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Antimicrobial Original Research Paper

Comparative in vitro effectiveness of ceftolozane/tazobactam against pediatric gram-negative drug-resistant isolates

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Pages 288-293 | Received 27 Dec 2020, Accepted 03 Feb 2021, Published online: 01 Mar 2021
 

Abstract

Ceftolozane/tazobactam (C/T), a cephalosporin/beta-lactamase inhibitor combination, was evaluated in vitro vs. 10 comparators against 299 pediatric extended-spectrum-cephalosporin-resistant or carbapenem-resistant (ESC-R/CR) Gram-negative Enterobacteriaceae from three freestanding pediatric centers. Isolates were from urine or other sterile sites of children and adolescents through 21 years of age. Susceptibilities were assayed by microbroth dilution via custom Sensititre plates (Thermo Fisher Scientific). Susceptibility was determined using the Sensititre Vizion® system (Thermo Fisher Scientific). Susceptibility breakpoint criteria were those of the Clinical and Laboratory Standards Institute (CLSI) for 2017, except for colistin (EUCAST 2019). Overall, 87.5% isolates were C/T susceptible (MIC ≤2 μg/ml; MIC50/90, 0.25/4 μg/ml). Susceptibility to C/T was detected more frequently as compared to all other antimicrobials tested except for colistin (95.4%) and meropenem (97.4%). Percent susceptibility to C/T was high for E. coli (91%) and Klebsiella spp. (73.3%). C/T demonstrated good in-vitro activity and high potency against most beta-lactam resistant pediatric Enterobacteriaceae from three geographically diverse U.S. regions.

Additional information

Funding

This work was supported by the Merck & Co., Inc under Grant [MISP #53804]

Notes on contributors

Neena Kanwar

Neena Kanwar's research interests are in the field of pediatric disease diagnostics. She is involved in industry based clinical trials for evaluating diagnostic equipment and assays. She is specifically interested in antimicrobial resistance and characterizing resistance mechanisms from pediatric clinical isolates. In addition, her interest includes detection and epidemiology of pediatric respiratory and enteric pathogens using advanced microbiological and molecular techniques.

Dithi Banerjee

Dithi Banerjee is a Research Scientist and her overall objective is to actively pursue collaborative scientific projects to bridge the gap between basic research and clinical science. Her areas of research interest include antimicrobial resistance, microbial pathogenesis and epidemiology of infectious diseases. In her current role at Children's Mercy, she is engaged in multiple and diverse research projects ranging from anti-microbial susceptibility, molecular epidemiology of pediatric viral pathogens, clinical trials for diagnostic assays and currently looking forward to taking the step into COVID-19 research.

Christopher J. Harrison

Christopher J Harrison is the Director of Infectious Disease Research Laboratory and the Director of Vaccine and Treatment Evaluation Unit at Children's Mercy, Department of Pediatric Infectious Diseases. His areas of research interest include Pediatric Infectious Diseases, Antimicrobials, Drug Resistance, Immune Responses to Herpes Viruses, Otitis Media, Toll-Like Receptor Signaling and Vaccines.

Jason G. Newland

Jason G. Newland focuses on the appropriate use of antimicrobials in all settings, including both human and animal health. His primary research focus has been in the dissemination and implementation of Antimicrobial Stewardship Programs for hospitalized children. He is the founder and leader of the SHaring Antimicrobial Reports for Pediatric Stewardship (SHARPS) national collaborative of over 50 children's hospitals across the United States. Additionally, he is involved with implementing strategies to improve antibiotic use in the ambulatory setting. His advocacy work has been in promoting appropriate antibiotic use in the agriculture industry.

Xuan Qin

Xuan Qin reserach interests include microbial revolution, microbial symbiosis, antimicrobial resistance, and microbial molecular biology with emphasis on molecular diagnosis.

Danielle M. Zerr

Danielle M. Zerr's research has focused on two main areas: (1) defining the epidemiology of viral pathogens in healthy children and immunocompromised hosts and (2) describing the epidemiology and defining prevention strategies for healthcare-associated infections. Recent work includes studies aimed at defining the epidemiology of human herpesvirus 6 (HHV-6) in hematopoietic stem cell transplant recipients. In addition, Dr. Zerr collaborates with Dr. Weissman and Dr. Qin in investigating the molecular epidemiology of broad-spectrum beta-lactam resistance in pediatric Enterobacteriaceae infections. Dr. Zerr also leads a multicenter trial aimed at reducing healthcare-associated infections in children with cancer.

Theoklis Zaoutis

Theoklis Zaoutis's research focuses on healthcare-acquired infections and antibiotic resistance. Within the area of healthcare-acquired infections, he is particularly interested in fungal infections. His work also focuses on pediatric pharmacoepidemiology as it relates to the judicious use of antimicrobial agents (antimicrobial stewardship), both in the hospital and in ambulatory care. Finally, Dr. Zaoutis is associate director of the Center for Pediatric Clinical Effectiveness Research at the Children's Hospital of Philadelphia.

Rangaraj Selvarangan

Rangaraj Selvarangan has over 18 years of experience in Clinical Laboratory Medicine Practice. He has published more than 80 manuscripts in peer-reviewed scientific journals and presented more than100 oral and poster presentations at national and international conferences. He is the Prinicipal Investigator of more than fifty industrial and federally funded research studies on epidemiology and diagnosis of infectious diseases in children.

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