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Clin Infect Dis ; 2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-31629365


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 2.5g-azithromycin cured 92% and 95% of macrolide-resistant and macrolide-susceptible infections, respectively. We now present the data on RGT using doxycycline-moxifloxacin, the regimen recommended in international guidelines, and extend the data on the efficacy of doxyxycline-2.5g azithromycin and subsequent de novo macrolide-resistance. METHODS: Patients attending Melbourne Sexual Health Centre between 2017-2018 with STI-related syndromes were treated with doxycycline for 7 days and recalled if positive for MG. Macrolide-susceptible cases then received 2.5g azithromycin (1g, then 500mg daily for 3 days) and resistant cases received moxifloxacin (400 mg daily, 7 days). Test of cure (TOC) was recommended 14-28 days post-completion of antimicrobials. Adherence and adverse effects were recorded. RESULTS: A total of 383 patients (81 females/106 heterosexual males/196 men-who-have-sex-with-men) were included. Microbial cure following doxycycline-azithromycin was 95.4% (95% CI 89.7-98.0) and doxycycline-moxifloxacin was 92.0%(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% (91.6-97.8). ParC mutations implicated in moxifloxacin failure were present in 15-22% of macrolide-resistant cases at baseline. CONCLUSION: These findings support the inclusion of moxifloxacin in resistance-guided strategies and extend the evidence for use of 2.5g azithromycin, and presumptive use of doxycycline. These data provide an evidence-base for current UK, Australian and European guidelines for the treatment of MG, an STI which is increasingly challenging to cure.

Clin Infect Dis ; 68(4): 554-560, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29873691


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.

Antibacterianos/uso terapêutico , Monitoramento de Medicamentos/métodos , Farmacorresistência Bacteriana , Macrolídeos/uso terapêutico , Infecções por Mycoplasma/tratamento farmacológico , Mycoplasma genitalium/efeitos dos fármacos , Mycoplasma genitalium/isolamento & purificação , Adulto , Antibacterianos/farmacologia , Feminino , Humanos , Macrolídeos/farmacologia , Masculino , Infecções por Mycoplasma/microbiologia , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem