Beta-Lactam/Beta-Lactamase Inhibitor Combinations in Empiric Management of Pediatric Infections

Abstract

Beta-lactam antibiotics have long played a central role in the management of pediatric infections. However, widespread beta-lactam resistance among community- and hospital-acquired pathogens, mainly due to beta-lactamase production, has reduced the usefulness of these trusted and well-tolerated agents. Many regions have reported an increase in beta-lactamase-mediated resistance to cephalosporins and carbapenems as well as penicillins among clinically important Gram-positive and Gram-negative aerobes and anaerobes. For some pathogens such as Moraxella catarrhalis, Klebsiella species and Pseudomonas aeruginosa, virtually all strains worldwide are beta-lactamase producers. The development of beta-lactamase inhibitors for co-administration with a number of established beta-lactam agents has restored their usefulness in pediatric patients. The combination of ampicillin plus sulbactam has broad anti-aerobic and anti-anaerobic activity in vitro and achieves high concentrations in many body tissues and fluids. The availability of a mutual oral prodrug, sultamicillin, has enabled the development of an oral formulation. Excellent clinical response and bacterial eradication rates with ampicillin/sulbactam and sultamicillin have been demonstrated for upper and lower respiratory tract infections, urinary tract infections, osteomyelitis, and meningitis in pediatric patients and neonates. Furthermore, many studies have demonstrated an excellent tolerability profile. Thus, ampicillin/sulbactam has an important role in the management of pediatric infections.