LITERATURE UPDATE
multiantigen sequence typing (NG- MAST). The majority of infections occurred among men with urogenital infections and 57.9% of male patients were men who have sex with men. Overall, the cefixime resistance remained stable during the time. An increase of azithromycin resistance was observed until 2018 (26.5%) with a slight decrease in the last year.
In 2019, gonococci showing
azithromycin minimum inhibitory concentration (MIC) above the EUCAST epidemiological cut-off value (ECOFF) accounted for 9.9%. Ciprofloxacin resistance and penicillinase-producing N. gonorrhoeae (PPNG) percentages increased reaching 79.1% and 18.7%, respectively, in 2019.
The most common sequence types identified were 5441, 1407, 6360, and 5624. The predominant genogroup (G) was the 1407; moreover, a new genogroup, G13070, was also detected. A variation in the antimicrobial resistance rates and high genetic variability were observed in this study. The main phenotypic and genotypic characteristics of N. gonorrhoeae isolates were described to monitor the spread of drug- resistant gonorrhoea.
Neisseria gonorrhoeae arthritis in a patient with systemic lupus: resistance and virulence profiles de Oliveira VF, Coracini Tonacio A, Marchi AP et al. Microbes Infect. 2023 Jan-Feb; 25 (1-2):105037. doi: 10.1016/j. micinf.2022.105037.
In this study, the authors describe a case report of gonococcal arthritis in a systemic lupus erythematosus (SLE) patient. Although several mechanisms favour disseminated gonococcal infection (DGI) in patients immunosuppressed by SLE, this association is rarely reported in literature.
The authors performed whole- genome sequencing (WGS) of the aetiologic agent involved and molecular analysis using a global collection of Neisseria gonorrhoeae strains. The sample reported here was derived from synovial fluid identified in this collection, the others being from the usual anatomical sites. Antimicrobial susceptibility was
determined by disk diffusion and Etest, and WGS was conducted to determine multilocus sequence typing profiles, group isolates based on core genome single nucleotide polymorphisms (SNP), and identify virulence genes and antimicrobial resistance determinants. The N. gonorrhoeae samples in the global collection were highly
heterogeneous. The SNP tree had a total of 19,532 SNPs in 320 samples. The authors’ sample displayed resistance to ciprofloxacin (MIC = 2 μg/mL) and tetracycline (zone diameter = 0 mm), belonged to ST 1588 and was not closely related to any isolate in the global collection of N. gonorrhoeae strains. The isolate had genetic features
related to beta-lactam, tetracycline and quinolone resistance. Seventy-one virulence genes were identified in the sample, belonging to the following classes: adherence, efflux pump, immune modulator, invasion, iron uptake, protease and stress adaptation. Moreover, no virulence genes for immune evasion and toxin were identified.
Molecular detection of ceftriaxone resistance in Neisseria gonorrhoeae clinical specimens: a tool for public health control
Day MJ, Boampong D, Pitt R et al. Sex Transm Infect. 2024 Jul 25:sextrans-2024-056132. doi: 10.1136/sextrans-2024-056132. Online ahead of print.
This study aimed to validate and implement a rapid screening assay for molecular detection of the penA-60 allele that is associated with ceftriaxone resistance in Neisseria gonorrhoeae for use on both isolate lysates and clinical specimen DNA extracts. An N. gonorrhoeae penA real-time
(RT)-PCR was adapted to include a species-specific pap confirmation target and a commercially available internal control to monitor for PCR inhibition. The modified assay was validated using N. gonorrhoeae-positive (n=24) and N. gonorrhoeae-negative (n=42) clinical specimens and isolate lysates. The panel included seven samples with resistance conferred by penA alleles targeted by the assay and four samples with different penA alleles. The feasibility of using the penA RT-PCR for molecular surveillance was assessed using clinical specimens from 54 individuals attending a London sexual health clinic who also had an N. gonorrhoeae isolate included in the 2020 Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP).
The assay correctly identified
N. gonorrhoeae specimens (n=7) with penA-60/64 alleles targeted by the assay. No penA false negatives/positives were detected, giving the penA target of the assay a sensitivity, specificity, positive and negative predicted values (PPV, NPV) of 100% (95% CIs; sensitivity 56.1–100%, specificity 93.6–100%, PPV 56.1–100%, NPV 93.6– 100%). No
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cross-reactivity with other Neisseria species or other urogenital pathogens was detected. The N. gonorrhoeae target (pap) was detected in 73 out of 78 of the N. gonorrhoeae-positive specimens, resulting in 92.6% sensitivity (95% CI 83.0–97.3%), 100% specificity (95% CI 75.9–100%) and PPV and NPV of 89.4% (95% CI 52.5–90.9%). No penA- 59/60/64 alleles were detected within the clinical specimens from the GRASP 2020 feasibility molecular surveillance study (n=54 individuals).
The implementation of this PCR assay for patient management, public health and surveillance purposes enables the rapid detection of gonococcal ceftriaxone resistance conferred by the most widely circulating penA alleles.
Target-Mediated Fluoroquinolone Resistance in Neisseria gonorrhoeae: Actions of Ciprofloxacin against Gyrase and Topoisomerase IV Collins JA, Oviatt AA, Chan PF, Osheroff N. ACS Infect Dis. 2024 Apr 12; 10 (4):1351–60.
doi: 10.1021/acsinfecdis.4c00041.
Fluoroquinolones make up a critically important class of antibacterials administered worldwide to treat human infections. However, their clinical utility has been curtailed by target-mediated resistance, which is caused by mutations in the fluoroquinolone targets, gyrase and topoisomerase IV.
An important pathogen that has been
affected by this resistance is Neisseria gonorrhoeae, the causative agent of gonorrhoea. Over 82 million new cases of this sexually transmitted infection were reported globally in 2020. Despite the impact of fluoroquinolone resistance on gonorrhoea treatment, little is known about the interactions of this drug class with its targets in this bacterium. Therefore, the authors investigated the effects of the fluoroquinolone ciprofloxacin on the catalytic and DNA cleavage activities of wild-type gyrase and topoisomerase IV and the corresponding enzymes that harbour mutations associated with cellular and clinical resistance to fluoroquinolones. Results indicate that ciprofloxacin interacts with both gyrase (its primary target) and topoisomerase IV (its secondary target) through a water-metal ion bridge that has been described in other species. Moreover, mutations in amino acid residues that anchor this bridge diminish the susceptibility of the enzymes for the drug, leading to fluoroquinolone resistance. Results further suggest that ciprofloxacin primarily induces its cytotoxic
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