Melatonin as an Antimicrobial Adjuvant and Anti-Inflammatory for the Management of Recurrent Clostridioides difficile Infection

Abstract

Background: Clostridioides difficile (C. difficile) infection (CDI) is strongly associated with inflammation and has the potential to cause recurrent infections. Pre-clinical data suggest that melatonin has beneficial effects in the gastrointestinal tract due to its anti-inflammatory and antibacterial properties. This analysis examines the association between melatonin and the risk of recurrent CDI. Methods: A retrospective cohort study was conducted among patients with an inpatient diagnosis of CDI along with a positive C. difficile polymerase chain reaction (PCR) or enzyme immunoassay (EIA) test result. Patients were followed until the first study end point (death) or the first instance of recurrent infection. Propensity-score weighting was utilized accounting for confounding factors and weighted Cox models were estimated. Results: A total of 24,782 patients met the inclusion criteria, consisting of 3457 patients exposed to melatonin and 21,325 patients with no melatonin exposure. The results demonstrate that those exposed to melatonin were associated with a 21.6% lower risk of recurrent CDI compared to patients without melatonin exposure (HR = 0.784; 95% CI = 0.674–0.912). Conclusion: Our results demonstrate a decreased rate of recurrent CDI in patients exposed to melatonin. Further research on melatonin as an antimicrobial adjuvant and anti-inflammatory is warranted for the management of recurrent CDI.

A Systematic Literature Review on Risk Factors for and Timing of Clostridioides difficile Infection in the United States

“…Fifteen studies assessed the impact of age on the risk of rCDI, eight of which found a significantly increased risk; however, results were not consistent across all age groups. In the database study by Ma et [20,44,106,[108][109][110][111][112][113][114][115][116], though two studies reported an increased risk for women [106,115]. In the large database study by Ma et al, women were at higher risk of rCDI compared with men (aOR 1.24, 95% CI 1.11-1.38; p \ 0.001) [106].…”

“…In eight of 15 studies on antibiotics, a significantly increased risk of rCDI was found. The classes or types of antibiotics used were compared in five of these studies [20,111,112,117,118]. Use of clindamycin, fluoroquinolones, third-or fourth-generation cephalosporins, ceftriaxone, or piperacillin/ tazobactam prior to the initial CDI event were risk factors for rCDI.…”

“…For cephalosporins, Appaneal et al, reported an aOR of 1.92 (95% CI 1.13-3.25) with first-or second-generation cephalosporins [117]. Sutton et al, reported a higher risk of rCDI when primary CDI was treated with fidaxomicin compared with vancomycin or vancomycin combinations, although only a small proportion of patients were treated with fidaxomicin [111]. During their CDI treatment, patients receiving vancomycin had a decreased risk of developing rCDI in comparison with patients receiving fidaxomicin (aHR 0.335, 95% CI 0.204-0.548; p value not presented) [111].…”

“…Sutton et al, reported a higher risk of rCDI when primary CDI was treated with fidaxomicin compared with vancomycin or vancomycin combinations, although only a small proportion of patients were treated with fidaxomicin [111]. During their CDI treatment, patients receiving vancomycin had a decreased risk of developing rCDI in comparison with patients receiving fidaxomicin (aHR 0.335, 95% CI 0.204-0.548; p value not presented) [111]. In contrast, a largescale study by Hall et al, found that rCDI was reduced in patients who were treated with fidaxomicin during initial CDI compared with vancomycin (aHR 0.67, 95% CI 0.50-0.90; p value not presented) [119].…”