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.

Eficácia e segurança de Sultamicilina (Ampicilina/Sulbactam) e Amoxacilina/Clavulanato no tratamento das infecções de via aéreas superiores em adultos: um estudo multicêntrico, aberto e randomizado

“…Such results correlate to literature reports on the use of Ampicillin/Sulbactan combination in the treatment of both upper and lower airway infections [24][25][26] .…”

“…The clinical response was, once again, comparable with efficacy rates varying between 84% and 94% 29 . Considering the treatment of otitis in children, Ampicillin/Sulbactan proved to be efficient, with cure rates above those seen with the use of Cefaclor 24 . From the safety stand point, our study confirms literature reports that Ampicillin/Sulbactan is a well tolerated drug.…”

Drug delivery approaches to overcome bacterial resistance to β-lactam antibiotics

“…Since the discovery in the 1940s that pathogenic bacteria exposed to penicillin become resistant due to β -lactamase production, efforts immediately became focused on finding penicillin analogs that could either resist hydrolytic cleavage or inhibit the catalytic activity of β -lactamases. The modification of the structure of the penicillin framework so that strong bactericidal activity is retained, but sensitivity to β -lactamase cleavage is diminished, was the first approach devised [16] . The structurally modified penicillins, including methicillin, oxacillin, nafcillin and cloxacillin ( Figure 2 ), rapidly led to the evolution of new pathogenic bacteria, having β -lactamasemediated resistance [17,18] .…”

Studi Penggunaan Antibiotika pada Neonatus Di NICU RSAL Dr. Ramelan Surabaya

“…Sulbaktam sebagai penghambat betalaktamase secara struktur mirip dengan penisilin tetapi mempunyai rantai samping yang dimodifikasi yang memungkinkannya untuk berperan sebagai penghambat, berikatan secara ireversibel dengan betalaktamase dan membuatnya tidak aktif. Oleh karena itu pemecahan antibiotik oleh betalaktamase dapat dicegah dan aktivitas bakterisidal dapat dipertahankan [4].…”