scholarly journals De novo mutations drive the spread of macrolide-resistant Mycoplasma genitalium: a mathematical modelling study

2018 ◽  
Author(s):  
Dominique Cadosch ◽  
Victor Garcia ◽  
Christian L. Althaus ◽  
Jørgen Skov Jensen ◽  
Nicola Low
Keyword(s):  
De Novo ◽  
Management Strategies ◽  
Mycoplasma Genitalium ◽  
Epidemiological Data ◽  
Macrolide Resistance ◽  
De Novo Mutations ◽  
Resistance Mutations ◽  
Treatment Rate ◽  
Rapid Spread ◽  
De Novo Resistance

AbstractBackgroundThe rapid spread of azithromycin resistance in sexually transmitted Mycoplasma genitalium infections is a growing concern. It is not yet clear to what degree macrolide resistance in M. genitalium results from the emergence of de novo mutations or the transmission of resistant strains.MethodsWe analyzed epidemiological data and developed a compartmental model to investigate the contribution of de novo macrolide resistance mutations to the spread of antimicrobial-resistant M. genitalium. We fitted the model to data from France, Denmark and Sweden and estimated treatment rates of infected individuals and the time point of azithromycin introduction.ResultsWe found a high probability of de novo resistance (12%, 95% CI 8–17%), which is responsible for the observed rapid spread of antimicrobial resistant M. genitalium. The estimated per capita treatment rate in France was lower than in Denmark and Sweden but confidence intervals for the three estimates overlap. The estimated dates of introduction of azithromycin in each country are consistent with published reports.ConclusionsSince de novo resistance is the main driver of macrolide resistance in M. genitalium, blind treatment of urethritis with azithromycin is not recommended. Clinical management strategies for M. genitalium should limit the unnecessary use of macrolides.

scholarly journals Understanding the spread of de novo and transmitted macrolide-resistance in Mycoplasma genitalium

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8913
Author(s):  
Dominique Cadosch ◽  
Victor Garcia ◽  
Jørgen S. Jensen ◽  
Nicola Low ◽  
Christian L. Althaus
Keyword(s):  
Single Dose ◽  
De Novo ◽  
Management Strategies ◽  
Mycoplasma Genitalium ◽  
Macrolide Resistance ◽  
Transmission Model ◽  
De Novo Mutations ◽  
Resistance Mutations ◽  
Relative Contribution ◽  
De Novo Resistance

Background The rapid spread of azithromycin resistance in sexually transmitted Mycoplasma genitalium infections is a growing concern. It is not yet clear to what degree macrolide resistance in M. genitalium results from the emergence of de novo mutations or the transmission of resistant strains. Methods We developed a compartmental transmission model to investigate the contribution of de novo macrolide resistance mutations to the spread of antimicrobial-resistant M. genitalium. We fitted the model to resistance data from France, Denmark and Sweden, estimated the time point of azithromycin introduction and the rates at which infected individuals receive treatment, and projected the future spread of resistance. Results The high probability of de novo resistance in M. genitalium accelerates the early spread of antimicrobial resistance. The relative contribution of de novo resistance subsequently decreases, and the spread of resistant infections in France, Denmark and Sweden is now mainly driven by transmitted resistance. If treatment with single-dose azithromycin continues at current rates, macrolide-resistant M. genitalium infections will reach 25% (95% confidence interval, CI [9–30]%) in France, 84% (95% CI [36–98]%) in Denmark and 62% (95% CI [48–76]%) in Sweden by 2025. Conclusions Blind treatment of urethritis with single-dose azithromycin continues to select for the spread of macrolide resistant M. genitalium. Clinical management strategies for M. genitalium should limit the unnecessary use of macrolides.

scholarly journals Levels ofMycoplasma genitaliumAntimicrobial Resistance Differ by Both Region and Gender in the State of Queensland, Australia: Implications for Treatment Guidelines

2019 ◽  
Vol 57 (3) ◽  
Author(s):  
E. L. Sweeney ◽  
E. Trembizki ◽  
C. Bletchly ◽  
C. S. Bradshaw ◽  
A. Menon ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Treatment Guidelines ◽  
Mycoplasma Genitalium ◽  
Macrolide Resistance ◽  
Quinolone Resistance ◽  
Resistance Mutations ◽  
Transmitted Infection ◽  
Content Type ◽  
Sexually Transmitted ◽  
And Gender

ABSTRACTMycoplasma genitaliumis frequently associated with urogenital and rectal infections, with the number of cases of macrolide-resistant and quinolone-resistantM. genitaliuminfection continuing to increase. In this study, we examined the levels of resistance to these two common antibiotic treatments in geographically distinct locations in Queensland, Australia. Samples were screened for macrolide resistance-associated mutations using a commercially available kit (ResistancePlus MG; SpeeDx), and quinolone resistance-associated mutations were identified by PCR and DNA sequencing. Comparisons between antibiotic resistance mutations and location/gender were performed. The levels ofM. genitaliummacrolide resistance were high across both locations (62%). Quinolone resistance mutations were found in ∼10% of all samples, with a number of samples harboring mutations conferring resistance to both macrolides and quinolones. Quinolone resistance was higher in southeast Queensland than in north Queensland, and this was consistent in both males and females (P = 0.007). TheM. genitaliumisolates in rectal swab samples from males harbored high levels of macrolide (75.9%) and quinolone (19%) resistance, with 15.5% harboring resistance to both classes of antibiotics. Overall, the lowest observed level of resistance was to quinolones in females from north Queensland (1.6%). These data highlight the high levels of antibiotic resistance inM. genitaliumisolates within Queensland and the challenges faced by sexually transmitted infection clinicians in managing these infections. The data do, however, show that the levels of antibiotic resistance may differ between populations within the same state, which has implications for clinical management and treatment guidelines. These findings also support the need for ongoing antibiotic resistance surveillance and tailored treatment.

scholarly journals P2.094 The Contribution of Macrolide Resistance Mutations to Failure of Azithromycin Treatment in Mycoplasma Genitalium Infection

2013 ◽  
Vol 89 (Suppl 1) ◽  
pp. A117.1-A117 ◽  
Author(s):  
M Bissessor ◽  
C K Fairley ◽  
M Y Chen ◽  
S N Tabrizi ◽  
J Hocking ◽  
...  
Keyword(s):  
Mycoplasma Genitalium ◽  
Macrolide Resistance ◽  
Resistance Mutations

scholarly journals Resistance-Guided Antimicrobial Therapy Using Doxycycline–Moxifloxacin and Doxycycline–2.5 g Azithromycin for the Treatment of Mycoplasma genitalium Infection: Efficacy and Tolerability

2019 ◽  
Vol 71 (6) ◽  
pp. 1461-1468 ◽  
Author(s):  
Duygu Durukan ◽  
Tim R H Read ◽  
Gerald Murray ◽  
Michelle Doyle ◽  
Eric P F Chow ◽  
...  
Keyword(s):  
De Novo ◽  
Health Centre ◽  
Mycoplasma Genitalium ◽  
Evidence Base ◽  
Macrolide Resistance ◽  
Transmitted Infection ◽  
Sexually Transmitted ◽  
European Guidelines ◽  
Sex With Men ◽  
Guided Therapy

Abstract Background Macrolide resistance in Mycoplasma genitalium (MG) exceeds 50% in many regions, and quinolone resistance is increasing. We recently reported that resistance-guided therapy (RGT) using doxycycline followed by sitafloxacin or 2.5 g azithromycin cured 92% and 95% of macrolide-resistant and macrolide-susceptible infections, respectively. We present data on RGT using doxycycline–moxifloxacin, the regimen recommended in international guidelines, and extend data on the efficacy of doxycycline–2.5 g azithromycin and de novo macrolide resistance. Methods Patients attending Melbourne Sexual Health Centre between 2017 and 2018 with sexually transmitted infection syndromes were treated with doxycycline for 7 days and recalled if MG-positive. Macrolide-susceptible cases received 2.5 g azithromycin (1 g, then 500 mg daily for 3 days), and resistant cases moxifloxacin (400 mg daily, 7 days). Test of cure was recommended 14–28 days post-antimicrobials. Results There were 383 patients (81 females/106 heterosexual males/196 men who have sex with men) included. Microbial cure following doxycycline–azithromycin was 95.4% (95% confidence interval [CI], 89.7–98.0) and doxycycline–moxifloxacin was 92.0% (95% CI, 88.1–94.6). De novo macrolide resistance was detected in 4.6% of cases. Combining doxycycline–azithromycin data with our prior RGT study (n = 186) yielded a pooled cure of 95.7% (95% CI, 91.6–97.8). ParC mutations were present in 22% of macrolide-resistant cases. Conclusions These findings support the inclusion of moxifloxacin in resistance-guided strategies and extend the evidence for 2.5 g azithromycin and presumptive use of doxycycline. These data provide an evidence base for current UK, Australian, and European guidelines for the treatment of MG.

scholarly journals Prospective Evaluation of ResistancePlus MG, a New Multiplex Quantitative PCR Assay for Detection of Mycoplasma genitalium and Macrolide Resistance

2017 ◽  
Vol 55 (6) ◽  
pp. 1915-1919 ◽  
Author(s):  
S. N. Tabrizi ◽  
J. Su ◽  
C. S. Bradshaw ◽  
C. K. Fairley ◽  
S. Walker ◽  
...  
Keyword(s):  
Quantitative Pcr ◽  
Clinical Performance ◽  
Simultaneous Detection ◽  
Mycoplasma Genitalium ◽  
Macrolide Resistance ◽  
23S Rrna ◽  
Rrna Gene ◽  
Resistance Mutations ◽  
Content Type ◽  
Conventional Culture

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.

scholarly journals Which azithromycin regimen should be used for treating Mycoplasma genitalium? A meta-analysis

2017 ◽  
Vol 94 (1) ◽  
pp. 14-20 ◽  
Author(s):  
Patrick Horner ◽  
Suzanne M Ingle ◽  
Frederick Garrett ◽  
Karla Blee ◽  
Fabian Kong ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Random Effects ◽  
Meta Analysis ◽  
Mycoplasma Genitalium ◽  
Macrolide Resistance ◽  
Resistance Mutations ◽  
Doxycycline Treatment ◽  
Online Databases ◽  
Conflicting Evidence ◽  
Resistance Rates

BackgroundThere is increasing evidence that azithromycin 1 g is driving the emergence of macrolide resistance in Mycoplasma genitalium worldwide. We undertook a meta-analysis of M. genitalium treatment studies using azithromycin 1 g single dose and azithromycin 500 mg on day 1 then 250 mg daily for 4 days (5-day regimen) to determine rates of treatment failure and resistance in both regimens.MethodsThe online databases PubMed and Medline were searched using terms “Mycoplasma genitalium”, “macrolide” or “azithromycin” and “resistance” up to April 2016. Studies were eligible if they: used azithromycin 1 g or 5 days, assessed patients for macrolide resistant genetic mutations prior to treatment and patients who failed were again resistance genotyped. Random effects meta-analysis was used to estimate failure and resistance rates.ResultsEight studies were identified totalling 435 patients of whom 82 (18.9%) had received the 5-day regimen. The random effects pooled rate of treatment failure and development of macrolide antimicrobial resistance mutations with azithromycin 1 g was 13.9% (95% CI 7.7% to 20.1%) and 12.0% (7.1% to 16.9%), respectively. Of individuals treated with the 5-day regimen, with no prior doxycycline treatment, fewer (3.7%; 95% CI 0.8% to 10.3%, p=0.012) failed treatment, all of whom developed resistance (p=0.027).ConclusionAzithromycin 1 g is associated with high rates of treatment failure and development of macrolide resistance in M. genitalium infection with no pre-existing macrolide mutations. There is moderate but conflicting evidence that the 5-day regimen may be more effective and less likely to cause resistance.

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