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
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
haematopoietic stem cell transplant recipients
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
gastrointestinal surgery
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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