Epidemiology and Clinical Outcomes of Multidrug-resistant, Gram-negative Bloodstream Infections in a European Tertiary Pediatric Hospital During a 12-month Period

Abstract

This study demonstrates the high mortality of hospital-acquired MDRGN bacteremia in children. International networks focusing on clinical management and outcomes of MDRGN in children are required. Study of novel antibiotics active against Gram-negative bacteria should include children early in the clinical trial development programs.

Stress responses as determinants of antimicrobial resistance in Pseudomonas aeruginosa: multidrug efflux and more

“…This latter effect is, in part, attributable to (i) the organism's intrinsically high resistance to many antimicrobials (Giamarellos-Bourboulis et al 2006) and (ii) the development of increased, particularly multidrug, resistance in health care settings (Bodro et al 2013(Bodro et al , 2014Chaisathaphol and Chayakulkeeree 2014;Chen et al 2013;Chittawatanarat et al 2014;Folgori et al 2014;Medell et al 2012;Pena et al 2013;Pourakbari et al 2012;Xiao et al 2012), both of which complicate antipseudomonal chemotherapy (Chaisathaphol and Chayakulkeeree 2014;Chittawatanarat et al 2014;Chung et al 2011;Folgori et al 2014;Hirsch et al 2012;Hirsch and Tam 2010;Kallen et al 2010;Keen et al 2010; Kerr and Snelling the Multidrug and Toxic Compound Export family, and the Resistance Nodulation Division (RND) family (Li and Nikaido 2009). While examples of all of these have been reported in P. aeruginosa (Poole 2013), by far the most significant contributors to resistance to clinically relevant agents and in clinical isolates are in the RND family (Poole 2001(Poole , 2004a(Poole , 2004b(Poole , 2005b(Poole , 2007Poole and Srikumar 2001).…”

Population Pharmacokinetic Assessment and Pharmacodynamic Implications of Pediatric Cefepime Dosing for Susceptible-Dose-Dependent Organisms

“…The incidence of multidrug-resistant GNB, based on the presence of extended-spectrum ␤-lactamases (ESBLs) and AmpC ␤-lactamases, is increasing globally (6)(7)(8)(9). Infections caused by these organisms are associated with a poor prognosis (10,11). Further complicating this clinical challenge is that development of new antibiotics effective against these important pathogens has been slow (12).…”

Pharmacokinetics and Pharmacodynamics of Continuous-Infusion Meropenem in Pediatric Hematopoietic Stem Cell Transplant Patients

“…Bacteremia and pneumonia are reported to be the most common infections in this setting (1,2), with Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa being the most frequently isolated etiological agents (3,4). Of note, among hospitalized children, the rate of infections due to MDR Gram-negative bacteria is reported to range from 9.1% to 39% (4,5).…”

“…Great concern exists not only in relation to the progressive rise of extended-spectrum ␤-lactamase (ESBL)-producing Enterobacteriaceae (6,7) but also in relation to the worrisome emergence of carbapenem-resistant Enterobacteriaceae (8) and extensively drug-resistant P. aeruginosa (2,9). Of note, MDR-related infections result in very high mortality rates, ranging between 22.6% and 67% (2,4,9).…”

“…Bacteremia and pneumonia are reported to be the most common infections in this setting (1,2), with Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa being the most frequently isolated etiological agents (3,4). Of note, among hospitalized children, the rate of infections due to MDR Gram-negative bacteria is reported to range from 9.1% to 39% (4,5). Great concern exists not only in relation to the progressive rise of extended-spectrum ␤-lactamase (ESBL)-producing Enterobacteriaceae (6,7) but also in relation to the worrisome emergence of carbapenem-resistant Enterobacteriaceae (8) and extensively drug-resistant P. aeruginosa (2,9).…”