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Optimal antibacterial therapy of neonates at risk of early onset sepsis
(Tartu University Press, 2010-04-27T10:53:25Z) Metsvaht, Tuuli
In industrial countries infection is the third common and in the developing world the most frequent cause of neonatal mortality. Antibacterial therapy is the cornerstone of treatment. Only a few studies have compared the clinical efficacy of different antibiotic regimens in this setting. Most of them date from time 15 to 20 years ago and study drugs or their combinations that are not even used in neonates today. Optimal drug dosing relies on the understanding of its pharmacokinetic and pharmacodynamic properties. In different age groups these may vary significantly due to differences in body composition and organ function. The thesis focuses on identification of optimal dosage of penicillin G in very low birth weight neonates and comparison of the clinical efficacy of two antibiotic regimens most widely used in the treatment of neonates at risk of sepsis. The half-life of penicillin G in very low birth weight neonates is significantly longer that in adults and the predominant renal mechanism of elimination is glomerular filtration in contrast to tubular secretion in adults. The dose of 25000 IU/kg q12h provides adequate serum concentrations of the drug in most cases. The clinical efficacy of ampicillin plus gentamicin and penicillin G plus gentamicin combinations is similar. Still, ampicillin containing regimen may be associated with lower mortality of extremely preterm (born before 26th week of gestation) neonates; with lower incidence rate of late onset sepsis due to coagulase negative staphylococci and lower use of late antibacterial therapy. Neonates who develop thrombocytopenia with concomitant need for vasoactive treatment or leucopenia or leucocytosis with hypoglycaemia within the first 72 h of life have high risk of treatment failure on ampicillin or penicillin G and gentamicin therapy. Further studies have to show, whether early change to broader spectrum agents would improve the outcomes for these babies.