Study objective: To compare the effectiveness of extended-infusion piperacillin-tazobactam with that of similar-spectrum, nonextended-infusion [H9252]-lactam antibiotics in the treatment of gram-negative infections.
Design: Multicenter, retrospective medical record review.
Setting: Fourteen hospitals throughout the United States.
Patients: A total of 359 adults treated for gram-negative infections between January 1, 2007, and February 28, 2010, with either 4-hour extended-infusion piperacillin-tazobactam (186 patients) or nonextended-infusion comparator antibiotics (173 patients), which consisted of cefepime, ceftazidime, imipenem-cilastatin, meropenem, doripenem, or piperacillin-tazobactam.
Measurements and main results: Deidentified data were collected on demographics, renal function, Acute Physiology and Chronic Health Evaluation II score, chronic health conditions, source of infection and type of organism, intensive care unit (ICU) length of stay, total length of stay, type and duration of antimicrobial therapy, and in-hospital mortality. The primary outcome was mortality rate of the patients receiving extended-infusion piperacillin-tazobactam versus those receiving nonextended-infusion comparator antibiotics. Secondary outcomes were hospital length of stay, ICU length of stay, and total duration of antibiotic therapy. Baseline characteristics were similar between groups, except a significantly lower proportion of patients in the extended-infusion group were treated with a concomitant intravenous aminoglycoside (5.9% vs 16.2%, p<0.01), were infected with Pseudomonas species (22.6% vs 39.9%, p<0.01), or had positive respiratory cultures (30.7% vs 43.4%, p=0.01). Antibiotic duration, hospital length of stay, and ICU length of stay were similar between groups. In-hospital mortality was significantly decreased in the extended-infusion piperacillin-tazobactam group versus those receiving comparator antibiotics (9.7% vs 17.9%, p=0.02). Multivariate analysis confirmed that extended-infusion piperacillin-tazobactam prolonged survival by 2.77 days (p<0.01) and reduced the risk of mortality (odds ratio 0.43, p=0.05).
Conclusion: Pharmacodynamic dosing using extended-infusion piperacillintazobactam demonstrated favorable outcomes, including mortality, when compared with nonextended-infusion, similar-spectrum [H9252]-lactams in the treatment of patients with documented gram-negative infections. Prospective, randomized trials are needed to further corroborate these findings.