Comparative safety and efficacy of cefdinir vs amoxicillin/clavulanate for treatment of suppurative acute otitis media in children.

OBJECTIVE: Two dosage regimens of cefdinir were compared with amoxicillin/clavulanate for the treatment of suppurative acute otitis media (AOM) in children. METHODS: This was an investigator-blinded, randomized, comparative, multicenter trial, in which tympanocentesis was performed in 384 patients, ages 6 months to 12 years, who had nonrefractory AOM. Patients were randomized to receive one of three 10-day treatment regimens: cefdinir 14 mg/kg daily (QD; n = 128); cefdinir 7 mg/kg twice a day (BID; n = 128); or amoxicillin/clavulanate 40/10 mg/kg/day divided for use three times a day (TID; n = 128). RESULTS: Of the 384 enrolled patients 303 were evaluable for clinical efficacy. Clinical success rates were statistically equivalent for the 3 treatment groups at the end of therapy: 85 of 102 (83.3%) for cefdinir QD; 81 of 101 (80.2%) for cefdinir BID; 86 of 100 (86%) for amoxicillin/clavulanate. Of the 197 evaluable patients from whom a susceptible pathogen was recovered, presumptive eradication rates at end of therapy were equivalent: 55 of 65 (84.6%), 54 of 66 (81.8%) and 55 of 66 (83.3%) for cefdinir QD-, cefdinir BID- and amoxicillin/clavulanate-treated patients, respectively. However, presumptive eradication rates for Streptococcus pneumoniae were significantly lower for cefdinir BID (55.2%) than for amoxicillin/clavulanate (89.5%; P = 0.0019) and marginally lower than for cefdinir QD (80%; P = 0.054). Diarrhea was the most common treatment-associated adverse reaction in all groups but was significantly more common in amoxicillin/clavulanate-treated patients (35%) than in patients who had been treated with cefdinir QD (10%, P<0.001) or cefdinir BID (13%, P<0.001). CONCLUSIONS: A 10-day regimen of cefdinir 14 mg/kg QD or 7 mg/kg BID was as clinically effective overall as a 10-day regimen of amoxicillin/ clavulanate 40/10 mg/kg/day divided TID in the treatment of tympanocentesis-confirmed, nonrefractory AOM in children. These data suggest that cefdinir QD may be a better alternative than cefdinir BID for refractory AOM. Both dosing regimens of cefdinir were associated with significantly fewer gastrointestinal adverse reactions than was amoxicillin/clavulanate.

Cefdinir versus cephalexin for the treatment of skin and skin-structure infections. The Cefdinir Adult Skin Infection Study Group.

Because of increasing resistance to older antimicrobial agents, newer drugs need to be evaluated for the treatment of skin and skin-structure infections (SSSIs). This double-masked, randomized, comparative, multicenter study enrolled patients aged 13 years or older with SSSIs to receive either cefdinir 300 mg BID or cephalexin 500 mg QID for 10 days. Nine hundred fifty-two patients (474 in the cefdinir group and 478 in the cephalexin group) took part, primarily white males between 18 and 65 years of age. There were two follow-up visits, with efficacy determined at the test-of-cure visit, 7 to 16 days posttherapy. Many patients were not microbiologically assessable, primarily because of negative cultures at study admission. Patients who required surgical intervention (e.g., incision and drainage) at the site of infection more than 24 hours after the initiation of drug therapy were defined as treatment failures. Significantly more isolated pathogens were resistant to cephalexin than to cefdinir. In the 178 efficacy-assessable cefdinir-treated patients, the rate of pathogen eradication was 93% (200/215), and the rate of successful clinical response was 88% (157/178), compared with 89% (221/247) and 87% (177/204), respectively, in the 204 efficacy-assessable cephalexin-treated patients. Using confidence-interval analysis, the microbiologic and clinical response rates of the cefdinir-treated patients were statistically equivalent to those of the cephalexin-treated patients. At the follow-up visits, patients were questioned about any adverse events occurring since their previous visit. Any untoward symptom occurring during or within 2 days after completion of drug treatment was considered an adverse reaction if the investigator judged it to be definitely, probably, or possibly related to the study drug. One hundred twenty-three (26%) cefdinir-treated patients and 77 (16%) cephalexin-treated patients experienced at least one adverse reaction, a statistically significant difference. Study drug was discontinued for adverse reactions in 20 (4%) cefdinir-treated patients and 13 (3%) cephalexin-treated patients; in the two groups, 10 and 7 patients, respectively, were discontinued for diarrhea. Cefdinir taken BID was as effective as cephalexin taken QID in the treatment of mild-to-moderate SSSIs and was well tolerated by most patients. The increased antibacterial activity of cefdinir must be balanced against the higher rate of diarrhea seen in patients treated with this drug.

Efficacy and safety of cefdinir in the treatment of patients with acute bronchitis. The Cefdinir Bronchitis Study Group.

In this randomized, open-label, dose-comparative study, 18 investigators enrolled 466 patients with acute bronchitis. Patients were randomly assigned to receive either 600 mg of cefdinir once daily (QD) or 300 mg of cefdinir twice daily (BID) for 10 days. Both microbiologic and clinical efficacy were assessed at the test-of-cure visit, 7 to 14 days after therapy stopped. A total of 296 patients were classified as assessable at the test-of-cure visit (n = 150 QD, n = 146 BID). Eradication rates of baseline pathogens in these assessable patients were similar in both groups; the baseline pathogen eradication rate for assessable patients in the QD arm was 92%, and that in the BID arm was 93%. Clinical success (cure or improvement) in assessable patients was 91% and 93%, respectively. No difference was seen in the incidence of adverse events, in the incidence of diarrhea, or in the incidence of treatment withdrawals between the two groups. We conclude that cefdinir is effective and safe for the treatment of patients with acute bronchitis.

Cefdinir versus cefaclor in the treatment of uncomplicated urinary tract infection.

OBJECTIVE: This multicenter, double-blind, randomized, parallel-group study was conducted in Europe, South Africa, and Australia to compare the clinical and microbiologic efficacy and the tolerability of a cephalosporin antibiotic, cefdinir, with those of cefaclor in the treatment of uncomplicated urinary tract infection. METHODS: Patients were randomized in a 1:1 ratio to 5 days of treatment with either cefdinir 100 mg BID or cefaclor 250 mg TID. RESULTS: A total of 661 patients were randomized to treatment. They were 90% female, with a median age of 44 years. There were no clinically important differences between groups in terms of demographic characteristics or symptoms on admission. The most frequently isolated pathogens in admission urine cultures were Escherichia coli (383 patients), Proteus mirabilis (20 patients), Staphylococcus saprophyticus (14 patients), and Klebsiella pneumoniae (9 patients). Of the admission pathogens with documented susceptibility results, significantly more were resistant to cefaclor (6.7%) than to cefdinir (3.7%; P < 0.003). Significantly more admission isolates of E. coli were resistant to cefaclor (5.1%) than to cefdinir (2.0%; P < 0.007). A total of 383 patients were assessable for efficacy, 196 in the cefdinir group and 187 in the cefaclor group. Clinical cure rates and microbiologic response rates for cefdinir and cefaclor were statistically equivalent at 5 to 9 days posttherapy (test-of-cure visit), using a 95% CI approach. The rate of treatment-related adverse events was higher in cefdinir-treated patients (20.2%) than in cefaclor-treated patients (13.0%; P = 0.025), mainly due to the greater frequency of diarrhea in the former group. However, only 4 patients (1.2%) discontinued cefdinir treatment due to diarrhea. CONCLUSION: Empiric therapy with cefdinir appears to be a reasonable choice for patients with uncomplicated urinary tract infection in whom cephalosporin treatment is indicated.

Comparison of cefdinir and penicillin for the treatment of pediatric streptococcal pharyngitis.

This multicenter, randomized, controlled, investigator-masked study was performed to assess the efficacy and tolerability of cefdinir for the treatment of streptococcal pharyngitis. Children aged 1 through 12 years with signs and symptoms of pharyngitis and a positive result on a rapid screening test for Streptococcus pyogenes were randomly assigned to receive cefdinir 14 mg/kg QD, cefdinir 7 mg/kg BID, or penicillin V 10 mg/kg 4 times daily for 10 days. Seven hundred ninety-two patients were enrolled, and 682 were clinically and microbiologically assessable. All treatment groups had similar demographic characteristics (-50.0% male, predominantly white, median age 7 years). The eradication rates of S pyogenes, determined 4 to 9 days after completion of therapy, were 94.3% in the cefdinir QD group, 94.3% in the cefdinir BID group, and 70.0% in the penicillin V group (95% confidence interval [CI] 17.6%-30.9%, P < 0.001 for cefdinir QD vs penicillin; CI 17.5%-30.9%, P < 0.001 for cefdinir BID vs penicillin). Clinical cure rates were 97.4%, 96.0%, and 86.3% for the cefdinir QD, cefdinir BID, and penicillin groups, respectively (CI 6.1%-15.9%, P = 0.001 for cefdinir QD vs penicillin; CI 4.6%-14.8%, P = 0.001 for cefdinir BID vs penicillin). Adverse reactions occurred in 8.3%, 8.7%, and 7.6% of cefdinir QD, cefdinir BID, and penicillin patients, respectively (P = NS). Treatment with cefdinir, either QD or BID, was associated with higher eradication rates of S pyogenes and higher clinical cure rates. Both cefdinir and penicillin were well tolerated. Three patients, 1 receiving cefdinir BID and 2 receiving penicillin, discontinued the study drug because of adverse reactions.

Comparison of cefdinir and penicillin for the treatment of streptococcal pharyngitis. Cefdinir Pharyngitis Study Group.

Cefdinir, an oral cephalosporin active against Streptococcus pyogenes (group A beta-hemolytic streptococci [GABHS]), is also resistant to degradation by most oropharyngeal beta-lactamases. This multicenter, randomized, controlled, double-masked study assessed the tolerability and efficacy of 2 dosing regimens of cefdinir in the treatment of pharyngitis due to GABHS. Adults and adolescents with pharyngitis due to GABHS received cefdinir 600 mg QD, cefdinir 300 mg BID, or penicillin V 250 mg QID each for 10 days. A throat culture and clinical assessment were obtained 4 to 9 days after completion of therapy. Of 919 patients enrolled, 644 (70.1%) were microbiologically assessable. The eradication rates 4 to 9 days after completion of therapy were 91.4% in the cefdinir QD group, 91.7% in the cefdinir BID group, and 83.4% in the penicillin group (P = 0.02 for cefdinir QD vs penicillin, P = 0.01 for cefdinir BID vs penicillin, P = 0.95 for cefdinir QD vs cefdinir BID). Clinical cure rates were also superior with cefdinir QD (94.8%, P = 0.02) and cefdinir BID (96.3%, P < 0.01) compared with penicillin (88.9%). Diarrhea was more common in the cefdinir groups (P < 0.001). Seventeen cefdinir patients and 4 penicillin patients discontinued therapy because of adverse reaction (P = 0.13). Ten days of treatment for streptococcal pharyngitis with cefdinir QD or BID is superior to treatment with penicillin V for the eradication of GABHS from the pharynx, although it is associated with a higher rate of adverse reactions.

International study comparing cefdinir and cefuroxime axetil in the treatment of patients with acute exacerbation of chronic bronchitis.

OBJECTIVES: To assess the efficacy and tolerability of three antibiotic regimens in patients with acute exacerbation of chronic bronchitis. METHODS: In this double-blind, randomized, multicentered, parallel-group study, patients received once-daily cefdinir 600 mg, twice-daily cefdinir 300 mg, or twice-daily cefuroxime axetil 250 mg for 10 days. Primary efficacy measures were microbiologic eradication rate, by pathogen and by patient, and clinical response rate, by patient. RESULTS: Of 1045 patients, 589 were evaluable for efficacy. At baseline, most patients had moderate or severe cough and sputum production as well as rhonchi, wheezing, and dyspnea. The microbiologic eradication rates by pathogen were 90% with once-daily cefdinir, 85% with twice-daily cefdinir, and 88% with twice-daily cefuroxime. The corresponding values for microbiologic eradication rate by patient were 90% (once-daily cefdinir), 85% (twice-daily cefdinir), and 86% (twice-daily cefuroxime). The respective clinical response rates by patient were 81%, 74%, and 80%. There were no significant differences in the incidence of drug-related adverse events or discontinuations due to adverse events. Diarrhea was the most frequent complaint. CONCLUSIONS: The results indicate that the efficacy and tolerability of cefdinir, once or twice daily, and cefuroxime were comparable with no significant differences between the regimens used.

Comparison of cefdinir and cefaclor in treatment of community-acquired pneumonia.

Six hundred ninety patients were enrolled in a multicenter, randomized, double-blind trial comparing the efficacy and safety of cefdinir with those of cefaclor in the treatment of community-acquired pneumonia. Patients received either 10 days of treatment with cefdinir (n = 347) at 300 mg twice daily or 10 days of treatment with cefaclor (n = 343) at 500 mg three times daily. Microbiological assessments were performed on sputum specimens obtained at admission and at the two posttherapy visits, if available. Respiratory tract pathogens were isolated from 538 (78%) of 690 patient admission sputum specimens, with the predominant pathogens being Haemophilus parainfluenzae, Haemophilus influenzae, Streptococcus pneumoniae, and Staphylococcus aureus. The microbiological eradication rates at the test-of-cure visit were 92% (238 of 260 pathogens) and 93% (245 of 264 pathogens) for the evaluable patients treated with cefdinir and cefaclor, respectively. A satisfactory clinical response (cure plus improvement) was achieved in 89% (166 of 187) and 86% (160 of 186) of the evaluable patients treated with cefdinir and cefaclor, respectively. Except for the incidence of diarrhea, adverse event rates while on treatment were equivalent between the two treatment groups. Diarrhea incidence during therapy was higher for patients treated with cefdinir (13.7%) than for patients treated with cefaclor (5.3%). These results indicate that cefdinir is effective and safe in the treatment of patients with pneumonia.

Study of use of cefdinir versus cephalexin for treatment of skin infections in pediatric patients. The Cefdinir Pediatric Skin Infection Study Group.

Three hundred ninety-four patients, aged 6 months to 12 years, entered a multicenter, randomized, controlled, investigator-blind study comparing cefdinir, 7 mg/kg of body weight twice a day, with cephalexin, 10 mg/kg four times a day, each given for 10 days. The most common infections treated were impetigo and secondary infection of preexisting dermatitis. The most common pathogens isolated were Staphylococcus aureus and Streptococcus pyogenes. Two hundred thirty-one patients were microbiologically evaluable. Microbiologic eradication rates were 164 of 165 pathogens (99.4%) in the cefdinir group and 152 of 156 pathogens (97.4%) in the cephalexin group (P = 0.14). Clinical cure rates were 116 of 118 patients (98.3%) in the cefdinir group and 106 of 113 patients (93.8%) in the cephalexin group (P = 0.056). Sixteen percent of cefdinir patients and 11% of cephalexin patients experienced adverse events (P = 0.11), the most common being diarrhea, which affected 8% of the cefdinir group and 4% of the cephalexin group. Cefdinir appears to be an effective and well-tolerated agent for the treatment of uncomplicated skin and skin structure infections in pediatric patients.

Comparison of a 5 day regimen of cefdinir with a 10 day regimen of cefprozil for treatment of acute exacerbations of chronic bronchitis.

Patients with acute exacerbations of chronic bronchitis were treated with cefdinir 300 mg bd for 5 days or cefprozil 500 mg bd for 10 days in a prospective, randomized, double-blind, multicentre study. Of the 548 patients enrolled, 281 (51%) were evaluable. The clinical cure rates at the test-of-cure visit were 80% (114/142) and 72% (100/139) for the evaluable patients treated with cefdinir and cefprozil, respectively. Respiratory tract pathogens were isolated from 409 (75%) of 548 admission sputum specimens, with the predominant pathogens being Haemophilus parainfluenzae, Haemophilus influenzae, Staphylococcus aureus and Moraxella catarrhalis. The microbiological eradication rates at the test-of-cure visit were 81% (157 of 193 pathogens) and 84% (166 of 198 pathogens) for the evaluable patients treated with cefdinir and cefprozil, respectively. Adverse event rates while on treatment were equivalent between the two treatment groups. The incidence of diarrhoea during therapy was higher for patients treated with cefdinir (17%) than for patients treated with cefprozil (6%) (P < 0.01), but most cases were mild and did not lead to discontinuation of treatment. These results indicate that a 5 day regimen of cefdinir is as effective and safe in the treatment of patients with acute exacerbations of chronic bronchitis as a 10 day regimen of cefprozil.

Five-day cefdinir treatment for streptococcal pharyngitis. Cefdinir Pharyngitis Study Group.

A multicenter, randomized, controlled, investigator-blind study was performed to evaluate the safety and efficacy of oral cefdinir versus oral penicillin V for the treatment of pharyngitis due to group A beta-hemolytic streptococci (GABHS). Patients 13 years of age and older were randomized to receive either oral cefdinir (300 mg twice a day) for 5 days followed by placebo for 5 days or oral penicillin V (250 mg four times a day) for 10 days. Throat cultures were obtained, and signs and symptoms of pharyngitis were recorded at study admission and follow-up visits on study days 11 to 15, 16 to 20, and 25 to 31. Patients kept a diary to record medication intake and their assessment of throat pain at admission and at each day of study treatment. Five hundred fifty-eight patients were enrolled, of whom 432 (77.4%) were clinically and microbiologically evaluable. The GABHS eradication rates 5 to 10 days after completion of therapy were 193 of 218 (88.5%) in the cefdinir group and 176 of 214 (82.2%) in the penicillin group (P = 0.053). Clinical cure rates were 89.0 and 84.6%, respectively (P = 0.80). By the time of the long-term follow-up visit, 2 to 3 weeks after completion of treatment, 156 of 191 (81.7%) of the assessable cefdinir patients and 152 of 195 (77.9%) of the penicillin patients remained free of GABHS. Both treatments were well tolerated, with adverse reaction rates of 18.3% in the cefdinir study arm and 15.0% in the penicillin study arm (P = 0.278). Five-day treatment with cefdinir is safe and effective therapy for GABHS pharyngitis. Based on its twice-a-day dosage and shorter course of therapy, leading to potentially greater patient compliance, cefdinir may be considered for use in the treatment of pharyngitis caused by GABHS.

A comparison of a five-day regimen of cefdinir with a seven-day regimen of loracarbef for the treatment of acute exacerbations of chronic bronchitis.

To compare the efficacy and safety of five-day cefdinir treatment with seven-day loracarbef treatment in patients with acute exacerbations of chronic bronchitis, 586 patients were enrolled in a multicentre, randomised, double-blind trial. Patients received either five days of treatment with cefdinir (n = 291) at 300 mg twice daily or seven days of treatment with loracarbef (n = 295) at 400 mg twice daily. Microbiological assessments were done on sputum specimens obtained at admission and at the two post-therapy visits, if available. The clinical cure rates were 86% (138/160) and 85% (141/166) for the evaluable patients treated with cefdinir and loracarbef, respectively. Respiratory tract pathogens were isolated from 457 (78%) of 586 admission sputum specimens, with the predominant pathogens being Haemophilus parainfluenzae, H. influenzae, Moraxella catarrhalis and Staphylococcus aureus. The microbiological eradication rates at the test-of-cure visit were 88% (193/219 pathogens) and 90% (227/251 pathogens) for the evaluable patients treated with cefdinir and loracarbef, respectively. Adverse event rates while on treatment were 30% and 21% for cefdinir- and loracarbef-treated patients, respectively. These results indicate that a five-day regimen of cefdinir is effective and safe for the treatment of patients with acute exacerbations of chronic bronchitis.