Antimicrobial treatment and resistance in sexually transmitted bacterial infections.

Sexually transmitted infections (STIs) have been part of human life since ancient times, and their symptoms affect quality of life, and sequelae are common. Socioeconomic and behavioural trends affect the prevalence of STIs, but the discovery of antimicrobials gave hope for treatment, control of the spread of infection and lower rates of sequelae. This has to some extent been achieved, but increasing antimicrobial resistance and increasing transmission in high-risk sexual networks threaten this progress. For Neisseria gonorrhoeae, the only remaining first-line treatment (with ceftriaxone) is at risk of becoming ineffective, and for Mycoplasma genitalium, for which fewer alternative antimicrobial classes are available, incurable infections have already been reported. For Chlamydia trachomatis, in vitro resistance to first-line tetracyclines and macrolides has never been confirmed despite decades of treatment of this highly prevalent STI. Similarly, Treponema pallidum, the cause of syphilis, has remained susceptible to first-line penicillin.

Bacterial Sexually Transmitted Infection Incidence Among Southern Men Who Have Sex With Men With Human Immunodeficiency Virus in the Treatment as Prevention Era, 2014-2019.

In this retrospective analysis of men who have sex with men with human immunodeficiency virus (HIV) in the South from 2014 through 2019, incident bacterial sexually transmitted infections (STIs) increased regardless of virologic control. Clinicians should prioritize STI screening and management in primary HIV care.

Shigella sonnei, an emerging multidrug-resistant sexually transmitted pathogen in Franche-Comté, France.

Shigella sonnei (S. sonnei) is sometimes sexually transmitted. Men, who have sex with men (MSM), may have sexual behaviours different from heterosexual population, and thus may be at risk for S. sonnei infection. We describe three cases of multidrug-resistant S. sonnei in MSM (one HIV-infected patient and two patients receiving pre-exposure prophylaxis against HIV). S. sonnei was isolated from stool specimens and all patients were successfully treated with parenteral third-generation cephalosporins following laboratory confirmation that the isolates were resistant to azithromycin. Two men (patients 2 and 3) were linked epidemiologically. These cases highlight the emergence of this pathogen and its association with some sexual behaviours among MSM in Franche-Comté, France.

Reactive arthritis: images.

Reactive arthritis is an extremely rare spondyloarthritis that affects the peripheral joints and spine, resulting in common symptoms such as arthritis, urethritis, conjunctivitis, and mucocutaneous lesions. On rare occasions, oral lesions such as circinate erosions on the hard and soft palate, gums, tongue, and cheeks may occur. Reactive arthritis may develop during or after genitourinary or gastrointestinal bacterial infections such as Shigella, Salmonella, Yersinia, and Chlamydia. A 36-year-old man presented with circinate balanitis, urethral discharge, oligoarthralgia, conjunctivitis, lymphadenopathy, pharyngitis, and erythematous lesions on the palate. Culture examination showed presence of Neisseria gonorrhoeae and antibiotic treatment resulted in improvement of conjunctivitis and the lesions on the penis. However, severe oligoarthralgia, palatal erosions that increased in severity and size, and depilated areas on the tongue were observed. The definitive diagnosis was reactive arthritis. The prevalence of sexually transmitted infections is increasing, highlighting the need to increase awareness of associated risks such as reactive arthritis. Moreover, consideration of non-specific oral manifestations in a systemic context may aid in effective diagnosis and treatment, suggesting the need for multidisciplinary teams.

The Impact of Selected Bacterial Sexually Transmitted Diseases on Pregnancy and Female Fertility.

Sexually transmitted infections (STIs) caused by Neisseria gonorrhoeae, Chlamydia trachomatis and Mycoplasma genitalium are a common cause of pelvic inflammatory disease (PID) which can lead to tubal factor infertility (TFI). TFI is one of the most common causes of infertility, accounting for 30% of female fertility problems. STIs can also have an impact on pregnancy, leading to adverse pregnancy outcomes. Escalating antibiotic resistance in Neisseria gonorrhoeae and Mycoplasma genitalium represents a significant problem and can be therapeutically challenging. We present a comprehensive review of the current treatment options, as well as the molecular approach to this subject. We have given special attention to molecular epidemiology, molecular diagnostics, current and new treatments, and drug resistance.

Macrolide and fluoroquinolone associated mutations in Mycoplasma genitalium in a retrospective study of male and female patients seeking care at a STI Clinic in Guangzhou, China, 2016-2018.

BACKGROUND: Antimicrobial resistance in M. genitalium is a growing clinical problem. We investigated the mutations associated with macrolide and fluoroquinolone resistance, two commonly used medical regimens for treatment in China. Our aim is to analyze the prevalence and diversity of mutations among M. genitalium-positive clinical specimens in Guangzhou, south China. METHODS: A total of 154 stored M. genitalium positive specimens from men and women attending a STI clinic were tested for macrolide and fluoroquinolone mutations. M. genitalium was detected via TaqMan MGB real-time PCR. Mutations associated with macrolide resistance were detected using primers targeting region V of the 23S rRNA gene. Fluoroquinolone resistant mutations were screened via primers targeting topoisomerase IV (parC) and DNA gyrase (gyrA). RESULTS: 98.7% (152/154), 95.5% (147/154) and 90.3% (139/154) of M. genitalium positive samples produced sufficient amplicon for detecting resistance mutations in 23S rRNA, gyrA and parC genes, respectively. 66.4% (101/152), 0.7% (1/147) and 77.7% (108/139) samples manifested mutations in 23S rRNA, gyrA and parC genes, respectively. A2072G (59/101, 58.4%) and S83I (79/108, 73.1%) were highly predominating in 23S rRNA and parC genes, respectively. Two samples had amino acid substitutions in gyrA (M95I and A96T, respectively). Two samples had two amino acid substitutions in parC (S83I + D87Y). 48.6% (67/138) of samples harbored both macrolide and fluoroquinolone resistance-associated mutations. The most common combination of mutations was A2072G (23S rRNA) and S83I (parC) (40/67, 59.7%). One sample had three amino acid changes in 23S rRNA, gyrA and parC genes (A2072G + A96T + S83I). CONCLUSIONS: The high antimicrobial resistance rate of M. genitalium in Guangzhou is a very worrying problem and suggests that antimicrobial resistance testing and the development of new antibiotic regimens are crucially needed.

Prevalence of mutations associated with resistance to macrolides and fluoroquinolones in Mycoplasma genitalium: a systematic review and meta-analysis.

BACKGROUND: Mycoplasma genitalium is now recognised as an important bacterial sexually transmitted infection. We summarised data from studies of mutations associated with macrolide and fluoroquinolone resistance in M genitalium to establish the prevalence of resistance. We also investigated temporal trends in resistance and aimed to establish the association between resistance and geographical location. METHODS: In this systematic review and meta-analysis, we searched PubMed, Embase, and MEDLINE for studies that included data for the prevalence of mutations associated with macrolide and fluoroquinolone resistance in M genitalium published in any language up to Jan 7, 2019. We defined prevalence as the proportion of M genitalium samples positive for key mutations associated with azithromycin resistance (23S rRNA gene, position 2058 or 2059) or moxifloxacin resistance (S83R, S83I, D87N, or D87Y in parC), or both, among all M genitalium samples that were successfully characterised. We used random-effects meta-analyses to calculate summary estimates of prevalence. Subgroup and meta-regression analyses by WHO region and time period were done. This study was registered with PROSPERO, number CRD42016050370. RESULTS: Overall, 59 studies from 21 countries met the inclusion criteria for our study: 57 studies of macrolide resistance (8966 samples), 25 of fluoroquinolone resistance (4003 samples), and 22 of dual resistance to macrolides and fluoroquinolones (3280 samples). The summary prevalence of mutations associated with macrolide resistance among M genitalium samples was 35·5% (95% CI 28·8-42·5); prevalence increased from 10·0% (95% CI 2·6-20·1%) before 2010, to 51·4% (40·3-62·4%) in 2016-17 (p<0·0001). Prevalence of mutations associated with macrolide resistance was significantly greater in samples in the WHO Western Pacific and Americas regions than in those from the WHO European region. The overall prevalence of mutations associated with fluoroquinolone resistance in M genitalium samples was 7·7% (95% CI 4·5-11·4%). Prevalence did not change significantly over time, but was significantly higher in the Western Pacific region than in the European region. Overall, the prevalence of both mutations associated with macrolide resistance and those associated with fluoroquinolone resistance among M genitalium samples was 2·8% (1·3-4·7%). The prevalence of dual resistance did not change significantly over time, and did not vary significantly by geographical region. INTERPRETATION: Global surveillance and measures to optimise the efficacy of treatments-including resistance-guided strategies, new antimicrobials, and antimicrobial combination approaches-are urgently needed to ensure cure in a high proportion of M genitalium infections and to prevent further spread of resistant strains. FUNDING: Australian National Health and Medical Research Council.

Testing the Interpersonal-Behavior model to explain intentions to use patient-delivered partner therapy.

BACKGROUND: Patient-delivered partner therapy (PDPT) is an evidence-based method of partner treatment, but further research was needed to understand theoretical underpinnings of potential PDPT use. PURPOSE: We sought to develop and test a theoretical framework to understand PDPT intentions. METHODS: A Midwestern sample of sexually transmitted infection clinic patients were recruited to participate in a three-phase study incorporating semi-structured interviews (n = 20, total), cognitive interviews (n = 5), and surveys (n = 197; Mage = 31.3, 61% male, 91% Black or African-American). Thematic analysis was conducted to identify major themes, which guided development and testing of a theoretical framework on PDPT intentions using structural equation modeling. RESULTS: We identified themes of information (knowledge); motivation (individual and partner protection beliefs, partner and provider motivation-to-comply); social support (sexual health and general); and behavioral skills (partner notification, medication delivery, and communication skills self-efficacy) in thematic analysis. The developed Interpersonal-Behavior model demonstrated good model fit in structural equation modeling [χ2(36) = 95.56, p<0.01; RMSEA = 0.09 (0.07-0.11, 90%C.I.); CFI = 0.94; SRMR = 0.05]. Information was associated with motivation (ß = 0.37, p<0.001) and social support (ß = 0.23, p = 0.002). Motivation was associated with social support (ß = 0.64, p<0.001) and behavioral skills (ß = 0.40, p<0.001), and social support was associated with behavioral skills (ß = 0.23, p = 0.025). Behavioral skills were associated with higher PDPT intentions (ß = 0.31, p<0.001), partially mediated the association of motivation with intentions (ßdirect = 0.53, p<0.001; ßindirect = 0.12, 95%CI: 0.03-0.30), and fully mediated the association of social support with intentions (ßindirect = 0.07, 95%CI: 0.00-0.21). CONCLUSIONS: The Interpersonal-Behavior model seems appropriate for PDPT intentions but should be tested longitudinally with PDPT outcomes and other interpersonal health behaviors.

Disseminated melioidosis in early pregnancy - an unproven cause of foetal loss.

BACKGROUND: Melioidosis is a potentially life-threatening infection caused by the Gram-negative bacterium Burkholderia pseudomallei. Melioidosis is difficult to diagnose due to its diverse clinical manifestations, which often delays administration of appropriate antibiotic therapy. CASE PRESENTATION: Melioidosis is uncommon in pregnancy but both spontaneous abortion and neonatal melioidosis have been reported. We report a case of bacteraemic melioidosis in a young woman with a subsequent spontaneous abortion, with B. pseudomallei cultured from a high vaginal swab as well as blood. CONCLUSION: It remains unclear in this and previously reported cases as to whether the maternal melioidosis was sexually transmitted.

Molecular basis of antimicrobial resistance in Mycoplasma genitalium.

Mycoplasma genitalium is a sexually transmitted urogenital pathogen, and infection can result in serious symptoms. As M. genitalium is rather difficult to culture, infections are usually detected by molecular methods. Unfortunately, there has recently been a significant increase in resistance to azithromycin and moxifloxacin used for the treatment of M. genitalium infections. The increased resistance to (often empirically prescribed) M. genitalium treatments has resulted in frequent therapy failures and stresses the need for routine detection of antimicrobial resistance. In M. genitalium, antimicrobial resistance is almost always the result of DNA mutations and thus can easily be detected by molecular techniques. Regrettably, many microbiology laboratories do not use molecular techniques for the detection of bacterial antimicrobial resistance. As molecular tests are becoming available for M. genitalium, both for the establishment of infection and the detection of antimicrobial resistance, it is now more important to ensure that knowledge on the resistance mechanisms is transferred from the laboratory to the clinician. This review will provide a brief summary of the current status of antimicrobial resistance, its molecular mechanisms and the impact on the current status of M. genitalium treatment.

High willingness to use novel HIV and bacterial sexually transmitted infection partner notification, testing, and treatment strategies among gay and bisexual men.

OBJECTIVES: We sought to determine willingness of gay and bisexual men (GBM) to give HIV self-testing (HIVST) kits with patient-delivered partner therapy (PDPT) and engage in geosocial sexual networking (GSN) app-based partner notification. METHODS: A nationwide sample of GBM who self-tested HIV negative (n=786) were asked about their willingness to give recent sex partners (main and casual) PDPT with an HIVST kit (PDPT+HIVST) after hypothetical bacterial STI (BSTI) diagnosis. Men were also asked about their willingness to notify sexual partners met on GSN apps using an anonymous app function after BSTI diagnosis. We examined associations of relationship status and condomless anal sex with casual partners, recent BSTI diagnosis and perceived risk of HIV on PDPT+HIVST and anonymous app-based partner notification willingness (dichotomised) using binary logistic regressions, adjusting for age, race/ethnicity, education and US region. From the partner's perspective after receiving an app-based referral, frequency measures were used to report intentions for obtaining subsequent HIV/BSTI counselling and testing, engaging in HIVST if provided a free voucher, and obtaining BSTI treatment from a pharmacy with prescription voucher. RESULTS: Most (90.1%) were willing to give PDPT+HIVST to recent sex partners after STI diagnosis, and nearly all (96.4%) were willing to notify sex partners met online using an anonymous function within GSN apps. Regardless of casual partner condomless anal sex engagement, partnered GBM had higher odds of reporting willingness to give PDPT+HIVST compared with single men who recently engaged in condomless anal sex with a casual partner. If anonymously notified via an app, 92.5% reported they would likely obtain counselling and testing, 92.8% would engage in HIVST if provided a free voucher, and 93.4% would obtain treatment from a pharmacy with prescription voucher. CONCLUSIONS: GBM generally found novel partner notification, testing, and treatment strategies acceptable, indicating the need for feasibility and cost-effectiveness evaluations.

Pharmacokinetic considerations regarding the treatment of bacterial sexually transmitted infections with azithromycin: a review.

Rates of bacterial sexually transmitted infections (STIs) continue to rise, demanding treatments to be highly effective. However, curing infections faces significant challenges due to antimicrobial resistance in Neisseria gonorrhoeae and Mycoplasma genitalium and especially treating STIs at extragenital sites, particularly rectal chlamydia and oropharyngeal gonorrhoea. As no new antimicrobials are entering the market, clinicians must optimize the currently available treatments, but robust data are lacking on how the properties or pharmacokinetics of antimicrobials can be used to inform STI treatment regimens to improve treatment outcomes. This paper provides a detailed overview of the published pharmacokinetics of antimicrobials used to treat STIs and how factors related to the drug (tissue distribution, protein binding and t½), human (pH, inflammation, site of infection, drug side effects and sexual practices) and organism (organism load and antimicrobial resistance) can affect treatment outcomes. As azithromycin is commonly used to treat chlamydia, gonorrhoea and M. genitalium infections, and its pharmacokinetics are well studied, it is the main focus of this review. Suggestions are also provided on possible dosing regimens when using extended and/or higher doses of azithromycin, which appropriately balance efficacy and side effects. The paper also emphasizes the limitations of currently published pharmacokinetic studies including oropharyngeal gonococcal infections, where very limited data exist around ceftriaxone pharmacokinetics and its use in combination with azithromycin. In future, the different anatomical sites of infections may require alternative therapeutic approaches.

Macrolide-resistant Mycoplasma genitalium infections in Cuban patients: an underestimated health problem.

BACKGROUND: The increasing prevalence of macrolide resistant Mycoplasma genitalium is a major concern worldwide. In Cuba, several cases of clinical treatment failure with 1 g single dose and extended azithromycin regimen have been detected and the aim of the present investigation was to retrospectively determine the prevalence of macrolide-resistance mediating mutations (MRMM) in M. genitalium-positive samples conserved at the Cuban National Reference Laboratory of Mycoplasma Research between 2009 and 2016. METHODS: A total of 280 positive DNA extracts were analysed by a 5' nuclease assay for detection of M. genitalium MRMM. Ten urogenital specimens from patients with azithromycin treatment failure and MRMM were inoculated in Vero cell to obtain the isolates for subsequent determination of antimicrobial susceptibility. RESULTS: The overall prevalence of MRMM was 32%. No MRMM was detected in samples collected between 2009 and 2013 but since 2014 a dramatic increase to 90% (95% CI, 76-96%) in 2016 was seen. Three new M. genitalium isolates were isolated in Vero cell cultures and confirmed phenotypic resistance to macrolides in a cell-culture assisted susceptibility test. Preliminary observations suggest that combination therapy with levofloxacin and doxycycline may represent an affordable option for treatment of macrolide resistant M. genitalium infections. CONCLUSIONS: This investigation showed the rapid emergence and high prevalence of MRMM in M. genitalium-infected patients in Cuba and confirmed the phenotypic resistance in isolates carrying MRMM. We suggest that Cuban guidelines for sexually transmitted infections are modified to include testing for M. genitalium and detection of MRMM in patients with failure of syndromic treatment, to ensure that in these cases, the treatment will be guided by etiologic diagnosis.

Mycoplasma genitalium in the Far North Queensland backpacker population: An observational study of prevalence and azithromycin resistance.

BACKGROUND: Mycoplasma genitalium is a sexually transmitted infection (STI), and a common cause of non-gonococcal urethritis (NGU). There is concern regarding the rise in prevalence of M. genitalium and rates of resistance to macrolide antibiotics. International backpackers represent a unique population that may be at an increased risk of STIs. The purpose of this study was to determine the prevalence of M. genitalium and antibiotic resistance in international backpackers. METHODS: First void urine samples were obtained utilising opportunistic sampling from 294 non-treatment-seeking international backpackers at a variety of hostels in Cairns, Queensland Australia. Participants also answered a fixed-answer survey regarding sociodemographic characteristics and sexual risk behaviours. Samples were tested for M. genitalium, Chlamydia trachomatis and Neisseria gonorrhoeae using polymerase chain reaction (PCR). Samples positive for M. genitalium were investigated for macrolide resistance-associated mutations in the 23S rRNA genome at positions A2058G, A2058C, A2058T, A2059G and A2059C (Escherichia coli numbering). RESULTS: Of the 294 samples, 23 failed the internal control. The prevalence of M. genitalium was 1.8% (5/271, 95% confidence interval [CI] ± 1.58), C. trachomatis was 4.1% (11/271, 95% CI ± 2.36) and N. gonorrhoeae was not detected. Macrolide resistance-associated mutations were identified in 40% (2/5) of M. genitalium-positive samples. M. genitalium infection was associated with reporting symptoms (odds ratio [OR] 14.36, 95% CI 2.17-94.94, p < 0.05). CONCLUSIONS: M. genitalium and C. trachomatis are relatively common amongst non-treatment seeking international backpackers, but may not differ from Australian population prevalence. This article provides evidence to further support the increased utilisation of M. genitalium PCR in the diagnosis of NGU, and for macrolide resistance testing for all identified M. genitalium infections.

Effects of Sexual Network Connectivity and Antimicrobial Drug Use on Antimicrobial Resistance in Neisseria gonorrhoeae.

Contemporary strategies to curtail the emergence of antimicrobial resistance in Neisseria gonorrhoeae include screening for and treating asymptomatic infections in high-prevalence populations in whom antimicrobial drug-resistant infections have typically emerged. We argue that antimicrobial resistance in these groups is driven by a combination of dense sexual network connectivity and antimicrobial drug exposure (for example, through screen-and-treat strategies for asymptomatic N. gonorrhoeae infection). Sexual network connectivity sustains a high-equilibrium prevalence of N. gonorrhoeae and increases likelihood of reinfection, whereas antimicrobial drug exposure results in selection pressure for reinfecting N. gonorrhoeae strains to acquire antimicrobial resistance genes from commensal pharyngeal or rectal flora. We propose study designs to test this hypothesis.

[Sexually transmitted Mycoplasma genitalium infection is difficult to treat].

Mycoplasma genitalium infection is sexually transmitted, and it is almost as common as chlamydia in most European settings. Symptoms are indistinguishable from those of chlamydia, and late sequelae are believed to be similar. Treatment of M. genitalium infection is complicated due to widespread antimicrobial resistance not only to first-line azithromycin but now also increasingly to second-line moxifloxacin, leaving no other antibiotics registered in Denmark available for effective treatment. In the absence of available antimicrobials, screening of asymptomatic individuals should be avoided.