Infectious Diseases I

Enzyme immunoassay (EIA) tests for C. difficile toxins A and B are rapid and widely available;

however, poor sensitivity may limit their utility. Obtaining serial samples has been used to increase

sensitivity. Sensitivity may also be increased using a two-step process with initial EIA to detect

the C. difficile antigen glutamate dehydrogenase and a follow-up stool culture with detection of the

toxigenic isolate.

The nucleic acid amplification test (NAAT) involves an illumigene C. difficile assay, which uses

loop-mediated isothermal DNA amplification to detect a specific genetic region responsible for

coding toxins A and B. It is recommended to only test patients with symptoms of CDI using NAAT

because of risk of potential false-positive results.

Recommended laboratory diagnostic pathways differ regarding whether an institution-specific protocol

for stool sample quality based on CDI likelihood is predefined. Briefly, the absence of predefined

criteria requires a multistep laboratory process that includes a toxin test (e.g., NAAT plus toxin assay)

rather than a NAAT alone. In contrast, the presence of predefined criteria for stool quality and clinical

presentation suggestive of CDI permits the use of NAAT alone or a multistep process over a strategy

using a toxin assay alone.

The same diagnostic criteria are used for recurrent CDI.

Management and Treatment

Removal of potential cause(s), as appropriate (e.g., discontinuation of associated antibiotic therapy)

Evaluation of need for surgical intervention

Subtotal colectomy with rectal preservation should be considered for severely ill patients.

Alternative colon-sparing operative surgical strategies have been described.

Antibiotic therapy targeted against C. difficile (Table 3)

Samples for diagnostic testing for C. difficile should be obtained before empiric antibiotic therapy

is initiated. Initiation of empiric antibiotic therapy before final test results should be based on

clinical assessment.

Antibiotic choices and respective routes of administration should be based on severity of CDI

and ability to achieve relevant intraluminal antibiotic concentrations relative to CDI. Special

considerations include:

Fidaxomicin, an oral, limited-bioavailability macrolide antibiotic, is indicated for treatment

of CDI. The 2021 IDSA/SHEA focused guideline update recommends (conditional

recommendation; moderate certainty of evidence) fidaxomicin as first-line therapy for first

episode, non-fulminant CDI when access to fidaxomicin is not inhibited by limited resources.

This recommendation is supported by systematic review and meta-analysis of four studies

noting increased sustained response to therapy at 4 weeks with fidaxomicin compared to oral/

enteral vancomycin. Initial cure, all-cause mortality, and drug adverse events were similar

between fidaxomicin and vancomycin. Data supporting fidaxomicin use in critically ill patients

are limited to small representative sample sizes and retrospective or observational studies.

ii.

Oral or enteral vancomycin continues to be an alternative for an initial episode of CDI when

access to and availability of fidaxomicin is limited. The optimal enteral vancomycin dosage

in critically ill patients is unknown. Although ACG and IDSA guidelines recommend enteral

vancomycin dosages of 125 mg four times daily for uncomplicated/nonfulminant CDI (Table

3), some practices consider dosages of 250 mg four times daily if there is lack of response or

if there is concern for subclinical GI dysmotility (e.g., incomplete enteral nutrition tolerance,

elevated gastric residuals, abdominal distention) (Int J Antimicrob Agents 2013;42:553-8; Clin

Infect Dis 2015;61:934-41).