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

Conclusion

Reported rates of MDRPA infection vary depending on geographic location and type of surveillance study. However, surveillance studies consistently report trends of increasing rates of MDRPA infection. Risk factors for MDRPA infection include prolonged hospitalization, exposure to protracted and broad-spectrum antimicrobial therapy, and immunocompromised states. Emergence of resistant P. aeruginosa isolates during therapy occurs at rates of 27-72% in current reports, but risk factors for the emergence of resistance remain unidentified. Although data are limited, patients with MDRPA infections appear to experience higher morbidity, mortality, and economic burden.

Prevention strategies including prudent antimicrobial use and infection control should be advocated to delay emergence of clinically significant MDRPA infections. In light of increasing prevalence of MDRPA, empiric therapy for severe nosocomial infections should consist of two antipseudomonal agents to avoid inadequate therapy or treatment failure. In patients with documented MDRPA infections, successful regimens have included parenteral colistin therapy, continuous-infusion meropenem, combination therapy with cefepime and amikacin, and combination therapy with rifampin and colistin. Although clinical data are lacking, synergy testing may be useful in selecting individual-specific regimens for treatment of MDRPA infections, especially when therapeutic options are restricted. Limited in vitro synergy data suggest combination therapy may be efficacious including an antipseudomonal β-lactam with an aminoglycoside, antipseudo-monal β-lactam with a fluoroquinolone, or colistin with rifampin despite resistance to one or both agents in the combination. Few data are available for fluoroquinolones in combination with aminoglycosides.

Further research is necessary to prevent MDRPA infections or adequately treat these patients. The definition of MDRPA should be standardized to allow for more accurate comparisons of studies. Additional in vitro synergy studies that use MDRPA clinical isolates need to be completed and correlated with in vivo clinical treatment regimens. The contribution of pharmacokinetic and pharmacodynamic properties and adequacy of dosing regimens of antipseudomonal agents should be evaluated, as these properties may explain selective pressures associated with specific antibiotics. Finally, clinical studies are needed to identify risk factors, assess economic impact, determine the most efficacious antimicrobial regimens, and specify appropriate duration of therapy to maximize outcomes in the treatment of MDRPA infections.

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