Antibacterial-induced nephrotoxicity in the newborn

Antibacterials are the primary cause of drug-induced kidney disease in all age groups and these agents bring about renal damage by 2 main mechanisms, namely, direct and immunologically mediated. For some antibacterials (aminoglycosides and vancomycin) nephrotoxicity is very frequent but generally reversible upon discontinuation of the drug. However, the development of acute renal failure with these agents is possible and its incidence in the newborn seems to be increasing. Antibacterials are very often used in the neonatal period especially in very low birthweight neonates. The role of neonatal age in developing nephrotoxicity has still to be defined. Since the traditional laboratory parameters of nephrotoxicity are abnormal only in the presence of substantial renal damage, the identification of early non-invasive markers of the renal damage (urinary microglobulins, enzymes and growth factors) is of importance. Aminoglycosides and glycopeptides are still frequently used, either alone or in combination, despite their low therapeutic index. Numerous factors intervene in bringing about the kidney damage induced by these 2 classes of antibacterials, such as factors related to the antibacterial itself and others related to the associated pathology as well as pharmacological factors. Nephrotoxicity can be caused by the beta-lactams and related compounds. Their potential to cause nephrotoxicity decreases in the order: carbapenems > cephalosporins > penicillins > monobactams. Third generation cephalosporins are frequently used in neonates. However, they are well tolerated compounds at the renal level. The nephrotoxicity of other classes of antibacterials is not discussed either because they are only used in neonates in exceptional circumstances, for example, chloramphenicol and cotrimoxazole (trimethoprim-sulfamethoxazole) or are not associated with significant nephrotoxicity, for example macrolides, clindamicin, quinolones, rifampicin (rifampin) and metronidazole. Antibacterial-induced nephrotoxicity is an important parameter to be considered when treating the newborn and this is particularly true when use of a combination of different antibacterials and/or drugs with a nephrotoxic potential is being considered. However, other parameters, such as antibacterial spectrum, pharmacokinetics, post-antibacterial effect, clinical efficacy, general adverse effect profile and cost, must also be considered in the choice of antibacterial therapy in the neonate. Knowledge of the renal safety of antibacterials and the correct approach to therapeutic drug monitoring may be useful elements for preventing iatrogenic renal disorders.