Successful prophylaxis against Pneumocystis carinii pneumonia in HIV-infected children using smaller than recommended dosages of trimethoprim-sulfamethoxazole

Prophylaxis against Pneumocystis carinii pneumonia (PCP) is an essential pa rt of the management of children with human immunodeficiency virus (HIV) in fection and acquired immune deficiency syndrome (AIDS). No dose-ranging stu dies were ever performed; therefore, the amount of trimethoprim-sulfamethox azole (TMP-SMX) needed to suppress PCP in children with HIV/AIDS is not kno wn. The dose recommended by the Centers for Disease Control (CDC) has been thought to be just above the threshold needed for prevention, based on anec dotal breakthrough PCP in cancer patients who were improperly dosed. We hav e been giving prophylaxis based on body weight rather than surface area, an d this, combined with growth of our children, has led to a large experience with dosages lower than the currently recommended 150 mg/m(2). The medical records of children with HIV who met CBC guidelines for institution of PCP prophylaxis were reviewed. To ascertain the per square meter (m(2)) dosage each child was receiving, body surface area was calculated from height and weight measurements. Dosages were recalculated every 6 months and at each dosage change. Data regarding PCP infection, bacterial infections, and side effects of TMP-SMX were extracted. Data were compiled front 1,719.5 child- months of TMP-SMX prophylaxis, including 1,532.5 child-months below the cur rently recommended dose. Sixty-seven percent of our child-months were at or below two-thirds the CBC recommended dose. There were no cases of proven o r suspected PCP. Incidence of other serious bacterial infections was low. B acteremia and sepsis with Streptococcus pneumoniae was the most common prov en bacterial infection, at a rate of 5.5 episodes per 100 child-years. The incidence of bacterial infection did not vary by the dose of TMP-SMX;. TMP- SMX prophylaxis was well tolerated; most reactions were mild and self-limit ed and did not recur with re-institution of the drug. Only 6.1% of this coh ort had TMP-SMX prophylaxis discontinued due to perceived toxicity. These d ata show that the currently recommended dose of TMP-SMX (150 mg/m(2)) may n ot be required to prevent PCP in children with HIV/AIDS. The drug is well t olerated at all dosage levels. The incidence of serious bacterial infection in this cohort of patients did not depend upon the amount of TMP-SMX presc ribed A prospective, controlled clinical trial of low-dose TMP-SMX for chil dren with HIV infection is warranted.