A multicentre, randomized comparative study of 500 mg versus 1,000 mg ceftazidime t.d.s. for treatment on gram-negative infections.

A multicentre, randomized study was performed to compare the clinical and bacteriological efficacy of 500 mg ceftazidime i.v. t.d.s. with 1,000 mg ceftazidime i.v. t.d.s. for treatment of hospitalised, non-compromised patients with gram-negative infections. The study was conducted in ten hospitals in The Netherlands. Hospitalised patients with a suspected gram-negative lower respiratory tract infection, complicated urinary tract infection or septicaemia were included. Excluded were patients with neutropenia, limited life expectancy, or severe renal insufficiency as well as those on antibiotics in the 48 h prior to entry. Ceftazidime was administered via an intravenous infusion every 8 h. For patients with moderately impaired renal function the frequency was reduced to 12 h. Treatment was continued for as long as clinically indicated. Clinical response (cure, improvement or failure) and bacteriological response (elimination, persistence or non-evaluable) were assessed primarily by the investigator. Final assessments were made by a panel of experts without prior knowledge. In total 127 patients were randomized, 64 patients to the 500 mg group and 63 to the 1,000 mg group; 47 patients were excluded from evaluation, usually due to an incorrect diagnosis prior to randomization. Ultimately 37 patients of the 500 mg group and 43 patients of the 1,000 mg group were available for evaluation. Between these two groups of evaluable patients there were no significant differences in baseline characteristics, types of infection, isolated bacterial pathogens or treatment characteristics.(ABSTRACT TRUNCATED AT 250 WORDS)

The passage of cloxacillin into cerebrospinal fluid in the absence of meningitis.

1. Eleven patients undergoing lumbar discectomy received cloxacillin by continuous i.v. infusion, starting before the operation. During the operation several blood samples and one CSF sample were taken. 2. Mean rate constants describing the passive transfer of drug from plasma to CSF (kp) and the largely active transfer in the opposite direction (kCSF) were estimated. 3. In some subjects the CSF albumin quotient, defined as the ratio between the albumin concentration in CSF and in plasma times 1000, was slightly elevated (up to 23) which caused a significant increase in the value of kp. 4. The estimate of mean kp for healthy individuals was 0.065 h-1, which corresponds to a half-life of 10 h. The estimate of mean kCSF was 2.10 h-1. This predicts a steady-state CSF drug concentration which is 3% of the unbound plasma drug concentration. 5. There was a significant lag between the time courses of plasma and CSF drug concentrations, presumably reflecting the time for drug to move from the choroid plexus to the lumbar sampling site. 6. Four other patients received cloxacillin for prophylactic or therapeutic reasons by continuous i.v. infusion. In three of those patients the albumin quotient was normal or slightly elevated and the steady-state CCSF/Cu ratio was similar to the predicted normal value. 7. These findings indicate that eradicating staphylococci from CSF in cases of meningitis with a low degree of inflammation may be difficult.