Attributable Mortality due to Nosocomial Infections

Summary

Objectives: Nosocomial infections constitute a major medical problem leading to increased morbidity and mortality of patients. Besides prolongation of length of hospital stay, hospital mortality attributable to those infections is often the quantity of interest when describing their impact and consequences. Since occurrence of nosocomial infections is a time-dynamic process, estimation of this quantity might be hampered by that fact. A general frameworkshall be developed for defining and estimating attributable mortality that in addition is taking discharge of patients as competing risk and potential censoring of observation time into account.

Methods: Since the term “attributable mortality” is used in a variety of meanings we first review basic definitions; the quantities of interest are then derived in terms of transition probabilities arising in a suitably defined multistate model that allows straightforward estimation and interpretation. Bootstrap resampling is used to calculate corresponding standard errors and confidence intervals.

Results: The methodology is applied to the data of the SIR-3 study, a prospective cohort study on the incidence of nosocomial infections in intensive care unit patients. Occurrence of nosocomial pneumonia is shown to be associated with increased mortality; the population-attributable fraction is estimated as 7.7% (95% confidence interval: 2.6-12.8%) for an observation period of 120 days.

Conclusion: Attributable mortality is an important risk measure in epidemiology. If risk exposure is time-dependent, multistate models provide an easily understandable framework to define and estimate attributable mortality. The approach is capable of handling competing events, which are omnipresent in clinical research and censoring.

Keywords

Attributable mortality - population-attributable fraction - time-to-event data - competing risks - multistate model - nosocomial infections

• References

• 1 Gastmeier P, Kampf G, Wischnewski N, Hauer T, Schulgen G, Schumacher M, Daschner F, Rüden H. Prevalence of nosocomial infections in representative German hospitals. J Hosp Infec 1998; 38: 37-49.
• 2 Rücker G, Schoop R, Beyersmann J, Schumacher M, Zuschneid I. Are KISS data representative of German intensive care units? – Statistical issues. Methods Inf Med 2006; 45: 424-429.
• 3 Gastmeier P, Geifers C, Sohr D, Dettenkofer M, Daschner F, Rüden H. Five years working with the German nosocomial infection surveillance system. Am J Infect Control 2003; 31: 316-321.
• 4 Zuschneid I, Geffers C, Sohr D, Kohlhase C, Schumacher M, Rüden H, Gastmeier P. Validation of surveillance in the intensive care unit component of the German Nosocomial Infections Surveillance System. Infect Control Hosp Epidemiol 2007; 28: 496-499.
• 5 Brossette SE, Sprague AP, Jones WT, Moser SA. A data mining system for infection control surveillance. Methods Inf Med 2000; 39: 303-310.
• 6 Girou E, Brun-Buisson C. Morbidity, mortality and the cost of nosocomial infections in critical care. Curr Opin Crit Care 1996; 2: 347-351.
• 7 Leu HS, Kaiser L, Mori M, Woolson RF, Wenzel RP. Hospital acquired pneumonia – attributable mortality and morbidity. Am J Epidemiol 1989; 129: 1258-1267.
• 8 Craig CP, Connelly S. Effect of intensive care unit nosocomial pneumonia on duration of stay and mortality. AmJInfect Control 1984; 12: 233-238.
• 9 Gefeller O. Definitions of attributable risk-revisited. Pub Health Rev 1995; 23: 343-355.
• 10 Pittet D, Tarara D, Wenzel RP. Nosocomial bloodstream infection in critically ill patients: Excess length of stay, extra costs, and attributable mortality. JAMA 1994; 271: 1598-1601.
• 11 Garcia-Martin M. et al. Proportion of hospital deaths potentially attributable to nosocomial infection. Infect Control Hosp Epidemiol 2001; 22: 708-714.
• 12 Hougaard Ε Analysis of multivariate survival data.. New York: Springer; 2000
• 13 Wangler M, Beyersmann J, Schumacher M. changeLOS: An R-package for change in length of hospital stay based on the Aalen-Johansen estimator. R News 2006; 6: 31-35.
• 14 Datta S, Satten GA. Validity of the Aalen-Johansen estimators of stage occupation probabilities and Nelson-Aalen estimators of integrated transition hazards for non-Markov models. Stat Probabil Lett 2001; 55: 403-411.
• 15 Glidden D. Robust inference for event probabilities with non-Markov data. Biometrics 2002; 58: 361-368.
• 16 Benichou J. A review of adjusted estimators of attributable risk. Stat Methods Med Res 2001; 10: 195-216.
• 17 Grundmann H, Bärwolff S, Tami A, Behnke M, Schwab F, Geffers C, Halle E, Göbel UB, Schiller R, Jonas D, Klare I, Weist K, Witte W, BeckBeilecke K, Schumacher M, Rüden H, Gastmeier P. How many infections are caused by patient-to-patient transmission in intensive care units?. Crit Care Med 2005; 33: 946-951.
• 18 Beyersmann J, Gastmeier P, Grundmann H, Bärwolff S, Geffers C, Behnke M, Rüden H, Schumacher M. Use of multistate models to assess prolongation of intensive care unit stay due to nosocomial infection. Infect Control Hosp Epidemiol 2006; 24: 493-499.
• 19 Garner JS, Emori WR, Horan TC, Hughes JM. CDC definitions for nosocomial infections. Am J Infect Control 1988; 16: 128-140.
• 20 Horan TC, Gaynes RP, Marone WF, Jarvis WR, Emori TG. CDC definitions of surgical site infections. A modification of CDC definitions of surgical wound infections. Infect Control Hosp Epidemiol 1992; 13: 606-608.
• 21 Fagon JY, Chastre J, Hance AJ, Montravers P, Novara A, Gilbert C. Nosocomial pneumonia in ventilated patients: a cohort study evaluating attributable mortality and hospital stay. Am J Med 1993; 94: 281-288.
• 22 Papazian L, Bregeon F, Thirion X. et al. Effect of ventilator-associated pneumonia on mortality and morbidity. Am J Respir Crit Care Med 1996; 154: 91-97.
• 23 Le Gall JR, Lemeshow S, Saulnier F. A new simplified acute physiology score (SAPS II) based on a European/North American multicenter study. J Am Medic Assoc 1993; 270: 2957-2963.
• 24 Escolano S, Golmard JL, Kormek AM, Mallet A. A multi-state model for evolution of intensive care unit patients: prediction of nosocomial infections and deaths. Stat Med 2000; 19: 3465-3482.
• 25 Chen YQ, Hu C, Wang Y. Attributable risk function in the proportional hazards model for censored time-to-event. Biostatistics 2006; 7: 515-529.
• 26 Land M, Vogel C, Gefeller O. Partitioning methods for multifactorial risk attribuation. Stat Methods Med Res 2001; 10: 217-230.
• 27 Rabe C, Gefeller O. The attributable risk in a multifactorial situation. Methods Inf Med 2006; 4: 404-408.
• 28 Andersen PK, Klein JP, Rosthøj S. Generalised linear models for correlated pseudo-observations, with applications to multi-state models. Biometrika 2003; 90: 15-27.