PMID- 37698430
OWN - NLM
STAT- Publisher
LR  - 20231020
IS  - 2165-0497 (Electronic)
IS  - 2165-0497 (Linking)
VI  - 11
IP  - 5
DP  - 2023 Sep 12
TI  - Subgroup analysis of phase 2 study of ceftolozane/tazobactam in neonates and 
      young infants with pyelonephritis.
PG  - e0180023
LID - 10.1128/spectrum.01800-23 [doi]
LID - e01800-23
AB  - Ceftolozane/tazobactam is approved for the treatment of patients from birth to 
      <18 y old with complicated urinary tract infections (cUTI). This post hoc 
      analysis evaluated the safety, efficacy, and pharmacokinetics (PK) of 
      ceftolozane/tazobactam compared with meropenem in neonates and young infants. 
      NCT03230838 was a phase 2, randomized, active comparator-controlled, double-blind 
      study of patients from birth to <18 y of age with cUTI, including pyelonephritis, 
      given ceftolozane/tazobactam or meropenem in a 3:1 ratio. This subset analysis 
      included only neonates and young infants < 3 mo of age. The microbiologic 
      modified intent-to-treat population (mMITT) included 20 patients 
      (ceftolozane/tazobactam, n = 14; meropenem, n = 6). All patients had 
      pyelonephritis at baseline; two patients in each treatment group had bacteremia 
      (overall 4/20, 20%). Escherichia coli was the most common baseline pathogen 
      (overall 16/20, 80%). Safety and efficacy results were similar between treatment 
      groups and consistent with the overall pediatric population. There were no 
      serious drug-related adverse events (AEs), no discontinuations due to AEs, and no 
      AEs leading to death in either treatment group. For the ceftolozane/tazobactam 
      and meropenem treatment groups, clinical cure rates in the mMITT population were 
      92.9% and 100%, respectively. The population PK analysis of neonates and young 
      infants demonstrated similar ceftolozane and tazobactam exposures to those of 
      adults, achieving pharmacodynamic targets associated with clinical and 
      microbiologic cure. Ceftolozane/tazobactam has a favorable safety profile and 
      achieves high clinical cure and microbiologic eradication rates in neonates and 
      young infants < 3 mo of age with cUTI and pyelonephritis. IMPORTANCE 
      Extrapolation of antibacterial agent pharmacokinetics from adults to newborns and 
      young infants may not be appropriate; similarly, the clinical manifestations of 
      infectious diseases and outcomes following antibacterial treatment may not be 
      similar. Ceftolozane/tazobactam is an antibacterial drug combination active 
      against Pseudomonas aeruginosa and other multidrug-resistant gram-negative 
      bacteria. A clinical study led to the approval for ceftolozane/tazobactam in 
      patients from birth to 18 y of age who have complicated urinary tract infections, 
      including those with serious kidney infections. Based on data collected during 
      that clinical study, we compared newborns and young infants who were treated with 
      ceftolozane/tazobactam (14 patients) and those who were treated with meropenem (6 
      patients). We found that ceftolozane/tazobactam treatment of newborns and young 
      infants up to 3 mo of age who have complicated urinary tract infections 
      demonstrated a favorable safety profile and high clinical cure and microbiologic 
      eradication rates, similar to meropenem.
FAU - Roilides, Emmanuel
AU  - Roilides E
AUID- ORCID: 0000-0002-0202-364X
AD  - Third Department of Pediatrics, Infectious Diseases Unit, School of Medicine, 
      Aristotle University and Hippokration General Hospital , Thessaloniki, Greece.
FAU - Bradley, John S
AU  - Bradley JS
AD  - Department of Pediatrics, University of California, San Diego School of Medicine 
      and Rady Children's Hospital of San Diego , San Diego, California, USA.
FAU - Lonchar, Julia
AU  - Lonchar J
AD  - Merck & Co., Inc. , Rahway, New Jersey, USA.
FAU - Huntington, Jennifer A
AU  - Huntington JA
AD  - Merck & Co., Inc. , Rahway, New Jersey, USA.
FAU - Wickremasingha, Prachi
AU  - Wickremasingha P
AD  - Merck & Co., Inc. , Rahway, New Jersey, USA.
FAU - Su, Feng-Hsiu
AU  - Su FH
AD  - Merck & Co., Inc. , Rahway, New Jersey, USA.
FAU - Bruno, Christopher J
AU  - Bruno CJ
AD  - Merck & Co., Inc. , Rahway, New Jersey, USA.
FAU - Johnson, Matthew G
AU  - Johnson MG
AUID- ORCID: 0000-0002-6023-1252
AD  - Merck & Co., Inc. , Rahway, New Jersey, USA.
LA  - eng
PT  - Journal Article
DEP - 20230912
PL  - United States
TA  - Microbiol Spectr
JT  - Microbiology spectrum
JID - 101634614
SB  - IM
PMC - PMC10581202
OTO - NOTNLM
OT  - cUTI
OT  - ceftolozane/tazobactam
OT  - neonates
OT  - pyelonephritis
OT  - young infants
COIS- E.R. reports grant funding and consulting fees from MSD to his institution. E.R. 
      and J.S.B. report funding to conduct the study from MSD to their institutions. 
      J.L., J.A.H., P.W., C.J.B., and M.G.J. are employees of MSD, who may own stock 
      and/or hold stock options in Merck & Co., Inc., Rahway, NJ, USA.
EDAT- 2023/09/12 12:42
MHDA- 2023/09/12 12:42
PMCR- 2023/09/12
CRDT- 2023/09/12 09:13
PHST- 2023/09/12 12:42 [medline]
PHST- 2023/09/12 12:42 [pubmed]
PHST- 2023/09/12 09:13 [entrez]
PHST- 2023/09/12 00:00 [pmc-release]
AID - 01800-23 [pii]
AID - spectrum.01800-23 [pii]
AID - 10.1128/spectrum.01800-23 [doi]
PST - aheadofprint
SO  - Microbiol Spectr. 2023 Sep 12;11(5):e0180023. doi: 10.1128/spectrum.01800-23.