Cefoperazone (10 mg/kg) and cephalothin (20 mg/kg) administered intramuscularly every 6 h were both effective in reducing the number of Staphylococcus aureus cells in vegetations in rabbits with endocarditis. Cefoperazone produced higher peak concentrations and greater bactericidal activity in serum than did cephalothin. Cefoperazone (40 mg/kg) administered every 6 h was significantly more effective than cefamandole (40 mg/kg) administered every 6 h in reducing the number of Enterobacter aerogenes cells in vegetations. Although cefamandole produced higher peak concentrations in serum, the serum bactericidal activity was greater with cefoperazone. The half-lives in serum were 0.64 h for cefoperazone and 0.46 h for cephalothin and cefamandole.

The effect of a standard regimen of cimetidine on the gastric flora of 20 male volunteers was studied in a double-blind manner and compared with the effects of a standard antacid regimen. Postprandial microbial titers in gastric aspirates were significantly higher at 4, 8, and 16 weeks of therapy in subjects taking antacids and at 4 weeks in subjects taking cimetidine when compared with their pretreatment titers. Although not significant, there was a tendency for fasting microbial titers to be higher in subjects receiving cimetidine as compared with pretreatment titers. The higher titers were primarily related to increases in survival of mouth flora (viridans streptococci and Neisseria spp.); Enterobacteriaceae and other nitratereducing organisms were unusual isolates. There was no significant difference in the total titers or types of organisms isolated when subjects taking cimetidine were compared with those taking antacid. In 1939 Garrod demonstrated the bactericidal activity of hydrochloric acid and gastric juice (6). Others have subsequently reported that the type and numbers of microbial flora present in the stomach are affected by gastric pH (3, 8, 9). Drasar et al. (3) and Giannella et al. (7) showed that, unlike normal stomachs, which contain few bacteria, stomachs of patients with hypochlorhydria or achlorhydria maintain high bacterial counts. Bacterial overgrowth in the stomach increases the risk of wound sepsis after gastric surgery (14).

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Moxalactam, a potent new f8-lactam antibiotic with a relatively wide spectrum of activity against facultative and anaerobic gram-negative bacilli, was evaluated in vitro and in 28 patients with a variety of severe infections with moxalactamsusceptible organisms (minimum inhibitory concentration c31 .tg/ml). Although therapy was successful in most of these patients, caution is suggested because of the development of resistance on therapy in one patient, persistence of Bacteroides fragilis endocarditis in another, and for certain organisms, a significant inoculum effect on the minimum inhibitory concentration and minimum bactericidal concentration of moxalactam. in serum and urine were determined in patients receiving 0.5 to 1.0 g of this drug on days 2 to 27 of therapy. Serum specimens were drawn at various intervals from 0.5 to 11.5 h after the end of a 20-min intravenous (i.v.) infusion of moxalactam. Urine specimens were obtained by having the patient void before receiving a dose of moxalactam and collecting urine voided over the dosage interval. One patient with renal failure was hemodialyzed with a Travenol RSP (Travenol Laboratories, Inc.). Serum and urine were stored (usually for less than 1 week) at -20°C until the time of assay. The concentrations of moxalactam in urine and serum were determined by the agar diffusion method with paper disks (7).The serum half-life (t12) was defined as the log, divided by the slope of the f3 phase of the serum decay curve beginning at 1 h after the end of the 20-min i.v.

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