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Review of Ceftazidime-Avibactam for the Treatment of Infections Caused by Pseudomonas aeruginosa1

 

Abstract:
Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen that causes a range of serious infections that are often challenging to treat, as this pathogen can express multiple resistance mechanisms, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) phenotypes. Ceftazidime–avibactam is a combination antimicrobial agent comprising ceftazidime, a third-generation semisynthetic cephalosporin, and avibactam, a novel non-β-lactam β-lactamase inhibitor. This review explores the potential role of ceftazidime–avibactam for the treatment of P. aeruginosa infections.1 

Ceftazidime–avibactam has good in vitro activity against P. aeruginosa relative to comparator β-lactam agents and fluoroquinolones, comparable to amikacin and ceftolozane–tazobactam. In Phase 3 clinical trials, ceftazidime–avibactam has generally demonstrated similar clinical and microbiological outcomes to comparators in patients with complicated intra-abdominal infections, complicated urinary tract infections or hospital-acquired/ventilator-associated pneumonia caused by P. aeruginosa. Although real-world data are limited, favourable outcomes with ceftazidime–avibactam treatment have been reported in some patients with MDR and XDR P. aeruginosa infections. Thus, ceftazidime–avibactam may have a potentially important role in the management of serious and complicated P. aeruginosa infections, including those caused by MDR and XDR strains.1

Review of Ceftazidime-Avibactam for the Treatment

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Clinical and Microbiological Outcomes of Ceftazidime-Avibactam Treatment in Adults with Gram-Negative Bacteremia: A Subset Analysis from the Phase 3 Clinical Trial Program2

Introduction: This exploratory analysis assessed efficacy and safety outcomes in patients with Gram-negative bacteremia treated with ceftazidime-avibactam or comparator across five phase 3, randomized, controlled, multi-center trials in adults with complicated intra-abdominal infection (cIAI), complicated urinary tractinfection (cUTI)/pyelonephritis, hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP).2 

Results: The overall safety population included 4.050 patients (ceftazidime-avibactam,n= 2024;comparator,n=2026). The GNeME population (bacteremia subset) comprised 101 patients (ceftazidime-avibactam,n= 54;comparator,n= 47). Clinical cure rates (all indications combined) were 47/54 (87.0%) for ceftazidime-avibactam and 39/47 (83.0%) for comparators;favorable microbiological response rates were 43/54 (79.6%) and 32/47 (68.1%), respectively. Clinical and microbiological responses in the bacteremia subset were generally similar to those in the overall set. The pattern of adverse events in patients with bacteremia was similar between treatment groups and was consistent with the known safety profile of ceftazidime-avibactam.2 

Conclusion: This analysis provides supportive evidence of the efficacy and safety of ceftazidime-avibactam in patients with Gram-negative bacteremia associated with cIAI, cUTI/pyelonephritis, or HAP/VAP.

Clinical and Microbiological Outcomes of Ceftazidime-Avibactam

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Ceftazidime-Avibactam for the Treatment of Serious Gram-Negative Infections with Limited Treatment Options: A Systematic Literature Review3

Introduction: A systematic literature review was undertaken to evaluate real-world use of ceftazidime-avibactam for infections due to aerobic Gram-negative organisms in adults with limited treatment options.3

Results: Seventy-three relevant publications (62 peer-reviewed articles; 10 abstracts) comprising 1.926 patients treated with ceftazidime-avibactam (either alone or combined with other antimicrobials) and 1.114 comparator/controlpatients were identified. All patients were hospitalised for serious illness and most had multiple comorbidities.  The  most  common infections were pneumonia, bacteraemia, and skin/soft tissue, urinary tract, or abdominal infections; smaller numbers of patients with meningitis, febrile neutropenia, osteomyelitis,and cystic fibrosis were also included. Carbapenem-resistant or carbapenemase-producing Enterobacterales (CRE;n= 1718)  and  carbapenem-resistant, multidrug-resistant (MDR),and extensively drug-resistant Pseudomonas aeruginosa (n= 150) were the most common pathogens. Most publications reported positive outcomes for ceftazidime-avibactam treatment (clinical success rates ranged from 45 to 100% and reported 30-day mortality from 0 to 63%), which were statistically superior versus comparators in some studies. Ceftazidime-avibactam resistance emergence occurred infrequently and mostly in Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae strains.3

Conclusion: This review provides qualitative evidence of successful use of ceftazidime-avibactam for the  treatment of hospitalised patients with CRE and MDR P. aeruginosa infections with limited treatment options.3

 

Ceftazidime-Avibactam for the Treatment of Serious

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Ceftazidime-Avibactam for the Treatment of Serious Gram-Negative Infections with Limited Treatment Options: A Systematic Literature Review4

Introduction: A systematic literature review was undertaken to evaluate real-world use of ceftazidime-avibactam for infections due to aerobic Gram-negative organisms in adults with limited treatment options.4

Results: Seventy-three relevant publications (62 peer-reviewed articles; 10 abstracts) comprising 1.926 patients treated with ceftazidime-avibactam (either alone or combined with other antimicrobials) and 1.114 comparator/control patients were identified. All patients were hospitalised for serious illness and most had multiple comorbidities. The most common infections were pneumonia, bacteraemia, and skin/soft tissue, urinary tract, or abdominal infections; smaller numbers of patients with meningitis, febrile neutropenia, osteomyelitis, and cystic fibrosis were also included. Carbapenem-resistant or carbapenemase-producing Enterobacterales (CRE; n = 1718) and carbapenem-resistant, multidrug-resistant (MDR), and extensively drug-resistant Pseudomonas aeruginosa (n=150) were the most common pathogens. Most publications reported positive outcomes for ceftazidime-avibactam treatment (clinical success rates ranged from 45 to 100% and reported 30-day mortality from 0 to 63%), which were statistically superior versus comparators in some studies. ceftazidime-avibactam resistance emergence occurred infrequently and mostly in Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae strains.4

Conclusion: This review provides qualitative evidence of successful use of ceftazidime-avibactam for the treatment of hospitalised patients with CRE and MDR P. aeruginosa infections with limited treatment options.4
 

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Referanser:

1. Daikos GL, Cunha CA, Rossolini GM et al. Review of Ceftazidime-Avibactam for the treatment of infections Caused by Pseudomons Aeruginosa. Antibiotics 2021:10;1126:1-24, 

2. Mazuski JE, Wagenlehner F, Torres A et al. Clinical and Microbiological Outcomes of Ceftazidime-Avibactam Treatment in Adults with Gram-Negative Bacteremia: A Subset Analysis from the Phase 3 Clinical Trial Program. Infect Dis Ther July 2021, 

3. Soriano A, Carmeli Y, Omrani AS et al. Ceftazidime-Avibactam for the Treatment of Serious Gram-Negative Infections with Limited Treatment Options: A Systematic Literature Review. Infect Dis Ther July 2021.

4. Soriano A, Carmeli Y, Omrani AS et al. Ceftazidime-Avibactam for the Treatment of Serious Gram-Negative Infections with Limited Treatment Options: A Systematic Literature Review. Infect Dis Ther 2021: 10;1989-2034.

PP-ZVA-NOR-0122