Resistance-guided Treatment Research Articles

Mycoplasma genitalium treatment outcomes among a cohort failing macrolide resistance-guided treatment across three London sexual health clinics

ObjectiveBritish guidelines advise treatment of Mycoplasma genitalium (Mgen) infection using the results of macrolide resistance-associated mutation (MRAM) assays. Limited data informs management when patients fail MRAM-guided treatment. This study evaluates...

Detection of Macrolide and/or Fluoroquinolone Resistance Genes in Mycoplasma genitalium Strains Isolated from Men in the Northwest Region of Croatia in 2018-2023.

Mycoplasma genitalium (M. genitalium) poses a significant public health challenge due to its association with non-gonococcal urethritis (particularly in men) and antimicrobial resistance. However, despite the prevalence of M. genitalium infections and the rise in resistance rates, routine testing and surveillance remain limited. This is the first study from Croatia that aimed to assess the prevalence and trends of resistance in M. genitalium strains isolated from male individuals by detecting macrolide and fluoroquinolone resistance genes. The study also aimed to explore the factors associated with resistance and changes in resistance patterns over time. Urine samples collected from male individuals in the Zagreb County and northwest region of Croatia between 2018 and 2023 were tested for M. genitalium with the use of molecular methods. Positive samples were subjected to DNA extraction and multiplex tandem polymerase chain reaction (MT-PCR) targeting genetic mutations associated with macrolide (23S rRNA gene) and fluoroquinolone (parC gene) resistance. Of the 8073 urine samples tested from 6480 male individuals (and following the exclusion of repeated specimens), we found that the prevalence of M. genitalium infection was 2.2%. Macrolide resistance was observed in 60.4% of strains, while fluoroquinolone resistance was found in 19.2%. Co-resistance to both antibiotics was present in 18.2% of cases. A statistically significant increase in fluoroquinolone resistance was noted over the study period (p = 0.010), but this was not evident for azithromycin resistance (p = 0.165). There were no statistically significant differences in resistance patterns between age groups, whereas re-testing of patients revealed dynamic changes in resistance profiles over time. The high burden of macrolide resistance and increasing fluoroquinolone resistance underscore the urgent need for comprehensive resistance testing and surveillance programs. The implementation of resistance-guided treatment strategies, along with enhanced access to molecular diagnostics, is pivotal for effectively managing M. genitalium infections.

Detection and Prevalence of Macrolide and Fluoroquinolone Resistance in Mycoplasma genitalium in Badalona, Spain

Macrolide and fluoroquinolone resistance (MLr/FQr) in Mycoplasma genitalium (MG) infections is concerning worldwide. Current guidelines recommend performing MLr detection in MG-positive cases to adjust antimicrobial therapy. We aimed to evaluate the usefulness of PCR followed by pyrosequencing for MLr detection in comparison with a one-step commercial assay and to assess the prevalence of MLr and FQr in Badalona, Spain. A total of 415 MG-positive samples by Allplex STI-7 (Seegene) were analyzed for MLr detection by pyrosequencing. From those, 179 samples were further analyzed for MG and MLr by ResistancePlus® MG kit (SpeeDx) and 100 of them also for fluoroquinolone resistance (FQr) by sequencing the parC gene. Regarding MG detection, Allplex and Resistance Plus® showed an overall agreement of 87%, but this value rose to 95.4% if we compare them for MLr detection. Prevalence of MLr was 23.1% in Badalona, but this rate increased to 73.7% in the HIV-positive patients cohort. FQr detection showed 3% of resistant strains. Pyrosequencing is a convenient and cheap technique for MLr detection, but one-step tools should be considered in high-throughput laboratories. Despite the fact that MLr remained moderate and FQr was low in our study, simultaneous MG and MLr detection would improve patient’s management applying resistance-guided treatment strategies.

Antibiotic Resistance and Genotypes of Mycoplasma genitalium during a Resistance-Guided Treatment Regime in a German University Hospital.

The treatment of infections from the sexually transmitted pathogen Mycoplasma genitalium is hampered by the rapidly increasing resistance to the recommended first- (macrolides) and second-line antibiotics (quinolones). Thus, resistance-guided therapy (RGT) is key for its successful eradication but the efficiency of this approach can be influenced by re-infections and treatment failures. The typing of strains is helpful to distinguish between ongoing colonization, re-infection or the development of resistance. In the present study, mgpB and MG_309 types as well as mutations associated with macrolide, quinolone and tetracycline resistance of strains in M. genitalium-positive samples accumulated in the years 2019 and 2020 at a university hospital were analyzed. Fifty-eight positive first and sixteen positive follow-up samples from patients (96.6% male, 84.5% men who have sex with men, 74.1% HIV-positive) were included. Twenty-three mgpB types (seven new types), nine MG_309 types and thirty-four mgpB/MG_309 types were identified. The prevalence of mutations associated with macrolide, quinolone and tetracycline resistance was 56.9%, 10.3% and 6.8%, respectively. Despite the fact that many asymptomatic patients were not treated and tests of cure were impossible in different cases, the preliminary rate of successful eradication (93.3%) in this study is promising for the continuation of the RGT strategy.

Mycoplasma genitalium: test positivity in syndromic presentations and clinicians' adherence with treatment guidelines at Sydney Sexual Health Centre.

Mycoplasma genitalium (M.genitalium) is associated with urethritis, cervicitis, pelvic inflammatory disease, proctitis and epididymitis. Its treatment is complicated by antimicrobial resistance. To assess clinicians' adherence to M.genitalium diagnostic testing recommendations for syndromic presentations, as well as resistance-guided management of M.genitalium at Sydney Sexual Health Centre, we reviewed patients presenting between August and December 2018. 349/372 (94%) syndromic presentations were tested for M.genitalium with 16% M.genitalium test positivity and 81% macrolide resistance. 16/27 (59%) macrolide-sensitive infections and 65/77 (84%) macrolide-resistant infections received resistance-guided treatment. Tests of cure (TOCs) were unnecessarily ordered for 82% macrolide-sensitive cases, while 88% macrolide-resistant cases were correctly ordered TOCs. Co-existing STIs at the time of macrolide-sensitive (p = 0.30) or macrolide-resistant M.genitalium (p = 0.94) diagnosis did not significantly affect adherence to treatment guidelines. This study confirms the expected prevalence of M.genitalium and macrolide resistance in syndromic presentations while our real-world data highlight the decision-making challenges involved with managing M.genitalium, offering insights for further research.

Resistance-guided treatment of Mycoplasma genitalium infection at a UK sexual health centre.

We evaluated the ResistancePlus® MG assay in providing macrolide resistance-guided treatment (RGT) for Mycoplasma genitalium infection at a UK sexual health centre. M. genitalium-positive samples from men with urethritis and women with pelvic inflammatory disease (PID) were tested for macrolide resistance-mediating mutations (MRMMs). MRMM-positive infections were given moxifloxacin 400mg; otherwise 2g azithromycin (1g single dose and then 500mg OD) was given. Among 57M. genitalium-positive patients (32 men and 25 women), MRMMs were detected in 41/57 (72% [95% confidence interval (95% CI) 58-83%). Thirty-two of 43 patients given RGT attended for test of cure. Treatment failure rate was significantly lower at 1/32 (3%) than 10/37 (27%) before RGT (n = 37 [men = 23 and women = 17]; p = 0.008). Treatment failure was lower in male urethritis (0/15 vs. 7/21 p = 0.027) but not in female PID. There was a trend of a shorter time to negative test of cure (TOC) in male urethritis (55.1 [95% 43.7-66.4] vs. 85.1 [95% CI CI 64.1-106.0] days, p = 0.077) but not in female PID. Macrolide resistance is higher than previous UK reports and higher than expected. RGT reduces overall treatment failure and is particularly beneficial in M. genitalium urethritis. Fluoroquinolone resistance will continue to rise with increasing fluoroquinolone use, and RGT is critical to direct appropriate azithromycin use and prevent overuse of moxifloxacin.

Erratum to: Resistance-Guided Treatment of Gonorrhea: A Prospective Clinical Study.

Erratum to: Resistance-Guided Treatment of Gonorrhea: A Prospective Clinical Study.

Optimizations to keep gonorrhoea treatable and reduce antimicrobial resistance selection.

Antimicrobial resistance in Neisseria gonorrhoeae compromises gonorrhoea treatment worldwide. Novel and optimized treatments and/or treatment strategies that effectively eradicate the infection with low selection of resistance are imperative. A new prospective clinical study provides further evidence that resistance-guided treatment of gonorrhoea with single-dose oral ciprofloxacin is efficacious in relevant settings and can reduce the selection pressure for resistance.

Prevalence of resistance associated substitutions and efficacy of baseline resistance-guided chronic hepatitis C treatment in Spain from the GEHEP-004 cohort.

Treatment guidelines differ in their recommendation to determine baseline resistance associated substitutions (RAS) before starting a first-line treatment with direct-acting antivirals (DAAs). Here we analyze the efficacy of DAA treatment with baseline RAS information. We conducted a prospective study involving 23 centers collaborating in the GEHEP-004 DAA resistance cohort. Baseline NS5A and NS3 RASs were studied by Sanger sequencing. After issuing a comprehensive resistance report, the treating physician decided the therapy, duration and ribavirin use. Sustained virological response (SVR12) data are available in 275 patients. Baseline NS5A RAS prevalence was between 4.3% and 26.8% according to genotype, and NS3 RASs prevalence (GT1a) was 6.3%. Overall, SVR12 was 97.8%. Amongst HCV-GT1a patients, 75.0% had >800,000 IU/ml and most of those that started grazoprevir/elbasvir were treated for 12 weeks. In genotype 3, NS5A Y93H was detected in 9 patients. 42.8% of the HCV-GT3 patients that started sofosbuvir/velpatasvir included ribavirin, although only 14.7% carried Y93H. The efficacy of baseline resistance-guided treatment in our cohort has been high across the most prevalent HCV genotypes in Spain. The duration of the grazoprevir/elbasvir treatment adhered mostly to AASLD/IDSA recommendations. In cirrhotic patients infected with GT-3 there has been a high use of ribavirin.