Nosocomial Infections Due to Multidrug-Resistant Pseudomonas Aeruginosa: Epidemiology and Treatment Options

Marilee D. Obritsch, PharmD; Douglas N. Fish, PharmD, FCCM; Robert MacLaren, PharmD; Rose Jung, PharmD

Disclosures

Pharmacotherapy. 2005;25(10):1353-1364. 

In This Article

Risk Factors for Colonization or Infection with Multidrug-Resistant Pseudomonas aeruginosa

Evaluation of risk factors for colonization or infection with MDRPA has been limited to small retrospective case-control studies. The populations reported to be most vulnerable to MDRPA infections include patients with immunocompromised states, protracted hospital stay, prolonged antimicrobial use, and mechanical ventilation.[8,9,22] In a retrospective case-control study of 45 patients, a multivariate analysis reported that length of hospitalization (p=0.03) and number of antimicrobial agents (p=0.006) were associated with nosocomial infections caused by MDRPA.[9] A retrospective case analysis of 12 patients identified that higher doses of antimicrobials (both antipseudomonal and nonantipseudomonal) were prescribed for a longer duration of therapy before recovery of MDRPA compared with susceptible P. aeruginosa.[22]

Additional retrospective studies have identified specific antimicrobials as potential risk factors in the development of MDRPA infections. A study of 51 patients with MDRPA bacteremia reported advanced age (odds ratio [OR] 1.07), human immunodeficiency virus infection (OR 3.94), intravenous drug abuse (OR 13.15), and previous fluoroquinolone therapy (OR 3.21) as independent risk factors.[8] In a case-control study of 68 patients with nosocomial infections, multivariate analysis identified duration of ciprofloxacin therapy to be a significant risk factor (OR 11.0) for infection or colonization with MDRPA, whereas a trend toward significance with duration of imipenem therapy (OR 3.17, 95% confidence interval 0.92-10.9) was noted.[23] Results of multiple logistic regression analysis of a case-control study involving 132 patients indicated exposure to imipenem or meropenem within 15 days before isolation of P. aeruginosa (OR 44.8) and duration of mechanical ventilation more than 48 hours (OR 8.2) to be risk factors for development of nosocomial infections due to MDRPA.[24] Because of the small samples and retrospective nature of these studies, attributing MDRPA infections to only one agent or one class of antimicrobials is not reasonable. Large, multicenter, prospective studies are need to determine the factors that increase the risk of MDRPA infections.

Emergence of resistance has been reported to occur during treatment of initially susceptible infections. In a study of 22 patients with MDRPA infection, 16 patients (73%) had a previously susceptible P. aeruginosa isolate before the MDRPA culture.[2] In a small case-control study, 27% (10/37) of patients with a fully susceptible P. aeruginosa isolate developed MDRPA, whereas 38% (14/37) of patients with strains initially resistant to one to three antimicrobials developed MDRPA during the study.[23]

Morbidity and mortality information in patients infected with MDRPA is limited, but available data show a significantly higher burden of MDRPA infections compared with more susceptible P. aeruginosa infections. In a retrospective study, MDRPA infections were associated with a mean hospitalization cost of $54,081 compared with a mean cost of $22,116 for patients with susceptible P. aeruginosa infections.[2] A separate study reported an overall mortality rate of 67% in patients with MDRPA bacteremia compared with 23% in those with susceptible P. aeruginosa bacteremia (OR 15.1, p=0.001).[8] The reason for increased mortality and health care costs in patients with MDRPA infections has been linked to inappropriate therapy or delays in starting appropriate therapy because of emergence of resistance during treatment.[25] The emergence of multidrug resistance during the treatment of P. aeruginosa infections was associated with a 3-fold increase in mortality, an increased hospital length of stay of 5.7 days, and an estimated increase in total hospital charges of $7340 compared with patients with susceptible infections or baseline resistance.

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