Healthcare-Acquired Infections Linked to Increased ICU Mortality

Laurie Barclay, MD

December 03, 2010

December 3, 2010 — Healthcare-acquired infections greatly increase the risk for mortality in patients admitted to the intensive care unit, but antimicrobial resistance has little additional effect, according to the results of a prospective cohort study reported online December 1 in Lancet Infectious Diseases.

"Patients admitted to intensive-care units are at high risk of health-care-associated infections, and many are caused by antimicrobial-resistant pathogens," write Marie-Laurence Lambert, MD, from the Healthcare-associated Infections Unit, Public Health and Surveillance Department, Scientific Institute for Public Health in Brussels, Belgium, and colleagues. "We aimed to assess excess mortality and length of stay in intensive-care units from bloodstream infections and pneumonia."

The investigators analyzed data from intensive care units reporting healthcare-associated infections with the most frequent causative microorganisms based on the European standard protocol for surveillance. They assessed 20 different exposures according to infection site, microorganism, and resistance to ceftazidime (Acinetobacter baumannii or Pseudomonas aeruginosa), third-generation cephalosporins (Escherichia coli), and oxacillin (Staphylococcus aureus).

With use of time-dependent regression modeling, outcomes for every exposure were compared for exposed and unexposed patients, after adjustment for patient factors and time-dependency of the exposure. The study cohort consisted of 119,699 patients admitted between January 1, 2005, and December 31, 2008, for more than 2 days to 537 intensive care units in 10 countries.

In the fully adjusted model, the hazard ratio (HR) for death from pneumonia ranged from 1.7 (95% confidence interval [CI], 1.4 - 1.9) for drug-sensitive S aureus to 3.5 (95% CI, 2.9 - 4.2) for drug-resistant P aeruginosa. For bloodstream infections, the excess risk ranged from 2.1 for drug-sensitive S aureus (95% CI, 1.6 - 2.6) to 4.0 for drug-resistant P aeruginosa (95% CI, 2.7 - 5.8).

Risk for death from antimicrobial resistance, in addition to risk for death because of the infection, was 1.2 (95% CI, 1.1 - 1.4) for pneumonia for a combination of all 4 bacterial species studied and 1.2 (95% CI, 0.9 - 1.5) for bloodstream infections. Excess risk for microorganisms was highest for S aureus (1.3 for pneumonia [95% CI, 1.0 - 1.6] and 1.6 for bloodstream infections [95% CI, 1.1 - 2.3]). Antimicrobial resistance was not associated with increased length of stay.

For all 4 combined drug-sensitive vs drug-resistant bacterial species, the HR for discharge, dead or alive, was 1.05 for pneumonia (95% CI, 0.97 - 1.13) and 1.02 for bloodstream infections (95% CI, 0.98 - 1.17). Because of the high prevalence of P aeruginosa and the pathogenicity of both its drug-sensitive and drug-resistant strains, this microorganism was associated with the highest burden of healthcare-acquired infections.

"Health-care-associated bloodstream infections and pneumonia greatly increase mortality and pneumonia increase length of stay in intensive-care units; the additional effect of the most common antimicrobial resistance patterns is comparatively low," the study authors write. "Prevention of health-care-related infections needs to be reasserted and emphasised as an absolute priority."

Limitations of this study include lack of follow-up beyond intensive care, estimates of the excess length of stay not fully adjusted for confounders other than time, and limitations of the statistical methods used.

In an accompanying comment, Jean-Louis Vincent, from Erasme University Hospital in Brussels, Belgium, warns that the findings of this study regarding microbial resistance should not discourage attempts to control multidrug-resistant bacteria.

"MRBs [multidrug-resistant bacteria] continue to be a threat, and one that will probably become more prevalent in the future," Dr. Vincent writes. "Present antibiotics have restricted effectiveness against resistant infections, and there are few new products in the development pipeline. We urgently need new antibiotics to be able to appropriately manage patients with such infections."

The European Commission (DG Sanco) supported this study. Some of the study authors have disclosed various financial relationships with Baxter, Pfizer, AstraZeneca, Johnson and Johnson, 3M, Nestlé, Novo Nordisk, Fresenius, and/or BBraun. Dr. Vincent has disclosed no relevant financial relationships.

Lancet Infect Dis. Published online December 1, 2010.