In vitro activity of LY127935

Barza, Michael; Tally, Francis P.; Jacobus, Nilda V.; Gorbach, Sherwood L.

doi:10.1128/aac.16.3.287

Cited by 93 publications

(54 citation statements)

References 20 publications

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“…It was the most active antibiotic against the Enterobacteriaceae and was also active against P. aeruginosa, inhibiting 50% of these organisms at a concentration of 25.0 ug/ml. Others have reported very similar results (1,3,4,10,12). Preliminary data for animals and humans have indicated very little toxicity.…”

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confidence: 67%

Clinical pharmacology of moxalactam in patients with malignant disease

Estey¹,

Weaver²,

Ho³

et al. 1981

Antimicrob Agents Chemother

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Pharmacological studies of moxalactam were conducted with 37 cancer patients. Intramuscular administration of 500 mg of moxalactam to 10 patients produced a mean peak serum concentration of 12.4 ,ug/ml. The serum terminal-phase halflife was 3.9 h. Intravenous administration of 500 mg of moxalactam over 5 min to the same 10 patients produced a mean serum concentration of 42.0 ,ug/ml at 15 min, which decreased to 3.3 ,ug/ml at 6 h. A dose of 1 g of moxalactam was given in an identical manner to the same 10 patients. The mean serum concentration was 69.6 ,ug/ml at 15 min and 7.4 ,ug/ml at 6 h. The mean proportions of drug recovered in the urine by 12 h after administration were 59% after the intramuscular dose and 61 and 55% after the single intravenous doses. Multiple-dose intravenous studies were also conducted. The serum terminal-phase half-life varied from 2.0 to 3.2 h. Continuous infusion studies were perforned for up to 9 days by using a loading dose of 1 g over 0.5 h, followed by 2 g every 6 h. Serum concentrations were maintained at about 30.0 Ag/ml during the study period.Moxalactam is a semisynthetic fi-lactam antibiotic with a spectrum of activity which includes most gram-positive cocci, the Enterobacteriaceae, and Pseudomonas aeruginosa. Although several substituent groups in combination are thought to contribute to these properties, the replacement of sulfur with oxygen in the sixmember ring of the conventional cephem nucleus is believed to be especially important. When the activity of moxalactam was compared with the activities of cephalothin, cefamandole, cefoxitin, carbenicillin, mezlocillin, and piperacillin against gram-negative organisms (11), moxalactam demonstrated the greatest potency and broadest spectrum, inhibiting a majority of isolates of all organisms except P. aeruginosa at concentrations below 6.25 ,ug/ml. It was the most active antibiotic against the Enterobacteriaceae and was also active against P. aeruginosa, inhibiting 50% of these organisms at a concentration of 25.0 ug/ml. Others have reported very similar results (1,3,4,10,12). Preliminary data for animals and humans have indicated very little toxicity. Because ofthese properties, moxalactam is of potential clinical utility in cancer patients since these patients have significant mortality and morbidity from bacterial infections, especially infections caused by gram-negative bacilli (5). Accordingly, we conducted pharmacological studies of moxalactam in a group of patients with malignant diseases. MATERIALS AND METMODSWe conducted a total of 41 studies with 37 cancer patients who ranged in age from 19 to 71 years (median, 46 years). The body surface area of these patients varied from 1.4 to 2.4 m2 (median, 1.9 m2), and their weight varied from 40 to 111 kg (median, 70 kg). All patients but one had normal serum creatinine levels. The exception was a male with an initial serum creatinine level of 1.6 mg/dl, in whom the level decreased to 1.1 mg/dl by the second study day; thereafter, this patient continued to have normal values. T...

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confidence: 67%

Clinical pharmacology of moxalactam in patients with malignant disease

Estey¹,

Weaver²,

Ho³

et al. 1981

Antimicrob Agents Chemother

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“…The compound exhibited great potency against Enterobacteriaceae, the median MIC for all species being c2 ,ug/ml. Only 2 of 108 strains (1 Enterobacter cloacae, 1 Enterobacter aerogenes) showed MICs higher than 8 ,ug/ml. Azthreonam was as potent as moxalactam and more potent than cefoperazone, cefamandole, cefoxitin, and ticarcillin for most of the genera within this group.…”

Section: Discussionmentioning

confidence: 99%

In vitro activity of azthreonam, a monobactam antibiotic

Jacobus¹,

Ferreira²,

Barza³

1982

Antimicrob Agents Chemother

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We studied the activity of azthreonam (SQ 26,776) Antibiotic susceptibility studies. For aerobic and facultative bacteria, susceptibility to antibiotics was determined by a broth dilution microtiter technique (1). Mueller-Hinton broth (GIBCO Diagnostics, Madison, Wis.) was used, and the inoculum was adjusted to contain 10' colony-forming units (CFU) per ml, resulting in a concentration of 5 x 10' organisms per well.The minimal inhibitory concentration (MIC) was determined as previously described (1).Anaerobic bacteria were studied by a modified agar dilution technique (9). To avoid confluent growth with spreading clostridia, the medium was altered to contain 2% instead of 1.5% agar when these organisms were tested.

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“…Moxalactam is a new beta-lactam antimicrobial agent with a broad spectrum of activity against aerobic and facultative gram-negative rods (2,4,5,8,16). Although there are fewer reports on N-formimidoyl thienamycin, this new more stable derivative of thienamycin also has an expanded spectrum of activity (7,14,17).…”

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confidence: 99%