Impact of Ceftolozane–Tazobactam vs. Best Alternative Therapy on Clinical Outcomes in Patients with Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Lower Respiratory Tract Infections

Dana J. Holger; Nicholas S. Rebold; Sara Alosaimy; Taylor Morrisette; Abdalhamid Lagnf; Ana Christine Belza; Ashlan J.Kunz Coyne; Amer El Ghali; Michael P. Veve; Michael J. Rybak

doi:10.1007/s40121-022-00687-9

Impact of Ceftolozane–Tazobactam vs. Best Alternative Therapy on Clinical Outcomes in Patients with Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Lower Respiratory Tract Infections

Dana J. Holger, Nicholas S. Rebold, Sara Alosaimy, Taylor Morrisette, Abdalhamid Lagnf, Ana Christine Belza, Ashlan J.Kunz Coyne, Amer El Ghali, Michael P. Veve, Michael J. Rybak

Pharmacy Practice and Science

Producción científica: Article › revisión exhaustiva

8 Citas (Scopus)

Resumen

Introduction: Infections caused by multidrug-resistant (MDR), extensively drug-resistant (XDR), and difficult-to-treat (DTR) Pseudomonas aeruginosa are increasingly challenging to combat. Ceftolozane–tazobactam (C/T) is a novel β-lactam–β-lactamase inhibitor combination now commonly used to treat MDR and XDR P. aeruginosa. Lower respiratory tract infections (LRTIs) remain the most common source of infection caused by MDR/XDR P. aeruginosa. Comparative effectiveness studies to date have been limited by the type of comparator agents (i.e., aminoglycosides and polymyxins) and the inclusion of multiple infection sources (i.e., urinary tract, abdominal, skin and soft tissue, etc.). Methods: We performed a multicenter, retrospective analysis of adults with LRTI caused by MDR or XDR P. aeruginosa admitted from January 2014 to December 2019. We aimed to compare clinical outcomes between patients who received C/T (n = 118) versus best alternative therapy (n = 88). The primary outcome was clinical failure, defined as 30-day mortality and/or an adverse drug reaction on antibiotic therapy. Results: Two hundred and six patients met inclusion criteria. The C/T group had a significantly higher proportion of XDR P. aeruginosa and ventilator-associated bacterial pneumonia (VABP). After multivariable logistic regression, C/T treatment was independently associated with a 73.3% reduction in clinical failure compared to those who received best alternative therapy (P < 0.001). The number needed to harm with best alternative therapy was 3. Conclusion: Our results suggest that C/T is a safe and effective therapeutic regimen for patients with MDR and XDR P. aeruginosa LRTI.

Idioma original	English
Páginas (desde-hasta)	1965-1980
Número de páginas	16
Publicación	Infectious Diseases and Therapy
Volumen	11
N.º	5
DOI	https://doi.org/10.1007/s40121-022-00687-9
Estado	Published - oct 2022

Nota bibliográfica

Publisher Copyright:
© 2022, The Author(s).

Financiación

Dana Holger, Nicholas Rebold, Sara Alosaimy, Taylor Morrisette, Abdalhamid Lagnf, Ana Belza, Ashlan Kunz Coyne, Amer El Ghali, and Michael Veve have no conflicts of interest to disclose. Michael Rybak has received funds for research and consulting or participated in speaking bureaus for Abbvie, Contrafect, Entasis, Ferring, Melinta, Merck, Paratek Pharmaceuticals, Shionogi, Spero, Tetraphase, and T2 Bioscience and was/is partially supported by National Institute of Allergy and Infectious Diseases R01 AI121400 and R21 AI163726. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. Sara Alosaimy was affiliated with Wayne State University, Detroit, Michigan, USA and Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University at the time of the study and is currently affiliated with Seres Therapeutics. Taylor Morrisette was affiliated with Wayne State University, Detroit, Michigan, USA and Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University at the time of the study and is currently affiliated with Department of Clinical Pharmacy & Outcomes Sciences, Medical University of South Carolina College of Pharmacy, Charleston, South Carolina, United States; Department of Pharmacy Services, Medical University of South Carolina Shawn Jenkins Children’s Hospital. No funding or sponsorship was received for the study or for publication of this article. Conceptualization, Dana Holger, Nicholas Rebold, Sara Alosaimy, and Taylor Morrisette; Data curation, Abdalhamid Lagnf, Ana Belza, Formal analysis, Dana Holger; Investigation, Dana Holger, Nicholas Rebold, Sara Alosaimy, Taylor Morrisette, Ashlan Kunz Coyne, Amer El Ghali, Michael Veve, and Michael Rybak; Methodology, Dana Holger, Nicholas Rebold, Sara Alosaimy, Taylor Morrisette, Ashlan Kunz Coyne, Amer El Ghali, and Michael Veve; Project administration, Dana Holger, Abdalhamid Lagnf, Michael Veve, and Michael Rybak; Supervision, Michael Veve and Michael Rybak; Writing—original draft, Dana Holger; Writing—review and editing, Nicholas Rebold, Sara Alosaimy, Taylor Morrisette, Ashlan Kunz Coyne, Amer El Ghali, Michael Veve, and Michael Rybak. Dana Holger, Nicholas Rebold, Sara Alosaimy, Taylor Morrisette, Abdalhamid Lagnf, Ana Belza, Ashlan Kunz Coyne, Amer El Ghali, and Michael Veve have no conflicts of interest to disclose. Michael Rybak has received funds for research and consulting or participated in speaking bureaus for Abbvie, Contrafect, Entasis, Ferring, Melinta, Merck, Paratek Pharmaceuticals, Shionogi, Spero, Tetraphase, and T2 Bioscience and was/is partially supported by National Institute of Allergy and Infectious Diseases R01 AI121400 and R21 AI163726. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. Sara Alosaimy was affiliated with Wayne State University, Detroit, Michigan, USA and Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University at the time of the study and is currently affiliated with Seres Therapeutics. Taylor Morrisette was affiliated with Wayne State University, Detroit, Michigan, USA and Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University at the time of the study and is currently affiliated with Department of Clinical Pharmacy & Outcomes Sciences, Medical University of South Carolina College of Pharmacy, Charleston, South Carolina, United States; Department of Pharmacy Services, Medical University of South Carolina Shawn Jenkins Children’s Hospital. Data from a proportion of patients in this analysis have been presented, in part, in the following publications: Jorgensen et al. [30 , 31]. The Wayne State Institutional Review Board (IRB) with Detroit Medical Center research authorization approved the study design and reporting and waived the requirement for patient consent. Data are available on request to [email protected] given patient confidentiality regulations from a limited dataset under the Health Insurance Portability and Accountability Act (HIPAA).

Financiadores	Número del financiador
HIPAA
Medical University of South Carolina Shawn Jenkins Children’s Hospital
Michael Rybak
Michael Veve
Taylor Morrisette
National Institute of Allergy and Infectious Diseases	R01 AI121400, R21 AI163726
Wayne State University

ASJC Scopus subject areas

Microbiology (medical)
Infectious Diseases

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Holger, D. J., Rebold, N. S., Alosaimy, S., Morrisette, T., Lagnf, A., Belza, A. C., Coyne, A. J. K., El Ghali, A., Veve, M. P., & Rybak, M. J. (2022). Impact of Ceftolozane–Tazobactam vs. Best Alternative Therapy on Clinical Outcomes in Patients with Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Lower Respiratory Tract Infections. Infectious Diseases and Therapy, 11(5), 1965-1980. https://doi.org/10.1007/s40121-022-00687-9

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title = "Impact of Ceftolozane–Tazobactam vs. Best Alternative Therapy on Clinical Outcomes in Patients with Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Lower Respiratory Tract Infections",

abstract = "Introduction: Infections caused by multidrug-resistant (MDR), extensively drug-resistant (XDR), and difficult-to-treat (DTR) Pseudomonas aeruginosa are increasingly challenging to combat. Ceftolozane–tazobactam (C/T) is a novel β-lactam–β-lactamase inhibitor combination now commonly used to treat MDR and XDR P. aeruginosa. Lower respiratory tract infections (LRTIs) remain the most common source of infection caused by MDR/XDR P. aeruginosa. Comparative effectiveness studies to date have been limited by the type of comparator agents (i.e., aminoglycosides and polymyxins) and the inclusion of multiple infection sources (i.e., urinary tract, abdominal, skin and soft tissue, etc.). Methods: We performed a multicenter, retrospective analysis of adults with LRTI caused by MDR or XDR P. aeruginosa admitted from January 2014 to December 2019. We aimed to compare clinical outcomes between patients who received C/T (n = 118) versus best alternative therapy (n = 88). The primary outcome was clinical failure, defined as 30-day mortality and/or an adverse drug reaction on antibiotic therapy. Results: Two hundred and six patients met inclusion criteria. The C/T group had a significantly higher proportion of XDR P. aeruginosa and ventilator-associated bacterial pneumonia (VABP). After multivariable logistic regression, C/T treatment was independently associated with a 73.3\% reduction in clinical failure compared to those who received best alternative therapy (P < 0.001). The number needed to harm with best alternative therapy was 3. Conclusion: Our results suggest that C/T is a safe and effective therapeutic regimen for patients with MDR and XDR P. aeruginosa LRTI.",

keywords = "Ceftolozane–tazobactam, HABP/VABP, Multidrug resistance, Pneumonia, Pseudomonas aeruginosa",

author = "Holger, \{Dana J.\} and Rebold, \{Nicholas S.\} and Sara Alosaimy and Taylor Morrisette and Abdalhamid Lagnf and Belza, \{Ana Christine\} and Coyne, \{Ashlan J.Kunz\} and \{El Ghali\}, Amer and Veve, \{Michael P.\} and Rybak, \{Michael J.\}",

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doi = "10.1007/s40121-022-00687-9",

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Holger, DJ, Rebold, NS, Alosaimy, S, Morrisette, T, Lagnf, A, Belza, AC, Coyne, AJK, El Ghali, A, Veve, MP & Rybak, MJ 2022, 'Impact of Ceftolozane–Tazobactam vs. Best Alternative Therapy on Clinical Outcomes in Patients with Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Lower Respiratory Tract Infections', Infectious Diseases and Therapy, vol. 11, n.º 5, pp. 1965-1980. https://doi.org/10.1007/s40121-022-00687-9

Impact of Ceftolozane–Tazobactam vs. Best Alternative Therapy on Clinical Outcomes in Patients with Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Lower Respiratory Tract Infections. / Holger, Dana J.; Rebold, Nicholas S.; Alosaimy, Sara et al.
En: Infectious Diseases and Therapy, Vol. 11, N.º 5, 10.2022, p. 1965-1980.

Producción científica: Article › revisión exhaustiva

TY - JOUR

T1 - Impact of Ceftolozane–Tazobactam vs. Best Alternative Therapy on Clinical Outcomes in Patients with Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Lower Respiratory Tract Infections

AU - Holger, Dana J.

AU - Rebold, Nicholas S.

AU - Alosaimy, Sara

AU - Morrisette, Taylor

AU - Lagnf, Abdalhamid

AU - Belza, Ana Christine

AU - Coyne, Ashlan J.Kunz

AU - El Ghali, Amer

AU - Veve, Michael P.

AU - Rybak, Michael J.

PY - 2022/10

Y1 - 2022/10

N2 - Introduction: Infections caused by multidrug-resistant (MDR), extensively drug-resistant (XDR), and difficult-to-treat (DTR) Pseudomonas aeruginosa are increasingly challenging to combat. Ceftolozane–tazobactam (C/T) is a novel β-lactam–β-lactamase inhibitor combination now commonly used to treat MDR and XDR P. aeruginosa. Lower respiratory tract infections (LRTIs) remain the most common source of infection caused by MDR/XDR P. aeruginosa. Comparative effectiveness studies to date have been limited by the type of comparator agents (i.e., aminoglycosides and polymyxins) and the inclusion of multiple infection sources (i.e., urinary tract, abdominal, skin and soft tissue, etc.). Methods: We performed a multicenter, retrospective analysis of adults with LRTI caused by MDR or XDR P. aeruginosa admitted from January 2014 to December 2019. We aimed to compare clinical outcomes between patients who received C/T (n = 118) versus best alternative therapy (n = 88). The primary outcome was clinical failure, defined as 30-day mortality and/or an adverse drug reaction on antibiotic therapy. Results: Two hundred and six patients met inclusion criteria. The C/T group had a significantly higher proportion of XDR P. aeruginosa and ventilator-associated bacterial pneumonia (VABP). After multivariable logistic regression, C/T treatment was independently associated with a 73.3% reduction in clinical failure compared to those who received best alternative therapy (P < 0.001). The number needed to harm with best alternative therapy was 3. Conclusion: Our results suggest that C/T is a safe and effective therapeutic regimen for patients with MDR and XDR P. aeruginosa LRTI.

AB - Introduction: Infections caused by multidrug-resistant (MDR), extensively drug-resistant (XDR), and difficult-to-treat (DTR) Pseudomonas aeruginosa are increasingly challenging to combat. Ceftolozane–tazobactam (C/T) is a novel β-lactam–β-lactamase inhibitor combination now commonly used to treat MDR and XDR P. aeruginosa. Lower respiratory tract infections (LRTIs) remain the most common source of infection caused by MDR/XDR P. aeruginosa. Comparative effectiveness studies to date have been limited by the type of comparator agents (i.e., aminoglycosides and polymyxins) and the inclusion of multiple infection sources (i.e., urinary tract, abdominal, skin and soft tissue, etc.). Methods: We performed a multicenter, retrospective analysis of adults with LRTI caused by MDR or XDR P. aeruginosa admitted from January 2014 to December 2019. We aimed to compare clinical outcomes between patients who received C/T (n = 118) versus best alternative therapy (n = 88). The primary outcome was clinical failure, defined as 30-day mortality and/or an adverse drug reaction on antibiotic therapy. Results: Two hundred and six patients met inclusion criteria. The C/T group had a significantly higher proportion of XDR P. aeruginosa and ventilator-associated bacterial pneumonia (VABP). After multivariable logistic regression, C/T treatment was independently associated with a 73.3% reduction in clinical failure compared to those who received best alternative therapy (P < 0.001). The number needed to harm with best alternative therapy was 3. Conclusion: Our results suggest that C/T is a safe and effective therapeutic regimen for patients with MDR and XDR P. aeruginosa LRTI.

KW - Ceftolozane–tazobactam

KW - HABP/VABP

KW - Multidrug resistance

KW - Pneumonia

KW - Pseudomonas aeruginosa

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Holger DJ, Rebold NS, Alosaimy S, Morrisette T, Lagnf A, Belza AC et al. Impact of Ceftolozane–Tazobactam vs. Best Alternative Therapy on Clinical Outcomes in Patients with Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Lower Respiratory Tract Infections. Infectious Diseases and Therapy. 2022 oct;11(5):1965-1980. doi: 10.1007/s40121-022-00687-9