The current study examined the correlation between gut bacterial composition of CDI patients and antibiotic treatment received prior to infection onset. The epidemiological data of the study population was in correlation with the known characteristics of CDI patients, i.e., older age and high mortality rate. Additionally, the numbers of nosocomial- and community-acquired cases were similar to earlier reports.17 Recently, the prevalence of community-acquired infections has increased due to elevated use of antibiotics that were previously only administered in hospitals via intravenous infusion.17
Most patients were diagnosed with mild disease, while only a few were diagnosed with severe disease. These results point to an increase in the prevalence of moderate-severe CDI compared to a study conducted in 2016 in northern Israel which found that most patients had mild disease, a few had moderate disease, and none were diagnosed with a severe disease.18 This increase in disease severity can be attributed to an increase in antibiotic resistance or emergence of more virulent strains.1
The majority of patients received one or two classes of antibiotics prior to CDI onset, corresponding with previous reports demonstrating that one type of antibiotic is sufficient to induce CDI.4 Cephalosporins and penicillins were the most commonly used antibiotics, two drugs which have previously been shown to significantly increase the risk of CDI as compared to other antibiotics.4,19−20 Fluoroquinolone and clindamycin have also been highly correlated with CDI development, yet, in our study, only a small percentage of patients received these antibiotics.
Examination of intestinal bacterial populations of CDI patients and their correlation with previous antibiotic treatment, showed that there was no phylum- and family-level composition common to all CDI patients, as has been described in other studies.21–23 In their study comparing the gut microbiome profile of CDI versus non-CDI patients, Manges et al. found an increase in Firmicutes, Proteobacteria and Actinobacteria phyla, as well as a decrease in Bacteroidetes.24Antharam et al., surveying the distal gut microbiota of individuals with CDI, found that these patients had significantly less diverse communities, particularly a less diverse Firmicutes population than patients with non-CD diarrhea or healthy controls.21 In addition, there was depletion of gut commensals such as the Ruminococcaceae and Lachnospiraceae families and butyrate-producing anaerobic fermenters. This lack of uniformity can be explained by the various factors affecting the intestinal bacteria, such as nutrition,25 although we tried to control for these factors during data analysis. More specifically, several parameters (such as age, gender, and disease severity) were tested, yet none had significant effects on bacterial population. In contrast, we found that the antibiotic combination administered to CDI patients before disease onset correlated with the intestinal microbiota. Patients who had received four classes of antibiotics had more similar microbiomes. In addition, an inverse correlation between bacterial richness and the number of antibiotics received was noted, with significant differences between patients who received four classes of antibiotics versus those who received one or two classes of antibiotics. These findings can likely be ascribed to the broader range of bacterial species targeted by multi-class antibiotic treatment regimens, which subsequently leads to reduced microbiota richness. A limitation of this study was the lack of a comparison to the gut microbiome of healthy individuals, due to the difficulty in finding healthy elderly controls. Such a comparison may have provided insights into the importance of the gut microbiota's capability of providing colonization resistance against C. difficile.