Pulmonary Penetration of Ceftazidime

Abstract

For an antibiotic to be effective in lower respiratory tract infections, it should be available in adequate concentrations in respiratory tissues and fluids. Cephalosporins usually achieve modest concentrations in the respiratory tract. In this study we have determined the pulmonary penetration of intramuscularly administered ceftazidime (a single dose of 1 g). Levels of ceftazidime in bronchial secretions (BS), bronchial mucosa (BM), epithelial lining fluid (ELF), and serum (S) were measured by microbiological assay in 25 patients suffering from acute exacerbation of chronic bronchitis who were divided into 5 groups of 5 subjects according to sampling time (1, 2, 4, 8 and 12 hours after the administration of the antibiotic). The peak S level was high (39.89 ± 10.42 μg/ml at 1 hour) and mean S concentrations decreased slowly and were still detectable at 12 hours (1.07 ± 0.45 μg/ml). In all other samples, mean concentrations were in excess of the ceftazidime minimum inhibitory concentrations (MICs) for many relevant respiratory pathogens (Haemophilus influenzae 0.15 μg/ml; Moraxella catarrhalis 0.06 μg/ml; Streptococcus pneumoniae 0.15 μg/ml; Klebsiella pneumoniae 0.4 μg/ml). Concentrations in BM (7.05 ± 2.38, 8.14 ± 2.23, 6.40 ± 1.63, 4.06 ± 0.99 and 0.45 ± 0.27 μg/g) were higher than that in BS (6.87 ± 1.96, 6.54 ± 1.84, 3.52 ± 1.23, 1.56 ± 0.92 and 0.23 ± 0.19 μg/ml). Concentrations in ELF were consistently much lower than those in BM (2.71 ± 0.88, 2.66 ± 0.64, 1.32 ± 0.64, 0.66 ± 0.36 and 0.12 ± 0.15 μg/ml) indicating that ceftazidime is unpredictably diluted as it diffuses into BS and ELF and these concentrations proved to be a poor guide to its pulmonary penetration. However, concentrations of beta-lactam antibiotics in BM have been described as a more reliable guide to penetration into the respiratory tract than concentrations in BS and ELF.