Antimicrobial therapy for infants and children: guidelines for the inpatient and outpatient practice of pediatriac infectious diseases.

In this article, we discuss antimicrobial regimens for both outpatient and inpatient use in infants and children. A substantial number of pediatric patient visits annually result in the prescribing of antimicrobial drugs. The emergence of bacteria resistant to commonly used antimicrobial agents is a growing concern. Information on newer drugs such as meropenem, which is active against penicillin-resistant Streptococcus pneumoniae and gram-negative bacilli, and cefepime, which has activity against gram-negative bacilli including Pseudomonas aeruginosa and against gram-positive cocci is also presented. Management of patients with congenital or acquired immunodeficiencies continues to be challenging in regard to the use of antimicrobial drugs to treat various fungal and viral infections. New formulations of older drugs such as aerosolized tobramycin and amphotericin B lipid complex are available. New antiviral agents have been approved, most of which are antiretroviral agents. Childhood tuberculosis is an ongoing concern, and regimens to treat Mycobacterium tuberculosis in children are discussed.

Concise review for primary-care physicians.

Acute otitis media (AOM) in young children consumes a substantial amount of medical care services provided by primary-care physicians. A recent increase in the number of young children with AOM prompted a review of the associated risk factors. Eustachian tube dysfunction, bacterial colonization, and host inflammatory response form the basis for the development of AOM. Signs and symptoms of AOM in young children are often nonspecific and subtle, particularly in infants. Physical examination and pneumatic otoscopy verify the diagnosis. New modalities including tympanometry and acoustic reflectometry may be helpful. Amoxicillin remains the drug of choice for AOM, despite recent trends in microbial resistance. Second- and third-line antimicrobial agents might be considered in selected clinical settings. Young children with recurrent episodes of otitis media must be monitored closely. Preventive measures and medical or surgical intervention should be considered in order to minimize the long-term medical and developmental effects of AOM.

Hypercalcemia in pheochromocytoma. Evidence for a novel mechanism.

A child with a pheochromocytoma had hypercalcemia but no evidence for excessive parathyroid hormone secretion from the parathyroid glands or the pheochromocytoma. Therapy with the catecholamine synthesis inhibitor metyrosine (alpha-methyltyrosine) reversed the catecholamine excess but had no effect on the hypercalcemia. Adrenalectomy promptly reversed the hypercalcemia. Extracts of the tumor contained a substance(s) that produced both potent in-vitro bone resorption and striking adenylate-cyclase-stimulating activity in renal cortical membranes. This stimulating activity was due to activation of the parathyroid hormone receptor/adenylate cyclase complex but was not due to parathyroid hormone. Our findings document hypercalcemia in association with pheochromocytoma and show that hypercalcemia occurred in the absence of previously proposed mechanisms. We also provide preliminary characterization of the presumed responsible substance(s) and suggest that this substance(s) may be related to that associated with the humoral hypercalcemia of malignancy.

Clinical pharmacology of two chloramphenicol preparations in children: sodium succinate (iv) and palmitate (oral) esters.

The clinical pharmacology of chloramphenicol was evaluated in 14 children with serious bacterial infections. The children received chloramphenicol sodium succinate intravenously for five to six days at which time orally administered chloramphenicol palmitate was substituted for an additional five to six days of therapy. The mean peak serum chloramphenicol concentration when given iv (28.2 +/- 5.1 micrograms/ml) occurred within one hour after the termination of the 60-minute iv infusion and when given orally (19.3 +/- 2.6 micrograms/ml) occurred two to three hours after ingestion. Differences in serum levels of chloramphenicol after iv compared to oral administration of the same dose could be demonstrated at various time points studied during the dose-response curves; however, the areas under the chloramphenicol curve were not significantly different after iv (140 +/- 116 micrograms/ml/hour) versus oral (95 +/- 26 micrograms/ml/hour) administration. In seven patients who had concomitant serum and CSF chloramphenicol levels determined, a CSF to serum ratio of 23 to 85% occurred. The CSF levels (5.5 to 13 micrograms/ml) were not directly proportional to serum levels. All patients recovered from their infection and no side effects from chloramphenicol were encountered. Administration of chloramphenicol orally in the palmitate form produces serum concentrations and areas under the disappearance curve similar to those achieved after iv administration of the same dose, indicating that the oral route is an effective method of achieving therapeutic concentrations of chloramphenicol in serum.

Current concepts of bacteremia in children with malignancies.

One hundred fifteen episodes of bacteremia occurred among 2790 children with malignancies hospitalized during a 45-month period. The mean age was 9.3 years with a male predilection (62%). A greater (p less than .025) number of children over 10 years of age died with bacteremia when compared to younger children. The majority of episodes occurred in children with leukemia (56%); however, once bacteremia developed, a significantly (p less than .05) greater number of children with lymphoma died when compared to children with other malignancies. Absolute polymorphonuclear leukocyte counts were greater in survivors (p less than .025) than in children who died. Thirty-seven different microorganisms were isolated with E. coli, S. Aureus, P. aeruginosa, and K. pneumoniae accounting for 50% of the episodes. Anaerobes were isolated from blood of 12 (10%) children. Twelve children had polymicrobial bacteremia and 14 had recurrent bacteremia which occurred during antibiotic therapy. Mortality (78%) in these children was significantly (p less than .001) greater then in children from whom one microorganism was isolated (47%). Interesting aspects include the resurgence of S. aureus, failure of development of meningitis in children with bacteremia, and unchanged antibiotic susceptibility since the last review of bacteremia in this institution. Polymicrobial and recurrent bacteremia necessitate obtaining simultaneous and sequential blood cultures to facilitate administration of appropriate antimicrobial therapy until bone marrow function improves.

Assays for chloramphenicol compared: radioenzymatic, gas chromatographic with electron capture, and gas chromatographic-mass spectrometric.

We compared these three techniques for measuring chloramphenicol in serum or urine. Although each has its particular advantages, any of them is shown to be satisfactory and may appropriately be used by clinical laboratories, according to the facilities available.

Clinical pharmacology of tobramycin in children.

The pharmacokinetics of tobramycin were evaluated in 50 pediatric patients (two to 18 years of age) with malignancies and normal renal function. Patients receiving either 240 or 300 mg/m2 per 24 hr (8 or 10 mg/kg per 24 hr) divided into doses given every 4 hr had peak serum concentrations (mean +/- standard error) of 3.10 +/- 0.23 microgram/ml and 4.23 +/- 0.25 microgram/ml, respectively, at the end of a 1-hr infusion. Serum concentrations at 4 hr were 0.82 +/- 0.15 and 1.05 +/- 0.15 microgram/ml, respectively. The half-life of the drug was 96.6 min and was inversely correlated with age of the patients. The total clearance rate of tobramycin was 164 +/- 15 mg/min per 1.73 m2 and was directly correlated with age. The mean volume of distribution was 0.42 +/- 0.038 liter/kg and was inversely correlated with age. No accumulation of tobramycin was noted, and no side effects occurred. If therapeutic serum concentrations of tobramycin are to be achieved and maintained in children, the currently recommended dose and frequency of administration should be changed to 300 mg/m2 per 24 hr given in divided doses every 4 hr.