In vitro activity, efficacy, and pharmacology of moxalactam, a new beta-lactam antibiotic

Abstract

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.

Emergence of resistance to beta-lactam and aminoglycoside antibiotics during moxalactam therapy of Pseudomonas aeruginosa infections

“…The extent of cross-resistance to other P-lactam antibiotics was not examined in previous studies (6,8,13,18,21). However, a pattern of cross-resistance similar to that seen here in posttherapy isolates from patient 4 has been observed in isolates that developed resistance to cefamandole during therapy with this drug (15).…”