FEV1 <50% predicted is a recognized risk factor for infection with Enterobacteriaciae (EB) and Pseudomonas aeruginosa (PA) in patients with ABECB. Other risk factors for infection with these pathogens need to be clarified. We hypothesized that stratification based on FEV1, number of exacerbations/year, and the presence of medical co-morbidity would identify patients at higher risk for EB and PA infection.
In this phase IIIB, randomized, blinded study, patients with ABECB were characterized as “uncomplicated” or “complicated” based on FEV1 (above or below 50% predicted), presence of medical co-morbidity, and frequency of exacerbations/year. “Uncomplicated” patients received levofloxacin 750mg/d for 3 days or azithromycin 500mg (day 1) followed by 250mg/d (days 2-5). “Complicated” patients received levofloxacin 750mg/d for 5 days or amoxicillin/clavulanate 875mg bid for 10 days.
To date, 642 patients have been randomized (345 uncomplicated, 297 complicated) of a planned 700 patients. Thus far, 278 organisms have been cultured from 102 patients. For patients recognized as “at risk” for EB and PA due to FEV1 <50% predicted (n=26), EB or PA were recovered from 9 (34.6%) patients. Among low risk patients with FEV1 >50% predicted, no medical co-morbidity, and <4 exacerbations per year (n=53), 14 (26.4%) patients had EB or PA cultured. In contrast, among patients with FEV1 >50% predicted with medical co-morbidity and ≥4 exacerbations/year (n=23), EB or PA were recovered from 12 (52.2%) (p=0.03 chi-square test).
ABECB patients with FEV1 >50% predicted, medical co-morbidity, and ≥4 exacerbations/year are at significantly greater risk for infection with EB and PA than patients with FEV1 >50% predicted but without co-morbidity and with <4 exacerbations/year.
Given the increased risk for infection with EB and PA, broad-spectrum antimicrobials should be employed for ABECB in patients with medical co-morbidity and frequent exacerbations, regardless of FEV1.
A.M. Tennenberg, Ortho-McNeil Pharmaceutical. Discussion of product research or unlabeled uses of Product.