Ceftazidime/Avibactam: Who Says You Can’t Teach an Old Drug New Tricks?

Barber, Katie E.; Ortwine, Jessica; Akins, Ronda L.

doi:10.18433/j3x31r

Cited by 13 publications

(11 citation statements)

References 42 publications

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“…(8)(9) Ceftazidime exerts its activity by binding to penicillin-binding proteins (PBPs) within the bacteria's cell wall, primarily PBP-3, interfering with cell division thus leading to cell death. (10) Ceftazidime is also known to have a photosensitizer property (7), but the mechanisms were remain unclear. Until recently, there have been no investigations of ceftazidime as a photosensitizer in erythrocytes through oxidative stress mechanism.…”

Section: Introductionmentioning

confidence: 99%

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The Role of Ceftazidime as a Photosensitizer in Human Erythrocytes Through Oxidative Stress Mechanism

et al. 2018

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BACKGROUND: Ceftazidime was known to cause photosensitization reactions. However, how it plays the role remained unclear. In our study, we aim to investigate the photosensitization effect of ceftazidime in erythrocytes via oxidative stress.METHODS: Samples were divided into six different groups: negative control group, positive control group and four experimental groups with 10%, 20%, 30%, and 40% ceftazidime, respectively. The positive control and experimental groups were exposed to ultraviolet (UV)-light for 2 hours. Superoxide radical, malondialdehyde (MDA), carbonyl compounds (CC) and methemoglobin (Met-Hb) levels were then measured.RESULTS: The results showed a significant increased of superoxide radical, MDA, CC and Met-Hb levels in all experimental groups compared to both negative or positive control groups (p< 0.05).CONCLUSION: In conclusion, our study confirmed the role of ceftazidime as a photosensitizer in erythrocytes via the oxidative stress mechanisms.KEYWORDS: ceftazidime, oxidative stress, photosensitizer, photosensitization.

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Section: Introductionmentioning

confidence: 99%

“…The Indonesian Biomedical Journal, Vol 10,. No.2, August 2018, p.128-32 Print ISSN: 2085-3297, Online ISSN: 2355-9179…”

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confidence: 99%

The Role of Ceftazidime as a Photosensitizer in Human Erythrocytes Through Oxidative Stress Mechanism

et al. 2018

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“…Ceftazidime/avibactam (CAZ-AVI) is a novel, β-lactam/β-lactamase inhibitor fixed-dose combination drug containing ceftazidime (an established, extended-spectrum and avibactam (a unique, non-β-lactam, β-lactamase inhibitor) [1, 8]. CAZ-AVI has been approved by the European Commission and the US Food and Drug Administration (FDA) for the indication of cIAI (in combination with metronidazole) in adult patients [1, 9]. The introduction of CAZ-AVI is encouraging as this novel combination drug is known to have potent activity against several Gram-negative organisms, including some with multidrug resistance [9].…”

Section: Introductionmentioning

confidence: 99%

“…CAZ-AVI has been approved by the European Commission and the US Food and Drug Administration (FDA) for the indication of cIAI (in combination with metronidazole) in adult patients [1, 9]. The introduction of CAZ-AVI is encouraging as this novel combination drug is known to have potent activity against several Gram-negative organisms, including some with multidrug resistance [9]. Hence, it could be a viable answer to rising incidence of resistance to most of the currently available antibiotic treatments that has not only become a challenge for clinicians to treat the disease but also has increased hospital stays as well as soaring healthcare costs related to cIAIs [3, 7].…”

Section: Introductionmentioning

confidence: 99%

Cost-effectiveness analysis comparing ceftazidime/avibactam (CAZ-AVI) as empirical treatment comparing to ceftolozane/tazobactam and to meropenem for complicated intra-abdominal infection (cIAI)

Kongnakorn¹,

Eckmann²,

Bassetti³

et al. 2019

Antimicrob Resist Infect Control

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BackgroundThe rising incidence of resistance to currently available antibiotics among pathogens, particularly Gram-negative pathogens, in complicated intra-abdominal infections (cIAIs) has become a challenge for clinicians. Ceftazidime/avibactam (CAZ-AVI) is a fixed-dose antibiotic approved in Europe and the United States for treating (in combination with metronidazole) cIAI in adult hospitalised patients who have limited or no alternative treatment options. The approval was based on the results of RECLAIM, a Phase III, parallel-group, comparative study (RECLAIM 1 [NCT01499290] and RECLAIM 2 [NCT01500239]). The objective of our study was to assess the cost-effectiveness of CAZ-AVI plus metronidazole compared with 1) ceftolozane/tazobactam plus metronidazole and 2) meropenem, as an empiric treatment for the management of cIAI in Italy.MethodsA sequential, patient-level simulation model, with a 5-year time horizon and 3% annual discount rate (applied to both costs and health benefits), was developed using Microsoft Excel® to demonstrate the clinical course of the disease. The impact of resistant pathogens was included as an additional factor.ResultsIn the base-case analysis, the CAZ-AVI sequence (CAZ-AVI plus metronidazole followed by a colistin + tigecycline + high-dose meropenem combination after treatment failure), when compared to sequences for ceftolozane/tazobactam (ceftolozane/tazobactam plus metronidazole followed by colistin + tigecycline + high-dose meropenem after treatment failure) and meropenem (meropenem followed by colistin + tigecycline + high-dose meropenem after treatment failure), had better clinical outcomes with higher cure rates (93.04% vs. 91.52%; 92.98% vs. 90.24%, respectively), shorter hospital stays (∆ = − 0.38 and ∆ = − 1.24 days per patient, respectively), and higher quality-adjusted life years (QALYs) gained per patient (4.021 vs. 3.982; 4.019 vs. 3.960, respectively). The incremental cost effectiveness ratio in the CAZ-AVI sequence was €4099 and €15,574 per QALY gained versus each comparator sequence, respectively, well below the willingness-to-pay threshold of €30,000 per QALY accepted in Italy.ConclusionsThe model results demonstrated that CAZ-AVI plus metronidazole could be a cost-effective alternative when compared with other antibiotic treatment options, as it is expected to provide better clinical benefits in hospitalised patients with cIAI in Italy.

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“…In a review on the topic, the value that the addition of avibactam brings to ceftazidime was demonstrated in a variety of difficult to treat Gram negative pathogens Pseudomonas aeruginosa, Carbapenemase producing bacteria etc. [10]. The approved indications for ceftazidime-avibactam combination (AVYCAZ ® ) are for the use in infections caused by Gram negative bacteria such as complicated Intra-abdominal Infections (cIAI) and complicated urinary tract infections (cUTI), including pyelonephritis [11].…”

Section: Introductionmentioning

confidence: 99%

Review of Clinical Pharmacokinetics of Avibactam, A Newly Approved non-β lactam β-lactamase Inhibitor Drug, In Combination Use With Ceftazidime

2018

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Avibactam, a potent non-β lactam β-lactamase inhibitor, was recently approved in the USA for combination use with ceftazidime, a cephalosporin antibiotic drug. The addition of avibactam potentiates the antimicrobial drug ceftazidime, which otherwise would have been susceptible to β-lactamases produced by variety of Gram negative pathogens. The focus of this review was to provide clinical pharmacokinetic data of avibactam to cover absorption, distribution, metabolism, and excretion aspects including any potential for avibactam to show drug-drug interactions in the clinic. Based on the review of the data, the pharmacokinetics of avibactam was generally stationary in the studied dosing regimen. The elimination half-life (approximately 1.4- 3.2 h) and volume of distribution at steady state (15.4-26.3 L) were found similar across the studies and therefore, provided the complementary pharmacokinetic attributes for combination use with ceftazidime. Renal excretion was the major pathway for the clearance of avibactam. In summary, any degree of renal dysfunction is expected to alter the pharmacokinetics of avibactam – this consideration should be factored in dosage adjustments while dosing in patients with renal impairment. Concomitant drugs that may influence renal mechanism of elimination of avibactam should be avoided and/or monitored for any impact on the pharmacokinetics of avibactam.

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Ceftazidime/Avibactam: Who Says You Can’t Teach an Old Drug New Tricks?

Cited by 13 publications

References 42 publications

The Role of Ceftazidime as a Photosensitizer in Human Erythrocytes Through Oxidative Stress Mechanism

The Role of Ceftazidime as a Photosensitizer in Human Erythrocytes Through Oxidative Stress Mechanism

Cost-effectiveness analysis comparing ceftazidime/avibactam (CAZ-AVI) as empirical treatment comparing to ceftolozane/tazobactam and to meropenem for complicated intra-abdominal infection (cIAI)

Review of Clinical Pharmacokinetics of Avibactam, A Newly Approved non-β lactam β-lactamase Inhibitor Drug, In Combination Use With Ceftazidime

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