Antibiotic options for treatment of pediatric infections with Enterobacteriaceae producing broad spectrum beta-lactamases

Enterobacteriaceae are major pediatric pathogens, but little is known regarding treatment options for multidrug-resistant strains. In this study, we investigated the susceptibility patterns of healthcare- and community-associated Enterobacteriaceae isolates expressing plasmid-borne, broad-spectrum beta-lactam resistance (PBLR). Using E-test methodology, we tested susceptibility to imipenem, meropenem, ertapenem, doripenem, piperacillin-tazobactam, minocycline, tigecycline, fosfomycin, and colistin in all 90 clinical isolates (Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca and Salmonella enterica) which are derived from urine (n=62), blood (n=12), and other specimens (n=16). These strains are confirmed to carry PBLR determinants. Although malignancy, urogenital and neurological diseases, and multiple antibiotic exposure were present in most patients, twenty three isolates (26%) were characterized as communityassociated. Enterobacteriaceae isolates expressing PBLR retained in vitro susceptibility to colistin (100%), minocycline (72%), tigecycline (97%), and fosfomycin (92%). Five unlinked isolates (6%; two isolates of E. coli and three of K. pneumoniae) showed resistance to one or all carbapenem agents. All community-associated isolates were susceptible to carbapenems and exhibited greater susceptibility to other agents compared to healthcare-associated isolates. In our study population, carbapenems remained broadly active and colistin, fosfomycin, and tigecycline demonstrated therapeutic potential against PBLR-positive isolates. Our findings have implications for susceptibility testing and empirical antimicrobial strategies targeting serious pediatric infections.