Use of Pristinamycin for Macrolide-Resistant<i>Mycoplasma genitalium</i>Infection

Read, Tim; Jensen, Jørgen Skov; Fairley, Christopher K.; Grant, M; Danielewski, Jennifer; Su, Jenny; Murray, Gerald L; Chow, Eric P F; Worthington, Karen; Garland, Suzanne M.; Tabrizi, Sepehr N.; Bradshaw, Catriona

doi:10.3201/eid2402.170902

Cited by 67 publications

(49 citation statements)

References 29 publications

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“…Infections caused by strains resistant to both macrolides and fluoroquinolones occurred in 20% of patients, who would require alternative treatment options to obtain clinical and microbiological cure. Although pristinamycin has been successfully used to treat patients with multidrug-resistant infections (14), this treatment is not publicly funded in New Zealand and is only available as an imported medicine by special approval, underscoring the importance of exploring new treatment strategies to manage patients with resistant strains.…”

Section: Discussionmentioning

confidence: 99%

Mycoplasma genitalium Antimicrobial Resistance in Community and Sexual Health Clinic Patients, Auckland, New Zealand

Vesty¹,

McAuliffe²,

Roberts³

et al. 2020

Emerg. Infect. Dis.

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M anagement of Mycoplasma genitalium infections is challenging because the limited treatment options have been affected by rapidly evolving resistance to antimicrobial drugs. Molecular approaches are the preferred method of M. genitalium detection, and resistance is determined genotypically. 23S rRNA mutations are associated with macrolide resistance and azithromycin treatment failures (1-3), whereas fluoroquinolone resistance is associated with mutations in the quinolone resistance-determining region, specifically in the gyrA and parC genes (4). Azithromycin is the first-line treatment for M. genitalium infections in New Zealand; second-line treatment relies on moxifloxacin, a fluoroquinolone. A high proportion (72%) of macrolide resistance has been reported in sexual health clinic (SHC) patients in our region (5), and elsewhere in New Zealand fluoroquinolone resistance is reported in 23.3% of M. genitalium-positive specimens from SHC attendees (3), consistent with the high prevalence of macrolide and fluoroquinolone resistance in the Asia-Pacific region (1,3,6). The Study We performed a retrospective study of all specimens referred to the Microbiology Department at Auckland City Hospital (Auckland, New Zealand) for M. genitalium testing in 2017. Referral sites were predominantly general practices in Auckland and SHCs in the Auckland, Northland, and Waikato regions. Ethics approval was granted by the Health and Disability Ethics Committee (approval no. 16/CEN/188). DNA had been extracted from specimens following a diagnostic workflow and stored at −80°C. We retrieved DNA samples that tested positive for M. genitalium using real-time PCR (5,7) for this study. We detected 23S rRNA mutations at nucleotide positions 2058 and 2059 (Escherichia coli numbering) by using the commercially available PlexPCR kit Resistance Plus MG (SpeeDx, https://plexpcr.com) (5) and gyrA and parC mutations by using PCR amplification of M. genitalium nucleotides 172-402 of gyrA and 164-483 of parC (8), followed by sequencing on the Applied Biosystems 3130xl sequencer (Life Technologies, https://www.thermofisher.com). Sequences were aligned against M. genitalium reference genes (Gen-Bank accession nos. CP003773 for gyrA and parC for U25549) by using SeqMan II (DNASTAR, https:// www.dnastar.com) and the mutations reported by using M. genitalium numbering. We compared prevalence of resistance-associated mutations in community and SHC cohorts by using a χ 2 test (α = 5%). We tested 302 clinical specimens from 247 patients; 33% (101/302) of samples from 34% (84/247) of patients were M. genitalium DNA-positive. Four samples from 3 patients were excluded from subsequent analyses because insufficient PCR products were obtained for sequencing. We used the remaining 97

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Section: Discussionmentioning

confidence: 99%

Mycoplasma genitalium Antimicrobial Resistance in Community and Sexual Health Clinic Patients, Auckland, New Zealand

Vesty¹,

McAuliffe²,

Roberts³

et al. 2020

Emerg. Infect. Dis.

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“… M. genitalium is also known to persist in men [27–31]. There are no cohort studies in men to observe the natural history of untreated infection.…”

Section: Natural Historymentioning

confidence: 99%

Mycoplasma genitalium: A Review

Gnanadurai

Fifer

2020

Microbiology

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Mycoplasma genitalium is a fastidious organism of the class Mollicutes, the smallest prokaryote capable of independent replication. First isolated in 1981, much is still unknown regarding its natural history in untreated infection. It is recognized as a sexually transmitted pathogen causing acute and chronic non-gonococcal urethritis (NGU) in men, with a growing body of evidence to suggest it also causes cervicitis and pelvic inflammatory disease in women. Its role in several other clinical syndromes is uncertain. The majority of people infected remain asymptomatic and clear infection without developing disease; asymptomatic screening is therefore not recommended. Prevalence rates are higher in patients attending sexual health clinics and in men with NGU. Limited availability of diagnostics has encouraged syndromic management, resulting in widespread antimicrobial resistance and given that few antimicrobial classes have activity against M. genitalium , there is significant concern regarding the emergence of untreatable strains. There is a need for wider availability of testing, which should include detection of macrolide resistance mediating mutations. Expertise in interpretation of microbiological results with clinical correlation ensures targeted treatment avoiding unnecessary antibiotic exposure. Public health surveillance nationally and internationally is vital in monitoring and responding to changing epidemiology trends. In this review, we summarize current knowledge of M. genitalium , including epidemiology, clinical and microbiological data, and discuss treatment challenges in the era of rising multidrug resistance.

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“…For treatment of macrolide-resistant strains of M. genitalium, three regimens of pristinamycin, including pristinamycin and doxycycline combination, were reported to eradicate the mycoplasmas in 85 (75%) of 114 patients [19]. In our previous study, we treated 11 men with M. genitalium-positive non-gonococcal urethritis with an extended minocycline regimen, 100 mg twice daily for 14 days, and eradicated the mycoplasma in 10 men [20].…”

Section: Discussionmentioning

confidence: 99%

Surveillance of the prevalence of macrolide and/or fluoroquinolone resistance-associated mutations in Mycoplasma genitalium in Japan

Deguchi

Ito²,

Yasuda

et al. 2018

Journal of Infection and Chemotherapy

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To clarify the status of macrolide and fluoroquinolone resistance of clinical strains of Mycoplasma genitalium in Japan, we amplified portions of the gyrA, parC, and 23S rRNA genes from DNAs in 627 first-voided urine specimens collected from men with M. genitalium-positive urethritis who visited clinics mainly in Sendai, Tokyo, and Osaka, Japan, from 2013 to 2017, by PCR and sequenced. The incidence of single amino acid changes at Met95 or Asp99 in GyrA increased chronologically and was approximately 10% from 2015 onward. The incidence of amino acid changes at Ser83 or Asp87 in ParC was approximately 50% in 2013 but increased to 60-70% from 2014 to 2017. The incidence of mutations at A2071 or A2072 in the 23S rRNA gene increased chronologically and reached over 70% in 2017. The prevalence of M. genitalium harboring alterations in ParC and mutations in the 23S rRNA gene increased and was approximately 50% in 2016 and 2017. The prevalence of M. genitalium with alterations in both GyrA and ParC and mutations in the 23S rRNA gene, which could be associated with treatment failures with the sitafloxacin and azithromycin regimens, were approximately 15% and 10% in 2016 and 2017, respectively. The prevalence of M. genitalium with genetic alterations associated with resistance to fluoroquinolones and/or macrolides is increasing rapidly in Japan. We must prevent the further selection of multi-drug-resistant M. genitalium so that M. genitalium infections will not become untreatable.

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Use of Pristinamycin for Macrolide-ResistantMycoplasma genitaliumInfection

Cited by 67 publications

References 29 publications

Mycoplasma genitalium Antimicrobial Resistance in Community and Sexual Health Clinic Patients, Auckland, New Zealand

Mycoplasma genitalium Antimicrobial Resistance in Community and Sexual Health Clinic Patients, Auckland, New Zealand

Mycoplasma genitalium: A Review

Surveillance of the prevalence of macrolide and/or fluoroquinolone resistance-associated mutations in Mycoplasma genitalium in Japan

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