| Background:The development of infectious complications significantly increases the mortality and healthcare burden in patients with Acute pancreatitis(AP),with mortality in Severe acute pancreatitis(SAP)combined with infection reaching30%-40%.Intestinal flora translocation is closely related to the development of infection.Rifaximin is a broad-spectrum antibiotic that only works in the intestinal tract,regulating intestinal flora imbalance and exerting an intestinal decontamination effect,but the efficacy and safety of rifaximin in preventing infection in patients with AP is not reported in prospective studies.Aim:The aim of this study was to preliminarily explore the effectiveness of rifaximin in preventing lately infectious complications in AP and the safety of rifaximin’s application in AP patients.Methods:This study was a single-centre,exploratory,open-label,randomized controlled trial that recruited and enrolled patients with predicted SAP or confirmed SAP who presented to our gastroenterology department from August 2022 to November 2022.Patients in the rifaximin group were given rifaximin on the basis of conventional treatment,i.e.rifaximin(0.2 g/dose,3 times a day)via oral or nasogastric/jejunal tube for 14 consecutive days starting from the day of enrolment,while the control group was given conventional treatment.The primary endpoint was the incidence of culture-confirmed infectious complications and the secondary endpoints were the incidence of clinical + culture-confirmed infectious complications,site of infection,the microbiological profile of infection,intestinal barrier markers(D-lactate(D-lac),diamine oxidase(DAO)),inflammatory markers(white blood cell count(WBC),C-reactive protein(CRP),procalcitonin(PCT),interleukins(IL)-6,neutrophil percentage(NE),tumor necrosis factor(TNF)-α)and other clinical prognoses.This study was designed using Intention-to-treat Analysis.Results:1.A total of 317 AP patients presenting to our gastroenterology department were recruited for this study,and 60 patients with predicted SAP or confirmed SAP were finally included and randomly assigned 1:1 to the rifaximin group(n=30)and the control group(n=30).The median age was 47.0(36.0,56.8)years,with 43(71.7%)males and 79(28.3%)females;the two groups were matched for baseline characteristics;2.There was a trend towards a reduction in the incidence of infectious complications of AP in the rifaximin group compared to the control group,but there was no statistically significant difference.The incidence of culture-confirmed infectious complications was 13.3% in both the rifaximin and control groups,(RR,1.000;95CI,0.275-3.634;P > 0.999);the incidence of cultured or clinically confirmed infectious complications was 20.0% and 33.3% in the two groups,(RR,0.600;95CI,0.250-1.442;P=0.243);3.The expression of blood inflammation indicators and intestinal barrier damage indicators were measured at two time points,before the intervention(T0)and the day after the end of the intervention(T1).Compared to T1 in the control group,T1 in the rifaximin group showed WBC(8.49(6.93,10.20)× 109/L versus 11.50(8.76,15.68)× 109/L;P=0.042)and TNF-α(11.00(8.74,15.40)pg/ml versus 15.05(12.73,19.75)pg/ml;P=0.009)were significantly decreased.Compared to the control group,there was a significantly greater decrease in TNF-α after rifaximin intervention(16.88(-11.00,57.29)% versus 4.54(-36.49,23.13)%;P=0.049)and a decrease in WBC(38.49(12.83,62.20)% versus 25.11(-16.24,49.98)%;P = 0.095)had a tendency to increase.whereas the remaining inflammatory indicators,including CRP,PCT,IL-6and NE,and indicators of intestinal barrier damage,including DAO and D-lac,were not significantly different between the two groups;4.In terms of clinical Prognosis,there were no significant differences between the rifaximin and control groups in the prognostic indicators of new organ failure,worsening intra-abdominal hypertension,new abdominal septal compartment syndrome,total local complications,total AP severity,minimally invasive operations,duration of intensive care,duration of intravenous antibiotics,hospital costs,length of stay and mortality;5.Subgroup analyses suggested no interaction between the effect of rifaximin intervention on the incidence of culture-confirmed infectious complications and mortality and pre-intervention multiple organ failure(MOF),intravenous antibiotic use during the course of the disease,and high-fat etiology(P for interaction > 0.05).In the pre-intervention subgroup with MOF,the incidence of culture-confirmed infectious complications was 50.0% in the rifaximin group and 25% in the control group(RR,2.000;95% CI,0.306-13.062),whereas in the pre-intervention subgroup without MOF there was a trend towards a lower incidence of infectious complications in the rifaximin group,4.2% in the rifaximin group and 11.5% in the control group(RR,11.5%).11.5%(RR,0.361;95% CI,0.040-3.240);6.In terms of safety assessment,one participant developed a rash after 3 days of rifaximin use,which resolved on its own after discontinuation of the drug.Fungal infections occurred in 2 patients in the rifaximin group and 1 patient in the control group,and multi-drug resistant bacterial infections occurred in 2 patients in the rifaximin group and 3 patients in the control group,with no serious adverse events attributed to rifaximin intervention.Conclusions:Prophylactic use of rifaximin may not reduce the incidence of infectious complications in patients predictable to SAP or confirmed SAP and does not significantly improve the prognosis,but it can improve systemic inflammation levels significantly.No serious adverse events were observed in the study,and there was no difference in the incidence of fungal and drug-resistant infections between the two groups,suggesting that rifaximin may be safe in patients with AP.The results of this study still need to be confirmed in further randomized controlled trials with large samples. |
