Purpose The clinical implications for patients who survive serious infections are not well understood. It has been hypothesized that the excess mortality for survivors of sepsis observed in epidemiological studies is due to increased vulnerability to subsequent infections. We undertook this study to identify characteristics of patients who are at high risk for death after surviving a common type of blood-stream infection. Materials and Methods At a single academic medical center, 237 patients with Staphylococcus aureus bacteremia admitted during a three-year period were retrospectively identified. The primary outcomes were 30-day and 31 to 90-day mortality after the first positive blood culture. The primary predictor variable of interest was clinical immune dysfunction prior to bacteremia. Results The 30-day mortality was not significantly different for patients with and without prior immune dysfunction. However, during days 31 to 90, 11 patients (20%) with prior immune dysfunction compared to 10 patients (8.6%) without prior immune dysfunction died (OR 2.59, 95% CI 1.03–6.53, p = 0.04). In a Cox-proportional hazard model controlling for age, there was a significant association between prior immune dysfunction and greater 31 to 90 day mortality (HR 2.44, 95% CI 1.01–5.90, p = 0.05) and a non-significant trend towards occurrence of subsequent infections and greater 31 to 90 day mortality (HR 2.12, 95% CI 0.89–5.07, p = 0.09). Conclusions Patients with prior immune dysfunction are at high risk for death 31 to 90 days, but not <30 days, after S. aureus bacteremia. Further investigation is needed to determine if this finding is due to poor prognosis of chronic disease or increased vulnerability to subsequent infections.
References
[1]
Martin GS, Mannino DM, Eaton S, Moss M (2003) The epidemiology of sepsis in the United States from 1979 through 2000. N? Engl? J? Med 348: 1546–1554. doi: 10.1056/nejmoa022139
[2]
Boomer JS, To K, Chang KC, Takasu O, Osborne DF, et al. (2011) Immunosuppression in patients who die of sepsis and multiple organ failure. JAMA 306: 2594–2605. doi: 10.1001/jama.2011.1829
[3]
Leentjens J, Kox M, van der Hoeven J, Netea MG, Pickkers P (2013) Immunotherapy for the Adjunctive Treatment of Sepsis: From Immunosuppression to Immunostimulation. Time for a Paradigm Change? Am? J? Respir Crit Care Med.
[4]
Winters BD, Eberlein M, Leung J, Needham DM, Pronovost PJ, et al. (2010) Long-term mortality and quality of life in sepsis: a systematic review. Crit Care Med 38: 1276–1283. doi: 10.1097/ccm.0b013e3181d8cc1d
[5]
Fox AC, Robertson CM, Belt B, Clark AT, Chang KC, et al. (2010) Cancer causes increased mortality and is associated with altered apoptosis in murine sepsis. Crit Care Med 38: 886–893. doi: 10.1097/ccm.0b013e3181c8fdb1
[6]
Kieslichova E, Rocen M, Merta D, Kudla M, Splichal I, et al. (2013) The effect of immunosuppression on manifestations of sepsis in an animal model of cecal ligation and puncture. Transplant Proc 45: 770–777. doi: 10.1016/j.transproceed.2012.07.159
[7]
Tavares E, Maldonado R, Ojeda ML, Minano FJ (2005) Circulating inflammatory mediators during start of fever in differential diagnosis of gram-negative and gram-positive infections in leukopenic rats. Clin Diagn Lab Immunol 12: 1085–1093. doi: 10.1128/cdli.12.9.1085-1093.2005
[8]
Azoulay E, Alberti C, Legendre I, Buisson CB, Le GallJR (2005) Post-ICU mortality in critically ill infected patients: an international study. Intensive Care Med 31: 56–63. doi: 10.1007/s00134-004-2484-1
[9]
Dimopoulos G, Karabinis A, Samonis G, Falagas ME (2007) Candidemia in immunocompromised and immunocompetent critically ill patients: a prospective comparative study. Eur? J? Clin Microbiol Infect Dis 26: 377–384. doi: 10.1007/s10096-007-0316-2
[10]
Lefort A, Panhard X, Clermont O, Woerther PL, Branger C, et al. (2011) Host factors and portal of entry outweigh bacterial determinants to predict the severity of Escherichia coli bacteremia. J? Clin Microbiol 49: 777–783. doi: 10.1128/jcm.01902-10
[11]
Nseir S, Di Pompeo C, Diarra M, Brisson H, Tissier S, et al. (2007) Relationship between immunosuppression and intensive care unit-acquired multidrug-resistant bacteria: a case-control study. Crit Care Med 35: 1318–1323. doi: 10.1097/01.ccm.0000261885.50604.20
[12]
Poutsiaka DD, Davidson LE, Kahn KL, Bates DW, Snydman DR, et al. (2009) Risk factors for death after sepsis in patients immunosuppressed before the onset of sepsis. Scand? J? Infect Dis 41: 469–479. doi: 10.1080/00365540902962756
[13]
Rubin LG, Levin MJ, Ljungman P, Davies EG, Avery R, et al.. (2013) 2013 IDSA Clinical Practice Guideline for Vaccination of the Immunocompromised Host. Clin Infect Dis.
[14]
Shorr AF, Tabak YP, Killian AD, Gupta V, Liu LZ, et al. (2006) Healthcare-associated bloodstream infection: A distinct entity? Insights from a large U.S. database. Crit Care Med 34: 2588–2595. doi: 10.1097/01.ccm.0000239121.09533.09
[15]
Kaech C, Elzi L, Sendi P, Frei R, Laifer G, et al. (2006) Course and outcome of Staphylococcus aureus bacteraemia: a retrospective analysis of 308 episodes in a Swiss tertiary-care centre. Clin Microbiol Infect 12: 345–352. doi: 10.1111/j.1469-0691.2005.01359.x
[16]
van Hal SJ, Jensen SO, Vaska VL, Espedido BA, Paterson DL, et al. (2012) Predictors of mortality in Staphylococcus aureus Bacteremia. Clin Microbiol Rev 25: 362–386. doi: 10.1128/cmr.05022-11
[17]
Kollef MH, Napolitano LM, Solomkin JS, Wunderink RG, Bae IG, et al. (2008) Health care-associated infection (HAI): a critical appraisal of the emerging threat-proceedings of the HAI Summit. Clin Infect Dis 47 Suppl 2: S55–99; quiz S100–101.
[18]
Li JS, Sexton DJ, Mick N, Nettles R, Fowler VG Jr, et al. (2000) Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis 30: 633–638. doi: 10.1086/313753
[19]
Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, et al. (1996) The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med 22: 707–710. doi: 10.1007/bf01709751
[20]
Horan TC, Andrus M, Dudeck MA (2008) CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am? J? Infect Control 36: 309–332. doi: 10.1016/j.ajic.2008.03.002
[21]
Ascioglu S, Rex JH, de Pauw B, Bennett JE, Bille J, et al. (2002) Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus. Clin Infect Dis 34: 7–14. doi: 10.1086/323335
[22]
Hill PC, Birch M, Chambers S, Drinkovic D, Ellis-Pegler RB, et al. (2001) Prospective study of 424 cases of Staphylococcus aureus bacteraemia: determination of factors affecting incidence and mortality. Intern Med? J 31: 97–103. doi: 10.1046/j.1445-5994.2001.00029.x
[23]
Fatkenheuer G, Preuss M, Salzberger B, Schmeisser N, Cornely OA, et al. (2004) Long-term outcome and quality of care of patients with Staphylococcus aureus bacteremia. Eur? J? Clin Microbiol Infect Dis 23: 157–162. doi: 10.1007/s10096-003-1083-3
[24]
Kang CI, Song JH, Ko KS, Chung DR, Peck KR (2011) Clinical features and outcome of Staphylococcus aureus infection in elderly versus younger adult patients. Int? J? Infect Dis 15: e58–62. doi: 10.1016/j.ijid.2010.09.012
[25]
Tacconelli E, Pop-Vicas AE, D'Agata EM (2006) Increased mortality among elderly patients with meticillin-resistant Staphylococcus aureus bacteraemia. J? Hosp Infect 64: 251–256. doi: 10.1016/j.jhin.2006.07.001
[26]
Chong YP, Park SJ, Kim HS, Kim ES, Kim MN, et al. (2013) Persistent Staphylococcus aureus bacteremia: a prospective analysis of risk factors, outcomes, and microbiologic and genotypic characteristics of isolates. Medicine (Baltimore) 92: 98–108. doi: 10.1097/md.0b013e318289ff1e
[27]
Lin SH, Liao WH, Lai CC, Liao CH, Tan CK, et al. (2010) Risk factors for mortality in patients with persistent methicillin-resistant Staphylococcus aureus bacteraemia in a tertiary care hospital in Taiwan. J? Antimicrob Chemother 65: 1792–1798. doi: 10.1093/jac/dkq188
[28]
Mylotte JM, Tayara A (2000) Staphylococcus aureus bacteremia: predictors of 30-day mortality in a large cohort. Clin Infect Dis 31: 1170–1174. doi: 10.1086/317421
[29]
Yzerman EP, Boelens HA, Tjhie JH, Kluytmans JA, Mouton JW, et al. (1996) Delta APACHE II for predicting course and outcome of nosocomial Staphylococcus aureus bacteremia and its relation to host defense. J? Infect Dis 173: 914–919. doi: 10.1093/infdis/173.4.914
[30]
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. doi: 10.1086/514686
[31]
Jenkins TC, Price CS, Sabel AL, Mehler PS, Burman WJ (2008) Impact of routine infectious diseases service consultation on the evaluation, management, and outcomes of Staphylococcus aureus bacteremia. Clin Infect Dis 46: 1000–1008. doi: 10.1086/529190
[32]
Lesens O, Methlin C, Hansmann Y, Remy V, Martinot M, et al. (2003) Role of comorbidity in mortality related to Staphylococcus aureus bacteremia: a prospective study using the Charlson weighted index of comorbidity. Infect Control Hosp Epidemiol 24: 890–896. doi: 10.1086/502156
[33]
Rose WE, Eickhoff JC, Shukla SK, Pantrangi M, Rooijakkers S, et al. (2012) Elevated serum interleukin-10 at time of hospital admission is predictive of mortality in patients with Staphylococcus aureus bacteremia. J? Infect Dis 206: 1604–1611. doi: 10.1093/infdis/jis552
[34]
Monneret G, Finck ME, Venet F, Debard AL, Bohe J, et al. (2004) The anti-inflammatory response dominates after septic shock: association of low monocyte HLA-DR expression and high interleukin-10 concentration. Immunol Lett 95: 193–198. doi: 10.1016/j.imlet.2004.07.009
[35]
Chen MJ, Tseng HM, Huang YL, Hsu WN, Yeh KW, et al. (2008) Long-term outcome and short-term survival of patients with systemic lupus erythematosus after bacteraemia episodes: 6-yr follow-up. Rheumatology (Oxford) 47: 1352–1357. doi: 10.1093/rheumatology/ken196
[36]
Norgaard M, Larsson H, Pedersen G, Schonheyder HC, Sorensen HT (2006) Risk of bacteraemia and mortality in patients with haematological malignancies. Clin Microbiol Infect 12: 217–223. doi: 10.1111/j.1469-0691.2005.01298.x