Pharmacokinetics of antibacterial agents in the CSF of children and adolescents.
Of 237 cases of gram-negative rod bacteremia observed at the UCLA Medical Center during a 12 month period, 52 (22 per cent) occurred while the patient was receiving antibiotics which inhibited the infecting organism by disc diffusion tests. One half of the plasma samples available from 42 such patients with "breakthrough" bacteremia had subinhibitory circulating antibiotic levels when cultures were positive. Sepsis documented within 72 hours of initiation of therapy was usually due to antibiotic-sensitive Esch. coli and was associated with inadequate antibiotic levels; the patient was usually treated with a penicillin or cephalosporin. The source of bacteremia was most frequently the urinary tract or the biliary tree. In contrast, sepsis occurring more than 72 hours after the administration of antibiotics was frequently caused by multiple antibiotic-resistant Esch. coli in patients treated with gentamicin in adequate dosage and was associated with leukopenia or undrained purulent collections. Therapy ultimately failed in 20 cases (48 per cent): in early "breakthrough" bacteremia, failure was associated with subinhibitory antibiotic levels, and in late "breakthrough" bacteremias with inadequate drainage or impaired host defenses.