Clostridioides difficile Infection: Diagnosis and Treatment Challenges

Abstract

Clostridioides difficile is the most important cause of healthcare-associated diarrhea in the United States. The high incidence and recurrence rates of C. difficile infection (CDI), associated with high morbidity and mortality, pose a public health challenge. Although antibiotics targeting C. difficile bacteria are the first treatment choice, antibiotics also disrupt the indigenous gut flora and, therefore, create an environment that is favorable for recurrent CDI. The challenge of treating CDI is further exacerbated by the rise of antibiotic-resistant strains of C. difficile, placing it among the top five most urgent antibiotic resistance threats in the USA. The evolution of antibiotic resistance in C. difficile involves the acquisition of new resistance mechanisms, which can be shared among various bacterial species and different C. difficile strains within clinical and community settings. This review provides a summary of commonly used diagnostic tests and antibiotic treatment strategies for CDI. In addition, it discusses antibiotic treatment and its resistance mechanisms. This review aims to enhance our current understanding and pinpoint knowledge gaps in antimicrobial resistance mechanisms in C. difficile, with an emphasis on CDI therapies.

“Primum, non nocere”: The Epidemiology of Toxigenic Clostridioides difficile Strains in the Antibiotic Era—Insights from a Prospective Study at a Regional Infectious Diseases Hospital in Eastern Europe

“…This includes individuals with no prior antibiotic exposure, young individuals, those without comorbidities, children, and pregnant women [8][9][10]. Conversely, therapeutic alternatives remain considerably constrained and have not demonstrated resounding success in effectively managing recurrent episodes [11][12][13][14].…”

“…Initially identified within healthcare facilities in Canada and the USA in 2003 [24], this strain presents unique challenges in terms of management, attributed to its potential for hypervirulence. This particular ribotype is linked to a more severe manifestation of the disease, with an observed increase in recurrence frequency, owing to its heightened resistance to antibiotic therapy [11,[24][25][26][27][28]. RT 027 has the capability to generate the binary toxin CDT (CD transferase) which comprises CDTa, the enzyme component responsible for ADP ribosyltransferase activity, and CDTb, which facilitates toxin binding, entry, endosome formation, and subsequent delivery into the cytosol.…”

Usefulness of Capillary Gel Electrophoresis-Based PCR for Detection of Clostridioides difficile Strains with Hypervirulent Ribotypes

“…It typically arises from prolonged therapy with clindamycin, third-and fourth-generation cephalosporins, fluoroquinolones, and proton pump inhibitors [21,22]. Additional factors contributing to the development of the disease include advanced age, compromised immunity, and hospitalization [23,24]. It is important to note that C. difficile infections (CDI) are gaining increased attention from clinicians around the world due to the continued rise in the number of cases of these infections [24,25].…”

“…The prevalent diagnostic criteria typically involve diarrhea, manifesting at least five times daily, along with symptoms indicative of toxic megacolon (toxic colonic dilatation syndrome). Additional indicators encompass abdominal pain, elevated fever, escalating leukocytosis, clinical signs of peritonitis and an overall deterioration of health [23,28].…”

“…The disease's progression is linked to an imbalance in the intestinal microbiota's homeostasis due to prolonged antibiotic exposure. The pathogenesis involves an elimination of certain competing bacteria which reduce environmental pressure, facilitating an unrestricted proliferation of C. difficile [23,28]. An excessive pathogen proliferation is further promoted by virulence factors: toxin A (tcdA) and toxin B (tcdB), encoded at the pathogenicity locus (PaLoc), which inactivate Rho and/or Ras GTPases by glucosylation [29,30].…”