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Antibiotic concentrations in middle ear fluid can be determined in the purulent effusions of acute otitis media or in chronic effusions at the time of myringotomy with tympanostomy tube insertion. Measurements are usually made using microbiological methods. The concentration of betalactamines in middle ear fluid is 20 to 40% serum concentrations. Therefore, in the treatment of otitis media, it is necessary to use high doses of antibiotics, so that the concentration in the middle ear fluid is higher than the minimum inhibitory concentration (MIC) for the most frequent infecting organisms. Sulfamides penetrate well into the middle ear. On the other hand, the concentration of macrolides is not significant until two or three doses have been delivered and a steady state is reached. While direct measurements of the antibiotic concentrations in middle ear fluid can provide information concerning the effectiveness of the antibiotic relative to the MIC, they do not replace clinical trials in confirming the indications of new antibiotic molecules in the treatment of otitis media. In addition, direct measurements are delicate and show great interindividual variations.

Cefixime was assayed by a microbiological method in the tonsils of 21 children (mean age 59 months). Tonsillectomy was performed 5 hours after a third dose of 4 mg/kg administered 12-hourly. Plasma cefixime levels were evaluated 10 hours after the second dose with a mean value of 0.84 mg/l (range: 0 to 1.35) and again after a third dose during amygdalectomy with a mean value of 1.24 mg/l (range: 0.1 to 3.9). Cefixime concentrations were 0.74 micrograms/g in the right tonsils and 0.53 micrograms/g in the left tonsils. The antibiotics could not be detected in both tonsils in 6 children and in one of the two tonsils in 11 children. The tissue penetration of cefixime in tonsils therefore was about 1 micrograms/g in those cases where cefixime was detectable. As with other beta-lactam antibiotics, this penetration is not regular, being dependent on the degree of tonsillar fibrosis inhibitin their diffusion.

Ceftazidime has the same antibacterial spectrum as the other third generation cephalosporins, but it is the most active of all against Pseudomonas aeruginosa. A review of the literature concerning severe infections shows that ceftazidime has been used in children mainly to treat superinfections on cystic fibrosis, infections in immunocompromised subjects and neonatal infections. The results in large series of patients were highly satisfactory and the drug was well tolerated. Other diseases treated in shorter series were: urinary tract infections in paediatric urology, ENT infections caused by P. aeruginosa, cellulitis and post-operative infections. A multicentre trial involving 344 children has recently been reported, showing very good results (clinical cure in 95 per cent of the cases). Ceftazidime dosage varies from one study to another, but a mean daily dose of 150 mg/kg is often necessary in septicaemias and infections associated with cystic fibrosis.

A pharmacokinetic study of ceftazidime was conducted in 1983, together with a clinical study, on 7 neonates (3 of them premature), 4 infants and 3 children. The antibiotic was administered by slow intravenous injection in mean doses of 30 mg/kg twice in 24 h in neonates and thrice in 24 h in older children. Blood samples were collected by micropuncture, and assays were performed by the microbiological method on agar plates. Curves of plasma concentrations over time showed two slopes compatible with a two-compartment model. The alpha half-life was the same in neonates and infants; the beta half-life varied from 1.9 to 5 h. The highest values were observed in the 3 youngest and most immature neonates. In infants and older children the mean beta half-life was the same as in adults: 1.4 +/- 0.19 h. The results of several studies performed on neonates differed as regards the influence of term, post-natal age and bodyweight on the pharmacokinetic constants of ceftazidime. A dose of 25 to 50 mg/kg twice a day administered to premature and full-term neonates during the 1st week of life gives therapeutically effective concentrations. Doses of 30 to 50 mg/kg 3 or 4 times a day are necessary in infants and older children. Dosage should be adjusted to renal maturity and renal functions as well as to the infection treated.