Short course therapy with cefuroxime axetil for acute otitis media: results of a randomized multicenter comparison with amoxicillin/clavulanate.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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.

Measuring antibiotic levels in otitis media.

Antibiotic concentrations in serum and middle ear effusion (MEE) are important in determining treatment success in acute otitis media, but studies to measure concentration levels are often performed in chronically infected patients where there is little inflammation. In this open, single-center study, 26 patients with acute otitis media were enrolled to assess antibiotic penetration in inflamed ears. Of the 26 patients, 4 were non-evaluable, 6 formed a control group and the others were randomized into three groups. Each of the three groups was given a single oral dose of cefuroxime axetil suspension, 15 mg/kg. Food was administered approximately 20 minutes before the drug in order to maximize drug absorption. Cefuroxime concentrations in serum and MEE were assessed at 2-3 (group 1), 3-4 (group 2) and 4-5 (group 3) hours following dosing. Sampling of MEE was performed with tympanocentesis under local anesthesia and the drug was assayed by HPLC-mass spectrometry. The serum concentrations of cefuroxime were found to be above the minimal inhibitory concentration (MIC) for penicillin-sensitive Streptococcus pneumoniae for 100% of the dosing interval and 42% of the time for intermediate-resistant strains. For both Haemophilus influenzae and Moraxella catarrhalis, serum cefuroxime levels were above the MIC for 42% of the time between doses. This study indicates that cefuroxime axetil penetrates the inflamed middle ear effectively in acute otitis media after oral dosing. Serum levels were maintained above the MICs of important bacterial pathogens in otitis media for more than 5 hours after dosing, which is equivalent to 42% of the dosing interval. Thus, the important statistic of 40-50% of time above MIC, required for beta-lactam antibiotics to produce the maximal bacteriological cure rate of 80-85%, is achieved.

Concentration of cefuroxime in middle ear effusion of children with acute otitis media.

BACKGROUND: Antibiotic concentrations in serum and middle ear effusion are important in determining therapeutic success in acute otitis media. For beta-lactams the most relevant pharmacokinetic index for clinical efficacy is the time for which serum concentrations exceed the minimum inhibitory concentration (MIC) of the pathogen, which should be at least 40 to 50% of the dosing interval. METHODS: In this open, single center study, the concentration of cefuroxime achieved in the serum and middle ear effusion of pediatric acute otitis media patients with purulent effusion was assessed between 2 and 5 h after a single oral dose of 15 mg/kg cefuroxime axetil suspension. RESULTS: Serum concentrations of cefuroxime ranged from 2.8 to 7.3 microg/ml and were consistent with the results of previous pharmacokinetic study. These results show that serum concentrations of cefuroxime remain above the MIC90 (2.0 microg/ml) for Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis for at least 5 h (42%) of the 12-h dosing interval. Cefuroxime was detected in 14 of 17 (82%) middle ear effusion samples and ranged from 0.2 to 3.6 microg/ml, indicating that cefuroxime penetrates well into the middle ear. CONCLUSIONS: Cefuroxime is well-absorbed and penetrates well into the middle ear after oral administration of cefuroxime axetil suspension.