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Om ZaviceftaVirkningsmekanismePatogen dekningTidlig hensiktsmessig behandlingIDSA anbefalingØkonomiske holdepunkterSpørsmål og svar om ZAVICEFTAPasientprofilerHAP/VAP pasientcUTI pasientcIAI pasientPediatriske pasienterSpørsmål og svar - FAQsEffekt Real-world evidenceEffektdataSpørsmål og svar om effektSikkerhetSikkerhet hos voksneSikkerhet hos barn/ungdomSpørsmål og svar om sikkerhetDoseringDosering hos voksneDosering hos barn/ungdomSpørsmål og svar om dosering
EffektdataZAVICEFTA (ceftazidime–avibactam) is as effective as a carbapenem, with the benefit of in vitro activity against carbapenem-resistant Gram-negative pathogens, including KPC- and OXA-48-producing strains1–6

HAP/VAP

cUTI

cIAI

Paediatrics

Bacteraemia

HAP/VAP is one of the most frequent nosocomial infections carrying a high morbidity, crude mortality and increased costs1,10

With mortality rates significantly higher in patients with inappropriate empirical therapy than in those with appropriate treatment (47% and 20% respectively), there is an unmet need for new, more effective treatment.10

ZAVICEFTA is as effective as a carbapenem in patients with HAP/VAP caused by Gram-negative pathogens1

REPROVE Phase III trial:1

879 patients hospitalised adults with HAP/VAP were randomised in a controlled setting to show noninferiority, compared with a carbapenem, of an antimicrobial therapy targeting Gram-negative pathogens in HAP/VAP.

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Baseline pathogens1
Predominantly K. pneumoniae and P. aeruginosa, including some ceftazidime-resistant strains.
100 patients (28%) had ≥1 ceftazidime-resistant isolate.

Trial design

REPROVE: International, non-inferiority, randomised, double-blind, Phase III trial1

Lung penetration PK/PD data

Complementary kinetic profile with proven penetration into the lung11

Concentration–time profiles following administration of 2 g of ceftazidime + 0.5 g of avibactam

Listen to Professor Antoni Torres

Professor of Pulmonology and Respiratory Critical Care Medicine at University of Barcelona, Spain, talks about hospital-acquired pneumonia and ventilator-associated pneumonia, as well as the REPROVE study, a Phase III randomised clinical trial comparing ceftazidime-avibactam to meropenem.

ZAVICEFTA is as effective as a carbapenem in patients with HAP/VAP caused by Gram-negative pathogens.1

cUTIs are potentially life-threatening infections of the urinary tract that frequently require hospitalisation and are associated with significant rates of antimicrobial resistance12-14

In cUTI the likelihood of initial antibiotic therapy failure and serious complications, particularly the development of antimicrobial resistance, is more common compared with uncomplicated UTI.15

ZAVICEFTA is as effective as a carbapenem in patients with cUTI caused by Gram-negative pathogens2

RECAPTURE Phase III trial:

1033 hospitalised adults with cUTI were randomised in a controlled setting to show noninferiority, compared with a carbapenem, of an antimicrobial therapy targeting Gram-negative pathogens in cUTI.

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Baseline pathogens
Predominantly E, coli and K. pneumoniae, including some ceftazidime-resistant strains.

Trial design

RECAPTURE: International, non-inferiority, randomised, double-blind, Phase III trial2

Listen to Dr Paschalis Vergidis

Infectious Diseases Consultant at Manchester University NHS Foundation Trust, sharing his view on the challenges of MDR Gram-negative infections. Learn about his clinical practice experience in a renal transplant patient and the role of ceftazidime-avibactam in patients with cUTI.

ZAVICEFTA is as effective as best-available therapy in patients with cUTI or cIAI caused by Gram-negative pathogens3

REPRISE Phase III trial:

333 hospitalised adults with cUTI or cIAI were randomised in a controlled setting. The REPRISE study is the first pathogen directed clinical trial for ceftazidime–avibactam examining its efficacy against ceftazidime resistant Gram-negative pathogens.

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Baseline pathogens
Ceftazidime-resistant Enterobacterales (most commonly E. coli or K. pneumoniae) and P. aeruginosa.

Trial design

REPRISE: Pathogen-directed, international, randomised, open-label, Phase III trial3

Example

Listen to Dr Matthew Dryden

Consultant Microbiologist at Hampshire Hospitals, discuss the REPRISE study.

ZAVICEFTA is as effective as a carbapenem in patients with cUTI and as effective as best-available therapy in cUTI or cIAI patients caused by Gram-negative pathogens.2,3​​​​​​​

cIAIs are serious, life-threatening infections associated with poor outcomes and high rates of mortality16

Underlying medical conditions and inadequate early antibiotic therapy are among the factors consistently associated with poor outcomes in patients with cIAIs.4,17

ZAVICEFTA is as effective as a carbapenem when combined with metronidazole in patients with cIAI caused by Gram-negative pathogens5

RECLAIM Phase III trial:

1066 hospitalised adults with cIAI were randomised in a controlled setting to show noninferiority, compared with a carbapenem, of an antimicrobial therapy targeting Gram-negative pathogens in cIAI.

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Baseline pathogens
E coli, K. pneumoniae and P. aeruginosa, including some ceftazidime-resistant strains. 417 patients (40%) had polymicrobial infection at baseline.

Trial design

RECLAIM: International, non-inferiority, randomised, double-blind, comparative, Phase III programme5

ZAVICEFTA is as effective as best-available therapy in patients with cUTI or cIAI caused by Gram-negative pathogens3

REPRISE Phase III trial:

333 hospitalised adults with cUTI or cIAI were randomised in a controlled setting. The REPRISE study is the first pathogen directed clinical trial for ceftazidime–avibactam examining its efficacy against ceftazidime resistant Gram-negative pathogens.

Scroll left to view table

Baseline pathogens
Predominantly E. coli and K. pneumoniae, including some ceftazidime-resistant strains.

Trial design

REPRISE: Pathogen-directed, international, randomised, open-label, Phase III trial3

Example

Listen to Dr Matthew Dryden

Consultant Microbiologist at Hampshire Hospitals, discuss the REPRISE study.

ZAVICEFTA is as effective as a carbapenem in patients with cUTI and as effective as best-available therapy in cUTI or cIAI patients caused by Gram-negative pathogens.2,3​​​​​​​

Infections due to MDR Gram-negative pathogens are increasing in children and have been associated with higher mortality18,19*****

Safe, effective treatment options are urgently needed to address the growing threat of MDR Gram-negative infections in paediatric patients.7,20

ZAVICEFTA achieved favourable clinical response rates in paediatric patients aged 3 months and older with cUTI, with similar effectiveness to cefepime8

Phase II trial:

95 hospitalised paediatric patients 3 months and older with cUTI. The first randomised controlled trial of ZAVICEFTA in paediatric patients with cUTI.

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Baseline pathogens
Predominantly E coli (92%)

Trial design

cUTI paediatric trial: Multicentre, single-blind, randomised, actively-controlled, Phase II trial8

ZAVICEFTA achieved favourable clinical response rates when combined with metronidazole in paediatric patients aged 3 months and older with cIAI, with similar effectiveness to meropenem7

Phase II trial:

83 hospitalised paediatric patients 3 months and older with cIAI. The first time randomised controlled trial of ZAVICEFTA in paediatric patients with cIAI.

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Baseline pathogens
Predominantly E coli (80%) and P. aeruginosa (33%)

Trial design

cIAI paediatric trial: Multicentre, single-blind, randomised, actively-controlled, Phase II trial7

Example

ZAVICEFTA achieved favourable clinical response rates in paediatric patients aged 3 months and older with cIAI¶¶¶¶¶¶ and cUTI, with similar effectiveness to comparator therapies when assessed in paediatric trials.7,8

Bloodstream infections are associated with increased mortality, hospital length of stay and costs, especially in critically ill patients21,22

With mortality rates as high as 48%, new effective treatment options are needed to address the increasing threat of MDR Gram-negative bacteraemia.23,26,27

The efficacy of ZAVICEFTA for the treatment of bacteraemia in adult patients is supported by data from a subset of 101 adult patients across the Phase III clinical trial programme6,9,28‡

Phase III clinical trial programme:

A post-hoc analysis******* of 101 adult patients in five Phase III international, randomised, non-inferiority trials in patients with bacteraemia††††††† associated with HAP/VAP, cIAI or cUTI.9,28

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Baseline pathogens9
E coli (69%), K pneumoniae (21%), P aeruginosa (17%)

Baseline diagnoses9
Acute pyelonephritis (69%), VAP (21%)

ZAVICEFTA showed favourable clinical and microbiological response rates in adult patients with bacteraemia††††††† associated with HAP/VAP, cIAI or cUTI.9,28

Explore moreSafety and tolerability

Learn more about ZAVICEFTA’s safety and tolerability.

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Download our spectrum of activity one-pager for more information on
ZAVICEFTA’s pathogen coverage in comparison to competitor treatments.
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Abbreviation:CE, clinically evaluable; CI, confidence interval; cIAI, complicated intrabdominal infection; cMITT, clinically modified intention-to-treat; cUTI, complicated urinary tract infection; ELF, epithelial lining fluid; HAP, hospital-acquired pneumonia; IV, intravenous; MITT, modified intention-to-treat; TOC, test of cure; VAP, ventilator-associated pneumonia.Footnotes:*ZAVICEFTA is as effective as a carbapenem when combined with metronidazole in hospitalised patients with Gram-negative cIAIs.5
†Use of ZAVICEFTA 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. ZAVICEFTA has proven clinical efficacy across four Phase III, international, randomised, non-inferiority trials in 1423 adult patients with HAP/VAP, cIAI or cUTI.1–3,5,7,8
‡Five Phase III international, randomised, non-inferiority trials in patients with HAP/VAP, cIAI or cUTI.6,28
¶Non-inferiority was concluded if the lower limit of the 95% CI was greater than -12.5%.1
**cMITT population comprised patients with minimum disease criteria but excluded patients with only non-target pathogens.1
††The CE population comprised patients in the cMITT population who received an adequate course of treatment and had an assessable clinical outcome within the assessment window, no protocol deviations that could affect the assessment of efficacy, and no unacceptable previous or concomitant antibiotics.1
‡‡Clinical cure was defined as resolution of all signs and symptoms of pneumonia such that no antibacterial therapy for nosocomial pneumonia was taken between end of treatment and test of cure inclusive.1
§§n=6 for ELF median concentrations at 2 and 4 hours in the 2 g ceftazidime + 0.5 g avibactam group.11
***Non-inferiority was concluded if the lower limit of the 95% CI was greater than -12.5%.2
†††The mMITT population comprised all randomised patients with minimum disease criteria and eligible baseline pathogen(s).2
‡‡‡Formal statistical comparison not performed; corresponding CIs for the efficacy of best available therapy were used to provide context for descriptive estimates of ceftazidime–avibactam efficacy.3

§§§Patients in the mMITT population included all patients who had a diagnosis of cUTI or cIAI with at least one ceftazidime-resistant Gram-negative pathogen, as confirmed by the central laboratory, and who received at least one dose of study drug.3
¶¶¶Preferred best-available therapy options for cUTI and cIAI were 5–21 days of treatment with meropenem, imipenem, doripenem, colistin and (for cIAI) tigecycline, administered intravenously, but any therapy, including combination treatment, was permitted.3
****Clinical cure defined as complete resolution or substantial improvement of signs and symptoms of the index infection such that no further antibacterial therapy was necessary. For cIAI patients, cure also required no drainage or surgical intervention needed after 96 hours from randomisation.3
††††Non-inferiority was considered met if the lower limit of the 95% CI for between-group difference was greater than the prespecified non-inferiority margin of -12.5%.5
‡‡‡‡Patients in the MITT population are defined as patients who received study drug and met the clinical disease criteria.5
§§§§Clinical cure defined as complete resolution or substantial improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage or surgery intervention was necessary. Non-inferiority was considered met if the lower limit of the 95% CI for between-group difference was greater than the prespecified non-inferiority margin of -12.5%.5
¶¶¶¶Patients in the MITT population are defined as patients who received study drug and met the clinical disease criteria.5
*****Multicentre retrospective cohort study using data from 48 US children’s hospitals to determine the proportion of MDR-GNE diagnoses among patients aged 0 to <18 years who were diagnosed with an Enterobacterales-associated infection between 1 January 2007, and 31 March 2015.17
†††††The 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 and pharmacokinetics was a secondary objective. Analysed in the micro-ITT population (all randomised patients with a study-qualifying baseline pathogen).8
‡‡‡‡‡A favourable clinical outcome was defined as clinical cure. A favourable per-patient microbiologic response was defined as eradication of the pathogen(s). If a patient had more than 1 pathogen, the outcome had to be favourable for each pathogen for it to be counted as a favourable response.7
§§§§§Dose adjusted depending on weight, age and renal status.7,8
¶¶¶¶¶Dose adjusted according to local prescribing information or as prescribed by the investigator.8
******All randomised patients who received ≥1 dose of IV study drug.8
††††††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. Safety and tolerability data included vital signs, physical examination, laboratory parameters, creatinine clearance and electrocardiogram data. The safety analysis set consisted of all randomised patients who received any amount of IV study drug.8
‡‡‡‡‡‡All randomised patients.8
§§§§§§All randomised patients with a baseline pathogen known to cause cIAI.8
¶¶¶¶¶¶ZAVICEFTA plus metronidazole for cIAI.28
*******Exploratory analysis of adult patients with Gram-negative bacteraemia.9
†††††††Defined as any patient with ≥1 bacteria identified from a blood culture at baseline for all studies, except for RECAPTURE, which also required the same pathogen to be identified in a urine sample at >105 CFUs/mL.28
‡‡‡‡‡‡‡Meropenem in HAP/VAP and cIAI; doripenem in cUTI.28 
References:Torres A, et al. Lancet Infect Dis 2018;18:285–95.Wagenlehner FM, et al. Clin Infect Dis 2016;63:754–62.Carmeli Y, et al. Lancet Infect Dis 2016;16:661–73.Mazuski Je, et al. Surg Infect (Larchmt) 2017;18:1–76.Mazuski JE, et al. Clin Infect Dis 2016;62:1380–9.ZAVICEFTA. Summary of Product Characteristics, 2022.Bradley JS, et al. Pediatr Infect Dis J 2019;38:816–24 and supplementary information.Bradley JS, et al. Pediatr Infect Dis J 2019;38:920–8.Mazuski JE, et al. ECCMID 2020; abstract 985.Torres A, et al. Eur Respir J 2017;50:1700582.Nicolau DP, et al. J Antimicrob Chemother 2015;70:2862–9.Vallejo-Torres L, et al. BMJ Open 2018; 8:e020251.Bonkat G, et al. European Association of Urology Guidelines on Urological Infections. 2018. Available at: https://uroweb.org/guidelines/urological-infections (last accessed July 2022) EAU guidelines 2022.Mnif MF, et al. Indian J Endocrinol Metab 2013;17:442–45.Pallett A, Hand K. J Antimicrob Chemother 2010;65Suppl 3:iii25–33.Sartelli M, et al. World J Emerg Surg 2017;12:29.Meropol SB, et al. J Pediatric Infect Dis Soc 2018;7:36–45.Aguilera-Alonso D, et al. Antimicrob Agents Chemother 2020;64:e02183-19.Sader HS, et al. Pediatr Infect Dis J 2018;37:549–54.
Sante L, et al. J Infect Public Health 2019;12:37–42.
Blot S. Infect Dis (Lond) 2019;51:23–5.Bassetti M, et al. Virulence 2016;7:267–79.Thaden JT, et al. Antimicrob Agents Chemother 2017;61:e01709-16.Mascitti H, et al. Antimicrob Resist Infect Control 2018;7:116.van Duin D, et al. Diagn Microbiol Infect Dis 2013;75:115–20.Morrill HJ, et al. Open Forum Infect Dis 2015;2:ofv050.Mazuski JE, et al. ECCMID 2020; abstract 985.European Medicines Agency. CHMP extension of indication variation assessment report for Zavicefta. EMA/CHMP/302938/2020.Bradley JS, et al. Antimicrob Agents Chemother 2016;60:6252–9.
Effekt
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