Amoxicillin-clavulanate potassium compared with cefaclor for acute otitis media in infants and children.

One hundred thirty-three infants and children with documented acute otitis media (OM) were randomized to receive the oral suspension of either amoxicillin-clavulanate potassium or cefaclor. Beta-lactamase-producing bacteria were found in 10.9 and 14.5% of subjects treated with amoxicillin-clavulanate potassium and cefaclor, respectively. Subjects were reexamined at 5, 10, 30, 60 and 90 days after the initiation of therapy and whenever signs/symptoms of acute otitis media recurred. All but two children had resolution of otalgia/otorrhea during the initial treatment period. The drug groups were not significantly different in the percentage of evaluable subjects with otitis media with effusion at each scheduled follow-up visit. Recurrence of acute OM/otorrhea [corrected] developed in a similar percentage of subjects in both treatment categories. Both subjects with and those without middle ear effusion at 10 days had approximately a 50% recurrence rate of subsequent middle ear disease. Adverse side effects/complaints, which occurred in significantly more children treated with amoxicillin-clavulanate potassium, were generally mild and primarily gastrointestinal.

An animal model of acute otitis media consequent to beta-lactamase-producing nontypable Haemophilus influenzae.

A chinchilla model of acute otitis media with effusion consequent to beta-lactamase-producing nontypable Haemophilus influenzae was developed using the method of direct inoculation of 145 colony-forming units (CFU) or 252 CFU of beta-lactamase-producing nontypable H influenzae into the right superior bullae of 40 chinchillas. The course of the disease was documented longitudinally by otomicroscopy, tympanometry, and periodic culturing of the middle ears. Onset of the disease occurred in 100% of the animals between two and six days postinoculation and resolution was complete in all ears by day 36. Results of rechallenge with the same organism support the combined effect of a local and weaker systemic middle ear protective mechanism rendering resistance to reinfection with a homologous organism in the chinchilla.

Pharmacokinetics of cefaclor in chronic middle ear effusions.

Fifty children aged 1 to 13 years with chronic or recurrent otitis media with effusion received a single dose of cefaclor (15 mg/kg body weight) by the oral route 30 minutes to seven hours before the removal of middle ear effusion and insertion of tympanostomy tubes. Serum and middle ear aspirate concentrations of the antibiotic were determined employing a microbiological assay technique by a disk diffusion method. Middle ear specimens were also cultured for aerobic bacteria. The mean peak serum concentration level (8.49 +/- 7.89 micrograms/ml) was observed after 30 minutes, whereas the middle ear peak level (0.47 +/- 0.78 micrograms/ml) occurred after one hour. Of the 87 middle ear specimens, 37 had cefaclor concentrations which were detectable within the resolution of the bioassay method (greater than 0.16 micrograms/ml). There was no correlation between the type of middle ear effusion (mucoid or serous) and the concentration of cefaclor in the middle ear. Only 18% of the middle ear cultures were positive for aerobic bacteria; Hemophilus influenzae was the most common organism.

Recurrent pneumococcal otitis media in the chinchilla. A longitudinal study.

To define the relative importance of the local and systemic immune mechanisms in otitis media, middle ear infections were induced in 47 chinchillas by unilateral intrabullar inoculation of Streptococcus pneumoniae type 6A. Bacterial challenges were repeated ipsilaterally or contralaterally several times during the five-month course of the study. The middle ear condition was assessed with the use of otomicroscopy, tympanometry, and direct inspection and culture through a bullar opening. Pneumococcal 6A antibodies were assayed periodically in the serum and middle ear effusions. The concentration levels of serum antibodies did not correlate with the course of otitis media, and antibiotics did not protect either the ipsilateral or contralateral ear from infection. There was a minimal number of bacteria that rendered the middle ear resistant to subsequent infection. This resistance was a local phenomenon and occurred only when the middle ear had previously been exposed to the same bacteria.

Sultamicillin (ampicillin-sulbactam) in the treatment of acute otitis media in children.

Sultamicillin, a dimer of ampicillin and a beta-lactamase-inhibiting agent, sulbactam, was given in oral form to 50 infants and children with acute otitis media. Tympanocentesis was performed on entry into the trial. Beta-lactamase-positive Haemophilus influenzae or Branhamella catarrhalis was isolated from 14 of 73 (19.2%) middle ear effusions in 9 children. Relief of symptoms (fever/otalgia) occurred in all children who completed therapy. However, in 8 children (16%), the antimicrobial agent was discontinued due to presumed adverse side effects (primarily gastrointestinal); vomiting which began prior to entry was noted in another subject who was withdrawn. An additional 14 children completed the course of treatment despite having diarrhea. Of the 41 children who completed drug therapy, 11 (26.8%) were effusion-free after 10 days, and 22 of 33 (66.7%) evaluable children were effusion-free after 6 weeks. Sultamicillin is a novel therapeutic approach to beta-lactamase-producing bacteria. In its oral form, however, diarrhea is a troublesome side effect.

Treatment of ampicillin-resistant acute otitis media in the chinchilla.

The efficacy of sulbactam sodium (CP45,899-2) was investigated using the chinchilla animal model of acute otitis media with effusion (AOME). Both ears of 78 chinchillas were inoculated with beta-lactamase-producing nontypable Hemophilus influenzae. Half of the animals were treated with ampicillin sodium alone (group A) and the remaining animals received ampicillin plus sulbactam (group B). On day 14, all of the ears in group B were culture-negative whereas H influenzae was recoverable in over 70% of the effusions in group A. Similarly, the course of middle ear effusion was significantly abbreviated in group B during the two-week study period. These findings suggest that sulbactam in combination with ampicillin is effective in treating AOME secondary to infection with beta-lactamase-producing nontypable H influenzae in the chinchilla animal model.