Dexamethasone therapy for bacterial meningitis. Results of two double-blind, placebo-controlled trials.

We enrolled 200 infants and older children with bacterial meningitis in two prospective double-blind, placebo-controlled trials to evaluate the efficacy of dexamethasone therapy in addition to either cefuroxime (Study 1) or ceftriaxone (Study 2). Altogether, 98 patients received placebo and 102 received dexamethasone (0.15 mg per kilogram of body weight every six hours for four days). At the beginning of therapy, the clinical and demographic characteristics of the patients in the treatment groups were comparable. The mean increase in the cerebrospinal fluid concentration of glucose and the decreases in lactate and protein levels after 24 hours of therapy were significantly greater in those who received dexamethasone than in those who received placebo (glucose, 2.0 vs. 0.4 mmol per liter [36.0 vs. 6.9 mg per deciliter], P less than 0.001; lactate, 4.0 vs. 2.1 mmol per liter [38.3 vs. 19.8 mg per deciliter], P less than 0.001; and protein, 0.64 vs. 0.25 g per liter [64.0 vs. 25.3 mg per deciliter], P less than 0.05). One patient in the placebo group in Study 1 died. As compared with those who received placebo, the patients who received dexamethasone became afebrile earlier (1.6 vs. 5.0 days; P less than 0.001) and were less likely to acquire moderate or more severe bilateral sensorineural hearing loss (15.5 vs. 3.3 percent; P less than 0.01). Twelve patients in the two placebo groups (14 percent) had severe or profound bilateral hearing loss requiring the use of a hearing aid, as compared with 1 (1 percent) in the two dexamethasone groups (P less than 0.001). We conclude that dexamethasone is beneficial in the treatment of infants and children with bacterial meningitis, particularly in preventing deafness.

Seven days of ceftriaxone therapy is as effective as ten days' treatment for bacterial meningitis.

Seventy-nine children were enrolled in a study to compare seven vs ten days of ceftriaxone therapy for bacterial meningitis. On the basis of a computer-generated list of therapy assignments, 35 children with Haemophilus, pneumococcal, or group B streptococcal meningitis each were assigned to seven- or ten-day treatment regimens; nine children with meningococcal meningitis received seven days of therapy. The population characteristics and etiologic agents were similar for the two treatment groups, as were also the findings on examination and culture of cerebrospinal fluid at completion of therapy. There were no significant differences in the frequency and types of neurological complications between the two treatment groups; four patients in each group had two or more neurological abnormalities. The rates of nosocomial infections and prolonged and secondary fever were similar in those who received seven days of therapy compared with patients treated for the conventional ten days. Diarrhea occurred in 44% of those receiving the drug. Patients treated with the seven-day regimen were discharged from the hospital approximately two days earlier than those with the ten-day regimen.

Pharyngeal colonization with Haemophilus influenzae type b in children in a day care center without invasive disease.

During an 18-month period, monthly pharyngeal cultures for Haemophilus influenzae type b (Hib) were obtained from 66 children and their caretakers in a day care center in which no systemic disease caused by Hib occurred. The average colonization rate for Hib was 10%, and ranged from 0% to 23% for a single month. Infants housed in a separate building with a cohorted staff were not colonized by Hib. However, 71% of the toddler group and 48% of the preschool group became colonized by Hib at some time during the 18-month-study. Of 89 Hib isolates, 93% were biotype 1 (Kilian), and 90% of these had a similar outer membrane protein profile, designated subtype 1L. This strain was recovered from children at the center for 15 of 18 months. No invasive disease occurred. Thus, Hib may be widespread among preschool children in a day care center and persist for longer than a year without resulting in systemic disease.

Rifampin prophylaxis v placebo for household contacts of children with Hemophilus influenzae type b disease.

The efficacy of rifampin prophylaxis (20 mg/kg/day in two doses for four days) in eliminating pharyngeal Hemophilus influenzae type b from household contacts of 38 patients with invasive Hemophilus disease was evaluated in a prospective, placebo-controlled fashion. At the end of treatment, rifampin efficacy was 91% in subjects younger than 5 years of age and 100% in those subjects older than 5 years. The H influenzae type b carrier rate of rifampin-treated subjects was significantly smaller than that of placebo-treated subjects one month after prophylaxis. However, 22% to 25% of rifampin-treated carriers younger than 5 years of age were colonized with H influenzae type b, based on cultures obtained one to four weeks after prophylaxis, while approximately 75% of placebo-treated carriers were still positive at this time.

Pharmacokinetics of cefuroxime in infants and children with bacterial meningitis.

A total of 38 patients with bacterial meningitis received either 50 or 75 mg of cefuroxime per kg of body weight given as a 15-min intravenous infusion during the first to third days of therapy. The mean peak plasma concentrations of cefuroxime after doses of 50 and 75 mg/kg were 105 and 152 micrograms/ml, respectively. In five patients, pharmacokinetic values were determined after multiple doses of 50 mg of cefuroxime per kg every 6 h. The mean peak plasma concentrations were 120 micrograms/ml after the first dose and 130 micrograms/ml after the last dose. The concentrations at 6 h were 3.25 and 11.0 micrograms/ml after the first and last doses, respectively. The elimination half-life was approximately 1.5 h, and the apparent volume of distribution was 650 ml/kg. The plasma clearance rate was 195 to 198 ml/min per 1.73 m2. Penetration into the cerebrospinal fluid, expressed as the ratio of the cerebrospinal fluid to serum areas under the curve times 100, was 6.4% in patients given 50 mg of cefuroxime per kg and 10% in those who received 75 mg/kg. The cerebrospinal bactericidal activity in 27 patients was less than or equal to 1:8; only 2 patients had bactericidal activity of less than or equal to 1:2.

Ototoxicity in neonates treated with gentamicin and kanamycin: results of a four-year controlled follow-up study.

This article reports the results of a four-year follow-up study initiated in 1970 on the long-term effects of gentamicin and kanamycin use in newborn infants. Audiometric, vestibular, and psychometric evaluations were performed on gentamicin-treated, kanamycin-treated, and untreated, matched control infants and children. No substantial sensorineural hearing loss or vestibular dysfunction was identified in these patients that could be attributed to aminoglycoside therapy. Performances on the Illinois Test of Psycholinguistic Abilities, Beery Test of Visual Motor Integration, the Peabody Picture Vocabulary Test, and on fine and gross motor examinations were comparable for the three study groups.