Sulfamethoxazole (SMX) and
trimethoprim (
TMP) individually and a combination known as
cotrimoxazole (SMX-
TMP) are widely used for the treatment of protozoan and
bacterial infections. SMX-
TMP is also one of the widely used
antibiotics administered orally in neonates, along with
gentamicin injection, for treating
pneumonia and
sepsis by home-based healthcare providers in Asian countries. Although the use of this
drug has successfully reduced neonate mortality, there is a concern for it causing neurotoxicity. Previous clinical studies with
sulfisoxazole have demonstrated occurrence of
kernicterus in neonates. This
sulfonamide is thought to displace
bilirubin from its
albumin-binding sites in plasma leading to an elevation of plasma
bilirubin, which crosses the blood-brain barrier, reaches central neurons to cause
kernicterus. We performed an extensive review of clinical and animal studies with
cotrimoxazole, which showed no reported incidences of
kernicterus with SMX-
TMP use in neonates. EndNote, BasicBiosis, Embase, PubMed and Toxline database searches were conducted using specific keywords yielding 74 full-length articles relevant to the review. This review has taken into account various factors, including the disease itself, direct effects of the
drug and its metabolism through conjugation and acetylation through a thorough review of the literature to examine the potentials of SMX-
TMP to cause
kernicterus in neonates. SMX-
TMP in oral doses administered to neonates for 7-10 days is unlikely to cause
kernicterus. Also, this review recommends warranting the need of future studies using animal models and clinical studies in humans to address SMX-
TMP toxicity.