Approaches to reduce the side effects of antibiotic therapy in premature newborns

Significant risk of drug therapy side effects in newborns, especially in premature neonates, is associated with the immaturity of a number of enzyme systems and biotransformation mechanisms and pharmacokinetics specificity. First of all, it is associated with the immaturity of the microsomal mechanism of hepatic cells. Newborns have lower concentrations of cytochrome P450, NADPH-oxidase, cytochrome-C reductase, (uridine diphosphate)-glucuronyl transferase, as well as enzymatic and non-enzymatic modulators of the thiol-disulfide system. Low activity of the antioxidant system and endogenous antioxidants enhances the ROS formation during biotransformation of antibiotics and increase their toxicity at concentrations safe for adults, resulting in increased hepatotoxicity. In Zaporizhzhya region (Ukraine), in chronic pulmonary suppuration, transaminase levels increased in 17% of children treated with chloramphenicol and aminoglycosides, in 7.8% with semi-synthetic penicillins and in 5.3% with cephalosporins and macrolides, as well as in 34.5% of children receiving combined therapy. This makes it necessary to reduce dosages, usually by infrequent administration of drugs, and to conduct laboratory monitoring not only of the hepatobiliary system, but also of the antioxidant glutathione system. Another important approach for premature infants in the first weeks of life to reduce antibiotic therapy side effects, including hepatotoxicity, is the administration of agents modulating the activity of the glutathione system. The difficulty in implementing this approach is the strict requirements for safety and proven efficiency for drugs in neonatal intensive care. We consider the use of thioazatate (thiotriazolin), a drug licensed in Ukraine with proven hepatoprotective and cardioprotective activity and a high safety profile.