ly-163892 and Streptococcal-Infections

Patients with acute group A- strepotococcal pharyngotonsillitis were randomly assigned to treatment for 10 d with either phenoxymethylpenicillin (PcV), loracarbef or clindamycin. The concentrations of the drugs, respectively, were determined in tonsillar surface fluid (TSF), serum and the saliva in each patient on altogether 5 occasions; before, during and 4 d after end of therapy. On the same occasions blood was drawn for analysis of C-reactive protein (CRP) and orosomucoid. On the last d of treatment PcV could be detected in TSF in 1 of 6 patients only. Loracarbef had a slower decrease in TSF during therapy and measurable levels did occur 2 d after end of therapy corresponding to MIC 100 for GAS. This may be related to the somewhat better clinical results of the cephalosporins than of PcV, and possibly indicates that an extended therapy with these drugs in primary GAS pharyngotonsillitis for more than the arbitrarily chosen 10 d could reduce the number of recurrent episodes. PcV and loracarbef were not detected in serum after the end of treatment. The concentration of clindamycin in both TSF and the saliva was fairly longstanding during therapy and reached levels exceeding MIC 100 for GAS, in both TSF and serum 2 d after the end of treatment. Several investigations have shown that GAS, especially in the stationary phase may invade respiratory epithelial cells and are present intracellularly in patients with acute pharyngotonsillitis as well as in asymptomatic carriers. The same T-type, identical DNA fingerprints and arbitrarily primed patterns are found in GAS before and after treatment failure indicating that the primary episode and the failures are caused by the same strain. The longstanding concentrations of clindamycin in TSF, roughly independent of the degree of the local inflammation combined with its intracellular accumulation and activity against resting GAS seem to explain the efficiency of the drug in recurrent GAS pharyngotonsillitis. CRP and orosomucoid were of limited value in differing between bacterial and viral pharyngtonsillitis and a correlation between antibiotic concentration and CRP/orosomucoid levels was not found.

Topics: Adult; Aged; Anti-Bacterial Agents; C-Reactive Protein; Cephalosporins; Clindamycin; Female; Humans; Male; Middle Aged; Orosomucoid; Palatine Tonsil; Penicillin V; Streptococcal Infections; Streptococcus pyogenes; Tissue Distribution; Tonsillitis

Knowledge of the treatment of recurrent group A streptococcal pharyngotonsillitis has, so far, been based on studies of non-recurrent rather than recurrent episodes of the disease. This multicentre, double-blind, randomized trial was designed to compare the efficacy of loracarbef (200 mg twice daily) vs phenoxymethylpenicillin (penicillin V) (800/1000 mg twice daily) each for 10 days in the treatment of recurrent group A streptococcal pharyngotonsillitis. Among the 331 patients enrolled in the study, 265 were evaluable for efficacy. The combined clinical and bacteriological failure rate was 8.2% in the loracarbef group and 21.5% in the penicillin V group (p = 0.008). Bacterial eradication was noted in 90% of loracarbef-treated patients compared to 66% of penicillin V-treated patients (p < 0.0005). The higher bacteriological eradication and clinical efficacy rate among loracarbef patients might be related to higher stability of loracarbef in the presence of beta-lactamases produced by the oral microflora. These results suggest loracarbef to be a strong candidate for treatment of patients with recurrent group A streptococcal pharyngotonsillitis.

Topics: Cephalosporins; Double-Blind Method; Humans; Penicillin V; Penicillins; Pharyngeal Diseases; Streptococcal Infections; Tonsillitis

A double blind, randomized clinical trial compared loracarbef (LY163892) with penicillin VK. Two hundred thirty-three pediatric patients (less than or equal to 12 years) with a diagnosis of pharyngitis or tonsillitis resulting from Group A beta-hemolytic streptococci were randomized to treatment. Patients in the loracarbef group (n = 120) received loracarbef as a 15-mg/kg/day oral suspension or 200-mg capsule taken twice daily for 10 days. Patients in the penicillin group (n = 113) received penicillin VK as a 20-mg/kg/day oral suspension or 250-mg capsule taken four times daily for 10 days. Successful clinical responses were demonstrated in 101 of the 104 (97.1%) evaluable patients treated with loracarbef compared with 83 of 88 (94.3%) of evaluable patients treated with penicillin. The clinical relapse rate for the loracarbef group was 2.9% vs. 5.7% for the penicillin group. Bacteriologic response data approximated the clinical response data, as eradication of Group A beta-hemolytic streptococci was found in 86.5 and 81.8% of the loracarbef group and the penicillin group, respectively. No statistically significant difference in the incidence of treatment-emergent adverse reactions was noted between the two groups. The results indicate that loracarbef taken twice daily was comparable in safety and efficacy to penicillin VK taken four times daily in the treatment of Group A beta-hemolytic Streptococcus-associated pharyngitis and tonsillitis in children.

Topics: Cephalosporins; Child; Child, Preschool; Double-Blind Method; Female; Humans; Infant; Male; Penicillin V; Pharyngitis; Streptococcal Infections; Streptococcus pyogenes; Tonsillitis

A double blind, randomized clinical trial involving 214 children, ages 6 months to 12 years, compared the safety and effectiveness of the new carbacephem loracarbef and the cephalosporin cefaclor for the treatment of skin and skin structure infections. The two agents were given primarily as oral suspensions. Dosages were 15 mg/kg/day in two divided doses for loracarbef and 20 mg/kg/day in three divided doses for cefaclor. Assessment 72 hours after completion of the 7-day course of treatment indicated a favorable clinical response plus eradication of the pretherapy pathogen in 97.3% of the 74 loracarbef-treated patients eligible for evaluation and 92.3% of 78 evaluable cefaclor-treated patients. Favorable response rates at a second posttreatment visit 10 to 14 days after the end of therapy were 95.6% in 68 evaluable loracarbef-treated patients and 86.2% in 65 treated with cefaclor. The incidence of adverse reactions, including gastrointestinal effects, was low in both groups. No statistical difference in clinical or bacteriologic efficacy or safety was detected between patients treated with loracarbef and cefaclor.

Topics: Cefaclor; Cephalosporins; Child; Child, Preschool; Double-Blind Method; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Male; Skin Diseases, Infectious; Staphylococcal Skin Infections; Staphylococcus aureus; Streptococcal Infections; Streptococcus pyogenes

Loracarbef, a member of the carbacephem class of beta-lactam antibiotics, is a potent anti-bacterial agent. In a double-blind, randomized clinical trial to assess the efficacy and safety of loracarbef in the treatment of streptococcal pharyngitis and tonsillitis, 107 adult patients were treated with loracarbef (200 mg capsules twice a day or 15 mg/kg/day suspension) and 111 patients were treated with penicillin VK (250 mg capsules four times a day or 20 mg/kg/day suspension) for 10 days. In the loracarbef treatment group, 96.6% of the evaluable patients had a favorable clinical response 3-5 days after therapy, a result that compared favorably with the 93.9% response rate achieved in the penicillin group. The clinical failure/relapse rates were 3.4% for loracarbef-treated patients and 6.1% for patients receiving penicillin. Bacteriologic response data approximated the clinical results, with a successful response in 89.9% of the loracarbef-treated patients and 91.5% of the penicillin recipients. Two (1.9%) loracarbef-treated patients with rash and one (0.9%) penicillin-treated patient with diarrhea discontinued the study early because of these adverse events. The incidence of adverse events was comparable in the two treatment groups except for increased cough, which was reported by 3.7% of the loracarbef-treated patients and none of the penicillin recipients. These data support the conclusion that loracarbef is comparable to penicillin VK in the treatment of streptococcal pharyngitis and tonsillitis in adults.

Topics: Adult; Cephalosporins; Cough; Diarrhea; Double-Blind Method; Headache; Humans; North America; Penicillin V; Pharyngitis; Streptococcal Infections; Streptococcus pyogenes; Tonsillitis

The in vitro activity of loracarbef, penicillin V, cefaclor and cefadroxil against log and stationary phase cultures of group A streptococci was compared. MICs and MBCs were determined with the broth dilution method and by a modified agar plate dilution technique where the beta-lactams were inactivated after the MICs were determined allowing inhibited but not killed organisms to grow on further incubation. The MICs of loracarbef and the two cephalosporins were 16-32 times higher than those of penicillin V. In plate dilution the MBC/MIC ratios of all agents were < or = 2 for log phase cultures. With stationary phase cultures, especially in the broth dilution test, the MBC/MIC ratios of loracarbef and the two cephalosporins were > or = 32 for a large number of strains. The phenotype response of stationary phase cultures to beta-lactam antibiotics may not only be related to the physiological status of the streptococci, to the culture conditions and to the beta-lactam under test. The present investigation indicated that the phenotypic response was also an intrinsic property of certain strains.

Topics: Anti-Bacterial Agents; Cefaclor; Cefadroxil; Cephalosporins; Humans; In Vitro Techniques; Microbial Sensitivity Tests; Penicillin V; Pharyngitis; Streptococcal Infections; Streptococcus pyogenes