Safety and Efficacy of Ceftolozane/Tazobactam Plus Metronidazole Versus Meropenem From a Phase 2, Randomized Clinical Trial in Pediatric Participants With Complicated Intra-abdominal Infection.

Background: Ceftolozane/tazobactam, a cephalosporin-β-lactamase inhibitor combination, is approved for the treatment of complicated urinary tract infections and complicated intra-abdominal infections (cIAI). The safety and efficacy of ceftolozane/tazobactam in pediatric participants with cIAI were assessed.

Methods: This phase 2 study (NCT03217136) randomized participants to either ceftolozane/tazobactam+metronidazole or meropenem for treatment of cIAI in pediatric participants (<18 years).

Safety and Efficacy of Ceftolozane/Tazobactam Versus Meropenem in Neonates and Children With Complicated Urinary Tract Infection, Including Pyelonephritis: A Phase 2, Randomized Clinical Trial.

Background: Ceftolozane/tazobactam, a cephalosporin-β-lactamase inhibitor combination, active against multidrug-resistant Gram-negative pathogens, is approved for treatment of adults with complicated urinary tract infections (cUTI). Safety and efficacy of ceftolozane/tazobactam in pediatric participants with cUTI, including pyelonephritis, were assessed.

Methods: This phase 2 study (NCT03230838) compared ceftolozane/tazobactam with meropenem for treatment of cUTI in participants from birth to <18 years of age.

A Phase 3, Randomized, Double-Blind Study Comparing Tedizolid Phosphate and Linezolid for Treatment of Ventilated Gram-Positive Hospital-Acquired or Ventilator-Associated Bacterial Pneumonia.

Background: Hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) are associated with high mortality rates. We evaluated the efficacy and safety of tedizolid (administered as tedizolid phosphate) for treatment of gram-positive ventilated HABP/VABP.

Methods: In this randomized, noninferiority, double-blind, double-dummy, global phase 3 trial, patients were randomized 1:1 to receive intravenous tedizolid phosphate 200 mg once daily for 7 days or intravenous linezolid 600 mg every 12 hours for 10 days.

Daptomycin for Pediatric Gram-Positive Acute Hematogenous Osteomyelitis.

Background: We prospectively evaluated efficacy and safety of daptomycin versus active comparator in children with acute hematogenous osteomyelitis (AHO).

Methods: Randomized, controlled, double-blind, global, multicenter, phase 3 trial. Patients 1-17 years of age with suspected/confirmed AHO requiring hospitalization and intravenous therapy were randomized 1:1 to intravenous daptomycin (once-daily, age-adjusted doses) or comparator (vancomycin, nafcillin or equivalent) ≥4 days, followed by oral therapy (14-42 days total).

Randomized Multicenter Study Comparing Safety and Efficacy of Daptomycin Versus Standard-of-care in Pediatric Patients With Staphylococcal Bacteremia.

Background: Staphylococcus aureus, including community-associated methicillin-resistant S. aureus, is an important cause of pediatric bacteremia. Daptomycin is a well-established treatment option for Gram-positive bacteremia in adults, but its safety and efficacy in children require confirmation.

Analysis of patients with diabetes and complicated intra-abdominal infection or complicated urinary tract infection in phase 3 trials of ceftolozane/tazobactam.

Background: Diabetes mellitus and hyperglycemia are associated with increased susceptibility to bacterial infections and poor treatment outcomes. This post hoc evaluation of the treatment of complicated intra-abdominal infections (cIAI) and complicated urinary tract infections (cUTI) aimed to evaluate baseline characteristics, efficacy, and safety in patients with and without diabetes treated with ceftolozane/tazobactam and comparators. Ceftolozane/tazobactam is an antibacterial with potent activity against Gram-negative pathogens and is approved for the treatment of cIAI (with metronidazole) and cUTI (including pyelonephritis).

PK/PD Target Attainment With Ceftolozane/Tazobactam Using Monte Carlo Simulation in Patients With Various Degrees of Renal Function, Including Augmented Renal Clearance and End-Stage Renal Disease.

Introduction: Ceftolozane/tazobactam is an antibacterial agent with potent in vitro activity against Gram-negative pathogens, including many extended-spectrum β-lactamase-producing Enterobacteriaceae and drug-resistant Pseudomonas aeruginosa. Because ceftolozane/tazobactam is primarily excreted renally, appropriate dose adjustments are needed for patients with renal impairment. Monte Carlo simulations were used to determine the probability of pharmacokinetic/pharmacodynamic target attainment for patients with varying degrees of renal function, including augmented renal clearance (ARC) and end-stage renal disease (ESRD) with hemodialysis.

Does moderate renal impairment affect clinical outcomes in complicated intra-abdominal and complicated urinary tract infections? Analysis of two randomized controlled trials with ceftolozane/tazobactam.

Objectives: For reasons not well understood, antibacterials can yield lower cure rates in renally impaired patients. We explored this subject for the novel antibacterial ceftolozane/tazobactam.

Methods: ASPECT-complicated intra-abdominal infections (cIAIs) and ASPECT-complicated urinary tract infections (cUTIs) were randomized, double-blinded clinical trials.

Efficacy of ceftolozane/tazobactam against urinary tract and intra-abdominal infections caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae: a pooled analysis of Phase 3 clinical trials.

Objectives: The increase in infections caused by drug-resistant ESBL-producing Enterobacteriaceae (ESBL-ENT) is a global concern. The characteristics and outcomes of patients infected with ESBL-ENT were examined in a pooled analysis of Phase 3 clinical trials of ceftolozane/tazobactam in patients with complicated urinary tract infections (ASPECT-cUTI) and complicated intra-abdominal infections (ASPECT-cIAI).

Methods: Trials were randomized and double blind.

Characteristics and Outcomes of Complicated Intra-abdominal Infections Involving Pseudomonas aeruginosa from a Randomized, Double-Blind, Phase 3 Ceftolozane-Tazobactam Study.

Ceftolozane-tazobactam is active against Gram-negative pathogens, including multidrug-resistant Pseudomonas aeruginosa In a subgroup analysis of patients with complicated intra-abdominal infections (cIAIs) involving P. aeruginosa from a phase 3 program, ceftolozane-tazobactam demonstrated potent in vitro activity against P. aeruginosa Clinical cure in the microbiologically evaluable population was 100% (26/26) for ceftolozane-tazobactam plus metronidazole and 93.

Ceftolozane/Tazobactam Plus Metronidazole for Complicated Intra-abdominal Infections in an Era of Multidrug Resistance: Results From a Randomized, Double-Blind, Phase 3 Trial (ASPECT-cIAI).

Background: Increasing antimicrobial resistance among pathogens causing complicated intra-abdominal infections (cIAIs) supports the development of new antimicrobials. Ceftolozane/tazobactam, a novel antimicrobial therapy, is active against multidrug-resistant Pseudomonas aeruginosa and most extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae.

Methods: ASPECT-cIAI (Assessment of the Safety Profile and Efficacy of Ceftolozane/Tazobactam in Complicated Intra-abdominal Infections) was a prospective, randomized, double-blind trial.