Effectiveness of sitafloxacin monotherapy for quinolone-resistant rectal and urogenital Mycoplasma genitalium infections: a prospective cohort study

Abstract

Background Mycoplasma genitalium has a tendency to develop macrolide and quinolone resistance. Objectives We investigated the microbiological cure rate of a 7 day course of sitafloxacin for the treatment of rectal and urogenital infections in MSM. Patients and methods This open-label, prospective cohort study was conducted at the National Center for Global Health and Medicine, Tokyo, Japan from January 2019 to August 2022. Patients with M. genitalium urogenital or rectal infections were included. The patients were treated with sitafloxacin 200 mg daily for 7 days. M. genitalium isolates were tested for parC, gyrA and 23S rRNA resistance-associated mutations. Results In total, 180 patients (median age, 35 years) were included in this study, of whom 77.0% (97/126) harboured parC mutations, including 71.4% (90/126) with G248T(S83I) in parC, and 22.5% (27/120) harboured gyrA mutations. The median time to test of cure was 21 days. The overall microbiological cure rate was 87.8%. The cure rate was 100% for microbes harbouring parC and gyrA WTs, 92.9% for microbes harbouring parC G248T(S83I) and gyrA WT, and 41.7% for microbes harbouring parC G248T(S83I) and gyrA with mutations. The cure rate did not differ significantly between urogenital and rectal infection (P = 0.359). Conclusions Sitafloxacin monotherapy was highly effective against infection caused by M. genitalium, except strains with combined parC and gyrA mutations. Sitafloxacin monotherapy can be used as a first-line treatment for M. genitalium infections in settings with a high prevalence of parC mutations and a low prevalence of gyrA mutations.

Concurrent parC and gyrA fluoroquinolone resistance mutations and associated strains in Mycoplasma genitalium in Queensland, Australia

“…The GyrA-M95I mutation was rarely found in samples considered to be ParC WT or non-S83I (2.2%; 2/93). Combined with results from Hamasuna et al ., 9 which showed elevated moxifloxacin MICs (≥2 mg/L) in M. genitalium strains with concomitant ParC-S83I and GyrA mutations, and recent studies linking the presence of concurrent ParC-S83I and GyrA mutations to significantly lower cure rates with sitafloxacin and moxifloxacin, 5 , 6 this study further highlights the utility of diagnostic tests that include both ParC-S83I and GyrA-M95I for precision treatment of M. genitalium .…”

“… 4 , 5 This has been further demonstrated by recent studies from Australia and Japan, showing an increased risk of moxifloxacin or sitafloxacin treatment failure where M. genitalium harboured both the ParC-S83I mutation (G248T DNA change) and a concurrent GyrA mutation affecting M95 (particularly M95I/G285A or G285T) or D99. 5 , 6 Here, we explored the proportion of concurrent ParC and GyrA mutations in M. genitalium in Queensland, Australia, to better understand their co-occurrence and diagnostic value for resistance-guided treatment, and their potential links with specific M. genitalium genotypes.…”

Efficacy of Sitafloxacin for Mycoplasma genitalium in an Era of Increasing Antimicrobial Resistance

“…Unfortunately, sequencing of these samples was not available due to the impact of coronavirus disease 2019 (COVID-19) on our laboratory services over the study period, but we know that the prevalence of clinically relevant parC mutations exceeded 20% in M genitalium infections in our clinic population during this study [ 4 , 10 , 11 ]. In addition, it is anticipated that approximately 30% of M genitalium infections with a parC mutation will have a concurrent gyrA mutation, further impacting on treatment outcome [ 7 , 10 ]. Sitafloxacin cured 94% of M genitalium infections that had not previously failed moxifloxacin compared to 69% of infections that had, highlighting the value of this immediately available information to clinicians to inform of decision making.…”

“…Sitafloxacin is a quinolone that is available across the Asia-Pacific region but is limited elsewhere. In Japan, sitafloxacin has been used for a number of years as monotherapy for M genitalium and was reported to achieve cure of approximately 90% [ 6 , 7 ]. However, in Australia, due to concerns about antimicrobial stewardship, sitafloxacin is now reserved for the treatment of resistant M genitalium infections.…”

Sitafloxacin- Versus Moxifloxacin-Based Sequential Treatment for Mycoplasma Genitalium Infections: Protocol for a Multicenter, Open-Label Randomized Controlled Trial

“…Given the unavailability of resistance testing for MRMs and the high prevalence of strains harboring MRMs (89.6%), sitafloxacin is the preferred treatment for M genitalium infections at our facility. Ando et al [ 20 ] reported that sitafloxacin monotherapy cleared strains harboring wild-type parC and gyrA . In addition to resistant strains, sitafloxacin demonstrated high effectiveness (92.9%) in clearing strains harboring parC G248T (S83I) mutations and wild-type gyrA , with 41.7% of those harboring parC G248T (S83I) and gyrA mutations.…”