Concentrations of antimicrobial agents in middle ear fluid, saliva and tears.

Antibiotics concentrations in middle ear fluid (MEF), saliva and tears were measured in children with persistent middle ear effusions undergoing tympanostomy tube placement. In 31 children given cefaclor, specimens of serum, saliva and MEF were collected at 0.5, 1, 2, 3 or 5 h after a dose. Another group of 37 children were randomized to receive a single dose of penicillin V, amoxicillin, ampicillin, erythromycin estolate, erythromycin ethylsuccinate, trimethoprim-sulfamethoxazole or cefaclor. Concentrations of antibiotics in saliva and tears bore no consistent relationship to those in MEF. Mean concentrations of all drugs in MEF were several-fold greater than the usual minimal inhibitory concentrations (MIC) of pneumococci, but only with trimethoprim and cefaclor were they greater than in usual MIC's for Haemophilus influenzae. Concentrations of antibiotics in MEF in persistent effusions were comparable to those previously reported in acute purulent effusions.

Comparative pharmacokinetics of cyclacillin and amoxicillin in infants and children.

Concentrations of cyclacillin in serum over a 6-h period were similar in fasted and milk-fed infants who received 25-mg/kg doses of cyclacillin suspension. Measured by the concentration in serum after oral administration of 15-mg/kg doses, cyclacillin was absorbed more rapidly, reached larger concentrations, and was cleared more promptly than was amoxicillin.

Comparative pharmacokinetics of bacampicillin and ampicillin suspensions in infants and children.

The pharmacokinetics of ampicillin and two preparations of bacampicillin, Veegum and microcapsules, were studied in 24 infants and children. For bacampicillin, mean peak concentrations of 7.6 and 14.4 micrograms/ml were found in the sera of fasting patients after administration of 27.8 mg of drug/ml in Veegum and microcapsular suspensions, respectively. Bacampicillin (27.8 mg/kg) and ampicillin (25 mg/kg) were compared in crossover fashion in 21 of the 24 children. Although the dosage of bacampicillin was 25% smaller on an equimolar basis than that of ampicillin, drug concentrations in serum were consistently higher with bacampicillin than with ampicillin; the differences were statistically significant 0.5, 1, and 2 hr after administration. The bioavailability of bacampicillin was two-to threefold greater than that of ampicillin. Urinary concentrations of drug were twofold higher with bacampicillin than with ampicillin. The proportion of saliva samples with detectable antimicrobial activity was similar among patients who received bacampicillin (31%) and those who received ampicillin (25%); however, the mean salivary concentrations 2 and 4 hr after administration of bacampicillin were substantially higher than those after ampicillin.

Pharmacokinetics of rifampin in infants and children: relevance to prophylaxis against Haemophilus influenzae type b disease.

Pharmacokinetic studies of rifampin were performed in 38 infants and children after administration of three different oral formulations. Mean peak serum concentrations of from 9 to 11.5 microgram/ml were observed one hour after a 10-mg/kg dose and the average half-life was 2.9 hours. Patients who received rifampin suspension in applesauce had smaller serum concentrations and area-under-the-curve values than did those who were given suspension alone. The mixture of rifampin powder and applesauce resulted in more variable serum levels. The concentrations of drug in tears from 18 subjects were similar to those in serum. All but one of 118 saliva specimens obtained from two to eight hours after the 10-mg/kg dose had antimicrobial activity. Of samples taken at two hours, 95% contained rifampin levels that exceeded the minimal bacterial concentration for 15 Haemophilus influenzae type b strains. Bactericidal activity against Haemophilus correlated with salivary rifampin concentrations and was detectable in virtually all specimens containing greater than or equal to 0.8 microgram/ml. These data provide the pharmacokinetic basis for rifampin prophylaxis of close contacts of H influenza type b disease, but are insufficient alone to recommend routine usage of rifampin for this purpose until results of additional epidemiologic studies are available.

Comparative pharmacokinetics of amoxicillin and ampicillin in infants and children.

The pharmacokinetics of amoxicillin and ampicillin were studied in 24 infants and children. Mean peak serum concentrations of 5.4 micrograms/ml in fasting and 3.2 micrograms/ml in nonfasting patients were observed after 15 mg/kg amoxicillin doses. Area under the curve values and serum half-life values were similar in fasting and nonfasting patients. The pharmacokinetics of amoxicillin (15 mg/kg) were compared to those of ampicillin (25 mg/kg). Peak serum concentrations, area under the curve values and half-life times were comparable for the two drugs. Amoxicillin (25 mg/kg) and ampicillin (25 mg/kg) were compared in cross-over fashion in 11 children. Serum concentrations of amoxicillin were consistently larger than those of ampicillin; the differences were of borderline significance at one and two hours and statistically significant at four and six hours after the dosage. The bioavailability of amoxicillin was twice that of ampicillin. Amoxicillin was detected in approximately half of the saliva samples studied. Although the salivary concentrations in many children exceeded the inhibitory level for most pneumococci and group A streptococci and for many non-beta lactamase-producing Haemophilus influenzae type b strains, the clinical relevance of these observations is unknown.

Pharmacologic evaluation of orally administered antibiotics in infants and children: effect of feeding on bioavailability.

The clinical pharmacology of orally administered antibiotics was investigated in 106 infants and children. The antibiotic suspensions studied were ampicillin, cephalexin, erythromycin estolate, erythromycin ethylsuccinate, penicillin G, and penicillin V. The feeding status of the patients was evaluated in relation to the concentrations of drugs in serum, saliva, and tears. Peak concentrations and area-under-the-curve values of cephalexin, penicillin V, and penicillin G were reduced 40% to 60% in patients given milk and drug concurrently. Absorption was enhanced when erythromycin ethylsuccinate was given milk. After administration of both erythromycin formulations, penicillin V and ampicillin, salivary concentrations exceeded the minimal inhibitory concentrations for most pneumococci and group A streptococci and for many meningococci. The clinical implications of these pharmacokinetic data are discussed.

Treatment of acute otitis media of infancy with cefaclor.

The emergence of ampicillin-resistant Haemophilus as a clinical problem in otitis media necessitates a search for alternative, effective therapy. An orally absorbable cephalosporin derivative, cefaclor, is equally effective in vitro against ampicillin-susceptible and -resistant Haemophilus and against other bacteria that cause acute otitis media. Two dosage schedules of cefaclor (40 and 60 mg/kg/day) were evaluated in 95 infants with acute otitis media. Bacterial origin was determined by a culture of tympanocentesis fluid. Success rates using the smaller dosage were inferior to those using the larger dosage. Results of therapy for pneumococcal and Haemophilus infection with 60 mg/kg/day were comparable to those previously found with amoxicillin trihydrate or with combinations of trisulfapyrimadines with erythromycin or penicillin V. One patient with an ampicillin-resistant Haemophilus infection responded well to cefaclor and did not have a relapse. Cefaclor was well tolerated and caused an acceptably low incidence of minor, adverse effects. Cefaclor deserves further testing as a candidate for preferred status as a single-drug treatment of acute otitis media.

Clinical pharmacology of cefadroxil in infants and children.

The pharmacokinetics of cefadroxil suspension were studied in 30 children, 13 months to 12 years of age (mean age, 5.7 years). Average peak concentrations in serum of 11 to 14 mug/ml and of 7 to 10 mug/ml after 15- and 10-mg/kg doses, respectively, were not substantially affected by the feeding status. The serum half-life values were 1.3 to 1.5 h. Cefadroxil was detected in saliva of all children 2 h after 15-mg/kg doses: the levels ranged from 0.17 to 2.6 mug/ml (mean, 0.46 mug/ml). The average concentrations in urine were 1,700 and 2,620 mug/ml at 0 to 2 and 2 to 4 h, respectively, after 15-mg/kg doses. In a randomized controlled study of 50 children with impetigo, cefadroxil was as effective as penicillin G in curing existing lesions and in preventing development of new lesions. Cefadroxil may be useful for therapy of mucocutaneous and urinary tract infections in infants and children.

Otitis media of infancy and early childhood. A double-blind study of four treatment regimens.

A double-blind, randomized trial of four antimicrobial regimens was conducted in 383 infants and children with acute otitis media. The drugs used were penicillin V, amoxicillin trihydrate, erythromycin estolate, and erythromycin estolate with trisulfapyrimidines. Aspiration of middle ear fluid for culture was done before treatment and repeated during treatment if fluid persisted. Etiologic bacteria were most commonly pneumococci (31%) or Haemophilus sp (22%), and an additional 5% of patients had both organisms. Amoxicillin was the most effective in promoting initial response in pneumococcal infection. For Haemophilus infections, the cure rates with amoxicillin and the erythromycin-trisulfapyrimidines mixture were significantly better than with the other two regimens, and serous otitis did not occur during the follow-up period; however, new episodes of otitis were comparable in the four groups. Amoxicillin and the erythromycin estolate-trisulfapyrimidines combination appear to be somewhat more effective than penicillin V or erythromycin estolate.