Dataset Information

Estimating the Economic and Clinical Value of Introducing Ceftazidime/Avibactam into Antimicrobial Practice in Japan: A Dynamic Modelling Study.

ABSTRACT:

Background

Antimicrobial resistance (AMR) is one of the most serious public health challenges worldwide, including in Japan. Globally, research and development of new antimicrobials has stalled due to unfavorable market conditions, which undervalue antimicrobials. Furthermore, Japan faces the additional challenge of delayed commercialization for a number of recently approved treatments.

Objective

This study aims to examine the impact on AMR of introducing a new anti-infective treatment, ceftazidime/avibactam, into current treatment strategies. It reports the resulting clinical and economic outcomes from the perspective of healthcare payers in Japan.

Methods

A previously published and validated dynamic disease transmission model was adapted to the Japanese setting. The model estimated health economic outcomes for treating three Gram-negative hospital-acquired infections, under different treatment strategies, from a healthcare payers' perspective. Outcomes were assessed over a 10-year time horizon with a willingness-to-pay threshold of ¥5,000,000 (US$45,556) per quality-adjusted life-year (QALY) gained and an annual discount rate of 2% applied to costs and benefits.

Results

Introducing ceftazidime/avibactam in the framework of a diversification strategy with piperacillin/tazobactam is associated with reducing 798,640 bed days, equating to ¥21.0 billion (US$190.9 million) savings in hospitalization costs, and a gain of 363,034 life-years, or 308,641 QALYs. This translates into a monetary benefit of ¥1.56 trillion (US$14.3 billion) to Japanese healthcare payers.

Discussion

Introducing a new antimicrobial agent into clinical practice is associated with considerable clinical and economic benefits. This analysis demonstrates that the approach taken to incorporate a new antimicrobial agent into clinical practice impacts on the scale of these clinical and economic benefits; greater benefits are associated with earlier use of antimicrobials as part of an antimicrobial stewardship program.

Conclusion

This analysis shows that changing the way in which a new antimicrobial is used within a treatment strategy has the potential for additional significant clinical and economic value.

SUBMITTER: Matsumoto T

PROVIDER: S-EPMC9476387 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Publications

Estimating the Economic and Clinical Value of Introducing Ceftazidime/Avibactam into Antimicrobial Practice in Japan: A Dynamic Modelling Study.

Matsumoto Tetsuya T Yuasa Akira A Miller Ryan R Pritchard Clive C Ohashi Takahisa T Taie Amer A Gordon Jason J

PharmacoEconomics - open 20220915 1

<h4>Background</h4>Antimicrobial resistance (AMR) is one of the most serious public health challenges worldwide, including in Japan. Globally, research and development of new antimicrobials has stalled due to unfavorable market conditions, which undervalue antimicrobials. Furthermore, Japan faces the additional challenge of delayed commercialization for a number of recently approved treatments.<h4>Objective</h4>This study aims to examine the impact on AMR of introducing a new anti-infective trea ...[more]

PMID: 36107306

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Project description:IntroductionAntimicrobial resistance remains a serious and growing threat to public health, both globally and in the UK, leading to diminishing effectiveness of antimicrobials. Despite a clear need for new antimicrobials, the clinical pipeline is insufficient, driven by high research and development costs and limited expected returns on investment. To counteract this, National Institute for Health and Care Excellence (NICE) and National Health Service (NHS) England have launched a reimbursement mechanism, de-linked from volume of sales, that aims to reduce economic risk by recognising the broader population-level value of antimicrobials. The objective of this study was to quantify the value of ceftazidime-avibactam for treating gram-negative infections in the UK considering some of these broader value elements unique to antimicrobials.MethodsA previously developed dynamic disease transmission and cost-effectiveness model was applied to assess the value of introducing ceftazidime-avibactam to UK treatment practice in the management of gram-negative hospital-acquired infections in line with the licenced indications for ceftazidime-avibactam. Model inputs were parameterised using sources aligned to the UK perspective.ResultsThe introduction of ceftazidime-avibactam into a two-line treatment sequence saved over 2300 lives, leading to a gain of 27,600 life years and 22,000 quality-adjusted life years (QALY) at an additional cost of £17 million, over a ten-year transmission period. Ceftazidime-avibactam was associated with a net monetary benefit of £642 million at willingness to pay threshold of £30,000 per QALY; even at a lower threshold of £20,000 per QALY, the net monetary benefit is £422 million.DiscussionIncreasing the diversity of antimicrobial treatments through the introduction of an additional antimicrobial, in this instance ceftazidime-avibactam, was associated with substantial clinical and economic benefits, when considering broader population-level value. Despite revealing considerable benefits, the value of ceftazidime-avibactam is only partially reflected in this analysis. Further efforts are required to fully operationalise the spectrum, transmission, enablement, diversity and insurance (STEDI) value framework and accurately reflect the population-level value of antimicrobials.

Project description:IntroductionCeftazidime-avibactam has proven activity against multidrug-resistant (MDR) bacteria in clinical trials and real-world studies. This study was conducted to describe the patterns of use of ceftazidime-avibactam (including indications and associated antibiotics), and the effectiveness and safety of ceftazidime-avibactam in real-world clinical practice.MethodsThis non-interventional medical chart review study was conducted in 11 countries across the European and Latin American (LATAM) regions. Consecutive patients treated in clinical practice with at least one dose of ceftazidime-avibactam for an approved indication per country label since 01 January 2018 (or launch date in the country if posterior) were enrolled. Effectiveness analyses were conducted in patients treated with ceftazidime-avibactam for at least 72 h.ResultsOf the 569 eligible patients enrolled, 516 (90.7%) were treated for at least 72 h (354 patients from Europe and 162 patients from LATAM); 390 patients (75.7%) had switched from another antibiotic line for Gram-negative coverage. Infection sources were intra-abdominal, urinary, respiratory, bloodstream infections, and other infections (approximately 20% each). K. pneumoniae was the most common microorganism identified in the latest microbiological evaluation before starting ceftazidime-avibactam (59.3%). Two-thirds of microorganisms tested for susceptibility were MDR, of which 89.3% were carbapenem-resistant. The common MDR mechanisms for K. pneumoniae were carbapenemase (33.9%), oxacillinase 48 (25.2%), extended-spectrum beta-lactamase (21.5%), or metallo-beta-lactamase (14.2%) production. Without prior patient exposure, 17 isolates (mostly K. pneumoniae) were resistant to ceftazidime-avibactam. Treatment success was achieved in 77.3% of patients overall (88.3% among patients with urinary infection), regardless of first or second treatment line. In-hospital mortality rate was 23.1%. Adverse events were reported for six of the 569 patients enrolled.ConclusionThis study provides important real-world evidence on treatment patterns, effectiveness, and safety of ceftazidime-avibactam in clinical practice through its recruitment in the European and LATAM regions. Ceftazidime-avibactam is one of the antibiotics to consider for treatment of MDR bacteria.Trial registrationClinicalTrials.gov identifier, NCT03923426.

Project description:BackgroundThis antimicrobial surveillance study reports in vitro antimicrobial activity and susceptibility data for a panel of agents against respiratory isolates of Enterobacterales and Pseudomonas aeruginosa.MethodsIsolates from respiratory specimens were collected in Africa/Middle East, Asia/South Pacific, Europe and Latin America between 2016 and 2018, as part of the Antimicrobial Testing Leadership and Surveillance (ATLAS) program. Broth microdilution methodology was used to quantify minimum inhibitory concentrations, from which rates of susceptibility were determined using EUCAST breakpoints (version 10). Rates of subsets with genes encoding β-lactamases (extended-spectrum β-lactamases [ESBLs], serine carbapenemases and metallo-β-lactamases [MBLs]) were also determined, as well as rates of multidrug-resistant (MDR) P. aeruginosa.ResultsAmong all respiratory Enterobacterales isolates, susceptibility to ceftazidime-avibactam, meropenem, colistin and amikacin was ≥94.4% in each region. For Enterobacterales isolates that were ESBL-positive or carbapenemase-positive/MBL-negative, ceftazidime-avibactam susceptibility was 93.6 and 98.9%, respectively. Fewer than 42.7% of MBL-positive Enterobacterales isolates were susceptible to any agents, except colistin (89.0% susceptible). Tigecycline susceptibility was ≥90.0% among Citrobacter koseri and Escherichia coli isolates, including all β-lactamase-positive subsets. ESBL-positive Enterobacterales were more commonly identified in each region than isolates that were ESBL/carbapenemase-positive; carbapenemase-positive/MBL-negative; or MBL-positive. Among all respiratory P. aeruginosa isolates, the combined susceptibility rates (susceptible at standard dosing regimen plus susceptible at increased exposure) were highest to ceftazidime-avibactam, colistin and amikacin (≥82.4% in each region). Susceptibility to colistin was ≥98.1% for all β-lactamase-positive subsets of P. aeruginosa. The lowest rates of antimicrobial susceptibility were observed among MBL-positive isolates of P. aeruginosa (≤56.6%), with the exception of colistin (100% susceptible). MDR P. aeruginosa were most frequently identified in each region (18.7-28.7%), compared with the subsets of ESBL-positive; carbapenemase-positive/MBL-negative; or MBL-positive isolates.ConclusionsRates of susceptibility among the collections of respiratory Enterobacterales and P. aeruginosa isolates were highest to ceftazidime-avibactam, colistin and amikacin in each region. Tigecycline was active against all subsets of C. koseri and E. coli, and colistin was active against all subsets of P. aeruginosa. The findings of this study indicate the need for continued antimicrobial surveillance among respiratory Gram-negative pathogens, in particular those with genes encoding MBLs.

Project description:The activities of the novel β-lactam-β-lactamase inhibitor combination ceftazidime-avibactam and comparator agents were evaluated against a contemporary collection of clinically significant Gram-negative bacilli. Avibactam is a novel non-β-lactam β-lactamase inhibitor that inhibits Ambler class A, C, and some D enzymes. A total of 10,928 Gram-negative bacilli-8,640 Enterobacteriaceae, 1,967 Pseudomonas aeruginosa, and 321 Acinetobacter sp. isolates-were collected from 73 U.S. hospitals and tested for susceptibility by reference broth microdilution methods in a central monitoring laboratory (JMI Laboratories, North Liberty, IA, USA). Ceftazidime was combined with avibactam at a fixed concentration of 4 μg/ml. Overall, 99.8% of Enterobacteriaceae strains were inhibited at a ceftazidime-avibactam MIC of ≤4 μg/ml. Ceftazidime-avibactam was active against extended-spectrum β-lactamase (ESBL)-phenotype Escherichia coli and Klebsiella pneumoniae, meropenem-nonsusceptible (MIC≥2 μg/ml) K. pneumoniae, and ceftazidime-nonsusceptible Enterobacter cloacae. Among ESBL-phenotype K. pneumoniae strains, 61.1% were meropenem susceptible and 99.3% were inhibited at a ceftazidime-avibactam MIC of ≤4 μg/ml. Among P. aeruginosa strains, 96.9% were inhibited at a ceftazidime-avibactam MIC of ≤8 μg/ml, and susceptibility rates for meropenem, ceftazidime, and piperacillin-tazobactam were 82.0, 83.2, and 78.3%, respectively. Ceftazidime-avibactam was the most active compound tested against meropenem-nonsusceptible P. aeruginosa (MIC50/MIC90, 4/16 μg/ml; 87.3% inhibited at ≤8 μg/ml). Acinetobacter spp. (ceftazidime-avibactam MIC50/MIC90, 16/>32 μg/ml) showed high rates of resistance to most tested agents. In summary, ceftazidime-avibactam demonstrated potent activity against a large collection of contemporary Gram-negative bacilli isolated from patients in U.S. hospitals in 2012, including organisms that are resistant to most currently available agents, such as K. pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae and meropenem-nonsusceptible P. aeruginosa.

Project description:BackgroundDetection of ceftazidime/avibactam (CAZ/AVI) antibacterial activity is absolutely vital with the rapid growth of carbapenem resistant Enterobacteriaceae (CRE). But now, there is no available automated antimicrobial susceptibility testing card for CAZ/AVI, so Kirby-Bauer has become an economical and practical method for detecting CAZ/AVI antibacterial activity against Enterobacteriaceae.ResultIn this study, antimicrobial susceptibility testing of CAZ/AVI against 386 Enterobacteriaceae (188 Klebsiella pneumoniae, 122 Escherichia coli, 76 Enterobacter cloacae) isolated from clinical patients was performed by broth microdilution. Of the 386 strains, 54 extended spectrum β lactamases negative (ESBL(-)), 104 extended spectrum β lactamases positive (ESBL(+)), 228 CRE. 287 isolates were susceptible to CAZ/AVI and 99 isolates were resistant to CAZ/AVI. At the same time, to obtain optimal content avibactam (AVI) disk containing ceftazidime (30 μg), inhibition zone diameter of four kinds of ceftazidime (30 μg) disk containing different AVI content (0 μg, 10 μg, 25 μg, 50 μg) were tested by Kirby-Bauer method. The microdilution broth method interpretation was used as the standard to estimate susceptible or resistance and then coherence analysis was carried out between Kirby-Bauer and broth microdilution. The result shows the inhibition zone diameter of 30 μg/50 μg disk, susceptible isolates: 20.5 mm-31.5 mm, resistance isolates: 8.25 mm-21.5 mm. The inhibition zone diameter of 30 μg/25 μg disk, susceptible isolates: 19.7 mm-31.3 mm, resistance isolates: 6.5 mm-19.2 mm. The inhibition zone diameter of 30 μg/10 μg disk, susceptible isolates: 19.5 mm-31 mm, resistance isolates: 6.5 mm-11 mm. The inhibition zone diameter of ceftazidime (30 μg), susceptible isolates: 6.5 mm-27.5 mm, resistance isolates 6.5 mm.ConclusionOur results show that 30 μg/50 μg, 30 μg/25 μg, 30 μg/10 μg CAZ/AVI disk have significant statistical differences to determinate CAZ/AVI antibacterial activity, but for 30 μg/50 μg disk, there has a cross section between susceptible isolates (minimum 20.5 mm) and resistance isolates (maximum 21.5 mm). For 30 μg/25 μg disk, it is hard to distinguish the difference between susceptible isolates (minimum 19.7 mm) and resistance isolates (maximum 19.2 mm), so 30 μg/10 μg CAZ/AVI disk is more conducive to determinate antibacterial activity.

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

Estimating the Economic and Clinical Value of Introducing Ceftazidime/Avibactam into Antimicrobial Practice in Japan: A Dynamic Modelling Study.

Background

Objective

Methods

Results

Discussion

Conclusion

Publications

Estimating the Economic and Clinical Value of Introducing Ceftazidime/Avibactam into Antimicrobial Practice in Japan: A Dynamic Modelling Study.

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