Indications & Broad-spectrum coverage
Efficacy
Safety
Dosing
Ceftazidime/Avibactam Pfizer (ceftazidime and avibactam) is indicated for the treatment of paediatric patients aged 3 months to <18 years for the treatment of the following infections:1*Complicated urinary tract infection (cUTI), including pyelonephritis1
Complicated intra-abdominal infection (cIAI)1
Hospital-acquired pneumonia, including ventilator-associated pneumonia (HAP/VAP)1
Infection due to aerobic Gram-negative organisms in patients with limited treatment options†
Broad-spectrum coverageCeftazidime/Avibactam Pfizer (ceftazidime and avibactam) is a combination of ceftazidime, an antipseudomonal cephalosporin, and avibactam, a novel β-lactamase inhibitor1,9–11CeftazidimeA broad-spectrum, third-generation Antipseudomonal cephalosporin with a well-characterised efficacy and tolerability Profile1,9,11The combination provides broad- spectrum coverage against Grem-negative Pathogens1,2Avibactam A novel B-lactamase inhibitor, which allows ceftazidime to maintain activity in the presence of certain resistance mechanisms1,9Ceftazidime/Avibactam Pfizer has proven bactericidal activity against a broad-spectrum of resistant Gram-negative pathogens1,9,11The combination of ceftazidime and avibactam provides broad-spectrum Gram-negative coverage, including in vitro activity against:1,12-14,16Ceftazidime/Avibactam Pfizer has shown similar in vitro activity against Gram-negative isolates of the same species from both paediatric patients (aged 3 months and older) and adult patients15
*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; CRE, carbapenem-resistant Enterobacterales; cSSTI, complicated skin and soft-tissue infection; cUTI, complicated urinary tract infection; ESBL, extended-spectrum β-lactamase; HAP, hospital-acquired pneumonia; IDSA, Infectious Diseases Society of America; KPC, Klebsiella pneumoniae carbapenemase; MDR, multidrug-resistant; OXA, oxacillinase; VAP, ventilator-associated pneumonia.References:
1. Ceftazidime/Avibactam Pfizer [SmPC], Pfizer; 2. T 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. 9. 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. 10. 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. 11. 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. 12. 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. 13. Pogue JM, Bonomo RA, Kaye KS. Ceftazidime/Avibactam, Meropenem/Vaborbactam, or Both? Clinical and Formulary Considerations. Clin Infect Dis. 2019;68:519–524. 14. Zhanel GG, Lawson CD, Adam H, et al. Ceftazidime-avibactam: a novel cephalosporin/β-lactamase inhibitor combination. Drugs. 2013;73:159–177. 15. Sader HS, Huband MD, Duncan LR, Flamm RK. Ceftazidime–Avibactam Antimicrobial Activity and Spectrum When Tested Against Gram-negative Organisms From Pediatric Patients. Pediatr Infect Dis J. 2018;37:549–54.
Ceftazidime/Avibactam Pfizer (ceftazidime and avibactam) has been evaluated in paediatric patients aged 3 months to <18 years in two Phase II, single-blind, randomised, comparative clinical studies1,2*Ceftazidime/Avibactam Pfizer achieved favourable clinical response rates when combined with metronidazole in paediatric patients aged 3 months and older with cIAI, with similar effectiveness to meropenem1Baseline pathogens1Predominantly E. coli (80%) and P. aeruginosa (33%)
Ceftazidime/Avibactam Pfizer achieved favourable clinical response rates in paediatric patients aged 3 months and older with cUTI, with similar effectiveness to cefepime2More paediatric patients treated with Ceftazidime/Avibactam Pfizer (72.2%) than with cefepime (60.9%) had both a favourable clinical and microbiological response2¶Baseline pathogens2Predominantly E. coli (92.2%)
*Use of Ceftazidime/Avibactam Pfizer in paediatric patients aged 3 months and older is also supported by evidence from adequate and well-controlled studies in adults, and additional pharmacokinetic and safety data from paediatric trials. Ceftazidime/Avibactam Pfizer has proven clinical efficacy across four Phase III, international, randomised, non-inferiority trials in 1423 adult patients with HAP/VAP, cIAI or cUTI.1,2,4–7
†The study was not powered for inferential statistical comparisons between treatment groups, so descriptive statistics were used to summarise all variables. The primary objective was to evaluate safety and tolerability; evaluation of clinical and microbiologic outcomes to provide a descriptive estimate of efficacy was a secondary objective. A favourable clinical outcome was defined as clinical cure at the TOC visit.1
‡All randomised patients.1
§All randomised patients with a baseline pathogen known to cause cIAI.1
ǁThe study was not powered for inferential statistical comparisons between treatment groups, so descriptive statistics were used to summarise safety and efficacy data. The primary objective was to evaluate safety and tolerability; evaluation of efficacy was a secondary objective. Analysed in the micro-ITT population (all randomised patients with a study-qualifying baseline pathogen).2
¶A favourable clinical outcome is defined as clinical cure. A favourable per-patient microbiologic response is defined as eradication of the pathogen(s). If a patient has more than 1 pathogen, the outcome has to be favourable for each pathogen for it to be counted as a favourable response.2cIAI, complicated intra-abdominal infection; cUTI, complicated urinary tract infection; HAP, hospital acquired pneumonia; IDSA, Infectious Diseases Society of America; ITT, intent-to-treat; MDR, multidrug-resistant; TOC, test of cure; VAP, ventilator-associated pneumonia.
References:
1. Bradley JS, Broadhurst H, Cheng K, et al. Safety and Efficacy of Ceftazidime-Avibactam Plus Metronidazole in the Treatment of Children ≥3 Months to <18 Years With Complicated Intra-Abdominal Infection: Results From a Phase 2, Randomized, Controlled Trial. Pediatr Infect Dis J. 2019;38:816–824. 2. . Bradley JS, Roilides E, Broadhurst H, et al. Safety and Efficacy of Ceftazidime-Avibactam in the Treatment of Children ≥3 Months to <18 Years With Complicated Urinary Tract Infection: Results from a Phase 2 Randomized, Controlled Trial. Pediatr Infect Dis J. 2019;38:920–928. 3. Bradley JS, Armstrong J, Arrieta A, et al. Phase I Study Assessing the Pharmacokinetic Profile, Safety, and Tolerability of a Single Dose of Ceftazidime-Avibactam in Hospitalized Pediatric Patients. Antimicrob Agents Chemother. 2016;60:6252–6259. 4. Torres A, Zhong N, Pach J, et al. Ceftazidime-avibactam versus meropenem in nosocomial pneumonia, including ventilator-associated pneumonia (REPROVE): a randomised, double-blind, phase 3 non-inferiority trial. Lancet Infect Dis. 2018;18:285–295. 5. Carmeli Y, Armstrong J, Laud PJ, et al. Ceftazidime-avibactam or best available therapy in patients with ceftazidime-resistant Enterobacteriaceae and Pseudomonas aeruginosa complicated urinary tract infections or complicated intra-abdominal infections (REPRISE): a randomised, pathogen-directed, phase 3 study. Lancet Infect Dis. 2016;16:661–673. 6. Mazuski JE, Gasink LB, Armstrong J, et al. Efficacy and Safety of Ceftazidime-Avibactam Plus Metronidazole Versus Meropenem in the Treatment of Complicated Intra-abdominal Infection: Results From a Randomized, Controlled, Double-Blind, Phase 3 Program. Clin Infect Dis. 2016;62:1380–1389. 7. Wagenlehner FM, Sobel JD, Newell P, et al. Ceftazidime-avibactam Versus Doripenem for the Treatment of Complicated Urinary Tract Infections, Including Acute Pyelonephritis: RECAPTURE, a Phase 3 Randomized Trial Program. Clin Infect Dis. 2016;63:754–762.
Ceftazidime/Avibactam Pfizer (ceftazidime and avibactam) has a similar safety and tolerability profile in paediatric patients aged 3 months and older with cIAI and cUTI to that observed in adults1-3The safety assessment in paediatric patients is based on data from two trials in which 61 patients with cIAI and 67 patients with cUTI aged 3 months to <18 years received Ceftazidime/Avibactam Pfizer 1–3
cIAI, complicated intra-abdominal infection; cUTI, complicated urinary tract infection; IDSA, Infectious Diseases Society of America.
References:
1. Ceftazidime/Avibactam Pfizer [SmPC], Pfizer; 2. Bradley JS, Broadhurst H, Cheng K, et al. Safety and Efficacy of Ceftazidime-Avibactam Plus Metronidazole in the Treatment of Children ≥3 Months to <18 Years With Complicated Intra-Abdominal Infection: Results From a Phase 2, Randomized, Controlled Trial. Pediatr Infect Dis J. 2019;38:816–824. 3. Bradley JS, Roilides E, Broadhurst H, et al. Safety and Efficacy of Ceftazidime-Avibactam in the Treatment of Children ≥3 Months to <18 Years With Complicated Urinary Tract Infection: Results from a Phase 2 Randomized, Controlled Trial. Pediatr Infect Dis J. 2019;38:920–928.
Ceftazidime/Avibactam Pfizer provides dosing options to treat paediatric patients aged 3 months to <18 years with consistent dosing across indications1Dosage in paediatric patients aged 3 months and older with CrCl* >50 mL/min/1.73 m2 (refer to SmPC for full dosing information)†‡§Adapted from Ceftazidime/Avibactam Pfizer [SmPC], Feb 2021.
Recommended dose adjustments in paediatric patients aged ≥2 years with CrCl* ≤50 mL/min/1.73 m2:1Adapted from Ceftazidime/Avibactam Pfizer [SmPC], Feb 2021.
Recommended dose adjustments in paediatric patients aged <2 years with CrCl* ≤50 mL/min/1.73 m2:1
*CrCl estimated using the Schwartz bedside formula for paediatric patients aged 3 months and older.1
†The dose of Ceftazidime/Avibactam Pfizer in patients with estimated CrCl ≤50 mL/min should be adjusted according to recommended doses.1
‡For the treatment of cIAI and infections due to aerobic Gram-negative organisms in patients with limited treatment options (LTO), Ceftazidime/Avibactam Pfizer should be used in combination with metronidazole when anaerobic pathogens are known or suspected to be contributing to the infectious process.1
§Across all indications, Ceftazidime/Avibactam Pfizer should be used in combination with an antibacterial agent active against Gram-positive pathogens when these are known or suspected to be contributing to the infectious process.1
¶The total treatment duration shown may include IV Ceftazidime/Avibactam Pfizer followed by appropriate oral therapy.1
‖There is very limited experience with the use of Ceftazidime/Avibactam Pfizer for more than 14 days.1
**There is limited experience with the use of Ceftazidime/Avibactam Pfizer in paediatric patients aged 3 months to <6 months.1
††Dose recommendations are based on PK modelling.1
‡‡Ceftazidime and avibactam are removed by haemodialysis. Dosing of Ceftazidime/Avibactam Pfizer on haemodialysis days should occur after completion of haemodialysis.1cIAI, complicated intra-abdominal infection; CrCl, creatinine clearance; cUTI, complicated urinary tract infection; ESRD, end-stage renal disease; HAP, hospital-acquired pneumonia; IDSA, Infectious Diseases Society of America; IV, intravenous; LTO, limited treatment options; PK, pharmacokinetic; VAP, ventilator-associated pneumonia.
Reference:
1. Ceftazidime/Avibactam Pfizer [SmPC], Pfizer