Pediatric Pharmacology and Therapeutics

Abstract

Intravenous trimethoprim,sulfamethoxazole in the treatment of serious infections in children Intravenous TMP-SMZ was used to treat 19 infectious episodes in 18 patients ranging in age from 3 weeks to 13 years. Thirteen patients with various soft tissue or skeletal infections caused by Haemophilus influenzae. Streptococcus pneumoniae, Staphylococcus aureus. Streptococcus pyogenes, or Acinetobacter anitratus were successfull) treated Three children with four episodes of CSF shunt injections due to coagulase-negative staphylococci were treated successfully also. The only treatment failures were m two newborn infants with entertc gram-negative bacterial ventriculitis. TMP-SMZ was given at a daily dose of 10 and 50 mg/kg, respectively, every six hours. The drug was administered intravenously for a mean duration of lO days (range 4 to 32); in ll patients this was followed by oral administration for a mean of nine days (range 2 to 18). Half-life of TMP after intravenous administration was 51/4 hours; that of SMZ was 81/2 hours. Levels determined three to four days after starting therapy were generally higher than levels obtained at eorresponding times after the first dose. CSF/blood TMP and SMZ ratios, determined in four patients, were 0.6 and O. 5, respectively. Side effects were observed in 14 patients, and neutropenia was the most common adverse reaction. Intravenous TMP-SMZ is an effective antimicrobie agent in the treatment of infections due to susceptible organisms. The frequent side 'effects, although reversible and of no major clinical consequence, suggest that future use of TMP-SMZ should be monitored closely. TRIMETHOPRIM-SULFAMETHOXAZOLE in the oral form has been useful in the treatment of various infections in children, including infections of the urinary tract. 1-3 the middle ear? and various other sites. 4-~ Outside the United States TMP-SMZ has been used parenterally in the treatment of serious infections in children and adults. 7~~ This study was designed to evaluate the efficacy arid safety of intravenous administration of TMP-SMZ in infants and children, and to determine the pharmacoki-netics of this antimicrobic combination in the pediatric age group. pyogenic arthritis, cellulitis, and other infections requiring intravenous antibiotic treatment were chosen for the study. Informed parental consent was obtained in each case. Patients with known glucose-6,phosphate dehydro-genase deficiency or a history of allergy to trimethoprim or sulf0namide drugs were excluded. Abbreviations used TMP: trimethoprlm SMZ: sulfamethoxazole PMN: polymorphonuclear leukocyte Microbiology. The causative organtsm was sought in each instance from the blood and from appropriate sites, such as soft tissues, lymph nodes, joints, and bone by needle aspiration. Bacterial isolation and identification were performed in the clinical microbiology laboratory. Disc susceptibilities were determined using standard labo-ratory procedures. 11 Drug therapy. After appropriate cultures were obtained.