Ceftazidime/Avibactam Pfizer

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Indications

Broad-Spectrum Coverage & Mechanism of Action

Ceftazidime/Avibactam Pfizer is indicated for the treatment of adult and paediatric patients aged 3 months and older for the treatment of the following infections:1*
Complicated urinary tract infection (cUTI), including pyelonephritis1Complicated intra-abdominal infection (clAl)1
Hospital-acquired pneumonia, including ventilator-associated pneumonia (HAP/VAP)1Infection due to aerobic Gram-negative organisms in patients with limited treatment options
Ceftazidime/Avibactam Pfizer is also indicated for the treatment of adult patients with bacteraemia that occurs in association  with, or is suspected to be associated with, cUTI, cIAI or HAP/VAP1
*Consideration should be given to the official guidance on the appropriate use of antibacterial agents.1
Data support the use of Ceftazidime/Avibactam Pfizer in adult patients with limited treatment options for the treatment of bacteraemia (both primary and secondary), cSSTI, BJI, meningitis due to KPC and OXA-48 resistance mechanisms, and MDR Pseudomonas.2–8

BJI, bone and joint infection; cIAI, complicated intra-abdominal infection; cUTI, complicated urinary tract infection; cSSTI, complicated skin and soft-tissue infection; HAP, hospital-acquired pneumonia; IDSA, Infectious Diseases Society of America; KPC, Klebsiella pneumoniae carbapenemase; MDR, multidrug-resistant; OXA, oxacillinase; VAP, ventilator-associated pneumonia.
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References:
1. Ceftazidime/Avibactam Pfizer [SmPC], Pfizer; Feb 2021. 2. Tumbarello M, Viale P, Viscoli C, et al. Predictors of mortality in bloodstream infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae: importance of combination therapy. Clin Infect Dis. 2012;55:943–950. 3. Caston JJ, Lacort-Peralta I, Martín-Dávila P, et al. Clinical efficacy of ceftazidime/avibactam versus other active agents for the treatment of bacteremia due to carbapenemase-producing Enterobacteriaceae in hematologic patients. Int J Infect Dis. 2017;59:118–123. 4. van Duin D, Lok JJ, Earley M, et al. Colistin Versus Ceftazidime-Avibactam in the Treatment of Infections Due to Carbapenem-Resistant Enterobacteriaceae. Clin Infect Dis. 2018;66:163–171. 5. Sousa A, Pérez-Rodríguez MT, Soto A, et al. Effectiveness of ceftazidime/avibactam as salvage therapy for treatment of infections due to OXA-48 carbapenemase-producing Enterobacteriaceae. J Antimicrob Chemother. 2018;73:3170–3175. 6. Temkin E, Torre-Cisneros J, Beovic B, et al. Ceftazidime-Avibactam as Salvage Therapy for Infections Caused by Carbapenem-Resistant Organisms. Antimicrob Agents Chemother. 2017;61:e01964-16. 7. Shields RK, Nguyen MH, Chen L, et al. Ceftazidime-Avibactam Is Superior to Other Treatment Regimens against Carbapenem-Resistant Klebsiella pneumoniae Bacteremia. Antimicrob Agents Chemother. 2017;61:e00883-17. 8. Tumbarello M, Trecarichi EM, Corona A, et al. Efficacy of Ceftazidime-Avibactam Salvage Therapy in Patients With Infections Caused by Klebsiella pneumoniae Carbapenemase-producing K. pneumoniae. Clin Infect Dis. 2019;68:355-364.
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Ceftazidime/Avibactam Pfizer is a combination of ceftazidime, an antipseudomonal cephalosporin, and avibactam, a novel β-lactamase inhibitor1–4
Ceftazidime/Avibactam Pfizer has proven bactericidal activity against a broad-spectrum of resistant Gram-negative pathogens1–3
The combination of ceftazidime and avibactam provides broad-spectrum Gram-negative coverage, including in vitro activity against:1,2,5–8
Spectrum of activity against Gram-negative pathogens:2,7–12
*Avibactam does not inhibit class B enzymes (metallo-β-lactamases) and is not able to inhibit many of the class D enzymes.2CRE, carbapenem-resistant Enterobacterales; CTX-M, cefotaximase-Munich; ESBL, extended-spectrum β-lactamase; IDSA, Infectious Diseases Society of America; KPC, Klebsiella pneumoniae carbapenemase; MBL, metallo-β-lactamase; MDR, multidrug-resistant; OXA, oxacillinase; SHV, sulphydryl variable; TEM, Temoniera.

References:
1. Liscio JL, Mahoney MV, Hirsch EB. Ceftolozane/tazobactam and ceftazidime/avibactam: two novel β-lactam/β-lactamase inhibitor combination agents for the treatment of resistant Gram-negative bacterial infections. Int J Antimicrob Agents. 2015;46:266–271. 2. Ceftazidime/Avibactam Pfizer [SmPC], Pfizer; 3. Nicolau DP, Siew L, Armstrong J, et al. Phase 1 study assessing the steady-state concentration of ceftazidime and avibactam in plasma and epithelial lining fluid following two dosing regimens. J Antimicrob Chemother. 2015;70:2862–2869. 4. Stone GG, Bradford PA, Tawadrous M, et al. In Vitro Activity of Ceftazidime-Avibactam against Isolates from Respiratory and Blood Specimens from Patients with Nosocomial Pneumonia, Including Ventilator-Associated Pneumonia, in a Phase 3 Clinical Trial. Antimicrob Agents Chemother. 2020;64:e02356-19. 5. Mazuski JE, Tessier JM, May AK, et al. The Surgical Infection Society Revised Guidelines on the Management of Intra-Abdominal Infection. Surg Infect. 2017;18:1–76. 6 Pogue JM, Bonomo RA, Kaye KS. Ceftazidime/Avibactam, Meropenem/Vaborbactam, or Both? Clinical and Formulary Considerations. Clin Infect Dis. 2019;68:519–524. 7. Zhanel GG, Lawson CD, Adam H, et al. Ceftazidime-avibactam: a novel cephalosporin/β-lactamase inhibitor combination. Drugs. 2013;73:159–177 8. Lagacé-Wiens P, Walkty A, Karlowsky JA. Ceftazidime-avibactam: an evidence-based review of its pharmacology and potential use in the treatment of Gram-negative bacterial infections. Core Evid. 2014;9:13–25. 9. Bush K. A resurgence of β-lactamase inhibitor combinations effective against multidrug-resistant Gram-negative pathogens. Int J Antimicrob Agents 2015;46:483–93; 10. Wright H, Bonomo RA, Paterson DL. New agents for the treatment of infections with Gram-negative bacteria: restoring the miracle or false dawn? Clin Microbiol Infect. 2017;23:704–12; 11. Sader HS, Castanheira M, Farrell DJ,  Flamm RK, Jones RN. Ceftazidime-avibactam activity when tested against ceftazidime-nonsusceptible Citrobacter spp., Enterobacter spp., Serratia marcescens, and Pseudomonas aeruginosa from Unites States medical centers (2011-2014). Diagn Microbiol Infect Dis. 2015;83:389–94; 12. Walkty A, DeCorby M, Lagacé-Wiens PRS, Karlowsky JA, Hoban DJ, Zhanel GG. In vitro activity of ceftazidime combined with NXL104 versus Pseudomonas aeruginosa isolates obtained from patients in Canadian hospitals (CANWARD 2009 study). Antimicrob Agents Chemother. 2011;55:2992–4.
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