ly-163892 and Otitis-Media

Acute otitis media with effusion is one of the most common infectious diseases of childhood. Two multicenter randomized controlled clinical trials were conducted to assess the relative safety and efficacy of loracarbef and either amoxicillin/clavulanate or amoxicillin in the treatment of acute otitis media. Patients were evaluated clinically and bacteriologically at a pretherapy visit (within 48 hours of study drug administration), a posttherapy visit (within 72 hours after completion of therapy), and a late posttherapy visit (10 to 16 days after completion of therapy). In both studies, etiologic agents were assessed by tympanocentesis. In both studies patients had to have a pathogen susceptible to both study drugs to be continued in the study and declared evaluable. The first study, conducted at 24 United States centers, compared loracarbef 30 mg/kg/day in two divided doses and amoxicillin/clavulanate 40 mg/kg/day in three divided doses each for 10 days. At the posttherapy visit 124 (87.3%) of 142 evaluable loracarbef-treated patients and 130 (91.5%) of 142 evaluable amoxicillin/clavulanate-treated patients had favorable (cure or improvement) clinical outcomes (P = 0.247). Loracarbef-treated patients were significantly less likely to experience adverse events, notably diarrhea, than amoxicillin/clavulanate-treated patients (P less than 0.001). The second study, conducted at 12 European sites, compared loracarbef 30 mg/kg/day in two divided doses and amoxicillin 40 mg/kg/day in three divided doses each for 7 days. At the posttherapy visit 120 (81.1%) of 148 evaluable loracarbef-treated patients and 125 (87.4%) of 143 amoxicillin-treated patients had favorable clinical outcomes (P = 0.139). Loracarbef and amoxicillin displayed comparable safety, although vomiting appeared more frequently among patients receiving amoxicillin (P = 0.011).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Amoxicillin; Cephalosporins; Clinical Trials as Topic; Europe; Humans; Otitis Media; United States

Factors affecting outcome were analyzed from 3 antibiotic clinical trials that had identical case definition and outcome criteria. Overall 102 subjects with acute otitis media had an initial tympanocentesis, were enrolled in one of the clinical trials, were randomized to receive 10 days of oral treatment and had a posttherapy visit. The antibiotics used were cefixime (38), cefaclor (25), loracarbef (14), amoxicillin plus clavulanate (16) or amoxicillin (9). Fifty-five of the 102 (54%) study subjects were classified as cured or improved at the 21- to 28-day posttherapy visit. Factors analyzed in relation to outcome included antibiotic administered, isolation of a pathogen from the middle ear aspirate, study subject age and sex, history of recurrent otitis media, unilateral vs. bilateral involvement, season of enrollment and history of antibiotic administration in the month before enrollment. Univariate analysis identified the following four factors associated with higher posttherapy visit failure rates: a history of recurrent otitis media; enrollment during winter respiratory season (December through March); a history of being treated with an antibiotic during the month before enrollment; and administration of cefaclor compared with other antibiotics. However, only a history of recurrent otitis media and enrollment during the winter respiratory season met the 0.05 significance level for entry into a model derived from logistic regression to assess interactions among factors. Clinical guidelines for the management of otitis media should take into consideration that children with a prior history or recurrent otitis media and infection during the winter season more often fail to respond to antibiotic treatment and have a higher risk of developing a persistent middle ear effusion.

Topics: Acute Disease; Amoxicillin; Anti-Bacterial Agents; Cefaclor; Cefixime; Cefotaxime; Cephalosporins; Child; Child, Preschool; Clinical Trials as Topic; Female; Follow-Up Studies; Humans; Infant; Male; Otitis Media; Regression Analysis; Risk Factors; Treatment Outcome

Acute otitis media with effusion is one of the most common infectious diseases of childhood. Two multicenter randomized controlled clinical trials were conducted to assess the relative safety and efficacy of loracarbef and either amoxicillin/clavulanate or amoxicillin in the treatment of acute otitis media. Patients were evaluated clinically and bacteriologically at a pretherapy visit (within 48 hours of study drug administration), a posttherapy visit (within 72 hours after completion of therapy), and a late posttherapy visit (10 to 16 days after completion of therapy). In both studies, etiologic agents were assessed by tympanocentesis. In both studies patients had to have a pathogen susceptible to both study drugs to be continued in the study and declared evaluable. The first study, conducted at 24 United States centers, compared loracarbef 30 mg/kg/day in two divided doses and amoxicillin/clavulanate 40 mg/kg/day in three divided doses each for 10 days. At the posttherapy visit 124 (87.3%) of 142 evaluable loracarbef-treated patients and 130 (91.5%) of 142 evaluable amoxicillin/clavulanate-treated patients had favorable (cure or improvement) clinical outcomes (P = 0.247). Loracarbef-treated patients were significantly less likely to experience adverse events, notably diarrhea, than amoxicillin/clavulanate-treated patients (P less than 0.001). The second study, conducted at 12 European sites, compared loracarbef 30 mg/kg/day in two divided doses and amoxicillin 40 mg/kg/day in three divided doses each for 7 days. At the posttherapy visit 120 (81.1%) of 148 evaluable loracarbef-treated patients and 125 (87.4%) of 143 amoxicillin-treated patients had favorable clinical outcomes (P = 0.139). Loracarbef and amoxicillin displayed comparable safety, although vomiting appeared more frequently among patients receiving amoxicillin (P = 0.011).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Amoxicillin; Cephalosporins; Clinical Trials as Topic; Europe; Humans; Otitis Media; United States

One hundred five infants and children with acute otitis media were randomized to therapy with loracarbef, an experimental carbacephem antibiotic, or amoxicillin-clavulanate (Augmentin), an approved drug for this disease. Ninety-two were evaluable (46 in each group). Middle ear fluid samples obtained for culture before therapy grew Haemophilus spp. in 30% of cases, pneumococci in 29% of cases, and Moraxella catarrhalis in 15% of cases. beta-Lactamase-producing bacteria were found in 37% of patients. Clinical failure occurred in four loracarbef-treated patients and one amoxicillin-clavulanate-treated patient (P = 0.361). Recurrence of acute otitis media was more common in the 2 to 3 weeks after loracarbef treatment (eight patients) than it was after amoxicillin-clavulanate therapy (three patients), but not significantly so (P = 0.197). Thus, combined failure and recurrence occurred in 12 loracarbef-treated patients and four amoxicillin-clavulanate-treated patients (P = 0.052). Gastrointestinal side effects occurred in 13 loracarbef-treated and 21 amoxicillin-clavulanate-treated patients (P = 0.13). Diaper rash was more common with amoxicillin-clavulanate (22 patients) than with loracarbef (10 patients; P = 0.016). Satisfactory results were achieved with both antibiotics, and adverse effects, although common, were minor.

Topics: Acute Disease; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Bacteria; Cephalosporins; Child, Preschool; Clavulanic Acids; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Infant; Male; Microbial Sensitivity Tests; Otitis Media; Random Allocation; Recurrence

We describe a biopsy-confirmed case of acute interstitial nephritis associated with the use of loracarbef in an 18-month-old boy, which resulted in end-stage renal failure. This complication has been documented with the use of beta-lactam antibiotics, and it seems likely the loracarbef was responsible for acute interstitial nephritis in this patient.

Topics: Acute Disease; Anti-Bacterial Agents; Biopsy; Cephalosporins; Humans; Infant; Kidney; Male; Necrosis; Nephritis, Interstitial; Otitis Media

We compared the in-vitro activities of cefprozil, a novel oral cephalosporin, and of loracarbef, a new oral carbacephem, with other agents against middle ear fluid isolates obtained from children with acute otitis media. These included Streptococcus pneumoniae, Haemophilus influenzae and Branhamella catarrhalis. Cefprozil activity (MIC50 and MIC90) against S. pneumoniae was 0.25 and 0.50 mg/l; against H. influenzae 8 and 16 mg/l; against B. catarrhalis 2 and 2 mg/l. Loracarbef activity (MIC50 and MIC90) against S. pneumoniae was 1 and 2 mg/l; against H. influenzae 8 and 16 mg/l; against B. catarrhalis 1 and 8 mg/l. Cefprozil was four-fold more active against S. pneumoniae than loracarbef but similar to amoxycillin, amoxycillin/clavulanate, cefaclor, cefixime, cefuroxime and trimethoprim/sulfamethoxazole (TMP/SMX). Against H. influenzae, cefprozil was similar to loracarbef and other agents through less active than TMP/SMX and cefixime. Against B. catarrhalis, cefprozil was four-fold more active than loracarbef, cefaclor and cefixime but similar to the comparative antibiotics. Cefprozil and loracarbef activities were unaffected at pH 6 and 8 or in the presence of human serum, but there was a major diminution of activity for both agents at pH 5 and at inoculum sizes greater than or equal to 10(7) cfu/ml. Cefoprozil and loracarbef have consistent activity against middle ear pathogens and further pharmacokinetic and clinical studies appear warranted.

Topics: Acute Disease; Cefprozil; Cephalosporins; Ear, Middle; Haemophilus influenzae; Moraxella catarrhalis; Otitis Media; Streptococcus pneumoniae

Loracarbef concentrations in plasma and middle ear fluid (MEF) were measured in specimens obtained approximately 2 h after doses of 7.5 or 15 mg/kg. The mean +/- standard deviation concentrations in MEF were 2.0 +/- 2.6 mg/liter (48% of the concentration in plasma) after the smaller dose and 3.9 +/- 2.6 mg/liter (42% of the concentration in plasma) after the larger dose. With the larger dose, the concentrations in MEF were greater than the MIC for 90% of strains of the usual pathogens of acute otitis media tested in 16 of 17 specimens.

Topics: Body Fluids; Cephalosporins; Child; Child, Preschool; Ear, Middle; Female; Humans; Infant; Male; Otitis Media; Tympanoplasty