Dose:    0.5 ml/kg/dose PO
              (see comments for IV)

Frequency: Q 12 hours PO          
                      (see comments for IV)

Indications: Trimethoprim-sulfamethoxazole (TMP-SMX) is effective in upper and lower respiratory tract infections caused by H. Influenza, pneumococci, and B. catarrhalis; UTI's caused by gram negative organisms (except Pseudomonas), systemic salmonella disease, and Pneumocystis carinii pneumonia. It may also be useful in treating severe staphylococcal disease. The IV solution contains benzyl alcohol.   Extremely well absorbed from upper intestinal tract. The major drawback to its use in the newborn, however, is the potential for displacing bilirubin from albumin (as is the case with all sulfonamides though compared to the other sulfonamides, sulfamethoxazole is weak in effecting displacement of bilirubin from albumin). TMP-SMX may inhibit the metabolism of phenytoin, and therefore levels should be followed during concurrent treatment. The recommended dose for treating otitis media and urinary tract infections is 8 mg/kg/day of TMP and 40 mg/kg/day of SMX. This would correspond to a dose of 0.5 ml/kg given orally every 12 hours. The recommendation for intravenous treatment of or other severe infections is to give a total daily dose of 20 mg/kg, based on the trimethoprim component, divided into three or four doses. Less serious infections are treated with a total daily dose of 8 to 10 mg/kg divided into two doses. Further comments on trimethoprim-sulfamethoxazole.

Toxicity:  Because of its limited use in infants, the information regarding toxicity is speculative. The drug appears to be well tolerated. Because of a risk of kernicterus in infants under 2 months of age or in older infants with jaundice, the drug should be used cautiously in these situations. See adverse effects associated with trimethoprim-sulfamethoxazole.

Preparation:
PO: Trimethoprim-sulfamethoxazole is available in an oral formulation containing 40 mg of trimethoprim and 200 mg of sulfamethoxazole per 5 ml (Bactrim, Septra).  Shake well. Store at room temperature.

IV: Trimethoprim-sulfamethoxazole is available in an IV formulation containing 80 mg of trimethoprim and 400 mg of sulfamethoxazole per 5 ml. The IV solution MUST be diluted prior to IV administration. Do not refrigerate concentrate and protect from light. The stability of the medication is increased if a greater volume of diluent is used (see table below). The pharmacy is currently preparing the drug using a 1:25 dilution as long as the infant can tolerate the extra fluid.

1:25 dilution (1 ml vial of drug with 25 ml D₅W (mix with  D₅W only) results in a concentration of 0.64 mg TMP and 3.2 mg SMX/ml.. Minimum infusion time is 60 minutes using a syringe pump. Store at room temperature. The mixture has a stability of six hours.  

1:15 dilution (5 ml vial of drug with 75 ml D₅W (mix with  D₅W only) results in a concentration of 1 mg TMP and 5 mg SMX/ml.. Minimum infusion time is 60 minutes using a syringe pump. Store at room temperature. The mixture has a stability of only two hours.  

Compatibility: Compatibility with filter and TPN are unknown. Dilute with D5W only.  Compatible with D5W, D5 with half-normal saline, LR, half-normal saline, normal saline, acyclovir, allopurinol, atracurium, aztreonam, enalaprilat, esmolol, filgrastim, heparin, labetalol, lorazepam, magnesium sulfate, morphine, pancuronium, piperacillin-tazobactam, vecuronium, and zidovudine. It is incompatible with fluconazole and midazolam.