1608 - Efficacy of Ceftolozane/Tazobactam for Multidrug-Resistant Gram-Negative Infections in Multiple Urban Hospitals

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Presenting Author(s)

NC

Nicolo Cabrera

Fellow
Stanford University
Redwood City, California
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.

Co-Author(s)

TT

Truc T. Tran

Assistant Professor
Center for Antimicrobial Resistance and Microbial Genomics, UTHealth, Houston, TX,
Houston, TX
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Travis J. Carlson

Assistant Professor
High Point University
Jamestown, North Carolina
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
FA

Faris S. Alnezary

Postdoctoral Fellow
University of Houston College of Pharmacy
Houston, Texas
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
William R. Miller

Assistant Professor
Houston Methodist Research Institute
Houston, TX
Disclosure: Entasis Therapeutics (Scientific Research Study Investigator)Merck (Grant/Research Support)Shionogi (Advisor or Review Panel member)
AD

An Q. Dinh

Research Engineer
Center for Antimicrobial Resistance and Microbial Genomics, UTHealth, Houston, TX,
Houston, Texas
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Blake M. Hanson

Assistant Professor
The University of Texas Health Science Center
Houston, Texas
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
JM

Jose M. Munita

MD
Instituto de Ciencias e Innovación en Medicina
Santiago, Region Metropolitana, Chile
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Samuel A. Shelburne

Professor
MD Anderson-University of Texas
Houston,, Texas
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Samuel L. Aitken

Clinical Pharmacist Specialist
Michigan Medicine
Ann Arbor, MI
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Kevin W. Garey

Professor and Chair
University of Houston
Houston, TX
Disclosure: Merck & Co. (Grant/Research Support, Scientific Research Study Investigator)
Laura A. Puzniak

Global Director, Outcomes Research
Merck & Co., Inc.
Kenilworth, New Jersey
Disclosure: Merck (Employee)
CA

Cesar A. Arias

Professor
Houston Methodist Hospital, Center for Infectious Diseases Research, Houston Methodist Research Institute
Houston, Texas
Disclosure: Entasis Therapeutics (Scientific Research Study Investigator)MeMed (Scientific Research Study Investigator)Merck (Grant/Research Support)

Background: Ceftolozane/tazobactam (C/T) is a novel cephalosporin/beta-lactamase inhibitor combination developed for use against multidrug-resistant (MDR) Gram-negative infections, particularly Pseudomonas aeruginosa (PA). C/T is approved for complicated urinary tract and intraabdominal infections as well as hospital-acquired/ventilator-associated bacterial pneumonias. However, comprehensive clinical characterization of patients treated with C/T in non-FDA-approved indications is limited.

Methods: Patients ≥18 years who received C/T for ≥48 hours while hospitalized in 9 acute care centers in Houston, TX from January 2016 through September 2018 were included. Demographic, microbiologic, treatment and clinical outcome data were retrospectively collected by chart review. In patients who received multiple inpatient courses of C/T, only the first course with C/T was assessed.

Results: 210 patients met inclusion criteria: 58% were non-white, 35% were female and 13% were immunocompromised. Median age was 61 years (IQR, 48 to 69). Median Charlson comorbidity index was 5 (IQR, 2 to 6). At the onset of the index episode, a significant proportion of patients required intensive care unit admission (44%), mechanical ventilation (37%) and pressor support (22%). Respiratory sources were the most common (50%) followed by urine (15%). Positive cultures were documented in 93% of the cases and PA was found in 86%. Majority (95%) of PA which were MDR. C/T use was guided by susceptibility testing of the index isolate in ca. 52%. In 5.7% of cases, C/T was used to escalate therapy without any documented C/T-susceptible organism. Half (51%) of the cohort received initial dosing appropriate for renal function while 36% receiving a lower than recommended dose. Clinical success (i.e., recovery from infection-related signs and symptoms) occured in 77%. The in-hospital mortality rate in our cohort was 15% with 26 of 31 deaths deemed infection-related.

Conclusion: We report a large multicenter observational cohort that received C/T. A 77% clinical success with the use of C/T was documented. These data support the use of C/T in critically ill patients infected with MDR PA.