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Ceftolozane-tazobactam: A new-generation cephalosporin.
Am J Health Syst Pharm. 2015 Dec 15; 72(24):2135-46.AJ

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.

Authors+Show Affiliations

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.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.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.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.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.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Review

Language

eng

PubMed ID

26637512

Citation

Cluck, David, et al. "Ceftolozane-tazobactam: a New-generation Cephalosporin." American Journal of Health-system Pharmacy : AJHP : Official Journal of the American Society of Health-System Pharmacists, vol. 72, no. 24, 2015, pp. 2135-46.
Cluck D, Lewis P, Stayer B, et al. Ceftolozane-tazobactam: A new-generation cephalosporin. Am J Health Syst Pharm. 2015;72(24):2135-46.
Cluck, D., Lewis, P., Stayer, B., Spivey, J., & Moorman, J. (2015). Ceftolozane-tazobactam: A new-generation cephalosporin. American Journal of Health-system Pharmacy : AJHP : Official Journal of the American Society of Health-System Pharmacists, 72(24), 2135-46. https://doi.org/10.2146/ajhp150049
Cluck D, et al. Ceftolozane-tazobactam: a New-generation Cephalosporin. Am J Health Syst Pharm. 2015 Dec 15;72(24):2135-46. PubMed PMID: 26637512.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ceftolozane-tazobactam: A new-generation cephalosporin. AU - Cluck,David, AU - Lewis,Paul, AU - Stayer,Brooke, AU - Spivey,Justin, AU - Moorman,Jonathan, PY - 2015/12/6/entrez PY - 2015/12/8/pubmed PY - 2016/9/22/medline SP - 2135 EP - 46 JF - American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists JO - Am J Health Syst Pharm VL - 72 IS - 24 N2 - 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. SN - 1535-2900 UR - https://www.unboundmedicine.com/medline/citation/26637512/Ceftolozane_tazobactam:_A_new_generation_cephalosporin_ L2 - https://academic.oup.com/ajhp/article-lookup/doi/10.2146/ajhp150049 DB - PRIME DP - Unbound Medicine ER -