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Methicillin resistance and vancomycin heteroresistance in Staphylococcus aureus in cystic fibrosis patients

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Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) infections are increasingly being reported among cystic fibrosis (CF) populations worldwide. In this paper, we sought to examine at the epidemiology, the molecular characterisation and the antibiotic resistance of MRSA isolates in our cohort of CF patients. All MRSA strains were collected prospectively at the University Hospital of Catania, Italy, during a two-year study between mid 2005 to mid 2007 and underwent molecular, pathotype and susceptibility characterisations. Our study demonstrates persisting infections with both hospital-associated (HA-) and community-associated (CA-)MRSA, including Panton–Valentine leukocidin (PVL)-positive strains, in our CF population with an overall prevalence of 7.8%. We demonstrated that, in these patients, persistence was sustained by either identical clones that underwent subtle changes in their toxin content or by different clones over time. The isolation of MRSA in our CF population aged 7–24 years was associated with an increased severity of the disease even if, due to the small sample of patients included and the paucity of data on the clinical outcome, these results cannot be conclusive. Furthermore, three strains were heteroresistant vancomycin-intermediate S. aureus (hVISA), questioning the use of glycopeptides in the treatment of MRSA infections in these patients.

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References

  1. Campana S, Taccetti G, Ravenni N, Masi I, Audino S, Sisi B, Repetto T, Döring G, de Martino M (2004) Molecular epidemiology of Pseudomonas aeruginosa, Burkholderia cepacia complex and methicillin-resistant Staphylococcus aureus in a cystic fibrosis center. J Cyst Fibros 3(3):159–163

    Article  CAS  PubMed  Google Scholar 

  2. Goodrich JS, Sutton-Shields TN, Kerr A, Wedd JP, Miller MB, Gilligan PH (2009) Prevalence of community-associated methicillin-resistant Staphylococcus aureus in patients with cystic fibrosis. J Clin Microbiol 47(4):1231–1233

    Article  PubMed  Google Scholar 

  3. Nadesalingam K, Conway SP, Denton M (2005) Risk factors for acquisition of methicillin-resistant Staphylococcus aureus (MRSA) by patients with cystic fibrosis. J Cyst Fibros 4(1):49–52

    Article  PubMed  Google Scholar 

  4. Boxerbaum B, Jacobs MR, Cechner RL (1988) Prevalence and significance of methicillin-resistant Staphylococcus aureus in patients with cystic fibrosis. Pediatr Pulmonol 4:159–163

    Article  CAS  PubMed  Google Scholar 

  5. Branger C, Fournier JM, Loulergue J, Bouvet A, Goullet P, Boutonnier A, de Gialluly C, Couetdic G, Chomarat M, Jaffar-Banjee MC, Mariani P (1994) Epidemiology of Staphylococcus aureus in patients with cystic fibrosis. Epidemiol Infect 112:489–500

    Article  CAS  PubMed  Google Scholar 

  6. Thomas SR, Gyi KM, Gaya H, Hodson ME (1998) Methicillin-resistant Staphylococcus aureus: impact at a national cystic fibrosis centre. J Hosp Infect 40:203–209

    Article  PubMed  Google Scholar 

  7. Dasenbrook EC, Merlo CA, Diener-West M, Lechtzin N, Boyle MP (2008) Persistent methicillin-resistant Staphylococcus aureus and rate of FEV1 decline in cystic fibrosis. Am J Respir Crit Care Med 178(8):814–821

    Article  PubMed  Google Scholar 

  8. Miall LS, McGinley NT, Brownlee KG, Conway SP (2001) Methicillin resistant Staphylococcus aureus (MRSA) infection in cystic fibrosis. Arch Dis Child 84(2):160–162

    Article  CAS  PubMed  Google Scholar 

  9. Ren CL, Morgan WJ, Konstan MW, Schechter MS, Wagener JS, Fisher KA, Regelmann WE; Investigators and Coordinators of the Epidemiologic Study of Cystic Fibrosis (2007) Presence of methicillin resistant Staphylococcus aureus in respiratory cultures from cystic fibrosis patients is associated with lower lung function. Pediatr Pulmonol 42(6):513–518

    Article  PubMed  Google Scholar 

  10. Boyce JM (1992) Methicillin-resistant Staphylococcus aureus in hospitals and long-term care facilities: microbiology, epidemiology, and preventive measures. Infect Control Hosp Epidemiol 13(12):725–737

    Article  CAS  PubMed  Google Scholar 

  11. Deurenberg RH, Stobberingh EE (2009) The molecular evolution of hospital- and community-associated methicillin-resistant Staphylococcus aureus. Curr Mol Med 9(2):100–115

    Article  CAS  PubMed  Google Scholar 

  12. Sakoulas G, Moise-Broder PA, Schentag J, Forrest A, Moellering RC Jr, Eliopoulos GM (2004) Relationship of MIC and bactericidal activity to efficacy of vancomycin for treatment of methicillin-resistant Staphylococcus aureus bacteremia. J Clin Microbiol 42(6):2398–2402

    Article  CAS  PubMed  Google Scholar 

  13. Stefani S, Bongiorno D, Cafiso V, Campanile F, Crapis M, Cristini F, Sartor A, Scarparo C, Spina D, Viale P (2009) Pathotype and susceptibility profile of a community-acquired methicillin-resistant Staphylococcus aureus strain responsible for a case of severe pneumonia. Diagn Microbiol Infect Dis 63(1):100–104

    Article  CAS  PubMed  Google Scholar 

  14. Higuchi W, Takano T, Teng LJ, Yamamoto T (2008) Structure and specific detection of staphylococcal cassette chromosome mec type VII. Biochem Biophys Res Commun 377:752–756

    Article  CAS  PubMed  Google Scholar 

  15. Stefani S, Monaco M, Campanile F, Cafiso V, Sanchini A, Marone P, Pantosti A (2009) Characterisation of Panton–Valentine leukocidine positive methicillin-resistant Staphylococcus aureus in Italy. In: Proceedings of the 19th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), Helsinki, Finland, May 2009, abstract number P1573

  16. Denis O, Deplano A, De Beenhouwer H, Hallin M, Huysmans G, Garrino MG, Glupczynski Y, Malaviolle X, Vergison A, Struelens MJ (2005) Polyclonal emergence and importation of community-acquired methicillin-resistant Staphylococcus aureus strains harbouring Panton–Valentine leucocidin genes in Belgium. J Antimicrob Chemother 56(6):1103–1106

    Article  CAS  PubMed  Google Scholar 

  17. Otter JA, French GL (2008) The emergence of community-associated methicillin-resistant Staphylococcus aureus at a London teaching hospital, 2000–2006. Clin Microbiol Infect 14(7):670–676

    Article  CAS  PubMed  Google Scholar 

  18. Tristan A, Bes M, Meugnier H, Lina G, Bozdogan B, Courvalin P, Reverdy ME, Enright MC, Vandenesch F, Etienne J (2007) Global distribution of Panton–Valentine leukocidin-positive methicillin-resistant Staphylococcus aureus, 2006. Emerg Infect Dis 13(4):594–600

    Article  CAS  PubMed  Google Scholar 

  19. Valentini P, Parisi G, Monaco M, Crea F, Spanu T, Ranno O, Tronci M, Pantosti A (2008) An uncommon presentation for a severe invasive infection due to methicillin-resistant Staphylococcus aureus clone USA300 in Italy: a case report. Ann Clin Microbiol Antimicrob 7:11

    Article  PubMed  Google Scholar 

  20. Boyle MP, Ross T, Goldberg JD, Podliska MZ, Cai M, Mogayzel PJ, Carroll KC (2005) Molecular epidemiology of MRSA infection in cystic fibrosis and its clinical implications. Pediatr Pulmonol 28:288–289

    Google Scholar 

  21. Glikman D, Siegel JD, David MZ, Okoro NM, Boyle-Vavra S, Dowell ML, Daum RS (2008) Complex molecular epidemiology of methicillin-resistant Staphylococcus aureus isolates from children with cystic fibrosis in the era of epidemic community-associated methicillin-resistant S. aureus. Chest 133(6):1381–1387

    Article  PubMed  Google Scholar 

  22. Campana S, Cocchi P, Döring G, Taccetti G, Moroney SM (2007) Emergence of an epidemic clone of community-associated methicillin-resistant Panton–Valentine leucocidin-negative Staphylococcus aureus in cystic fibrosis patient populations. J Clin Microbiol 45(9):3146

    Article  PubMed  Google Scholar 

  23. Campanile F, Bongiorno D, Borbone S, Venditti M, Giannella M, Franchi C, Stefani S (2007) Characterization of a variant of the SCCmec element in a bloodstream isolate of Staphylococcus intermedius. Microb Drug Resist 13(1):7–10

    Article  CAS  PubMed  Google Scholar 

  24. Mato R, Campanile F, Stefani S, Crisóstomo MI, Santagati M, Sanches SI, de Lencastre H (2004) Clonal types and multidrug resistance patterns of methicillin-resistant Staphylococcus aureus (MRSA) recovered in Italy during the 1990s. Microb Drug Resist 10(2):106–113

    Article  CAS  PubMed  Google Scholar 

  25. Kondo Y, Ito T, Ma XX, Watanabe S, Kreiswirth BN, Etienne J, Hiramatsu K (2007) Combination of multiplex PCRs for staphylococcal cassette chromosome mec type assignment: rapid identification system for mec, ccr, and major differences in junkyard regions. Antimicrob Agents Chemother 51(1):264–274

    Article  CAS  PubMed  Google Scholar 

  26. Milheiriço C, Oliveira DC, de Lencastre H (2007) Multiplex PCR strategy for subtyping the staphylococcal cassette chromosome mec type IV in methicillin-resistant Staphylococcus aureus: ‘SCCmec IV multiplex’. J Antimicrob Chemother 60(1):42–48

    Article  PubMed  Google Scholar 

  27. Oliveira DC, de Lencastre H (2002) Multiplex PCR strategy for rapid identification of structural types and variants of the mec element in methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 46(7):2155–2161

    Article  CAS  PubMed  Google Scholar 

  28. Lina G, Boutite F, Tristan A, Bes M, Etienne J, Vandenesch F (2003) Bacterial competition for human nasal cavity colonization: role of Staphylococcal agr alleles. Appl Environ Microbiol 69(1):18–23

    Article  CAS  PubMed  Google Scholar 

  29. Cafiso V, Bertuccio T, Santagati M, Campanile F, Amicosante G, Perilli MG, Selan L, Artini M, Nicoletti G, Stefani S (2004) Presence of the ica operon in clinical isolates of Staphylococcus epidermidis and its role in biofilm production. Clin Microbiol Infect 10:1081–1088

    Article  CAS  PubMed  Google Scholar 

  30. Cafiso V, Bertuccio T, Santagati M, Demelio V, Spina D, Nicoletti G, Stefani S (2007) agr-Genotyping and transcriptional analysis of biofilm-producing Staphylococcus aureus. FEMS Immunol Med Microbiol 51(1):220–227

    Article  CAS  PubMed  Google Scholar 

  31. Christensen GD, Simpson WA, Younger JJ, Baddour LM, Barrett FF, Melton DM, Beachey EH (1985) Adherence of coagulase-negative staphylococci to plastic tissue culture plates: a quantitative model for the adherence of staphylococci to medical devices. J Clin Microbiol 22:996–1006

    CAS  PubMed  Google Scholar 

  32. Ziebuhr W, Krimmer V, Rachid S, Lössner I, Götz F, Hacker J (1999) A novel mechanism of phase variation of virulence in Staphylococcus epidermidis: evidence for control of the polysaccharide intercellular adhesin synthesis by alternating insertion and excision of the insertion sequence element IS256. Mol Microbiol 32:345–356

    Article  CAS  PubMed  Google Scholar 

  33. Clinical and Laboratory Standards Institute (CLSI) (2009) Performance standards for antimicrobial susceptibility testing. CLSI M100 and S19 vol. 29, no. 3. CLSI, Wayne, PA, USA

  34. Borbone S, Campanile F, Bongiorno D, Perez M, Stefani S (2009) Heteroresistance to glycopeptides in Italian methicillin-resistant Staphylococcus aureus isolates. In: Proceedings of the 49th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICCAC), San Francisco, CA, September 2009, C2-114

  35. Cassone M, Campanile F, Pantosti A, Venditti M, Stefani S (2004) Identification of a variant “Rome clone” of methicillin-resistant Staphylococcus aureus with decreased susceptibility to vancomycin, responsible for an outbreak in an intensive care unit. Microb Drug Resist 10(1):43–49

    Article  CAS  PubMed  Google Scholar 

  36. Campanile F, Bongiorno D, Borbone S, Falcone M, Giannella M, Venditti M, Stefani S (2008) In vitro activity of daptomycin against methicillin- and multi-resistant Staphylococcus haemolyticus invasive isolates carrying different mec complexes. Diagn Microbiol Infect Dis 61(2):227–231

    Article  CAS  PubMed  Google Scholar 

  37. Baba T, Takeuchi F, Kuroda M, Yuzawa H, Aoki K, Oguchi A, Nagai Y, Iwama N, Asano K, Naimi T, Kuroda H, Cui L, Yamamoto K, Hiramatsu K (2002) Genome and virulence determinants of high virulence community-acquired MRSA. Lancet 359(9320):1819–1827

    Article  CAS  PubMed  Google Scholar 

  38. Cystic Fibrosis Foundation (CFF) (2007) Patient registry: annual data report 2006. CFF, Bethesda, MD, USA

  39. Elizur A, Orscheln RC, Ferkol TW, Atkinson JJ, Dunne WM Jr, Buller RS, Armstrong JR, Mardis ER, Storch GA, Cannon CL (2007) Panton–Valentine leukocidin-positive methicillin-resistant Staphylococcus aureus lung infection in patients with cystic fibrosis. Chest 131(6):1718–1725

    Article  PubMed  Google Scholar 

  40. Wulf M, Voss A (2008) MRSA in livestock animals—an epidemic waiting to happen? Clin Microbiol Infect 14(6):519–521

    Article  CAS  PubMed  Google Scholar 

  41. Witte W, Strommenger B, Stanek C, Cuny C (2007) Methicillin-resistant Staphylococcus aureus ST398 in humans and animals, Central Europe. Emerg Infect Dis 13(2):255–258

    Article  CAS  PubMed  Google Scholar 

  42. Park C, Shin HH, Kwon EY, Choi SM, Kim SH, Park SH, Choi JH, Yoo JH, Lee DG, Shin WS (2009) Two variants of staphylococcal cassette chromosome mec type IVA in community-associated meticillin-resistant Staphylococcus aureus strains in South Korea. J Med Microbiol 58(Pt 10):1314–1321

    Article  CAS  PubMed  Google Scholar 

  43. Schuenck RP, Nouér SA, Winter Cde O, Cavalcante FS, Scotti TD, Ferreira AL, Giambiagi-de Marval M, dos Santos KR (2009) Polyclonal presence of non-multiresistant methicillin-resistant Staphylococcus aureus isolates carrying SCCmec IV in health care-associated infections in a hospital in Rio de Janeiro, Brazil. Diagn Microbiol Infect Dis 64(4):434–441

    Article  CAS  PubMed  Google Scholar 

  44. Denis O, Nonhoff C, Byl B, Knoop C, Bobin-Dubreux S, Struelens MJ (2002) Emergence of vancomycin-intermediate Staphylococcus aureus in a Belgian hospital: microbiological and clinical features. J Antimicrob Chemother 50(3):383–391

    Article  CAS  PubMed  Google Scholar 

  45. Soriano A, Marco F, Martínez JA, Pisos E, Almela M, Dimova VP, Alamo D, Ortega M, Lopez J, Mensa J (2008) Influence of vancomycin minimum inhibitory concentration on the treatment of methicillin-resistant Staphylococcus aureus bacteremia. Clin Infect Dis 46(2):193–200

    Article  CAS  PubMed  Google Scholar 

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Acknowledgement

We gratefully acknowledge the Network on Antimicrobial Resistance in Staphylococcus aureus (NARSA) for providing the Mu3 (NRS2) and Mu50 (NRS1) control strains and Antony Bridgewood for the language revision of the manuscript. Partial support for this study was provided by grants from the Italian Minister of Health and from MIUR-Cofin 2007, 2007SCA9RK.

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Authors and Affiliations

  1. Department of Microbiology, University of Catania, Via Androne 81, 95124, Catania, Italy

    V. Cafiso, T. Bertuccio, D. Spina, F. Campanile, D. Bongiorno, M. Santagati, A. Sciacca & S. Stefani

  2. University Hospital of Catania, Catania, Italy

    A. Sciacca

  3. Paediatric Department, University Hospital of Catania, Catania, Italy

    C. Sciuto

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  1. V. Cafiso
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  2. T. Bertuccio
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  9. S. Stefani
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Correspondence to S. Stefani.

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Cafiso, V., Bertuccio, T., Spina, D. et al. Methicillin resistance and vancomycin heteroresistance in Staphylococcus aureus in cystic fibrosis patients. Eur J Clin Microbiol Infect Dis 29, 1277–1285 (2010). https://doi.org/10.1007/s10096-010-1000-5

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  • DOI: https://doi.org/10.1007/s10096-010-1000-5

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