877-879 MW3593 Brief Rep

In Pseudomonas aeruginosa infections in patients with cystic fibrosis, antibiotics that kill the bacteria in vitro fail to eradicate them in the patient, while treatment with antibiotics to which the bacteria are apparently resistant in vitro can be associated with clinical improvement. In P. aeruginosa infections in other patients, both rifampicin and chloramphenicol, to which the organisms were insensitive in vitro, appeared to confer benefit when each was given in combination with other drugs (Korvick et al. and Woodhead, M., personal communication). Standard sensitivity test media contain iron but sputum contains lactoferrin which limits iron availability to bacteria. Lactoferrin also has a direct effect, damaging the Gram-negative outer membrane and thus increasing the susceptibility of Escherichia coli to rifampicin and of Salmonella typhimurium to rifampicin, ampicillin, ciprofloxacin, chloramphenicol and erythromycin. We have therefore investigated the effect of lactoferrin at the very high concentration found in sputum from patients with cystic fibrosis (0.9 mg/mL) on the sensitivity of P. aeruginosa to ceftazidime and gentamicin, antibiotics routinely used in pseudomonas infections, and to rifampicin and chloramphenicol which have little activity in vitro as measured by MIC but appear to benefit patients with respiratory infections caused by P. aeruginosa. Materials and methods