Study Results
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Basic Information
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RECRUITING
PHASE4
108 participants
INTERVENTIONAL
2025-01-30
2027-02-28
Brief Summary
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Current treatments include polymyxins (Colistin, Polymyxin B), which are effective but can lead to resistance, aminoglycosides (Amikacin, Gentamicin), which are limited by resistance, and tetracyclines (Tigecycline, Eravacycline), which are effective against CRAB. Fosfomycin is effective in combination treatments, and combination therapy (e.g., colistin with sulbactam, fosfomycin, or eravacycline) can enhance outcomes.
Previous research shows promise for combination therapies, improving treatment efficacy and reducing mortality. New regimens are being studied to find optimal combinations. Individualized dosing is crucial, considering patient-specific factors like age, weight, and renal function. Adjustments depend on the infection site and comorbidities.
Strict infection control and antimicrobial stewardship programs (ASPs) are essential. ASPs focus on optimizing antibiotic use and reducing resistance through education and surveillance. Future directions include continued research for new drugs or combinations and strategies to overcome resistance and improve treatment efficacy.
Study goals include achieving negative samples after 10 days of therapy, 30-day survival, discharge rates, reduced SOFA scores, and improved clinical and radiological findings. A randomized study will compare colistin combined with fosfomycin, ampicillin/sulbactam, and eravacycline.
In summary, treating CRAB infections is complex, requiring combination therapy, individualized dosing, and strict infection control measures.
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Detailed Description
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The secondary objectives will include 30-day survival, discharge from the ICU, discharge from the hospital, reduction in SOFA score, rate of reinfection, and frequency of complications (deterioration of renal function). Reduction of CRP, PCT, and leukocytes, improvement of the clinical picture, improvement of radiological findings (such as X-ray of the lungs), and reduction of elevated body temperature will also be included.
Patients who require treatment in the ICU with a positive sample (surveillance or diagnostic) for A. baumannii, with clinical signs of infection (temperature \>38.5, CPR \>50, L \>10000) (in which no infection can be explained by another cause) will be included.
Three groups will be formed:
1. colistin + fosfomycin
2. colistin + ampicilin/sulbactam
3. colistin + eravacyclin
The outcomes will include a negative sample, length of stay in the ICU, length of stay in the hospital, and reduction of SOFA score.
The hypothesis will be that the combination of fosfomycin with colistin and eravacyclin with colistin will lead to faster negative samples than the combination of ampicillin/sulbactam with colistin in intensive care unit patients diagnosed with carbapenem-resistant A. baumannii.
After obtaining approval from the ethics committee of KBC Zagreb, this study will be conducted at the UHC Zagreb, Department of Anesthesiology and ICU. Patients will be randomly divided according to a predetermined randomization table.
Upon arrival of a positive microbiological finding on A. baumannii, the Fosfomycin group will receive fosfomycin 8 g every 8 h, together with a colistin bolus of 6 million IJ, followed by 3 million IJ every 8 h. After the first day, the dose will be adjusted according to kidney and liver function. Therapy will be administered for 10 days.
Upon arrival of a positive microbiological finding on A. baumannii, the Ampicilin/sulbactam group will receive a bolus dose of ampicillin/sulbactam 2 g + 1 g and a continuous infusion of 8 g + 4 g over 24 h together (maximum daily dose 12 g/day) with a colistin bolus of 6 million IJ, followed by 3 million IJ every 8 h. After the first day, the dose will be adjusted according to kidney and liver function. Therapy will be performed for 10 days.
Upon arrival of a positive microbiological finding for A. baumannii, the Eravacyclin group will receive eravacycline at a dose of 1 mg/kg every 12 h for 60 min together with a colistin bolus of 6 million IU, and then 3 million IU every 8 h. After the first day, the dose will be adjusted according to kidney and liver function. Therapy will be administered for 10 days.
After the first positive microbiological finding for A. baumannii, the test will be repeated on the 4th, 7th, and 10th days from the start of therapy. The Charlson Comorbidity Index will be calculated for each patient upon inclusion in the study. The SOFA score will be calculated daily for each patient over 10 days.
Patient data from a hospital information system will be used in this study. Demographic data, comorbidities, habits (alcohol and cigarettes), Charlson comorbidity index, SOFA score, allergies, and the type of positive sample will be recorded. The Charlson Comorbidity Index will be calculated for each patient upon inclusion in the study. The SOFA score will be calculated daily for each patient over 10 days. Patients will be included in the study after the arrival of a microbiological test positive for A. baumannii. A routine antimicrobial susceptibility test will be performed when the microbiological findings are positive for A. baumannii. The sensitivity of all A. baumannii strains included in the study, regardless of the group to which they belonged (fosfomycin, ampicilin/sulbactam, and eravacyclin), will be determined during the microbiological analysis of all A. baumannii strains included in the study. After the first positive microbiological finding for A. baumannii, the test will be repeated on the 3th, 7th, and 10th days from the start of therapy. For each patient included in the study, inflammatory parameters (leukocytes, CRP, procalcitonin) and the number of days and discharge from the ICU and hospital as well as 30-day mortality and cause of death, complications (AKI and ALF), and reinfection will be monitored.
For a test power of 80% and the use of an independent t-test for the primary objective and a chi-square test for the secondary objective with a statistical significance of 0.05, it will be necessary to include 108 patients, divided into three groups, with 36 subjects per group. The test for power calculation will be conducted using G Power Version 3.1.9.6. The results will be processed using IBM SPSS Statistics v27.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
DOUBLE
Study Groups
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Fosfomycin
Upon the detection of a positive microbiological finding for A. baumannii, the Fosfomycin group will receive 8 grams of fosfomycin every 8 hours, along with an initial colistin bolus of 6 million IU, followed by 3 million IU every 8 hours. After the first day, the dosage will be adjusted based on kidney and liver function. This therapy will be administered for a total of 10 days.
Fosfomycin
Patients will be randomly divided according to a predetermined randomization table Upon arrival of a positive microbiological finding on A. baumannii, patient will be randomised to one of groups (Colistin with Unasyn OR Colistin with Xerava OR Colistin with Fosfomycin
Ampicilin/sulbactam
Upon the detection of a positive microbiological finding for A. baumannii, the Ampicilin/sulbactam group will receive an initial bolus dose of 2 grams of ampicillin and 1 gram of sulbactam, followed by a continuous infusion of 8 grams of ampicillin and 4 grams of sulbactam over 24 hours (maximum daily dose of 12 grams per day), along with a colistin bolus of 6 million IU, followed by 3 million IU every 8 hours. After the first day, the dosage will be adjusted based on kidney and liver function. This therapy will be administered for a total of 10 days.
ampicillin/sulbactam
Patients will be randomly divided according to a predetermined randomization table Upon arrival of a positive microbiological finding on A. baumannii, patient will be randomised to one of groups (Colistin with Unasyn OR Colistin with Xerava OR Colistin with Fosfomycin
Eravacyclin
Upon the detection of a positive microbiological finding for A. baumannii, the Eravacyclin group will receive eravacycline at a dose of 1 mg/kg every 12 hours for 60 minutes, along with a colistin bolus of 6 million IU, followed by 3 million IU every 8 hours. After the first day, the dosage will be adjusted based on kidney and liver function. This therapy will be administered for a total of 10 days.
Eravacycline
Patients will be randomly divided according to a predetermined randomization table Upon arrival of a positive microbiological finding on A. baumannii, patient will be randomised to one of groups (Colistin with Unasyn OR Colistin with Xerava OR Colistin with Fosfomycin
Interventions
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Fosfomycin
Patients will be randomly divided according to a predetermined randomization table Upon arrival of a positive microbiological finding on A. baumannii, patient will be randomised to one of groups (Colistin with Unasyn OR Colistin with Xerava OR Colistin with Fosfomycin
Eravacycline
Patients will be randomly divided according to a predetermined randomization table Upon arrival of a positive microbiological finding on A. baumannii, patient will be randomised to one of groups (Colistin with Unasyn OR Colistin with Xerava OR Colistin with Fosfomycin
ampicillin/sulbactam
Patients will be randomly divided according to a predetermined randomization table Upon arrival of a positive microbiological finding on A. baumannii, patient will be randomised to one of groups (Colistin with Unasyn OR Colistin with Xerava OR Colistin with Fosfomycin
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Older than 18 years
* Require postoperative treatment in the ICU
* A positive sample (surveillance or diagnostic) for A. baumannii with signs of systemic infection
Infection will be defined as a diagnostic microbiologically positive sample for A. baumannii and a surveillance microbiologically positive sample for A. baumannii with signs of systemic infection (elevated CRP, leukocytes, and body temperature).
Colonization will be defined as a positive surveillance microbiological sample for A. baumannii in the absence of signs of systemic infection (normal CRP, leukocytes, and body temperature).
Exclusion Criteria
* Positive surveillance swabs for A. baumannii without signs of systemic infection
* Positive findings (surveillance or diagnostic) for carbapenem-sensitive A. baumannii
* Refusal to participate in the research
18 Years
90 Years
ALL
No
Sponsors
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Clinical Hospital Centre Zagreb
OTHER
Responsible Party
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Ivan Šitum, MD
Principal invesigator
Principal Investigators
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Ivan Šitum
Role: PRINCIPAL_INVESTIGATOR
UHC Zagreb
Locations
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University Hospital Centre Zagreb
Zagreb, , Croatia
Countries
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Central Contacts
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Facility Contacts
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Robert Baronica
Role: backup
References
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Šitum I, Mamić G, Džaja N, Hrvoić L, Lovrić D, Siroglavić M, et al. Upala pluća povezana s mehaničkom ventilacijom uzrokovana bakterijom Acinetobacter baumannii u razdoblju pandemije COVID-19. Medicina Fluminensis : Medicina Fluminensis [Internet]. 2023 Jun 1 [cited 2024 Apr 30];59(2):139-48. Available from: http://hrcak.srce.hr/medicinamedicinafluminensis
Carbapenem-resistant Acinetobacter baumannii (CRAB): An urgent public health threat in United States healthcare facilities | A.R. & Patient Safety Portal [Internet]. [cited 2024 May 2]. Available from: https://arpsp.cdc.gov/story/cra-urgent-public-health-threat
Shields RK, Paterson DL, Tamma PD. Navigating Available Treatment Options for Carbapenem-Resistant Acinetobacter baumannii-calcoaceticus Complex Infections. Clin Infect Dis. 2023 May 1;76(Suppl 2):S179-S193. doi: 10.1093/cid/ciad094.
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Viehman JA, Nguyen MH, Doi Y. Treatment options for carbapenem-resistant and extensively drug-resistant Acinetobacter baumannii infections. Drugs. 2014 Aug;74(12):1315-33. doi: 10.1007/s40265-014-0267-8.
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Nartey YA, Donkor AB, Siaw ADJ, Ekor OE, Jimah BB. Carbapenem-Resistant Acinetobacter baumannii Bloodstream Infection in a Ghanaian Patient with Unilateral Diaphragmatic Eventration and HIV Type 1 Infection. Case Rep Infect Dis. 2023 Oct 12;2023:9930291. doi: 10.1155/2023/9930291. eCollection 2023.
Kim SH, Wi YM, Peck KR. Clinical Effectiveness of Tetracycline-Class Agents Based Regimens in Patients With Carbapenem-Resistant Acinetobacter baumannii Bacteremia: A Single-Center Retrospective Cohort Study. J Korean Med Sci. 2023 Aug 28;38(34):e263. doi: 10.3346/jkms.2023.38.e263.
Jung SY, Lee SH, Lee SY, Yang S, Noh H, Chung EK, Lee JI. Antimicrobials for the treatment of drug-resistant Acinetobacter baumannii pneumonia in critically ill patients: a systemic review and Bayesian network meta-analysis. Crit Care. 2017 Dec 20;21(1):319. doi: 10.1186/s13054-017-1916-6.
Pogue JM, Zhou Y, Kanakamedala H, Cai B. Burden of illness in carbapenem-resistant Acinetobacter baumannii infections in US hospitals between 2014 and 2019. BMC Infect Dis. 2022 Jan 6;22(1):36. doi: 10.1186/s12879-021-07024-4.
Seok H, Choi WS, Lee S, Moon C, Park DW, Song JY, Cheong HJ, Kim J, Kim JY, Park MN, Kim YR, Lee HJ, Kim B, Pai H, Jo YM, Kim JH, Sohn JW. What is the optimal antibiotic treatment strategy for carbapenem-resistant Acinetobacter baumannii (CRAB)? A multicentre study in Korea. J Glob Antimicrob Resist. 2021 Mar;24:429-439. doi: 10.1016/j.jgar.2021.01.018. Epub 2021 Feb 8.
Gatti M, Viaggi B, Rossolini GM, Pea F, Viale P. An Evidence-Based Multidisciplinary Approach Focused on Creating Algorithms for Targeted Therapy of Infection-Related Ventilator-Associated Complications (IVACs) Caused by Pseudomonas aeruginosa and Acinetobacter baumannii in Critically Ill Adult Patients. Antibiotics (Basel). 2021 Dec 28;11(1):33. doi: 10.3390/antibiotics11010033.
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Saelim W, Changpradub D, Thunyaharn S, Juntanawiwat P, Nulsopapon P, Santimaleeworagun W. Colistin plus Sulbactam or Fosfomycin against Carbapenem-Resistant Acinetobacter baumannii: Improved Efficacy or Decreased Risk of Nephrotoxicity? Infect Chemother. 2021 Mar;53(1):128-140. doi: 10.3947/ic.2021.0007.
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Bartal C, Rolston KVI, Nesher L. Carbapenem-resistant Acinetobacter baumannii: Colonization, Infection and Current Treatment Options. Infect Dis Ther. 2022 Apr;11(2):683-694. doi: 10.1007/s40121-022-00597-w. Epub 2022 Feb 17.
Other Identifiers
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CRAB01
Identifier Type: -
Identifier Source: org_study_id
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