Clostridium difficile infection (CDI) causes inflammation of the colon and is a potentially life-threatening diarrheal illness.
CDI has become the most common microbial cause of healthcare-associated infections in US hospitals, resulting in $4.8 billion yearly in excess healthcare costs for acute care facilities alone.[1] The most recent data suggest an incidence of approximately 500,000 cases annually, with as many as 29,000 patients dying within 30 days of their initial diagnosis.[1] Additionally, patients with CDI are twice as likely to be readmitted to the hospital as those without CDI. The length of stay upon readmission was also significantly higher, adding 4 to 7 days over other admission diagnoses.[2,3]
Given the importance of CDI, five key focus areas are highlighted here; while they might not all be well recognized, they need to be known.
1. Spores Are Hardy and Hard to Kill
C difficile spores are extremely hardy and can survive for long periods on exposed surfaces. An important mechanism of transmission is via the hands of healthcare providers or other individuals who have touched a contaminated surface. But transmission from an infected patient is not the only mode, or even the primary mode of transmission, within the hospital setting. Another mechanism of C difficiledissemination is asymptomatic colonization.[4,5] Despite having no symptoms of disease, colonized patients can serve as an infectious reservoir, posing an under-recognized risk to vulnerable patients. Colonization may be the result of antibiotic therapy, which disrupts the intestinal microbial composition, enabling colonization with C difficile.[6]
Isolation reduces patient-to-patient transmission within the institutional setting. Private rooms and dedicated toilets are recommended for infected patients to prevent transmission to noninfected patients. Gloves and gowns are standard practice for healthcare providers and any visitors of patients with suspected disease. The recommendation is to continue this practice for at least 48 hours after resolution of the diarrhea. Handwashing before and after wearing gloves is also recommended.[7]
2. Metronidazole May Be on the Way Out
Although previous guidelines recommended metronidazole for mild CDI, in the most recent guidelines, oral vancomycin (125 mg four times daily) or fidaxomicin (200 mg twice daily) for 10 days are the preferred treatments. Further support for the avoidance of metronidazole as initial therapy comes from a recent study demonstrating that the risk for 30-day mortality for all combined severities is reduced with vancomycin versus metronidazole.[8] Of note, branded oral vancomycin is an expensive drug.[9] Clinicians may wish to investigate the cost savings of using a compounding pharmacy to encapsulate parenteral vancomycin powder, which might be less expensive.
The recommended vancomycin dose for fulminant disease with hypotension, shock, ileus, or toxic megacolon is 500 mg four times daily. In patients with ileus or megacolon, using vancomycin 500 mg in 100 cc normal saline per rectum every 6 hours as a retention enema may be considered.[7] It is important to roll the patient onto his or her right side to facilitate transfer of the solution to the right colon. Use a large Foley catheter and inflate the 30-cc balloon, leaving it inflated for an hour while repositioning the patient.[10] Metronidazole given intravenously (500 mg every 8 hours) is recommended in addition to rectal vancomycin if ileus is present.
Oral metronidazole is an alternative for CDI only when access to vancomycin or fidaxomicin is limited.
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3. A New Agent Could Prevent Recurrence
In 2017, the US Food and Drug Administration approved another drug option for patients who are at high risk for a recurrence of CDI: bezlotoxumab, a human monoclonal antibody to C difficile toxin B. Bezlotoxumab is not an antimicrobial; therefore, it is indicated only for adults who are being treated with an antibiotic for CDI and are at risk for a recurrence. Results from two large randomized, controlled studies demonstrated a rate reduction of approximately 10% for bezlotoxumab compared with placebo.[11] It is administered as a single infusion over 1 hour. Bezlotoxumab does carry a precaution about use in patients with heart failure. Cost could be a barrier to the use of bezlotoxumab, and more research is needed to compare the cost-effectiveness of this drug with that of other treatments for CDI.
4. Recurrent Disease Is More Common Than You Might Think
Recurrent CDI occurs in approximately 25% of patients who initially responded to treatment, and can be caused by a relapse from the original infecting strain or reinfection with a new strain.[12]
Recommended treatments of a first CDI recurrence include a 10-day course of oral vancomycin followed by a tapered regimen of vancomycin: 125 mg twice daily for 7 days, then 125 mg once daily for 7 days, and finally, 125 mg every 2 to 3 days for 2 to 8 weeks.[7] Fidaxomicin 200 mg twice daily for 10 days is an alternative if oral vancomycin was used for the first episode. Metronidazole is not recommended for recurrent disease.
Patients with recurrent disease, and their families, also should be instructed on high-level disinfection of the entire bathroom at home. This includes mechanical disruption of C difficile spores in the toilet bowl using a toilet brush and cleaning surfaces with wipes that contain bleach. All toothbrush heads and water glasses should be replaced. High-level cleaning of ancillary oral devices (eg, dentures, mouth guards) should also be performed
While probiotics have been used to reduce recurrence, they are not recommended by the most recent guideline.[10] Some evidence shows that probiotics taken with antibiotics may be associated with a lower risk for abdominal cramping and nausea but not recurrence of CDI.[13]
Antibiotic stewardship is key to prevention. The overuse of quinolones can cause CDI; this class of antibiotics should be used only in the absence of an alternative.[7]The use of proton pump inhibitors (PPIs) and risk for CDI has been an area of controversy, but the evidence does not support a recommendation that PPIs be discontinued as a method for preventing recurrent disease.[7,14]
5. The Latest Scoop on Poop for CDI
Fecal microbiota transplantation (FMT) is indicated for patients who have failed antibiotic treatments, have had multiple (ie, two or more) recurrences of CDI, or have severe disease complications. To minimize any transmissible infections or even metabolic and inflammatory changes relative to the transfer of fecal microbiota, the stool donor should be appropriately screened.
Most experts recommend a 3- to 4-day "induction course" of oral vancomycin for patients who are not already being treated for CDI to reduce the burden of vegetative CDI prior to FMT.[7]
Although most research has looked at colonic instillation of fecal microbiota (typically by colonoscopy), upper gastrointestinal administration has been shown to be effective.[15] Consultation with local clinicians who have expertise in this procedure should be considered.
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The Burden of CDI
Clostridium difficile infection (CDI) causes inflammation of the colon and is a potentially life-threatening diarrheal illness.
CDI has become the most common microbial cause of healthcare-associated infections in US hospitals, resulting in $4.8 billion yearly in excess healthcare costs for acute care facilities alone.[1] The most recent data suggest an incidence of approximately 500,000 cases annually, with as many as 29,000 patients dying within 30 days of their initial diagnosis.[1] Additionally, patients with CDI are twice as likely to be readmitted to the hospital as those without CDI. The length of stay upon readmission was also significantly higher, adding 4 to 7 days over other admission diagnoses.[2,3]
Given the importance of CDI, five key focus areas are highlighted here; while they might not all be well recognized, they need to be known.
1. Spores Are Hardy and Hard to Kill
C difficile spores are extremely hardy and can survive for long periods on exposed surfaces. An important mechanism of transmission is via the hands of healthcare providers or other individuals who have touched a contaminated surface. But transmission from an infected patient is not the only mode, or even the primary mode of transmission, within the hospital setting. Another mechanism of C difficiledissemination is asymptomatic colonization.[4,5] Despite having no symptoms of disease, colonized patients can serve as an infectious reservoir, posing an under-recognized risk to vulnerable patients. Colonization may be the result of antibiotic therapy, which disrupts the intestinal microbial composition, enabling colonization with C difficile.[6]
Isolation reduces patient-to-patient transmission within the institutional setting. Private rooms and dedicated toilets are recommended for infected patients to prevent transmission to noninfected patients. Gloves and gowns are standard practice for healthcare providers and any visitors of patients with suspected disease. The recommendation is to continue this practice for at least 48 hours after resolution of the diarrhea. Handwashing before and after wearing gloves is also recommended.[7]
2. Metronidazole May Be on the Way Out
Although previous guidelines recommended metronidazole for mild CDI, in the most recent guidelines, oral vancomycin (125 mg four times daily) or fidaxomicin (200 mg twice daily) for 10 days are the preferred treatments. Further support for the avoidance of metronidazole as initial therapy comes from a recent study demonstrating that the risk for 30-day mortality for all combined severities is reduced with vancomycin versus metronidazole.[8] Of note, branded oral vancomycin is an expensive drug.[9] Clinicians may wish to investigate the cost savings of using a compounding pharmacy to encapsulate parenteral vancomycin powder, which might be less expensive.
The recommended vancomycin dose for fulminant disease with hypotension, shock, ileus, or toxic megacolon is 500 mg four times daily. In patients with ileus or megacolon, using vancomycin 500 mg in 100 cc normal saline per rectum every 6 hours as a retention enema may be considered.[7] It is important to roll the patient onto his or her right side to facilitate transfer of the solution to the right colon. Use a large Foley catheter and inflate the 30-cc balloon, leaving it inflated for an hour while repositioning the patient.[10] Metronidazole given intravenously (500 mg every 8 hours) is recommended in addition to rectal vancomycin if ileus is present.
Oral metronidazole is an alternative for CDI only when access to vancomycin or fidaxomicin is limited.
3. A New Agent Could Prevent Recurrence
In 2017, the US Food and Drug Administration approved another drug option for patients who are at high risk for a recurrence of CDI: bezlotoxumab, a human monoclonal antibody to C difficile toxin B. Bezlotoxumab is not an antimicrobial; therefore, it is indicated only for adults who are being treated with an antibiotic for CDI and are at risk for a recurrence. Results from two large randomized, controlled studies demonstrated a rate reduction of approximately 10% for bezlotoxumab compared with placebo.[11] It is administered as a single infusion over 1 hour. Bezlotoxumab does carry a precaution about use in patients with heart failure. Cost could be a barrier to the use of bezlotoxumab, and more research is needed to compare the cost-effectiveness of this drug with that of other treatments for CDI.
4. Recurrent Disease Is More Common Than You Might Think
Recurrent CDI occurs in approximately 25% of patients who initially responded to treatment, and can be caused by a relapse from the original infecting strain or reinfection with a new strain.[12]
Recommended treatments of a first CDI recurrence include a 10-day course of oral vancomycin followed by a tapered regimen of vancomycin: 125 mg twice daily for 7 days, then 125 mg once daily for 7 days, and finally, 125 mg every 2 to 3 days for 2 to 8 weeks.[7] Fidaxomicin 200 mg twice daily for 10 days is an alternative if oral vancomycin was used for the first episode. Metronidazole is not recommended for recurrent disease.
Patients with recurrent disease, and their families, also should be instructed on high-level disinfection of the entire bathroom at home. This includes mechanical disruption of C difficile spores in the toilet bowl using a toilet brush and cleaning surfaces with wipes that contain bleach. All toothbrush heads and water glasses should be replaced. High-level cleaning of ancillary oral devices (eg, dentures, mouth guards) should also be performed
While probiotics have been used to reduce recurrence, they are not recommended by the most recent guideline.[10] Some evidence shows that probiotics taken with antibiotics may be associated with a lower risk for abdominal cramping and nausea but not recurrence of CDI.[13]
Antibiotic stewardship is key to prevention. The overuse of quinolones can cause CDI; this class of antibiotics should be used only in the absence of an alternative.[7]The use of proton pump inhibitors (PPIs) and risk for CDI has been an area of controversy, but the evidence does not support a recommendation that PPIs be discontinued as a method for preventing recurrent disease.[7,14]
5. The Latest Scoop on Poop for CDI
Fecal microbiota transplantation (FMT) is indicated for patients who have failed antibiotic treatments, have had multiple (ie, two or more) recurrences of CDI, or have severe disease complications. To minimize any transmissible infections or even metabolic and inflammatory changes relative to the transfer of fecal microbiota, the stool donor should be appropriately screened.
Most experts recommend a 3- to 4-day "induction course" of oral vancomycin for patients who are not already being treated for CDI to reduce the burden of vegetative CDI prior to FMT.[7]
Although most research has looked at colonic instillation of fecal microbiota (typically by colonoscopy), upper gastrointestinal administration has been shown to be effective.[15] Consultation with local clinicians who have expertise in this procedure should be considered.
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