Epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection: secular trends over 19 years at a university hospital

Oriol Gasch, Josefina Ayats, Maria Ángeles Dominguez, Fe Tubau, Josefina Liñares, Carmen Peña, Immaculada Grau, Román Pallarés, Francesc Gudiol, Javier Ariza, Miquel Pujol, Oriol Gasch, Josefina Ayats, Maria Ángeles Dominguez, Fe Tubau, Josefina Liñares, Carmen Peña, Immaculada Grau, Román Pallarés, Francesc Gudiol, Javier Ariza, Miquel Pujol

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) is a cause of concern in health systems all over the world, due to the high incidence rates and the associated undesirable outcomes. In our tertiary 900-bed university hospital, all episodes of MRSA-BSI have been prospectively followed up since the identification of the first episode in 1990. We conducted the current study to report changes in the epidemiology of MRSA-BSI over the 19-year period between 1990 and 2008, comparing 4 periods (1990-1994, 1995-1999, 2000-2004, and 2005-2008). Overall, 524 patients developed MRSA-BSI. Cumulative incidence was 10.0 episodes/100,000 patient days (range, 1.3-17.4). Although no trend in the incidence rate was observed between the 4 consecutive periods, significant upward trends in patient age and comorbidities, health care acquisition, and non-intravascular catheter source were all identified (p < 0.05). While the Iberian clone (ST247/SCCmecI) was dominant during the first and second periods, almost all the strains isolated in the subsequent periods belonged to Clonal Complex 5 (ST125/SCCmecIV and ST228/SCCmecI). A significant downward trend in vancomycin geometric minimum inhibitory concentration (MIC) was also observed from 2.04 mg/L to 0.88 mg/L, coinciding with the clonal replacement and the reduction in the hospital vancomycin prescription. Therefore, no MRSA vancomycin MIC creep was observed since higher MICs were associated with strains belonging to the Iberian clone. Glycopeptides were the most frequently used antibiotics for MRSA-BSI during all 4 periods. No differences in MRSA-BSI outcomes were found, and the mortality rate at 30 days was close to 29% in each of the 4 periods. In conclusion, we identified significant changes in demographic and clinical characteristics and in the molecular epidemiology of MRSA-BSI during the study period, but found no significant trends in cumulative incidence or in overall mortality rate.

References

    1. Aires de Sousa M, De Lencastre H. Bridges from hospitals to the laboratory: genetic portraits of methicillin-resistant S. aureus clones. FEMS Immunol Med Microbiol. 2004;40:101-111.
    1. Ariza J, Pujol M, Cabo J, Pena C, Fernandez N, Linares J, Ayats J, Gudiol F. Vancomycin in surgical infections due to methicillin-resistant Staphylococcus aureus with heterogeneous resistance to vancomycin. Lancet. 1999;353:1587-1588.
    1. Benfield T, Espersen F, Frimodt-Moller N, Jensen AG, Larsen AR, Pallesen LV, Skov R, Westh H, Skinhoj P. Increasing incidence but decreasing in-hospital mortality of adult Staphylococcus aureus bacteremia between 1981 and 2000. Clin Microbiol Infect Dis. 2007;13:257-263.
    1. Boyce JM, White RL, Spruill EY. Impact of methicillin-resistant Staphylococcus aureus on the incidence of nosocomial staphylococcal infections. J Infect Dis. 1983;148:763.
    1. Buehlmann M, Frei R, Fenner L, Dangel M, Fluckiger U, Widmer AF. Highly effective regimen for decolonization of methicillin-resistant Staphylococcus aureus carriers. Infect Control Hosp Epidemiol. 2008;29:510-516.
    1. Calfee DP, Salgado CD, Classen D, Arias KM, Podgorny K, Anderson DJ, Burstin H, Coffin SE, Dubberke ER, Fraser V, Gerding DN, Griffin FA, Gross P, Kaye KS, Klompas M, Lo E, Marschall J, Mermel LA, Nicolle L, Pegues DA, Perl TM, Saint S, Weinstein RA, Wise R, Yokoe DS. Strategies to prevent transmission of methicillin-resistant Staphylococcus aureus in acute care hospitals. Infect Control Hosp Epidemiol. 2008;29:S62-S80.
    1. Cartolano GL, Cheron M, Benabid D, Leneveu M, Boisivon A. Methicillin-resistant Staphylococcus aureus (MRSA) with reduced susceptibility to glycopeptides (GISA) in 63 French general hospitals. Clin Microbiol Infect. 2004;10:448-451.
    1. Chang FY, MacDonald BB, Peacock JE Jr, Musher DM, Triplett P, Mylotte JM, O'Donnell A, Wagener MM, Yu VL. A prospective multicenter study of Staphylococcus aureus bacteremia: incidence of endocarditis, risk factors for mortality, and clinical impact of methicillin resistance. Medicine (Baltimore). 2003;82:322-332.
    1. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40:373-383.
    1. Chung M, de Lencastre H, Matthews P, Tomasz A, Adamsson I, Aires de Sousa M, Camou T, Cocuzza C, Corso A, Couto I, Dominguez A, Gniadkowski M, Goering R, Gomes A, Kikuchi K, Marchese A, Mato R, Melter O, Oliveira D, Palacio R, Sa-Leao R, Santos Sanches I, Song JH, Tassios PT, Villari P. Molecular typing of methicillin resistant Staphylococcus aureus (MRSA) by pulsed field gel electrophoresis: comparison of results obtained in a multilaboratory effort using identical protocols and MRSA strains. Microb Drug Resist. 2000;6:189-197.
    1. Corbella X, Dominguez MA, Pujol M, Ayats J, Sendra M, Pallares R, Ariza J, Gudiol F. Staphylococcus aureus nasal carriage as a marker for subsequent staphylococcal infections in intensive care unit patients. Eur J Clin Microbiol Infect Dis. 1997;16:351-357.
    1. Cosgrove SE, Sakoulas G, Perencevich EN, Schwaber MJ, Karchmer AW, Carmeli Y. Comparison of mortality associated with methicillin-resistant and methicillin-susceptible Staphylococcus aureus bacteremia: a meta-analysis. Clin Infect Dis. 2003;36:53-59.
    1. Cuevas O, Cercenado E, Goyanes MJ, Vindel A, Trincado P, Boquete T, Marin M, Bouza E. Staphylococcus spp. in Spain: present situation and evolution of antimicrobial resistance (1986-2006). Enferm Infecc Microbiol Clin. 2008;26:269-277.
    1. Da Silva MV, Silva-Carvalho MC, Wisplinghoff H, Hall GO, Tallent S, Wallace S, Edmond MB, Figueiredo AM, Wenzel RP. Clonal spread of methicillin-resistant S. aureus in a large geographic area of the United States. J Hosp Infect. 2003;53:103-110.
    1. Dominguez MA, De Lencastre H, Linares J, Tomasz A. Spread and maintenance of a dominant methicillin-resistant Staphylococcus aureus (MRSA) clone during an outbreak of MRSA disease in a Spanish hospital. J Clin Microbiol. 1994;32:2081-2087.
    1. Enright MC, Day NP, Davies CE, Peacock SJ, Spratt BG. Multilocus sequence typing for characterization of methicillin-resistant and methicillin-susceptible clones of Staphylococcus aureus. J Clin Microbiol. 2000;38:1008-1015.
    1. Enright MC, Robinson DA, Randle G, Feil EJ, Grundmann H, Spratt BG. The evolutionary history of methicillin-resistant and methicillin-susceptible clones of S. aureus. J Clin Microbiol. 2002;99:7687-7692.
    1. Fowler VG Jr, Justice A, Moore C, Benjamin DK Jr, Woods CW, Campbell S, Reller LB, Corey GR, Day NP, Peacock SJ. Risk factors for hematogenous complications of intravascular catheter-associated Staphylococcus aureus bacteremia. Clin Infect Dis. 2005;40:695-703.
    1. Friedman ND, Kaye KS, Stout JE, McGarry SA, Trivette SL, Briggs JP, Lamm W, Clark C, MacFarquhar J, Walton AL, Reller LB, Sexton DJ. Health care-associated bloodstream infections in adults: a reason to change the accepted definition of community-acquired infections. Ann Intern Med. 2002;137:791-797.
    1. Heym B, Le Moal M, Armand-Lefevre L, Nicolas-Chanoine MH. Multilocus sequence typing (MLST) shows that the Iberian clone of methicillin-resistant S. aureus has spread to France and acquired reduced susceptibility to teicoplanin. J Antimicrob Chemother. 2002;50:323-329.
    1. Hiramatsu K, Hanaki H, Ino T, Yabuta K, Oguri T, Tenover FC. Methicillin-resistant Staphylococcus aureus clinical strain with reduced vancomycin susceptibility. J Antimicrob Chemother. 1997;40:135-136.
    1. Horne KC, Howden BP, Grabsch EA, Graham M, Ward PD, Xie S, Mayall BC, Johnson PDR, Grayson ML. Prospective comparison of the clinical impact of heterogeneous vancomycin-intermediate methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-susceptible MRSA. Antimicrob Agents Chemother. 2009;53:3447-3452.
    1. Howden BP, Davies JK, Johnson PD, Stinear TP, Grayson ML. Reduced vancomycin susceptibility in Staphylococcus aureus, including vancomycin-intermediate and heterogeneous vancomycin-intermediate strains: resistance mechanisms, laboratory detection, and clinical implications. Clin Microbiol Rev. 2010;23:99-139.
    1. Howden BP, Ward PB, Charles PG, Korman TM, Fuller A, du Cros P, Grabsch EA, Roberts SA, Robson J, Read K, Bak N, Hurley J, Johnson PD, Morris AJ, Mayall BC, Grayson ML. Treatment outcomes for serious infections caused by methicillin-resistant Staphylococcus aureus with reduced vancomycin susceptibility. Clin Infect Dis. 2004;38:521-528.
    1. Huang SS, Diekema DJ, Warren DK, Zuccotti G, Winokur PL, Tendolkar S, Boyken L, Datta R, Jones RM, Ward MA, Aubre T, Ondedonk AB, Garcia C, Platt R. Strain-relatedness of methicillin-resistant S. aureus isolates recovered from patients with repeated infection. Clin Infect Dis. 2008;46:1241-1247.
    1. Jensen AG, Wachmann CH, Espersen F, Scheibel J, Skinhoj P, Frimodt-Moller N. Treatment and outcome of Staphylococcus aureus bacteremia: a prospective study of 278 cases. Arch Intern Med. 2002;162:25-32.
    1. Kallen AJ, Mu Y, Bulens S, Reingold A, Petit S, Gershman K, Ray SM, Harrison LH, Lynfield R, Dumyati G, Townes JM, Schaffner W, Patel PR, Fridkin SK; Active Bacterial Core surveillance (ABCs) MRSA Investigators of the Emerging Infections Program. Health care-associated invasive MRSA infections, 2005-2008. JAMA. 2010;304:641-648.
    1. Khatib R, Johnson LB, Fakih MG, Riederer K, Khosrovaneh A, Shamse Tabriz M, Sharma M, Saeed S. Persistence in Staphylococcus aureus bacteremia: incidence, characteristics of patients and outcome. Scand J Infect Dis. 2006;38:7-14.
    1. Klevens RM, Morrison MA, Nadle J, Petit S, Gershman K, Ray S, Harrison LH, Lynfield R, Dumyati G, Townes JM, Craig AS, Zell ER, Fosheim GE, McDougal LK, Carey RB, Fridkin SK. Invasive methicillin-resistant Staphylococcus aureus infections in the United States. JAMA. 2007;298:1763-1771.
    1. Krzyszton-Russjan J, Gniadkowski M, Polowniak-Pracka H, Hagmajer E, Hryniewicz W. The first S. aureus isolates with reduced susceptibility to vancomycin in Poland. J Antimicrob Chemother. 2002;50:1065-1069.
    1. Laurent F, Lelievre H, Cornu M, Vandenesch F, Carret G, Etienne J, Flandrois JP. Fitness and competitive growth advantage of new gentamicin-susceptible MRSA clones spreading in French hospitals. J Antimicrob Chemother. 2001;47:277-283.
    1. Liebowitz LD. MRSA burden and interventions. Int J Antimicrob Agents. 2009;34(Suppl 3):S11-S13.
    1. Limbago B, Fosheim GE, Schoonover V, Crane CE, Nadle J, Petit S, Heltzel D, Ray SM, Harrison LH, Lynfield R, Dumyati G, Townes JM, Schaffner W, Mu Y, Fridkin SK; Active Bacterial Core Surveillance MRSA Investigators. Characterization of methicillin-resistant Staphylococcus aureus isolates collected in 2005 and 2006 from patients with invasive disease: a population-based analysis. J Clin Microbiol. 2009;47:1344-1351.
    1. Linnemann CC Jr, Mason M, Moore P, Korfhagen TR, Staneck JL. Methicillin-resistant Staphylococcus aureus: experience in a general hospital over four years. Am J Epidemiol. 1982;115:941-950.
    1. Lodise TP, McKinnon PS, Swiderski L, Rybak MJ. Outcomes analysis of delayed antibiotic treatment for hospital-acquired Staphylococcus aureus bacteremia. Clin Infect Dis. 2003;36:1418-1423.
    1. Lowy FD. Staphylococcus aureus infections. N Engl J Med. 1998;339:520-532.
    1. Manzur A, Dominguez AM, Pujol M, Gonzalez MP, Limon E, Hornero A, Martin R, Gudiol F, Ariza J. Community-acquired methicillin-resistant Staphylococcus aureus infections: an emerging threat in Spain. Clin Microbiol Infect. 2008;14:377-380.
    1. Manzur A, Vidal M, Pujol M, Cisnal M, Hornero A, Masuet C, Pena C, Gudiol F, Ariza J. Predictive factors of methicillin resistance among patients with Staphylococcus aureus bloodstream infections at hospital admission. J Hosp Infect. 2007;66:41435-41441.
    1. McDougal LK, Steward CD, Killgore GE, Chaitram JM, McAllister SK, Tenover FC. Pulsed-field gel electrophoresis typing of oxacillin-resistant Staphylococcus aureus isolates from the United States: establishing a national database. J Clin Microbiol. 2003;41:5113-5120.
    1. Moise PA, Sakoulas G, Forrest A, Schentag JJ. Vancomycin in vitro bactericidal activity and its relationship to efficacy in clearance of methicillin-resistant Staphylococcus aureus bacteremia. Antimicrob Agents Chemother. 2007;51:2582-2586.
    1. Moise PA, Schentag JJ. Vancomycin treatment failures in Staphylococcus aureus lower respiratory tract infections. Int J Antimicrob Agents. 2000;16:S31-S34.
    1. Noskin GA, Rubin RJ, Schentag JJ. National trends in Staphylococcus aureus infection rates: impact on economic burden and mortality over a 6-year period (1998-2003). Clin Infect Dis. 2007;45:1132-1140.
    1. Oliveira DC, De Lencastre H. Multiplex PCR strategy for rapid identification of structural types and variants of the mec element in methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 2002;46:2155-2161.
    1. Oliveira D, Santos Sanches I, Mato R, Tamayo M, Ribeiro G, Costa D, De Lencastre H. Virtually all methicillin-resistant S. aureus infections in the largest Portuguese teaching hospital are caused by two internationally spread multiresistant stains: the Iberian and the Brazilian clones. Clin Microbiol Infect. 1998;4:373-384.
    1. Oliveira DC, Tomasz A, De Lencastre H. Secrets of success of a human pathogen: molecular evolution of pandemic clones of methicillin-resistant S. aureus. Lancet Infect Dis. 2002;2:180-189.
    1. Pearson A, Chronias A, Murray M. Voluntary and mandatory surveillance for methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) bacteraemia in England. J Antimicrob Chemother. 2009;64:S11-S17.
    1. Perez-Roth E, Lorenzo-Diaz F, Batista N, Moreno A, Mendez-Alvarez S. Tracking methicillin-resistant S. aureus clones during a 5-year period (1998 to 2002) in a Spanish hospital. J Clin Microbiol. 2004;42:4649-4656.
    1. Polgreen PM, Herwaldt LA. Staphylococcus aureus colonization and nosocomial infections: implications for prevention. Curr Infect Dis Rep. 2004;6:435-441.
    1. Prakash V, Lewis JS, Jorgensen JH. Vancomycin MICs for methicillin-resistant Staphylococcus aureus isolates differ based upon the susceptibility test method used. Antimicrob Agents Chemother. 2008;52:4528.
    1. Pujol M, Pena C, Pallares R, Ariza J, Ayats J, Dominguez MA, Gudiol F. Nosocomial Staphylococcus aureus bacteremia among nasal carriers of methicillin-resistant and methicillin-susceptible strains. Am J Med. 1996;100:509-516.
    1. Pujol M, Pena C, Pallares R, Ayats J, Ariza J, Gudiol F. Risk factors for nosocomial bacteremia due to methicillin-resistant Staphylococcus aureus. Eur J Clin Microbiol Infect Dis. 1994;13:96-102.
    1. Roberts RB, Tennenberg AM, Eisner W, Hargrave J, Drusin LM, Yurt R, Kreiswirth BN. Outbreak in a New York City teaching hospital burn center caused by the Iberian epidemic clone of MRSA. Microb Drug Resist. 1998;4:175-183.
    1. Rodriguez-Bano J, Dominguez M, Blas Millan A, Borraz C, Pau Gonzalez M, Almirante B, Cercenado E, Padilla B, Pujol M. Clinical and molecular epidemiology of community-acquired, healthcare-associated and nosocomial methicillin-resistant S. aureus in Spain. Clin Microbiol Infect. 2009;15:1111-1118.
    1. Rodriguez-Bano J, Milan BA, Dominguez MA, Borraz C, Gonzalez MP, Almirante B, Cercenado E, Padilla B, Pujol M. Impact of inappropriate empirical therapy for sepsis due to health care-associated methicillin-resistant Staphylococcus aureus. J Infect. 2009;58:131-137.
    1. Rybak MJ, Leonard SN, Rossi KL, Cheung CM, Sader HS, Jones RN. Characterization of vancomycin-heteroresistant Staphylococcus aureus from the metropolitan area of Detroit, Michigan, over a 22-year period (1986 to 2007). J Clin Microbiol. 2008;46:2950-2954.
    1. Sakoulas G, Moise-Broder PA, Schentag J, Forrest A, Moellering RC Jr, Eliopoulos GM. Relationship of MIC and bactericidal activity to efficacy of vancomycin for treatment of methicillin-resistant Staphylococcus aureus bacteremia. J Clin Microbiol. 2004;42:2398-2402.
    1. Santos Sanches I, Ramirez M, Troni H, Abecassis M, Padua M, Tomasz A, De Lencastre H. Evidence for the geographic spread of a methicillin-resistant S. aureus clone between Portugal and Spain. J Clin Microbiol. 1995;33:1243-1246.
    1. Shurland S, Zhan M, Bradham DD, Roghmann MC. Comparison of mortality risk associated with bacteremia due to methicillin-resistant and methicillin-susceptible Staphylococcus aureus. Infect Control Hosp Epidemiol. 2007;28:273-279.
    1. Soriano A, Marco F, Martinez JA, Pisos E, Almela M, Dimova VP, Alamo D, Ortega M, Lopez J, Mensa J. Influence of vancomycin minimum inhibitory concentration on the treatment of methicillin-resistant Staphylococcus aureus bacteremia. Clin Infect Dis. 2008;46:193-200.
    1. Soriano A, Martinez JA, Mensa J, Marco F, Almela M, Moreno-Martinez A, Sanchez F, Munoz I, Jimenez de Anta MT, Soriano E. Pathogenic significance of methicillin resistance for patients with Staphylococcus aureus bacteremia. Clin Infect Dis. 2000;30:368-373.
    1. Stefani S, Varaldo PE. Epidemiology of methicillin-resistant staphylococci in Europe. Clin Microbiol Infect. 2003;9:1179-1186.
    1. Steinkraus G, White R, Friedrich L. Vancomycin MIC creep in non-vancomycin-intermediate Staphylococcus aureus (VISA), vancomycin-susceptible clinical methicillin-resistant S. aureus (MRSA) blood isolates from 2001-05. J Antimicrob Chemother. 2007;60:788-794.
    1. Tenover FC, Arbeit RD, Goering RV, Mickelsen PA, Murray BE, Persing DH, Swaminathan B. Interpreting chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis: criteria for bacterial strain typing. Clin Microbiol. 1995;33:2233-2239.
    1. Vindel A, Cuevas O, Cercenado E, Marcos C, Bautista V, Castellares C, Trincado P, Boquete T, Perez-Vazquez M, Marin M, Bouza E. Methicillin-resistant Staphylococcus aureus in Spain: molecular epidemiology and utility of different typing methods. J Clin Microbiol. 2009;47:1620-1627.
    1. Vindel A, Trincado P, Gomez E, Cabrera R, Boquete T, Sola C, Valdezate S, Saez-Nieto JA. Prevalence and evolution of methicillin-resistant S. aureus in Spanish hospitals between 1996 and 2002. J Clin Microbiol. 2006;44:266-270.
    1. Wang G, Hindler JF, Ward KW, Bruckner DA. Increased vancomycin MICs for Staphylococcus aureus clinical isolates from a university hospital during a 5-year period. J Clin Microbiol. 2006;44:3883-3886.
    1. Weinsten HJ. The relation between the nasal staphylococcal carriage state and the incidence of post-operative complications. N Engl J Med. 2009;260:1303-1308.
    1. Wenzel RP, Nettleman MD, Jones RN, Pfaller MA. Methicillin-resistant Staphylococcus aureus: implications for the 1990s and effective control measures. Am J Med. 1991;91:S221-S227.

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