Dana J Holger1,2, Nicholas S Rebold3,4, Sara Alosaimy3,4,5, Taylor Morrisette3,4,6,7, Abdalhamid Lagnf3,4, Ana Christine Belza3, Ashlan J Kunz Coyne3,4, Amer El Ghali3,4, Michael P Veve3,8, Michael J Rybak9,10,11. 1. Wayne State University, Detroit, MI, USA. dholger@wayne.edu. 2. Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Detroit, MI, 48201, USA. dholger@wayne.edu. 3. Wayne State University, Detroit, MI, USA. 4. Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Detroit, MI, 48201, USA. 5. Seres Therapeutics, Cambridge, MA, 02139, USA. 6. Department of Clinical Pharmacy and Outcomes Sciences, College of Pharmacy, Medical University of South Carolina, Charleston, SC, USA. 7. Department of Pharmacy Services, Medical University of South Carolina Shawn Jenkins Children's Hospital, Charleston, SC, USA. 8. Department of Pharmacy, Henry Ford Hospital, Detroit, MI, USA. 9. Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Detroit, MI, 48201, USA. m.rybak@wayne.edu. 10. Department of Pharmacy Services, Detroit Receiving Hospital, Detroit Medical Center, Detroit, MI, USA. m.rybak@wayne.edu. 11. School of Medicine, Wayne State University, Detroit, MI, USA. m.rybak@wayne.edu.
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.
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.
Authors: Yu Mi Wi; Kerryl E Greenwood-Quaintance; Audrey N Schuetz; Kwan Soo Ko; Kyong Ran Peck; Jae-Hoon Song; Robin Patel Journal: Antimicrob Agents Chemother Date: 2017-12-21 Impact factor: 5.191
Authors: A I López-Calleja; E Morilla Morales; R Nuñez Medina; M Fernández Esgueva; J Sahagún Pareja; J M García-Lechuz Moya; I Ferrer Cerón; J Viñuelas Bayon; A Rezusta López Journal: Rev Esp Quimioter Date: 2018-12-14 Impact factor: 1.553