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1.
Emerg Infect Dis ; 26(8): 1870-1874, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32687029

RESUMO

Antimicrobial-resistant Mycoplasma genitalium is becoming increasingly common and creating major treatment challenges. We present early data on combination therapy with doxycycline and sitafloxacin to treat highly resistant M. genitalium. We found the regimen was well tolerated and cured 11/12 infections that had failed prior regimens with moxifloxacin and pristinamycin.

2.
J Infect Dis ; 221(6): 1017-1024, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32031634

RESUMO

BACKGROUND: The basis of fluoroquinolone treatment failure for Mycoplasma genitalium is poorly understood. METHODS: To identify mutations associated with failure we sequenced key regions of the M. genitalium parC and gyrA genes for patients undergoing sequential therapy with doxycycline-moxifloxacin (201 patients, including 21 with failure) or doxycycline-sitafloxacin (126 patients, including 13 with failure). RESULTS: The parC G248T/S83I mutation was more common among patients with failed sequential doxycycline-moxifloxacin (present in 76.2% of failures vs 7.8% cures, P < .001) or doxycycline-sitafloxacin (50% vs 16.8%, respectively; P = .01) treatment. Doxycycline-sitafloxacin was more efficacious than doxycycline-moxifloxacin against infections carrying the parC mutation conferring S83I amino acid change. Treatment was more likely to fail in these infections if they had a concurrent gyrA mutation (M95I or D99N) (P = .07 for doxycycline-moxifloxacin group and P = .009 for doxycycline-sitafloxacin group), suggesting an additive effect. CONCLUSIONS: This study indicates that parC G248T/S83I mutations contribute to failure of moxifloxacin and sitafloxacin, and the findings will inform the development of quinolone resistance assays needed to ensure optimal selection of antimicrobials for M. genitalium.

3.
J Clin Microbiol ; 57(11)2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31434719

RESUMO

Mycoplasma genitalium causes a common sexually transmitted infection with a marked propensity to develop antimicrobial resistance. As few treatment options exist, this poses significant challenges to clinicians. Recent diagnostic advances have resulted in tests that report the simultaneous detection of M. genitalium and any resistance to macrolides, the first-line treatment. This allows for therapy to be tailored to the individual, thereby optimizing treatment outcomes. However, resistance to fluoroquinolones, the second-line treatment, is increasing in M. genitalium In this study, we describe a new assay, MG+parC (beta), which simultaneously reports the detection of M. genitalium and five parC mutations that have been associated with resistance to fluoroquinolones. These mutations affect the amino acid sequence of ParC at residues S83R (A247C), S83I (G248T), D87N (G259A), D87Y (G259T), and D87H (G259C). The study tested the MG+parC (beta) assay with 202 M. genitalium-positive clinical samples from Australia (n = 141) and Spain (n = 61). Compared to Sanger sequencing, the assay performed with a kappa value of 0.985 (95% confidence interval [CI], 0.955 to 1.000), with a mutation detection sensitivity of 97.6% (95% CI, 87.4 to 99.9), and specificity of 100.0% (95% CI, 97.7 to 100.0). Fluoroquinolone resistance-associated mutations in parC targeted by the assay were more prevalent among the Australian cohort (23.4% [95% CI,16.3 to 31.8]) compared to the Spanish population (8.8% [95% CI, 2.9% to 19.3%]) (P = 0.019). The MG+parC (beta) kit is a simple and reliable method for simultaneous detection of M. genitalium and fluoroquinolone resistance-associated mutations in clinical settings. This novel diagnostic tool may extend the utility of the second line of antimicrobial therapies in M. genitalium infection.

4.
J Clin Microbiol ; 57(9)2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31243085

RESUMO

Mycoplasma genitalium is a common sexually transmitted infection with a propensity to acquire resistance to commonly used antimicrobial therapies. Bacterial load has been linked to patient symptoms and the success of treatment. In this study, we demonstrate methodology to estimate load from routine diagnostic assays using the ResistancePlus MG test (SpeeDx Pty Ltd., Australia). The method gave comparable quantitation to an M. genitalium-specific 16S rRNA quantitative PCR (qPCR; Spearman r = 0.94) for the samples analyzed (n = 499, including urine and swab types as detailed below) and was, therefore, employed to analyze typical load levels for samples in a diagnostic laboratory (total of 1,012 tests). When stratified by sample type, female urine (median, 826 genomes/ml) had the lowest load. This was significantly lower than median loads for all other sample types (male urine [6.91 × 103 genomes/ml], anal swabs [5.50 × 103], cervical swabs [8.15 × 103], endocervical swabs [3.97 × 103], and vaginal swabs [6.95 × 103]) (P < 0.0001). There were no significant differences in load estimates between the other sample types. Reproducibility of load estimates conducted on the same samples was high (r > 0.85). In conclusion, this methodology to provide load estimates for M. genitalium can be easily integrated into routine diagnostic laboratory workflow. Given the association between organism load, symptoms, and treatment success, load assessment has future diagnostic potential.

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