Male urethritis is a common disease for urologists, with the most common pathogens being, Chlamydia trachomatis and Neisseria gonorrhoeae. When the tests fail to detect these pathogens, the presented ...urethritis is called non‐chlamydial non‐gonococcal urethritis. Mycoplasma genitalium is one of the pathogens for non‐chlamydial non‐gonococcal urethritis. The test for detecting M. genitalium, which is commercially available in Japan, is not accepted by the Japanese insurance system now. The detection rate of M. genitalium from patients with non‐gonococcal urethritis is 10–20% in Japan. Antimicrobial susceptibility testing for M. genitalium showed that macrolide has the strongest activity and the minimum inhibitory concentrations of tetracyclines were not substantially lower. Some kinds of fluoroquinolones, such as sitafloxacin and moxifloxacin, have stronger activities against M. genitalium. For non‐gonococcal urethritis, macrolides and tetracycline are recommended in some guidelines. In clinical studies, tetracyclines are less effective against M. genitalium than azithromycin, and azithromycin regimens including 1 g stat or 2 g stat are now recommended for urethritis with M. genitalium. However, macrolide‐resistant M. genitalium strains have recently emerged and are spreading worldwide. This macrolide‐resistance is closely related to mutations on the 23S rRNA gene. Sitafloxacin and moxifloxacin have shown good efficacies for M. genitalium in some clinical studies. If the azithromycin regimens fail, we must consider the use of fluoroquinolones, such as sitafloxacin, in Japan. The most important issues include the acceptance of M. genitalium examinations by the national insurance system and the individual treatment of C. trachomatis and M. genitalium in the not‐too‐distant future.
Macrolide or fluoroquinolone-resistant Mycoplasma genitalium is spreading worldwide. We aimed to determine the influence of single nucleotide polymorphisms (SNPs) in the quinolone resistance ...determining regions (QRDR) of parC and gyrA in cultured M. genitalium strains. In addition, we examined the prevalence of macrolide- and fluoroquinolone resistance mediating mutations in specimens collected from Japanese male patients with urethritis in two time-periods between 2005-2009 and 2010-2017, respectively, by sequencing the QRDR of parC and gyrA and domain V of the 23S rRNA gene. The minimum inhibitory concentrations (MIC) of moxifloxacin, sitafloxacin, ciprofloxacin, levofloxacin, doxycycline, minocycline, azithromycin and clarithromycin were determined in 23 M. genitalium strains. Three cultured strains had elevated MICs for moxifloxacin at 16, 4 and 2 mg/L and had SNPs with the amino-acid change Ser83→Ile in ParC (p<0.001) and 3 kinds of SNPs with amino-acid changes Asp99→Asn, Gly93→Cys and Met95→Ile in GyrA, respectively. Among a total of 148 M. genitalium positive urine specimens, the prevalence of A2058G and A2059G SNPs in the 23S rRNA gene and any SNPs in ParC increased from 4.8% and 22.6% in 2005-2009 to 42.2% and 53.1% in 2010-2017, respectively. If M. genitalium is considered multi-drug resistant in clinical specimens carrying SNPs in the 23S rRNA gene and Ser83→Ile in ParC, the prevalence of multi-drug resistance is 12.5% in 2010-2017 in Japan. In conclusion, the SNP resulting in Ser83→Ile in ParC is closely related to moxifloxacin resistance even though other factors may also affect treatment outcomes by moxifloxacin. The prevalence of circulating multi-drug resistant M. genitalium strains with macrolide- and fluoroquinolone-resistance is dramatically increasing in Japan.
Abstract 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 r RNA 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.
Urinary tract infections, genital tract infections and sexually transmitted infections are the most prevalent infectious diseases, and the establishment of locally optimized guidelines is critical to ...provide appropriate treatment. The Urological Association of Asia has planned to develop the Asian guidelines for all urological fields, and the present urinary tract infections, genital tract infections and sexually transmitted infections guideline was the second project of the Urological Association of Asia guideline development, which was carried out by the Asian Association of Urinary Tract Infection and Sexually Transmitted Infection. The members have meticulously reviewed relevant references, retrieved via the PubMed and MEDLINE databases, published between 2009 through 2015. The information identified through the literature review of other resources was supplemented by the author. Levels of evidence and grades of recommendation for each management were made according to the relevant strategy. If the judgment was made on the basis of insufficient or inadequate evidence, the grade of recommendation was determined on the basis of committee discussions and resultant consensus statements. Here, we present a short English version of the original guideline, and overview its key clinical issues.
Non-chlamydial non-gonococcal urethritis (NCNGU) is defined as urethritis with neither Neisseria gonorrhoeae nor Chlamydia trachomatis. Possible causative agents of NCNGU include Mycoplasma ...genitalium, Ureaplasma urealyticum, Ureaplasma parvum, Mycoplasma hominis, Trichomonas vaginalis, and so on. Among these microorganisms, the pathogenicity of M. genitalium and T. vaginalis to the male urethra has been confirmed so far.
The Asian Association of Urinary Tract Infection and Sexually Transmitted Infection (AAUS) belonging to the Urological Association of Asia (UAA) had developed the guidelines regarding NCNGU and the present guidelines were updated from previous edition. Relevant references were meticulously reviewed again and latest studies were collected. In addition to the levels of evidence, the recommendation grades were defined using the modified GRADE methodology. Herein, we present the new edition of the UAA-AAUS guidelines for M. genitalium and non-chlamydial non-gonococcal urethritis.
After publication of the initial version of the Japanese guidelines for urological surgery in 2007, new surgical techniques have been introduced. Furthermore, several important issues, such as ...criteria for use of single‐dose antimicrobial prophylaxis and control of hospitalized infection, were also established, which led to alterations of the methods used for antimicrobial prophylaxis as well as perioperative management. The purpose of antimicrobial prophylaxis is to protect the surgical wound from contamination by normal bacterial flora. Antimicrobial prophylaxis should be based on penicillins with beta‐lactamase inhibitors, or first‐ or second‐generation cephalosporins, though penicillins without beta‐lactamase inhibitors should not be prescribed because of the high prevalence of antimicrobial resistance. As an adequate intratissue concentration of the antimicrobial at the surgical site should be accomplished by the time of initiation of surgery, antimicrobial prophylaxis should be started up to 30 min before beginning the operation. Antimicrobial prophylaxis should be terminated within 24 h in clean and clean‐contaminated surgery, and within 2 days of surgery using the bowels, because a longer duration is a risk factor for surgical site infection development. Importantly, possible risk factors for surgical site infections include the antimicrobial prophylaxis methodology used as well as others, such as duration of preoperative hospitalization, hand washing, the American Society of Anesthesiologists score, diabetes and smoking history. These guidelines are to be applied only for preoperatively non‐infected low‐risk patients. In cases with preoperative infection or bacteriuria that can cause a surgical site infection or urinary tract infection after surgery, patients must receive adequate preoperative treatment based on the individual situation.
Mycoplasma genitalium is a known causative pathogen for some sexually transmitted infections. Nucleic acid amplification tests are a recommended method for detecting M. genitalium. A ...transcription-mediated amplification (TMA) nucleic acid amplification test to detect M. genitalium, the Aptima Mycoplasma genitalium assay was approved by the Food and Drug Administration in the United States and has been used in other countries. The purpose of this study is to determine the sensitivity of TMA test as the detection limit for 20 strains.
The sensitivity of the TMA test was re-examined using 20 strains in vitro and the detection limit was estimated by comparison with the MgPa quantitative real-time PCR (qPCR) method. The M. genitalium strains used were isolated from Denmark, Norway, Sweden, France and Japan, and included macrolide or fluoroquinolone resistance. Stock strains were used at several dilutions, with each dilution of each strain examined using both TMA test and qPCR methods.
Estimated DNA loads of M. genitalium as the detection limit were 0.03–0.87 genome equivalents/mL. Sensitivity for TMA test was almost 100-fold higher than for the qPCR method.
The mechanisms of fluoroquinolone-resistance of Mycoplasma genitalium were analysed by a new method.
M. genitalium strains from urinary sediments of patients with urethritis were isolated and ...examined antimicrobial susceptibilities and the mutations in ParC, GyrA and 23S rRNA. Docking models between gyrase and topoisomerase IV with sitafloxacin showed that two binding modes in which the amine moiety at the C-7 position rotated could be constructed.
Among 18 strains, 13 strains had mutations with amino-acid changes at Serine 83 in ParC. The MICs of moxifloxacin or sitafloxacin for three strains with only S83I in ParC were 2, 1 and 8 mg/L (moxifloxacin) or 0.13, 0.13 and 1 mg/L (sitafloxacin), respectively. In contrast, the MICs of moxifloxacin or sitafloxacin for 3 strain with S83N in ParC were 0.25, 0.13 and 0.25 mg/L (moxifloxacin) or 0.06, 0.03, and 0,03 mg/L (sitafloxacin), respectively, not significantly different from wild-type isolates. The docking model of sitafloxacin and topoisomerase IV showed that the oxygen atom at the gamma position of Serine 83 of ParC interacted with the sitafloxacin carboxylate moiety. When the S83I substitution occurs, the isoleucine side chain is lipophilic and the residue hydropathy changes from hydrophilicity to hydrophobicity and important H-bond interactions between serine and the carboxylate moiety are lost. When the serine 83 to asparagine substitution (S83N) occurred, the asparagine side chain is hydrophilic and the residue hydropathy does not change.
The docking model suggests that Ser83 replacements causes attenuation or loss of activity of fluoroquinolones such as sitafloxacin.
Isolating oropharyngeal Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) from oral wash specimens (OWSs) is uncommon. Therefore, we evaluated the performance of the Abbott RealTime CT/NG ...assay and the Cobas 4800 CT/NG assay in detecting NG and CT in OWSs.
This multicenter prospective study included 457 patients from 14 medical facilities suspected of having untreated male urethritis or female cervicitis from November 2014 to December 2015. OWSs were collected and tested using the Abbott and Cobas assays. Finally, the discordant results were confirmed using the APTIMA Combo 2 transcription-mediated amplification assay and retested using each assay.
The sensitivity and specificity of the Abbott assay were 100% and 97.2% for NG and 87.5% and 100% for CT, respectively, and of the Cobas assay were 100% and 98.8% for NG and 93.8% and 99.8% for CT, respectively. Both assays had high negative but low positive predictive values for oropharyngeal NG (Abbott assay: 65.7%, Cobas assay: 82.1%). Based on the definition of “true positive,” the prevalence of oropharyngeal NG and CT were 5.0% and 3.5%, respectively.
The Abbott and Cobas assays using OWSs had high sensitivity and specificity, which can help diagnose oropharyngeal NG and CT. We consider that if a positive result is obtained, the patient should be treated because the negative predictive values were high. However, limited data are available on oropharyngeal NG and CT detection, and further studies are needed to clarify the role of oropharyngeal sexually transmitted infections.
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