PULMONARY PENETRATION OF CEFTAZIDIME

For an antibiotic to be effective in lower respiratory tract infection s, it should be available in adequate concentrations in respiratory ti ssues and fluids. Cephalosporins usually achieve modest concentrations in the respiratory tract. In this study we have determined the pulmon ary penetration of intramuscularly administered ceftazidime (a single dose of 1 g). Levels of ceftazidime in bronchial secretions (BS), bron chial mucosa (BM), epithelial lining fluid (ELF), and serum (S) were m easured by microbiological assay in 25 patients suffering from acute e xacerbation 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 mu g/ml at 1 hour) and mean S concentrations decreased slowly and were still detectable at 12 hours (1.07 +/- 0.45 mu g/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 mu g/ml; Moraxella catarrhalis 0.06 mu g/ml; Streptococcus pneumoniae 0.15 mu g/ml; Klebsiella pneum oniae 0.4 mu g/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 mu g/g) were higher t han that in BS (6.87 +/- 1.96, 6.54 +/- 1.84, 3.52 +/- 1.23, 1.56 +/- 0.92 and 0.23 +/- 0.19 mu g/ml). Concentrations in ELF were consistent ly 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 mu g/ml), indicating that cefta zidime is unpredictably diluted as it diffuses into BS and ELF and the se concentrations proved to be a poor guide to its pulmonary penetrati on. However, concentrations of beta-lactam antibiotics in BM have been described as a more reliable guide to penetration into the respirator y tract than concentrations in BS and ELF.