Antimicrobial chemotherapy of<i>Mycoplasma genitalium</i>-positive non-gonococcal urethritis

Deguchi, Takashi; Ito, Shin; Hagiwara, Noriyasu; Yasuda, Mitsuru; Maeda, Satoshi

doi:10.1586/eri.12.38

Cited by 15 publications

(15 citation statements)

References 69 publications

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“…It has been reported that the rates of eradication of M. genitalium from NGU patients treated with levofloxacin or ofloxacin tend to be inferior to those obtained with gatifloxacin or moxifloxacin (34). In this study, gatifloxacin and moxifloxacin were shown to exhibit more-potent inhibitory activities than levofloxacin against all topoisomerases tested, including mutant topoisomerase IV.…”

Section: Discussionmentioning

confidence: 60%

Contribution of Topoisomerase IV Mutation to Quinolone Resistance in Mycoplasma genitalium

Yamaguchi

Takei²,

Kishii³

et al. 2013

Antimicrob Agents Chemother

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bThe mechanism of quinolone resistance in Mycoplasma genitalium remains poorly understood due to difficulties with in vitro culture, especially of clinical isolates. In this study, to confirm the association between mutations in topoisomerases and antimicrobial susceptibilities to quinolones, ciprofloxacin-resistant mutant strains were selected using the cultivable type strain ATCC 33530. Sequence analysis revealed that the mutant strains harbored mutations in topoisomerase IV: Gly81Cys in ParC, Pro261Thr in ParC, or Asn466Lys in ParE. The MICs of all quinolones tested against the mutant strains were 2-to 16-fold higher than those against the wild-type strain. No cross-resistance was observed with macrolides or tetracyclines. We determined the inhibitory activities of quinolones against DNA gyrase and topoisomerase IV in order to investigate the correlation between antimicrobial susceptibility and inhibitory activity against the target enzymes, considered the primary targets of quinolones. Furthermore, using enzymatic analysis, we confirmed that Gly81Cys in the ParC quinolone resistance-determining region (QRDR) contributed to quinolone resistance. This is the first study to isolate quinolone-resistant mutant strains of M. genitalium harboring substitutions in the parC or parE gene in vitro and to measure the inhibitory activities against the purified topoisomerases of M. genitalium. Mycoplasma genitalium was first isolated in urethral cultures from men with nongonococcal urethritis (NGU) in 1981 (1). M. genitalium is an important cause of NGU in men and has been shown to be associated with cervicitis, endometritis, salpingitis, and pelvic inflammatory diseases in women (2-5).M. genitalium has been reported to be susceptible to macrolides and is highly susceptible to azithromycin. The current guidelines recommend an azithromycin regimen for the treatment of NGU (6, 7). On the other hand, macrolide-resistant clinical strains of M. genitalium have emerged due to selection by the azithromycin regimen, and these clinical isolates with elevated azithromycin MICs have been shown to harbor an A2058G or A2059G substitution in the 23S rRNA gene (8).Some quinolones, such as moxifloxacin, have potent activity against M. genitalium, and treatment with moxifloxacin is considered an effective second-line treatment for persistent or recurrent NGU (9). The antibacterial activities of quinolones are due to their inhibitory activities against type II topoisomerases, DNA gyrase (composed of two GyrA and two GyrB subunits), and topoisomerase IV (composed of two ParC and two ParE subunits). It has been reported that mutations in the quinolone resistance-determining regions (QRDR) of the genes encoding DNA gyrase and/or topoisomerase IV contribute to quinolone resistance in various bacterial species, including other mycoplasmas (10-13). We recently detected the amino acid substitution Ser83Asn, Asp87Tyr, or Asp87Val in the ParC QRDR of M. genitalium DNAs in urine specimens from men with NGU (14-16).Due to the difficulties of isolatin...

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Section: Discussionmentioning

confidence: 60%

Contribution of Topoisomerase IV Mutation to Quinolone Resistance in Mycoplasma genitalium

Yamaguchi

Takei²,

Kishii³

et al. 2013

Antimicrob Agents Chemother

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“…These seven men were excluded from the analyses of the demographic and clinical characteristics of monomicrobial NGU and all-examined microorganism-negative NGU. The characteristics of 22,14,21,12, and 11 men with NGU positive only for MG, UU, HI, AV and HSV-1 or HSV-2, respectively, and 29 men with NGU negative for all microorganisms examined were compared with those of the 110 men positive only for CT (Table 3).…”

Section: Resultsmentioning

confidence: 99%

“…The DOXY regimens are not effective on MG-positive NGU. 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.…”

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confidence: 99%

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

Ito¹,

Hanaoka

Shimuta

et al. 2016

Int J of Urology

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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.

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“…Azithromycin regimens have been recommended for the treatment of M. genitalium infections, but recently, azithromycin treatment failures have been observed [2]. Moxifloxacin regimens have been highly effective for persistent M. genitalium infections unsuccessfully treated with azithromycin [2].…”

Section: Introductionmentioning

confidence: 99%

Sitafloxacin: Antimicrobial activity against ciprofloxacin-selected laboratory mutants of Mycoplasma genitalium and inhibitory activity against its DNA gyrase and topoisomerase IV

Deguchi

Kikuchi

Yasuda

et al. 2015

Journal of Infection and Chemotherapy

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Antimicrobial chemotherapy ofMycoplasma genitalium-positive non-gonococcal urethritis

Cited by 15 publications

References 69 publications

Contribution of Topoisomerase IV Mutation to Quinolone Resistance in Mycoplasma genitalium

Contribution of Topoisomerase IV Mutation to Quinolone Resistance in Mycoplasma genitalium

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

Sitafloxacin: Antimicrobial activity against ciprofloxacin-selected laboratory mutants of Mycoplasma genitalium and inhibitory activity against its DNA gyrase and topoisomerase IV

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