Kernicterus

Host factors can help to ensure selection of the most appropriate antimicrobial agent. Age is an important factor in antimicrobial selection. With regard to dose and interval, renal and hepatic function varies with age. Populations with diminished renal function include neonates and the elderly. Hepatic function in the neonate is not fully developed, and drugs that are metabolized or eliminated by this route may produce adverse effects. For example, sulfonamides and ceftriaxone may compete with bilirubin for binding sites and may result in hyperbilirubinemia and kernicterus. Gastric acidity also depends on... 

Cephalexin is considered safe and effective. Nitrofurantoin should not be used after week 37 due to concern for hemolytic anemia in the newborn. Sulfa-containing drugs may increase risk for kernicterus in the newborn and should be avoided during the last weeks of gestation. Folate antagonists, such as trimethoprim, are relatively contraindicated during the first trimester because of their association with cardiovascular malformations. Fluoroquinolones and tetracyclines are contraindicated. 

Jaundice (yellow color of skin, whites of the eyes) may occur when blood levels of bilirubin exceed normal (icterus). Jaundice may be characterized by an increase in unconjugated (indirect) bilirubin, conjugated (direct) bilirubin, or both. Accumulation of bilirubin (usually unconjugiated) in the brain (kernicterus) may result in death. When conjugated bilirubin increases, it may be excreted, giving a deep yeUow-red color to the urine. Examples of conditions associated with increased bilirubin and jaundice include the following. 

With severe hemolysis, more bihrubin is released into the blood than can be transported on albumin and conjugated in the liver. Unconjugated and total bilirubin increase and may produce jaundice and kernicterus. Examples include ... 

Conjugation with glucuronyl residues is of great importance for the metabolic fate of bilirubin (S3), steroids (L5, M2, R8), catecholamines (W17) and other hydrophobic compounds (D8, D9). Neonatal accumulation of bilirubin in man and rats may trigger maturation of UDP-glucuronyltransferase (Bl, B2, T6). Delayed maturation of the enzyme, or its partial or total deficiency, are critical factors in the development of kernicterus (P6). Compared to other species partial deficiency of the... 

Lactation Sulfonamides are excreted in breast milk. In newborns, they compete with bilirubin for binding sites on the plasma proteins and may cause kernicterus. Children The safety and efficacy of sulfasalazine in pediatric patients younger than 2 years of age with ulcerative colitis have not been established. 

Pregnancy Category 6 Category D near term. Significant levels may persist in the neonate if these drugs are given near term jaundice, hemolytic anemia, and kernicterus may occur. Do not use at term. 

Children Do not administer atazanavir to pediatric patients younger than 3 months of age because of the risk of kernicterus. 

Lactation TMP-SMZ is not recommended in the nursing period because sulfonamides are excreted in breast milk and may cause kernicterus. Premature infants and infants with hyperbilirubinemia or G-6-PD deficiency are also at risk for adverse effects. 

Jaundice is notitseifa disease but is an important diagnostic indicator of many underiying conditions, in newborns, jaundice can iead to toxic encephalopathy due to deposition of bilirubin within the lipid regions of membranes of the brain (kernicterus). 

Sulfasalazine is contraindicated in individuals with hypersensitivity to salicylates, sulfonamides, sulfonylureas, and certain diuretics (furosemide, thiazides, and carbonic anhydrase inhibitors). Because it can cause kernicterus, sulfasalazine is contraindicated in infants and children under 2 years of age. Sulfasalazine passes into breast milk and is therefore contraindicated for nursing mothers. Similarly, pregnant women near term should not use this drug, although it appears to be the safest of the DMARDs during early pregnancy. 

Sulfonamides compete for sites on plasma proteins that are responsible for the binding of bilirubin. As a result, less bilirubin is bound, and in the newborn, the unbound bilirubin can be deposited in the basal ganglia and subthalamic nuclei, causing kernicterus, a toxic encephalopathy. For this reason, sulfonamides should not be administered to newborns or to women during the last 2 months of pregnancy. 

A 3-day-old baby is given a presumptive diagnosis of kernicterus. Which of the following mechanisms is involved in sulfonamide-induced kernicterus ... 

Rubaltelli, RF and Griffith, P.F. (1992) Management of neonatal hy-perbilirubinaemia and prevention of kernicterus. Drugs 43 864-872. 

Sulfonamides can cause hemolytic or aplastic anemia, granulocytopenia, thrombocytopenia, or leukemoid reactions. Sulfonamides may provoke hemolytic reactions in patients with glucose-6-phosphate dehydrogenase deficiency. Sulfonamides taken near the end of pregnancy increase the risk of kernicterus in newborns. 

C8. Crigler, J. F., and Najjar, V. A., Congenital familial nonhemolytic jaundice with kernicterus. Pediatrics 10, 169-179 (1952). 

D4. Day, R., Kernicterus Further observations on the toxicity of heme pigments. Pediatrics 17, 925-928 (1956). 

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