Use of Pristinamycin for Macrolide-Resistant Mycoplasma genitalium Infection.
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SUBMITTER: Read TRH
PROVIDER: S-EPMC5782881 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: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.
| S-EPMC5403035 | biostudies-literature
Project description:Rapid and sensitive detection of macrolide resistance in Mycoplasma genitalium is required for the guidance of adequate antimicrobial treatment. Previous studies have confirmed that single-base mutations at position 2058 or 2059 in domain V of the 23S rRNA gene of M. genitalium result in high-level macrolide resistance. Sequencing of PCR products remains the gold standard for the identification of mutations conferring resistance to macrolides but is laborious and time-consuming. The aim of the present study was to develop a 5' nuclease genotyping assay to detect single nucleotide polymorphisms in the 23S rRNA gene of Mycoplasma genitalium that are associated with macrolide resistance by combining PCR with hydrolysis probes and subsequent endpoint genotyping analysis. The 5' nuclease genotyping assay was used as a referral test to be used on M. genitalium-positive samples and was validated on 259 positive samples, of which 253 (97.7%) were successfully sequenced. With the newly developed assay, 237/259 (91.5%) investigated M. genitalium-positive samples were genotyped. The positive and the negative predictive values were 100% when evaluated on successfully genotyped samples. The newly developed assay discriminated macrolide-resistant M. genitalium in clinical specimens possessing A2058G, A2058C, A2058T, and A2059G mutations with a sensitivity of 94.4% (95% confidence interval [CI], 90.7% to 98.2%) and a specificity of 92.7% (95% CI, 87.8% to 97.6%) when evaluated on successfully sequenced samples. The assay can correctly guide antimicrobial treatment of M. genitalium infections.
| S-EPMC4879279 | biostudies-literature
Project description:BackgroundMycoplasma genitalium (MG) causes urethritis, cervicitis and pelvic inflammatory disease. The MG treatment failure rate using 1 g azithromycin at an Australian Sexual Health clinic in 2007-9 was 31% (95%CI 23-40%). We developed a rapid high resolution melt analysis (HRMA) assay targeting resistance mutations in the MG 23S rRNA gene, and validated it against DNA sequencing by examining pre- and post-treatment archived samples from MG-infected patients.Methodology/principal findingsAvailable MG-positive pre-treatment (n = 82) and post-treatment samples from individuals with clinical treatment failure (n = 20) were screened for 23S rRNA gene mutations. Sixteen (20%) pre-treatment samples possessed resistance mutations (A2058G, A2059G, A2059C), which were significantly more common in patients with symptomatic azithromycin-treatment failure (12/26; 44%) than in those clinically cured (4/56; 7%), p<0.001. All 20 patients experiencing azithromycin-failure had detectable mutations in their post-treatment samples. In 9 of these cases, the same mutational types were present in both pre- and post-treatment samples indicating transmitted resistance, whilst in 11 of these cases (55%), mutations were absent in pre-treatment samples indicating likely selection of resistant isolates have occurred. HRMA was able to detect all mutational changes determined in this study by DNA sequencing. An additional HRMA assay incorporating an unlabelled probe was also developed to detect type 4 single-nucleotide polymorphisms found in other populations, with a slightly lower sensitivity of 90%.Conclusions/significanceTreatment failure is associated with the detection of macrolide resistance mutations, which appear to be almost equally due to selection of resistant isolates following exposure to 1 g azithromycin and pre-existing transmitted resistance. The application of a rapid molecular assay to detect resistance at the time of initial detection of infection allows clinicians to shorten the time to initiate effective second line treatment. This has the potential to reduce transmission of resistant strains and to avoid sequelae associated with persistent untreated infection.
| S-EPMC3331984 | biostudies-literature
Project description:In Japan and Australia, multidrug-resistant Mycoplasma genitalium infections are reported with increasing frequency. Although macrolide-resistant M. genitalium strains are common in Europe and North America, fluoroquinolone-resistant strains are still exceptional. However, an increase of multidrug-resistant M. genitalium in Europe and America is to be expected. The aim of this paper is to increase awareness on the rising number of multidrug-resistant M. genitalium strains. Here, one of the first cases of infection with a genetically proven multidrug-resistant M. genitalium strain in Europe is described. The patient was a native Dutch 47-year-old male patient with urethritis. Mycoplasma genitalium was detected, but treatment failed with azithromycin, doxycycline and moxifloxacin. A urogenital sample was used to determine the sequence of the 23S rRNA, gyrA, gyrB and parC genes. The sample contained an A2059G single nucleotide polymorphism (SNP) in the 23S rRNA gene and an SNP in the parC gene, resulting in an amino acid change of Ser83 → Ile, explaining both azithromycin and moxifloxacin treatment failure. The SNPs associated with resistance were probably generated de novo, as a link with high-prevalence areas was not established. It is, thus, predictable that there is going to be an increase of multidrug-resistant M. genitalium strains in Europe. As treatment options for multidrug-resistant M. genitalium are limited, the treatment of M. genitalium infections needs to be carefully considered in order to limit the rapid increase of resistance to macrolides and fluoroquinolones.
| S-EPMC5554300 | biostudies-other
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:BACKGROUND:Little is known about the natural history of Mycoplasma genitalium (MG) infection in women. We retrospectively tested archived vaginal fluid samples to assess MG prevalence, incidence, persistence, recurrence and antimicrobial resistance markers among women participating in the Preventing Vaginal Infections trial, a randomized trial of monthly presumptive treatment to reduce vaginal infections. METHODS:High-risk, nonpregnant, HIV-negative women aged 18 to 45 years from Kenya and the United States were randomized to receive metronidazole 750 mg + miconazole 200 mg intravaginal suppositories or placebo for 5 consecutive nights each month for 12 months. Clinician-collected swabs containing cervicovaginal fluid were tested for MG using Hologic nucleic acid amplification testing at enrollment and every other month thereafter. Specimens that were MG+ underwent additional testing for macrolide resistance-mediating mutations by DNA sequencing. RESULTS:Of 234 women enrolled, 221 had available specimens and 25 (11.3%) had MG at enrollment. Among 196 women without MG at enrollment, there were 52 incident MG infections (incidence, 33.4 per 100 person-years). Smoking was independently associated with incident MG infection (adjusted hazard ratio, 3.02; 95% confidence interval, 1.32-6.93), and age less than 25 years trended toward an association (adjusted hazard ratio, 1.70; 95% confidence interval, 0.95-3.06). Median time to clearance of incident MG infections was 1.5 months (interquartile range, 1.4-3.0 months). Of the 120 MG+ specimens, 16 specimens from 15 different women were macrolide resistance-mediating mutation positive (13.3%), with no difference by country. CONCLUSIONS:M. genitalium infection is common among sexually active women in Kenya and the Southern United States. Given associations between MG and adverse reproductive health outcomes, this high burden of MG in reproductive-aged women could contribute to substantial morbidity.
| S-EPMC6043389 | biostudies-literature
Project description:We sought to understand the situation of macrolide-resistant genotypes of Mycoplasma pneumoniae, and analyze the relationship between macrolide-resistant genotypes and clinical manifestations of Mycoplasma pneumoniae pneumonia (MPP). Full-length sequencing of the 23S rRNA gene of M. pneumoniae was performed in 235 nasopharyngeal aspirates (NPAs) from children with MPP. We also retrospectively compared the clinical characteristics of macrolide-resistant (MR) M. pneumoniae infections and macrolide-sensitive (MS) M. pneumoniae infections. A total of 206 patients had point mutations in the M. pneumoniae 23S rRNA gene, and these patients are referred to as MR patients. The remaining 29 patients without point mutations are referred to as MS patients. Among 206 MR patients, 199 (96.6%) had A2063G mutations, 6 had A2063T mutations, and the remaining patients had an A2064G mutation. Among the clinical manifestations, we found that the median fever durations were 8 days (range, 0 to 42 days) and 6 days (0 to 14 days) (P < 0.01), the median hospitalization durations were 8 days (2 to 45 days) and 6 days (3 to 16 days) (P < 0.01), and the median fever durations after macrolide therapy were 5 days (0 to 42 days) and 3 days (0 to 10 days) (P < 0.01), respectively, in the MR and MS groups. We also found that the incidence of extrapulmonary complications in the MR group was significantly higher than that in the MS group (P < 0.05). Moreover, the radiological findings were more serious in the MR group than in the MS group (P < 0.05). The increasing prevalence of MR M. pneumoniae has become a significant clinical issue in the pediatric patients, which may lead to more extrapulmonary complications and severe clinical features and radiological manifestations.
| S-EPMC3910883 | biostudies-literature
Project description:Emergence of macrolide-resistant Mycoplasma pneumoniae (MRMp) challenges empiric macrolide therapy. Our goal was to determine MRMp rates and define characteristics of children infected with macrolide-sensitive M. pneumoniae (MSMp) versus MRMp in Ohio, USA. We cultured PCR-positive M. pneumoniae specimens and sequenced M. pneumoniae-positive cultures to detect macrolide resistance mutations. We reviewed medical records to compare characteristics of both groups. We identified 14 (2.8%) MRMp and 485 (97.2%) MSMp samples. Patients in these groups had similar demographics and clinical characteristics, but patients with MRMp had longer hospitalizations, were more likely to have received previous macrolides, and were more likely to have switched to alternative antimicrobial drugs. MRMp-infected patients also had ≈5-fold greater odds of pediatric intensive care unit admission. Rates of MRMp infections in children in central Ohio are low, but clinicians should remain aware of the risk for severe illness caused by these pathogens.
| S-EPMC8153876 | biostudies-literature
Project description:Mycoplasma pneumoniae is a major pathogen causing community-acquired pneumoniae (CAP), which is generally treated with macrolides. In recent years, however, although macrolide-resistant M. pneumoniae has been reported frequently, particularly in China, very little is known about the prevalence of macrolide-resistant M. pneumoniae infection in adults. In this study, we survey the macrolide-resistant M. pneumoniae in adults in Zhejiang province and characterize the mechanisms of resistance to macrolide. Six hundred fifty throat swab samples were collected from adult patients with CAP from January 2012 to August 2014. These samples were assayed by nested PCR and then cultivated for M. pneumoniae. All isolates were sequenced to determine the mutation in domain V of the 23S rRNA gene. The activities of 10 antibiotics against macrolide-resistant M. pneumoniae isolates were also investigated in vitro. Moreover, restriction fragment length polymorphism (RFLP) analysis of the amplified P1 gene was used to type 50 resistant strains. One hundred percent (71/71) of M. pneumoniae strains isolated from adults with CAP were resistant to erythromycin (MIC=128 to >256 μg/ml), clarithromycin (MIC=128 to >256 μg/ml), and azithromycin (MIC=32 to >64 μg/ml). Furthermore, all macrolide-resistant M. pneumoniae strains identified had an A2063G mutation in domain V of the 23S rRNA gene. Forty-six resistant strains (92.0%) were classified into type I strain on the basis of P1 gene PCR-RFLP analysis. According to these findings, it is suggested that macrolide-resistant M. pneumoniae infection is very prevalence among adults in Zhejiang province. Thus, there is necessary to perform the epidemiological monitoring of macrolide-resistant M. pneumoniae in the future.
| S-EPMC4335877 | biostudies-literature
Project description:We have found that early corticosteroid therapy was effective for reducing morbidity during five Korea-wide epidemics. We evaluated the clinical and laboratory parameters of 56 children who received early corticosteroid treatment for pneumonia that was caused by macrolide-resistant Mycoplasma pneumoniae (M. pneumoniae) or macrolide-sensitive M. pneumoniae between July 2019 and February 2020. All subjects had dual positive results from a PCR assay and serological test, and received corticosteroids within 24–36 h after admission. Point mutation of residues 2063, 2064, and 2067 was identified in domain V of 23S rRNA. The mean age was 6.8 years and the male:female ratio was 1.2:1 (31:25 patients). Most of the subjects had macrolide-resistant M. pneumoniae (73%), and all mutated strains had the A2063G transition. No significant differences in clinical and laboratory parameters were observed between macrolide-resistant and macrolide-sensitive M. pneumoniae groups that were treated with early dose-adjusted corticosteroids. Higher-dose steroid treatment may be needed for patients who have fever that persists for >48 h or increased biomarkers such as lactate dehydrogenase concentration at follow-up despite a usual dose of steroid therapy.
| S-EPMC8004593 | biostudies-literature