Risk factors for Clostridium difficile infections – an overview of the evidence base and challenges in data synthesis

Abstract

BackgroundRecognition of a broad spectrum of disease and development of Clostridium difficile infection (CDI) and recurrent CDI (rCDI) in populations previously considered to be at low risk has renewed attention on differences in the risk profile of patients. In the absence of primary prevention for CDI and limited treatment options, it is important to achieve a deep understanding of the multiple factors that influence the risk of developing CDI and rCDI.MethodsWe conducted a review of systematic reviews and meta–analyses on risk factors for CDI and rCDI published between 1990 and October 2016.Results22 systematic reviews assessing risk factors for CDI (n = 19) and rCDI (n = 6) were included. Meta–analyses were conducted in 17 of the systematic reviews. Over 40 risk factors have been associated with CDI and rCDI and can be classified into three categories: pharmacological risk factors, host–related risk factors, and clinical characteristics or interventions. Most systematic reviews and meta–analyses have focused on antibiotic use (n = 8 for CDI, 3 for rCDI), proton pump inhibitors (n = 8 for CDI, 4 for rCDI), and histamine 2 receptor antagonists (n = 4 for CDI) and chronic kidney disease (n = 4 for rCDI). However, other risk factors have been assessed. We discuss the state of the evidence, methods, and challenges for data synthesis.ConclusionSeveral studies, synthesized in different systematic review, provide valuable insights into the role of different risk factors for CDI. Meta–analytic evidence of association has been reported for factors such as antibiotics, gastric acid suppressants, non–selective NSAID, and some co–morbidities. However, despite statistical significance, issues of high heterogeneity, bias and confounding remain to be addressed effectively to improve overall risk estimates. Large, prospective primary studies on risk factors for CDI with standardised case definitions and stratified analyses are required to develop more accurate and robust estimates of risk effects that can inform targeted–CDI clinical management procedures, prevention, and research.

Peer Review #2 of "Machine learning analysis to identify the association between risk factors and onset of nosocomial diarrhea: a retrospective cohort study (v0.2)"

“…After 5 days of use, its use Manuscript to be reviewed slowly increased the risk. Although previous studies revealed that antibiotic use is an important risk factor for nosocomial diarrhea (McFarland, 1995;Arevalo-Manso et al, 2014;Eze et al, 2017), this convex upward association could be a new finding. A recent study showed that the diversity of gut microbiome is affected by antibiotic administration and that the component of gut microbiome changes with time (Bulow et al, 2018).…”

“…The following variables were considered as risk factors or confounding factors for nosocomial diarrhea and were included in the analysis: age, sex, severity of illness, and number of days of use of tube feeding, PPI, H2RA, and antibiotics (McFarland, 1995;Kyne et al, 2002b;Thorson, Bliss & Savik, 2008;Arevalo-Manso et al, 2014;Eze et al, 2017;Thabit, Varugehese & Levine, 2019). The modified Rankin Scale (mRS) (van Swieten et al, 1988) was used as the index of disease severity and was scored 2 days after admission.…”

“…It increases length of stay and healthcare costs (Kyne et al, 2002a) and is important for hospital infection control. Several risk factors for nosocomial diarrhea have been identified, including history of hospitalization, gastrointestinal surgery, severity of disease, and tube feeding, proton pump inhibitor (PPI), histamine 2-receptor antagonist (H2RA), and antibiotic use (McFarland, 1995;Kyne et al, 2002b;Thorson, Bliss & Savik, 2008;Arevalo-Manso et al, 2014;Eze et al, 2017;Thabit, Varugehese & Levine, 2019). However, details about association between these risk factors and the onset of nosocomial diarrhea remains unclear.…”

Host factors are more important in predicting recurrent Clostridium difficile infection than ribotype and use of antibiotics

“…Several previous studies have provided valuable insights into the role of different risk factors for recurrent CDI [17]. However, to our knowledge, we are the first to provide insight into the risk factors for development of recurrent CDI during an outbreak.…”

Clostridioides difficile -Associated Antibiotics Alter Human Mucosal Barrier Functions by Microbiome-Independent Mechanisms

“…A clinically relevant risk factor for CDAD is recent antibiotic treatment (12). There is substantial evidence supporting a causal link between microbiome disruption by antibiotics and CDAD (reviewed in (13)); however, the antibiotic effect on the microbiome seems unlikely to be the sole causal mechanism for CDAD.…”