The primary goal will be to negativize positive samples (surveillance or diagnostic)
after 10 days of therapy. In addition to the control samples with the same name, samples
will be taken on the 4th, 7th, and 10th day after starting treatment.
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:
colistin + fosfomycin
colistin + ampicilin/sulbactam
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, IL6) 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.