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


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

In This Article

Abstract and Introduction

Pseudomonas aeruginosa is one of the leading gram-negative organisms associated with nosocomial infections. The increasing frequency of multi-drug-resistant Pseudomonas aeruginosa (MDRPA) strains is concerning as efficacious antimicrobial options are severely limited. By searching MEDLINE from January 1966-February 2005 and relevant journals for abstracts, we reviewed the frequency, risk factors, and patient outcomes of MDRPA nosocomial infections in critically ill patients, determined the available antimicrobial therapies, and then provided recommendations for clinicians. The definition of MDRPA was established as isolates intermediate or resistant to at least three drugs in the following classes: β-lactams, carbapenems, aminoglycosides, and fluoroquinolones. Reported rates of MDRPA varied from 0.6-32% according to geographic location and type of surveillance study. Risk factors for MDRPA infection included prolonged hospitalization, exposure to antimicrobial therapy, and immunocompromised states such as human immunodeficiency virus infection. Emergence of MDRPA isolates during therapy was reported in 27-72% of patients with initially susceptible P. aeruginosa isolates. Patients with severe MDRPA infections should be treated with combination therapy, consisting of an antipseudomonal β-lactam with an aminoglycoside or fluoroquinolone rather than aminoglycoside and fluoroquinolone combinations, to provide adequate therapy and improve patient outcomes. Synergy has been observed when resistant antipseudomonal drugs were combined in vitro against MDRPA with successful clinical application reported in two centers. Colistin with adjunctive therapy, such as a β-lactam or rifampin, may be a useful agent in MDRPA when antimicrobial options are limited, but patients should be monitored closely for toxicities associated with this agent. Standardization of terminology for MDRPA isolates is needed for consistency and comparability of surveillance and institutional reports. Clinical studies are needed to identify risk factors for MDRPA development and to determine the economic impact of these infections, as well as to determine the most efficacious antimicrobial regimens and duration of therapy to maximize outcomes in the treatment of MDRPA infections.

Nosocomial infections caused by Pseudomonas aeruginosa are frequently life threatening and often challenging to treat.[1] Selection of resistance during antipseudomonal therapy among initially susceptible isolates occurs frequently with this pathogen, resulting in the emergence of resistance to multiple drugs.[2] Although multi drug-resistant P. aeruginosa (MDRPA) infections have been described in patients with cystic fibrosis or immunocompromised conditions and in isolated outbreaks in intensive care units,[3,4,5,6,7] recent reports in critically ill patients in non outbreak settings have raised concerns because of the scarcity of novel agents to effectively treat MDRPA infections.[8,9]

In the treatment of infectious diseases in critically ill patients, an early start to appropriate antimicrobial therapy improves patient outcomes, whereas inadequate therapy is one of the most important determinants of hospital mortality.[10,11,12,13] However, therapeutic options for MDRPA infections in critically ill patients are limited.

To review the frequency, risk factors, and patient outcomes of MDRPA infections in critically ill adult patients who do not have cystic fibrosis and to determine available treatment options, a computerized search of MEDLINE from January 1966-February 2005 was conducted by using the following keywords: multi drug-resistant, multi resistant, P. aeruginosa, nosocomial infections, and treatment. References of identified articles were further reviewed for additional articles. A manual search of critical care, respiratory, surgery, microbiology, infectious diseases, and pharmacy journals was conducted to identify relevant abstracts. Data from duplicate publications of a study or versions of a study are reported as aggregate results. Both clinical and in vitro studies related to the epidemiology and treatment of MDRPA infections were summarized, and recommendations are provided accordingly.

The definition of multi drug resistance is not standardized in many of the studies published on this topic. Different agents within antimicrobial classes are selected as standards for resistance within each class, and the number of agents required for a strain to be classified as MDRPA is not always specified within these studies. For the purposes of this study, an MDRPA strain was defined as an isolate intermediate or resistant to at least three drugs of the following classes: β-lactams (piperacillin, piperacillin-tazobactam, ceftazidime, cefepime, ticarcillin, ticarcillin-clavulanate), carbapenems (imipenem, meropenem), aminoglycosides (gentamicin, tobramycin, amikacin), and fluoroquinolones (ciprofloxacin). Studies in which the P. aeruginosa isolates were consistent with this definition are presented, and the strains were classified as MDRPA.