ly-163892 and Nausea

The treatment of bacterial pneumonia requires an agent with activity against a wide range of bacterial pathogens, including pathogens that produce beta-lactamase. Loracarbef, a member of the carbacephem class of antibiotics, was tested in a series of clinical trials for its efficacy and safety in the treatment of lobar and bronchial bacterial pneumonia. Successful clinical responses were achieved in 97.6% of the evaluable patients receiving 400 mg twice daily of loracarbef. This compared favorably with the respective response rates of 92.3% for patients receiving 500 mg three times a day of amoxicillin/clavulanate and 95.0% for patients receiving 500 mg three times a day of amoxicillin for the same illnesses. Proven or presumed elimination of the pretherapy pathogen was found in 89% of the patients receiving loracarbef, 92.3% of the amoxicillin/clavulanate-treated patients, and 70.0% of those receiving amoxicillin. Loracarbef was also well tolerated, although nausea and vomiting were associated with the use of all three agents. Nevertheless, treatment with loracarbef resulted in the lowest rate of discontinuation of therapy due to drug-related adverse events. Thus, these clinical trials support the conclusion that loracarbef is a safe and effective treatment for bacterial pneumonia.

Topics: Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Bacterial Infections; Cephalosporins; Clavulanic Acids; Drug Therapy, Combination; Humans; Nausea; Pneumonia; Randomized Controlled Trials as Topic; Vomiting

Optimal therapy for pyelonephritis requires the immediate administration of an effective broad-spectrum antibiotic. Because conventional oral antibiotics such as the sulfonamides and the aminopenicillins are limited by the development of resistant bacteria associated with this common disease, the therapeutic effectiveness of a new oral carbacephem antibiotic was investigated. Two double-blind, randomized clinical trials of loracarbef (LY163892) were conducted. A total of 245 patients (greater than or equal to 18 years old) with uncomplicated pyelonephritis were enrolled in parallel studies. One study compared loracarbef with cefaclor; the other compared loracarbef with norfloxacin. In the combined patient population, 119 patients were treated with loracarbef (400 mg twice daily), 43 with cefaclor (500 mg three times daily), and 83 with norfloxacin (400 mg twice daily). All treatment regimens continued for greater than or equal to 14 days. A total of 68 patients in the loracarbef group, 25 in the cefaclor group, and 43 in the norfloxacin group qualified for efficacy analysis. Escherichia coli was the causative pathogen in 85.0% of these patients. Successful posttherapy clinical and bacteriologic responses were similar for all three study drugs: 94.1 and 86.8%, 96.0 and 80.0%, 97.7 and 88.4% for loracarbef, cefaclor, and norfloxacin, respectively. Late posttherapy clinical responses were 87.4, 83.3, and 91.7% for the loracarbef, cefaclor, and norfloxacin groups, respectively. Bacteriologic responses for the three groups were 79.6, 60.0, and 88.9%. The most frequent adverse effects (headache, diarrhea, and nausea) were experienced by three patients (2.5%) in the loracarbef group; headaches were noted in two (4.7%) cefaclor patients, diarrhea was noted in three (7.0%) patients in the cefaclor group, and nausea was noted in four (9.3%). Gastrointestinal events were noted in four patients (4.8%) in the norfloxacin group. The data demonstrate that loracarbef is comparable in efficacy and safety to both cefaclor and norfloxacin as oral therapy for uncomplicated pyelonephritis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cefaclor; Cephalosporins; Diarrhea; Double-Blind Method; Europe; Female; Headache; Humans; Male; Middle Aged; Nausea; Norfloxacin; Pyelonephritis; Treatment Outcome; United States