Antimicrobial chemotherapy of Mycoplasma genitalium-positive non-gonococcal urethritis

Expert Review of Anti-Infective Therapy

Volumn 10, Issue 7, 2012, Pages 791-803

  Deguchi, Takashi ^a   Ito, Shin ^a   Hagiwara, Noriyasu ^a   Yasuda, Mitsuru ^a   Maeda, Shin Ichi ^a  

^a GIFU UNIVERSITY   (Japan)

Author keywords

23S rRNA; azithromycin; doxycycline; moxifloxacin; Mycoplasma genitalium; non gonococcal urethritis; ParC

Indexed keywords

ANTIINFECTIVE AGENT; AZITHROMYCIN; CLARITHROMYCIN; DNA TOPOISOMERASE (ATP HYDROLYSING) A; DOXYCYCLINE; ERYTHROMYCIN; GARENOXACIN; GATIFLOXACIN; GEMIFLOXACIN; GREPAFLOXACIN; LEVOFLOXACIN; LYMECYCLINE; MACROLIDE; MINOCYCLINE; MOXIFLOXACIN; OFLOXACIN; PROTEIN PARC; QUINOLINE DERIVED ANTIINFECTIVE AGENT; RNA 23S; SITAFLOXACIN; SOLITHROMYCIN; SPARFLOXACIN; TELITHROMYCIN; TETRACYCLINE; TINIDAZOLE; TOSUFLOXACIN; TROVAFLOXACIN;

ACUTE DISEASE; AMINO ACID SUBSTITUTION; ANTIMICROBIAL ACTIVITY; BACTERIAL LOAD; BACTERIAL STRAIN; BACTERIUM ISOLATE; DISEASE CONTROL; DRUG ACTIVITY; DRUG BINDING SITE; DRUG EFFICACY; HUMAN; IN VITRO STUDY; MINIMUM INHIBITORY CONCENTRATION; MYCOPLASMA GENITALIUM; MYCOPLASMA PNEUMONIAE; NONHUMAN; NONSPECIFIC URETHRITIS; RECURRENT DISEASE; REVIEW; SINGLE DRUG DOSE;

ANTI-INFECTIVE AGENTS; AZA COMPOUNDS; AZITHROMYCIN; DOXYCYCLINE; DRUG RESISTANCE, BACTERIAL; HUMANS; MALE; MYCOPLASMA GENITALIUM; MYCOPLASMA INFECTIONS; QUINOLINES; TREATMENT OUTCOME; URETHRITIS;

EID: 84865774677     PISSN: 14787210     EISSN: 17448336     Source Type: Journal    
DOI: 10.1586/eri.12.38     Document Type: Review

References (69)

1. Krieger JN. Trichomoniasis in men: Old issues and new data. Sex. Transm. Dis. 22(2), 83-96 (1995).
2. Swenson PD, Lowens MS, Celum CL, Hierholzer JC. Adenovirus types 2, 8, and 37 associated with genital infections in patients attending a sexually transmitted disease clinic. J. Clin. Microbiol. 33(10), 2728-2731 (1995).
3. Sturm AW. Haemophilus influenzae and Haemophilus parainfluenzae in nongonococcal urethritis. J. Infect. Dis. 153(1), 165-167 (1986). (Pubitemid 16212474)
4. Hawkins DA, Fontaine EA, Thomas BJ, Boustouller YL, Taylor-Robinson D. The enigma of non-gonococcal urethritis: Role for Bacteroides ureolyticus. Genitourin. Med. 64(1), 10-13 (1988). (Pubitemid 18082111)
5. Deguchi T, Yoshida T, Miyazawa T et al. Association of Ureaplasma urealyticum (biovar 2) with nongonococcal urethritis. Sex. Transm. Dis. 31(3), 192-195 (2004). (Pubitemid 38252905)
6. Tully JG, Taylor-Robinson D, Cole RM, Rose DL. A newly discovered mycoplasma in the human urogenital tract. Lancet 1(8233), 1288-1291 (1981). (Pubitemid 11111354)
7. Deguchi T, Maeda S. Mycoplasma genitalium: Another important pathogen of nongonococcal urethritis. J. Urol. 167(3), 1210-1217 (2002). (Pubitemid 34132058)
8. Yokoi S, Maeda S, Kubota Y et al. The role of Mycoplasma genitalium and Ureaplasma urealyticum biovar 2 in postgonococcal urethritis. Clin. Infect. Dis. 45(7), 866-871 (2007). Analyzes the association of Mycoplasma genitalium with post-gonococcal urethritis to verify a pathogenic role of this mycoplasma in non-gonococcal urethritis. (Pubitemid 47580378)
9. Jensen JS. Mycoplasma genitalium: The aetiological agent of urethritis and other sexually transmitted diseases. J. Eur. Acad. Dermatol. Venereol. 18(1), 1-11 (2004).
10. Taylor-Robinson D, Jensen JS. Mycoplasma genitalium: From chrysalis to multicolored butterfly. Clin. Microbiol. Rev. 24(3), 498-514 (2011). Detailed review of the pathogenic roles of M. genitalium in genitourinary infections in men and women.
11. Manhart LE, Broad JM, Golden MR. Mycoplasma genitalium: Should we treat and how? Clin. Infect. Dis. 53(Suppl. 3), S129-S142 (2011). Comprehensive review of M. genitalium infections, including their antimicrobial chemotherapy.
12. Workowski KA, Berman S; CDC. Sexually transmitted diseases treatment guidelines, 2010. MMWR. Recomm. Rep. 59(RR-12), 1-110 (2010).
13. Shahmanesh M, Moi H, Lassau F, Janier M; IUSTI/WHO. 2009 European guideline on the management of male non-gonococcal urethritis. Int. J. STD AIDS 20(7), 458-464 (2009).
14. Wong ES, Hooton TM, Hill CC, McKevitt M, Stamm WE. Clinical and microbiological features of persistent or recurrent nongonococcal urethritis in men. J. Infect. Dis. 158(5), 1098-1101 (1988). (Pubitemid 18266065)
15. Hooton TM, Roberts MC, Roberts PL, Holmes KK, Stamm WE, Kenny GE. Prevalence of Mycoplasma genitalium determined by DNA probe in men with urethritis. Lancet 1(8580), 266-268 (1988). (Pubitemid 18052261)
16. Taylor-Robinson D, Gilroy CB, Hay PE. Occurrence of Mycoplasma genitalium in different populations and its clinical significance. Clin. Infect. Dis. 17(Suppl. 1), S66-S68 (1993). (Pubitemid 23227109)
17. Horner P, Thomas B, Gilroy CB, Egger M, Taylor-Robinson D. Role of Mycoplasma genitalium and Ureaplasma urealyticum in acute and chronic nongonococcal urethritis. Clin. Infect. Dis. 32(7), 995-1003 (2001). (Pubitemid 32299633)
18. Maeda SI, Tamaki M, Kojima K et al. Association of Mycoplasma genitalium persistence in the urethra with recurrence of nongonococcal urethritis. Sex. Transm. Dis. 28(8), 472-476 (2001). Emphasizes the significant association of the persistence of M. genitalium in the urethra after antibiotic treatments with persistent and recurrent urethritis. (Pubitemid 32730296)
19. Tully JG, Taylor-Robinson D, Rose DL, Cole RM, Bove JM. Mycoplasma genitalium, a new species from the human urogenital tract. Int. J. Syst. Bacteriol. 33(2), 387-396 (1983). (Pubitemid 13136753)
20. Taylor-Robinson D, Furr PM, Hanna NF. Microbiological and serological study of non-gonococcal urethritis with special reference to Mycoplasma genitalium. Genitourin. Med. 61(5), 319-324 (1985). (Pubitemid 15248172)
21. Jensen JS, Uldum SA, Søndergård- Andersen J, Vuust J, Lind K. Polymerase chain reaction for detection of Mycoplasma genitalium in clinical samples. J. Clin. Microbiol. 29(1), 46-50 (1991).
22. Palmer HM, Gilroy CB, Furr PM, Taylor-Robinson D. Development and evaluation of the polymerase chain reaction to detect Mycoplasma genitalium. FEMS Microbiol. Lett. 61(2-3), 199-203 (1991).
23. Deguchi T, Yoshida T, Yokoi S et al. Longitudinal quantitative detection by real-time PCR of Mycoplasma genitalium in first-pass urine of men with recurrent nongonococcal urethritis. J. Clin. Microbiol. 40(10), 3854-3856 (2002).
24. Renaudin H, Tully JG, Bebear C. In vitro susceptibilities of Mycoplasma genitalium to antibiotics. Antimicrob. Agents Chemother. 36(4), 870-872 (1992).
25. Yasuda M, Maeda S, Deguchi T. In vitro activity of fluoroquinolones against Mycoplasma genitalium and their bacteriological efficacy for treatment of M. genitalium-positive nongonococcal urethritis in men. Clin. Infect. Dis. 41(9), 1357-1359 (2005). (Pubitemid 41532684)
26. Hamasuna R, Jensen JS, Osada Y. Antimicrobial susceptibilities of Mycoplasma genitalium strains examined by broth dilution and quantitative PCR. Antimicrob. Agents Chemother. 53(11), 4938-4939 (2009). Examines clinical isolates of M. genitalium for antimicrobial susceptibilities to various antibiotics.
27. Hagiwara N, Yasuda M, Maeda SI, Deguchi T. In vitro activity of azithromycin against Mycoplasma genitalium and its efficacy in the treatment of male Mycoplasma genitalium-positive nongonococcal urethritis. J. Infect. Chemother. 17(6), 821-824 (2011).
28. Jensen JS, Bradshaw CS, Tabrizi SN, Fairley CK, Hamasuna R. Azithromycin treatment failure in Mycoplasma genitalium-positive patients with nongonococcal urethritis is associated with induced macrolide resistance. Clin. Infect. Dis. 47(12), 1546-1553 (2008). Reports the selection of macrolideresistant clinical strains of M. genitalium by azithromycin treatments and analyzes the mechanisms of macrolide resistance.
29. Bebear CM, Renaudin H, Bryskier A, Bebear C. Comparative activities of telithromycin (HMR 3647), levofloxacin, and other antimicrobial agents against human mycoplasmas. Antimicrob. Agents Chemother. 44(7), 1980-1982 (2000). (Pubitemid 30422960)
30. Waites KB, Crabb DM, Duffy LB. Comparative in vitro susceptibilities of human mycoplasmas and ureaplasmas to a new investigational ketolide, CEM-101. Antimicrob. Agents Chemother. 53(5), 2139-2141 (2009).
31. Bébéar CM, de Barbeyrac B, Pereyre S, Renaudin H, Clerc M, Bébéar C. Activity of moxifloxacin against the urogenital mycoplasmas Ureaplasma spp., Mycoplasma hominis and Mycoplasma genitalium and Chlamydia trachomatis. Clin. Microbiol. Infect. 14(8), 801-805 (2008).
32. Bébéar CM, Renaudin H, Schaeverbeke T, Leblanc F, Bébéar C. In-vitro activity of grepafloxacin, a new fluoroquinolone, against mycoplasmas. J. Antimicrob. Chemother. 43(5), 711-714 (1999). (Pubitemid 29231699)
33. Pereyre S, Renaudin H, Bébéar C, Bébéar CM. In vitro activities of the newer quinolones garenoxacin, gatifloxacin, and gemifloxacin against human mycoplasmas. Antimicrob. Agents Chemother. 48(8), 3165-3168 (2004). (Pubitemid 38989195)
34. Bebear CM, Renaudin H, Charron A, Gruson D, Lefrancois M, Bebear C. In vitro activity of trovafloxacin compared to those of five antimicrobials against mycoplasmas including Mycoplasma hominis and Ureaplasma urealyticum fluoroquinolone-resistant isolates that have been genetically characterized. Antimicrob. Agents Chemother. 44(9), 2557-2560 (2000). (Pubitemid 30650917)
35. Horner PJ, Gilroy CB, Thomas BJ, Naidoo RO, Taylor-Robinson D. Association of Mycoplasma genitalium with acute non-gonococcal urethritis. Lancet 342(8871), 582-585 (1993). (Pubitemid 23259235)
36. Gambini D, Decleva I, Lupica L, Ghislanzoni M, Cusini M, Alessi E. Mycoplasma genitalium in males with nongonococcal urethritis: Prevalence and clinical efficacy of eradication. Sex. Transm. Dis. 27(4), 226-229 (2000). (Pubitemid 30210801)
37. Johannisson G, Enström Y, Löwhagen GB et al. Occurrence and treatment of Mycoplasma genitalium in patients visiting STD clinics in Sweden. Int. J. STD AIDS 11(5), 324-326 (2000). (Pubitemid 30245746)
38. Falk L, Fredlund H, Jensen JS. Tetracycline treatment does not eradicate Mycoplasma genitalium. Sex. Transm. Infect. 79(4), 318-319 (2003). (Pubitemid 37026351)
39. Björnelius E, Anagrius C, Bojs G et al. Antibiotic treatment of symptomatic Mycoplasma genitalium infection in Scandinavia: A controlled clinical trial. Sex. Transm. Infect. 84(1), 72-76 (2008). (Pubitemid 351195859)
40. Mena LA, Mroczkowski TF, Nsuami M, Martin DH. A randomized comparison of azithromycin and doxycycline for the treatment of Mycoplasma genitaliumpositive urethritis in men. Clin. Infect. Dis. 48(12), 1649-1654 (2009). Reports that the doxycycline regimen that is recommended for treatment of non-gonococcal urethritis is ineffective against M. genitalium-positive non-gonococcal urethritis.
41. Schwebke JR, Rompalo A, Taylor S et al. Re-evaluating the treatment of nongonococcal urethritis: Emphasizing emerging pathogens-a randomized clinical trial. Clin. Infect. Dis. 52(2), 163-170 (2011).
42. Dupin N, Bijaoui G, Schwarzinger M et al. Detection and quantification of Mycoplasma genitalium in male patients with urethritis. Clin. Infect. Dis. 37(4), 602-605 (2003). (Pubitemid 37011787)
43. Roberts MC, Koutsky LA, Holmes KK, LeBlanc DJ, Kenny GE. Tetracyclineresistant Mycoplasma hominis strains contain streptococcal tetM sequences. Antimicrob. Agents Chemother. 28(1), 141-143 (1985). (Pubitemid 15029709)
44. Roberts MC, Kenny GE. Dissemination of the tetM tetracycline resistance determinant to Ureaplasma urealyticum. Antimicrob. Agents Chemother. 29(2), 350-352 (1986). (Pubitemid 16162957)
45. Bradshaw CS, Jensen JS, Tabrizi SN et al. Azithromycin failure in Mycoplasma genitalium urethritis. Emerging Infect. Dis. 12(7), 1149-1152 (2006). Reports the emergence of macrolide-resistant M. genitalium in clinical practice. (Pubitemid 44061291)
46. Stamm WE, Batteiger BE, McCormack WM, Totten PA, Sternlicht A, Kivel NM; Rifalazil Study Group. A randomized, double-blind study comparing single-dose rifalazil with single-dose azithromycin for the empirical treatment of nongonococcal urethritis in men. Sex. Transm. Dis. 34(8), 545-552 (2007). (Pubitemid 47207142)
47. Bradshaw CS, Chen MY, Fairley CK. Persistence of Mycoplasma genitalium following azithromycin therapy. PLoS ONE 3(11), e3618 (2008).
48. Jernberg E, Moghaddam A, Moi H. Azithromycin and moxifloxacin for microbiological cure of Mycoplasma genitalium infection: An open study. Int. J. STD AIDS 19(10), 676-679 (2008). Reports that the moxifloxacin regimen is effective against M. genitalium infections unsuccessfully treated with azithromycin.
49. Wikström A, Jensen JS. Mycoplasma genitalium: A common cause of persistent urethritis among men treated with doxycycline. Sex. Transm. Infect. 82(4), 276-279 (2006). (Pubitemid 44229437)
50. Roberts MC, Sutcliffe J, Courvalin P, Jensen LB, Rood J, Seppala H. Nomenclature for macrolide and macrolide-lincosamide-streptogramin B resistance determinants. Antimicrob. Agents Chemother. 43(12), 2823-2830 (1999).
51. Vester B, Douthwaite S. Macrolide resistance conferred by base substitutions in 23S rRNA. Antimicrob. Agents Chemother. 45(1), 1-12 (2001). (Pubitemid 32039086)
52. Fraser CM, Gocayne JD, White O et al. The minimal gene complement of Mycoplasma genitalium. Science 270(5235), 397-403 (1995).
53. Shimada Y, Deguchi T, Nakane K et al. Macrolide resistance-associated 23S rRNA mutation in Mycoplasma genitalium, Japan. Emerging Infect. Dis. 17(6), 1148-1150 (2011).
54. Ito S, Shimada Y, Yamaguchi Y et al. Selection of Mycoplasma genitalium strains harbouring macrolide resistanceassociated 23S rRNA mutations by treatment with a single 1 g dose of azithromycin. Sex. Transm. Infect. 87(5), 412-414 (2011).
55. Yew HS, Anderson T, Coughlan E, Werno A. Induced macrolide resistance in Mycoplasma genitalium isolates from patients with recurrent nongonococcal urethritis. J. Clin. Microbiol. 49(4), 1695-1696 (2011).
56. Diner EJ, Hayes CS. Recombineering reveals a diverse collection of ribosomal proteins L4 and L22 that confer resistance to macrolide antibiotics. J. Mol. Biol. 386(2), 300-315 (2009).
57. Peric M, Bozdogan B, Jacobs MR, Appelbaum PC. Effects of an efflux mechanism and ribosomal mutations on macrolide susceptibility of Haemophilus influenzae clinical isolates. Antimicrob. Agents Chemother. 47(3), 1017-1022 (2003). (Pubitemid 36254229)
58. Zaman S, Fitzpatrick M, Lindahl L, Zengel J. Novel mutations in ribosomal proteins L4 and L22 that confer erythromycin resistance in Escherichia coli. Mol. Microbiol. 66(4), 1039-1050 (2007). (Pubitemid 350050427)
59. Reinert RR, Wild A, Appelbaum P, Lütticken R, Cil MY, Al-Lahham A. Ribosomal mutations conferring resistance to macrolides in Streptococcus pneumoniae clinical strains isolated in Germany. Antimicrob. Agents Chemother. 47(7), 2319-2322 (2003). (Pubitemid 36753592)
60. Takahashi S, Ichihara K, Hashimoto J et al. Clinical efficacy of levofloxacin 500 mg once daily for 7 days for patients with non-gonococcal urethritis. J. Infect. Chemother. 17(3), 392-396 (2011).
61. Hamasuna R, Takahashi S, Kiyota H et al. Effect of gatifloxacin against Mycoplasma genitalium-related urethritis: An open clinical trial. Sex. Transm. Infect. 87(5), 389-390 (2011).
62. Ito S, Yasuda M, Seike K. Clinical and microbiological outcomes in treatment of men with non-gonococcal urethritis with a 100-mg twice-daily dose of sitafloxacin. J. Infect. Chemother. 18(3), 414-418 (2012).
63. Bebear CM, Renaudin J, Charron A et al. Mutations in the gyrA, parC, and parE genes associated with fluoroquinolone resistance in clinical isolates of Mycoplasma hominis. Antimicrob. Agents Chemother. 43(4), 954-956 (1999). (Pubitemid 29165766)
64. Gruson D, Pereyre S, Renaudin H, Charron A, Bébéar C, Bébéar CM. In vitro development of resistance to six and four fluoroquinolones in Mycoplasma pneumoniae and Mycoplasma hominis, respectively. Antimicrob. Agents Chemother. 49(3), 1190-1193 (2005). (Pubitemid 40327745)
65. Beeton ML, Chalker VJ, Kotecha S, Spiller OB. Comparison of full gyrA, gyrB, parC and parE gene sequences between all Ureaplasma parvum and Ureaplasma urealyticum serovars to separate true fluoroquinolone antibiotic resistance mutations from non-resistance polymorphism. J. Antimicrob. Chemother. 64(3), 529-538 (2009).
66. Shimada Y, Deguchi T, Nakane K et al. Emergence of clinical strains of Mycoplasma genitalium harbouring alterations in ParC associated with fluoroquinolone resistance. Int. J. Antimicrob. Agents 36(3), 255-258 (2010).
67. Shimada Y, Deguchi T, Yamaguchi Y et al. gyrB and parE mutations in urinary Mycoplasma genitalium DNA from men with non-gonococcal urethritis. Int. J. Antimicrob. Agents 36(5), 477-478 (2010).
68. Deguchi T, Maeda S, Tamaki M et al. Analysis of the gyrA and parC genes of Mycoplasma genitalium detected in first-pass urine of men with nongonococcal urethritis before and after fluoroquinolone treatment. J. Antimicrob. Chemother. 48(5), 742-744 (2001). Analyzes the fluoroquinolone resistance-associated mutations of the gyrA and parC genes of M. genitalium in men unsuccessfully treated with the levofloxacin regimen. (Pubitemid 33100328)
69. zur Wiesch PA, Kouyos R, Engelstädter J, Regoes RR, Bonhoeffer S. Population biological principles of drug-resistance evolution in infectious diseases. Lancet Infect. Dis. 11(3), 236-247 (2011).