ly-163892 and Pyelonephritis

There is increasing resistance to the oral antibiotics currently recommended for the treatment of pyelonephritis, and increased healthcare costs are associated with the reliance on alternative intravenous agents. We, therefore, performed a systematic review of randomised controlled trials to determine the clinical efficacy and safety of oral antibiotics for the treatment of pyelonephritis in adults. A search of four major medical databases (MEDLINE, Embase+ Embase classic, CENTRAL and Cochrane Database for Systematic Reviews) in addition to manual reference searching of relevant reviews was conducted. Clinical cure and adverse event rates were reported, and trial quality and bias were assessed. A total of 277 studies were reviewed; five studies matched all eligibility criteria and were included. Antibiotics included were cefaclor, ciprofloxacin, gatifloxacin, levofloxacin, lomefloxacin, loracarbef, norfloxacin, rufloxacin and trimethoprim-sulfamethoxazole. In included studies, the clinical success of the outpatient treatment of pyelonephritis by cefaclor, ciprofloxacin and norfloxacin at 4 to 6 weeks was comparable at between 83 to 95%. Relatively high rates of adverse events were noted in a trial of ciprofloxacin (24%) and trimethoprim-sulfamethoxazole (33%). Significant heterogeneity between all aspects of the trial designs was identified, with all studies having a potential for bias. This review demonstrates a need for high-quality clinical trials into the oral antibiotic treatment of pyelonephritis, with more consistent designs and reporting of outcomes. There are data to support further research into oral norfloxacin and cefaclor for the outpatient treatment of pyelonephritis in adults.

Topics: Acute Disease; Administration, Oral; Anti-Bacterial Agents; Cephalosporins; Ciprofloxacin; Drug Combinations; Humans; Norfloxacin; Pyelonephritis; Randomized Controlled Trials as Topic; Sulfamethizole; Trimethoprim

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