Clinical and economic consequences of hospital-acquired resistant and multidrug-resistant Pseudomonas aeruginosa infections: a systematic review and meta-analysis.
BACKGROUND
Increasing rates of resistant and multidrug-resistant (MDR) P. aeruginosa in hospitalized patients constitute a major public health threat. We present a systematic review of the clinical and economic impact of this resistant pathogen.


METHODS
Studies indexed in MEDLINE and Cochrane databases between January 2000-February 2013, and reported all-cause mortality, length of stay, hospital costs, readmission, or recurrence in at least 20 hospitalized patients with laboratory confirmed resistant P. aeruginosa infection were included. We accepted individual study definitions of MDR, and assessed study methodological quality.


RESULTS
The most common definition of MDR was resistance to more than one agent in three or more categories of antibiotics. Twenty-three studies (7,881 patients with susceptible P. aeruginosa, 1,653 with resistant P. aeruginosa, 559 with MDR P. aeruginosa, 387 non-infected patients without P. aeruginosa) were analyzed. A random effects model meta-analysis was feasible for the endpoint of all-cause in-hospital mortality. All-cause mortality was 34% (95% confidence interval (CI) 27% - 41%) in patients with any resistant P. aeruginosa compared to 22% (95% CI 14% - 29%) with susceptible P. aeruginosa. The meta-analysis demonstrated a > 2-fold increased risk of mortality with MDR P. aeruginosa (relative risk (RR) 2.34, 95% CI 1.53 - 3.57) and a 24% increased risk with resistant P. aeruginosa (RR 1.24, 95% CI 1.11 - 1.38), compared to susceptible P. aeruginosa. An adjusted meta-analysis of data from seven studies demonstrated a statistically non-significant increased risk of mortality in patients with any resistant P. aeruginosa (adjusted RR 1.24, 95% CI 0.98 - 1.57). All three studies that reported infection-related mortality found a statistically significantly increased risk in patients with MDR P. aeruginosa compared to those with susceptible P. aeruginosa. Across studies, hospital length of stay (LOS) was higher in patients with resistant and MDR P. aeruginosa infections, compared to susceptible P. aeruginosa and control patients. Limitations included heterogeneity in MDR definition, restriction to nosocomial infections, and potential confounding in analyses.


CONCLUSIONS
Hospitalized patients with resistant and MDR P. aeruginosa infections appear to have increased all-cause mortality and LOS. The negative clinical and economic impact of these pathogens warrants in-depth evaluation of optimal infection prevention and stewardship strategies.
Ninewells Hospital and Medical School, Dundee, Scotland DD19SY UK.
Dilip
D
Nathwani
Tufts Medical Center for Evidence Synthesis, Institute for Clinical Research and Health Policy Studies, 800 Washington Street, Box 63, Boston, MA 02111 USA.
Gowri
G
Raman
GfK Market Access, LLC, 21 Cochituate Rd, Wayland, MA 01778 USA.
Katherine
K
Sulham
GfK Market Access, LLC, 21 Cochituate Rd, Wayland, MA 01778 USA.
Meghan
M
Gavaghan
Cubist Pharmaceuticals, 65 Hayden Ave, Lexington, MA 02421 USA.
Vandana
V
Menon
All-cause mortality; Pseudomonas aeruginosa; Resistance