• Abstract and Figures
• Public Full-text

MEDICAL GRAND ROUNDS TAKE-HOME CME MOC Constantine Tsigrelis, MD POINTS FROM Department of Infectious Disease, Cleveland Clinic; LECTURES BY Assistant Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, CLEVELAND Cleveland, OH CLINIC AND VISITING FACULTY Recurrent Clostridioides difficile infection: Recognition, management, prevention ABSTRACT LOSTRIDIOIDES (formerly Clostridium) C difficile)is an anaerobic spore-forming ba- Clostridioides difficile infection (CDI) is the cillus that colonizes the intestinal tract in pa- most common cause of diarrhea in hospi- tients whose normal gut microbiota is disrupt- talized patients and results in substantial ed by antibiotic therapy.1 C difficile produces morbidity, mortality, and costs. Its clinical 2 major toxins—toxins A and B—that cause management, primarily with antibiotics, is intestinal mucosal injury, diarrhea, and colitis, often complicated by recurrent episodes. and in some cases, fulminant infection leading These recurrent CDI episodes are thought to shock, ileus, and toxic megacolon.2 C difficile to be caused by antibiotic disruption of co- infection (CDI) recurs in up to one-quarter or lonic microbiota and usually occur within 4 more of treated patients, complicating its man- weeks of completing antibiotic therapy. The agement. risk of recurrent CDI increases after the first In the United States, C difficile is a com- episode, creating a need for management mon hospital-acquired infection, affecting strategies to diagnose, treat, and prevent about 500,000 patients annually, causing up these complications. to 30,000 deaths, and incurring inpatient costs Diagnosis of nearly $5 billion.2–4 This article reviews the KEY POINTS current standards for diagnosing and treating requires CDI and discusses strategies for managing and unexplained Diagnostic testing for CDI should be per- preventing recurrent disease. formed only in symptomatic patients. new-onset ■ DIAGNOSIS diarrhea Diagnosis is based on unexplained diar- The current standard for diagnosis of CDI re- and a positive rhea and a positive C difficile assay. quires both unexplained new diarrhea and a C difficile assay positive result on a C difficile assay.2,5 Guide- The goal of therapy for recurrent CDI is lines recommend laboratory testing for C dif- to allow the normal colonic microbiota ficile only in patients who have symptoms, de- to restore itself. fined as unexplained new onset of 3 or more unformed stools per day. Also, practitioners Fecal microbiota transplantation has need to rule out use of a laxative (eg, polyeth- ylene glycol) in the preceding 48 hours or a shown efficacy for treating recurrent CDI. history of chronic diarrhea with no change in symptoms. Table 1 lists laboratory assays for Antimicrobial stewardship and infection detecting C difficile toxin or organism.2,5 prevention are key strategies for pre- venting CDI. Colonization vs infection: Is it important? C difficile colonization is the existence of the Medical Grand Rounds articles are based on edited transcripts from organism or toxin in the stool of patients who Medicine Grand Rounds presentations at Cleveland Clinic. They are approved by the author but are not peer-reviewed. do not have unexplained new diarrhea. C dif- doi:10.3949/ccjm.87gr.20001 ficile infection is the existence of the organism CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 87 • NUMBER 6 JUNE 2020 347 Downloaded from www.ccjm.org on September 24, 2021. For personal use only. All other uses require permission. CLOSTRIDIOIDES DIFFICILE TABLE 1 Diagnostic tests for Clostridioides difficile Test Characteristics Sensitivity, specificity Organism detection assays Nucleic acid amplification tests Detects toxin gene (ie, organism) High sensitivity (eg, polymerase chain reaction) but not toxins Low to moderate specificity Glutamate dehydrogenase C difficile common antigen High sensitivity Low specificity Toxigenic C difficile culture Growth of C difficile organism High sensitivity Testing not readily available Low specificity Slow turnaround time Toxin detection assays Enzyme immunoassay Detects free toxins Low sensitivity Moderate specificity Cell culture cytotoxicity Detects free toxins High sensitivity neutralization assay Lacks standardization High specificity, if optimized Slow turnaround time Information from McDonald et al, reference 2. Laboratory or toxin in patients with unexplained new di- • Order a nucleic acid amplification test testing cannot arrhea. Laboratory testing cannot distinguish (NAAT) alone (eg, PCR) between asymptomatic C difficile colonization or distinguish and symptomatic CDI. • Order a stool toxin test as part of a multi- between The prevalence of asymptomatic C diffi- step algorithm: cile stool colonization varies from 3% to 26% 1) NAAT plus toxin test, or asymptomatic in adult hospitalized patients to 5% to 7% in 2) Glutamate dehydrogenase (GDH) C difficile elderly patients in long-term care facilities. plus toxin test, or colonization In asymptomatic adults without any recent 3) GDH plus toxin test, arbitrated by healthcare exposure, the prevalence is less NAAT. and than 2%.2 If the facility does not have a policy to sub- symptomatic A patient presenting with no diarrhea, a mit stool specimens for CDI testing only from positive polymerase chain reaction (PCR) patients who have unexplained new-onset di- CDI test, and a negative enzyme immunoassay arrhea, a NAAT (eg, PCR) test alone is not (EIA) test likely has C difficile colonization. recommended because it increases the chance However, a patient can have a positive EIA of detecting colonization. Instead, the recom- result without symptoms, so the best approach mendation is to perform a stool toxin test as is to carefully assess the patient for unex- part of a multistep algorithm: plained new-onset diarrhea. 1) NAAT plus toxin test, or Institutional policies will determine which 2) GDH plus toxin test, or CDI tests are used. If the policy is to test only 3) GDH plus toxin test, arbitrated by stool specimens from patients with unex- NAAT plained and new onset of at least 3 unformed In addition, repeat C difficile testing is not stools in 24 hours, one has the following op- recommended to evaluate for cure in patients tions2: whose symptoms have improved or resolved. 348 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 87 • NUMBER 6 JUNE 2020 Downloaded from www.ccjm.org on September 24, 2021. For personal use only. All other uses require permission. TSIGRELIS That is because C difficile can continue to be Fulminant cases are characterized by hy- shed in stools for more than 1 month, even potension, shock, ileus, or toxic megacolon. after a patient’s symptoms have resolved.6 Treatment is with vancomycin 500 mg by This is important because treatment of asymp- mouth or nasogastric tube 4 times a day, plus tomatic C difficile carriers with either metro- metronidazole 500 mg intravenously every 8 nidazole or vancomycin has not been shown hours, especially if the patient has ileus. In ad- to be beneficial, and vancomycin can prolong dition, if the patient has ileus, one can consid- C difficile colonization or increase the risk of er rectal installation of vancomycin 500 mg.2 acquiring a new C difficile strain.7 Oral vancomycin therapy for fulminant CDI carries a strong recommendation based ■ TREATMENT OF A FIRST EPISODE on a moderate level of evidence; intravenous metronidazole carries a strong recommenda- The first step in treating CDI is to stop the tion based on a moderate level of evidence, inciting antibiotic therapy as soon as possible. and rectal vancomycin carries a weak recom- Antiperistaltic therapy should be avoided, es- mendation based on a low level of evidence.2 pecially if the patient is not receiving antibi- 2,8 With respect to other therapies for fulmi- otics for CDI. Additionally, empiric anti-C nant CDI, there are limited data regarding the difficile therapy is not recommended unless a use of fidaxomicin. Patients with life-threat- substantial delay in C difficile testing results is ening or fulminant CDI or toxic megacolon anticipated or the patient has fulminant CDI. were excluded from clinical trials evaluating Treatment of initial episodes of CDI, as fidaxomicin.9,10 Additionally, there are limited outlined in clinical practice guidelines from data on the use of fecal microbiota transplan- the Infectious Diseases Society of America tation (FMT) for fulminant CDI.2 (IDSA) and Society for Healthcare Epidemi- ology of America (SHEA),2 is based on the ■ RECURRENT CDI severity of disease. A major clinical challenge is recurrent CDI, Nonsevere cases are defined as those in which usually occurs within 4 weeks after which the white blood cell count remains less completion of anti-C difficile therapy. The risk Stop than or equal to 15.0 × 109/L and the serum of recurrence increases with each episode11,12: creatinine level is less than 1.5 mg/dL. In such the inciting • Up to 20% to 25% after the first CDI epi- cases, there are 3 options for treatment: sode antibiotic • Vancomycin 125 mg by mouth 4 times a • Up to 40% to 45% after the second CDI as soon day for 10 days episode as possible • Fidaxomicin 200 mg by mouth twice a day • More than 60% to 65% after 3 or more for 10 days (more about this agent below) CDI episodes. to avoid • Metronidazole 500 mg by mouth 3 times a It is recommended that patients with CDI increasing day for 10 days (if access to vancomycin or be counseled regarding the risk of recurrence. fidaxomicin is limited). If a patient’s diarrhea initially improves, but the risk of The first 2 options carry strong recom- the patient subsequently develops new-onset recurrent CDI mendations based on high levels of evidence, or worsening diarrhea after CDI treatment is whereas the third has a weak recommendation completed, the recommendation is to submit 2 based on a high level of evidence. a stool sample for CDI testing to evaluate for Severe cases are those in which the white recurrent CDI. However, in the absence of blood cell count is 15.0 × 109/L or higher or new-onset or worsening diarrhea, repeat test- the serum creatinine level is higher than 1.5 ing for CDI is not recommended to avoid the mg/dL.

Load more

  13

Copy Link