Open-Label, parallel-group, multicenter, randomized study of cefprozil versus erythromycin in children with group A streptococcal pharyngitis/tonsillitis.

BACKGROUND: Cefprozil and erythromycin are acceptable alternatives to penicillin in the treatment of pharyngitis/tonsillitis due to group A beta-hemolytic streptococcus (GABHS). OBJECTIVE: The purpose of this trial was to determine the relative efficacy and tolerability of cefprozil and erythromycin in the treatment of pediatric pharyngitis/tonsillitis due to GABHS. METHODS: This trial compared the bacteriologic and clinical efficacy of erythromycin and cefprozil in children 2 to 12 years of age with culture-documented GABHS pharyngitis/ tonsillitis. Children who were allergic to penicillin, cefprozil, or erythromycin were excluded. Patients were prospectively randomly assigned to receive 10 days of oral therapy with either cefprozil suspension 15 mg/kg per day in 2 divided doses or erythromycin ethylsuccinate suspension 30 mg/kg per day in 3 divided doses. Primary efficacy end points were bacteriologic and clinical response 2 to 8 days after treatment ended. The frequency and severity of adverse events and their relationship to treatment were also assessed. RESULTS: A total of 199 patients were enrolled and treated (cefprozil, 99; erythromycin, 100); 12 patients in the cefprozil group and 15 in the erythromycin group were not evaluable. The GABHS eradication rate was significantly higher with cefprozil (95%) than with erythromycin (74%) (P = 0.001). The posttreatment carrier rate was lower in the cefprozil group (5%) than in the erythromycin group (18%) (95% CI, -22.3 to -3.8). Clinical cure rate was 90% (78/87) with cefprozil and 91% (77/85) with erythromycin (P = 0.95) (treatment group difference, -0.93; 95% CI, -9.9% to 8.0%). The overall incidence of drug-related adverse events was not significantly different in the 2 groups (11% with cef- prozil, 18% with erythromycin). The most common adverse events were diarrhea and vomiting. Two patients in the erythromycin group discontinued therapy because of adverse events. CONCLUSIONS: The bacteriologic eradication rate was significantly greater with cefprozil compared with erythromycin in children with pharyngitis/tonsillitis. Both cefprozil and erythromycin produced a clinical cure in >90% of patients.

Antimicrobial therapy of acute otitis media: review of treatment recommendations.

OBJECTIVE: This paper reviews 3 previously published articles that provided recommendations for antimicrobial therapy of acute otitis media (AOM) and combines them to provide revised recommendations. BACKGROUND: AOM is one of the most common pediatric infections requiring a prescription for an antimicrobial agent. The optimal approach to treatment of AOM requires early, efficacious, and practical therapy. Several experts and organizations have developed recommendations for the management of AOM, but the number of these may overwhelm the busy primary care practitioner. A MEDLINE search of the pediatric and infectious disease literature on AOM treatment recommendations was used to select 3 representative, previously published articles for this review. When selecting an agent, physicians should consider in vitro activity, particularly against drug-resistant Streptococcus pneumoniae; pharmacokinetics; adverse events; palatability of the suspension; and cost. In addition, physicians' clinical experience is an important determinant. CONCLUSIONS: Amoxicillin is recommended as the first-line agent to treat uncomplicated AOM. For clinical treatment failures after 3 days of amoxicillin, recommended antimicrobial agents include oral amoxicillin/clavulanate, cefuroxime axetil, cefprozil, cefpodoxime proxetil, and intramuscular (i.m.) ceftriaxone. I.m. ceftriaxone should be reserved for severe cases or patients in whom noncompliance is expected. Tympanocentesis for identification of pathogens and susceptibility to antimicrobial agents is recommended for selection of third-line agents.

Equivalent efficacy and reduced occurrence of diarrhea from a new formulation of amoxicillin/clavulanate potassium (Augmentin) for treatment of acute otitis media in children.

OBJECTIVE: To compare the safety and efficacy, in treating acute otitis media (AOM) in children, of a new formulation of amoxicillin/clavulanate potassium (Augmentin) oral suspension providing 45/6.4 mg/kg/day and administered twice daily (bid) for 5 and 10 days, respectively, with the safety and efficacy of the original formulation providing 40/10 mg/kg/day and administered three times daily (tid) for 10 days. STUDY DESIGN: Eight hundred sixty-eight children ages 2 months to 12 years with AOM were randomly assigned to one of the three treatment groups. Stringent criteria were used for the diagnosis of AOM and for determinations of "cure" and "improvement." Subjects were reexamined on Days 12 to 14 and 32 to 38. RESULTS: Among subjects whose treatment and follow-up conformed fully to protocol, the proportion of treatment successes (clinically cured or improved) on Days 12 to 14 was 78.8% (149 of 189) in the tid 10-day group, 86.5% (154 of 178) in the bid 10-day group and 71.1% (140 of 197) in the bid 5-day group. Corresponding values on Days 32 to 38 were 64.2% (95 of 148) in the tid 10-day group, 63.1% (94 of 149) in the bid 10-day group and 57.8% (93 of 161) in the bid 5-day group. None of the differences between the tid 10-day regimen and either of the 2 bid regimens were statistically significant, but the bid 10-day regimen was significantly more effective than the bid 5-day regimen in younger subjects. In the study population as a whole, results were similar to those in per protocol subjects. Overall the incidence of protocol-defined diarrhea was 26.7% (74 of 277) in the tid 10-day group, compared with 9.6% (27 of 280) in the bid 10-day group (P < 0.0001) and 8.7% (25 of 286) in the bid 5-day group (P < 0.0001). CONCLUSIONS: In comparison with the original formulation of Augmentin administered tid for 10 days in the treatment of AOM in children, the new formulation administered bid for 10 days provides at least equivalent efficacy and causes substantially less diarrhea. Administration for 5 days appears not to provide equivalent efficacy, but the difference appears limited to younger children and the margin of difference is small.

Efficacy of cefuroxime axetil suspension compared with that of penicillin V suspension in children with group A streptococcal pharyngitis.

The bacteriological and clinical efficacies of cefuroxime axetil suspension (20 mg/kg of body weight per day in two divided doses) were compared with those of penicillin V suspension (50 mg/kg/day in three divided doses) in a multicenter, randomized, evaluator-blinded study. Children aged 2 to 13 years with clinical signs and symptoms of acute pharyngitis and a positive throat culture for group A beta-hemolytic streptococci (GABHS) were eligible. Patients were assessed and samples from the throat for culture were obtained at the time of diagnosis, 3 to 7 days after the initiation of treatment, and 4 to 8 days and 19 to 25 days after the completion of 10 days of therapy. Of the 385 evaluable patients, GABHS were eradicated from 244 of 259 (94.2%) cefuroxime-treated patients and 106 of 126 (84.1%) penicillin-treated patients (P = 0.001). Complete resolution of the signs and symptoms present at the time of diagnosis was achieved in 238 of 259 (91.9%) cefuroxime-treated patients and 102 of 126 (81.0%) penicillin-treated patients (P = 0.001). Potential drug-related adverse events were reported in 7.0 and 3.2% of the cefuroxime- and penicillin-treated patients, respectively (P = 0.078). In the present study, cefuroxime axetil suspension given twice daily resulted in significantly greater bacteriological and clinical efficacies than those of penicillin V suspension given three times daily to pediatric patients with acute pharyngitis and a positive throat culture for GABHS.

Comparison of cefuroxime axetil, cefaclor, and amoxicillin-clavulanate potassium suspensions in acute otitis media in infants and children.

In this randomized, blinded, multicenter comparison study, 377 infants and children with acute otitis media (AOM) received a 10-day course of an oral suspension of one of the following: cefuroxime axetil (CAE), 30 mg/kg/day; cefaclor (CEC), 40 mg/kg/day; or amoxicillin-clavulanate potassium (AMX-CL), 40 mg/kg/day. Clinical efficacy was determined by pneumatic otoscopy and tympanometric testing 3 to 5, 11 to 14, and 22 to 26 days after the initiation of therapy. There was a statistically significant difference among the three treatment groups with respect to clinical outcome; more patients in the CAE group (62%) than in the CEC group (46%) or the AMX-CL group (52%) had complete resolution of signs and symptoms of AOM (including effusion). Paired comparisons revealed a significant difference in efficacy between CAE and CEC and a nearly significant difference between AMX-CL and CEC. Taste acceptability was highest for CEC and lowest for this formulation of CAE. Significantly more patients in the AMX-CL group than in the CAE or CEC group had a side effect, primarily diarrhea, vomiting, or diaper rash. We conclude that CAE suspension has greater clinical efficacy than CEC and fewer side effects than AMX-CL.

Treatment of otitis media with cefuroxime axetil.

Cefuroxime axetil and cefaclor were compared for efficacy in the treatment of acute otitis media with effusion. Sixty-four pediatric outpatients had tympanocentesis for culture, and then were randomized to a ten-day course of treatment with cefuroxime axetil or cefaclor. Streptococcus pneumoniae and Haemophilus influenzae were isolated from 25 (39%) and 23 (36%) patients, respectively. Treatment was beneficial in 26 (90%) of the patients who received cefuroxime axetil, and in 16 (76%) of the cefaclor-treated patients. Treatment failed in five (24%) of the cefaclor-treated patients, and in only three (10%) patients who received cefuroxime axetil. Haemophilus influenzae was the initial causative pathogen in a disproportionate number of treatment failures. This study demonstrates the efficacy of cefuroxime axetil in the treatment of otitis media.

A multicenter, randomized, single-blind evaluation of cefuroxime axetil and phenoxymethyl penicillin in the treatment of streptococcal pharyngitis.

Ninety-three children from four pediatric practices, with clinical and bacteriologic evidence of acute Group A beta-hemolytic streptococcal pharyngitis (GABHS) randomly received cefuroxime axetil (60 cases) or phenoxymethyl penicillin (33 cases). Cefuroxime axetil was given twice daily (125 mg). Phenoxymethyl penicillin was given three times daily (250 mg). The treatment groups were similar. Throat cultures were routine 2 to 7 days after the start of therapy and 2 days and 14 days after the end of therapy. The bacterial cure rates were 85 percent (51/60) for cefuroxime axetil, and 88 percent (29/33) for phenoxymethyl penicillin treated patients. Clinical results were comparable in both treatment groups. It was concluded that cefuroxime axetil given twice daily is as effective as phenoxymethyl penicillin given three times daily in producing bacteriologic eradication and clinical symptomatic improvement in children with GABHS.

Randomized, single-blind evaluation of cefadroxil and phenoxymethyl penicillin in the treatment of streptococcal pharyngitis.

A total of 150 children from two pediatric practices with clinical and bacteriologic evidence of acute group A beta-hemolytic streptococcal (GABHS) pharyngitis randomly received cefadroxil monohydrate (75 children) or phenoxymethyl penicillin (75 children). Cefadroxil was given once daily, while penicillin was given three times daily. The treatment groups were similar in age, sex, race, illness severity, and acute GABHS symptomatology. Throat cultures were routine 3 to 5 days after the start of therapy and 2 and 14 days after the end of therapy. The bacterial cure rates were 90% (62 of 69) for cefadroxil-treated patients and 76% (52 of 68) for penicillin-treated patients. This difference was significant (P less than 0.04). The clinical response was satisfactory in 91% of cefadroxil-treated patients and 89% of penicillin-treated patients. We conclude that once-daily cefadroxil is at least as effective as three-times-daily penicillin in producing bacteriologic eradication and clinical symptomatic improvement in children with GABHS pharyngitis.

Comparison between cephalexin two- and four-time per day regimens in group A streptococcal pharyngitis.

In previous studies, twice daily (bid) and four times daily (qid) administration of most antibiotics approved for group A streptococcus (GAS) pharyngitis therapy have been demonstrated to be equally effective. In this study, four investigators collaborated in a double-blind, randomized multicenter study assessing the efficacy of cephalexin given in doses of 1.0 g or 0.5 g daily on a bid or qid regimen for 10 to 14 days to 157 patients with GAS pharyngitis. The mean daily doses for patients on the bid and qid regimens were 30 mg/kg and 29 mg/kg, respectively. Pretreatment and two follow-up cultures, usually 2 to 6 and 12 to 16 days after the end of treatment, were taken on all patients. Failure, defined as recurrence of the original GAS M-precipitin and T-agglutination types on follow-up culture, occurred in 7.3 percent of 82 patients on the bid and 5.3 percent of 75 patients on the qid regimen. We conclude that cephalexin bid and qid regimens are equally effective, and that the bid regimen can be recommended for all antibiotics approved for GAS pharyngitis therapy.

Treatment of otitis media with cefaclor, a new oral cephalosporin.

Cefaclor, a new semisynthetic cephalosporin, was evaluated for efficacy in the treatment of otitis media in 46 pediatric patients who had aspiration of the middle ear for culture. The dose of cefaclor ranged from 29 to 42 mg/kg/day administered in three divided doses. No organism was isolated in nine of the 46 patients. Streptococcus pneumoniae was isolated in 43% and Hemophilus influenzae in 27% of the remainder. A bacteriologic cure was achieved in 97% of cases with culturable organisms. The one treatment failure was due to a cefaclor-resistant strain of H influenzae. The medication was well tolerated with the exception of one case of eosinophilia that was possibly drug related. Cefaclor given three times a day is an effective program for the treatment of otitis media.