History and exam

Key diagnostic factors

common

presence of risk factors

Key risk factors include antibiotic exposure, advanced age, hospitalisation or residence in a nursing home, and history of Clostridioides difficile-associated disease.

diarrhoea

May range from loose stools to severe diarrhoea; absence of diarrhoea may be related to toxic megacolon or paralytic ileus.

abdominal pain

May be mild or absent but can be severe, especially in fulminant colitis.

Other diagnostic factors

common

fever

May be low grade in mild cases.

abdominal tenderness

Often present, especially in lower abdomen.

uncommon

nausea and vomiting

May be absent.

abdominal distension

May be absent.

symptoms of shock

Systemic symptoms of shock including hypotension and tachycardia with severe abdominal pain and tenderness suggest fulminant colitis.

Risk factors

strong

antibiotic exposure

  • The most common antibiotics involved are ampicillin, cephalosporins, clindamycin, carbapenems, and fluoroquinolones, especially in the preceding 3 months.[21][22]

  • Cephalosporins (third- and fourth-generation) and carbapenems are most strongly associated with healthcare facility-associated infection; modest associations were also noted for fluoroquinolones, clindamycin, and beta-lactamase inhibitor/penicillin combinations.[25]

  • An analysis of the Food and Drug Administration adverse event reporting system found that lincosamides (e.g., clindamycin) had the greatest proportion of reports of Clostridioides difficile infection, followed by monobactams, beta-lactamase inhibitor/penicillin combinations (e.g., piperacillin/tazobactam), carbapenems, cephalosporins, tetracyclines, macrolides, fluoroquinolones, and trimethoprim/sulfamethoxazole.[26] However, a meta-analysis suggests that tetracyclines may be associated with a decreased risk of infection compared with other antibiotics.[27]

  • Restricting the use of fluoroquinolones appeared to reduce the incidence of C difficile infection in England. Antimicrobial stewardship should be a central component of C difficile infection control programmes.[28] One meta-analysis found that stewardship programmes have been shown to significantly reduce the incidence of C difficile infections by 32% in hospital inpatients, and were more effective when implemented with infection-control measures.[29]

  • Patients with an allergy to penicillin may be at an increased risk of infection due to the use of beta-lactam antibiotic alternatives (e.g., fluoroquinolones) in these patients.[30]

advanced age

  • Patients of advanced age are at increased risk of C difficile infection.[10]​​​

hospitalisation or residence in a nursing home

  • C difficile infection is the most important cause of nosocomial diarrhoea in adults. Asymptomatic carriers of toxigenic C difficile increase the risk of infection in other patients in hospitals.[31] The risk of infection increases with length of hospital stay.

exposure to infected family member

  • Exposure to a family member with C difficile infection is associated with an increased risk of infection. A case-control study of 224,000 cases of C difficile infection found that 4.8% of infections occurred following a diagnosis in a separate family member. In an adjusted analyses, the incidence was nearly 13 times higher among people exposed to an infected family member compared with unexposed people.[24]​​

history of Clostridioides difficile-associated disease

  • Recurrence rates have been reported to vary from 5% to 50%, although one study found at least one recurrence in 21% of healthcare-associated infections and 14% of community-associated infections.[6]

  • A small number of patients have repeated relapses, necessitating several courses of treatment.[21]

use of acid-suppressing drugs

  • Proton-pump inhibitors (PPIs) have been associated with an increased risk of C difficile infection.[32][33][34]​​​[35]​ The association between PPI use and C difficile infection is controversial and there is much debate about it. However, a meta-analysis of controlled observational studies found that there is a significant risk of C difficile infection among patients on PPIs, especially in patients on general wards.[36]​ Older patients also appear to be at increased risk.[37]

  • The effect may also be seen with H2 antagonists; however, a meta-analysis found that the risk of hospital-acquired C difficile infection is 38.6% greater with PPIs compared with H2 antagonists.[38]

inflammatory bowel disease

  • Patients with inflammatory bowel disease are at increased risk of primary C difficile infection and recurrent disease, as well as increased morbidity and mortality from infection.[39][40] Infection was associated with increased mortality in patients with ulcerative colitis, but not in patients with Crohn's disease.[41] Risk factors for C difficile infection in patients with inflammatory bowel disease include use of antibiotics within 30 days of diagnosis, use of biological agents for the treatment of the condition, and colon involvement in patients with Crohn's disease.[42]

solid organ transplant recipients

  • Rates of C difficile infection are 5-fold higher in this population compared with general medicine patients.[43]​​[44]

haematopoietic stem cell transplant recipients

  • Rates of C difficile infection are 9-fold higher in this population compared with hospitalised patients overall.[45] Prevalence was higher among allogeneic transplant patients compared with autologous transplant patients.[46]

chronic kidney disease

  • Rates of C difficile infection are 2- to 2.5-fold higher in this population, with an increased risk in patients with end-stage renal disease.[47]

HIV infection

  • Patients are at increased risk due to underlying immunosuppression, exposure to healthcare settings and antibiotics, or a combination of these factors.[48]

weak

immunosuppressive agents or chemotherapy

  • An association between the use of immunosuppressants and the development of C difficile infection has been reported, as well as an increased risk of complicated outcomes.[49][50]

gastrointestinal surgery

  • An association between gastrointestinal surgery and C difficile infection has been reported.[51] However, a meta-analysis found that the incidence of infection in patients who undergo colorectal surgery is very low, regardless of the bowel preparation regimen used.[52]

  • One systematic review found the overall incidence of C difficile infection in patients undergoing ileostomy closure to be 1.8%.[53]

  • One systematic review and meta-analysis found the overall incidence of C difficile infection in patients undergoing stoma reversal to be 2.1%.[54]

vitamin D deficiency

  • A meta-analysis suggests that low serum levels of 25-hydroxyvitamin D are associated with an increased risk for C difficile infection; however, this is based on weak evidence.[55]

consumption of C difficile contaminated food

Contamination of food with C difficile spores is known to occur (e.g., from environmental or hand contamination). Therefore, consumption of contaminated food may be a risk factor for transmission. The overall prevalence of C difficile in various foods was 6.3%, with the highest levels found in seafood.[56]

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