Clinical characteristics, microbiology and outcomes of a cohort of patients treated with ceftolozane/tazobactam in acute care inpatient facilities, Houston, Texas, USA

Author:

Tran Truc T12,Cabrera Nicolo L3,Gonzales-Luna Anne J45ORCID,Carlson Travis J6ORCID,Alnezary Faris57,Miller William R12ORCID,Sakurai Aki8,Dinh An Q2,Rydell Kirsten2,Rios Rafael9,Diaz Lorena910,Hanson Blake M11ORCID,Munita Jose M10,Pedroza Claudia12,Shelburne Samuel A13ORCID,Aitken Samuel L14ORCID,Garey Kevin W45ORCID,Dillon Ryan15,Puzniak Laura15,Arias Cesar A12

Affiliation:

1. Center for Infectious Diseases Research, Houston Methodist Research Institute , Houston, TX , USA

2. Division of Infectious Diseases, Department of Medicine, Houston Methodist Hospital , Houston, TX , USA

3. Division of Infectious Diseases, John T. Milliken Department of Internal Medicine, Washington University School of Medicine , St. Louis, MO , USA

4. Department of Pharmacy, Baylor St. Luke’s Medical Center, CHI St. Luke’s Health , Houston, TX , USA

5. Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy , Houston, TX , USA

6. Department of Clinical Sciences, Fred Wilson School of Pharmacy, High Point University , High Point, NC , USA

7. Department of Clinical and Hospital Pharmacy, College of Pharmacy, Taibah University , Medina , Saudi Arabia

8. Department of Infectious Diseases and Microbiology, Fujita Health University School of Medicine , Aichi , Japan

9. Molecular Genetics and Antimicrobial Resistance Unit, International Center for Microbial Genomics, Universidad El Bosque , Bogota , Colombia

10. Genomics and Resistant Microbes Group, Facultad de Medicina Clinica Alemana, Universidad del Desarrollo and Millennium Initiative for Collaborative Research On Bacterial Resistance (MICROB-R) , Santiago , Chile

11. Center for Infectious Diseases, University of Texas Health Science Center School of Public Health , Houston, TX , USA

12. Center for Clinical Research and Evidence-Based Medicine, The University of Texas Health Science Center at Houston , Houston, TX , USA

13. Department of Infectious Diseases, Infection Control & Employee Health, University of Texas MD Anderson Cancer Center , Houston, TX , USA

14. Division of Pharmacy, University of Texas MD Anderson Cancer Center , Houston, TX , USA

15. Center for Observational and Real-World Evidence (CORE), Merck and Co., Inc. , Kenilworth, NJ , USA

Abstract

Abstract Background Ceftolozane/tazobactam is a β-lactam/β-lactamase inhibitor combination with activity against a variety of Gram-negative bacteria, including MDR Pseudomonas aeruginosa. This agent is approved for hospital-acquired and ventilator-associated bacterial pneumonia. However, most real-world outcome data come from small observational cohorts. Thus, we sought to evaluate the utilization of ceftolozane/tazobactam at multiple tertiary hospitals in Houston, TX, USA. Methods We conducted a multicentre retrospective study of patients receiving at least 48 h of ceftolozane/tazobactam therapy from January 2016 through to September 2019 at two hospital systems in Houston. Demographic, clinical and microbiological data were collected, including the infecting bacterial isolate, when available. The primary outcome was composite clinical success at hospital discharge. Secondary outcomes included in-hospital mortality and clinical disposition at 14 and 30 days post ceftolozane/tazobactam initiation. Multivariable logistic regression analysis was used to identify predictors of the primary outcome and mortality. Recovered isolates were tested for susceptibility to ceftolozane/tazobactam and underwent WGS. Results A total of 263 patients were enrolled, and composite clinical success was achieved in 185 patients (70.3%). Severity of illness was the most consistent predictor of clinical success. Combination therapy with ceftolozane/tazobactam and another Gram-negative-active agent was associated with reduced odds of clinical success (OR 0.32, 95% CI 0.16–0.63). Resistance to ceftolozane/tazobactam was noted in 15.4% of isolates available for WGS; mutations in ampC and ftsI were common but did not cluster with a particular ST. Conclusions Clinical success rate among this patient cohort treated with ceftolozane/tazobactam was similar compared with previous experiences. Ceftolozane/tazobactam remains an alternative agent for treatment of susceptible isolates of P. aeruginosa.

Funder

funding from Merck

National Institute of Allergy and Infectious Diseases

National Institutes of Health

Publisher

Oxford University Press (OUP)

Subject

Microbiology (medical),Infectious Diseases,Immunology and Allergy,Microbiology,Immunology

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