Abstract and Introduction
Abstract
Objectives: To compare once-daily intramuscular cefepime with ceftriaxone controls.
Design: Double-blind study.
Setting: Six skilled nursing facilities.
Participants: Residents aged 60 and older with nursing home–acquired pneumonia.
Intervention: Cultures were obtained, and patients were randomized to cefepime or ceftriaxone 1 g intramuscularly every 24 hours.
Measurements: Clinical success: cure or improvement. Cure was defined as complete resolution of all symptoms and signs of pneumonia or a return to the patient's baseline state. Improvement was defined as clear improvement but incomplete resolution of all pretherapy symptoms or signs or incomplete return to the patient's usual baseline status. Safety and pharmacoeconomics were also assessed.
Results: Sixty-nine patients were randomized; 61 were evaluable: (32 to cefepime, 29 ceftriaxone). Patients were predominately female (76%). They had a mean age ± standard deviation of 85 ± 6, with a mean 5.8 ± 1.9 comorbidities; they had age-appropriate renal dysfunction, with a mean estimated creatinine clearance of 35 ± 7 mL/min. Clinical success occurred in 78% of cefepime- and 66% of ceftriaxone-treated patients (P=.39). Fifty-seven patients (93%) were switched to oral antibiotics after 3 days. Antibiotic-related adverse events occurred in 5% of patients. Seven patients (11.5%) were hospitalized. The overall mortality rate was 8%. Mean antibiotic costs were $117 ± 40 for cefepime- and $215 ± 68 for ceftriaxone-treated patients (P < .001). Cost-effectiveness analysis of total costs showed that cefepime would cost $597 and ceftriaxone $1,709 per expected successfully treated patient. One- and two-way sensitivity analyses using a generic price for ceftriaxone and improving its comparative efficacy revealed that the results were robust.
Conclusions: Once-daily cefepime was a cost-effective alternative to ceftriaxone for the treatment of elderly nursing home residents who developed pneumonia and did not require hospitalization.
Introduction
Nursing home–acquired pneumonia (NHAP) is a significant cause of morbidity, mortality, and healthcare resource consumption for residents of long-term care facilities (LTCFs). Frequently isolated bacteria are similar to those found in community-acquired pneumonia (CAP): Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus (although frequently methicillin-resistant), Moraxella catarrhalis, and other aerobic gram-negative bacilli;Chlamydia pneumoniae and Legionella pneumophila are rarely implicated, although outbreaks can occur in individual LTCFs.
There is increasing support for treating NHAP without hospitalization. Intramuscular (IM) cephalosporins are often administered to residents of LTCFs who develop NHAP not amenable to oral treatment but not requiring hospitalization. Ceftriaxone is frequently used, because its broad spectrum of activity covers most of the pathogens commonly found in NHAP, with the exception of methicillin-resistant S. aureus (MRSA). Ceftriaxone's long serum half-life supports once-daily dosing in most patients, and its efficacy in treating lower respiratory tract infections has been well established. Ceftriaxone given 1 g every 24 hours resulted in clinical efficacy rates between 73% and 95%, with bacteriologic eradication rates of 93% to 100%.
Cefepime has excellent in vitro activity against gram-positive organisms associated with NHAP (excluding MRSA) with minimum inhibitory concentrations (MICs) equivalent to ceftriaxone. Cefepime is also active against gram-negative pathogens associated with NHAP, including several that are resistant to ceftriaxone. The efficacy of cefepime 2 g every 12 hours was compared with that of ceftriaxone 1 g every 12 hours for the intravenous treatment of 115 hospitalized patients with CAP. Success rates (clinical, microbiological) were similar in cefepime- (95%, 100%) and ceftriaxone-treated patients (98%, 97%). Although cefepime has a half-life of 2.3 hours in healthy adults, as creatinine clearance (ClCr) decreases below 60 mL/min, its half-life progressively increases from 4.9 to 10.5 hours, enabling once-daily dosing for all but the most difficult to treat infections.
The IM route of administration of cefepime and ceftriaxone is well tolerated. IM cefepime is at least as safe and perhaps less painful on injection than IM ceftriaxone. The cost to LTCFs for 1 g of ceftriaxone was three times that of 1 g of cefepime during the study. With equivalent gram-positive and superior gram-negative activity, cefepime may provide a cost-effective alternative to ceftriaxone. The study objective was to assess and compare the efficacy, safety, and pharmacoeconomics of once-daily IM cefepime with those of ceftriaxone for the treatment of elderly LTCF residents with NHAP.