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Published in: Antimicrobial Resistance & Infection Control 1/2020

01-12-2020 | Infertility | Research

Spread of multidrug resistance among Ureaplasma serovars, Tunisia

Authors: Safa Boujemaa, Béhija Mlik, Amina Ben Allaya, Helmi Mardassi, Boutheina Ben Abdelmoumen Mardassi

Published in: Antimicrobial Resistance & Infection Control | Issue 1/2020

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Abstract

Background

Ureaplasma spp. have been implicated in a variety of clinical conditions and certain serovars are likely to be disease-associated. Hence, the ascending trend of Ureaplasma spp. resistance to antimicrobials should deserve more attention. Here we assessed the extent of antimicrobial resistance of Ureaplasma serovars in Tunisia, and investigated the underlying molecular basis.

Methods

This study included 101 molecularly typed Ureaplasma spp. clinical strains isolated over a 12-year time period (2005–2017). The antimicrobial susceptibility was tested against nine antibacterial agents using the broth microdilution method. Neighbor-joining tree was constructed to establish the phylogenetic relationships among isolates.

Results

We found that all ureaplasma isolates were resistant to ciprofloxacin and erythromycin, intermediately resistant to azithromycin, and susceptible to doxycycline, moxifloxacin and josamycin. Ofloxacin and levofloxacin resistance was found in 73.27 and 17.82%, respectively, while 37.62% of isolates proved resistant to tetracycline. Consequently, we detected an elevated multidrug resistance rate among ureaplasma isolates (37.62%), particularly among serovars 2, 5, 8, and 9 (77.77% overall), as well as serovars 4, 10, 12, and 13 (52.63% overall). In most cases, drug resistance was found to be associated with known molecular mechanisms, yet we have identified two novel mutations in the L22 protein, which might be associated with macrolide-resistance.

Conclusion

To our knowledge, this is the first study that reports the widespread expansion of multidrug resistance among Ureaplasma serovars, a finding of importance in terms of both surveillance and antimicrobial usage.
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Literature
1.
go back to reference Clegg A, Passey M, Yoannes M, Michael A. High rates of genital mycoplasma infection in the highlands of Papua New Guinea determined both by culture and by a commercial detection kit. J Clin Microbiol. 1997;35:197–200.CrossRef Clegg A, Passey M, Yoannes M, Michael A. High rates of genital mycoplasma infection in the highlands of Papua New Guinea determined both by culture and by a commercial detection kit. J Clin Microbiol. 1997;35:197–200.CrossRef
2.
go back to reference Paralanov V, Lu J, Duffy LB, Crabb DM, Shrivastava S, Methé BA, et al. Comparative genome analysis of 19 Ureaplasma urealyticum and Ureaplasma parvum strains. BMC Microbiol. 2012;12:88.CrossRef Paralanov V, Lu J, Duffy LB, Crabb DM, Shrivastava S, Methé BA, et al. Comparative genome analysis of 19 Ureaplasma urealyticum and Ureaplasma parvum strains. BMC Microbiol. 2012;12:88.CrossRef
3.
go back to reference Waites KB, Katz B, Schelonka RL. Mycoplasmas and ureaplasmas as neonatal pathogens. Clin Microbiol Rev. 2005;18:757–89.CrossRef Waites KB, Katz B, Schelonka RL. Mycoplasmas and ureaplasmas as neonatal pathogens. Clin Microbiol Rev. 2005;18:757–89.CrossRef
4.
go back to reference Murtha AP, Edwards JM. The role of mycoplasma and Ureaplasma in adverse pregnancy outcomes. Obstet Gynecol Clin N Am. 2014;41:615–27.CrossRef Murtha AP, Edwards JM. The role of mycoplasma and Ureaplasma in adverse pregnancy outcomes. Obstet Gynecol Clin N Am. 2014;41:615–27.CrossRef
5.
go back to reference Waites KB, Schelonka RL, Xiao L, Grigsby PL, Novy MJ. Congenital and opportunistic infections: Ureaplasma species and mycoplasma hominis. Semin Fetal Neonatal Med. 2009;14:190–9.CrossRef Waites KB, Schelonka RL, Xiao L, Grigsby PL, Novy MJ. Congenital and opportunistic infections: Ureaplasma species and mycoplasma hominis. Semin Fetal Neonatal Med. 2009;14:190–9.CrossRef
6.
go back to reference Zhu X, Li M, Cao H, Yang X, Zhang C. Epidemiology of Ureaplasma urealyticum and mycoplasma hominis in the semen of male outpatients with reproductive disorders. Exp Ther Med. 2016;12:1165–70.CrossRef Zhu X, Li M, Cao H, Yang X, Zhang C. Epidemiology of Ureaplasma urealyticum and mycoplasma hominis in the semen of male outpatients with reproductive disorders. Exp Ther Med. 2016;12:1165–70.CrossRef
7.
go back to reference Mardassi BBA, Aissani N, Moalla I, Dhahri D, Dridi A, Mlik B. Evidence for the predominance of a single tet (M) gene sequence type in tetracycline-resistant Ureaplasma parvum and mycoplasma hominis isolates from Tunisian patients. J Med Microbiol. 2012;61:1254–61.CrossRef Mardassi BBA, Aissani N, Moalla I, Dhahri D, Dridi A, Mlik B. Evidence for the predominance of a single tet (M) gene sequence type in tetracycline-resistant Ureaplasma parvum and mycoplasma hominis isolates from Tunisian patients. J Med Microbiol. 2012;61:1254–61.CrossRef
8.
go back to reference Abele-Horn M, Wolff C, Dressel P, Pfaff F, Zimmermann A. Association of Ureaplasma urealyticum biovars with clinical outcome for neonates, obstetric patients, and gynecological patients with pelvic inflammatory disease. J Clin Microbiol. 1997;35:1199–202.CrossRef Abele-Horn M, Wolff C, Dressel P, Pfaff F, Zimmermann A. Association of Ureaplasma urealyticum biovars with clinical outcome for neonates, obstetric patients, and gynecological patients with pelvic inflammatory disease. J Clin Microbiol. 1997;35:1199–202.CrossRef
9.
go back to reference Deguchi T, Yoshida T, Miyazawa T, Yasuda M, Tamaki M, Ishiko H, et al. Association of Ureaplasma urealyticum (biovar 2) with nongonococcal urethritis. Sex Transm Dis. 2004;31:192–5.CrossRef Deguchi T, Yoshida T, Miyazawa T, Yasuda M, Tamaki M, Ishiko H, et al. Association of Ureaplasma urealyticum (biovar 2) with nongonococcal urethritis. Sex Transm Dis. 2004;31:192–5.CrossRef
10.
go back to reference Ondondo RO, Whittington WLH, Astete SG, Totten PA. Differential association of ureaplasma species with non-gonococcal urethritis in heterosexual men. Sex Transm Infect. 2010;86:271–5.CrossRef Ondondo RO, Whittington WLH, Astete SG, Totten PA. Differential association of ureaplasma species with non-gonococcal urethritis in heterosexual men. Sex Transm Infect. 2010;86:271–5.CrossRef
11.
go back to reference Kong F, Ma Z, James G, Gordon S, Gilbert GL. Species identification and subtyping of Ureaplasma parvum and Ureaplasma urealyticum using PCR-based assays. J Clin Microbiol. 2000;38:1175–9.CrossRef Kong F, Ma Z, James G, Gordon S, Gilbert GL. Species identification and subtyping of Ureaplasma parvum and Ureaplasma urealyticum using PCR-based assays. J Clin Microbiol. 2000;38:1175–9.CrossRef
12.
go back to reference Zhang Y, Hua C, Li S-L. The relationship between the biovars and the antimicrobial resistance of Ureaplasma urealyticum in female patients with urogenital infections. J Clin Lab Anal. 2017;32(1):e22211.CrossRef Zhang Y, Hua C, Li S-L. The relationship between the biovars and the antimicrobial resistance of Ureaplasma urealyticum in female patients with urogenital infections. J Clin Lab Anal. 2017;32(1):e22211.CrossRef
13.
go back to reference Redelinghuys MJ, Ehlers MM, Dreyer AW, Lombaard HA, Kock MM. Antimicrobial susceptibility patterns of Ureaplasma species and mycoplasma hominis in pregnant women. BMC Infect Dis. 2014;14:171.CrossRef Redelinghuys MJ, Ehlers MM, Dreyer AW, Lombaard HA, Kock MM. Antimicrobial susceptibility patterns of Ureaplasma species and mycoplasma hominis in pregnant women. BMC Infect Dis. 2014;14:171.CrossRef
14.
go back to reference Song T, Ye A, Xie X, Huang J, Ruan Z, Kong Y, et al. Epidemiological investigation and antimicrobial susceptibility analysis of ureaplasma species and mycoplasma hominis in outpatients with genital manifestations. J Clin Pathol. 2014;67:817–20.CrossRef Song T, Ye A, Xie X, Huang J, Ruan Z, Kong Y, et al. Epidemiological investigation and antimicrobial susceptibility analysis of ureaplasma species and mycoplasma hominis in outpatients with genital manifestations. J Clin Pathol. 2014;67:817–20.CrossRef
15.
go back to reference Magiorakos A-P, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect. 2012;18:268–81.CrossRef Magiorakos A-P, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect. 2012;18:268–81.CrossRef
16.
go back to reference Braam JF, van Dommelen L, Henquet CJM, van de Bovenkamp JHB, Kusters JG. Multidrug-resistant mycoplasma genitalium infections in Europe. Eur J Clin Microbiol Infect Dis. 2017;36:1565–7.CrossRef Braam JF, van Dommelen L, Henquet CJM, van de Bovenkamp JHB, Kusters JG. Multidrug-resistant mycoplasma genitalium infections in Europe. Eur J Clin Microbiol Infect Dis. 2017;36:1565–7.CrossRef
18.
go back to reference Kong F, Zhu X, Wang W, Zhou X, Gordon S, Gilbert GL. Comparative analysis and serovar-specific identification of multiple-banded antigen genes of Ureaplasma urealyticum biovar 1. J Clin Microbiol. 1999;37:538–43.CrossRef Kong F, Zhu X, Wang W, Zhou X, Gordon S, Gilbert GL. Comparative analysis and serovar-specific identification of multiple-banded antigen genes of Ureaplasma urealyticum biovar 1. J Clin Microbiol. 1999;37:538–43.CrossRef
19.
go back to reference Knox CL, Giffard P, Timms P. The phylogeny of Ureaplasma urealyticum based on the mba gene fragment. Int J Syst Bacteriol. 1998;48(Pt 4):1323–31.CrossRef Knox CL, Giffard P, Timms P. The phylogeny of Ureaplasma urealyticum based on the mba gene fragment. Int J Syst Bacteriol. 1998;48(Pt 4):1323–31.CrossRef
20.
go back to reference Hall TA. BioEdit: a user-friendly biological sequence alignment editor and analysis program for windows 95/98/NT. Nucleic Acids Symp Ser. 1999;41:95–8. Hall TA. BioEdit: a user-friendly biological sequence alignment editor and analysis program for windows 95/98/NT. Nucleic Acids Symp Ser. 1999;41:95–8.
21.
go back to reference Tamura K, Stecher G, Peterson D, Filipski A, Kumar S. MEGA6: molecular evolutionary genetics analysis version 6.0. Mol Biol Evol. 2013;30:2725–9.CrossRef Tamura K, Stecher G, Peterson D, Filipski A, Kumar S. MEGA6: molecular evolutionary genetics analysis version 6.0. Mol Biol Evol. 2013;30:2725–9.CrossRef
22.
go back to reference CLSI. Methods for Antimicrobial Susceptibility Testing for Human Mycoplasmas; Approved Guideline. CLSI document M43-A. Wayne: Clinical and Laboratory Standards Institute; 2011. CLSI. Methods for Antimicrobial Susceptibility Testing for Human Mycoplasmas; Approved Guideline. CLSI document M43-A. Wayne: Clinical and Laboratory Standards Institute; 2011.
23.
go back to reference 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. 2000;44:2557–60.CrossRef 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. 2000;44:2557–60.CrossRef
24.
go back to reference Pereyre S, Métifiot M, Cazanave C, Renaudin H, Charron A, Bébéar C, et al. Characterisation of in vitro-selected mutants of Ureaplasma parvum resistant to macrolides and related antibiotics. Int J Antimicrob Agents. 2007;29:207–11.CrossRef Pereyre S, Métifiot M, Cazanave C, Renaudin H, Charron A, Bébéar C, et al. Characterisation of in vitro-selected mutants of Ureaplasma parvum resistant to macrolides and related antibiotics. Int J Antimicrob Agents. 2007;29:207–11.CrossRef
26.
go back to reference Mansour W. Tunisian antibiotic resistance problems: three contexts but one health. Afr Health Sci. 2018;18:1202.CrossRef Mansour W. Tunisian antibiotic resistance problems: three contexts but one health. Afr Health Sci. 2018;18:1202.CrossRef
27.
go back to reference Valentine-King MA, Brown MB. Antibacterial resistance in Ureaplasma species and mycoplasma hominis isolates from urine cultures in college-aged females. Antimicrob Agents Chemother. 2017;61:e01104–17.CrossRef Valentine-King MA, Brown MB. Antibacterial resistance in Ureaplasma species and mycoplasma hominis isolates from urine cultures in college-aged females. Antimicrob Agents Chemother. 2017;61:e01104–17.CrossRef
28.
go back to reference Beeton ML, Chalker VJ, Jones LC, Maxwell NC, Spiller OB. Antibiotic resistance among clinical Ureaplasma isolates recovered from neonates in England and Wales between 2007 and 2013. Antimicrob Agents Chemother. 2016;60:52–6.CrossRef Beeton ML, Chalker VJ, Jones LC, Maxwell NC, Spiller OB. Antibiotic resistance among clinical Ureaplasma isolates recovered from neonates in England and Wales between 2007 and 2013. Antimicrob Agents Chemother. 2016;60:52–6.CrossRef
29.
go back to reference Bayraktar MR, Ozerol IH, Gucluer N, Celik O. Prevalence and antibiotic susceptibility of mycoplasma hominis and Ureaplasma urealyticum in pregnant women. Int J Infect Dis. 2010;14:90–5.CrossRef Bayraktar MR, Ozerol IH, Gucluer N, Celik O. Prevalence and antibiotic susceptibility of mycoplasma hominis and Ureaplasma urealyticum in pregnant women. Int J Infect Dis. 2010;14:90–5.CrossRef
30.
go back to reference Díaz L, Cabrera LE, Fernández T, Ibáñez I, Torres Y, Obregón Y, et al. Frequency and antimicrobial sensitivity of Ureaplasma urealyticum and mycoplasma hominis in patients with vaginal discharge. MEDICC Rev. 2013;15:45–7.PubMed Díaz L, Cabrera LE, Fernández T, Ibáñez I, Torres Y, Obregón Y, et al. Frequency and antimicrobial sensitivity of Ureaplasma urealyticum and mycoplasma hominis in patients with vaginal discharge. MEDICC Rev. 2013;15:45–7.PubMed
31.
go back to reference Dégrange S, Renaudin H, Charron A, Bébéar C, Bébéar CM. Tetracycline resistance in Ureaplasma spp. and mycoplasma hominis: prevalence in Bordeaux, France, from 1999 to 2002 and description of two tet (M)-positive isolates of M. hominis susceptible to tetracyclines. Antimicrob Agents Chemother. 2008;52:742–4.CrossRef Dégrange S, Renaudin H, Charron A, Bébéar C, Bébéar CM. Tetracycline resistance in Ureaplasma spp. and mycoplasma hominis: prevalence in Bordeaux, France, from 1999 to 2002 and description of two tet (M)-positive isolates of M. hominis susceptible to tetracyclines. Antimicrob Agents Chemother. 2008;52:742–4.CrossRef
32.
go back to reference Fernández J, Karau MJ, Cunningham SA, Greenwood-Quaintance KE, Patel R. Antimicrobial susceptibility and Clonality of clinical Ureaplasma isolates in the United States. Antimicrob Agents Chemother. 2016;60:4793–8.CrossRef Fernández J, Karau MJ, Cunningham SA, Greenwood-Quaintance KE, Patel R. Antimicrobial susceptibility and Clonality of clinical Ureaplasma isolates in the United States. Antimicrob Agents Chemother. 2016;60:4793–8.CrossRef
33.
go back to reference Song J, Qiao Y, Kong Y, Ruan Z, Huang J, Song T, et al. Frequent topoisomerase IV mutations associated with fluoroquinolone resistance in Ureaplasma species. J Med Microbiol. 2015;64:1315–20.CrossRef Song J, Qiao Y, Kong Y, Ruan Z, Huang J, Song T, et al. Frequent topoisomerase IV mutations associated with fluoroquinolone resistance in Ureaplasma species. J Med Microbiol. 2015;64:1315–20.CrossRef
34.
go back to reference Zeng X-Y, Xin N, Tong X-N, Wang J-Y, Liu Z-W. Prevalence and antibiotic susceptibility of Ureaplasma urealyticum and mycoplasma hominis in Xi’an, China. Eur J Clin Microbiol Infect Dis. 2016;35:1941–7.CrossRef Zeng X-Y, Xin N, Tong X-N, Wang J-Y, Liu Z-W. Prevalence and antibiotic susceptibility of Ureaplasma urealyticum and mycoplasma hominis in Xi’an, China. Eur J Clin Microbiol Infect Dis. 2016;35:1941–7.CrossRef
35.
go back to reference O’Connor S, Rifkin D, Yang YH, Wang JF, Levine OS, Dowell SF. Physician control of pediatric antimicrobial use in Beijing, China, and its rural environs. Pediatr Infect Dis J. 2001;20:679–84.CrossRef O’Connor S, Rifkin D, Yang YH, Wang JF, Levine OS, Dowell SF. Physician control of pediatric antimicrobial use in Beijing, China, and its rural environs. Pediatr Infect Dis J. 2001;20:679–84.CrossRef
36.
go back to reference Piddock LJ. Mechanisms of fluoroquinolone resistance: an update 1994-1998. Drugs. 1999;58(Suppl 2):11–8.CrossRef Piddock LJ. Mechanisms of fluoroquinolone resistance: an update 1994-1998. Drugs. 1999;58(Suppl 2):11–8.CrossRef
37.
go back to reference Kawai Y, Nakura Y, Wakimoto T, Nomiyama M, Tokuda T, Takayanagi T, et al. In Vitro Activity of Five Quinolones and Analysis of the Quinolone Resistance-Determining Regions of gyrA , gyrB , parC , and parE in Ureaplasma parvum and Ureaplasma urealyticum Clinical Isolates from Perinatal Patients in Japan. Antimicrob Agents Chemother. 2015;59:2358–64.CrossRef Kawai Y, Nakura Y, Wakimoto T, Nomiyama M, Tokuda T, Takayanagi T, et al. In Vitro Activity of Five Quinolones and Analysis of the Quinolone Resistance-Determining Regions of gyrA , gyrB , parC , and parE in Ureaplasma parvum and Ureaplasma urealyticum Clinical Isolates from Perinatal Patients in Japan. Antimicrob Agents Chemother. 2015;59:2358–64.CrossRef
38.
go back to reference Chang J, Yu JK, Song C, Park IY, Park Y-J. Prevalence and Antimicrobial Susceptibility of Genital Mycoplasmataceae in Korean Women: Correlation between Phenotypic Test and Resistance Genes. Ann Clin Microbiol. 2016;19:13.CrossRef Chang J, Yu JK, Song C, Park IY, Park Y-J. Prevalence and Antimicrobial Susceptibility of Genital Mycoplasmataceae in Korean Women: Correlation between Phenotypic Test and Resistance Genes. Ann Clin Microbiol. 2016;19:13.CrossRef
39.
go back to reference Damião Gouveia AC, Unemo M, Jensen JS. In vitro activity of zoliflodacin (ETX0914) against macrolide-resistant, fluoroquinolone-resistant and antimicrobial-susceptible mycoplasma genitalium strains. J Antimicrob Chemother. 2018;73:1291–4.CrossRef Damião Gouveia AC, Unemo M, Jensen JS. In vitro activity of zoliflodacin (ETX0914) against macrolide-resistant, fluoroquinolone-resistant and antimicrobial-susceptible mycoplasma genitalium strains. J Antimicrob Chemother. 2018;73:1291–4.CrossRef
40.
go back to reference Xiao L, Crabb DM, Duffy LB, Paralanov V, Glass JI, Hamilos DL, et al. Mutations in ribosomal proteins and ribosomal RNA confer macrolide resistance in human Ureaplasma spp. Int J Antimicrob Agents. 2011;37:377–9.CrossRef Xiao L, Crabb DM, Duffy LB, Paralanov V, Glass JI, Hamilos DL, et al. Mutations in ribosomal proteins and ribosomal RNA confer macrolide resistance in human Ureaplasma spp. Int J Antimicrob Agents. 2011;37:377–9.CrossRef
Metadata
Title
Spread of multidrug resistance among Ureaplasma serovars, Tunisia
Authors
Safa Boujemaa
Béhija Mlik
Amina Ben Allaya
Helmi Mardassi
Boutheina Ben Abdelmoumen Mardassi
Publication date
01-12-2020

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