Extended-Infusion Cefepime Reduces Mortality in Patients with Pseudomonas aeruginosa Infections

Abstract

In an era of escalating resistance and a lack of new antimicrobial discovery, stewardship programs must utilize knowledge of pharmacodynamics to achieve maximal exposure in the treatment of Pseudomonas aeruginosa infections. We evaluated the clinical and economic outcomes associated with extended-infusion cefepime in the treatment of P. aeruginosa infections. This single-center study compared inpatients who received cefepime for bacteremia and/or pneumonia admitted from 1 January 2008 through 30 June 2010 (a 30-min infusion of 2 g every 8 h) to those admitted from 1 July 2010 through 31 May 2011 (a 4-h infusion of 2 g every 8 h). The overall mortality was significantly lower in the group that received extended-infusion treatment (20% versus 3%; P ‫؍‬ 0.03). The mean length of stay was 3.5 days less for patients who received extended infusion (P ‫؍‬ 0.36), and for patients admitted to the intensive care unit the mean length of stay was significantly less in the extended-infusion group (18.5 days versus 8 days; P ‫؍‬ 0.04). Hospital costs were $23,183 less per patient, favoring the extended-infusion treatment group (P ‫؍‬ 0.13). We conclude that extended-infusion treatment with cefepime provides increased clinical and economic benefits in the treatment of invasive P. aeruginosa infections.A ntimicrobial resistance has emerged as a global health crisis, gaining the attention of the World Health Organization and the U.S. Department of Health and Human Services (1). As antimicrobial resistance continues to emerge and new antimicrobial development stagnates, antimicrobial stewardship programs are being implemented worldwide. The goal of antimicrobial stewardship is to optimize antimicrobial therapy with maximal impact on the subsequent development of resistance (2-4). The Healthcare Infection Control Practices Advisory Committee, in partnership with the U.S. Department of Health and Human Services, lists antimicrobial stewardship as a top 5 message for health care workers (5).Pseudomonas aeruginosa infections constitute a tremendous burden on hospitals in the United States in terms of morbidity, mortality, and health care costs. P. aeruginosa infections are associated with a mortality rate of 18 to 60%, and the cost of treatment is substantial, ranging from $20,000 to $80,000 per infection (6-11). Antimicrobial therapy for P. aeruginosa is limited because of the organism's multiple resistance mechanisms, often resulting in higher .Cefepime is a "fourth-generation" cephalosporin with activity against Gram-positive and Gram-negative organisms, including P. aeruginosa. Because of its broad activity, cefepime is used as empirical antibiotic therapy for serious infections, including pneumonia and bacteremia. Like other ␤-lactam antibiotics, cefepime displays time-dependent bactericidal activity, and its efficacy is optimized when free drug concentrations exceed the MIC (fT Ͼ MIC) for at least 60 to 70% of the dosing interval (15-18). Recent evidence suggests that conventional regimens may not attain this fT Ͼ MIC (19-21). ...

Absceso Cerebral por Nocardia spp. en paciente inmunocompetente. Presentación de 2 casos

“…Extrapolando datos de estudios de meropenem en infusión extendida en infecciones graves por gram (-) y meningitis es presumible que esta estrategia logre adecuada concentración y tiempo sobre la concentración inhibitoria míni-ma (CIM) en el sistema nervioso central (SNC) 11 . Esta estrategia ha demostrado beneficios, especialmente en tratamientos con beta lactámicos antipseudomonas en SNC 12 . De acuerdo a la literatura existente, tanto la excisión quirúrgica o aspiración guiada por TC del absceso cerebral ha demostrado efectividad en erradicación de la enfermedad [13][14] .…”

Success With Extended-Infusion Meropenem After Recurrence of Baclofen Pump-Related Achromobacter Xylosoxidans Meningitis in an Adolescent

“…22 Extending infusion times of antipseudomonal beta-lactams has been shown to improve pharmacodynamic target attainment in both adults and children and has been associated with reduced mortality in critically ill adults with serious gram-negative bacterial infections. 21,[23][24][25][26] This is especially important when treating infections where the site of infection may be difficult to penetrate with antibiotics or infections caused by organisms with higher MICs, such as Pseudomonas aeruginosa. Failed initial treatment with a 30-minute interval could have been related to lack of achievement of 40% T>MIC which could lead to suboptimal or incomplete killing and potential organism regrowth.…”

Application of Antibiotic Pharmacodynamics and Dosing Principles in Patients With Sepsis

“…Although data are limited on prolonged or continuous infusion of cefepime on patients' outcomes, observational evidence 23 suggests that patients infected with P aeruginosa who do not achieve 60% T > MIC are 8 times more likely to persistently have cultures positive for P aeruginosa than are patients who do achieve 60% T > MIC. A retrospective quasi-experimental study 27 of cefepime 2000 mg intravenously every 8 hours with a 30-minute infusion compared with a 4-hour infusion indicated decreased mortality (20% vs 3%; P = .03) and decreased median hospital length of stay (14.5 days vs 11 days; P = .36 ) and intensive care unit length of stay (18.5 days vs 8 days; P = .36) with prolonged infusion.…”