Antimicrobial therapy in neonates, infants and children

Many antimicrobial medications may be administered to paediatric patients with a degree of impunity because they are relatively non-toxic and have a wide therapeutic margin. However, because of different pharmacokinetics from those in adults, the potential for toxicity exists with the use of some of these agents. Drug absorption in paediatric patients, either orally or parenterally, is generally similar to that in adults, except among neonates and, particularly, premature neonates. Similarly, in neonates, drug distribution is altered, plasma protein binding is decreased and hepatic metabolism and renal excretory capacity are limited by physiological immaturity. Thus, in neonates, only drugs that have pharmacokinetically derived dosage schedules should be used, and therapeutic monitoring of plasma drug concentrations is recommended during therapy with aminoglycosides, vancomycin and chloramphenicol. In older infants and children, the pharmacokinetics of antimicrobial drugs generally approximate those in adults, and recommended dosages have been determined relative to bodyweight. Therapeutic monitoring of plasma drug concentrations may be important in certain patients, such as those with major organ failure, and may be useful in cases of suspected noncompliance. Additional pharmacokinetic considerations concerning antimicrobial medication and paediatric patients are the extent to which drug therapy penetrates the cerebrospinal fluid in meningitis, and the potential for and implications of exposure of infants to antimicrobial medications excreted in breast milk.