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Healthcare-associated pneumonia (HCAP) develops in patients who have recently had contact with nosocomial and drug-resistant pathogens, because of a history of hospitalization in the past 90 days, need for hemodialysis or home wound care, or residence in a nursing home. HCAP was included in the 2005 American Thoracic Society/Infectious Diseases Society of America guidelines for nosocomial pneumonia, with the recommendation that all such patients receive empiric therapy with a multidrug regimen directed against drug-resistant organisms. The purpose of this review was to examine articles published since the guidelines were developed to see whether this therapy recommendation is correct.All articles published since July 2004 were identified using PubMed and the key words HCAP, nursing home-acquired pneumonia, and antibiotic therapy. The search was limited to adults, with a focus on clinical trials, reviews, meta-analyses, or practice guidelines.We identified eight unique studies of HCAP, which were either prospective or retrospective series, with bacteriologic data on both Gram-negative and Gram-positive organisms. We also examined three prospective, randomized therapy trials of nursing home-acquired pneumonia that included limited bacteriologic data. We found that patients with HCAP were a heterogeneous group, with some at risk for multidrug-resistant organisms, and others not, and this accounted for the observation that many patients were successfully treated with monotherapy regimens or with regimens used for patients with community-acquired pneumonia. Patients at risk for multidrug-resistant pathogens were those with severe illness or those with other risk factors including: hospitalization in the past 90 days, antibiotic therapy in the past 6 months, poor functional status as defined by activities of daily living score, and immune suppression.On the basis of the risk factors identified in recent studies, we developed an algorithm for empiric therapy of HCAP, which suggests that not all such patients require a broad-spectrum multidrug regimen in order to achieve appropriate and effective therapy. This algorithm needs validation in future studies.