Clinical Presentations and Treatment Outcomes of Mycoplasma genitalium Infections at a Large New York City Health Care System.

BACKGROUND: Mycoplasma genitalium (MG) is an emerging sexually transmitted infection. Treatment of MG is complicated by increasing resistance to primary treatment regimens, including macrolides and fluoroquinolones. Understanding the various clinical presentations and relative effectiveness of treatments for MG is crucial to optimizing care. METHODS: Patients with a positive MG nucleic acid amplification test between July 1, 2019, and June 30, 2021, at a large health system in New York City were included in a retrospective cohort. Demographics, clinical presentations, coinfections, treatment, and follow-up microbiologic tests were obtained from the electronic medical record. Associations with microbiologic cure were evaluated in bivariate and multivariable logistic regression models. RESULTS: Five hundred two unique patients had a positive MG nucleic acid amplification test result during the study period. Male individuals presented predominantly with urethritis (117 of 187 [63%]) and female individuals with vaginal symptoms (142 of 315 [45%]). Among patients with follow-up testing who received a single antibiotic at the time of treatment, 43% (90 of 210) had persistent infection and 57% (120 of 210) had microbiologic cure. Eighty-two percent of patients treated with moxifloxacin had microbiologic cure compared with 41% of patients receiving azithromycin regimens ( P < 0.001). In multivariable analysis, treatment with moxifloxacin was associated with 4 times the odds of microbiologic cure relative to low-dose azithromycin (adjusted odds ratio [aOR], 4.18; 95% confidence interval, 1.73-10.13; P < 0.01). CONCLUSIONS: Clinical presentations of MG vary, with urethritis or vaginal symptoms in most cases. Among patients who received a single antibiotic, only treatment with moxifloxacin was significantly associated with microbiologic cure relative to low-dose azithromycin.

[The efficiency of combination therapy of non-gonococcal urethritis in men].

AIM: To carry out a comparative assessment of the efficiency of combination therapy for non-gonococcal urethritis (NGU) in men. MATERIALS AND METHODS: a total of 124 patients with NGU and laboratory-confirmed urogenital infection were included in the study. The diagnostic methods included microscopy of urethral smear, real-time polymerase chain reaction (PCR) for the detection of uropathogens and laser Doppler flowmetry for evaluating the urethral microcirculation. All patients were randomized into three groups matched for age, clinical manifestations, and disease duration. Patients of the group 1 received targeted antibiotic therapy. In the group 2, local peloid therapy was added, while patients in group 3 additionally received vibromagnetotherapy. The control group consisted of 22 patients aged 18 to 55 years. The study included 2 visits, at the baseline and 4 weeks after the end of treatment. RESULTS: After the treatment, the frequency of microbiological cure was 89%. In the group 3, more pronounced improvement in main symptoms of NGU was observed. The analysis of microcirculation after treatment in the groups 2 and 3 showed a significant increase in perfusion and modulation of urethral blood flow and a decrease in venous congestion after combined therapy. CONCLUSION: The combined treatment, including antibiotic, peloid therapy, and vibromagnetotherapy, promotes more pronounced clinical improvement, restoration of urethral microcirculation and relief of inflammatory process in patients with NGU and can be recommended for routine clinical practice.

High rates of treatment failure for Mycoplasma genitalium among men and women attending a sexual health clinic.

BACKGROUND: Mycoplasma genitalium (Mgen) causes non-gonococcal urethritis (NGU) and is believed to cause pelvic inflammatory disease (PID). High rates of macrolide resistance are well documented globally for Mgen. In Brighton, patients with NGU and PID are tested for Mgen and test of cure (TOC) offered post-treatment. METHODS: Demographic, clinical and treatment history data were collected over a 12-month period for all Mgen-positive patients in a Brighton-based genitourinary clinic. RESULTS: There were 114 patients with Mgen. 18% (61/339) of men with NGU and 9% (15/160) of women with PID had Mgen. 62/114 (54%) returned for first test TOC 4 weeks after treatment. 27/62 (44%) had a positive TOC; 25/27 (92.6%) had received azithromycin first line (500 mg stat then 250 mg OD for 4 days), 1/27 (3.7%) had received moxifloxacin first line (400 mg OD for 14 days) and 1/27 (3.7%) had received doxycycline first line (100 mg BD for 7 days). 20/27 (74%) returned for a second TOC 4 weeks later. 5/20 (25%) patients were positive on second TOC; 3/5 (60%) had received azithromycin second line and 2/5 (40%) had received moxifloxacin second line. Patients were more likely to have a positive TOC if they were at risk of reinfection (9/27 positive TOC vs 3/35 negative TOC; p=0.02). Patients given moxifloxacin were more likely to have a negative TOC (1/27 positive TOC vs 9/35 negative TOC; p=0.03) than those who received other antibiotic regimens. CONCLUSIONS: Treatment failure rates for Mgen following azithromycin use are substantial, raising concerns regarding resistance. However, reinfection risk may contribute, suggesting a requirement for improved public awareness and clinician knowledge.

An overview of reactive arthritis.

Reactive arthritis, also known as Reiter syndrome, is a spondyloarthropathy that typically follows a urogenital or gastrointestinal infection, and is characterized by conjunctivitis, urethritis, and arthritis. The frequency of reactive arthritis in the United States is estimated at 3.5 to 5 patients per 100,000. Physician assistants (PAs) can manage the condition; therefore, they should be familiar with the disease's signs and symptoms, diagnostic criteria, and treatment regimens. Without proper management, reactive arthritis can progress to a chronic destructive arthritis. Prompt recognition of the condition is key to early intervention and a better patient outcome with fewer complications.

Evaluation of the Microbiological Efficacy of a Single 2-Gram Dose of Extended-Release Azithromycin by Population Pharmacokinetics and Simulation in Japanese Patients with Gonococcal Urethritis.

The objective of this study was to analyze the relationship between the pharmacokinetic (PK)/pharmacodynamic (PD) parameters of a single 2-g dose of extended-release formulation of azithromycin (AZM-SR) and its microbiological efficacy against gonococcal urethritis. Fifty male patients with gonococcal urethritis were enrolled in this study. In 36 patients, the plasma AZM concentrations were measured using liquid chromatography-tandem mass spectrometry, the AZM MIC values for the Neisseria gonorrhoeae isolates were determined, and the microbiological outcomes were assessed. AZM-SR monotherapy eradicated N. gonorrhoeae in 30 (83%) of the 36 patients. AZM MICs ranged from 0.03 to 2 mg/liter. The mean value of the area under the concentration-time curve (AUC), estimated by population PK analysis using a two-compartment model, was 20.8 mg · h/liter. Logistic regression analysis showed that the PK/PD target value required to predict an N. gonorrhoeae eradication rate of ≥95% was a calculated AUC/MIC of ≥59.5. The AUC/MIC value was significantly higher in patients who achieved microbiological cure than in patients who achieved microbiological failure. Monte Carlo simulation using this MIC distribution revealed that the probability that AZM-SR monotherapy would produce an AUC/MIC exceeding the AUC/MIC target of 59.5 was 47%. Furthermore, the MIC distribution for strains isolated in this study was mostly consistent with that for strains currently circulating in Japan. In conclusion, in Japan, AZM-SR monotherapy may not be effective against gonococcal urethritis. Therefore, use of a single 2-g dose of AZM-SR either with or without other antibiotics could be an option to treat gonococcal urethritis if patients are allergic to ceftriaxone and spectinomycin or are diagnosed to be infected with an AZM-sensitive strain.

Multidrug-resistant Neisseria gonorrhoeae infection with ceftriaxone resistance and intermediate resistance to azithromycin, Denmark, 2017.

We describe a multidrug-resistant Neisseria gonorrhoeae infection with ceftriaxone resistance and azithromycin intermediate resistance in a heterosexual man in Denmark, 2017. Whole genome sequencing of the strain GK124 identified MSLT ST1903, NG-MAST ST1614 and all relevant resistance determinants including similar penA resistance mutations previously described in ceftriaxone-resistant gonococcal strains. Although treatment with ceftriaxone 0.5 g plus azithromycin 2 g was successful, increased awareness of spread of gonococcal strains threatening the recommended dual therapy is crucial.

Multiplex Assay for Simultaneous Detection of Mycoplasma genitalium and Macrolide Resistance Using PlexZyme and PlexPrime Technology.

Mycoplasma genitalium is a cause of non-gonoccocal urethritis (NGU) in men and cervicitis and pelvic inflammatory disease in women. Recent international data also indicated that the first line treatment, 1 gram stat azithromycin therapy, for M. genitalium is becoming less effective, with the corresponding emergence of macrolide resistant strains. Increasing failure rates of azithromycin for M. genitalium has significant implications for the presumptive treatment of NGU and international clinical treatment guidelines. Assays able to predict macrolide resistance along with detection of M. genitalium will be useful to enable appropriate selection of antimicrobials to which the organism is susceptible and facilitate high levels of rapid cure. One such assay recently developed is the MG 23S assay, which employs novel PlexZyme™ and PlexPrime™ technology. It is a multiplex assay for detection of M. genitalium and 5 mutations associated with macrolide resistance. The assay was evaluated in 400 samples from 254 (186 males and 68 females) consecutively infected participants, undergoing tests of cure. Using the MG 23S assay, 83% (331/440) of samples were positive, with 56% of positives carrying a macrolide resistance mutation. Comparison of the MG 23S assay to a reference qPCR method for M. genitalium detection and high resolution melt analysis (HRMA) and sequencing for detection of macrolide resistance mutations, resulted in a sensitivity and specificity for M. genitalium detection and for macrolide resistance of 99.1/98.5% and 97.4/100%, respectively. The MG 23S assay provides a considerable advantage in clinical settings through combined diagnosis and detection of macrolide resistance.

2016 European guideline on the management of non-gonococcal urethritis.

We present the updated International Union against Sexually Transmitted Infections (IUSTI) guideline for the management of non-gonococcal urethritis in men. This guideline recommends confirmation of urethritis in symptomatic men before starting treatment. It does not recommend testing asymptomatic men for the presence of urethritis. All men with urethritis should be tested for Chlamydia trachomatis and Neisseria gonorrhoeae and ideally Mycoplasma genitalium using a nucleic acid amplification test (NAAT) as this is highly likely to improve clinical outcomes. If a NAAT is positive for gonorrhoea, a culture should be performed before treatment. In view of the increasing evidence that azithromycin 1 g may result in the development of antimicrobial resistance in M. genitalium, azithromycin 1 g is no longer recommended as first line therapy, which should be doxycycline 100 mg bd for seven days. If azithromycin is to be prescribed an extended course of 500 mg stat, then 250 mg daily for four days is to be preferred over 1 g stat. In men with persistent NGU, M. genitalium NAAT testing is recommended if not previously undertaken, as is Trichomonas vaginalis NAAT testing in populations where T. vaginalis is detectable in >2% of symptomatic women.

Gonococcal Conjunctivitis Despite Successful Treatment of Male Urethritis Syndrome.

We report a case of progressive, cephalosporin-susceptible, Neisseria gonorrhoeae conjunctivitis despite successful treatment of male urethritis syndrome. We hypothesize that conjunctival infection progressed due to insufficient penetration of cefixime and azithromycin and point out that extragenital infection and male urethritis may not be cured simultaneously in settings where the syndromic approach is used.

2015 UK National Guideline on the management of non-gonococcal urethritis.

We present the updated British Association for Sexual Health and HIV guideline for the management of non-gonococcal urethritis in men. This document includes a review of the current literature on its aetiology, diagnosis and management. In particular it highlights the emerging evidence that azithromycin 1 g may result in the development of antimicrobial resistance in Mycoplasma genitalium and that neither azithromycin 1 g nor doxycycline 100 mg twice daily for seven days achieves a cure rate of >90% for this micro-organism. Evidence-based diagnostic and management strategies for men presenting with symptoms suggestive of urethritis, those confirmed to have non-gonococcal urethritis and those with persistent symptoms following first-line treatment are detailed.

Efficacy of Antimicrobial Therapy for Mycoplasma genitalium Infections.

Mycoplasma genitalium has been causally linked with nongonococcal urethritis in men and cervicitis, pelvic inflammatory disease, preterm birth, spontaneous abortion, and infertility in women, yet treatment has proven challenging. To inform treatment recommendations, we reviewed English-language studies describing antimicrobial susceptibility, resistance-associated mutations, and clinical efficacy of antibiotic therapy, identified via a systematic search of PubMed supplemented by expert referral. Minimum inhibitory concentrations (MICs) from some contemporary isolates exhibited high-level susceptibility to most macrolides and quinolones, and moderate susceptibility to most tetracyclines, whereas other contemporary isolates had high MICs to the same antibiotics. Randomized trials demonstrated poor efficacy of doxycycline and better, but declining, efficacy of single-dose azithromycin therapy. Treatment failures after extended doses of azithromycin similarly increased, and circulating macrolide resistance was present in high levels in several areas. Moxifloxacin remains the most effective therapy, but treatment failures and quinolone resistance are emerging. Surveillance of M. genitalium prevalence and antimicrobial resistance patterns is urgently needed.

Management of non-gonococcal urethritis.

Non-gonococcal urethritis (NGU), or inflammation of the urethra, is the most common treatable sexually transmitted syndrome in men, with approximately 20-50 % of cases being due to infection with Chlamydia trachomatis and 10-30 % Mycoplasma genitalium. Other causes are Ureaplasma urealyticum, Trichomonas vaginalis, anaerobes, Herpes simplex virus (HSV) and adenovirus. Up to half of the cases are non-specific. Urethritis is characterized by discharge, dysuria and/or urethral discomfort but may be asymptomatic. The diagnosis of urethritis is confirmed by demonstrating an excess of polymorpho-nuclear leucocytes (PMNLs) in a stained smear. An excess of mononuclear leucocytes in the smear indicates a viral etiology. In patients presenting with symptoms of urethritis, the diagnosis should be confirmed by microscopy of a stained smear, ruling out gonorrhea. Nucleid acid amplifications tests (NAAT) for Neisseria gonorrhoeae, C. trachomatis and for M. genitalium. If viral or protozoan aetiology is suspected, NAAT for HSV, adenovirus and T. vaginalis, if available. If marked symptoms and urethritis is confirmed, syndromic treatment should be given at the first appointment without waiting for the laboratory results. Treatment options are doxycycline 100 mg x 2 for one week or azithromycin 1 gram single dose or 1,5 gram distributed in five days. However, azithromycin as first line treatment without test of cure for M. genitalium and subsequent Moxifloxacin treatment of macrolide resistant strains will select and increase the macrolide resistant strains in the population. If positive for M. genitalium, test of cure samples should be collected no earlier than three weeks after start of treatment. If positive in test of cure, moxifloxacin 400 mg 7-14 days is indicated. Current partner(s) should be tested and treated with the same regimen. They should abstain from intercourse until both have completed treatment. Persistent or recurrent NGU must be confirmed with microscopy. Reinfection and compliance must be considered. Evidence for the following recommendations is limited, and is based on clinical experience and guidelines. If doxycycline was given as first therapy, azithromycin five days plus metronidazole 4-500 mg twice daily for 5-7 days should be given. If azithromycin was prescribed as first therapy, doxycycline 100 mg x 2 for one week plus metronidazole, or moxifloxacin 400 mg orally once daily for 7-14 days should be given.

Sexually transmitted diseases treatment guidelines, 2015.

These guidelines for the treatment of persons who have or are at risk for sexually transmitted diseases (STDs) were updated by CDC after consultation with a group of professionals knowledgeable in the field of STDs who met in Atlanta on April 30-May 2, 2013. The information in this report updates the Sexually Transmitted Diseases Treatment Guidelines, 2010 (MMWR Recomm Rep 2010;59 [No. RR-12]). These updated guidelines discuss 1) alternative treatment regimens for Neisseria gonorrhoeae; 2) the use of nucleic acid amplification tests for the diagnosis of trichomoniasis; 3) alternative treatment options for genital warts; 4) the role of Mycoplasma genitalium in urethritis/cervicitis and treatment-related implications; 5) updated HPV vaccine recommendations and counseling messages; 6) the management of persons who are transgender; 7) annual testing for hepatitis C in persons with HIV infection; 8) updated recommendations for diagnostic evaluation of urethritis; and 9) retesting to detect repeat infection. Physicians and other health-care providers can use these guidelines to assist in the prevention and treatment of STDs.

Failure of azithromycin 2.0 g in the treatment of gonococcal urethritis caused by high-level resistance in California.

We report a treatment failure to azithromycin 2.0 g caused by a urethral Neisseria gonorrhoeae isolate with high-level azithromycin resistance in California. This report describes the epidemiological case investigation and phenotypic and genetic characterization of the treatment failure isolate.

Diagnosis and antimicrobial treatment of Mycoplasma genitalium infection: sobering thoughts.

The discovery of Mycoplasma genitalium in 1980-1981 eventually led to it becoming recognized as an important cause of non-gonococcal urethritis in men and also some genital tract diseases in women. Subsequent to the original isolation, further attempts failed over the next decade and reliable detection only became possible with the use of nucleic acid amplification techniques. Although tetracyclines, particularly doxycycline, were the first choice for treatment of non-gonococcal urethritis prior to the finding of M. genitalium, they were unsatisfactory for the treatment of M. genitalium-associated disease; the organisms were often not eliminated leading, for example, to chronic urethritis. However, the introduction of azithromycin, used as single-dose therapy for chlamydial infections, resulted in clearance of the mycoplasmal organisms from the genital tract and clinical recovery without the development of chronic disease. Nevertheless, such success was short-lived as M. genitalium, through mutation, began to develop resistance to azithromycin and M. genitalium mutants also began to circulate in some populations. In an attempt to counteract this, clinicians should give extended therapy, and in the future, microbiologists, using real-time PCRs, might be able to determine the existence of resistant strains in the local population and so advise on the most appropriate antibiotic. Other than azithromycin, there are a few options, moxifloxacin being one, although the recently reported resistance to this antibiotic is disturbing. In the short to medium term, combination therapy and/or the advent of a new antibiotic might abate the spread of resistance, but in the long term, there is potential for increasing prevalence of untreatable M. genitalium disease. In the future, attempts to develop a vaccine and, of equal importance, one to Chlamydia trachomatis, would not be out of place.

Identification of treatment strategies for Mycoplasma genitalium-related urethritis in male patients by culturing and antimicrobial susceptibility testing.

Mycoplasma genitalium was first isolated from urethral swab specimens of male patients with non-gonococcal urethritis. However, the isolation of M. genitalium strains from clinical specimens has been difficult. Co-cultivation with Vero cells is one available technique for the isolation of M. genitalium. The strains that can be used for antimicrobial susceptibility testing by broth dilution or agar dilution methods are limited. Macrolides, such as azithromycin (AZM), have the strongest activity against M. genitalium. However, AZM-resistant strains have emerged and spread. Mutations in the 23S rRNA gene contribute to the organism's macrolide resistance, which is similar to the effects of the mutations in macrolide-resistant Mycoplasma pneumoniae. Of the fluoroquinolones, moxifloxacin (MFLX) and sitafloxacin have the strongest activities against M. genitalium, while levofloxacin and ciprofloxacin are not as effective. Some clinical trials on the treatment of M. genitalium-related urethritis are available in the literature. A doxycycline regimen was microbiologically inferior to an AZM regimen. For cases of treatment failure with AZM regimens, MFLX regimens were effective.

Antimicrobial chemotherapy of Mycoplasma genitalium-positive non-gonococcal urethritis.

Mycoplasma genitalium is an important pathogen of acute non-gonococcal urethritis (NGU) in men and plays a significant role in persistent or recurrent NGU. In the management of patients with M. genitalium-positive NGU, eradication of the mycoplasma from the urethra is necessary to prevent persistent or recurrent NGU. Therefore, M. genitalium should be considered for antimicrobial chemotherapy of NGU. This article reviews the in vitro antimicrobial activities of antibiotics against M. genitalium and the efficacies of various antibiotic regimens against M. genitalium-positive NGU, including the doxycycline and azithromycin regimens recommended as first-line treatments for NGU in the guidelines. Selection of macrolide-resistant M. genitalium by treatment with the single-dose regimen of 1-g azithromycin and mechanisms of macrolide resistance in M. genitalium are discussed. The effectiveness of the moxifloxacin regimen against persistent or recurrent NGU, unsuccessfully treated with azithromycin and/or doxycycline regimens, is emphasized.