Mycoplasma genitalium

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Jorgen Skov Jensen - One of the best experts on this subject based on the ideXlab platform.

  • lack of association between the s83i parc mutation in Mycoplasma genitalium and treatment outcomes among men who have sex with men with nongonococcal urethritis
    Sexually Transmitted Diseases, 2019
    Co-Authors: Laura C Chambers, Matthew R Golden, Patricia A. Totten, Jorgen Skov Jensen, Jennifer Morgan, M Lowens, Sarah S Romano, Olusegun O Soge, James P Hughes, Lisa E. Manhart
    Abstract:

    From February 2015 to October 2017, among 20 men who have sex with men with Mycoplasma genitalium-associated nongonococcal urethritis, 15% had macrolide resistance and S83I ParC mutations. Azithromycin followed by moxifloxacin cleared Mycoplasma genitalium in 2 of 2 with and 11 of 13 without S83I mutations. Dual failures were cleared after doxycycline. S83I mutations were not associated with moxifloxacin failure.

  • Mutations in ParC and GyrA of moxifloxacin-resistant and susceptible Mycoplasma genitalium strains.
    'Public Library of Science (PLoS)', 2018
    Co-Authors: Ryoichi Hamasuna, Satoshi Kutsuna, Keiichi Furubayashi, Masahiro Matsumoto, Norio Ohmagari, Naohiro Fujimoto, Tetsuro Matsumoto, Jorgen Skov Jensen
    Abstract:

    Macrolide or fluoroquinolone-resistant Mycoplasma genitalium is spreading worldwide. We aimed to determine the influence of single nucleotide polymorphisms (SNPs) in the quinolone resistance determining regions (QRDR) of parC and gyrA in cultured M. genitalium strains. In addition, we examined the prevalence of macrolide- and fluoroquinolone resistance mediating mutations in specimens collected from Japanese male patients with urethritis in two time-periods between 2005-2009 and 2010-2017, respectively, by sequencing the QRDR of parC and gyrA and domain V of the 23S rRNA gene. The minimum inhibitory concentrations (MIC) of moxifloxacin, sitafloxacin, ciprofloxacin, levofloxacin, doxycycline, minocycline, azithromycin and clarithromycin were determined in 23 M. genitalium strains. Three cultured strains had elevated MICs for moxifloxacin at 16, 4 and 2 mg/L and had SNPs with the amino-acid change Ser83→Ile in ParC (p

  • Use of Pristinamycin for Macrolide-Resistant Mycoplasma genitalium Infection
    Emerging infectious diseases, 2018
    Co-Authors: Tim R.h. Read, Christopher K Fairley, Jorgen Skov Jensen, Mieken Grant, Jennifer Danielewski, Gerald L. Murray, Eric P F Chow, Karen Worthington, Suzanne M Garland
    Abstract:

    High levels of macrolide resistance and increasing fluoroquinolone resistance are found in Mycoplasma genitalium in many countries. We evaluated pristinamycin for macrolide-resistant M. genitalium in a sexual health center in Australia. Microbiologic cure was determined by M. genitalium-specific 16S PCR 14-90 days after treatment began. Of 114 persons treated with pristinamycin, infection was cured in 85 (75%). This percentage did not change when pristinamycin was given at daily doses of 2 g or 4 g or at 3 g combined with 200 mg doxycycline. In infections with higher pretreatment bacterial load, treatment was twice as likely to fail for each 1 log10 increase in bacterial load. Gastrointestinal side effects occurred in 7% of patients. Pristinamycin at maximum oral dose, or combined with doxycycline, cured 75% of macrolide-resistant M. genitalium infections. Pristinamycin is well-tolerated and remains an option where fluoroquinolones have failed or cannot be used.

  • increasing macrolide and fluoroquinolone resistance in Mycoplasma genitalium
    Emerging Infectious Diseases, 2017
    Co-Authors: Gerald L. Murray, Catriona S. Bradshaw, Melanie Bissessor, Sepehr N Tabrizi, Christopher K Fairley, Jorgen Skov Jensen, Suzanne M Garland, Jennifer Danielewski
    Abstract:

    Abstract Escalating resistance to azithromycin and moxifloxacin is being reported for Mycoplasma genitalium in the Asia-Pacific region. Analyzing 140 infections, we found pretreatment fluoroquinolone-resistance mutations in parC (13.6%) and gyrA (5%). ParC S83 changes were associated with moxifloxacin failure. Combined macrolide/fluoroquinolone-resistance mutations were in 8.6% of specimens, for which recommended therapies would be ineffective.

  • antimicrobial resistant sexually transmitted infections gonorrhoea and Mycoplasma genitalium
    Nature Reviews Urology, 2017
    Co-Authors: Magnus Unemo, Jorgen Skov Jensen
    Abstract:

    Gonorrhoea andMycoplasma genitaliuminfections 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.

Lisa E. Manhart - One of the best experts on this subject based on the ideXlab platform.

  • lack of association between the s83i parc mutation in Mycoplasma genitalium and treatment outcomes among men who have sex with men with nongonococcal urethritis
    Sexually Transmitted Diseases, 2019
    Co-Authors: Laura C Chambers, Matthew R Golden, Patricia A. Totten, Jorgen Skov Jensen, Jennifer Morgan, M Lowens, Sarah S Romano, Olusegun O Soge, James P Hughes, Lisa E. Manhart
    Abstract:

    From February 2015 to October 2017, among 20 men who have sex with men with Mycoplasma genitalium-associated nongonococcal urethritis, 15% had macrolide resistance and S83I ParC mutations. Azithromycin followed by moxifloxacin cleared Mycoplasma genitalium in 2 of 2 with and 11 of 13 without S83I mutations. Dual failures were cleared after doxycycline. S83I mutations were not associated with moxifloxacin failure.

  • efficacy of antimicrobial therapy for Mycoplasma genitalium infections
    Clinical Infectious Diseases, 2015
    Co-Authors: Lisa E. Manhart, Matthew R Golden, Catriona S. Bradshaw, Jorgen Skov Jensen, David H Martin
    Abstract:

    Mycoplasma genitalium has been causally linked with nongonococcal urethritis in men and cervicitis, pelvic inflammatory disease, preterm birth, spontaneous abortion, and infertility in women, yet treatment has proven challenging. To inform treatment recommendations, we reviewed English-language studies describing antimicrobial susceptibility, resistance-associated mutations, and clinical efficacy of antibiotic therapy, identified via a systematic search of PubMed supplemented by expert referral. Minimum inhibitory concentrations (MICs) from some contemporary isolates exhibited high-level susceptibility to most macrolides and quinolones, and moderate susceptibility to most tetracyclines, whereas other contemporary isolates had high MICs to the same antibiotics. Randomized trials demonstrated poor efficacy of doxycycline and better, but declining, efficacy of single-dose azithromycin therapy. Treatment failures after extended doses of azithromycin similarly increased, and circulating macrolide resistance was present in high levels in several areas. Moxifloxacin remains the most effective therapy, but treatment failures and quinolone resistance are emerging. Surveillance of M. genitalium prevalence and antimicrobial resistance patterns is urgently needed.

  • Mycoplasma genitalium infection and female reproductive tract disease a meta analysis
    Clinical Infectious Diseases, 2015
    Co-Authors: Rebecca Lis, Ali Rowhanirahbar, Lisa E. Manhart
    Abstract:

    To determine the association between Mycoplasma genitalium infection and female reproductive tract syndromes through meta-analysis, English-language, peer-reviewed studies were identified via PubMed, Embase, Biosis, Cochrane Library, and reference review. Two reviewers independently extracted data. Random-effects models were employed to calculate summary estimates, between-study heterogeneity was evaluated using I(2) statistics, publication bias was assessed via funnel plots and the Begg and Egger tests, and methodologic quality was rated. Mycoplasma genitalium infection was significantly associated with increased risk of cervicitis (pooled odds ratio [OR], 1.66 [95% confidence interval {CI}, 1.35-2.04]), pelvic inflammatory disease (pooled OR, 2.14 [95% CI, 1.31-3.49]), preterm birth (pooled OR, 1.89 [95% CI, 1.25-2.85]), and spontaneous abortion (pooled OR, 1.82 [95% CI, 1.10-3.03]). Risk of infertility was similarly elevated (pooled OR, 2.43 [95% CI, .93-6.34]). In subanalyses accounting for coinfections, all associations were stronger and statistically significant. Testing of high-risk symptomatic women for M. genitalium may be warranted.

  • Mycoplasma genitalium an emergent sexually transmitted disease
    Infectious Disease Clinics of North America, 2013
    Co-Authors: Lisa E. Manhart
    Abstract:

    This article summarizes the epidemiologic evidence linking Mycoplasma genitalium to sexually transmitted disease syndromes, including male urethritis, and female cervicitis, pelvic inflammatory disease, infertility, and adverse birth outcomes. It discusses the relationship of this bacterium to human immunodeficiency virus infection and reviews the available literature on the efficacy of standard antimicrobial therapies against M genitalium.

  • Mycoplasma genitalium should we treat and how
    Clinical Infectious Diseases, 2011
    Co-Authors: Lisa E. Manhart, Matthew R Golden, Jennifer M Broad
    Abstract:

    Mycoplasma genitalium is associated with acute and chronic urethritis in men. Existing data on infection in women are limited and inconsistent but suggest that M. genitalium is associated with urethritis, cervicitis, pelvic inflammatory disease, and possibly female infertility. Data are inconclusive regarding the role of M. genitalium in adverse pregnancy outcomes and ectopic pregnancy. Available data suggest that azithromycin is superior to doxycycline in treating M. genitalium infection. However, azithromycin-resistant infections have been reported in 3 continents, and the proportion of azithromycin-resistant M. genitalium infection is unknown. Moxifloxacin is the only drug that currently seems to uniformly eradicate M. genitalium. Detection of M. genitalium is hampered by the absence of a commercially available diagnostic test. Persons with persistent pelvic inflammatory disease or clinically significant persistent urethritis or cervicitis should be tested for M. genitalium, if possible. Infected persons who have not previously received azithromycin should receive that drug. Persons in whom azithromycin therapy fails should be treated with moxifloxicin.

Suzanne M Garland - One of the best experts on this subject based on the ideXlab platform.

  • Use of Pristinamycin for Macrolide-Resistant Mycoplasma genitalium Infection
    Emerging infectious diseases, 2018
    Co-Authors: Tim R.h. Read, Christopher K Fairley, Jorgen Skov Jensen, Mieken Grant, Jennifer Danielewski, Gerald L. Murray, Eric P F Chow, Karen Worthington, Suzanne M Garland
    Abstract:

    High levels of macrolide resistance and increasing fluoroquinolone resistance are found in Mycoplasma genitalium in many countries. We evaluated pristinamycin for macrolide-resistant M. genitalium in a sexual health center in Australia. Microbiologic cure was determined by M. genitalium-specific 16S PCR 14-90 days after treatment began. Of 114 persons treated with pristinamycin, infection was cured in 85 (75%). This percentage did not change when pristinamycin was given at daily doses of 2 g or 4 g or at 3 g combined with 200 mg doxycycline. In infections with higher pretreatment bacterial load, treatment was twice as likely to fail for each 1 log10 increase in bacterial load. Gastrointestinal side effects occurred in 7% of patients. Pristinamycin at maximum oral dose, or combined with doxycycline, cured 75% of macrolide-resistant M. genitalium infections. Pristinamycin is well-tolerated and remains an option where fluoroquinolones have failed or cannot be used.

  • prospective evaluation of resistanceplus mg a new multiplex quantitative pcr assay for detection of Mycoplasma genitalium and macrolide resistance
    Journal of Clinical Microbiology, 2017
    Co-Authors: Catriona S. Bradshaw, Sepehr N Tabrizi, Christopher K Fairley, Suzanne M Garland, Sue Walker, Lit Yeen Tan, Elisa Mokany
    Abstract:

    Mycoplasma genitalium is a significant pathogen for which first-line treatment is becoming less effective due to increased resistance to macrolides. As conventional culture and antimicrobial susceptibility testing is not feasible for routine detection of this pathogen, molecular markers such as detection of mutations in the 23S rRNA gene have been described to predict resistance. Recently, a novel multiplex quantitative PCR (qPCR) assay, ResistancePlus MG, has been described for the simultaneous detection of Mycoplasma genitalium and macrolide resistance. In the current study, the clinical performance of the assay was evaluated on 1,089 consecutive urine and anogenital swab samples in symptomatic and asymptomatic male and female patients. Overall, 6.0% were positive for M. genitalium, with 63.1% having macrolide resistance-associated mutations. Compared to the laboratory-validated qPCR method targeting the 16S rRNA gene and Sanger sequencing to determine 23S rRNA mutations, the sensitivity and specificity of M. genitalium detection were 98.5% and 100% and for detection of macrolide resistance mutations were 100.0% and 96.2%, respectively. This assay offers a considerable advantage in clinical settings for M. genitalium testing by making the results of macrolide resistance and mutation analyses simultaneously available, which is increasingly important with escalating macrolide resistance.

  • increasing macrolide and fluoroquinolone resistance in Mycoplasma genitalium
    Emerging Infectious Diseases, 2017
    Co-Authors: Gerald L. Murray, Catriona S. Bradshaw, Melanie Bissessor, Sepehr N Tabrizi, Christopher K Fairley, Jorgen Skov Jensen, Suzanne M Garland, Jennifer Danielewski
    Abstract:

    Abstract Escalating resistance to azithromycin and moxifloxacin is being reported for Mycoplasma genitalium in the Asia-Pacific region. Analyzing 140 infections, we found pretreatment fluoroquinolone-resistance mutations in parC (13.6%) and gyrA (5%). ParC S83 changes were associated with moxifloxacin failure. Combined macrolide/fluoroquinolone-resistance mutations were in 8.6% of specimens, for which recommended therapies would be ineffective.

  • macrolide resistance and azithromycin failure in a Mycoplasma genitalium infected cohort and response of azithromycin failures to alternative antibiotic regimens
    Clinical Infectious Diseases, 2015
    Co-Authors: Melanie Bissessor, Sepehr N Tabrizi, Jimmy Twin, Houda Abdo, Christopher K Fairley, Marcus Y Chen, Lenka A Vodstrcil, Jorgen Skov Jensen, Jane S Hocking, Suzanne M Garland
    Abstract:

    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. Multivariable 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.

  • prevalence of Mycoplasma genitalium in health clinic attendees complaining of vaginal discharge in bangladesh
    International Journal of Std & Aids, 2008
    Co-Authors: Saifur Rahman, Sepehr N Tabrizi, Suzanne M Garland, Marian J Currie, Motiur Rahman, Khairun Nessa, Francis J Bowden
    Abstract:

    The objective of the study was to determine the prevalence of Mycoplasma genitalium in a sample of health clinic attendees complaining of vaginal discharge. A subsample of 399 vaginal and cervical swabs was randomly selected from 2579 samples collected during a study to determine the causes of vaginal discharge in women attending primary health-care clinics in Dhaka, Bangladesh. Cervical samples were tested for M. genitalium by polymerase chain reaction. In addition, the samples were tested for Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, bacterial vaginosis and candida. M. genitalium was detected in three samples (0.8%; 95% confidence interval: 0.00-1.6). The prevalence of C. trachomatis, N. gonorrhoeae T. vaginalis, bacterial vaginosis and candida was 1.3, 3.8, 8, 23.25 and 32.5%, respectively. Two women with M. genitalium were co-infected with T. vaginalis or candida. This is the first study to document the existence of M. genitalium in Bangladesh. Although the prevalence of this infection is low in the population tested, further research into this pathogen in other Bangladeshi populations is justified.

Catriona S. Bradshaw - One of the best experts on this subject based on the ideXlab platform.

  • prospective evaluation of resistanceplus mg a new multiplex quantitative pcr assay for detection of Mycoplasma genitalium and macrolide resistance
    Journal of Clinical Microbiology, 2017
    Co-Authors: Catriona S. Bradshaw, Sepehr N Tabrizi, Christopher K Fairley, Suzanne M Garland, Sue Walker, Lit Yeen Tan, Elisa Mokany
    Abstract:

    Mycoplasma genitalium is a significant pathogen for which first-line treatment is becoming less effective due to increased resistance to macrolides. As conventional culture and antimicrobial susceptibility testing is not feasible for routine detection of this pathogen, molecular markers such as detection of mutations in the 23S rRNA gene have been described to predict resistance. Recently, a novel multiplex quantitative PCR (qPCR) assay, ResistancePlus MG, has been described for the simultaneous detection of Mycoplasma genitalium and macrolide resistance. In the current study, the clinical performance of the assay was evaluated on 1,089 consecutive urine and anogenital swab samples in symptomatic and asymptomatic male and female patients. Overall, 6.0% were positive for M. genitalium, with 63.1% having macrolide resistance-associated mutations. Compared to the laboratory-validated qPCR method targeting the 16S rRNA gene and Sanger sequencing to determine 23S rRNA mutations, the sensitivity and specificity of M. genitalium detection were 98.5% and 100% and for detection of macrolide resistance mutations were 100.0% and 96.2%, respectively. This assay offers a considerable advantage in clinical settings for M. genitalium testing by making the results of macrolide resistance and mutation analyses simultaneously available, which is increasingly important with escalating macrolide resistance.

  • increasing macrolide and fluoroquinolone resistance in Mycoplasma genitalium
    Emerging Infectious Diseases, 2017
    Co-Authors: Gerald L. Murray, Catriona S. Bradshaw, Melanie Bissessor, Sepehr N Tabrizi, Christopher K Fairley, Jorgen Skov Jensen, Suzanne M Garland, Jennifer Danielewski
    Abstract:

    Abstract Escalating resistance to azithromycin and moxifloxacin is being reported for Mycoplasma genitalium in the Asia-Pacific region. Analyzing 140 infections, we found pretreatment fluoroquinolone-resistance mutations in parC (13.6%) and gyrA (5%). ParC S83 changes were associated with moxifloxacin failure. Combined macrolide/fluoroquinolone-resistance mutations were in 8.6% of specimens, for which recommended therapies would be ineffective.

  • efficacy of antimicrobial therapy for Mycoplasma genitalium infections
    Clinical Infectious Diseases, 2015
    Co-Authors: Lisa E. Manhart, Matthew R Golden, Catriona S. Bradshaw, Jorgen Skov Jensen, David H Martin
    Abstract:

    Mycoplasma genitalium has been causally linked with nongonococcal urethritis in men and cervicitis, pelvic inflammatory disease, preterm birth, spontaneous abortion, and infertility in women, yet treatment has proven challenging. To inform treatment recommendations, we reviewed English-language studies describing antimicrobial susceptibility, resistance-associated mutations, and clinical efficacy of antibiotic therapy, identified via a systematic search of PubMed supplemented by expert referral. Minimum inhibitory concentrations (MICs) from some contemporary isolates exhibited high-level susceptibility to most macrolides and quinolones, and moderate susceptibility to most tetracyclines, whereas other contemporary isolates had high MICs to the same antibiotics. Randomized trials demonstrated poor efficacy of doxycycline and better, but declining, efficacy of single-dose azithromycin therapy. Treatment failures after extended doses of azithromycin similarly increased, and circulating macrolide resistance was present in high levels in several areas. Moxifloxacin remains the most effective therapy, but treatment failures and quinolone resistance are emerging. Surveillance of M. genitalium prevalence and antimicrobial resistance patterns is urgently needed.

  • the efficacy of azithromycin for the treatment of genital Mycoplasma genitalium a systematic review and meta analysis
    Clinical Infectious Diseases, 2015
    Co-Authors: Andrew Lau, Catriona S. Bradshaw, Christopher K Fairley, Marcus Y Chen, Dyani Lewis, Fabian Yuh Shiong Kong
    Abstract:

    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%; I(2) = 80.8%, P < .01). For the 12 studies conducted prior to 2009, pooled microbial cure was 85.3% (CI, 82.3%-88.3%; I(2) = 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%; I(2) = 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.

  • management of Mycoplasma genitalium infections can we hit a moving target
    BMC Infectious Diseases, 2015
    Co-Authors: Jorgen Skov Jensen, Catriona S. Bradshaw
    Abstract:

    Mycoplasma genitalium is an etiological agent of sexually transmitted infections, but due to its fastidious growth requirements, only a few M. genitalium strains are available for determination of the activity of currently used and new antimicrobial agents.

Christopher K Fairley - One of the best experts on this subject based on the ideXlab platform.

  • Use of Pristinamycin for Macrolide-Resistant Mycoplasma genitalium Infection
    Emerging infectious diseases, 2018
    Co-Authors: Tim R.h. Read, Christopher K Fairley, Jorgen Skov Jensen, Mieken Grant, Jennifer Danielewski, Gerald L. Murray, Eric P F Chow, Karen Worthington, Suzanne M Garland
    Abstract:

    High levels of macrolide resistance and increasing fluoroquinolone resistance are found in Mycoplasma genitalium in many countries. We evaluated pristinamycin for macrolide-resistant M. genitalium in a sexual health center in Australia. Microbiologic cure was determined by M. genitalium-specific 16S PCR 14-90 days after treatment began. Of 114 persons treated with pristinamycin, infection was cured in 85 (75%). This percentage did not change when pristinamycin was given at daily doses of 2 g or 4 g or at 3 g combined with 200 mg doxycycline. In infections with higher pretreatment bacterial load, treatment was twice as likely to fail for each 1 log10 increase in bacterial load. Gastrointestinal side effects occurred in 7% of patients. Pristinamycin at maximum oral dose, or combined with doxycycline, cured 75% of macrolide-resistant M. genitalium infections. Pristinamycin is well-tolerated and remains an option where fluoroquinolones have failed or cannot be used.

  • prospective evaluation of resistanceplus mg a new multiplex quantitative pcr assay for detection of Mycoplasma genitalium and macrolide resistance
    Journal of Clinical Microbiology, 2017
    Co-Authors: Catriona S. Bradshaw, Sepehr N Tabrizi, Christopher K Fairley, Suzanne M Garland, Sue Walker, Lit Yeen Tan, Elisa Mokany
    Abstract:

    Mycoplasma genitalium is a significant pathogen for which first-line treatment is becoming less effective due to increased resistance to macrolides. As conventional culture and antimicrobial susceptibility testing is not feasible for routine detection of this pathogen, molecular markers such as detection of mutations in the 23S rRNA gene have been described to predict resistance. Recently, a novel multiplex quantitative PCR (qPCR) assay, ResistancePlus MG, has been described for the simultaneous detection of Mycoplasma genitalium and macrolide resistance. In the current study, the clinical performance of the assay was evaluated on 1,089 consecutive urine and anogenital swab samples in symptomatic and asymptomatic male and female patients. Overall, 6.0% were positive for M. genitalium, with 63.1% having macrolide resistance-associated mutations. Compared to the laboratory-validated qPCR method targeting the 16S rRNA gene and Sanger sequencing to determine 23S rRNA mutations, the sensitivity and specificity of M. genitalium detection were 98.5% and 100% and for detection of macrolide resistance mutations were 100.0% and 96.2%, respectively. This assay offers a considerable advantage in clinical settings for M. genitalium testing by making the results of macrolide resistance and mutation analyses simultaneously available, which is increasingly important with escalating macrolide resistance.

  • increasing macrolide and fluoroquinolone resistance in Mycoplasma genitalium
    Emerging Infectious Diseases, 2017
    Co-Authors: Gerald L. Murray, Catriona S. Bradshaw, Melanie Bissessor, Sepehr N Tabrizi, Christopher K Fairley, Jorgen Skov Jensen, Suzanne M Garland, Jennifer Danielewski
    Abstract:

    Abstract Escalating resistance to azithromycin and moxifloxacin is being reported for Mycoplasma genitalium in the Asia-Pacific region. Analyzing 140 infections, we found pretreatment fluoroquinolone-resistance mutations in parC (13.6%) and gyrA (5%). ParC S83 changes were associated with moxifloxacin failure. Combined macrolide/fluoroquinolone-resistance mutations were in 8.6% of specimens, for which recommended therapies would be ineffective.

  • the efficacy of azithromycin for the treatment of genital Mycoplasma genitalium a systematic review and meta analysis
    Clinical Infectious Diseases, 2015
    Co-Authors: Andrew Lau, Catriona S. Bradshaw, Christopher K Fairley, Marcus Y Chen, Dyani Lewis, Fabian Yuh Shiong Kong
    Abstract:

    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%; I(2) = 80.8%, P < .01). For the 12 studies conducted prior to 2009, pooled microbial cure was 85.3% (CI, 82.3%-88.3%; I(2) = 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%; I(2) = 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.

  • macrolide resistance and azithromycin failure in a Mycoplasma genitalium infected cohort and response of azithromycin failures to alternative antibiotic regimens
    Clinical Infectious Diseases, 2015
    Co-Authors: Melanie Bissessor, Sepehr N Tabrizi, Jimmy Twin, Houda Abdo, Christopher K Fairley, Marcus Y Chen, Lenka A Vodstrcil, Jorgen Skov Jensen, Jane S Hocking, Suzanne M Garland
    Abstract:

    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. Multivariable 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.

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