Elliot L. Francke

Use of cefotaxime, a β-lactamase stable cephalosporin, in the therapy of serious infections, including those due to multiresistant organisms

Cefotaxime is a cephalosporin active against most gram-positive and gram-negative organisms, including streptococci, Staphylococcus aureus, Enterobacteriaceae, Proteus, and many Pseudomonas and Bacteroides fragilis--all but the latter two are inhibited at concentrations below 0.5 micrograms/ml. We evaluated cefotaxime as the sole therapy for 32 infections in 31 patients. Infection sites included 18 bacteremias; pulmonary, urinary tract, deep tissue infections; and meningitis. Clinical cures were achieved in 88 percent and bacteriologic cures in 86 percent of the patients--including those with infections due to organisms resistant to cephalosporins, chloramphenicol, carbenicillin and aminoglycosides; and in two patients with meningitis due to multiresistant Klebsiella pneumoniae. Serum and cerebrospinal levels were readily maintained above the inhibitory levels of susceptible organisms. Adverse reactions were minimal. Cefotaxime was a safe, effective antibiotic in the treatment of infections due to susceptible organisms, including those resistant to other agents.

Kinetics of intravenous amoxicillin in patients on long-term dialysis.

The kinetics of intravenous amoxicillin was studied in 8 patients with creatinine clearances of less than 7 ml/min who were on long‐term hemodialysis. Kinetic parameters were determined using a 2‐compartment linear model. The serum half‐life (t½) of amoxicillin in these patients ranged from 7.5 to 21 hr. The t½ fell to 2.84 ± 0.45 hr during dialysis. Approximately 30% of the dose was recovered in the dialysate during 4 hr of dialysis and there was a 25% reduction per hour in serum concentration. We present a dosage schedule for intravenous amoxicillin in patients with reduced renal function who are undergoing hemodialysis.

Pharmacokinetics of intravenous cefotaxime in patients undergoing chronic hemodialysis.

Summary The pharmacokinetics of intravenously administered cefotaxime were studied in 11 patients with creatinine clearances of less than 7 ml/min who were undergoing chronic hemodialysis. Eight were studied during dialysis, and 3 were studied between dialyses. Pharmacokinetic parameters were determined using a two-compartment linear model. The serum half-life of cefotaxime off dialysis ranged from 1.48 to 3.78 hr. The half-life during dialysis was 2.52 ± 0.34 hr. There was a 28% reduction in serum concentration per hour. A dosage schedule for the use of intravenously administered cefotaxime in patients undergoing hemodialysis is presented.

Kinetics of intravenous mezlocillin in chronic hemodialysis patients

The kinetics of intravenous mezlocillin was studied in 8 patients with creatinine clearances under 7 ml/min who were undergoing chronic hemodialysis. Kinetic parameters were determined using a 2‐compartment linear model. The mezlocillin serum half‐life (t½) in these patients ranged from 2.9 to 7.8 hr (mean, 5.4). The t½ decreased to l .57 ± 0.09 hr during dialysis. Approximately 18% of the dose was recovered in the dialysate in 4 hr of dialysis. There was a 30% reduction per hour in serum concentration. The kinetics of mezlocillin, due to removal by nonrenal mechanisms, more closely resemble the kinetics of penicillin G and ampicillin than of carbenicillin and ticarcillin. A dosage schedule for use of intravenous mezlocillin in patients undergoing hemodialysis is presented.

Pharmacokinetics of amdinocillin and pivamdinocillin in normal volunteers

The pharmacokinetic parameters of amdinocillin and pivamdinocillin were studied in 12 normal volunteers. Plasma amdinocillin concentrations were determined by microbiologic assay and urine concentrations by high performance liquid chromatography. Pharmacokinetic parameters were calculated by a two-compartment open model for the intravenous infusion and by a one-compartment model with zero-order absorption for the oral doses. The mean peak serum level after the intravenous infusion of 500 mg was 39 micrograms/ml. At one and a half hours after the oral administration of 250 mg and 500 mg doses, mean peaks were 1.93 and 2.66 micrograms/ml respectively. Half-life was one hour for all doses. Maximal plasma concentration did not increase proportionally with dose. Bioavailability was 45 percent after the 250 mg dose and 38 percent after the 500 mg dose.