The emergence of resistance to established antibiotic agents such as beta-lactams has been reported worldwide and poses a serious challenge to the management of pediatric infections. The most common mechanism of resistance involves the production of an enzyme that inactivates the antibiotic before it can be effective. Streptococcus pneumoniae, the most common cause of pediatric respiratory tract infections, exhibits variable resistance to penicillins and aminopenicillin due to alterations in its penicillin-binding proteins (PBPs). Haemophilus influenzae and Moraxella catarrhalis show moderate and high beta-lactamase-mediated resistance to aminopenicillins, although they remain susceptible to beta-lactam/beta-lactamase inhibitor combinations. Methicillin-resistant Staphylococcus aureus, a frequent cause of skin and soft-tissue infections, has shown PBP-mediated beta-lactam resistance, prompting the wide-spread use of vancomycin to eradicate this pathogen. Finally, PBP-mediated resistance has been observed in a large proportion of isolates of coagulase-negative staphylococci, which account for a high proportion of nosocomial infections, particularly in neonatal intensive care units. The challenge is to control the emergence of beta-lactamase-mediated resistance by using beta-lactams judiciously. In this regard, the beta-lactam/beta-lactamase inhibitor combinations have an important role to play in extending the usefulness of established beta-lactam agents.
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