C.

difficile Infection
By Kevin W. Garey, Pharm.D., M.S.
Reviewed by Amy Pakyz, Pharm.D., M.S., BCPS; and Clarence Chant, Pharm.D., FCSHP, FCCP , BCPS

Learning Objectives

Epidemiology and Economics
According to the Centers for Disease Control and
Prevention (CDC), the annual incidence of CDI in the
United States exceeds 250,000 hospitalized cases with
a mortality rate of 1% to 2.5%. The annual costs caused
by CDI ranges from $433 million to $797 million. The
increased incidence of CDI in industrialized countries is
likely caused by many factors involving the host, microbe,
and health care environment (Table 3-1). An aging population with a decreased immune response and increased
exposure to the health care environment and hospital
procedures are classic risk factors for CDI. The epidemic
strain produces increased quantities of toxin, has a higher
rate of sporulation, and shows increased virulence compared with the non-epidemic strain.
Drugs that reduce colonic flora, usually broad-spectrum antibiotics, remain the most important component
in the pathogenesis of CDI. Although almost all antimicrobials have been implicated as causative agents
for CDI, broad-spectrum antibiotics or antibiotics that
eliminate anaerobic flora generally are the most highly
implicated. Decreasing the use of clindamycin and
third-generation cephalosporins can reduce CDI rates.
Although replacement of the offending antimicrobial
may reduce individual risk, a focus on overall reduction of total dose or total days of antibiotic exposure is
likely the best method to decrease CDI rates. The use
of fluoroquinolones has been associated with the BI/

1. Classify risk factors for Clostridium difficile infection (CDI) on the basis of epidemiologic definitions
and risk factors.
2. Stratify CDIs on the basis of presenting severity of
infection.
3. Design a nonpharmacologic treatment plan for a
patient with CDI.
4. Design a pharmacologic treatment plan for a patient
with new or recurrent CDI.

Introduction
History
First described in 1978, Clostridium difficile infection (CDI) has emerged during the past 3 decades as the
most important enteric disease associated with health
care settings. Underscoring the growing importance of
CDI management, mortality rates in the United States
increased from 5.7 per million in 1999 to 23.7 per million in 2004.
Current epidemic rates of CDI in the United States,
Canada, and Europe have been associated with a
hyper-virulent strain (i.e., BI/NAP1/027). This strain
is associated with increased toxin production and
increased mortality and morbidity. This chapter focuses
on the evolving epidemiology of CDI and updated treatment recommendations.

Baseline Review Resources
The goal of PSAP is to provide only the most recent (past 3–5 years) information or topics. Chapters do not provide an overall review. Suggested resources for background information on this topic include:
• Kelly CP, LaMont JT. Clostridium difficile—more difficult than ever. N Engl J Med 2008;359:1932–40.
• Cohen SH, Gerding DN, Johnson S, Kelly CP, Loo VG, McDonald LC, et al. Clinical practice guidelines
for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of
America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol
2010;31:431–55.

PSAP-VII • Infectious Diseases

193

C. difficile Infection

Risk factors for CA-CDI are similar to health care–associated CDI. difficile. gram-positive spore-bearing bacillus. leading to propagation of C. they are not recommended. the disease is classified as CA-CDI. and a dose response-effect has been shown..e. C. PPIs have been shown to be a primary risk factor for CDI recurrence. Fluoroquinolones may also increase the risk of CDI in the community. masks) are not recommended. If the patient was admitted to a hospital more than 12 weeks before the onset of CDI. IL = interleukin. These agents are thought to facilitate the survival of the vegetative forms of C. where growth is favored Increased levels of IL-8 associated with increased risk of primary and recurrent CDI In community-onset CDI. Use of gowns and gloves is also important to prevent transmission to other patients by health care workers. Elimination of the normal intestinal flora by the use of broad-spectrum antibiotics allows germination of C. difficile. nosocomial). and hospitalization Antibiotic depletion of colonic flora during antimicrobial therapy predisposes to CDI.g.. Risk of CDI with PPI use also appears to be highly correlated with the number of antibiotics a patient is given. difficile in the small bowel with eventual colonization in the colon. The use of gastric acid suppressant agents. skin. release of toxins in colon is mediated by microbial-host interactions Colonization resistance is decreased. comorbidities. difficile through the stomach to the bile-rich small bowel. Although recent studies have shown aerosolization of C. has also emerged as a risk factor for CDI. Progression from colonization to active disease is associated with a lack of immunoglobulin response to colonization and host genetics in the interleukin (IL)-8 promoter gene associated with the inflammatory response to infection. Although the relationship between PPIs and CDI is not as well defined as the one between antibacterials and CDI. previous hospitalization Persistence of spores may lead to CDI weeks to months after initial within the past 4 weeks to 6 months has often occurred disease upon regrowth of vegetative phase and release of toxins The importance of CDI in developing countries CDI may be more common in developing countries than in needs additional study industrialized regions CDI = Clostridium difficile infection. Hospital-onset CDI is when the patient receives a diagnosis of CDI after 48 hours of admission. difficile and conversion from spores to vegetative forms of C. routine aerosol precautions (e. difficile. especially underlying gastrointestinal disease. but the patient was discharged from a hospital less than 4 weeks earlier. Prevention methods for CDI include adherence to infection control procedures. particularly proton pump inhibitors (PPIs). As the number of antibiotics a patient is given increases. fluoroquinolones implicated in current epidemic Use of proton pump inhibitors and histamine-2 receptor blockers Host polymorphism in the IL-8 gene promoter Microbial-Environmental-Host Interactions Environmental presence of spores spread by hands. thus. C. difficile Infection 194 PSAP-VII • Infectious Diseases . difficile is an anaerobic. as evidenced by a recent case series of four international travelers with diarrhea treated with ciprofloxacin who developed CDI. Emerging Epidemiology and Risk Factors for CDI Host Risk Factors Advanced age. If symptoms occur outside the hospital. Although there is considerable overlap in their Table 3-1. difficile by decreasing the acidic environment.after contact with the patient or patient surroundings remains the cornerstone of prevention techniques for infection control with CDI. leading to release of toxins A and B Inhibition of gastric acid facilitates the transit of vegetative C. Abbreviations in This Chapter CA-CDI CDI IDSA PCR PPI Community-associated CDI Clostridium difficile infection Infectious Diseases Society of America Polymerase chain reaction Proton pump inhibitor NAP1/027 strain. this is considered hospital associated as well (i. possibly aerosolization to patients. the additional risk posed by PPI tends to decrease. including receipt of an antibiotic in the previous 4 weeks or contact with an infant. community-associated CDI (CA-CDI) is increasingly being recognized in children and adults. the case is classified as community onset but health care associated. the case is classified as indeterminate. If a patient was admitted between 4 and 12 weeks before CDI symptom onset. Previously thought to be a disease of hospitalized patients. difficile produces disease by the elaboration of two toxins. Alcohol-based hand sterilization agents promote spore formation with C. Thorough hand washing with soap and water Microbiology and Pathophysiology C.

leukocytosis. lack of disease recurrence. In mild cases. The dual-study diagnostic approach of GDH antigen screening followed by ELISA identification has a turnaround time of 4 hours. There are no data to support higher oral vancomycin doses. and symptoms of CDI include diarrhea. although the likelihood of detecting false positives increases with this technique and is not recommended. difficile using ELISAs. Long-term use of metronidazole is associated with irreversible neurotoxicity. There is no rationale in prolonging metronidazole treatment beyond 14 days because this drug acts by secretion into the colonic lumen. and initiating anti–C. fever. Clinical Presentation C. followed by screening of the positive isolates by rapid toxin A/B ELISA assay or cell culture cytotoxicity assay. but they require more time (at least 2 days) and are more labor-intensive. After two CDI recurrences. Although most patients experience treatment success. tissue culture cytotoxicity for toxin B. difficile disease can range from an asymptomatic carrier state to antibiotic-associated diarrhea. fever. Historically. The wide range of disease may be related to host immune response and virulence factors of the organism itself. and peripheral leukocytosis. some clinicians have advocated for multiple testing of C. Although not labeled for this indication. In addition. The deletion of tcdC is associated with increased toxin production. recurrences do not usually result in increased disease severity. Pharmacotherapy Discontinuing predisposing antibiotics. Notable microbiologic characteristics of the BI/NAP1/027 strain are the presence of an additional binary toxin of unknown significance and a deletion of the tcdC gene. toxin A (enterotoxin) induces an inflammatory reaction leading to fluid accumulation. 500 mg every 6 hours) for severely ill patients on the basis of expert Diagnosis of CDI The tests available for CDI diagnosis are enzymelinked immunoassay (ELISA) for toxins A and B. Treatment Goals The treatment goals for CDI include resolution of diarrhea and other signs and symptoms of disease (sometimes referred to as clinical or treatment success). abdominal pain. and fulminant colitis. difficile Infection . and rising creatinine concentrations that can progress to kidney failure. Antibiotic treatment is chosen on the basis of clinical disease including severity of diarrhea. Severe complications can include abdominal perforation and peritonitis. the tissue culture assay and culture are the most sensitive. difficile spores that germinate after CDI therapy discontinuation. The epidemic strain is resistant to gatifloxacin and moxifloxacin. difficile antibiotics form the treatment framework (Box 3-1). The standard dose of oral vancomycin is 125 mg four times/ day for 10–14 days (see Box 3-1). Characteristic signs. optimal intravenous therapy for patients unable to tolerate oral antibiotics does not exist. it may become the preferred diagnostic test in hospitals with real-time PCR capabilities because of its fast turnaround time and relative ease of use. the risk that additional episodes will occur increases to 65%.5–15 mg/kg in children) three times/ day for 10–14 days (Table 3-2).S. Because of the sensitivity of the GDH in identifying CDI. if possible. Oral vancomycin has U. Real-time polymerase chain reaction (PCR) has been employed to detect CDI rapidly and identify the hypervirulent strain. Recurrent disease is observed in about 20% of patients and is generally caused by the intraluminal persistence of C.for the glutamate dehydrogenase (GDH) antigen. although the sensitivity of these assays is not as good as the cytotoxicity assay. Oral metronidazole and oral vancomycin are the antibiotics most often used to treat CDI.e. discontinuation of the offending antibiotic is usually enough. The presence of inflammatory bowel disease worsens the course of CDI. Of these. Increased requirement for colectomy has been observed with the BI/NAP1/027 strain. In general. metronidazole has historically been more commonly used because of lower cost. generally occurring within 5 days of illness onset. the guidelines recommend higher doses (i. For these reasons. a two-step algorithm has been investigated to facilitate the evaluation of many stool specimens for CDI and to provide more rapid diagnosis. and acute kidney failure. negative results can be assumed negative for the organism. and culture of the organism. however. and no other serious sequelae of disease. pseudomembranous colitis. whereas toxin B (cytotoxin) is primarily responsible for the destruction of cell cytoskeleton. optimal therapy to prevent disease recurrence is an unmet medical need. Food and Drug Administration (FDA) label approval for the treatment of CDI. The standard initial therapy for metronidazole is 500 mg orally (7. Laboratory findings of severe disease include hypoalbuminemia. ileus. and serum creatinine concentration should be considered when initiating treatment because these predict poor outcomes. age. Recurrence risk may be higher if the patient is exposed to antibiotics in the first 6 weeks after a CDI episode. a negative regulator of toxin A and B production. which is negligible once watery diarrhea is contained. nausea.. pseudomembranous colitis. The first step is an assay PSAP-VII • Infectious Diseases 195 C. More recently. malaise. lack of requirement for colectomy. white blood cell count. Age. most hospitals use an ELISA. function.

Oral vancomycin capsules are expensive.g.g. as recommended for treatment of the initial CDI episode. correction of fluid and electrolyte imbalances).org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/ cdiff2010a. b Recommendation of high-dose oral vancomycin in severe cases is made on the basis of expert opinion. Oral vancomycin is not absorbed into the systemic circulation and is concentrated in the stool irrespective of the consistency. initiate empiric treatment. a dose of 125 mg every 3 days for 3 weeks) strategy ƒƒIf oral therapy is not possible: metronidazole 500 mg TID intravenously for 10–14 days plus retention enema of vancomycin 500 mg in 100 mL of normal saline every 4–12 hours and/or vancomycin 500 mg every 6 hoursb by nasogastric tube a Do not use metronidazole beyond the first recurrence of CDI or for long-term therapy because of the potential for cumulative neurotoxicity. or if the disease is severe. the intravenous vancomycin formulation is used to make an oral solution to decrease costs. Available at www. 2011. clearly induced by antibiotic use. Although not an FDA-labeled indication.. Other factors for severe disease were presence of two or more of the following factors: age older than 60 years. In 2007.g. Other measures are C. McDonald LC. no signs of severe colitis). difficile Infection (CDI) •• Discontinue therapy with the inciting antimicrobial agent(s) as soon as possible because this may influence the risk of CDI recurrence. the compounded solution has been used in clinical trials with good results. Loo VG. a prospective. Clinical Practice Guidelines for Clostridium difficile Infection in Adults: 2010 Update by he Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA).pdf. Johnson S. Information from: Cohen SH. after three or four days or for clinical instability). Treatment of C. Patients were considered to have severe disease if they showed endoscopic evidence of colitis or were admitted to the intensive care unit. •• Treatment of the first recurrence of CDI is usually with the same regimen as for the initial episode and should be stratified by disease severity (mild to moderate.idsociety.. Vancomycin given intravenously is not effective for the treatment of CDI. and in many hospitals. or severe complicated). The therapeutic plan for CDI should also include the provision of supportive care (e. Gerding DN. •• Observe patients closely for any signs of clinical deterioration and place on therapy immediately if this occurs. 196 PSAP-VII • Infectious Diseases . •• Treatment of an initial episode: ƒƒIf oral therapy is possible: ‚‚ Nonsevere: metronidazole 500 mg TID orally for 10–14 daysa ‚‚ Severe: vancomycin 125 mg every 6 hours orally for 10–14 days ƒƒIf oral therapy is impossible: ‚‚ Nonsevere: metronidazole 500 mg TID intravenously for 10 days ‚‚ Severe: metronidazole 500 mg TID intravenously for 10 days plus intracolonic vancomycin 500 mg in 100 mL of normal saline every 4–12 hours and/or vancomycin 500 mg every 6 hoursb by nasogastric tube ƒƒPerform colectomy to treat CDI in any of the following situations: perforation of the colon or systemic inflammation and deterioration of the clinical condition not responding to antibiotic therapy. et al. discontinue. the infection is nonresponsive to metronidazole (e. decreasing vancomycin daily dose by 125 mg every 7–14 days)/pulse (e. Accessed December 8.g. the decision to initiate. double-blind study compared metronidazole with oral vancomycin for CDI stratified by disease severity. opinion. TID = three times/day.. •• If the result of the stool toxin assay is negative. Treatment Stratification by Disease Severity Cumulative clinical data from trials in the late 1990s and early 2000s reported increasing treatment failure rates with metronidazole. although recurrence rates were similar (from 18% to 20%). may be treated by discontinuing the inducing antibiotic. if needed. •• Treatment for a second recurrence of CDI and later recurrences: ƒƒIf oral therapy is possible: ‚‚ Vancomycin 125 mg every 6 hours orally for at least 10 days ‚‚ Then consider a taper (e. •• When severe or complicated CDI is suspected. severe. Oral vancomycin is preferred if metronidazole is contraindicated. difficile Infection avoidance of antiperistaltic agents and placement of the infected patient on contact precautions.Box 3-1. •• Mild CDI (stool frequency less than four times/day. •• If possible. Kelly CP. avoid the use of antiperistaltic agents because they may obscure symptoms and precipitate toxic megacolon. •• Change to a narrow-spectrum antibiotic if possible. or continue treatment must be individualized..

combination high-dose oral vancomycin and intravenous metronidazole are often used in acute fulminant disease. Abdominal pain (6%) Intravenous option CDI = Clostridium difficile infection. then rectal 197 C. a toxin-binding agent. Any patient with a score of 2 or above was considered to have severe disease. 125 mg orally four times/day (Glycopeptide) 250 mg Alternative Agents Fidaxomicin Tablet: (Macrocyclic) 200 mg Nitazoxanide (Antiprotozoal thiazoline) Rifaximin (Rifamycin) Tablet: 500 mg Suspension: 100 mg/5 mL Tablets: 200. temperature.9°F (38. This study has been criticized for using a low dose of metronidazole (i. although not all clinical trials have used the IDSA severity measures. Although data are lacking to support this approach. and white blood cell count.5 mg/dL. Consider in patients requiring concomitant antibiotics or known non-epidemic strain May be useful in patients intolerant of first-line agents Tolerability Nausea (12%) Headache (5% to 18%) Vaginal irritation/ discharge (9% to 12%) Dizziness (1% to 4%) Bitter taste (10%) Nausea (11%) Vomiting (7%) Abdominal pain (6%) Abdominal pain (7%) Diarrhea (2% to 4%) Nausea (3%) 200–400 mg orally May be used in recurrent two or three CDI as a “chaser” times/day Nausea (14%) Dizziness (13%) Fatigue (12%) 100 mg IV followed May be used in patients Nausea (26%) by 50 mg IV every with severe CDI Vomiting (18%) 12 hours refractory to vancomycin Diarrhea (12%) and metronidazole. A score of 1 was given to patients on the basis of age. compared with metronidazole and oral vancomycin. albumin.e. whereas a score of 2 was given to patients with endoscopic evidence of colitis or admitted to the intensive care unit.. or white blood cell count greater than 15 x 103 cells/mm3. 250 mg given four times/day) and its requirement for a negative toxin test at day 7 to assess the primary outcome measure. but the cure rate for patients with severe disease was higher with oral vancomycin than with metronidazole. IV = intravenously. temperature greater than 100. If oral therapy is not possible because of ileus.Table 3-2. These variables have been associated with increased mortality. ER = extended release.3°C). 550 mg Tigecycline (Glycylcycline) Vials: 50 mg 200 mg orally twice daily 500 mg orally twice daily Use or Possible Role in C. difficile Recommended by guidelines for the treatment of mild/ moderate disease Treatment of severe CDI. albumin less than 2. Treatment Options for CDI Drug (Drug Class) Dosage Form First-line Agents Common Dosage Metronidazole Tablet: 250. These results are similar to those reported in a phase III comparator trial of tolevamer. A standardized definition for severity is required and is an area of research in CDI. difficile Infection . Complicated Disease Intravenously administered metronidazole may be used in the patient with an ileus because oral vancomycin may not be delivered to the colon in this situation. The Infectious Diseases Society of America (IDSA) guidelines use a different severity scoring measure but recommend metronidazole for mild to moderate diseases and oral vancomycin for severe disease. The cure rate was similar for patients given metronidazole and oral vancomycin for mild CDI. nonresponse to metronidazole or after first recurrence Cost may limit utility. PSAP-VII • Infectious Diseases Treatment of Severe. The IDSA guidelines use only changing creatinine values and an abnormally high white blood cell count to define severity. 500 mg 500 mg orally/IV three times/day (Nitroimidazole) Capsule: 375 mg ER tablet: 750 mg IV premixed suspension: 500 mg/100 mL Vancomycin Capsule: 125.

and other anionexchange resins bind vancomycin capsules. nitazoxanide has not been shown to be superior to currently available first-line regimens. Risk factors for recurrence include continued use of concomitant antibiotics. difficile but limited activity against other gram-positive bacteria. Treatment of Recurrent CDI Recurrence of CDI occurs in about 20% of patients. Life-saving colectomy may be performed in patients with megacolon or colonic perforation. administration of vancomycin. All cases used rifaximin as a “chaser” (follow up) therapy after successful resolution of diarrhea using oral vancomycin or metronidazole. Clinical data for treatment of CDI with tigecycline stem from a case series of four patients with severe refractory CDI (two men and two women). they should not be used concomitantly. difficile strains with reduced susceptibility against rifaximin have been identified. fidaxomicin received FDA label approval for the treatment of CDI in adults. difficile antibiotic (usually oral vancomycin). nitazoxanide was well tolerated in these studies. In colonic perforation. The drug may also spare enteric flora. together with intravenous metronidazole. Cholestyramine. Nitazoxanide Nitazoxanide. which shows potent activity against C. Adding cholestyramine or rifampin to the pulse-taper regimen does not decrease recurrence rates. The most promising is the nonabsorbable agent rifaximin. difficile. which should be a very intense area of research in the future. In a multicenter trial that compared fidaxomicin with oral vancomycin in patients with CDI. has activity against bacterial enteric pathogens including C.to 14-day therapy of oral vancomycin every 6 hours. colestipol. 198 PSAP-VII • Infectious Diseases . It may be considered for intolerance or nonresponse to first-line agents. Two studies showed equivalent cure rates with nitazoxanide compared with metronidazole or oral vancomycin for patients with CDI. a vancomycin tapered regimen is recommended on the basis of moderate evidence (B-I). with no serious adverse events reported. in patients infected with the hyper-virulent strain (BI/NAP1/027). A small trial that randomized patients to rifaximin or placebo after conventional therapy with metronidazole or oral vancomycin also showed decreased diarrhea recurrence rates with the addition of rifaximin. The drug may be cost-effective if given to patients at high risk of rehospitalization because of CDI recurrence or other serious and costly sequelae. However. use of anti-ulcer agents (e. and monoclonal antibodies. A follow-up study combined the results of two phase III trials to investigate the association between concomitant use of antibiotics and recurrence rates. Several new therapies were evaluated recently for preventing CDI recurrence. Rifamycins Several agents in the rifamycin class have been investigated for the treatment of CDI. Alternative Therapies for CDI Fidaxomicin Fidaxomicin is a narrow-spectrum. making it a potentially useful agent for preventing recurrence.and vancomycin-treated patients. may be used and is recommended in the guidelines on the basis of expert opinion. non-absorbable macrocyclic antibiotic with in vitro activity against C.g. fidaxomicin had similar rates of clinical cure but a lower recurrence rate. or underlying medical conditions requiring concomitant antibiotic therapy. fidaxomicin. Recurrence rates were lower when patients who required concomitant antibiotics were given fidaxomicin. and older age. In 2011. Larger trials are required before this regimen is recommended routinely.this patient population to ensure adequate killing of germinating spores. difficile. including rifaximin. However. The IDSA treatment recommendations for the first recurrence of CDI are the same as for the initial episode (treatment based on presenting severity). These therapies are reviewed below and are summarized in Table 3-2. For patients with their second recurrence. Overall. After the patient receives the usual 10. there was no significant difference in recurrence rate between fidaxomicin. PPIs). it is unknown how to identify this patient population. The therapy is costly (about $2700 for a course) compared with either oral vancomycin or metronidazole. a tapering regimen is initiated with twice-daily dosing for 14 days. The patient is then initiated on oral rifaximin for an additional period averaging 2–4 weeks. difficile strains and achieves high colonic concentrations (more than 8000 mcg/g). a nitrothiazole benzamide. oral or rectal administration of any antimicrobial agent should be discontinued. However. Possible reasons for the lack of difference in these patients include properties of the organism (higher toxin production or spore formation).. infection severity. Recurrence rates were not significantly different from those of either metronidazole or oral vancomycin. Intravenous immunoglobulin (150–400 mg/kg) therapy has been used for some patients with success. An intriguing possibility would be that longer therapy durations are required in C. Using this chaser regimen. Three case series have shown benefit with the use of rifaximin to prevent CDI recurrence. a higher rate was seen in patients on antibiotics historically associated with a high risk of CDI recurrence. although C. a patient is treated with a full course of an anti-C. difficile Infection Tigecycline Tigecycline is a glycylcycline antibiotic and a derivative of minocycline with in vitro activity against C.

or patients in an intensive care unit because of a higher likelihood of developing fungemia. These patients. increased exposure to the health care setting. are the same ones at high risk of CDI recurrences. Use of this agent is not listed in the CDI guidelines because of the lack of convincing data. However. immunocompromised patients. On the basis of these results. Microbiologic Therapy Stool transplantation delivered by enema. However. use of these agents in otherwise stable outpatients can be an option. Owens RC Jr. is also important. including limiting the inappropriate use of PPIs. Probiotic Therapy There are conflicting reports about the utility of probiotics in the treatment and prevention of primary or recurrent CDI. The epidemic strain is associated with increased mortality and a higher likelihood of colectomy. Many other modifiable risk factors. nasogastric tube. including a two-step algorithm and real-time PCR. difficile with monoclonal antibodies. Kazakova SV. Both historic and current strains were toxin type III and contained a binary toxin as well as an 18-bp deletion in the tcdC gene. N Engl J Med 2005.353:2433–41. and other antibiotics have decreased CDI rates in the hospital. Annotated Bibliography 1. This treatment may be an option for patients experiencing a third or higher recurrence of CDI. The current strains were Role of the Pharmacist A pharmacist can play an instrumental role in the prevention and treatment of CDI. One hundred eighty-seven C. Metronidazole and oral vancomycin remain the cornerstone of treatment. An epidemic.reducing inappropriate antibiotic use. which in turn could decrease the incidence of CDI. difficile strains belonging to one specific restriction endonuclease analysis group called the BI or APNAP1 strain accounted for at least one-half of all isolates. although new treatment regimens are emerging. Symptomatic relief was reported 3–7 days after tigecycline initiation. New diagnostic tests. Other Therapies for CDI Immunization with Monoclonal Antibodies A phase II multicenter study investigated the use of a one-time infusion of human monoclonal antibodies directed toward toxins A and B. or colostomy to restore colonic microflora has been reported to be effective. C. nonabsorbable antibiotics or passive immunization against the toxins of C. A close relative of the patient is usually the donor. The isolates were strain typed and compared with previous isolates from the CDC or the Hines Veterans Affairs (VA) collection. The most recent IDSA guidelines for the treatment of CDI stressed the importance of optimizing CDI therapy by stratifying it by severity. This strain was identified in 1984 but was uncommon. a phase III trial is planned to investigate the role of monoclonal antibodies as adjuvant therapy to prevent CDI recurrence. et al. Killgore GE. may improve the sensitivity of commonly used diagnostic tests. A decrease in recurrent CDI was observed in patients who received the monoclonal antibodies compared with placebo. Newly identified risk factors for CDI include PPIs and fluoroquinolone antibiotics. Future novel therapies include narrow-spectrum. Lactobacillus has also shown some efficacy in recurrent CDI but mainly in case series or small trials. Although some studies have shown benefit of prophylactic Saccaromyces boulardii in reducing the incidence of CDI. an intravenous alternative to metronidazole is an unmet medical need in CDI. Avoiding unnecessary antibiotic therapy within the first 6 weeks after a CDI episode. and an ongoing epidemic strain of C. although inadvertent spread of pathogenic organisms from donor as well as distaste by patients have limited use of this treatment modality. Although the toxicity of this agent may limit its use. may positively affect CDI rates. This classic article expanded on previous reports of a new strain of C. The IDSA Antimicrobial Stewardship guidelines stress the importance of PSAP-VII • Infectious Diseases McDonald LC. boulardii should not be used routinely in patients with central venous catheters. Instances of bacteremia have been reported. Conclusion Rates and severity of CDI are increasing because of an aging population. third-generation cephalosporins. the treatment efficacy or recurrence prevention has been conflicting. a negative regulator of toxin A and B production. toxin gene-variant strain of Clostridium difficile. The current CDI guidelines do not recommend probiotics because of the lack of consistent data. difficile in North America and Europe that was associated with increased incidence and severity. 199 C. clindamycin. difficile. Thompson A. Decreased rates of fluoroquinolones. host genetics. Patients with CDI should be stratified by severity and then treated with oral vancomycin for severe disease. difficile Infection . clinical case series have described more than 90% efficacy using this technique. Sambol SP. S. and no relapse was reported in 3 months follow-up. Unmet medical needs include an unacceptably high recurrence rate and need for intravenous antibiotic therapy. if possible. difficile isolates were collected from eight health care institutions in six states. unfortunately.

The emergence of VRE depends on the killing of normal enteric flora usually with antibiotics and recolonization with VRE. and after treatment for CDI. Proton pump inhibitors decrease gastric acid synthesis by binding to the gastric parietal cell. Li Y. In this prospective cohort study. CDI is very uncommon and is not generally expected after antibiotic treatment for traveler’s diarrhea. Tam VH. In this case series. Jiang ZD. Ghantoji S. Proton pump inhibitors and risk for recurrent Clostridium difficile infection. which distinguished them from historic strains. p=0. The hypothesis of this study was that increased IL-8 production leads to more inflammation at the colonic epithelium. Sethi AK.01–7. Theoretically. Outpatient CDI is considered an emerging problem. Morocco. 87 veterans with CDI treated with oral vancomycin or metronidazole were examined for acquisition and concentration of VRE stool colonization. defined as a return of diarrhea that required treatment after the initial symptom resolution. difficile toxin test. Interleukin (IL)-8 is a key component in the inflammatory response to infection and is associated with increased neutrophil influx to the infection site. Arch Intern Med 2010. These authors set the definition for the BI/NAP1 hypervirulent strain and began the discussion on the role of fluoroquinolones and risk of CDI with the BI strain. This is the first study to identify a host genetically determined risk factor for CDI. A common polymorphism in the interleukin-8 gene promoter is associated with an increased risk for recurrent Clostridium difficile infection. This was a prospective cohort study of 96 hospitalized adult patients with their first CDI episode. Pultz MJ. Riggs MM. Patients with the A/A genotype were much more likely to experience recurrent CDI than were patients with the A/T or T/T genotypes (odds ratio [OR] 2. and all improved. 5. 2. 95% CI. Antimicrob Agents Chemother 2008. Bolivia. the association between CDI and PPIs has been controversial. Metronidazole also kills enteric flora. Because the spores of C.8%) did not.51:1406–10. With the decreasing costs of polymorphism testing. Clin Infect Dis 2010. and it is possible that metronidazole promotes VRE overgrowth to the same extent as oral vancomycin.82) especially in patients older than 80 years or those who continued to receive antibiotics not targeted to C. difficile during follow-up. Arora V. The authors questioned the routine use of oral fluoroquinolones for traveler’s diarrhea because of the BI/NAP1 strain association with this class of antibiotics. the patients received a diagnosis of CDI because of persistent or new-onset diarrhea and a positive C. Patients were followed for 3 months to assess for recurrent CDI. Navarro M.2%) patients received an oral PPI within 14 days of CDI infection. New VRE in patients previously without VRE was found in 14% of patients given metronidazole and in 8% of patients given oral vancomycin. Norman F. difficile that are killed in the presence of gastric acid may pass the gastric lumen in the absence of gastric acid and increase a host’s risk of infection. Clin Infect Dis 2008. Garey KW. Al-Nassir W.4. Although diarrhea is common in international travelers. Before.52:2403–6. and a polymorphism at the -251 position is associated with increased IL-8 levels. more likely to be resistant to gatifloxacin and moxifloxacin. All patients were treated with metronidazole. C. Peru. About 1 week to 2 months later. 95% confidence interval [CI]. stools were collected and cultured for VRE. Fonda JR. Five hundred twenty-seven (45. Clostridium difficile-associated diarrhea after antibiotic treatment for traveler’s diarrhea. In 56 treatment courses in patients already colonized with VRE. Donskey CJ. Recurrent CDI was more common in patients exposed to PPIs during treatment (relative risk 1. In this retrospective study of a VA database.46:1060–3. leading to increased risk of symptomatic recurrent CDI. Lawler EV.11–1. de Ayala P. The series also highlights the need for vigilance and the diagnosis of CDI in places not usually associated with the disease. organisms such as the vegetative forms of C. it is possible that host polymorphism testing will become standard practice as a preventive measure for primary or recurrent CDI.The host inflammatory response is important in the pathogenesis of CDI. Perez-Molina J. Linsky A. 1. the authors describe six separate cases of travelers who went to foreign destinations (Cambodia. Jimenez B. Hermos JA. This case series highlights the role of outpatient CDI.42. Gupta K. difficile Infection 200 PSAP-VII • Infectious Diseases . Recommendations to preferentially use metronidazole over oral vancomycin because of concerns about VRE may not be warranted on the basis of these results. usually a fluoroquinolone. 1. and Kenya) who were treated with antibiotics for traveler’s diarrhea.7. Production of IL-8 is genetically determined. oral vancomycin and metronidazole each equally promoted VRE overgrowth with increased VRE quantities during treatment that persisted for about 2 weeks after discontinuation. with quantity counts performed. 4. One of the primary concerns with the use of oral vancomycin for the treatment of CDI has been the potential for emergence of vancomycin-resistant enterococci (VRE). and 639 (54. India. Both oral metronidazole and oral vancomycin promote persistent overgrowth of vancomycin-resistant Enterococci during treatment of Clostridium difficile-associated disease. during. This study builds on the previous finding on the role of IL-8 polymorphisms and the risk of primary CDI. This study provides important evidence that metronidazole may promote persistent overgrowth and new-onset VRE colonization equal to oral vancomycin. difficile can survive passage through the stomach regardless of gastric acid. 3. Dupont HL.170:772–8. Lopez-Velez R. several patients (1166) with CDI treated with metronidazole or oral vancomycin were identified.043).

nonabsorbable antibiotic with in vitro activity against C. Logan N. in patients not responding to or intolerant of metronidazole. The most recent IDSA/Society for Healthcare Epidemiology of America (SHEA) guidelines incorporate this study. The small sample of this study precludes generalized use of nitazoxanide for CDI treatment. This small case series of four patients describes tigecycline use for severe refractory CDI. received tigecycline intravenously. However. Clin Infect Dis 2007. Bakkanagari SR. Clinical cure rates were similar for fidaxomicin (88. 24%. Fidaxomicin versus vancomycin for Clostridium difficile infection. Biemond-Moeniralam HS. difficile stool test on days 6–10) were 84% in the metronidazole group and 97% in the vancomycin group (p=0.6. Significantly fewer patients in the fidaxomicin group than in the vancomycin group had a recurrence of the infection. placebocontrolled trial.02). One of the unmet medical needs in the treatment of CDI is appropriate pharmacotherapy when a patient is unable to take antibiotics orally. p=0.4% vs. cure rates were 76% in the metronidazole group and 97% in the vancomycin group (p=0.48:e41–6. placebo-controlled. Lentnek A. Bressler AM. This is the first randomized clinical trial to show the superiority of one agent over another for CDI treatment. In this randomized.006). the safety and efficacy of fidaxomicin were compared with those of oral vancomycin in 548 patients with mild-moderate CDI. phase III study. including the antibiotics used to treat CDI (metronidazole and oral vancomycin). There were no significant differences in recurrent CDI in patients with the BI/NAP1 strain. A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea. The reasons for the difference in recurrence rates on the basis of strain type is poorly understood and should be an area of significant research in the future. Patients were stratified by severity of C. Limited conclusions can be drawn from a small case series such 201 C. even though not done clinically or required. Symptoms of CDI resolved 3–7 days later with a documented negative C. Global cure was also similar in patients given oral vancomycin or nitazoxanide.8%) in the intent-to-treat analysis and were similar for fidaxomicin (92. Rossignol JF. doubleblind study. N Engl J Med 2011. Hornef M. Clin Infect Dis 2009. randomized clinical trials have never shown the superiority of one agent. Davis MB. a drug that interferes with the anaerobic metabolism of protozoa and bacteria. Miller MA. Burkhardt O. although reports of metronidazole failures have increased. 25. Current suggested regimens include intravenous metronidazole given in combination with vancomycin enema or high-dose oral vancomycin. non-inferiority. are intolerant of oral vancomycin or metronidazole. Johnson DP. three of whom had not responded to conventional therapy. All four patients were followed for 3 months with no relapses observed.45:302–7. 49 patients with CDI were given either oral vancomycin 125 mg every 6 hours or oral nitazoxanide 500 mg every 12 hours for 10 days and assessed for clinical cure at the end of therapy and global cure (clinical success with no recurrence) at day 31. Zar FA. Weiss K. in patients who are not responding to or who PSAP-VII • Infectious Diseases Louie TJ. Golan Y. Blom H. The incidence and severity of CDI has increased because of many factors. Two men and two women. The lower recurrence rate was seen only in patients with non–BI/NAP1 strains. Musher DM. Patients were given either fidaxomicin 200 mg two times/day or vancomycin 125 mg four times/ day orally for 10 days and assessed for clinical cure at day 10. double-blind. placebo-controlled. in both the modified intent-to-treat analysis (15. 9. Nitazoxanide. difficile strains. The high recurrence rate of CDI is believed to be associated with continued destruction of the enteric flora because of continued use of antibiotics. Vlaminckx B.005) and the per-protocol analysis (13. This study enrolled 172 patients with CDI into a randomized. Clinical cure was achieved in 74% of patients given oral vancomycin and in 77% of patients given nitazoxanide (p=nonsignificant). Mullane KM. The severity score is explained in the chapter text.364:422–31. Updated guideline recommendations are to base treatment choice on the severity of disease using oral vancomycin for more severe disease in which oral therapy is possible. Clin Infect Dis 2009. Current treatment regimens for CDI are generally limited to oral vancomycin and metronidazole. double-blind.2%) and vancomycin (85. Herpers BL. of whom 150 completed the study. Moorthi KM. difficile Infection .3% vs. Although a small observational study showed faster response times with oral vancomycin than with metronidazole. Intravenous tigecycline as adjunctive or alternative therapy for severe refractory Clostridium difficile infection. including a recently described epidemic strain associated with increased toxin production commonly referred to as the hyper-virulent strain. no clear intravenous option exists.1%) and vancomycin (89. Fidaxomicin is a narrow-spectrum. et al. Metronidazole is generally recommended as first-line therapy in published guidelines. and global cure (clinical cure with no recurrence). 8. stratified by disease severity.8%) in the per-protocol analysis (p=nonsignificant). Nitazoxanide versus vancomycin in Clostridium difficile infection: a randomized. 7. p=0.3%. double-dummy study. Fidaxomicin has a minimal impact on host enteric flora. if possible. A previous clinical trial showed similar outcomes in patients treated with metronidazole or nitazoxanide. et al. has good in vitro activity against C. difficile. However. In this randomized. CDI recurrence within 30 days. difficile illness and given either oral metronidazole 250 mg or oral vancomycin 125 mg four times/day with matching placebo. Disease recurrence at 21 days did not differ between the two groups (14% to 15%). difficile toxin test shortly after symptom resolution.004). Among patients with severe CDI (n=86). Overall cure rates (defined as symptom resolution by day 6 and negative C.48:1732–5. nitazoxanide may be a therapeutic option.

Recurrence rates of CDI were lower in patients given monoclonal antibodies (7%) than in those given placebo (25%. C. double-blind.as this. Two hundred patients received a one-time infusion of the antibodies or matching placebo while taking conventional antibiotics (metronidazole or oral vancomycin) for CDI.0001). Gerding DN. The decreased recurrence rates were observed in patients infected with the BI/NAP1 and non-epidemic strains. it provides initial data for future studies and data on another intravenous treatment option for severe. 10. difficile was conducted. placebo-controlled study of two neutralizing monoclonal antibodies directed against toxins A and B of C. et al. p<0. However. A decade later. The antibody was safe in this study.362:197–205. difficile Infection 202 PSAP-VII • Infectious Diseases . N Engl J Med 2010. this randomized. Blair BM. refractory CDI. Treatment with monoclonal antibodies against Clostridium difficile toxins. Lowy I. with reported rates of serious events less than placebo. Leav BA. Baxter R. Studies published in 2000 and 2001 showed that a host antibody response to toxin A significantly decreased the incidence of CDI and recurrent CDI in hospitalized patients. Molrine DC.

A 65-year-old man is in the intensive care unit (ICU) on day 8 of oral vancomycin for CDI and day 2 of intravenous vancomycin (1 g every 12 hours) for methicillin-resistant Staphylococcus aureus bacteremia.8°C). B. A patient arrives at the home infusion clinic for long-term antibiotic treatment of osteomyelitis. D. 42. Add Saccaromyces boulardii to oral vancomycin. B. and 1+ proteinuria. Which one of the following would best decrease the possibility of another CDI recurrence in this patient? Health care (HC)-onset. Indeterminate disease. she responded well to two previous metronidazole courses. 44. She is initiated on a 14-day course of oral vancomycin 125 mg every 6 hours. Community-associated CDI (CA-CDI). Discontinue metronidazole and add oral vancomycin. Hand hygiene with alcohol-based sanitizer. 41. A. and takes only a daily multivitamin. The physical examination reveals no guarding and a mild case of diarrhea with a suspicion of CDI. Add ciprofloxacin to metronidazole. a 79-year-old man was prescribed amoxicillin/clavulanate for bronchitis. C.to fourth-generation cephalosporins. Full contact precautions with face shields. HC-associated CDI. He was later hospitalized with his first episode of CDI and was discharged from the hospital last week. A 42-year-old woman is given a diagnosis of a second recurrence of CDI. Give intravenous fluids. Hand hygiene with soap and water. A laboratory test for Clostridium difficile toxin is positive.3°F (36. The patient reports that she has never before had diarrhea this severe and has not been in a hospital since last December when she delivered her first child. Prospectively monitor all patients with CDI and place on appropriate therapy. C. Today his urinalysis for proteinuria monitoring shows 5 white blood cells per high-power field (0–5). Monitor patients on antibiotics to reduce the total duration. D. tertiary care medical center. She has no chronic illnesses. Which one of the following is most likely to decrease the CDI rates? A. The patient has taken 10 days of the 14-day course of metronidazole for CDI and reports normal bowel movements and no other symptoms. Discontinue metronidazole and add ciprofloxacin. Complete therapy with metronidazole. difficile reduction taskforce in your hospital. Which one of the following has the highest likelihood of lowering the risk of cross-contamination of patients with CDI? A. B. you are reviewing the infection control policies associated with CDI. A 38-year-old African American woman arrives in the emergency department on July 1 with a history of severe diarrhea for the past 2 days. Community-onset. C. Today she reports four diarrheal bowel movements in the past 24 hours. 1+ bacteria. A steady-state vancomycin trough is reported as 28 mcg/mL (desired trough is 10–15 mcg/mL). difficile infection (CDI)? A. Use a rifaximin “chaser” after oral vancomycin is completed. A. You are the clinical infectious diseases pharmacist at a large. Which one of the following is the best plan for this patient? PSAP-VII • Infectious Diseases Discontinue ceftriaxone. As part of the C. B. difficile Infection . C. The patient has diabetes and chronic lung disease. 45. Start a tapering oral vancomycin regimen at 125 mg twice daily now. 46. Five weeks ago. D. Which one of the following is best for this patient? 43.Self-Assessment Questions A. Start oral vancomycin. Start loperamide. B. 47. Which one of the following best describes this case of C. Increase vancomycin dose to 500 mg every 6 hours. Vital signs include blood pressure (BP) 120/83 mm Hg and temperature 98. C. HC-associated CDI. C. The hospital has an above-average rate of CDI. D. D. and an antibiotic stewardship program has been implemented specifically to decrease CDI rates. D. Which one of the following is the best plan for this patient? 203 C. Minimal use of antimicrobials. He reports two diarrheal bowel movements during the past 2 days with an unusual odor. He has completed 5 weeks of a planned 6-week course with ceftriaxone 2 g intravenously every 24 hours. Make a formulary change from third. no known allergies. Restrict clindamycin to infectious diseases consult only. B.

and arthritis. Score of 3. A. the patient experiences his first recurrence of CDI. severe disease. After 4 days of therapy. BP 138/40 mm Hg. There is an increased rate of CDI severity as well as CDI recurrence. Wait until the toxin test is done. Discontinue both oral and intravenous vancomycin. You are to formulate empiric therapy guidelines for CDI with the desire to give empiric therapy that will ensure appropriate treatment of severe disease and minimize the likelihood of resistance. B. lowgrade fever (99. C. 52. Discontinue pantoprazole. She has diabetes. Last month. Which one of the following is the best option for this patient? A. A. 50. PSAP-VII • Infectious Diseases .7°C).Z. Intravenous metronidazole.? A. difficile toxin test is ordered. hematocrit 32%. A. hemoglobin 11 g/dL. You note on the chart that the patient has completed 5 days of a 14-day course of meropenem for multidrug-resistant Escherichia coli bacteremia and is receiving pantoprazole for stress ulcer prophylaxis. A. D. A 75-year-old woman has had two previous episodes of CDI treated with metronidazole. A patient receives a 10-day course of oral metronidazole for his first episode of CDI. Which one of the following would be the best 14-day treatment for A. Metronidazole orally 500 mg three times/day. Salmonella. and platelet count 300. Follow-up blood cultures show no growth after 3 days. Which one of the following is best for this patient? 49. chloride 101 mEq/L. hypertension. difficile toxin B. 51. Her previous use of antibiotics was caused by chronic urinary tract infections. C. and there is no guarding on abdominal examination. A C. serum creatinine 1. D. Vancomycin 250 mg orally every 6 hours. Laboratory results show sodium 138 mEq/L.6°C]). and negative for Shigella. 53. is a 62-year-old woman (weight 82 kg) admitted to the hospital for severe abdominal pain and 8–10 bowel movements per day. A stool sample tests positive for C. Admit to the hospital. Which one of the following is best for this patient? 48. the patient is not responding to vancomycin and has continued diarrhea. Oral rifaximin. serum bicarbonate 29 mEq/L. Discontinue meropenem. 204 Change to fidaxomicin. Score of 2. Give oral metronidazole. potassium 4. B. D.6°F (38.Z.2 mEq/L. severe disease. Today she presents to the ambulatory care clinic with chronic diarrhea. Vancomycin orally 250 mg four times/day.2°C). The team has given oral vancomycin to a 78-year-old ICU patient with severe CDI because the patient was experiencing the third recurrence of the disease. Which one of the following empiric treatment strategies would be best for patients hospitalized with severe disease? Oral metronidazole. B. negative for ova and parasites. A.? A. C.9 mg/dL). Her vital signs today include temperature 101. Questions 49 and 50 pertain to the following case. Continue both oral and intravenous vancomycin. D. Two days after discontinuing his antibiotic. and respiratory rate 18 breaths/minute. difficile Infection Vancomycin orally 125 mg four times/day. received levofloxacin for a urinary tract infection. B. and abdominal pain. and Campylobacter. B. His temperature is 98.9°F (37. WBC 17 x 103 cells/mm3. Score of 2. Score of 1. cell cytotoxicity assay. C. C. difficile outbreak caused by the BI/NAP1/027 strain. D.Z.B. C. Give oral vancomycin.2 mg/dL. for its toxin assay. Change to rectal vancomycin.Z. D. Continue oral and hold intravenous vancomycin. He reports three liquid bowel movements in the past 24 hours. You are a clinical pharmacist in a hospital that is experiencing a C. Metronidazole 500 mg orally every 8 hours. albumin 3. His laboratory results show white blood cell count (WBC) 8 x 103 cells/mm3 and creatinine of 0. The laboratory is currently using the gold standard. D. Metronidazole 500 mg intravenously every 8 hours. Fidaxomicin orally 200 mg twice daily. mild disease.8°F [37.8 mg/dL.’s score and severity level of CDI using the criteria proposed by Zar et al. C. his BP is 125/78 mm Hg. Vancomycin 125 mg orally every 6 hours.6 g/dL. mild disease. A. You are a clinical pharmacist rounding with the infectious diseases consult team. Oral metronidazole with cholestyramine.000 cells/mm3.5 mg/dL (baseline 0. Discontinue oral vancomycin and hold intravenous vancomycin. He has a WBC of 14 x 103 cells/mm3 and serum creatinine of 1. B. Which one of the following is the best assessment of A. C.

Add oral metronidazole 500 mg every 6 hours. B. Patients on combination antibiotics and PPIs. D. Change therapy to oral vancomycin 500 mg every 6 hours. difficile Infection . Fecal biotherapy. Age-dependent risk factors for CDI. B. 57. 58. 59. Patients on single antibiotic therapy but no PPIs. Your pharmacy resident is beginning a new study to assess the relationship between CDI and proton pump inhibitor (PPI) use. Patients on PPIs but no antibiotics. D. Now. C. Which one of the following is the best plan for this patient? PSAP-VII • Infectious Diseases 205 C. Continue oral vancomycin at current dose while on antibiotics. The medical director of your stewardship team would like to implement a therapeutic intervention targeting the rates of recurrent CDI. Change therapy to tigecycline intravenously 50 mg given every 12 hours. Decreasing the likelihood of contracting CDI. A patient who has experienced four recurrences of CDI in the past year is desperate for a cure and comes to you for expert advice. Rifaximin 200 mg three times/day chaser. You specifically want to target a population at high risk of developing CDI. D.9°F (37. Long-term use of probiotics. Patients on single antibiotic therapy and PPIs. temperature of 99. B. The patient is appropriately placed in isolation. Evaluations have shown that previous CDI cases in the hospital were not caused by the hyper-virulent strain. No further action is necessary.A. Using proper hand hygiene. You are an ICU pharmacist treating a patient with severe CDI. C. C. C. Which one of the following would be best for patients with severe disease? A. A. the patient is symptomatic with five bowel movements in the past 18 hours. aureus bacteremia. Increase metronidazole to 1000 mg given every 8 hours. Oral vancomycin and rifaximin. the patient was unable to tolerate oral drugs and required intravenous therapy. C. You are responsible for designing the program. He requires initiation of cefazolin for methicillin-sensitive S. You are an ambulatory care pharmacist working with a local gastroenterology clinic. Sanitize hands with alcohol gel. which have been increasing in your hospital. Complete oral vancomycin and use fidaxomicin while on antibiotics. Your clinic is a major referral center for CA-CDI. boulardii. after 7 days of treatment with intravenous metronidazole 500 mg given every 8 hours. 54. D. Continue vancomycin and add S. On physical examination. A 67-year-old man is hospitalized for profuse diarrhea and fever and is eventually given a diagnosis of CDI on the basis of a C. and you wear double gloves during the examination.7°C). Which one of the following is best for this patient? 60. Which one of the following topics is most important to target in this educational series? A. A severely ill patient is in the ICU receiving total parenteral nutrition to supplement low oral intake caused by GI intolerance. which you discard in the designated receptacle. C. Which one of the following hospital populations is best to study? A. Monoclonal antibodies against toxins A and B. and WBC of 25 x 103 cells/mm3. Intravenous immunoglobulin. D. B. B. Sanitize hands with soap and water. The patient has CDI and is finishing a 14-day course of oral vancomycin today. On the basis of existing evidence. 55. You would like to begin a new clinical service whereby you evaluate the indication for PPI use and discontinue drugs as appropriate. D. difficile toxin test. and the ICU team would like to prevent a CDI recurrence. You are asked to prepare an educational series directed at decreasing rates of CDI in the community setting. Patients with underlying GI disease. Because of an ileus. D. Fidaxomicin 200 mg twice-daily chaser. C. which one of the following would be best to recommend for this patient? A. Which one of the following would best ensure hand hygiene after you leave the patient’s room? A. the abdomen is mildly tender with very active bowel sounds. B. 56. Sanitize hands with a sporicidal wipe. Rifaximin chaser regimen. B. Complete oral vancomycin course today and monitor for recurrence.

difficile Infection 206 PSAP-VII • Infectious Diseases .C.