Drugs for protozoan infections.
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Biomedical subjects
Publications and source records attributed to J L Lefrock.
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Cefmenoxime, a new parenteral beta-lactamase-resistant cephalosporin, was evaluated for safety and efficacy in 15 patients (10 male and five female) with acute (1 patient) and chronic (14 patients) osteomyelitis. Diagnosis was made by culture of the surgical biopsy specimen. Osteomyelitis was treated with 8 to 12 g of cefmenoxime per day (mean 9.1 g) for 42 to 66 days (mean 47.3). Staphylococcus aureus was the most frequently isolated organism. Minimum inhibitory concentrations (MICs) of cefmenoxime were determined and all pathogens were inhibited by 12.5 micrograms/ml or less, except for Enterobacter cloacae and Acinetobacter species, both of which had an MIC of 25.0 micrograms/ml. All patients had at least one surgical debridement. Of the 15 patients, 10 (67 percent) had the osteomyelitis "arrested." These patients have been followed up five to 14 months after completion of cefmenoxime therapy. Toxicity studies indicated mild elevations in serum glutamic oxalacetic transaminase and serum glutamic pyruvic transaminase in two patients. Cefmenoxime appears to be a safe and effective antibiotic in the treatment of osteomyelitis.
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Macrophages are important for host defense against syphilitic infection. Our results show that C3b-mediated ingestion (C3bMI), a characteristic of activated macrophages, was inhibited in vitro by nonadherent cells from hamsters infected with Treponema pallidum subspecies endemicum. When macrophage target cells from normal, syphilitic, or lipopolysaccharide-treated animals were co-cultured with nonadherent cells derived from normal or syphilitic hamsters, noticeable differences were detected. Nonadherent syphilitic cells significantly suppressed macrophage C3bMI, whereas normal nonadherent cells displayed little or no suppressive activity. In general, macrophage C3bMI was reduced by nonadherent cells obtained throughout the course of syphilitic infection, although it eventually began to recover. The syphilitic nonadherent cells with maximum suppressive effect were those obtained from hamsters infected for 3 to 6 wk. The addition of treponemal antigens additionally inhibited C3bMI. The inhibitory effect of syphilitic nonadherent cells on either lipopolysaccharide-treated or syphilitic macrophages was sustained even when the nonadherent cells were removed from the cultures, and the effect continued for at least 72 hr thereafter. Fractionation of syphilitic nonadherent cell populations by two independent methods produced T cell-enriched preparations with significantly more suppressive activity than non-T cell-enriched preparations. These observations may account for the chronicity of syphilitic infection.
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Ceforanide, a new cephalosporin antibiotic with a long half-life (three hours), was evaluated for its antimicrobial activity, pharmacology, and clinical efficacy. Fifty-two patients with 56 infections due to susceptible organisms received ceforanide, 0.5 g, 1 g, or 2 g, intramuscularly or intravenously every 12 hours for four to 60 days (average: 14.1 days). The in vitro studies of our clinical isolates showed that 12.0 micrograms/ml or less of ceforanide inhibited all Streptococcus pneumoniae, beta hemolytic streptococci group A, B, F, Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and Hemophilus influenzae. After a 1 gram intramuscular dose, the mean peak serum concentration at one hour was 44.0 micrograms/ml, and at 12 hours was 3.8 micrograms/ml. After a 1 gram intravenous dose, the mean peak serum concentration was 65.0 micrograms/ml, and the mean trough serum concentration at 12 hours was 9.6 micrograms/ml. The infections treated included ten pneumonias, ten urinary tract infections, seven bacteremias, two osteomyelitis, and 35 skin-soft tissue infections. Of the 56 evaluable infections treated, 52 had a clinical cure with only four failures. Ceforanide was well tolerated, with no patients developing thrombophlebitis, or liver or renal abnormalities. Three patients developed abnormal Coombs' reactions and one had diarrhea.
A 54-year-old woman with recurrent adenocarcinoma of the uterus was treated with new third-generation cephalosporin, cefmenoxime, for a urinary tract infection. She received an alcohol-containing tylenol elixir while receiving the drug on two occasions. A disulfiram-like reaction was noticed each time. Such reactions have been described in patients receiving certain drugs such as 5-nitroimidazoles, nitrofurans, sulfonylureas and certain newer cephalosporins with a methyltetrazolethiol side chain. This is the first report of a disulfiram-like reaction with cefmenoxime. The mechanism, causes, and significance of disulfiram-like reactions are discussed.