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PLOS ONE  2009 

Factors Predicting and Reducing Mortality in Patients with Invasive Staphylococcus aureus Disease in a Developing Country

DOI: 10.1371/journal.pone.0006512

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Background Invasive Staphylococcus aureus infection is increasingly recognised as an important cause of serious sepsis across the developing world, with mortality rates higher than those in the developed world. The factors determining mortality in developing countries have not been identified. Methods A prospective, observational study of invasive S. aureus disease was conducted at a provincial hospital in northeast Thailand over a 1-year period. All-cause and S. aureus-attributable mortality rates were determined, and the relationship was assessed between death and patient characteristics, clinical presentations, antibiotic therapy and resistance, drainage of pus and carriage of genes encoding Panton-Valentine Leukocidin (PVL). Principal Findings A total of 270 patients with invasive S. aureus infection were recruited. The range of clinical manifestations was broad and comparable to that described in developed countries. All-cause and S. aureus-attributable mortality rates were 26% and 20%, respectively. Early antibiotic therapy and drainage of pus were associated with a survival advantage (both p<0.001) on univariate analysis. Patients infected by a PVL gene-positive isolate (122/248 tested, 49%) had a strong survival advantage compared with patients infected by a PVL gene-negative isolate (all-cause mortality 11% versus 39% respectively, p<0.001). Multiple logistic regression analysis using all variables significant on univariate analysis revealed that age, underlying cardiac disease and respiratory infection were risk factors for all-cause and S. aureus-attributable mortality, while one or more abscesses as the presenting clinical feature and procedures for infectious source control were associated with survival. Conclusions Drainage of pus and timely antibiotic therapy are key to the successful management of S. aureus infection in the developing world. Defining the presence of genes encoding PVL provides no practical bedside information and draws attention away from identifying verified clinical risk factors and those interventions that save lives.


[1]  Nickerson EK, Wuthiekanun V, Day NP, Chaowagul W, Peacock SJ (2006) Meticillin-resistant Staphylococcus aureus in rural Asia. Lancet Infect Dis 6: 70–71.
[2]  Nickerson EK, West TE, Day NP, Peacock SJ (2009) Staphylococcus aureus disease and drug resistance in resource-limited countries in south and east Asia. Lancet Infect Dis 9: 130–135.
[3]  Nickerson EK, Hongsuwan M, Limmathurotsakul D, Wuthiekanun V, Shah KR, et al. (2009) Staphylococcus aureus bacteraemia in a tropical setting: patient outcome and impact of antibiotic resistance. PLoS ONE 4: e4308.
[4]  Benfield T, Espersen F, Frimodt-Moller N, Jensen AG, Larsen AR, et al. (2007) Increasing incidence but decreasing in-hospital mortality of adult Staphylococcus aureus bacteraemia between 1981 and 2000. Clin Microbiol Infect 13: 257–263.
[5]  Das I, O'Connell N, Lambert P (2007) Epidemiology, clinical and laboratory characteristics of Staphylococcus aureus bacteraemia in a university hospital in UK. J Hosp Infect 65: 117–123.
[6]  McClelland RS, Fowler VG Jr, Sanders LL, Gottlieb G, Kong LK, et al. (1999) Staphylococcus aureus bacteremia among elderly vs younger adult patients: comparison of clinical features and mortality. Arch Intern Med 159: 1244–1247.
[7]  Fowler VG Jr, Olsen MK, Corey GR, Woods CW, Cabell CH, et al. (2003) Clinical identifiers of complicated Staphylococcus aureus bacteremia. Arch Intern Med 163: 2066–2072.
[8]  Jensen AG, Wachmann CH, Espersen F, Scheibel J, Skinhoj P, et al. (2002) Treatment and outcome of Staphylococcus aureus bacteremia: a prospective study of 278 cases. Arch Intern Med 162: 25–32.
[9]  Topeli A, Unal S, Akalin HE (2000) Risk factors influencing clinical outcome in Staphylococcus aureus bacteraemia in a Turkish University Hospital. Int J Antimicrob Agents 14: 57–63.
[10]  Cosgrove SE, Sakoulas G, Perencevich EN, Schwaber MJ, Karchmer AW, et al. (2003) Comparison of mortality associated with methicillin-resistant and methicillin-susceptible Staphylococcus aureus bacteremia: a meta-analysis. Clin Infect Dis 36: 53–59.
[11]  Lautenschlager S, Herzog C, Zimmerli W (1993) Course and outcome of bacteremia due to Staphylococcus aureus: evaluation of different clinical case definitions. Clin Infect Dis 16: 567–573.
[12]  Fowler VG Jr, Sanders LL, Sexton DJ, Kong L, Marr KA, et al. (1998) Outcome of Staphylococcus aureus bacteremia according to compliance with recommendations of infectious diseases specialists: experience with 244 patients. Clin Infect Dis 27: 478–486.
[13]  Lodise TP, McKinnon PS, Swiderski L, Rybak MJ (2003) Outcomes analysis of delayed antibiotic treatment for hospital-acquired Staphylococcus aureus bacteremia. Clin Infect Dis 36: 1418–1423.
[14]  Wilson R, Hamburger M (1957) Fifteen years' experience with staphylococcus septicemia in a large city hospital; analysis of fifty-five cases in the Cincinnati General Hospital 1940 to 1954. Am J Med 22: 437–457.
[15]  Korownyk C, Allan GM (2007) Evidence-based approach to abscess management. Can Fam Physician 53: 1680–1684.
[16]  Holmes A, Ganner M, McGuane S, Pitt TL, Cookson BD, et al. (2005) Staphylococcus aureus isolates carrying Panton-Valentine leucocidin genes in England and Wales: frequency, characterization, and association with clinical disease. J Clin Microbiol 43: 2384–2390.
[17]  Cribier B, Prevost G, Couppie P, Finck-Barbancon V, Grosshans E, et al. (1992) Staphylococcus aureus leukocidin: a new virulence factor in cutaneous infections? An epidemiological and experimental study. Dermatology 185: 175–180.
[18]  Lina G, Piemont Y, Godail-Gamot F, Bes M, Peter MO, et al. (1999) Involvement of Panton-Valentine leukocidin-producing Staphylococcus aureus in primary skin infections and pneumonia. Clin Infect Dis 29: 1128–1132.
[19]  Gillet Y, Issartel B, Vanhems P, Fournet JC, Lina G, et al. (2002) Association between Staphylococcus aureus strains carrying gene for Panton-Valentine leukocidin and highly lethal necrotising pneumonia in young immunocompetent patients. Lancet 359: 753–759.
[20]  Tristan A, Ferry T, Durand G, Dauwalder O, Bes M, et al. (2007) Virulence determinants in community and hospital meticillin-resistant Staphylococcus aureus. J Hosp Infect 65: Suppl 2105–109.
[21]  Vandenesch F, Naimi T, Enright MC, Lina G, Nimmo GR, et al. (2003) Community-acquired methicillin-resistant Staphylococcus aureus carrying Panton-Valentine leukocidin genes: worldwide emergence. Emerg Infect Dis 9: 978–984.
[22]  Tang YW, Kilic A, Yang Q, McAllister SK, Li H, et al. (2007) StaphPlex system for rapid and simultaneous identification of antibiotic resistance determinants and Panton-Valentine leukocidin detection of staphylococci from positive blood cultures. J Clin Microbiol 45: 1867–1873.
[23]  Renwick L, Hardie A, Girvan EK, Smith M, Leadbetter G, et al. (2008) Detection of meticillin-resistant Staphylococcus aureus and Panton-Valentine leukocidin directly from clinical samples and the development of a multiplex assay using real-time polymerase chain reaction. Eur J Clin Microbiol Infect Dis 27: 791–796.
[24]  NCCLS (2004) National Committee for Clinical Laboratory Standards. Performance Standards for Antimicrobial Susceptibility Testing; Fourteenth Informational Supplement (M100-S14). 24: 40–47.
[25]  Kondo Y, Ito T, Ma XX, Watanabe S, Kreiswirth BN, et al. (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: 264–274.
[26]  Zhang K, Sparling J, Chow BL, Elsayed S, Hussain Z, et al. (2004) New quadriplex PCR assay for detection of methicillin and mupirocin resistance and simultaneous discrimination of Staphylococcus aureus from coagulase-negative staphylococci. J Clin Microbiol 42: 4947–4955.
[27]  Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, et al. (2006) Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 34: 1589–1596.
[28]  Neela V, Ehsanollah GR, Zamberi S, Van Belkum A, Mariana NS (2008) Prevalence of Panton-Valentine leukocidin genes among carriage and invasive Staphylococcus aureus isolates in Malaysia. Int J Infect Dis.
[29]  Afroz S, Kobayashi N, Nagashima S, Alam MM, Hossain AB, et al. (2008) Genetic characterization of Staphylococcus aureus isolates carrying Panton-Valentine leukocidin genes in Bangladesh. Jpn J Infect Dis 61: 393–396.
[30]  Melles DC, van Leeuwen WB, Boelens HA, Peeters JK, Verbrugh HA, et al. (2006) Panton-Valentine leukocidin genes in Staphylococcus aureus. Emerg Infect Dis 12: 1174–1175.
[31]  Prevost G, Couppie P, Prevost P, Gayet S, Petiau P, et al. (1995) Epidemiological data on Staphylococcus aureus strains producing synergohymenotropic toxins. J Med Microbiol 42: 237–245.
[32]  Gillet Y, Vanhems P, Lina G, Bes M, Vandenesch F, et al. (2007) Factors predicting mortality in necrotizing community-acquired pneumonia caused by Staphylococcus aureus containing Panton-Valentine leukocidin. Clin Infect Dis 45: 315–321.


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