1887

Abstract

We investigated antimicrobial susceptibility and the molecular mechanism involved in conferring high-level macrolide resistance in 47 clinical isolates of from Japan. Antimicrobial susceptibility was determined using Etest and agar dilution methods. Thirty-two erythromycinnon-susceptible strains were evaluated for the possibility of clonal spreading, using PFGE. To analyse the mechanism related to macrolide resistance, mutations in the 23S rRNA gene and the ribosomal proteins, and the presence of methylase genes were investigated by PCR and sequencing. The efflux system was examined using appropriate inhibitors. Penicillin, ampicillin, amoxicillin, cefixime, levofloxacin and antimicrobials containing β-lactamase inhibitors showed strong activity against 47 isolates. Thirty-two (68.1 %) of the 47 isolates showed high-level MICs to macrolides (MIC ≥128 mg l) and shared the A2058T mutation in the 23S rRNA gene. The geometric mean MIC to macrolides of A2058T-mutated strains was significantly higher than that of WT strains (<0.0001). Thirty-two isolates with high-level macrolide MICs clustered into 30 patterns on the basis of the PFGE dendrogram, indicating that the macrolide-resistant strains were not clonal. In contrast, no common mutations of the ribosomal proteins or methylase genes, or overproduction of the efflux system were observed in A2058T-mutated strains. Moreover, of the 47 strains, 43 (91.5 %) were and 4 (8.5 %) were positive. Our results suggest that most clinical isolates show high-level macrolide resistance conferred by the A2058T mutation in the 23S rRNA gene. This study represents the first characterization of .

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.061788-0
2014-02-01
2019-10-19
Loading full text...

Full text loading...

/deliver/fulltext/jmm/63/2/242.html?itemId=/content/journal/jmm/10.1099/jmm.0.061788-0&mimeType=html&fmt=ahah

References

  1. Berisio R. , Corti N. , Pfister P. , Yonath A. , Böttger E. C. . ( 2006; ). 23S rRNA 2058A→G alteration mediates ketolide resistance in combination with deletion in L22. . Antimicrob Agents Chemother 50:, 3816–3823. [CrossRef] [PubMed]
    [Google Scholar]
  2. Chironna M. , Sallustio A. , Esposito S. , Perulli M. , Chinellato I. , Di Bari C. , Quarto M. , Cardinale F. . ( 2011; ). Emergence of macrolide-resistant strains during an outbreak of Mycoplasma pneumoniae infections in children. . J Antimicrob Chemother 66:, 734–737. [CrossRef] [PubMed]
    [Google Scholar]
  3. Chisholm S. A. , Dave J. , Ison C. A. . ( 2010; ). High-level azithromycin resistance occurs in Neisseria gonorrhoeae as a result of a single point mutation in the 23S rRNA genes. . Antimicrob Agents Chemother 54:, 3812–3816. [CrossRef] [PubMed]
    [Google Scholar]
  4. Chung W. O. , Werckenthin C. , Schwarz S. , Roberts M. C. . ( 1999; ). Host range of the ermF rRNA methylase gene in bacteria of human and animal origin. . J Antimicrob Chemother 43:, 5–14. [CrossRef] [PubMed]
    [Google Scholar]
  5. CLSI ( 2010; ). Methods for Antimicrobial Dilution and Disk Susceptibility Testing of Infrequently Isolated or Fastidious Bacteria; Approved Standard M45-A2. . Wayne, PA:: Clinical and Laboratory Standards Institute;.
  6. Davis J. M. , Whipp M. J. , Ashhurst-Smith C. , DeBoer J. C. , Peel M. M. . ( 2004; ). Mucoid nitrate-negative Moraxella nonliquefaciens from three patients with chronic lung disease. . J Clin Microbiol 42:, 3888–3890. [CrossRef] [PubMed]
    [Google Scholar]
  7. Eliasson I. , Kamme C. , Vang M. , Waley S. G. . ( 1992; ). Characterization of cell-bound papain-soluble beta-lactamases in BRO-1 and BRO-2 producing strains of Moraxella (Branhamella) catarrhalis and Moraxella nonliquefaciens . . Eur J Clin Microbiol Infect Dis 11:, 313–321. [CrossRef] [PubMed]
    [Google Scholar]
  8. Flamm R. K. , Sader H. S. , Farrell D. J. , Jones R. N. . ( 2012; ). Macrolide and tetracycline resistance among Moraxella catarrhalis isolates from 2009 to 2011. . Diagn Microbiol Infect Dis 74:, 198–200. [CrossRef] [PubMed]
    [Google Scholar]
  9. Grover M. L. , Mookadam M. , Rutkowski R. H. , Cullan A. M. , Hill D. E. , Patchett D. C. , Simon E. O. , Mulheron M. , Noble B. N. . ( 2012; ). Acute respiratory tract infection: a practice examines its antibiotic prescribing habits. . J Fam Pract 61:, 330–335.[PubMed]
    [Google Scholar]
  10. Higashi T. , Fukuhara S. . ( 2009; ). Antibiotic prescriptions for upper respiratory tract infection in Japan. . Intern Med 48:, 1369–1375. [CrossRef] [PubMed]
    [Google Scholar]
  11. Kawai Y. , Miyashita N. , Yamaguchi T. , Saitoh A. , Kondoh E. , Fujimoto H. , Teranishi H. , Inoue M. , Wakabayashi T. . & other authors ( 2012; ). Clinical efficacy of macrolide antibiotics against genetically determined macrolide-resistant Mycoplasma pneumoniae pneumonia in paediatric patients. . Respirology 17:, 354–362. [CrossRef] [PubMed]
    [Google Scholar]
  12. Khan M. A. , Northwood J. B. , Levy F. , Verhaegh S. J. , Farrell D. J. , Van Belkum A. , Hays J. P. . ( 2010; ). bro β-lactamase and antibiotic resistances in a global cross-sectional study of Moraxella catarrhalis from children and adults. . J Antimicrob Chemother 65:, 91–97. [CrossRef] [PubMed]
    [Google Scholar]
  13. Laukeland H. , Bergh K. , Bevanger L. . ( 2002; ). Posttrabeculectomy endophthalmitis caused by Moraxella nonliquefaciens . . J Clin Microbiol 40:, 2668–2670.[PubMed] [CrossRef]
    [Google Scholar]
  14. Leclercq R. , Courvalin P. . ( 1998; ). Streptogramins: an answer to antibiotic resistance in Gram-positive bacteria. . Lancet 352:, 591–592. [CrossRef] [PubMed]
    [Google Scholar]
  15. Li B. B. , Wu C. M. , Wang Y. , Shen J. Z. . ( 2011; ). Single and dual mutations at positions 2058, 2503 and 2504 of 23S rRNA and their relationship to resistance to antibiotics that target the large ribosomal subunit. . J Antimicrob Chemother 66:, 1983–1986. [CrossRef] [PubMed]
    [Google Scholar]
  16. Liu Y. , Zhao C. , Zhang F. , Chen H. , Chen M. , Wang H. . ( 2012; ). High prevalence and molecular analysis of macrolide-nonsusceptible Moraxella catarrhalis isolated from nasopharynx of healthy children in China. . Microb Drug Resist 18:, 417–426. [CrossRef] [PubMed]
    [Google Scholar]
  17. Murphy T. F. , Parameswaran G. I. . ( 2009; ). Moraxella catarrhalis, a human respiratory tract pathogen. . Clin Infect Dis 49:, 124–131. [CrossRef] [PubMed]
    [Google Scholar]
  18. Nakaminami H. , Noguchi N. , Ikeda M. , Hasui M. , Sato M. , Yamamoto S. , Yoshida T. , Asano T. , Senoue M. , Sasatsu M. . ( 2008; ). Molecular epidemiology and antimicrobial susceptibilities of 273 exfoliative toxin-encoding-gene-positive Staphylococcus aureus isolates from patients with impetigo in Japan. . J Med Microbiol 57:, 1251–1258. [CrossRef] [PubMed]
    [Google Scholar]
  19. Rafiq I. , Parthasarathy H. , Tremlett C. , Freeman L. J. , Mullin M. . ( 2011; ). Infective endocarditis caused by Moraxella nonliquefaciens in a percutaneous aortic valve replacement. . Cardiovasc Revasc Med 12:, 184–186. [CrossRef] [PubMed]
    [Google Scholar]
  20. Roberts M. C. , Sutcliffe J. , Courvalin P. , Jensen L. B. , Rood J. , Seppala H. . ( 1999; ). Nomenclature for macrolide and macrolide-lincosamide-streptogramin B resistance determinants. . Antimicrob Agents Chemother 43:, 2823–2830.[PubMed]
    [Google Scholar]
  21. Saito R. , Nonaka S. , Nishiyama H. , Okamura N. . ( 2012; ). Molecular mechanism of macrolide-lincosamide resistance in Moraxella catarrhalis . . J Med Microbiol 61:, 1435–1438. [CrossRef] [PubMed]
    [Google Scholar]
  22. Sutcliffe J. , Grebe T. , Tait-Kamradt A. , Wondrack L. . ( 1996; ). Detection of erythromycin-resistant determinants by PCR. . Antimicrob Agents Chemother 40:, 2562–2566.[PubMed]
    [Google Scholar]
  23. Tait-Kamradt A. , Davies T. , Cronan M. , Jacobs M. R. , Appelbaum P. C. , Sutcliffe J. . ( 2000; ). Mutations in 23S rRNA and ribosomal protein L4 account for resistance in pneumococcal strains selected in vitro by macrolide passage. . Antimicrob Agents Chemother 44:, 2118–2125. [CrossRef] [PubMed]
    [Google Scholar]
  24. Vaneechoutte M. , Dijkshoorn L. , Nemec A. , Kampfer P. , Wauters G. . ( 2012; ). Acinetobacter, Chryseobacterium, Moraxella, and Other Nonfermentative Gram-Negative Rods, Manual of Clinical Microbiology, , 10th edn.. Washington, DC, USA:: ASM Press;.
    [Google Scholar]
  25. Versalovic J. , Osato M. S. , Spakovsky K. , Dore M. P. , Reddy R. , Stone G. G. , Shortridge D. , Flamm R. K. , Tanaka S. K. , Graham D. Y. . ( 1997; ). Point mutations in the 23S rRNA gene of Helicobacter pylori associated with different levels of clarithromycin resistance. . J Antimicrob Chemother 40:, 283–286. [CrossRef] [PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.061788-0
Loading
/content/journal/jmm/10.1099/jmm.0.061788-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error