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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. 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. 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. 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. Australian National Health and Medical Research Council.

Treating Mycoplasma genitalium with a sequence of first doxycycline to reduce bacterial load, and then using a resistance assay to choose either high-dose azithromycin or sitafloxacin, cured >92% of infections in a population with high levels of antibiotic resistance. Abstract Background Rising macrolide and quinolone resistance in Mycoplasma genitalium necessitate new treatment approaches. We evaluated outcomes of sequential antimicrobial therapy for M. genitalium guided by a macrolide-resistance assay. Methods In mid-2016, Melbourne Sexual Health Centre switched from azithromycin to doxycycline (100 mg twice daily for 7 days) for nongonococcal urethritis, cervicitis, and proctitis. Cases were tested for M. genitalium and macrolide-resistance mutations (MRMs) by polymerase chain reaction. Directly after doxycycline, MRM-negative infections received 2.5 g azithromycin (1 g, then 500 mg daily for 3 days), and MRM-positive infections received sitafloxacin (100 mg twice daily for 7 days). Assessment of test of cure and reinfection risk occurred 14-90 days after the second antibiotic. Results Of 244 evaluable M. genitalium infections (52 women, 68 heterosexual men, 124 men who have sex with men) diagnosed from 20 June 2016 to 15 May 2017, MRMs were detected in 167 (68.4% [95% confidence interval {CI}, 62.2%-74.2%]). Treatment with doxycycline decreased bacterial load by a mean 2.60 log10 (n = 56; P < .0001). Microbiologic cure occurred in 73 of 77 MRM-negative infections (94.8% [95% CI, 87.2%-98.6%]) and in 154 of 167 MRM-positive infections (92.2% [95% CI, 87.1%-95.8%]). Selection of macrolide resistance occurred in only 2 of 76 (2.6% [95% CI, .3%-9.2%]) macrolide-susceptible infections. Conclusions In the context of high levels of antimicrobial resistance, switching from azithromycin to doxycycline for presumptive treatment of M. genitalium, followed by resistance-guided therapy, cured ≥92% of infections, with infrequent selection of macrolide resistance.

ObjectivesIn 2016, WHO estimated 376 million new cases of the four main curable STIs: gonorrhoea, chlamydia, trichomoniasis and syphilis. Further, an estimated 290 million women are infected with human papillomavirus. STIs may lead to severe reproductive health sequelae. Low-income and middle-income countries carry the highest global burden of STIs. A large proportion of urogenital and the vast majority of extragenital non-viral STI cases are asymptomatic. Screening key populations and early and accurate diagnosis are important to provide correct treatment and to control the spread of STIs. This article paints a picture of the state of technology of STI point-of-care testing (POCT) and its implications for health system integration.MethodsThe material for the STI POCT landscape was gathered from publicly available information, published and unpublished reports and prospectuses, and interviews with developers and manufacturers.ResultsThe development of STI POCT is moving rapidly, and there are much more tests in the pipeline than in 2014, when the first STI POCT landscape analysis was published on the website of WHO. Several of the available tests need to be evaluated independently both in the laboratory and, of particular importance, in different points of care.ConclusionThis article reiterates the importance of accurate, rapid and affordable POCT to reach universal health coverage. While highlighting the rapid technical advances in this area, we argue that insufficient attention is being paid to health systems capacity and conditions to ensure the swift and rapid integration of current and future STI POCT. Unless the complexity of health systems, including context, institutions, adoption systems and problem perception, are recognised and mapped, simplistic approaches to policy design and programme implementation will result in poor realisation of intended outcomes and impact.

Mycoplasma phocimorsus is an identified zoonotic agent of musculoskeletal infections. Osteomyelitis developed in a patient after injury sustained while skinning a bear, and he experienced delayed diagnosis after ineffective treatments. Clinicians should use doxycycline or moxifloxacin therapy in treatment-refractory cases with exposure to seals, cats, or bears while awaiting molecular diagnostics results.

Key Points The burden of Neisseria gonorrhoeae and Mycoplasma genitalium infections and multidrug-resistance in the aetiological agents are major global public health concerns that are poorly surveyed and controlled N. gonorrhoeae and M. genitalium are evolving into so-called superbugs; infections with these bacteria have become exceedingly difficult to treat and they might become untreatable in certain circumstances Current dual antimicrobial therapy for gonorrhoea (ceftriaxone plus azithromycin) should be considered in all settings where regular, local and quality-assured antimicrobial resistance (AMR) data do not support other therapeutic options Dual antimicrobial therapy might also need to be considered for M. genitalium infections Development of novel antimicrobials and treatment algorithms that emphasizes dual antimicrobial therapy and AMR testing is imperative to minimize AMR emergence, enhance AMR surveillance and, ideally, guide personalized treatment Some newly developed antimicrobials, for example the fluoroketolide solithromycin, the spiropyrimidinetrione zoliflodacin and the pleuromutilin lefamulin, need further evaluation in clinical trials as potential future treatments of gonorrhoea and M. genitalium infections Gonorrhoea and Mycoplasma genitalium infections are evolving to be exceedingly difficult to treat or untreatable. Unemo and Jensen provide an overview and discussion of prevalence data, diagnostics, current treatment recommendations and potential future therapies of these infections, highlighting priorities to retain their treatability. The emergence of antimicrobial resistance (AMR) is a major concern worldwide and already compromises treatment effectiveness and control of several bacterial sexually transmitted infections (STIs). Neisseria gonorrhoeae and Mycoplasma genitalium are evolving into so-called superbugs that can become resistant, both in vitro and clinically, to essentially all antimicrobials available for treatment, causing exceedingly difficult-to-treat or untreatable STIs and threatening global public health. Widespread AMR in these bacteria is likely to persist and even worsen in the future, owing to the high number of infections, widespread and uncontrolled use of antimicrobials, limited surveillance of AMR and clinical failures, as well as the extraordinary capacity of these bacteria to develop AMR. This development would not only result in an increased prevalence of N. gonorrhoeae and M. genitalium infections but also in a considerably increasing number of severe complications affecting reproductive health. To combat this threat, clinicians need to be aware of the current guidelines on diagnostic procedures, recommended treatment regimens, as well as therapeutic options for multidrug-resistant bacteria. AMR testing needs to be more frequently performed, inform treatment decisions and elucidate how AMRs compromise treatment effectiveness, guiding research for effective future therapies.

Background. Mycoplasma genitalium (MG) is associated with nongonococcal urethritis in men and cervicitis in women. Current guidelines recommend treatment with 1 gram of azithromycin; however, treatment failure has increasingly been reported. This meta-analysis estimates treatment efficacy following treatment with 1 gram of azithromycin. Methods. Electronic databases were searched for articles published to the end of February 2015 using the following search terms: (Mycoplasma genitalium) AND (azithromycin OR zithromax OR [treatment efficacy]). Studies were included if they were English language, had participants aged ≥12 years diagnosed with urogenital MG, and had microbial cure measured within 12 months of treatment. Treatment efficacy was measured as microbial cure at last follow-up after treatment. Results. A total of 21 studies, including 1490 participants, fulfilled the inclusion criteria. Most studies were observational, with only 5 controlled trials identified. The random-effects pooled microbial cure was 77.2% (95% confidence interval [CI], 71.1%–83.4%; I2 = 80.8%, P < .01). For the 12 studies conducted prior to 2009, pooled microbial cure was 85.3% (CI, 82.3%–88.3%; I2 = 19.7%, P = .25); for the 9 studies conducted since the beginning of 2009, pooled microbial cure was 67.0% (CI, 57.0%–76.9%; I2 = 80.9%, P < .01). Conclusions. The efficacy of a single dose of 1 gram of azithromycin for the treatment of urogenital MG has decreased to approach 60%. Even though most of the available evidence is based on observational studies that have considerable variability in sample size and timing of microbial cure, this low efficacy is of considerable concern. It is vital that new treatment options for MG are investigated.

Background To investigate the epidemiological profile and antimicrobial resistance patterns of genital mycoplasma in Eastern China and provide evidence-based guidance for clinical management. Methods A retrospective analysis was conducted on clinical records, mycoplasma culture results, and antimicrobial susceptibility testing data from patients with suspected urogenital tract infections between 2018 and 2023. Results Among 47,619 suspected infected patients, 20,830 cases tested positive for genital mycoplasma infection, with an overall infection rate of 43.74%. The infection rate of pure Ureaplasma spp. was 37.00%, for pure Mycoplasma hominis (Mh) was 0.66%, and for the co-infections with Ureaplasma spp. and Mh was 6.08%. The infection rate in females (44.00%) was significantly higher than that in males (20.12%), with a statistically significant difference ( P  < 0.001). The observed changes in each age group showed statistically significant differences ( P  < 0.001). Seasonally, the infection rate of mycoplasma in spring was slightly higher than that in winter. Regarding drug resistance, genital mycoplasmas generally exhibited a higher resistance rate to fluoroquinolone drugs, while the resistance rates to tetracycline, doxycycline, pristinamycin, and josamycin were relatively low. The average resistance rates to ciprofloxacin and ofloxacin in patients with pure Ureaplasma spp. infections were relatively high, at 83.39% and 66.34%, respectively. And the resistance rates showed an increasing trend year by year ( P  < 0.001). Patients with pure Mh infections had the highest resistance rate to ofloxacin (80.32%), followed by ciprofloxacin (69.21%), with no significant differences in resistance rates across the years. Patients co-infected with Ureaplasma spp. and Mh had the highest average resistance rates to both ofloxacin and ciprofloxacin, exceeding 90.00%. Conclusion The infection rate of genital mycoplasma in Eastern China is relatively high, predominantly Ureaplasma spp., with significant resistance to fluoroquinolone drugs. It is necessary for the hospital to enhance monitoring for the genital mycoplasma infections and to conduct drug resistance analysis to guide rational medication use and infection control measures. Clinical trial number Not applicable.

Background. Our aim was to determine the efficacy of 1 g azithromycin and alternative antibiotic regimens in a prospective cohort of Mycoplasma genitalium–infected participants, and factors associated with azithromycin failure. Methods. Consecutive eligible M. genitalium–infected men and women attending the Melbourne Sexual Health Centre between July 2012 and June 2013 were treated with 1 g of azithromycin and retested by polymerase chain reaction (PCR) on days 14 and 28. Cure was defined as PCR negative on day 28. Cases failing azithromycin were treated with moxifloxacin, and those failing moxifloxacin were treated with pristinamycin. Pre- and posttreatment samples were assessed for macrolide resistance mutations (MRMs) by high-resolution melt analysis. Mycoplasma genitalium samples from cases failing moxifloxacin were sequenced for fluoroquinolone resistance mutations. Multi-variable analysis was used to examine associations with azithromycin failure. Results. Of 155 participants treated with 1 g azithromycin, 95 (61% [95% confidence interval {CI}, 53%–69%]) were cured. Pretreatment MRM was detected in 56 (36% [95% CI, 28%–43%]) participants, and strongly associated with treatment failure (87% [95% CI, 76%–94%]; adjusted odds ratio, 47.0 [95% CI, 17.1–129.0]). All 11 participants who had MRM detected in posttreatment samples failed azithromycin. Moxifloxacin was effective in 53(88% [95% CI, 78%–94%]) of 60 cases failing azithromycin; all failures had gyrA and parC mutations detected in pretreatment samples. Six of 7 patients failing moxifloxacin treatment received pristinamycin, and all were PCR negative 28 days after pristinamycin treatment. Conclusions. We report a high azithromycin failure rate (39%) in an M. genitalium–infected cohort in association with high levels of pretreatment macrolide resistance. Moxifloxacin failure occurred in 12% of patients who received moxifloxacin; all had pretreatment fluoroquinolone mutations detected. Pristinamycin was highly effective in treating macrolide- and quinolone-resistant strains.

Background. We evaluated the impact of extended azithromycin (1.5g over 5 days) on selection of macrolide resistance and microbiological cure in men with Mycoplasma genitalium urethritis during 2013–2015 and compared this to cases treated with azithromycin 1g in 2012–2013. Methods. Microbiological cure was determined for men with M. genitalium urethritis treated with azithromycin 1.5g using quantitative polymerase chain reaction specific for M. genitalium DNA on samples 14–100 days post-treatment. Pre- and post-treatment macrolide resistance mutations were detected by sequencing the 23 S gene. Results. There was no difference in proportions with microbiological cure between azithromycin 1.5g and 1g: 62/106 (58%; 95% confidence interval [CI], 49%, 68%) and 56/107 (52%; 95%CI 42–62%), P = .34, respectively. Also, there was no difference in the proportion of wild-type 23 S rRNA (presumed macrolide sensitive) infections cured after 1.5g and azithromycin 1g: 28/34 (82%; 95%CI 65–92%) and 49/60 (82%; 95%CI 70–90%), P=1.0, respectively. There was no difference between 1.5g and 1g in the proportions of wild-type infections with post-treatment resistance mutations: 4/34 (12%; 95%CI 3–27%) and 11/60 (18%; 95%CI 10–30%), respectively, P = .40. Pre-treatment resistance was present in 51/98 (52%; 95%CI 42–62%) cases in 2013–2015 compared to 47/107 (44%; 95%CI 34–54%) in 2012–2013, P = .25. Conclusions. Extended azithromycin 1.5g was no more effective than a single 1g dose at achieving cure of M. genitalium urethritis and importantly did not reduce the selection of macrolide resistance. Nonmacrolide and new approaches for the treatment of M. genitalium urethritis are required.

Background Mycoplasma genitalium is increasingly seen as an emerging sexually transmitted pathogen, and has been likened to Chlamydia trachomatis, but its natural history is poorly understood. The objectives of this systematic review were to determine M. genitalium incidence, persistence, concordance between sexual partners and the risk of pelvic inflammatory disease (PID).MethodsWe searched Medline, EMBASE, LILACS, IndMed and African Index Medicus from 1 January 1981 until 17 March 2018. Two independent researchers screened studies for inclusion and extracted data. We examined results in forest plots, assessed heterogeneity and conducted meta-analysis where appropriate. Risk of bias was assessed for all studies.ResultsWe screened 4634 records and included 18 studies; six (4201 women) reported on incidence, five (636 women) on persistence, 10 (1346 women and men) on concordance and three (5139 women) on PID. Incidence in women in two very highly developed countries was 1.07 per 100 person-years (95% CI 0.61 to 1.53, I2 0%). Median persistence of M. genitalium was estimated from one to three months in four studies but 15 months in one study. In 10 studies measuring M. genitalium infection status in couples, 39%–50% of male or female sexual partners of infected participants also had M. genitalium detected. In prospective studies, PID incidence was higher in women with M. genitalium than those without (risk ratio 1.73, 95% CI 0.92 to 3.28, I2 0%, two studies).DiscussionIncidence of M. genitalium in very highly developed countries is similar to that for C. trachomatis, but concordance might be lower. Taken together with other evidence about age distribution and antimicrobial resistance in the two infections, M. genitalium is not the new chlamydia. Synthesised data about prevalence, incidence and persistence of M. genitalium infection are inconsistent. These findings can be used for mathematical modelling to investigate the dynamics of M. genitalium.Registration numbersCRD42015020420, CRD42015020405