Increasing Macrolide and Fluoroquinolone Resistance in Mycoplasma genitalium.
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ABSTRACT:
SUBMITTER: Murray GL
PROVIDER: S-EPMC5403035 | biostudies-literature | 2017 May
REPOSITORIES: biostudies-literature
Publications
Increasing Macrolide and Fluoroquinolone Resistance in Mycoplasma genitalium.
Murray Gerald L GL Bradshaw Catriona S CS Bissessor Melanie M Danielewski Jennifer J Garland Suzanne M SM Jensen Jørgen S JS Fairley Christopher K CK Tabrizi Sepehr N SN
Emerging infectious diseases 20170501 5
Escalating resistance to azithromycin and moxifloxacin is being reported for Mycoplasma genitalium in the Asia-Pacific region. Analyzing 140 infections, we found pretreatment fluoroquinolone-resistance mutations in parC (13.6%) and gyrA (5%). ParC S83 changes were associated with moxifloxacin failure. Combined macrolide/fluoroquinolone-resistance mutations were in 8.6% of specimens, for which recommended therapies would be ineffective. ...[more]
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Project description:BackgroundMycoplasma genitalium (MG) is a sexually transmitted pathogen associated with inflammatory syndromes in men and women. Macrolides and fluoroquinolones are recommended MG treatments. The frequency of MG strains with macrolide resistance-associated mutations (MRMs) and quinolone resistance-associated mutations (qRMs) is increasing worldwide, however these data are sparse in populations in the United States.MethodsWe investigated the prevalence of MG infections with MRMs and qRMs and MG infection concordance within African American couples in Birmingham, AL. We used a real-time polymerase chain reaction to detect MG and identify MRMs. quinolone resistance-associated mutations were detected using traditional polymerase chain reactions amplifying regions in gyrA, gyrB, parC, and parE. The MG concordance in couples was evaluated by MG positivity and MG genotypes.ResultsOral, anal, urine, and/or vaginal specimens were tested from 116 couples. Twenty-eight (12.1%) participants comprising 22 couples tested MG-positive (11.2% in men and 12.9% in women). Macrolide resistance-associated mutations were detected in 17 (60.7%) MG-positive participants, with gender-specific resistance rates of 69.2% for men and 53.3% for women. quinolone resistance-associated mutations were detected in 3 (11.1%) MG-positive participants, all of whom also had MRMs. By MG positivity status, 27.3% of couples were concordant. If MG strain genotypes are also considered, then concordance was 20.0%.ConclusionsAmong heterosexual African Americans with MG infection, about 60% had strains with MRMs and 11% had strains with both MRMs and qRMs, highlighting the potential for MG treatment failure to not only macrolides, but also quinolones. These findings may help to guide clinicians in MG testing and treatment decisions in the United States.
| S-EPMC6289787 | biostudies-literature
Project description:BackgroundMycoplasma genitalium is an emerging sexually transmitted infection, with increasing rates of resistance to fluroquinolones and macrolides, the recommended treatments. Despite this, M. genitalium is not part of routine screening for Sexually Transmitted Infections (STIs) in many countries and the prevalence of infection and patterns of disease remain to be determined in many populations. Such data is of particular importance in light of the reported rise in antibiotic resistance in M. genitalium isolates.MethodsUrine and urethral swab samples were collected from the primary public sexual health clinic in Singapore and tested for C. trachomatis (CT) or N. gonorrhoeae (NG) infection and for the presence of M. genitalium. Antibiotic resistance in M. genitalium strains detected was determined by screening for genomic mutations associated with macrolide and fluroquinolone resistance.ResultsWe report the results of a study into M. genitalium prevalence at the national sexual health clinic in Singapore. M. genitalium was heavily associated with CT infection (8.1% of cases), but present in only of 2.4% in CT negative cases and not independently linked to NG infection. Furthermore, we found high rates of resistance mutations to both macrolides (25%) and fluoroquinolones (37.5%) with a majority of resistant strains being dual-resistant. Resistance mutations were only found in strains from patients with CT co-infection.ConclusionsOur results support targeted screening of CT positive patients for M. genitalium as a cost-effective strategy to reduce the incidence of M. genitalium in the absence of comprehensive routine screening. The high rate of dual resistance also highlights the need to ensure the availability of alternative antibiotics for the treatment of multi-drug resistant M. genitalium isolates.
| S-EPMC7189604 | biostudies-literature
Project description:Macrolide (MLR) and fluoroquinolone (FQR) resistance in Mycoplasma genitalium (MG) has recently become a major problem worldwide. The available data on the prevalence of MLR and FQR in MG in Russia are limited. In this study, we aimed to evaluate the prevalence and pattern of mutations in 213 MG-positive urogenital swabs from patients in Moscow between March 2021 and March 2022. MLR- and FQR-associated mutations were searched in 23S rRNA as well as in the parC and gyrA genes using Sanger sequencing. The prevalence of MLR was 55/213 (26%), with A2059G and A2058G substitutions being the two most common variants (36/55, 65%, and 19/55, 35%, respectively). FQR detection showed 17% (37/213); two major variants were D84N (20/37, 54%) and S80I (12/37, 32.4%) and three minor variants were S80N (3/37, 8.1%), D84G (1/37, 2.7%), and D84Y (1/37, 2.7%). Fifteen of the fifty-five MLR cases (27%) simultaneously harbored FQR. This study revealed the high frequency of MLR and FQR. We conclude that the improvement of patient examination algorithms and therapeutic approaches should be combined with the routine monitoring of antibiotic resistance based on the sensitivity profiles presented. Such a complex approach will be essential for restraining the development of treatment resistance in MG.
| S-EPMC10058343 | biostudies-literature
Project description:BackgroundTraditional drug susceptibility testing cannot be performed in clinical laboratories due to the slow-growing characteristics of Mycoplasma genitalium when cultured in vitro. Sanger sequencing is the standard method for detecting drug resistance-associated mutations. It has been used in some laboratories to guide the choice of macrolide antibiotics for Mycoplasma genitalium infected patients. Furthermore, resistance to fluoroquinolone has become another emerging clinical challenge.ObjectiveSequencing analysis can detect unknown mutations, but it is time-consuming, requires professional analytical skills and the appropriate testing equipment. The main objective of this study was to establish a nested real-time PCR method for the simultaneous detection of 23S rRNA and parC genotypes in relation to the macrolide and fluoroquinolone resistance.Results105 MG-positive samples and 27 samples containing other pathogens were used for validation. The limit of the nested real-time PCR detection was 500 copies/reaction and there was no cross-reaction with Ureaplasma urealyticum, Mycoplasma hominis, Chlamydia trachomatis, Neisseria gonorrhoeae, Human papillomavirus, Herpes simplex virus, Candida albicans and Ureaplasma parvum, but the 23S rRNA assay cross-reacted with Mycoplasma pneumoniae. Compared with sequencing results, the sensitivity of 23S rRNA was 100% (95% CI; 93.3 -100), the specificity was 94.3% (95% CI; 79.4 - 99.0), the overall consistency was 98% (95% CI; 92.5 - 99.7) and kappa value was 0.96 (P < 0.001); the sensitivity of parC was 100% (95% CI; 93.4 - 100), the specificity was 89.7% (95% CI; 71.5 - 97.3) and the overall consistency was 96.9% (95% CI; 90.7 - 99.2) with a kappa value of 0.92 (P < 0.001).ConclusionsThe results of this sensitive and rapid alternative for identifying resistant genotypes of Mycoplasma genitalium are intuitive and easy to interpret, especially for mixed MG populations. Although the relevant 23S rRNA primers need further adjustment, this reliable method would provide an effective diagnostic tool for the selection of antibiotics in clinical practice.
| S-EPMC10623348 | biostudies-literature
Project description:BackgroundMycoplasma genitalium (MG) causes symptomatic urethritis in men, and can infect alone or together with other sexually transmitted infection (STI) agents.MethodsThe prevalence of MG and other STIs was determined in 1816 men with symptomatic urethritis. Resistance of MG to macrolides and fluoroquinolones was determined by sequencing; the impact of recent antimicrobial usage on the distribution of MG single or mixed infections was determined.ResultsOverall, prevalence of MG infection was 19.7% (358/1816). Fifty-four percent (166/307) of MG infections occurred alone in the absence of other STI agents. Men with single MG infection self-administered or were prescribed antibiotics more often in the 30 days prior to enrollment than subjects with urethritis caused by MG coinfection (P < .0001). Higher rates (96.7%) of infection with macrolide resistance in MG were identified in men who had taken macrolides prior to enrollment (P < .03). Overall, 88.9% (303/341) of 23S ribosomal RNA (rRNA) genes contained mutations responsible for macrolide resistance; 89.5% (308/344) of parC and 12.4% (42/339) of gyrA genes had mutations responsible for fluoroquinolone resistance. Approximately 88% (270/308) of MG had combined mutations in 23S rRNA and parC genes; 10.4% (32/308) had mutations in all 3 genes.ConclusionsMG was the single pathogen identified in 11% of men with symptomatic urethritis. Overall, nearly 90% of MG infections were resistant to macrolides and fluoroquinolones. Men who took macrolides in the 30 days prior to enrollment had higher rates (97%) of macrolide-resistant MG. Resistance was associated with numerous mutations in 23SrRNA, parC, and gyrA genes.
| S-EPMC7390511 | biostudies-literature
Project description:ObjectivesMycoplasma genitalium, a sexually transmitted bacterium, faces increasing antibiotic resistance, particularly to azithromycin. However, presence of macrolide resistance-associated mutations (MRAMs) does not evidently implicate azithromycin treatment failure. This study aimed to establish an in vitro co-culture system of M. genitalium isolates and perform phenotypic susceptibility testing for different antibiotics, focusing on azithromycin to evaluate genotypic and phenotypic resistance across MRAMs.MethodsUrine specimens testing positive for M. genitalium via nucleic acid amplification were co-cultured with Vero cells. Phenotypic susceptibility testing was performed for eight antibiotics. Growth inhibition and MIC of M. genitalium by azithromycin were compared across different MRAMs.ResultsM. genitalium was cultured from 20/40 (50.0%) positive urine samples, with phenotypic susceptibility tested in a subset. MICs ranged as follows: azithromycin (0.008->32 mg/L), levofloxacin (1-4 mg/L), moxifloxacin (<0.25-1 mg/L), sitafloxacin (<0.032-0.25 mg/L), minocycline (<0.25-1 mg/L), doxycycline (<0.125-2 mg/L), spectinomycin (<2.5->25 mg/L) and lefamulin (<0.004-0.063 mg/L). Isolates with A2058T demonstrated 24-, 7-, 15- and 12-fold increases in growth inhibition compared with A2058G at azithromycin concentrations of 4, 8, 16 and 32 mg/L, respectively (P < 0.01). MRAMs ranked from low to high impact on MIC range were as follows: wildtype (0.008-0.016), A2058T (8-32), A2059G (≥32) and A2058G (>32).ConclusionsThis study revealed that M. genitalium isolates vary in azithromycin-induced growth inhibition across MRAMs, potentially explaining differences in clinical treatment efficacy. Phenotypic susceptibility testing for other antibiotics demonstrated relatively low MICs. Future studies should incorporate clinical treatment efficacy and symptom severity to optimize treatment for M. genitalium.
| S-EPMC11787896 | biostudies-literature
Project description:High levels of macrolide resistance and increasing fluoroquinolone resistance are found in Mycoplasma genitalium in many countries. We evaluated pristinamycin for macrolide-resistant M. genitalium in a sexual health center in Australia. Microbiologic cure was determined by M. genitalium-specific 16S PCR 14-90 days after treatment began. Of 114 persons treated with pristinamycin, infection was cured in 85 (75%). This percentage did not change when pristinamycin was given at daily doses of 2 g or 4 g or at 3 g combined with 200 mg doxycycline. In infections with higher pretreatment bacterial load, treatment was twice as likely to fail for each 1 log10 increase in bacterial load. Gastrointestinal side effects occurred in 7% of patients. Pristinamycin at maximum oral dose, or combined with doxycycline, cured 75% of macrolide-resistant M. genitalium infections. Pristinamycin is well-tolerated and remains an option where fluoroquinolones have failed or cannot be used.
| S-EPMC5782881 | biostudies-literature
Project description:BackgroundMycoplasma genitalium infection is a sexually transmitted infection that has rapidly become resistant to mainstay treatments. While individualized treatment approaches have been recommended and adopted for macrolides, individualized therapy for fluoroquinolones has not yet been explored, due to a lack of commercial molecular assays and a lack of confidence in specific mutations associated with resistance. In another recent study, we defined a clear role and diagnostic utility in focusing on the absence of resistance mutations to inform microbial cure with fluoroquinolone antimicrobials.MethodsWe developed two proof-of-concept molecular tests that focus on detection of M. genitalium and characterization of WT parC sequences that are strongly linked to fluoroquinolone susceptibility.ResultsWe screened a total of 227 M. genitalium-positive samples using novel molecular beacon and dual hybridization probe assays. These assays were able to detect M. genitalium and characterize fluoroquinolone susceptibility in 143/227 (63%) samples, based on clear differences in melting peak temperatures. The results of these molecular assays were in 100% agreement with 'gold standard' Sanger sequencing. Additionally, WT parC sequences were readily distinguished from M. genitalium samples harbouring parC mutations of known or suspected clinical significance. The ability of the assays to successfully characterize fluoroquinolone susceptibility and resistance was reduced in low M. genitalium load samples.ConclusionsThese proof-of-concept assays have considerable potential to improve individualized treatment approaches and rationalize tests of cure for M. genitalium infection. The ability to initiate individualized treatment in up to two-thirds of cases will enhance antimicrobial stewardship for this challenging pathogen.
| S-EPMC9155627 | biostudies-literature
Project description:BackgroundMycoplasma genitalium (MG), a sexually transmitted infection (STI), has emerged as a common cause of non-gonococcal urethritis and cervicitis worldwide, with documented resistance to commonly used antibiotics including doxycycline and azithromycin. Data in Ghana regarding the prevalence of MG is limited.MethodsThis retrospective study investigated MG presence and macrolide resistance among patients who previously reported to selected clinics for STI symptoms between December 2012 and June 2020. Samples were screened for MG and mutations associated with azithromycin resistance were investigated using Nucleic Acid Amplification Testing (NAAT) including the Resistance Plus MG® kit from SpeeDx and the LightMix® kit for MG, combined with the Modular Mycoplasma Macrolide from TIB Molbiol.ResultsA total of 1,015 samples were screened, out of which MG infection rate by TIB Molbiol and SpeeDx were 3.1% and 3.4%, respectively. The mutation responsible for macrolide resistance was detected in one MG positive sample by both assays. Both diagnostic tests revealed no significant association between MG infection and socio-demographic characteristics, clinical symptoms, gonorrhea, and chlamydia infection status. There was no significant difference in the mycoplasma percentage positivity rate detected using SpeeDx (3.4%) and TIB Molbiol (3.1%).ConclusionsWhile not commonly tested as a cause of STI symptoms, MG is widespread in Ghana, exhibiting symptoms and prevalence comparable to those in other countries and linked to antimicrobial resistance. Future research using various molecular techniques is essential to monitor resistance trends and guide future antibiotic choices.
| S-EPMC11403770 | biostudies-literature
Project description: Not available
| S-EPMC10832590 | biostudies-literature