ml, except that for one isolate of M. genitalium, for which the MIC was 2 μg/ml. Eravacycline was markedly more potent than tetracycline, azithromycin, moxifloxacin, and clindamycin against all isolates tested, which included 37 macrolide, tetracycline, and/or fluoroquinolone-resistant organisms.