Conventional vs Short Duration of Antibiotics in Patients With Moderate or Severe Cholangitis: Noninferiority Randomized Trial

Abstract

Background: Successful biliary drainage and antibiotics are the mainstays of therapy in management of patients with acute cholangitis. However, the duration of antibiotic therapy after successful biliary drainage has not been prospectively evaluated. We conducted a single centre, randomized, non-inferiority trial to compare short and conventional duration of antibiotic therapy in patients with moderate or severe cholangitis. Methods: Consecutive patients were screened for the inclusion criteria and randomized into either conventional duration(CD group; 8 days) or short duration (SD group; 4 days) of antibiotic therapy. Primary outcome was clinical cure (absence of recurrence of cholangitis at day 30 and >50% reduction of bilirubin at day 15). Secondary outcomes were total days of antibiotic therapy and hospitalization within 30 days, antibiotic related adverse events and all-cause mortality at day 30. Results: The study included 120 patients(mean age was 55.85±13.52 years and 50% were males). Of them, 51.7% patients had malignant aetiology and 76.7% patients had moderate cholangitis. Clinical cure was seen in 79.66% (95%CI, 67.58%- 88.12%) patients in CD group and 77.97% (95%CI, 65.74%-86.78%) patients in SD group (p=0.822). On multivariate analysis, malignant aetiology and hypotension at presentation were associated with lower clinical cure. Total duration of antibiotics required post intervention was lower in SD group (8.58±1.92 and 4.75±2.32 days; p<0.001). Duration of hospitalization and mortality were similar in both the groups. Conclusions: Short duration of antibiotics is non-inferior to conventional duration in patients with moderate to severe cholangitis in terms of clinical cure, recurrence of cholangitis and overall mortality.

Antimicrobial therapy outcomes in acute cholangitis: Hilar multiple obstructions versus single hilar and common bile duct obstructions

“…Clinical cure was defined as the absence of initial presenting symptoms by day 14 after biliary drainage, coupled with no recurrence or death by day 30. 24 , 25 Recurrence was defined as the initiation of a new antibiotic therapy for recurrent cholangitis, subsequent infection in the hepatic–pancreatic–biliary region, or any other subsequent infection possibly related to the initial episode of cholangitis. 5 , 26 , 27 …”

When to Stop Antibiotics in the Critically Ill?

“…In the STOP-IT trial, for patients with severe or complicated intra-abdominal infections who received adequate source control, antibiotics were continued for a fixed duration (4 days) or for 2 days after resolution of signs of infection (total of 8 to 10 days). Patients treated with shorter fixed-durations of antibiotics had similar clinical cure rates to those treated with more prolonged durations [ 27 , 28 ]. The DURAPOP trial of critically ill patients with intra-abdominal infections similarly showed that shorter courses of antibiotics (8 versus 15 days) were associated with more antibiotic-free days while maintaining similar rates of mortality and length of stay [ 29 ].…”

Caution on Interpretation of Noninferiority Trial Results

“…I read with interest the noninferiority randomized controlled trial by Srinu et al (1), which compared 4- and 8-day treatments of moderate-to-severe acute cholangitis. The authors concluded that the short duration (SD) treatment group was noninferior to the conventional duration (CD) group for the primary outcome, clinical cure; however, I do not think they can conclude that from the results.…”