Etiology of acute otitis media in childhood and evaluation of two different protocols of antibiotic therapy: 10 days cefaclor vs. 3 days azitromycin. Single-dose ceftriaxone versus 10 days of cefaclor for otitis media. Single intramuscular dose of ceftriaxone as compared to 7-day amoxicillin therapy for acute otitis media in children. A double-blind clinical trial. High-dose azithromycin versus high-dose amoxicillin-clavulanate for treatment of children with recurrent or persistent acute otitis media. An open study to compare azithromycin with cefaclor in the treatment of children with acute otitis media. One dose ceftriaxone vs. ten days of amoxicillin/clavulanate therapy for acute otitis media: clinical efficacy and change in nasopharyngeal flora. Comparison of azithromycin and co-amoxiclav in the treatment of otitis media in children. A randomized, multicenter, double blind, double dummy trial of single dose azithromycin versus high dose amoxicillin for treatment of uncomplicated acute otitis media. A comparative study of azithromycin and amoxycillin in paediatric patients with acute otitis media. Randomized, double-blind study of the clinical efficacy of 3 days of azithromycin compared with co-amoxiclav for the treatment of acute otitis media. Large dosage amoxicillin/clavulanate, compared with azithromycin, for the treatment of bacterial acute otitis media in children. Comparison of ceftriaxone and trimethoprim-sulfamethoxazole for acute otitis media. Greater Boston Otitis Media Study Group. Two versus seven days penicillin treatment for acute otitis media. A placebo controlled trial in children. Five vs. ten days of therapy for acute otitis media. A multicenter, double blind comparison of azithromycin and amoxicillin/ clavulanate for the treatment of acute otitis media in children. A multicenter, randomized, double-blind trial of 5 versus 10 days of antibiotic therapy for acute otitis media in young children. A multicenter, open label trial of azithromycin vs. amoxicillin/ clavulanate for the management of acute otitis media in children. Comparison of five-day cefdinir treatment with ten-day low dose amoxicillin/clavulanate treatment for acute otitis media. Comparison of amoxicillin with second and third generation cephalosporins in the treatment of acute otitis media. Comparative trial of 3 days of azithromycin versus 10 days of clarithromycin in the treatment of children with acute otitis media with effusion. Comparative trial of 3-day azithromycin versus 10-day amoxycillin/clavulanate potassium in the treatment of children with acute otitis media with effusion. Equivalent efficacy and reduced occurrence of diarrhea from a new formulation of amoxicillin/clavulanate potassium (Augmentin) for treatment of acute otitis media in children. Intramuscular ceftriaxone compared with oral amoxicillin-clavulanate for treatment of acute otitis media in children. Azithromycin in upper respiratory tract infections: a clinical trial in children with otitis media. [Clinical efficacy and tolerability of short course therapy with cefaclor compared with long-term therapy for treatment of acute otitis media in children]. Intramuscular ceftriaxone in comparison with oral amoxicillin-clavulanate for the treatment of acute otitis media in infants and children. Five vs. ten days of antibiotic therapy for acute otitis media in young children. Bacterial etiology of acute otitis media and clinical efficacy of amoxicillin-clavulanate versus azithromycin. Short course therapy with cefuroxime axetil for acute otitis media: results of a randomized multicenter comparison with amoxicillin/clavulanate. Five-day versus ten-day treatment of acute otitis media with cefprozil. Single dose amoxicillin treatment of acute otitis media. Bacteriologic efficacies of oral azithromycin and oral cefaclor in treatment of acute otitis media in infants and young children. Bacteriologic and clinical efficacy of amoxicillin/clavulanate vs. azithromycin in acute otitis media. Penicillin treatment of acute otitis media in children. A study of the duration of treatment. Effectiveness of five days of therapy with cefuroxime axetil suspension for treatment of acute otitis media. Multicentre evaluation of azithromycin in comparison with co-amoxiclav for the treatment of acute otitis media in children.
Acute otitis media (AOM) is a common childhood infection that is frequently treated by antibiotics. There are no prospective and comprehensive trials evaluating childhood AOM for etiologic pathogens and resistance pattern in Turkey. The aims of the study were to determine the bacterial etiologies and resistance patterns, and identify the efficacy and the relapse rates of 3 days of azitromycin and 10 days of cefaclor therapy in AOM.
                This prospective, randomized, single-blind, open study was carried out in 78 cases of AOM. Mean age was 30.7+/-27 months. Tympanocentesis and aspiration of middle ear fluid (MEF) were used to obtain purulent material from the middle ear. Group 1 consisted of the cases (n=41) on azitromycin therapy and Group 2 (n=37) on cefaclor. Dosage of azitromycin was 10 mg/kg per day for 3 days and cefaclor 40 mg/kg per day for 10 days. The patients were evaluated on days 3-5 (second visit), day 10 (third visit), and day 30 (fourth visit) during follow-up.
                A total of 50 species were isolated from 44 of 78 cases from which materials were obtained (44/78; 56.4%). Most frequently isolated microorganism was Streptococcus pneumoniae (n=18; 36%), followed by Haemophilus influenzae (n=11; 22%), S. aureus (n=9; 18%), Moraxella catarrhalis (n=4; 8%), and group A beta-hemolytic streptococcus (GAS, n=4; 8%). Enterococcus faecalis was isolated from three cases and H. parainfluenzae from one. Penicillin and amoxicillin resistances of bacteria were found to be 40 and 36%, respectively. The frequency of penicillin and amoxicillin resistance in </=24-month age group was 59 and 66.6%, respectively. The patients did not demonstrate significant differences in terms of cure rate on the third to fifth day (Group 1: 32.5%; Group 2: 36.4%), 10th day (Group 1: 76.9%; Group 2: 84.8%), and on 30th day (Group 1: 91.3%; Group 2: 81.8%). There were no significant differences with respect to side effects, relapse, and re-infection rate between the two groups.
                In more than half of the AOM cases, bacteria were isolated from MEF and most frequently isolated organisms were S. pneumoniae, H. influenzae, and S. aureus. Three-day azitromycin therapy was as effective as 10-day cefaclor therapy. We conducted a controlled clinical trial to determine the efficacy of single-dose intramuscular ceftriaxone for the treatment of acute otitis media. Fifty-four children aged 18 months to 6 years with clinical and tympanometric evidence of otitis media were randomized to receive either 50 mg/kg ceftriaxone or 10 days of oral cefaclor 40 mg/kg/day. Resolution of symptoms and clinical and tympanometric appearance of the tympanic membrane at follow-up visits were used to determine outcome. Thirty-one children received ceftriaxone and 23 received oral cefaclor. There were no treatment failures. There were no significant differences between groups in persistence of effusion or recurrence of acute otitis media. We conclude that a single intramuscular dose of ceftriaxone compares favorably with 10 days of oral cefaclor for the treatment of acute otitis media. Fifty-two children (mean age 23 months) with acute otitis media were treated randomly with either a single intramuscular dose of ceftriaxone (Rocephin) 50 mg/kg (27 patients) or 7 days of amoxicillin 12.5 mg/kg t.i.d. (25 patients). The rate of resolution of acute symptoms and incidence of recurrences and relapses during the first months after commencement of the therapy was similar in the two groups. One week following the start of treatment no difference was observed in the proportion of patients with tympanometric evidence of middle ear effusion (MEE) in either of the two groups. On day 30, however, significantly more patients from the ceftriaxone group had flat tympanograms-83% as compared to 47% in the amoxicillin group. Therefore, single-dose ceftriaxone therapy cannot be suggested at present as routine therapy for acute otitis, although it may be considered a reasonable alternative in noncompliant patients. Infants and young children, especially those in day care, are at risk for recurrent or persistent acute otitis media (AOM). There are no data on oral alternatives to high-dose amoxicillin-clavulanate for treating AOM in these high-risk patients. In this double-blind, double-dummy multicenter clinical trial, we compared a novel, high-dose azithromycin regimen with high-dose amoxicillin-clavulanate for treatment of children with recurrent or persistent AOM. Three hundred four children were randomized; 300 received either high-dose azithromycin (20 mg/kg of body weight once a day for 3 days) or high-dose amoxicillin-clavulanate (90 mg/kg divided twice a day for 10 days). Tympanocentesis was performed at baseline; clinical response was assessed at day 12 to 16 and day 28 to 32. Two-thirds of patients were aged < or =2 years. A history of recurrent, persistent, or recurrent plus persistent AOM was noted in 67, 18, and 14% of patients, respectively. Pathogens were isolated from 163 of 296 intent-to-treat patients (55%). At day 12 to 16, clinical success rates for azithromycin and amoxicillin-clavulanate were comparable for all patients (86 versus 84%, respectively) and for children aged < or =2 years (85 versus 79%, respectively). At day 28 to 32, clinical success rates for azithromycin were superior to those for amoxicillin-clavulanate for all patients (72 versus 61%, respectively; P = 0.047) and for those aged < or =2 years (68 versus 51%, respectively; P = 0.017). Per-pathogen clinical efficacy against Streptococcus pneumoniae and Haemophilus influenzae was comparable between the two regimens. The rates of treatment-related adverse events for azithromycin and amoxicillin-clavulanate were 32 and 42%, respectively (P = 0.095). Corresponding compliance rates were 99 and 93%, respectively (P = 0.018). These data demonstrate the efficacy and safety of high-dose azithromycin for treating recurrent or persistent AOM. An open, multicentre study involving 259 children between 6 months and 13 years of age was performed to assess the efficacy and safety of azithromycin and to compare it with cefaclor as treatment of acute otitis media. Patients were randomized to receive either azithromycin 10 mg/kg once daily for 3 days or cefaclor 40 mg/kg daily in divided doses every 8 h for 10 days. Cure or improvement in signs and symptoms was observed in 112/114 (98%) evaluable azithromycin-treated patients and 116/120 (97%) evaluable cefaclor-treated patients on days 11-15. In contrast to cefaclor, however, azithromycin was associated with a significantly (P = 0.033) higher cure rate 1 month after completion of treatment. In those patients who were followed up to days 25-30, the response was satisfactory (cure or improvement) in 31/32 (97%) patients who had received azithromycin and in 31/36 (86%) to whom cefaclor had been administered. Patients tolerated both treatments well and no severe adverse events related to therapy were recorded in either group. The results of this study show that a 3-day, once-daily regimen of azithromycin has comparable clinical efficacy and tolerability to a thrice-daily course of cefaclor administered for 10 days, but the azithromycin is associated with a lower incidence of relapse. To compare the efficacy and the safety of a single intramuscular dose of ceftriaxone, 50 mg/kg, vs. a 10-day course of amoxicillin/clavulanate (amox/clav) therapy, 80 mg/kg/day of amoxicillin: 10 mg/kg/day of clavulanate in three divided doses, in children with acute otitis media (AOM) and to evaluate the changes in nasopharyngeal flora after treatment.
                In a prospective, comparative, open randomized, multicenter trial, children were scheduled to return for visits on Days 12 to 14 (main end point) and Days 28 to 42 after the beginning of treatment for AOM. A nasopharyngeal swab for bacterial culture was obtained before the treatment and at Days 12 to 14.
                Between February, 1995, and May, 1996, 513 children with a mean age of 14.2 +/- 6.7 months were enrolled. All the patients were evaluable for the safety and intent-to-treat analyses and 463 for the per protocol efficacy. At Days 12 to 14 clinical success was obtained in 186 of the 235 children (79%) given ceftriaxone and in 188 of the 228 children (82.5%) treated with amox/clav. Among the patients with clinical success on Days 12 to 14, the success was maintained at Days 28 to 42 for 108 of 183 (59%) patients in the ceftriaxone group and 103 of 187 (55%) patients in the amox/clav group. Before the antibiotic treatment the percentages of children carrying Streptococcus pneumoniae (59.1%), Haemophilus influenzae (39.4%), Moraxella catarrhalis (55.7%) and the rate of penicillin-resistant S. pneumoniae (52.2%) were comparable between the 2 groups. At Days 12 to 14 the carriage of S. pneumoniae and M. catarrhalis was significantly different between the patients treated with ceftriaxone, 43.9 and 42.2, respectively, and the patients treated with amox/clav, 17.4 and 11.1%, respectively. Among the children carrying S. pneumoniae at Days 12 to 14, the percentage of penicillin-resistant strains reached 63.4% in the ceftriaxone treatment group and 83.0% in the amox/clav treatment group, (P = 0.02). Adverse events (mainly diarrhea) related to the study medication were reported more frequently (P < 0.0001) in the amox/clav treatment group.
                In an area with a high rate of penicillin-resistant S. pneumoniae, a single dose of ceftriaxone is as efficient as a 10-day course of amox/clav in the treatment of AOM in young children. There was for the two regimens an increased rate of penicillin-resistant strains among the pneumococci carried, whereas the chance for a child to carry a penicillin resistant S. pneumoniae did not increase after treatment. An open randomized trial was conducted in 159 children (aged 1 to 8 years) with acute otitis media to compare the clinical efficacy of azithromycin (n = 105) and co-amoxiclav (n = 54). Azithromycin (10 mg/kg/day) was administered as a single dose for three days and co-amoxiclav was given tid for ten days at a dosage according to the manufacturer's instructions for the country. Of 103 evaluable azithromycin patients on day 3 to 5 after the start of therapy, 31 (30%) were considered cured, 67 (65%) improved and five (5%) failed compared with eight (15%) cured, 45 (83%) improved and one (2%) failed among the 54 evaluable co-amoxiclav treated patients. There was a higher number of azithromycin patients with complete resolution of symptoms at this first visit (P = 0.056). By day 10 to 12, clinical equivalence between the two treatment groups was observed with clinical cure in 86 (88%), improvement in 11 (11%) and failure in one (1%) of the 98 azithromycin patients, and in the 54 patients treated with co-amoxiclav, clinical cure was observed in 45 (83%), and improvement in nine (17%) patients. Both drugs were well tolerated and treatment related side-effects were reported in 8/105 (8%) azithromycin and 2/54 (4%) co-amoxiclav patients. In the azithromycin treatment group, these were predominantly mild to moderate gastrointestinal effects, whilst in the co-amoxiclav treatment group, both reports were of mild erythematous rash. One patient from each treatment group was withdrawn due to side-effects (azithromycin--diarrhoea and vomiting; co-amoxiclav--erythematous pruritic rash).(ABSTRACT TRUNCATED AT 250 WORDS) High dose amoxicillin is recommended for the initial treatment of children with acute otitis media (AOM), particularly patients at risk for having drug-resistant Streptococcus pneumoniae. Single dose azithromycin (30 mg/kg) is considered an alternative agent for the treatment of AOM.
                To compare the clinical efficacy and safety of single dose azithromycin with that of high dose amoxicillin among children with uncomplicated AOM.
                This was a double blind, double dummy, multinational, clinical trial in which children (6-30 months of age) with AOM were randomized to treatment with single dose azithromycin (30 mg/kg) or high dose amoxicillin (90 mg/kg/d, in 2 divided doses) for 10 days. Tympanocentesis was performed at baseline and clinical responses were assessed at days 12-14 (end of therapy) and at days 25-28 (end of study).
                The study enrolled 313 patients, and 83% of the patients were < or =2 years of age. A total of 158 patients in the azithromycin group and 154 in the amoxicillin group were considered clinical modified intent-to-treat patients. A middle ear pathogen was detected for 212 patients (68%). Haemophilus influenzae was the most common pathogen (isolated for 96 patients), followed by S. pneumoniae (92 patients), Moraxella catarrhalis (23 patients) and Streptococcus pyogenes (23 patients). beta-Lactamase production was observed for 17% of H. influenzae isolates and 100% of M. catarrhalis isolates. Thirty-five (38%) S. pneumoniae isolates were penicillin-nonsusceptible and 24 (26%) isolates were macrolide-resistant. At the end of therapy, clinical success rates for azithromycin and amoxicillin were comparable for all patients (84 and 84%, respectively) and for children < or =2 years of age (82 and 82%, respectively). At the end of therapy and end of study, clinical efficacies among all microbiologic modified intent-to-treat evaluable subjects were comparable for patients treated with azithromycin (80%) and patients treated with amoxicillin (83%). The rates of treatment-related adverse events for azithromycin and amoxicillin were 20% and 29%, respectively (P = 0.064). Diarrhea was more common in the amoxicillin group than in the azithromycin group (17.5 and 8.2%, respectively) (P = 0.017). Compliance, defined as completion of > or =80% of the study medication, was higher in the azithromycin group (100%) than in the amoxicillin group (90%) (P = 0.001).
                In this study, single dose azithromycin was as effective as high dose amoxicillin for the treatment of children with AOM, whereas rates of adverse events were lower and compliance improved with the simplified single dose regimen. In this open study, a three-day regimen of azithromycin (single daily dose of 10 mg/kg) was compared with a ten-day regimen of amoxycillin paediatric suspension (30 mg/kg/day in three divided doses; children > 20 kg received 250 mg tid daily) in 154 children (aged 2-12 years) with a clinical diagnosis of acute otitis media (13 recurrent). Full clinical, bacteriological and laboratory safety assessments were performed during and after the study. Of the 77 azithromycin patients, 61 (79%) were considered cured, 15 (19%) improved and one (1%) failed, compared with 45 (58%) cured, 28 (36%) improved and four (5%) failed among the 77 amoxycillin patients. Excluding from analysis the 13 patients with recurrent otitis media, azithromycin was found to be significantly superior to amoxycillin (P = 0.003). The incidence of side-effects was low, with only two (3%) and three (4%) patients reporting adverse events with azithromycin and amoxycillin, respectively. These were gastrointestinal in nature and of mild or moderate severity, except for one case of severe diarrhoea in the amoxycillin group. No treatment-related abnormalities in the laboratory safety tests were observed, and no patients withdrew from therapy. A three-day regimen of azithromycin was therefore shown to be more effective than, and as well tolerated as, amoxycillin in the treatment of children with acute otitis media. Compared with 5 days of dosing, a 3 day dosing regimen of azithromycin for treatment of acute otitis media (AOM) may improve compliance, will simplify therapy for the caregiver and, by giving the same total dose as the 5 day regimen, provide more drug when the bacterial burden is highest.
                Children of 6 months-12 years were enrolled if they had had symptoms and signs of AOM for <4 weeks and tympanic membrane effusion by acoustic reflectometry. Eligible children were randomized to azithromycin 10 mg/kg/day x 3 days or co-amoxiclav 45 mg/kg/day x 10 days. The primary endpoint was clinical response at day 28.
                One hundred and eighty-eight children (mean age 3.5 years) were randomized to azithromycin and 185 to co-amoxiclav. At day 10, the clinical success rate was 153/185 (83%) in children treated with azithromycin and 159/181 (88%) in children treated with co-amoxiclav. At day 28, 134/182 (74%) of the children were cured on azithromycin compared with 124/180 (69%) on co-amoxiclav. Also at day 28, signs of AOM, such as abnormal reflectometry (45% versus 59%; P = 0.017), bulging of the eardrum (10% versus 16%; P = 0.059) and loss of tympanic membrane landmarks (11% versus 22%; P = 0.010) were seen less frequently in azithromycin- than co-amoxiclav-treated children, respectively. Adverse events related to therapy were seen in 11% of azithromycin patients compared with 20% on co-amoxiclav (P = 0.014).
                Azithromycin given over 3 days is as effective as co-amoxiclav for treatment of AOM, may result in more complete resolution of tympanic membrane disease, and is better tolerated. A large dosage pediatric formulation of amoxicillin/clavulanate with an improved pharmacokinetic/pharmacodynamic profile was developed to eradicate many penicillin-resistant strains of Streptococcus pneumoniae and Haemophilus influenzae (including beta-lactamase-producing strains).
                This randomized, investigator-blinded, multicenter trial examined treatment of bacterial acute otitis media (AOM) in children 6-30 months of age with amoxicillin/clavulanate (90/6.4 mg/kg/d in 2 divided doses for 10 days) versus azithromycin (10 mg/kg for 1 day followed by 5 mg/kg/d for 4 days). Tympanocentesis was performed at entry for bacteriologic assessment, at the on-therapy visit (day 4-6) to determine bacterial eradication and at any time before the end-of-therapy visit (day 12-14) if the child was categorized as experiencing clinical failure. Clinical assessments were performed at the on-therapy, end-of-therapy and follow-up (day 21-25) visits.
                We enrolled 730 children; AOM pathogens were isolated at baseline for 249 of the amoxicillin/clavulanate group and 245 of the azithromycin group. For children with AOM pathogens at baseline, clinical success rates at the end-of-therapy visit were 90.5% for amoxicillin/clavulanate versus 80.9% for azithromycin (P < 0.01), and those at the on-therapy and follow-up visits were 94.9% versus 88.0% and 80.3% versus 71.1%, respectively (all P < 0.05). At the on-therapy visit, pretherapy pathogens were eradicated for 94.2% of children receiving amoxicillin/clavulanate versus 70.3% of those receiving azithromycin (P < 0.001). Amoxicillin/clavulanate eradicated 96.0% of S. pneumoniae (92.0% of fully penicillin-resistant S. pneumoniae) and 89.7% of H. influenzae (85.7% [6 of 7 cases] of beta-lactamase-positive H. influenzae). Corresponding rates for azithromycin were 80.4% (54.5%) for S. pneumoniae and 49.1% (100% [1 of 1 case]) for H. influenzae (all P < 0.01 for between-drug comparisons).
                Amoxicillin/clavulanate was clinically and bacteriologically more effective than azithromycin among children with bacterial AOM, including cases caused by penicillin-resistant S. pneumoniae and beta-lactamase-positive H. influenzae. The purpose of this prospective, randomized, single-blind trial was to assess the clinical efficacy of a single intramuscular dose of ceftriaxone compared with 10 days of oral trimethoprim-sulfamethoxazole (TMP-SMZ) in treating acute otitis media (AOM).
                Children aged 3 months through 3 years diagnosed with AOM (signs of acute illness plus evidence of middle-ear effusion) were randomized to treatment with either a single intramuscular dose of ceftriaxone (maximum dose of 50 mg/kg) or 10 days of oral trimethoprim-sulfamethoxazole (8 mg of TMP and 40 mg of SMZ/kg/day in two divided doses). Children were evaluated at scheduled visits on days 3, 14, and 28, and the parents were telephoned on day 5. Children were assessed as cured, improved, or failed on day 3, and as cured or failed on days 14 and 28. Children ill at other times during the study period were, if possible, seen and assessed by the study team.
                Of 596 children enrolled during the study period, 484 were evaluable. Characteristics of evaluable subjects did not differ significantly by drug. On day 3, 223/241 children in the ceftriaxone group (92.5%) and 231/243 (95.1%) in the TMP-SMZ group were cured or improved. On day 14, 158/197 (80.2%) in the ceftriaxone group and 174/212 (82.1%) in the TMP-SMZ group were cured. On day 28, 108/136 (79.4%) in the ceftriaxone group and 124/155 (80%) in the TMP-SMZ group were cured. Persistence of middle-ear fluid did not differ between groups at day 14 (55% in the ceftriaxone group vs 47% in the TMP-SMZ group; P = .16) or at day 28 (39% vs 43%; P = .48). Pain at the injection site persisting at day 3 occurred in 8.4% of children receiving ceftriaxone. New diarrhea was more common in the ceftriaxone group (23.6% vs 9.2%; P < .001).
                A single intramuscular dose of ceftriaxone is comparable in clinical efficacy to 10 days of oral TMP-SMZ for treatment of AOM. 103 children between 1 and 10 years of age participated in a double-blind placebo-controlled trial testing the effect of penicillin-V, 55 mg/kg/day, for two days versus seven days in acute otitis media. No significant differences could be demonstrated with regard to earache, healing of the tympanic membrane, tympanometry, fever or common cold symptoms. 76% in the group treated for seven days had a satisfactory course of the disease, compared to 71% in the group treated for two days (p greater than 0.1). In spite of the relatively small number of patients, it is concluded that the effect of penicillin for additional five days in acute otitis media after the initial treatment for two days, can at most be marginal. The advantages of a shortened treatment period are several; the authors have outlined a new treatment modality, consisting of masterful inactivity for 8-12 hours, penicillin-V for two days, and myringotomy in refractory cases, after a new evaluation by the otologist. We believe hereby to be able to reduce penicillin consumption in children with acute otitis media to about 15% of the previous level, without increasing the risk of serious complications. In a double blind study 175 patients with acute otitis media were randomized into 2 treatment groups: 10 days of therapy with cefaclor or 5 days of therapy followed by 5 days of placebo. The dosage of cefaclor was 40 mg/kg/day administered orally in equally divided doses at 12-hour intervals. Tympanocentesis before treatment yielded specimens that contained Streptococcus pneumoniae or Haemophilus influenzae or both in 55% of specimens. Branhamella catarrhalis was isolated from 21% of specimens. Culture of material from the ear canal of patients with spontaneous perforation of the tympanic membrane of less than 24 hours duration yielded pneumococci or H. influenzae or both in 38% of specimens and staphylococci in 31%. Patients were scheduled for follow-up examinations at 5 or 6, 10, 30, 60 and 90 days. Of the 175 children 151 were evaluable at 10 days. There were 123 patients with both tympanic membranes intact at the time of diagnosis. There were 6 (10%) treatment failures of therapy in the 59 patients assigned to 5 days of therapy and 4 (6%) failures and 1 (2%) early relapse in the 64 assigned to 10 days of therapy (difference not significant). There were 28 evaluable patients with spontaneous perforation. There were 8 (53%) failures in the 15 children assigned to 5 days of therapy and only 1 (8%) failure in the 13 children assigned to receive 10 days of therapy (P = 0.016, Fisher exact test). Rates of reinfection and persistent middle ear effusion at 10, 30, 60 and 90 days follow-up were not significant different in patients assigned to 5 to 10 days of therapy. In patients with acute otitis media with intact tympanic membranes we have not been able to show any advantage of the standard duration of 10 days of therapy over a shortened course of 5 days. A 5-day course of antibiotic therapy does not appear to be sufficient for children with acute otitis media and spontaneous purulent drainage. To compare the efficacy and safety of azithromycin and amoxicillin/clavulanate in pediatric acute otitis media.
                Investigators from 12 US centers recruited 677 children. In a randomized, double blind, double dummy fashion, participants received either azithromycin suspension (n = 341) once daily for 5 days or amoxicillin/clavulanate suspension (n = 336) in three divided doses daily for 10 days.
                Among evaluable patients satisfactory clinical response rates (cured and improved) measured 11 days after therapy began were 87.5% in the azithromycin group and 87.9% in the amoxicillin/clavulanate group; corresponding rates at 30 days were 73.5% in the azithromycin and 71.2% in the amoxicillin/clavulanate groups. Relapse rates were comparable for the treatment groups. Treatment-related side effects, primarily gastrointestinal, were reported significantly less frequently with azithromycin (8.8%) than with amoxicillin/clavulanate (30.8%) (P < 0.0001). Two (0.6%) azithromycin patients and 12 (3.6%) amoxicillin/ clavulanate patients discontinued therapy because of treatment-related side effects (P < 0.006 between groups).
                In these children with acute otitis media, azithromycin given once daily for 5 days and amoxicillin/clavulanate given three times daily for 10 days had similar efficacy; however, azithromycin was significantly better tolerated. All but 2 of the 15 published trials have failed to show a difference in efficacy between short (3 to 5 days) and standard (7 to 10 days) antibiotic regimens for acute otitis media (AOM). These studies involved relatively few patients under 2 years of age, who are at a higher risk for treatment failure.
                In a prospective, comparative, double-blind, randomized, multicenter trial, we compared amoxicillin/clavulanate in 3 divided doses for 10 days with an identical 5-day regimen, followed by a 5-day placebo period.
                Between February 1995 and May 1996, 385 children (mean age, 13.3 months) were enrolled, 194 in the 5-day treatment group and 191 in the 10-day treatment group. In the per protocol analysis, clinical success was obtained on days 12 to 14 after the beginning of treatment (main analysis) in 125 (76.7%) of the 163 children receiving the 5-day regimen and 148 (88.1%) of the 168 receiving the 10-day regimen (P = .006). Clinical success persisted on days 28 to 42 among 57 (40.4%) of the 141 assessable patients in the 5-day group and 64 (46%) of the 139 assessable patients in the 10-day group. (P = .34). Multivariate analysis showed that the 10-day course was statistically superior only among children cared for outside their homes (86.8% vs 70.8%; P = .008).
                When assessed on days 12 to 14 after the outset of treatment, a 5-day regimen is not equivalent to a 10-day regimen among young children with AOM. This randomized, open label study compared the efficacy and safety of a 5-day course of once daily azithromycin to those of a 10-day course of three times daily amoxicillin/ clavulanate.
                One hundred sixty-nine children with confirmed acute bacterial otitis media were randomized to treatment with 10 mg/kg of azithromycin oral suspension on Day 1, followed by 5 mg/kg once daily for the next 4 days or 40 mg/kg/ day of amoxicillin/clavulanate suspension in three divided doses for 10 days. Clinical efficacy and safety were evaluated on Days 11 and 30.
                Analysis of evaluable patients 11 days after the start of treatment demonstrated that 87.8% of patients treated with azithromycin and 100.0% of the patients treated with amoxicillin/ clavulanate were cured or improved. Presumed bacteriologic eradication of the baseline pathogens Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pyogenes was comparable in the two groups: 87.8% in patients treated with azithromycin; and 100.0% in patients receiving amoxicillin/clavulanate. At Day 30, 82.2% of patients treated with azithromycin and 80.0% of patients treated with amoxicillin/clavulanate were cured or improved. Presumed bacteriologic eradication of the base-line pathogens was similar in the two groups: 82.2% in patients treated with azithromycin; and 81.1% in patients receiving amoxicillin/clavulanate. Relapses occurred in 5.1% of patients receiving azithromycin and 21.1% of patients taking amoxicillin/clavulanate (P = 0.047). Treatment-related side effects occurred in 3.5% of the azithromycin patients compared with 31.0% of amoxicillin/clavulanate patients (P < 0.001).
                Azithromycin was comparable to amoxicillin/clavulanate in achieving clinical cure or improvement and presumed eradication of baseline pathogens in pediatric patients with acute otitis media. Azithromycin was significantly better tolerated and was associated with fewer relapses than seen after amoxicillin/clavulanate therapy. Short course beta-lactam antibiotic therapy for acute otitis media (AOM) should improve patient adherence, but it has not been evaluated since the heptavalent pneumococcal conjugate vaccine became routinely used in the United States.
                In a prospective, investigator-blinded, multicenter study, 425 patients, age 6 months-6 years, with a clinical diagnosis of nonrefractory AOM were randomized to receive either 5 days of cefdinir therapy (14 mg/kg divided twice daily) or 10 days of amoxicillin/clavulanate therapy (45/6.4 mg/kg divided twice daily). Clinical response was assessed at end of therapy (2-4 days postantibiotic, respectively) and week 4 (study days 25-28).
                With no difference in demographics between treatment groups, overall the mean age (+/-SD) was 2.8 +/- 1.8 years, 65% had received conjugated pneumococcal vaccination and 48% had bilateral AOM. The satisfactory clinical response rate at end of therapy was comparable for cefdinir versus amoxicillin/clavulanate (88%, 170 of 194 versus 85%, 164 of 192; 95% CI -4.9, 9.3). Although this must be interpreted with caution, cefdinir showed an apparent trend for higher efficacy than amoxicillin/clavulanate (92%, 72 of 78 versus 77%, 55 of 71; P = 0.019) in a subsample of patients 6-24 months old who had received conjugated pneumococcal vaccination. The incidence of drug-related adverse events was less for cefdinir than for amoxicillin/clavulanate (24%, 50 of 211 versus 38%, 82 of 214; P = 0.0018)
                For children with nonrefractory AOM, based only on clinical endpoints, 5 days of therapy with cefdinir 14 mg/kg divided twice daily was comparable overall with 10 days of therapy with low dose amoxicillin/clavulanate 45/6.4 mg/kg divided twice daily. The aim of the present study was to compare the efficacy and the tolerability of three different antibiotic regimens for the treatment of acute otitis media in paediatric patients. 75 children, age range 6 months-6 years, divided into three groups, were involved in the study, each group consisting of 25 randomly assigned children (Group 1, amoxicillin 40 mg/kg tid per os for 10 days; Group 2, cefuroxime axetil 30 mg/kg bid per os for 10 days; ceftriaxone 50 mg/kg single-dose i.m.). No statistically significant difference was noted in the clinical efficacy among the different groups. Although amoxicillin is the drug of choice in paediatric otitis media, single dose ceftriaxone might be considered as an interesting alternative regimen when ease of administration and cost of therapy are considered. The authors compared the efficacy, safety and tolerance of azithromycin and clarithromycin in pediatric patients with acute otitis media. A randomized, open clinical trial was performed comparing azithromycin and clarithromycin in children aged 6 months to 12 years of age with acute otitis media with effusion. Patients were allocated to azithromycin at 10 mg/kg once daily for 3 days or to clarithromycin at 15 mg/kg day divided into two equal doses for 10 days. Clinical examinations and tympanometric evaluations were performed at baseline, day 3-5, day 10-14, day 28-30 and day 50-60. Tympanocentesis fluid cultures were collected at enrollment and urine and blood samples were obtained at baseline and day 10-14. Of 100 patients enrolled, 97 were considered evaluable. The most common middle ear pathogens were Streptococcus pneumoniae (60%), Haemophilus influenzae (15%) and Staphylococcus aureus (13%). Fifty patients (100%) treated with azithromycin and 45 (95.7%) patients treated with clarithromycin had a satisfactory clinical response. Rates of persistence of middle ear effusion and possible drug related side effects were comparable. Based on the efficacy and safety results, azithromycin for 3 days and clarithromycin for 10 days are considered to represent an attractive alternative for the treatment of children with acute otitis media. A randomized, open clinical trial was performed to compare azithromycin and amoxycillin/clavulanate potassium in children with acute otitis media with effusion. Patients were allocated to therapy with azithromycin (10 mg/kg once daily for 3 days) or amoxycillin/clavulanate potassium (40 mg/kg/day divided into three equal doses for 10 days). Clinical examination and tympanometric evaluation were performed at baseline, and at day 3 to 5, day 10 to 14, day 28 to 30 and day 55 to 60 after the initiation of therapy. Tympanocentesis fluid cultures were collected at enrolment, and urine and blood samples were obtained at baseline and at day 10 to 11. Of 100 patients enrolled, 92 were considered evaluable. Middle ear cultures were positive in 53.2% of the patients; the most common pathogens were Streptococcus pneumoniae (33%) and Haemophilus influenzae (33%). The response was satisfactory in 47 (100%) patients treated with azithromycin and 42 (95.4%) patients receiving A/C. Rates of persistence of middle ear effusion were comparable. Nausea and loose stools were more common in children treated with amoxycillin/clavulanate potassium (P < or = 0.02). Based on the comparable efficacy noted in this study, the lower incidence of side-effects and the convenience of a shorter duration of treatment, azithromycin represents an attractive therapeutic alternative to amoxycillin/clavulanate potassium and should be further evaluated in larger-scale clinical trials including patients with penicillin-resistant organisms. 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.
                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.
                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).
                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. Two hundred and fifteen children aged 4 months 6 years with acute otitis media (AOM) were randomized to be treated either by a single i.m. injection of ceftriaxone, 50 mg/kg, with a second dose in the event of unsatisfactory response after 48 h or a history of recurrent AOM (109 patients) or amoxicillin clavulanate 12.5 mg tid (106 patients). The failure rate was similar in children treated by ceftriaxone and amoxicillin clavulanate, 4.6% and 4.7%, respectively (standard error for intergroup difference -2.87%, 95% confidence interval -5.62% to 5.87%). No significant differences between the groups were found in the dynamics of the resolution of the acute symptomatology, otoscopy findings, relapse rate at 30 days or tympanographic evidence of middle ear effusion at the scheduled visits on days 30, 60 and 90. Recurrence of AOM between days 31 and 90 was observed significantly in more children treated with amoxicillin clavulanate than with ceftriaxone--25 out of 84 (29.4%) versus 11 out of 81 (13.6%) (P = 0.012). Conclusion: Ceftriaxone injection(s) is as efficient at least as 10-day oral amoxicillin clavulanate for treatment of acute otitis media in children. Although not recommended as routine, ceftriaxone can be considered in the management of acute otitis media under special circumstances, particularly in cases when the ability to tolerate or absorb oral drugs is compromised, in children refusing or unable to take oral therapy or when the compliance is questionable. Azithromycin is a newly developed azalide antibiotic which is very active against microbes causing respiratory tract infections; tissue concentrations remain elevated for a long time after discontinuation of treatment. A clinical study was conducted to compare azithromycin (10 mg/kg administered as a single daily dose for 3 days) with amoxycillin/clavulanic acid (50 mg/kg/day given b.i.d. for 10 days) in 30 children with otitis media. Sensitivity testing demonstrated good azithromycin activity against beta-haemolytic streptococci, Moraxella catarrhalis, Haemophilus influenzae and Staphylococcus aureus. By day 12, clinical cure was recorded in 14/15 children treated with azithromycin and this was maintained at day 30. In the day 12 and 13/15 children by day 30. It was concluded that a 3-day azithromycin regimen produces a satisfactory clinical response and the eradication of key pathogens, and was acceptable for children. Clinical efficacy and tolerability of two different regimens of cefaclor were studied in 410 paediatric patients affected by non-recurrent acute otitis media (AOM). 204 patients were randomly treated with cefaclor given at the dosage of 50 mg/kg/die in two doses for 5 days; 206 patients with 40 mg/kg/die in two doses for 10 days. Diagnosis of acute otitis media was based on the following signs and symptoms: otalgia, fever, possible otorrhea, alterations of tympanic membrane under otoscopic examination. At the end of the treatment 95.5% of patients were cured after short-term therapy and 94.8% after long-term therapy. At the follow-up (two months after the interruption of treatment) 19 and 17 patients respectively had a recurrence. Side effects were observed in 6.9% and 8.7% of patients respectively (not statistically significant); they were mild, never requiring interruption of the treatment. Cefaclor therapy is very effective for treating children aged 2-6 years affected by acute otitis media, with no significant difference related to treatment duration. Short-course treatments appear better in terms of compliance and tolerability. In order to evaluate the clinical efficacy and safety profiles of single-dose ceftriaxone (50 mg/kg, not exceeding 1 g) and a 10-day course of amoxicillin-clavulanate (amoxi-clav) [45 mg/kg/day, in 3 divided doses] in children with acute otitis media (AOM), we conducted a prospective, comparative, randomized trial. Between February 2000 and April 2002, 110 children with a mean age of 30.73 +/- 20.79 months were enrolled. 109 patients were evaluated for the safety assessment. The intent-to treat population included 96 patients who completed at least 3 days of treatment. The standard analysis population included 73 patients who completed the 10-day treatment period without any major violation. For the standard analysis population, 57 out of 73 patients experienced treatment success; 31 out of 41 patients in the ceftriaxone group were cured compared with 25 out of 32 patients in the amoxi-clav group. The rate of persistence of middle-ear fluid did not differ between the 2 groups at day 11 or day 28. A higher treatment preference rate was observed in the ceftriaxone group (93.9% vs 58.6%). The most common drug-related adverse effects were found in the digestive system, skin and appendages in both treatment groups. A single dose of ceftriaxone is as safe and effective as amoxi-clav for curing patients with acute otitis media. In addition, a substantially higher proportion of patients receiving single-dose ceftriaxone showed a preference for the study medication compared with those treated with amoxi-clav for 10 days. Many publications in recent years have argued in favor of shortened therapy for acute otitis media. However, doubt persists regarding children younger than 2 years, and some authors therefore restrict short course therapy to children older than 2 years.
                In a prospective, comparative, double blind, randomized, multicenter trial we compared cefpodoxime-proxetil, 8 mg/kg/day in two divided doses for 10 days, with an identical 5-day regimen followed by a 5-day placebo period.
                Between October, 1996, and April, 1997, 450 children (mean age, 14.3 months) were enrolled, 227 in the 5-day group and 223 in the 10-day group. In the per protocol analysis clinical success was obtained on Days 12 to 14 after the beginning of treatment (main analysis) in 175 (84.1%) of the 208 children receiving the 5-day regimen and 194 (92.4%) of the 210 children receiving the 10-day regimen (P = 0.009). The superiority of the standard regimen was more marked among children cared for outside their homes (92.5% vs. 81.5%). Clinical success persisted on Days 28 to 42 among 134 (85.4%) of the 157 assessable patients in the 5-day group and 144 (83.7%) of the 172 assessable patients in the 10-day group (P = 0.68).
                The 10-day regimen resulted in a higher success rate at the conclusion of therapy, but there were no differences between the two study groups 4 to 6 weeks after enrollment in the study protocol. Acute otitis media (AOM) is one of the most common acute bacterial infection in childhood and also the most frequent reason for outpatient antibiotic therapy. Little recent information about susceptibility patterns of AOM bacterial pathogens in Turkish children has been reported.
                To determine the bacterial etiology of acute otitis media in children and to compare the efficiency of 3 days course of azithromycin with a 10 days course of amoxicillin-clavulanate.
                This prospective, single blind, randomised comparative study was carried out in 180 children with AOM. Paracentesis was performed for middle ear fluid culture before the first dose antibiotic therapy. Children with acute otitis media were randomised to receive either low dose amoxicillin-clavulanate (45/6.4 mg/kg/day in two divided doses for 10 days) or low dose azithromycin (10mg/kg/day for 3 days). Clinical response was assessed on days 2-4, 11-13, 26-28.
                Bacterial pathogens were isolated from 108 (60%) of 180 children. Streptococcus pneumoniae was the most common isolated pathogen (39.7%), followed by Haemophilus influenzae (20.7%), Moraxella catarrhalis (15.5%), Staphylococcus aureus (13.8%), Group A beta-hemolytic streptococcus (5.1%), Escherichia coli (3.4%) and Enterococcus faecalis (1.7%). This study demonstrated low resistance rates compared to studies of different countries. Although clinical response rates were better in patients treated with amoxicillin-clavulanate, this was not statistically significant [86.6% (78 of 90)] versus [95.2% (80 of 84)]. Success rates of amoxicillin-clavulanate were high for both S. pneumoniae and H. influenzae. Difference between success rates was not statistically significant (P=0.144 and 0.352).
                Bacteria were isolated in 60% of AOM cases. The clinical efficiency of amoxicillin-clavulanate was found to be equal compared to azithromycin in children with acute otitis media. Otitis media is a common infection of childhood. Increasing antibiotic resistance rates among the principal causative pathogens, Streptococcus pneumoniae and Haemophilus influenzae, are associated with failure of first line agents.
                This open, randomized, multicenter study compared the clinical efficacy of a short 5-day course of cefuroxime axetil (CAE) suspension with that of amoxicillin/clavulanate (A/CA) suspension for 8 or 10 days.
                Children age 6 to 36 months with acute otitis media with effusion, diagnosed by tympanocentesis and microbiologic culture, were randomized to receive CAE (30 mg/kg/day in two divided doses for 5 days) or A/CA 40 mg/kg/day in three divided doses for 10 days (A/CA-10). In French centers A/CA was given at 80 mg/kg/day in three divided doses for 8 days (A/CA-8). Patients were assessed 1 to 4 days after completing the course (posttreatment) and followed up at 21 to 28 days after completing the course.
                Of the 716 patients randomized, 252 were treated with CAE, 255 with A/CA-10 and 209 with A/CA-8. In the clinically evaluable population, the proportions of patients with clinical cure at posttreatment were 175 of 203 (86%), 181 of 205 (88%) and 145 of 164 (88%) in the CAE, A/CA-10 and A/CA-8 groups, respectively, demonstrating equivalence among the three treatments. For patients <18 months old, clinical cures were 111 of 134 (83%), 116 of 131 (89%) and 83 of 99 (84%) in the CAE, A/CA-10 and A/CA-8 groups, respectively; equivalence was also demonstrated. At follow-up, 130 of 175 (74%) CAE, 121 of 172 (70%) A/CA-10, and 112 of 142 (79%) A/CA-8 had maintained cure. A total of 837 pretreatment pathogens were isolated from middle ear fluid in 73% (522 of 716) patients, the majority of isolates were S. pneumoniae (30%) and H. influenzae (27%). The most common adverse events were gastrointestinal, the incidence of drug-related diarrhea being higher in the A/CA-10 group (18%) than in either the CAE or A/CA-8 groups (10%).
                A 5-day course of CAE, given twice daily, was shown to be equivalent to the two regimens of A/CA for treatment of acute otitis media with effusion in children. A randomized comparative clinical trial was conducted to investigate the possibility of decreasing the duration of treatment of acute otitis media by comparing the clinical outcome and safety of a five-day and a ten-day course of cefprozil. A total of 708 pediatric patients were enrolled in the study, 560 of whom were evaluable for efficacy. Cefprozil was found to be completely effective in 87.1% of cases after five days of treatment, and in 91.2% after ten days of treatment. Of 19 patients with three or more previous episodes of acute otitis media, ten patients in the ten-day treatment group had a 100% cure rate, while in the five-day group four experienced cure, three improvement, and two failure. A five-day course of treatment with cefprozil can be recommended only if children have no history of recurrent acute otitis media. A double blind study comparing a single dose of amoxicillin versus a 10-day course of amoxicillin in the treatment of acute otitis media (AOM) was undertaken. All children diagnosed with AOM in a pediatric clinic were requested to participate. After tympanocentesis was performed, patients were randomly assigned to receive either amoxicillin (100 mg/kg) followed by placebo every 8 hours for 10 days or placebo followed by amoxicillin (40 mg/kg/D) for 10 days. Patients returned to clinic on days 3 and 10 post-treatment. Seventeen patients were enrolled: 7 received single dose therapy and 10 received 10 days of therapy. There were no failures in the control group and 3 failures in the single dose group (day 5, day 6, and 11) (p = 0.05). Middle ear isolates included: S. pneumoniae 7, H. influenzae 4, B. catarrhalis 1, and no pathogen in 5. Due to the significant number of failures in the treatment group, the study was prematurely terminated. A prospective, open-label, randomized study was conducted in order to determine the bacteriologic efficacies of cefaclor and azithromycin in acute otitis media (AOM). Tympanocentesis was performed on entry into the study and 3 to 4 days after initiation of treatment. Bacteriologic failure after 3 to 4 days of treatment with both drugs occurred in a high proportion of culture-positive patients, especially in those in whom AOM was caused by Haemophilus influenzae (16 of 33 [53%] of those treated with azithromycin and 13 of 34 [52%] of those treated with cefaclor). Although a clear correlation of the persistence of the pathogen with increased MICs of the respective drugs could be demonstrated for Streptococcus pneumoniae, no such correlation was found for H. influenzae. It is proposed that susceptibility breakpoints for H. influenzae should be considerably lower than the current ones for both cefaclor and azithromycin for AOM caused by H. influenzae. To compare the bacteriologic and clinical efficacy of amoxicillin/clavulanate and azithromycin in patients with acute otitis media (AOM), particularly the ability to eradicate the predominant AOM pathogens from middle ear fluid as assessed by mandatory second tympanocentesis.
                In this single blind study 238 infants and children with AOM were randomized to receive amoxicillin/clavulanate (45/6.4 mg/kg/day in two divided doses for 10 days) or azithromycin (10 mg/kg on Day 1, then 5 mg/kg daily on Days 2 through 5). Tympanocentesis was performed before the first dose and repeated on Day 4, 5 or 6. Clinical response was assessed at end of therapy between Days 12 and 14 and at follow-up between Days 22 and 28.
                Amoxicillin/clavulanate was significantly more likely to eradicate all bacterial pathogens [83% (54 of 65) vs. 49% (35 of 71), P = 0.001] and Haemophilus influenzae [87% (26 of 30) vs. 39% (13 of 33), P = 0.0001] from middle ear fluid than was azithromycin. Amoxicillin/clavulanate was also more likely to eradicate Streptococcus pneumoniae, but the difference was not statistically significant [90% (18 of 20) vs. 68% (13 of 19) [corrected], P = 0.095]. On Days 12 to 14, signs and symptoms were more likely to resolve completely or improve in all culture-positive patients [86% (60 of 70) vs. 70% (51 of 73), P = 0.023] and in those with H. influenzae infections [91% (30 of 33) vs. 65% (22 of 34), P = 0.010] who received amoxicillin/clavulanate compared with those who received azithromycin. Otherwise there were no significant differences between groups in clinical outcomes on Days 12 to 14 or at follow-up.
                Our findings indicate that amoxicillin/clavulanate has superior bacteriologic and clinical efficacy compared with azithromycin in children with AOM. Two hundred and ninety-seven children, aged 6 months to 7 years, with AOM were treated with penicillin V. One hundred and forty-eight children were given 25 or 50 mg/kg body weight twice a day for 5 days, and 149 children 25 mg/kg body weight twice a day for 10 days. No differences were found in the rate of healing between the 5- and 10-day groups. The larger penicillin dose, which was given to half the 5-day group, did not lead to improved healing. Treatment with penicillin for 5 days instead of 10 does not mean any increased risk of complications such as SOM, relapses, or therapeutic failure. Nor does the risk of a recurrence of otitis increase either. The investigation showed that the treatment of AOM with penicillin for 10 days, which is the rule in Sweden, can be reduced to 5 days with maintained satisfactory healing and without risk of increasing the number of complications. In recent years there has been considerable interest in reducing the duration of antibiotic treatment regimens in patients with common bacterial infections. We conducted two independent, investigator-blinded, multicenter, randomized clinical trials, one of which included microbiologic evaluation of middle ear fluid obtained by tympanocentesis, comparing the efficacy and safety of 5 or 10 days of treatment with cefuroxime axetil suspension (CAE) with that of 10 days of treatment with amoxicillin/clavulanate suspension (AMX/CL) in children with acute otitis media.
                A total of 719 pediatric patients from the ages of 3 months to 12 years were enrolled in the 2 studies. Patients received CAE for either 5 or 10 days at 30 mg/kg/day in 2 divided doses (n = 242 and 235, respectively) or AMX/CL for 10 days at 40 mg/kg/day in 3 divided doses (n = 242). Patients in the CAE (5 days) group received placebo on Days 6 through 10. In the study that included tympanocentesis, bacteriologic assessments were based on middle ear fluid cultures obtained pretreatment and, when possible, after treatment in patients with an unsatisfactory clinical outcome.
                Organisms were isolated from the pretreatment middle ear fluid specimens of 177 of 244 (73%) patients undergoing tympanocentesis, with the primary pathogens being Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis (37, 35 and 12% of isolates, respectively). Pathogens were eradicated or presumed to be eradicated in 92% (24 of 26), 84% (32 of 38) and 95% (36 of 38) of bacteriologically evaluable patients treated with CAE for 5 or 10 days or with AMX/CL, respectively. A satisfactory clinical outcome (cure or improvement) occurred in 69% (101 of 147), 70% (121 of 173) and 74% (131 of 177) of clinically evaluable patients treated with CAE (5 days), CAE (10 days) or AMX/CL, respectively. Treatment with AMX/CL was associated with a significantly higher incidence of drug-related adverse events than was treatment with CAE for either 5 or 10 days (P < 0.001), primarily reflecting a higher incidence of drug-related gastrointestinal adverse events (34% vs. 17 and 12%, respectively; P < 0.001), particularly diarrhea.
                Treatment with CAE given twice daily for 5 days is equivalent to treatment for 10 days either with the same regimen of CAE or with AMX/CL given three times daily in pediatric patients with acute otitis media. A total of 389 children (age 0.6-10.2 years) with typical signs and symptoms of acute otitis media were randomized (1:1) to treatment with either azithromycin or co-amoxiclav. The dosage schedule for azithromycin was 10 mg/kg/day, in a single daily dose, administered for three days. Co-amoxiclav was given at a dose of 13.3 mg/kg (amoxycillin equivalent) tid for ten days. Patients were evaluated 4-6 days and 12-16 days after the start of therapy. A satisfactory clinical response was reported for 93.2% of the 192 evaluable azithromycin-treated patients (144 cured, 35 improved), and for 97.3% of the 189 evaluable co-amoxiclav-treated patients (148 cured, 36 improved). Six (3.0%) relapses occurred in the azithromycin group, and four (2.1%) in the co-amoxiclav treatment group, respectively. Side-effects were recorded in a significantly fewer number of the azithromycin patients (23 of 197; 11.7%) compared with the co-amoxiclav patients (43 of 192; 22.4%, P < 0.02). Adverse events were mainly gastrointestinal in nature, with diarrhoea the most frequent complaint (32 cases with co-amoxiclav; five with azithromycin; P < 0.001). One patient from each group discontinued therapy because of treatment-related adverse events. Laboratory analyses (mainly haematological in nature) showed abnormalities in six of 100 azithromycin patients and ten of 101 co-amoxiclav patients. It was concluded that three-day, single-dose azithromycin and ten-day tid co-amoxiclav therapy have comparable clinical efficacy in paediatric patients with acute otitis media; however, there was a lower incidence of side effects in the azithromycin group.
Clinicians need to evaluate whether the minimal short-term benefit from longer treatment of antibiotics is worth exposing children to a longer course of antibiotics.