Prevalence of mutations associated with macrolide and fluoroquinolone resistance in Neisseria gonorrhoeae with Allplex™ NG&DR Assay (Seegene®) in a tertiary hospital from Madrid, Spaina / Prevalencia de mutaciones asociadas a resistencia a macrólidos y fluoroquinolonas en Neisseria gonorrhoeae con el kit Allplex™ NG&DR Assay (Seegene®) en un hospital terciario de la Comunidad de Madrid, España

Background. The prevalence of drug-resistant Neisseria gonorrhoeae (NG) infections is increasing. Studies report the prevalence of NG strains presenting A2059G/C2611T (rRNA 23S) and S91F (parC) mutations conferring resistance to azith romycin and ciprofloxacin. Material and methods. We conducted a prospective cohort study evaluating first void-urine urines, rectal, and oropharyngeal swabs collected from a cohort of patients in a tertiary hospital in Madrid between October 2022 and January 2023. Samples were screened by Allplex™ 7-STI Essential As say (Seegene®). Drug resistances were performed by Allplex™ NG&DR Assay (Seegene®). Results. A total of 1,415 patients were included, of which 112 had a positive sample for NG infection. One patient had a C2611T mutation (0.9%) and neither patient showed A2059G mutation. We found 67 (59.8%) S91F-positive patients. For ty-four patients (39.3%) not had any mutations. Conclusions. We report a low-prevalence of mutations A2059G/C2611T to macrolides and a high-prevalence to S91F in NG infections. Molecular methods for the detection of NG resistance could be useful in direct non-culturable samples (AU)

Introducción. La infección por Neisseria gonorrhoeae (NG) resistente está aumentando. Se ha descrito la prevalencia de cepas de NG con mutaciones A2059G/C2611T (rRNA 23S) y S91F (parC) que confieren resistencia a azitromicina y cipro floxacino. Material y métodos. Realizamos un estudio prospecti vo evaluando orinas de primera micción, hisopos anales y fa ríngeos recogidos de una cohorte de pacientes en un hospital terciario de Madrid entre octubre de 2022 y enero de 2023. El cribado de las muestras se realizó mediante Allplex™ 7-STI Es sential Assay (Seegene®). Las resistencias a macrólidos y fluo roquinolonas se realizaron mediante Allplex™ NG&DR Assay (Seegene®). Resultados. Se incluyeron 1.415 pacientes, de los cua les 112 fueron positivos para NG. Un paciente presentaba una mutación C2611T (0,9%) y en ningún paciente se detec tó A2059G. Encontramos 67 pacientes (59,8%) positivos pa ra S91F. Cuarenta y cuatro pacientes (39,3%) no presentaban mutaciones. Conclusiones. Reportamos una baja prevalencia de mu taciones A2059G/C2611T a macrólidos y una alta prevalencia de S91F en NG. Los métodos moleculares para la detección de resistencias en NG podrían ser útiles en muestras directas no cultivables (AU)

Australian Gonococcal Surveillance Programme Annual Report, 2022.

The Australian Gonococcal Surveillance Programme (AGSP) has continuously monitored antimicrobial resistance in Neisseria gonorrhoeae for more than 40 years. In 2022, a total of 8,199 isolates from patients in the public and private sectors, in all jurisdictions, were tested for in vitro antimicrobial susceptibility by standardised methods. The current treatment recommendation for gonorrhoea, for the majority of Australia, continues to be dual therapy with ceftriaxone and azithromycin. In 2022, of N. gonorrhoeae isolates tested, 0.51% (42/8,199) met the WHO criterion for ceftriaxone decreased susceptibility (DS), defined as a minimum inhibitory concentration value ≥ 0.125 mg/L. Resistance to azithromycin was reported in 3.9% of N. gonorrhoeae isolates, proportionally stable since 2019. There were nine isolates with high-level resistance to azithromycin (MIC value ≥ 256 mg/L) reported in Australia: Queensland (4), New South Wales (3), Victoria (1) and non-remote Western Australia (1). This is the highest number detected annually by the AGSP. In 2022, penicillin resistance was found in 38.8% of gonococcal isolates, and ciprofloxacin resistance in 63.3%, however, there was considerable variation by jurisdiction. In some remote settings, penicillin resistance remains low; in these settings, penicillin continues to be recommended as part of an empiric therapy strategy. In 2022, in remote Northern Territory, one penicillin-resistant isolate was reported; in remote Western Australia, 11.8% of gonococcal isolates (9/76) were penicillin resistant. There were three ciprofloxacin-resistant isolates reported from remote Northern Territory; ciprofloxacin resistance rates remain comparatively low in remote Western Australia (6/76; 7.9%).

Rapid expansion of Neisseria gonorrhoeae ST7827 clone in Australia, with variable ceftriaxone phenotype unexplained by genotype.

BACKGROUND: Neisseria gonorrhoeae is identified as a priority pathogen due to its capacity to rapidly develop antimicrobial resistance (AMR). Following the easing of SARS-CoV-2 pandemic travel restrictions across international borders in the state of New South Wales (NSW), Australia, a surge of gonococcal isolates with raised ceftriaxone MIC values were detected. METHODS: All N. gonorrhoeae isolates (n = 150) with increased ceftriaxone MIC values in NSW between 1 January 2021 and July 2022 from males and females from all sites were sequenced. RESULTS: A new emergence and rapid expansion of an N. gonorrhoeae ST7827 clone was documented within NSW, Australia and provides further evidence of the ability of N. gonorrhoeae to undergo sufficient genomic changes and re-emerge as a geographically restricted subclone. Mapping AMR determinants to MIC results did not reveal any genomic pattern that correlated with MIC values. CONCLUSIONS: The rapid dissemination and establishment of this clone at the population level is a new and concerning demonstration of the agility of this pathogen, and underscores concerns about similar incursions and establishment of MDR clones. Moreover, it is notable that in this context the AMR genotype-phenotype correlates remain unclear, which requires further investigation to enable better understanding of genomic aspects of AMR in N. gonorrhoeae.

Interactions between Loci Contributing to Antimicrobial Resistance and Virulence in Neisseria gonorrhoeae.

In a recent mBio article, Ayala et al. (mBio 13:e00276-22, 2022, https://doi.org/10.1128/mbio.00276-22) identified a single nucleotide variant in the repressor gdhR in Neisseria gonorrhoeae that reduces binding to the promoter of the virulence factor lctP and thereby increases its expression. The allele (gdhR6) frequently co-occurs with mutations in the mtr operon promoter that reduce expression of another repressor, mtrR, resulting in overexpression of the efflux pump-encoding mtrCDE and increased antimicrobial resistance. Because mtrR also represses gdhR, a decline in mtrR would decrease expression of lctP. Hypothesizing that gdhR6 arose to circumvent the impact of mtrR promoter mutations on lctP expression, the authors analyzed these loci in genomes of N. gonorrhoeae isolates from the preantibiotic era. Surprisingly, they found isolates with gdhR6 prior to selection for mtrR resistance-associated alleles. These results suggest that independent and perhaps interacting pressures have influenced the co-occurrence of these alleles.

Ribonucleotide reductase, a novel drug target for gonorrhea.

Antibiotic-resistant Neisseria gonorrhoeae (Ng) are an emerging public health threat due to increasing numbers of multidrug resistant (MDR) organisms. We identified two novel orally active inhibitors, PTC-847 and PTC-672, that exhibit a narrow spectrum of activity against Ng including MDR isolates. By selecting organisms resistant to the novel inhibitors and sequencing their genomes, we identified a new therapeutic target, the class Ia ribonucleotide reductase (RNR). Resistance mutations in Ng map to the N-terminal cone domain of the α subunit, which we show here is involved in forming an inhibited α4ß4 state in the presence of the ß subunit and allosteric effector dATP. Enzyme assays confirm that PTC-847 and PTC-672 inhibit Ng RNR and reveal that allosteric effector dATP potentiates the inhibitory effect. Oral administration of PTC-672 reduces Ng infection in a mouse model and may have therapeutic potential for treatment of Ng that is resistant to current drugs.

Coumarins effectively inhibit bacterial α-carbonic anhydrases.

Coumarins are known to act as prodrug inhibitors of mammalian α-carbonic anhydrases (CAs, EC 4.2.1.1) but they were not yet investigated for the inhibition of bacterial α-CAs. Here we demonstrate that such enzymes from the bacterial pathogens Neisseria gonorrhoeae (NgCAα) and Vibrio cholerae (VchCAα) are inhibited by a panel of simple coumarins incorporating hydroxyl, amino, ketone or carboxylic acid ester moieties in various positions of the ring system. The nature and the position of the substituents in the coumarin ring were the factors which strongly influenced inhibitory efficacy. NgCAα was inhibited with KIs in the range of 28.6-469.5 µM, whereas VchCAα with KIs in the range of 39.8-438.7 µM. The two human (h)CA isoforms included for comparison reason in the study, hCA I and II, were less prone to inhibition by these compounds, with KIs of 137-948.9 µM for hCA I and of 296.5-961.2 µM for hCA II, respectively. These findings are relevant for discovering coumarin bacterial CA inhibitors with selectivity for the bacterial over human isoform, with potential applications as novel antibacterial agents.

Dissemination and genome analysis of high-level ceftriaxone-resistant penA 60.001 Neisseria gonorrhoeae strains from the Guangdong Gonococcal antibiotics susceptibility Programme (GD-GASP), 2016-2019.

Background: After Neisseria gonorrhoeae FC428 was first found in Japan, ceftriaxone-resistant strains disseminated globally, and the gonococcal resistance rate increased remarkably. Epidemiological investigations are greatly significant for the analysis of antimicrobial resistance (AMR) trends, molecular features and evolution. Objectives: To clarify the AMR trend from 2016-2019 and reveal the molecular characteristics and evolution of ceftriaxone-resistant penA 60.001 isolates. Methods: The minimum inhibitory concentrations (MICs) of antibiotics against 4113 isolates were detected by the agar dilution method. N. gonorrhoeae multiantigen sequence typing (NG-MAST), multilocus sequence typing (MLST) and N.gonorrhoeae sequence typing for antimicrobial resistance (NG-STAR) were used to identify the sequence types. Genome analysis was conducted to analyze resistance genes, virulence factors, and evolutionary sources. Results: Isolates with decreased ceftriaxone susceptibility have increased from 2.05% (2016) to 16.18% (2019). Six ceftriaxone-resistant isolates possessing penA 60.001 appeared in Guangdong Province, and were resistant to ceftriaxone, penicillin, tetracycline, ciprofloxacin and cefixime, but susceptible to azithromycin and spectinomycin. Single-nucleotide polymorphisms (SNPs) in the porB gene were the major cause of different NG-MAST types. ST1903 was the main NG-STAR genotype and only strain-ZH545 was ST7365, with molecular features consistent with the MICs. Furthermore, different MLSTs suggested diverse evolutionary sources. Genome analysis revealed a set of virulence factors along with the resistance genes "penA" and "blaTEM-1B". Half of penA 60.001 strains were fully mixed with global FC428-related strains. Conclusions: Global FC428-related clones have disseminated across Guangdong, possibly causing decreased ceftriaxone susceptibility. Enhanced gonococcal surveillance will help elucidate the trajectory of transmission and curb further dissemination.

Single gene targeted nanopore sequencing enables simultaneous identification and antimicrobial resistance detection of sexually transmitted infections.

OBJECTIVES: To develop a simple DNA sequencing test for simultaneous identification and antimicrobial resistance (AMR) detection of multiple sexually transmitted infections (STIs). METHODS: Real-time PCR (qPCR) was initially performed to identify Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), Mycoplasma genitalium (MG) and Trichomonas vaginalis (TV) infections among a total of 200 vulvo-vaginal swab samples from female sex workers in Ecuador. qPCR positive samples plus qPCR negative controls for these STIs were subjected to single gene targeted PCR MinION-nanopore sequencing using the smartphone operated MinIT. RESULTS: Among 200 vulvo-vaginal swab samples 43 were qPCR positive for at least one of the STIs. Single gene targeted nanopore sequencing generally yielded higher pathogen specific read counts in qPCR positive samples than qPCR negative controls. Of the 26 CT, NG or MG infections identified by qPCR, 25 were clearly distinguishable from qPCR negative controls by read count. Discrimination of TV qPCR positives from qPCR negative controls was poorer as many had low pathogen loads (qPCR cycle threshold >35) which produced few specific reads. Real-time AMR profiling revealed that 3/3 NG samples identified had gyrA mutations associated with fluoroquinolone resistance, 2/10 of TV had mutations related to metronidazole resistance, while none of the MG samples possessed 23S rRNA gene mutations contributing to macrolide resistance. CONCLUSIONS: Single gene targeted nanopore sequencing for diagnosing and simultaneously identifying key antimicrobial resistance markers for four common genital STIs shows promise. Further work to optimise accuracy, reduce costs and improve speed may allow sustainable approaches for managing STIs and emerging AMR in resource poor and laboratory limited settings.

Dithiocarbamates effectively inhibit the α-carbonic anhydrase from Neisseria gonorrhoeae.

Recently, inorganic anions and sulphonamides, two of the main classes of zinc-binding carbonic anhydrase inhibitors (CAIs), were investigated for inhibition of the α-class carbonic anhydrase (CA, EC 4.2.1.1) from Neisseria gonorrhoeae, NgCA. As an extension to our previous studies, we report that dithiocarbamates (DTCs) derived from primary or secondary amines constitute a class of efficient inhibitors of NgCA. KIs ranging between 83.7 and 827 nM were measured for a series of 31 DTCs that incorporated various aliphatic, aromatic, and heterocyclic scaffolds. A subset of DTCs were selected for antimicrobial testing against N. gonorrhoeae, and three molecules displayed minimum inhibitory concentration (MIC) values less than or equal to 8 µg/mL. As NgCA was recently validated as an antibacterial drug target, the DTCs may lead to development of novel antigonococcal agents.

Repurposing FDA-approved sulphonamide carbonic anhydrase inhibitors for treatment of Neisseria gonorrhoeae.

Neisseria gonorrhoeae is a high-priority pathogen of concern due to the growing prevalence of resistance development against approved antibiotics. Herein, we report the anti-gonococcal activity of ethoxzolamide, the FDA-approved human carbonic anhydrase inhibitor. Ethoxzolamide displayed an MIC50, against a panel of N. gonorrhoeae isolates, of 0.125 µg/mL, 16-fold more potent than acetazolamide, although both molecules exhibited almost similar potency against the gonococcal carbonic anhydrase enzyme (NgCA) in vitro. Acetazolamide displayed an inhibition constant (Ki) versus NgCA of 74 nM, while Ethoxzolamide's Ki was estimated to 94 nM. Therefore, the increased anti-gonococcal potency of ethoxzolamide was attributed to its increased permeability in N. gonorrhoeae as compared to that of acetazolamide. Both drugs demonstrated bacteriostatic activity against N. gonorrhoeae, exhibited post-antibiotic effects up to 10 hours, and resistance was not observed against both. Taken together, these results indicate that acetazolamide and ethoxzolamide warrant further investigation for translation into effective anti-N. gonorrhoeae agents.

Antimicrobial susceptibility testing of Neisseria gonorrhoeae using a phenotypic-molecular assay and lyophilized antimicrobials.

Gonorrhea is an urgent global public health threat as Neisseria gonorrhoeae (Ng) has progressively developed resistance to all antibiotics commonly used for treatment. Surveillance of antimicrobial susceptibility trends is critical to monitor the emergence and spread of antimicrobial resistance. The gold standard methods for antimicrobial susceptibility testing (AST) of Ng are laborious and time-consuming. We evaluated a phenotypic molecular approach, involving a short cultivation step and quantitative PCR, with lyophilized antimicrobials to characterize antimicrobial susceptibility in Ng. There was excellent concordance between AST performed with liquid and lyophilized ciprofloxacin, penicillin, and tetracycline using the pheno-molecular assay, following a 4-hour incubation step. The categorical agreement between the pheno-molecular assay and the gold standard AST results was 92.4% for characterization of antimicrobial susceptibility. Essential agreement between the 2 methods was 91.9%. Characterization of ceftriaxone susceptibility in Ng using the pheno-molecular assay required a 6-hour incubation step.

Lipophilic quinolone derivatives: Synthesis and in vitro antibacterial evaluation.

This paper reports on the design of a series of 10 novel lipophilic piperazinyl derivatives of the 1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, their synthesis, their characterisation by 1H, 13C and 19F NMR, IR spectroscopy and HRMS, as well as their biological activity against bacteria of medical interest. Among these derivatives, 2 were as potent as the parent quinolone against Neisseriagonorrhoeae whereas all the compounds displayed lower activity than the parent quinolone against other bacteria of medical interest. Our results showing that the increased lipophilicity was deleterious for antibacterial activity may help to design new quinolone derivatives in the future, especially lipophilic quinolones which have been poorly investigated previously.

Promising Antifungal and Antibacterial Agents Based on 5-Aryl-2,2'-bipyridines and Their Heteroligand Salicylate Metal Complexes: Synthesis, Bioevaluation, Molecular Docking.

A series of new 5-aryl-2,2'-bipyridines and their (polyfluoro)salicylate complexes of Cu(II), Co(II) and Mn(II) were synthesized. Their antimicrobial activity was evaluated in vitro against six strains of Trichophytons, E. floccosum, M. canis, C. ablicans and Gram-negative bacteria N. gonorrhoeae. Among azo-ligands, Ph-bipy and Tol-bipy showed promising antifungal activity (minimum inhibitory concentration (MIC)<0.8-27 µM). Their antifungal action was found can be realized via binding Fe(III) ions. Tol-bipy suppressed growth of Gram-positive bacteria S. aureus, S. aureus MRSA and their monospecies biofilms (MIC 6-16 µM). Using molecular docking, the anti-staphylococcal action mechanism based on the inhibition of S. aureus DNA gyrase GyrB was proposed for the lead compounds. Among metal complexes, Cu(II) and Mn(II) complexes based on tetrafluorosalicylic acid and Tol-bipy or Ph-bipy had the high antifungal activity (MIC<0.24-32 µM). Mn(SalF4 -2H)2 (Tol-bipy)2 ] suppressed the growth of seven Candida strains at MIC 12-24 µM. [Cu(Sal-2H)(Ph-bipy)] and [Cu(SalF3 -2H)(Ph-bipy)2 ] showed the promising anti-gonorrhoeae activity (MIC 4.2-5.2 µM). (Cu(SalFn -2H)(Tol-bipy)2 ], [Cu(SalF4 -2H)(Ph-bipy)2 ] and [Cu(SalF3 -2H)(Ph-bipy)2 ]) were found active against the bacteria of S. aureus, S. aureus MRSA and their biofilms (MIC 2.4-41.4 µM). The most active compounds were tested for toxicity in vitro against human embryonic kidney (HEK-293) cells and in vivo experiments with CD-1 mice.

The emergence of the ceftriaxone-resistant Neisseria gonorrhoeae FC428 clone by transfer of resistance from an oral Neisseria subflava reservoir of resistance.

BACKGROUND: The ceftriaxone-resistant Neisseria gonorrhoeae FC428 clone was first discovered in Japan in 2015. OBJECTIVES: We investigated the possibility of horizontal gene transfer from Neisseria subflava harbouring the mosaic-like PBP-2 in the emergence of the FC428 clone. We also analysed whether there were fitness costs associated with the sustained international dissemination of the clone. METHODS: Sequencing of the penA gene in ceftriaxone-resistant N. subflava strains was performed. For transformation experiments between donor N. subflava and ciprofloxacin-resistant wild-type penA N. gonorrhoeae recipient, the full-length PCR amplification product of the penA gene, including DUS regions, was used as the donor DNA. Biological fitness of the transformants was measured by growth competition assays. The impact of QRDR and mtrR mutations, which have been reported as compensatory mutations, on fitness was also assessed. RESULTS: The penA mosaic allele of the FC428 clone showed 100%, 91.8%, and 89.8% homology, respectively, with penA genes of three ceftriaxone-resistant N. subflava strains, No. 30, No. 9 and No. 14. Results were consistent with homologous recombination with the donated penA mosaic allele. In co-cultures with the parent strain, transformants showed comparable growth indicating that a gyrA mutation compensates for the fitness cost of mosaic penA alleles. CONCLUSIONS: Our findings support the hypothesis that the FC428 clone was generated by transformation of the mosaic penA allele from oropharyngeal N. subflava to N. gonorrhoeae. Furthermore, it suggests that mutations in the gyrA QRDR region compensate for fitness costs and contribute to the continued transmission of the FC428 clone.

Large Increase in Azithromycin-Resistant Neisseria gonorrhoeae in Northern Spain.

The aim of this study was to characterize the evolution of gonorrhea in the general population by correlating epidemiological, genotypic, and antimicrobial resistance data of Neisseria gonorrhoeae isolates collected in northern Spain from 2014 to 2018. One hundred ninety-four strains underwent antimicrobial susceptibility testing and were genetically analyzed by N. gonorrhoeae multiantigen sequence typing. Increasing cases of gonococcal infections have been observed after 2015. Most occurred in male with urethritis. Sequence type (ST)-9972 and ST-1576, the predominant genotypes identified, have not been previously described as epidemic clones. Of great concern was the significant increase in azithromycin-resistant N. gonorrhoeae. More than 30% of these isolates were obtained from men who have sex with men (MSM). ST-12302 was the most prevalent clone among the azithromycin-resistant strains, and was also resistant to penicillin, ciprofloxacin, and tetracycline. This multidrug-resistant clone was exclusively isolated from MSM during 2018. The incidence rates of gonorrhea and azithromycin-resistant N. gonorrhoeae have significantly increased due to the emergence of new clones. ST-12302 has recently been recognized as an epidemic clone; therefore, its surveillance could be the key in controlling further dissemination of azithromycin resistance. These data highlight the need to perform local studies to update treatment guidelines and reinforce preventive measures against gonorrhea.

Septic Arthritis: Diagnosis and Treatment.

Septic arthritis must be considered and promptly diagnosed in any patient presenting with acute atraumatic joint pain, swelling, and fever. Risk factors for septic arthritis include age older than 80 years, diabetes mellitus, rheumatoid arthritis, recent joint surgery, hip or knee prosthesis, skin infection, and immunosuppressive medication use. A delay in diagnosis and treatment can result in permanent morbidity and mortality. Physical examination findings and serum markers, including erythrocyte sedimentation rate and C-reactive protein, are helpful in the diagnosis but are nonspecific. Synovial fluid studies are required to confirm the diagnosis. History and Gram stain aid in determining initial antibiotic selection. Staphylococcus aureus is the most common pathogen isolated in septic arthritis; however, other bacteria, viruses, fungi, and mycobacterium can cause the disease. After synovial fluid has been obtained, empiric antibiotic therapy should be initiated if there is clinical concern for septic arthritis. Oral antibiotics can be given in most cases because they are not inferior to intravenous therapy. Total duration of therapy ranges from two to six weeks; however, certain infections require longer courses. Consideration for microorganisms such as Neisseria gonorrhoeae, Borrelia burgdorferi, and fungal infections should be based on history findings and laboratory results.

Antimicrobial resistance in Neisseria gonorrhoeae and Mycoplasma genitalium isolates from the private healthcare sector in South Africa: A pilot study.

BACKGROUND: Reports have emerged globally of antimicrobial resistance (AMR) in Neisseria gonorrhoeae and Mycoplasma genitalium infections. In South Africa (SA), there are substantial differences between private and public healthcare with regard to antimicrobial drug prescribing practice, which could affect AMR patterns of private and public healthcare patients. OBJECTIVES: To perform a pilot study to determine the frequency of AMR of N. gonorrhoeae and M. genitalium in patients accessing SA's private healthcare sector. METHODS: In this cross-sectional study, N. gonorrhoeae-positive cultures and M. genitalium DNA samples were collected from a private healthcare reference laboratory from August 2018 to August 2019. In N. gonorrhoeae-positive cultures, antimicrobial susceptibility testing was performed, followed by N. gonorrhoeae multiantigen sequence typing (NG-MAST) to determine genetic relatedness of the isolates. To determine macrolide and fluoroquinolone resistance rates, M. genitalium-positive samples were analysed by sequencing the 23S rRNA, gyrA and parC genes. RESULTS: Twenty-one N. gonorrhoeae- and 27 M. genitalium-positive specimens were included in this analysis. High rates of resistance were detected among gonococcal isolates, with 90% resistance to tetracycline, 86% to penicillin and 62% to ciprofloxacin, but no resistance to azithromycin, cefixime and ceftriaxone. NG-MAST revealed genetically diverse isolates with 83% novel NG-MAST sequence types. Macrolide and fluoroquinolone resistance-associated mutations were detected in 18.5% (n=5/27) and 7.4% (n=2/27) of M. genitalium strains, respectively. CONCLUSIONS: We observed high frequencies of ciprofloxacin, penicillin and tetracycline resistance in N. gonorrhoeae and macrolide resistance-associated mutations in M. genitalium in private healthcare sector patients in SA. This finding highlights the need to use diagnostics for sexually transmitted infections and to include the private healthcare sector in antimicrobial surveillance and stewardship programmes.

Modelling response strategies for controlling gonorrhoea outbreaks in men who have sex with men in Australia.

The ability to treat gonorrhoea with current first-line drugs is threatened by the global spread of extensively drug resistant (XDR) Neisseria gonorrhoeae (NG) strains. In Australia, urban transmission is high among men who have sex with men (MSM) and importation of an XDR NG strain in this population could result in an epidemic that would be difficult and costly to control. An individual-based, anatomical site-specific mathematical model of NG transmission among Australian MSM was developed and used to evaluate the potential for elimination of an imported NG strain under a range of case-based and population-based test-and-treat strategies. When initiated upon detection of the imported strain, these strategies enhance the probability of elimination and reduce the outbreak size compared with current practice (current testing levels and no contact tracing). The most effective strategies combine testing targeted at regular and casual partners with increased rates of population testing. However, even with the most effective strategies, outbreaks can persist for up to 2 years post-detection. Our simulations suggest that local elimination of imported NG strains can be achieved with high probability using combined case-based and population-based test-and-treat strategies. These strategies may be an effective means of preserving current treatments in the event of wider XDR NG emergence.