Dataset Information

Evaluation of the stability of ceftazidime/avibactam in elastomeric infusion devices used for outpatient parenteral antimicrobial therapy utilizing a national stability protocol framework.

ABSTRACT:

Objectives

To evaluate the stability of ceftazidime/avibactam in elastomeric infusers, utilizing the UK's Yellow Cover Document (YCD) stability testing framework, in conditions representative of OPAT practice.

Methods

Ceftazidime/avibactam was reconstituted with sodium chloride 0.9% (w/v) in two elastomeric infusers at concentrations (dose) levels of 1500/375, 3000/750 and 6000 mg/1500 mg in 240 mL. The infusers were exposed to a fridge storage (2°C-8°C) for 14 days followed by 24 h in-use temperature (32°C).

Results

After 14 days of fridge storage and subsequent 24 h exposure to 32°C, mean ± SD of ceftazidime percent remaining was 75.5% ± 1.8%, 79.9% ± 1.1%, 82.4% ± 0.6%, for Easypump, and 81.7% ± 1.2%, 82.5% ± 0.5%, 85.4% ± 1.1% for Dosi-Fuser devices at the high, intermediate and low doses tested, respectively. For avibactam, mean ± SD percent remaining was 83.2% ± 1.8%, 87.4% ± 2.0%, 93.1% ± 0.9% for Easypump, and 85.1% ± 2.0%, 86.7% ± 0.1%, 92.5% ± 0.1% for Dosi-Fuser devices. The cumulative amount of pyridine generated in the devices ranged from 10.4 mg at low dose to 76.9 mg at high dose. Regression-based simulation showed that the degradation of both ceftazidime and avibactam was <10% for at least 12 h of the running phase, if stored in a fridge for not more than 72 h prior to in-use temperature exposure.

Conclusions

Whilst not meeting the strict UK YCD criteria for ≤5% degradation, ceftazidime/avibactam may be acceptable to administer as a continuous 12 hourly infusion in those territories where degradation of ≤10% is deemed acceptable.

SUBMITTER: Naicker S

PROVIDER: S-EPMC10995722 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature

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Publications

Evaluation of the stability of ceftazidime/avibactam in elastomeric infusion devices used for outpatient parenteral antimicrobial therapy utilizing a national stability protocol framework.

Naicker Saiyuri S Roberts Jason A JA Won Hayoung H Wallis Steven C SC Unwin Sean S Jamieson Conor C Hills Tim T Gilchrist Mark M Santillo Mark M Seaton R Andrew RA Drummond Felicity F Sime Fekade B FB

JAC-antimicrobial resistance 20240405 2

<h4>Objectives</h4>To evaluate the stability of ceftazidime/avibactam in elastomeric infusers, utilizing the UK's Yellow Cover Document (YCD) stability testing framework, in conditions representative of OPAT practice.<h4>Methods</h4>Ceftazidime/avibactam was reconstituted with sodium chloride 0.9% (w/v) in two elastomeric infusers at concentrations (dose) levels of 1500/375, 3000/750 and 6000 mg/1500 mg in 240 mL. The infusers were exposed to a fridge storage (2°C-8°C) for 14 days followed by 24 ...[more]

PMID: 38585225

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Project description:Gram-negative resistance has reached a crucial point, with emergence of pathogens resistant to most or all available antibiotics. Ceftazidime-avibactam is a newly approved agent combining ceftazidime and a novel β-lactamase inhibitor with activity against multidrug-resistant gram-negative bacteria. Avibactam has increased potency and expanded spectrum of inhibition of class A and C β-lactamases relative to available β-lactamase inhibitors, including extended-spectrum β-lactamases, AmpC, and Klebsiella pneumoniae carbapenemase (KPC) enzymes. Avibactam expands ceftazidime's spectrum of activity to include many ceftazidime- and carbapenem-resistant Enterobacteriaceae and Pseudomonas aeruginosa. Early clinical data indicate that ceftazidime-avibactam is effective and well tolerated in patients with complicated urinary tract infections (cUTIs) and complicated intraabdominal infections (cIAI). In a phase II trial of patients with cUTIs, ceftazidime-avibactam produced similar rates of clinical and microbiologic success compared with imipenem-cilastatin (70.5% and 71.4% microbiologic success rates, respectively). Likewise, patients receiving ceftazidime-avibactam plus metronidazole in a phase II study of patients with cIAI had similar response rates to those receiving meropenem (91.2% and 93.4% clinical success rates, respectively). Based on available in vitro, in vivo, and phase II trial data, as well as preliminary phase III trial results in ceftazidime-resistant, gram-negative cUTI and cIAI, ceftazidime-avibactam received U.S. Food and Drug Administration approval for treatment of cUTI, including pyelonephritis, and cIAI, in combination with metronidazole, in adult patients with limited or no alternative treatment options. The approved dosage, ceftazidime 2 g-avibactam 0.5 g administered as a 2-hour infusion every 8 hours, was selected based on pharmacodynamic analysis and available clinical data. This dosage is under further investigation in patients with cUTI, cIAI, and nosocomial or ventilator-associated pneumonia. The current body of evidence suggests that ceftazidime-avibactam is a promising addition to our therapeutic armamentarium with potential to answer an urgent unmet medical need. Further data in highly resistant gram-negative infections, particularly those caused by KPC-producing Enterobacteriaceae, are needed. As it is introduced into clinical use, careful stewardship and rational use are essential to preserve ceftazidime-avibactam's potential utility.

Project description:Objective: To systematically review and compare the efficacy and posttreatment resistance of ceftazidime-avibactam therapy and ceftazidime-avibactam-based combination therapy in patients with Gram-negative pathogens. Methods: PubMed, Embase, Web of Science, CNKI, and Wanfang Data databases were searched from their inception up to March 31, 2021, to obtain studies on ceftazidime-avibactam therapy versus ceftazidime-avibactam-based combination therapy in patients with carbapenem-resistant Gram-negative pathogens. The primary outcome was mortality rate, and the second outcomes were microbiologically negative, clinical success, and the development of resistance after ceftazidime-avibactam treatment. Results: Seventeen studies representing 1,435 patients (837 received ceftazidime-avibactam-based combination therapy and 598 received ceftazidime-avibactam therapy) were included in the meta-analysis. The results of the meta-analysis showed that no statistically significant difference was found on mortality rate (Petos odds ratio (OR) = 1.03, 95% confidence interval (CI) 0.79-1.34), microbiologically negative (OR = 0.99, 95% CI 0.54-1.81), and clinical success (OR =0.95, 95% CI 0.64-1.39) between ceftazidime-avibactam-based combination therapy and ceftazidime-avibactam therapy. Although there was no difference in posttreatment resistance of ceftazidime-avibactam (OR = 0.65, 95% CI 0.34-1.26) in all included studies, a trend favoring the combination therapy was found (according to the pooled three studies, OR = 0.18, 95% CI 0.04-0.78). Conclusions: The current evidence suggests that ceftazidime-avibactam-based combination therapy may not have beneficial effects on mortality, microbiologically negative, and clinical success to patients with carbapenem-resistant Gram-negative pathogens. A trend of posttreatment resistance occurred more likely in ceftazidime-avibactam therapy than the combination therapy. Due to the limited number of studies that can be included, additional high-quality studies are needed to verify the above conclusions.

Dataset Information

Evaluation of the stability of ceftazidime/avibactam in elastomeric infusion devices used for outpatient parenteral antimicrobial therapy utilizing a national stability protocol framework.

Objectives

Methods

Results

Conclusions

Publications

Evaluation of the stability of ceftazidime/avibactam in elastomeric infusion devices used for outpatient parenteral antimicrobial therapy utilizing a national stability protocol framework.

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