Monotherapy versus Combination Therapy Targeting Pseudomonas aeruginosa in Hospital-Acquired and Ventilator-Associated Pneumonia

Purpose: Pseudomonas aeruginosa is a major cause of serious infections and contributes significantly to morbidity and mortality. This life-threatening pathogen is a common cause of pneumonia and is resistant to multiple antibiotics. The 2016 Infectious Diseases Society of America recommends combination therapy for the treatment of hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) caused by P. aeruginosa in patients with intravenous antibiotics use within previous 90 days and in those at high risk of mortality. This review analyzes literature that supports the use of combination therapy versus monotherapy for the empiric treatment of P. aeruginosa in HAP and VAP. Methods: Online databases were used to find articles published pertaining to combination therapy versus monotherapy in the treatment of HAP and/or VAP. Databases used in online literature searches were Google Scholar, Science Direct, and PubMed, using keywords Pseudomonas aeruginosa , monotherapy , combination therapy , and pneumonia . Studies were selected from the search results if they met the following inclusion criteria: Study evaluated pneumonia (HAP and VAP) as well as compared monotherapy and combination therapy in the treatment of P. aeruginosa pneumonia. Risk factors such as intravenous antibiotic use in the past 90 days and mortality risk were also reviewed in these studies. During the online search, studies were excluded if it pertained to bacteremia, cystic fibrosis, and/or community acquired pneumonia. Results: Most of the observational studies included in this review found no significant difference in overall mortality between combination therapy and monotherapy, with mortality assessed at 14, 28, 30, and 90 days. Microbiological cure rates were also similar between the two approaches for HAP and VAP. Each study also included its own specific antibiotic regimens or interventions. It was noted that initiating appropriate antibiotic therapy is essential to reducing mortality. The monotherapy groups typically had more participants than the combination therapy groups. The most recent studies are mostly observational in nature where retrospective and prospective studies were the primary methods for comparing combination therapy and monotherapy in HAP and VAP. Randomized controlled trials in HAP and VAP are more than thirty years old and infrequently conducted in this patient population. Conclusion: Treating pneumonia caused by P. aeruginosa, whether hospital-acquired or ventilator-associated, is complex. The evidence of combination therapy compared to monotherapy in treating P. aeruginosa pneumonia is limited. While current guidelines recommend combination therapy, supporting evidence is weak. After reviewing available studies, mortality between combination therapy and monotherapy is inconclusive. A well designed randomized controlled trial is necessary for updating current guidelines so the most appropriate strategies can be used to treat P. aeruginosa HAP or VAP. Future trials should focus on comparing safety and efficacy of combination therapy, monotherapy, and newer agents for treating P. aeruginosa pneumonia.