David Cluck1, Paul Lewis2, Brooke Stayer2, Justin Spivey2, Jonathan Moorman2. 1. David Cluck, Pharm.D., is Clinical Assistant Professor, Department of Pharmacy Practice, East Tennessee State University (ETSU) Gatton College of Pharmacy, Johnson City. Paul Lewis, Pharm.D., is Clinical Pharmacist-Infectious Diseases, Department of Pharmacy, Johnson City Medical Center, Johnson City. Brooke Stayer, Pharm.D., is Clinical Pharmacist-Infectious Diseases, Department of Pharmacy, Holston Valley Medical Center, Kingsport, TN. Justin Spivey, Pharm.D., is Clinical Pharmacist-Infectious Diseases, Department of Pharmacy, James H. Quillen Veterans Affairs (VA) Medical Center, Johnson City. Jonathan Moorman, M.D., is Professor of Medicine and Chief, Division of Infectious Diseases, ETSU Quillen College of Medicine, Johnson City. cluckd@etsu.edu. 2. David Cluck, Pharm.D., is Clinical Assistant Professor, Department of Pharmacy Practice, East Tennessee State University (ETSU) Gatton College of Pharmacy, Johnson City. Paul Lewis, Pharm.D., is Clinical Pharmacist-Infectious Diseases, Department of Pharmacy, Johnson City Medical Center, Johnson City. Brooke Stayer, Pharm.D., is Clinical Pharmacist-Infectious Diseases, Department of Pharmacy, Holston Valley Medical Center, Kingsport, TN. Justin Spivey, Pharm.D., is Clinical Pharmacist-Infectious Diseases, Department of Pharmacy, James H. Quillen Veterans Affairs (VA) Medical Center, Johnson City. Jonathan Moorman, M.D., is Professor of Medicine and Chief, Division of Infectious Diseases, ETSU Quillen College of Medicine, Johnson City.
Abstract
PURPOSE: The chemistry, pharmacokinetic and pharmacodynamic properties, efficacy, and safety of the recently introduced combination antimicrobial agent ceftolozane-tazobactam are reviewed. SUMMARY: Ceftolozane-tazobactam (Zerbaxa, Cubist Pharmaceuticals) is a cephalosporin β-lactam and β-lactamase inhibitor marketed as a fixed-dose combination agent for the treatment of complicated urinary tract and intraabdominal infections. Its dosing and chemistry provide expansive antimicrobial coverage of gram-negative organisms, including Pseudomonas aeruginosa, and stable activity against many β-lactamases, as well as coverage of most extended-spectrum β-lactamase-producing organisms and some anaerobes. Ceftolozane-tazobactam is susceptible to hydrolysis by carbapenemase enzymes but is not affected by other resistance mechanisms such as efflux pumps and porin loss. Clinical trials demonstrated that combination treatment with ceftolozane-tazobactam plus metronidazole had efficacy comparable to that of levofloxacin in patients with complicated urinary tract infections, including pyelonephritis, and comparable to that of meropenem against complicated intraabdominal infections. A Phase III trial of ceftolozane-tazobactam versus meropenem for treatment of bacterial pneumonia, including ventilator-associated pneumonia, is underway. Adverse effects reported with ceftolozane-tazobactam use are comparable to those seen with other β-lactams (e.g., hypersensitivity, nausea, diarrhea, headache). Initially, ceftolozane-tazobactam may be reserved for targeted therapy against multidrug-resistant pathogens. CONCLUSION: Ceftolozane-tazobactam is a new cephalosporin with enhanced activity against multidrug-resistant P. aeruginosa and other gram-negative pathogens.
PURPOSE: The chemistry, pharmacokinetic and pharmacodynamic properties, efficacy, and safety of the recently introduced combination antimicrobial agent ceftolozane-tazobactam are reviewed. SUMMARY:Ceftolozane-tazobactam (Zerbaxa, Cubist Pharmaceuticals) is a cephalosporin β-lactam and β-lactamase inhibitor marketed as a fixed-dose combination agent for the treatment of complicated urinary tract and intraabdominal infections. Its dosing and chemistry provide expansive antimicrobial coverage of gram-negative organisms, including Pseudomonas aeruginosa, and stable activity against many β-lactamases, as well as coverage of most extended-spectrum β-lactamase-producing organisms and some anaerobes. Ceftolozane-tazobactam is susceptible to hydrolysis by carbapenemase enzymes but is not affected by other resistance mechanisms such as efflux pumps and porin loss. Clinical trials demonstrated that combination treatment with ceftolozane-tazobactam plus metronidazole had efficacy comparable to that of levofloxacin in patients with complicated urinary tract infections, including pyelonephritis, and comparable to that of meropenem against complicated intraabdominal infections. A Phase III trial of ceftolozane-tazobactam versus meropenem for treatment of bacterial pneumonia, including ventilator-associated pneumonia, is underway. Adverse effects reported with ceftolozane-tazobactam use are comparable to those seen with other β-lactams (e.g., hypersensitivity, nausea, diarrhea, headache). Initially, ceftolozane-tazobactam may be reserved for targeted therapy against multidrug-resistant pathogens. CONCLUSION:Ceftolozane-tazobactam is a new cephalosporin with enhanced activity against multidrug-resistant P. aeruginosa and other gram-negative pathogens.
Authors: Ghady Haidar; Nathan J Philips; Ryan K Shields; Daniel Snyder; Shaoji Cheng; Brian A Potoski; Yohei Doi; Binghua Hao; Ellen G Press; Vaughn S Cooper; Cornelius J Clancy; M Hong Nguyen Journal: Clin Infect Dis Date: 2017-07-01 Impact factor: 9.079
Authors: Stephanie E Giancola; Monica V Mahoney; Tiffany E Bias; Elizabeth B Hirsch Journal: Ther Clin Risk Manag Date: 2016-05-19 Impact factor: 2.423