Remarkable increase in fluoroquinolone-resistant Mycoplasma genitalium in Japan

Kikuchi, Mina; Ito, Shin; Yasuda, Mitsuru; Tsuchiya, Tomohiro; Hatazaki, Kyoko; Takanashi, Masaki; Ezaki, Takayuki; Deguchi, Takashi

doi:10.1093/jac/dku164

Cited by 97 publications

(119 citation statements)

References 30 publications

Supporting

Mentioning

104

Contrasting

Unclassified

Order By: Relevance

“…The high frequency of resistance and the limited treatment options necessitate rapid resistance assays to spare secondary treatment options (6). Indeed, emerging resistance to secondary treatment options using fluoroquinolones has already been reported in selected populations (3,4,8,17).…”

Section: Discussionmentioning

confidence: 99%

A 5′ Nuclease Genotyping Assay for Identification of Macrolide-Resistant Mycoplasma genitalium in Clinical Specimens

2016

View full text Add to dashboard Cite

M ycoplasma genitalium is a sexually transmitted bacterium that causes nongonococcal urethritis in men and has been associated with cervicitis and pelvic inflammatory disease in women (1). The current recommended treatment of M. genitalium infection in Scandinavia is an extended course of oral macrolide. However, if empirical treatment of nongonococcal urethritis is initiated, usually only a single dose of azithromycin is given as treatment for suspected Chlamydia infection. Single-dose azithromycin treatment of M. genitalium infection is associated with a suboptimal treatment response and, in the case of treatment failure, with the development of M. genitalium macrolide resistance (2, 3). Macrolide-resistant M. genitalium strains are consequently prevalent, and resistance rates of 41% in a cohort of men with urethritis in London (4) and 38% in a recent population-based Danish survey (5) have been reported. In proven M. genitalium infection, macrolide susceptibility reporting is therefore necessary to guide therapy (6).Macrolide resistance in M. genitalium is strongly associated with the mutations A2058G and A2059G in the gene encoding 23S rRNA (3,7,8). In a recent Dutch study, a high proportion of the A2058T mutation causing resistance was observed (9). Resistance-associated mutations can be identified by PCR amplification and sequencing. This method is best suited to process samples in bulk and may result in unacceptable reporting times. Highresolution melting (HRM) analysis is another powerful tool to detect mutations in a target sequence, and PCR assays using HRM analysis for detecting mutations associated with macrolide resistance have recently been reported (10, 11). An alternative method for identifying known mutations is genotyping assays using differentially labeled hydrolysis probes targeting wild-type and mutated alleles (12,13). In the present study, we report such a 5= nuclease genotyping assay for the detection of the macrolide resistance-associated mutations in M. genitalium. The assay was used to determine macrolide resistance in 259 samples that had previously tested positive for the presence of M. genitalium, and the results obtained using this assay were compared to sequencing of the region of interest in the 23S rRNA gene. The 5= nuclease genotyping assay was highly accurate compared to sequencing. MATERIALS AND METHODSM. genitalium detection. Between 8 October 2013 and 12 September 2014, the Department of Clinical Microbiology received 3,147 samples to test for the presence of M. genitalium. Testing was done using a laboratory-developed quantitative PCR (qPCR) using hydrolysis probes targeting the pdhD and mgpB genes of M. genitalium and an additional sampleprocessing control. The primers and probes of this laboratory-developed test have previously been published (14-16). In the multiplex qPCR, the final concentrations of M. genitalium-specific primers and of probes were 500 nM and 100 nM, respectively. Reactions were done in a total volume of 20 l with LightCycler 480 probes master (Roche A...

show abstract

Section: Discussionmentioning

confidence: 99%

A 5′ Nuclease Genotyping Assay for Identification of Macrolide-Resistant Mycoplasma genitalium in Clinical Specimens

2016

View full text Add to dashboard Cite

show abstract

“…21 Recently, we have reported the emergence and increase of MG clinical strains harboring mutations in the 23S rRNA gene associated with macrolide resistance and/or those in the parC gene associated with fluoroquinolone resistance. 29 The single-dose regimen of azithromycin 1 g or extended-release azithromycin 2 g failed to eradicate MG strains with the mutant 23S rRNA gene in some cases of NGU, but the regimen of sitafloxacin 100 mg twice daily for 7 days was still effective on NGU caused by MG strains with the mutant parC gene. 29 In addition, sitafloxacin has been reported to be highly active against HI.…”

mentioning

confidence: 97%

“…29 The single-dose regimen of azithromycin 1 g or extended-release azithromycin 2 g failed to eradicate MG strains with the mutant 23S rRNA gene in some cases of NGU, but the regimen of sitafloxacin 100 mg twice daily for 7 days was still effective on NGU caused by MG strains with the mutant parC gene. 29 In addition, sitafloxacin has been reported to be highly active against HI.…”

mentioning

confidence: 97%

Male non‐gonococcal urethritis: From microbiological etiologies to demographic and clinical features

Ito¹,

Hanaoka

Shimuta

et al. 2016

Int J of Urology

View full text Add to dashboard Cite

Objectives: To detect microorganisms responsible for male acute urethritis and to define the microbiology of non-gonococcal urethritis. Methods: The present study comprised 424 men with symptoms and signs compatible with acute urethritis. Their urethral swabs and first-voided urine underwent detection of the microorganisms. Demographic characteristics and clinical features of Mycoplasma genitalium-, Ureaplasma urealyticum-, Haemophilus influenza-, adenovirusor Herpes simplex virus-positive monomicrobial non-gonococcal urethritis, or allexamined microorganism-negative urethritis in heterosexual men were compared with urethritis positive only for Chlamydia trachomatis. Results: Neisseria gonorrhoeae was detected in 127 men (30.0%). In 297 men with non-gonococcal urethritis, C. trachomatis was detected in 143 (48.1%). In 154 men with non-chlamydial non-gonococcal urethritis, M. genitalium (22.7%), M. hominis (5.8%), Ureaplasma parvum (9.1%), U. urealyticum (19.5%), H. influenzae (14.3%), Neisseria meningitidis (3.9%), Trichomonas vaginalis (1.3%), human adenovirus (16.2%), and Herpes simplex virus types 1 (7.1%) and 2 (2.6%) were detected. Although some features of monomicrobial non-chlamydial non-gonococcal urethritis or all-examined microorganismnegative urethritis were significantly different from those of monomicrobial chlamydial nongonococcal urethritis, most features were superimposed. Conclusions: Predicting causative microorganisms in men with non-gonococcal urethritis based on demographic and clinical features is difficult. However, the present study provides useful information to better understand the microbiological diversity in non-gonococcal urethritis, and to manage patients with non-gonococcal urethritis appropriately.

show abstract

“…Kikuchi et al [69] from Japan reported that in 27 MG specimens in 2011 and in 24 in 2012, no macrolide resistance-associated mutations in the Moreover, three isolates in 2013 coincidentally carried both antibiotic resistance-associated phenotypes. As the case of macrolide resistance with 23S rRNA mutations, fluoroquinolone resistance in MG is frequently associated with the mutations of the molecular target genes in MG. During prokaryotic DNA replication and transcription, DNA strands are subjected to various conformational stresses.…”

Section: ) Topoisomerase Iiamentioning

confidence: 99%

“…The antibacterial activities of the quinolones may be due to their inhibitory activities against bacterial type II topoisomerases, such as DNA gyrase and topoisomerase IV (Table 6) [54,[67][68][69]71,72]. Therefore, it has been reported that mutations in the quinolone resistance-determining regions of the type II topoisomerases contribute to quinolone resistance in various bacterial species, including MG [67][68][69].…”

Section: ) Topoisomerase Iiamentioning

confidence: 99%

Genetic Variation inMycoplasma genitalium

Lee

2017

Urogenit Tract Infect

View full text Add to dashboard Cite

Mycoplasma genitalium (MG) is the smallest self-replicating bacterium. Although small in size, unique MG genome induces distinctive and often serious characteristics in the infected cells. Due to its small genome and chronic symptomatic characteristics in the infected host, it first appears as a weak, insignificant, and easily controllable microbe. However, it is not a monotonous chrysalis, but rather a multicolored butterfly with various capabilities. Repetitive DNA sequence in MG's immunodominant MgPa operon has been considered as an efficient strategy to evade the host immune surveillance and mediate MG's genetic flexibility. Because of MG's pathogenicity in multiple organs, various antimicrobials are prescribed, further exerting selection pressure on microbes. Consequently, a rapidly increasing drug resistance in macrolide and moxifloxacin has been frequently reported globally, radically decreasing the overall cure rate of infection. Re-infection can be defined as a new MG infection through antigenic variation, while persistent infection refers to recurrent infections caused by the same MG isolate through acquisition of antimicrobial resistance. Therefore, we must differentiate between re-infection and persistent MG infection, and approach them accordingly. The genetic mechanisms of DNA variation in the MgPa operon and antibiotic resistance must be considered for the management of multicolored infection. In this respect, the unique genetic characteristics of MG will be described in detail. We hope that with this manuscript, clinicians can expand their understanding of recurrent MG infections and better choose an appropriate treatment for the infection in clinical setting.

show abstract

Remarkable increase in fluoroquinolone-resistant Mycoplasma genitalium in Japan

Cited by 97 publications

References 30 publications

A 5′ Nuclease Genotyping Assay for Identification of Macrolide-Resistant Mycoplasma genitalium in Clinical Specimens

A 5′ Nuclease Genotyping Assay for Identification of Macrolide-Resistant Mycoplasma genitalium in Clinical Specimens

Male non‐gonococcal urethritis: From microbiological etiologies to demographic and clinical features

Genetic Variation inMycoplasma genitalium

Contact Info

Product

Resources

About