C. difficile difficult for outpatient physicians and patients, too
By Stacey Butterfield
Where are most Clostridium difficile cases in the U.S. diagnosed?
If you answered “in the hospital,” you’re wrong, but not alone.
“It’s thought to be a hospital-acquired infection. There’s a lot of hype about it in hospitals,” said John G. Bartlett, MD, MACP, infectious disease specialist and professor of medicine at Johns Hopkins in Baltimore.
But that hype obscures that although the vast majority of C. difficile cases stem from an encounter with health care, most patients are actually diagnosed outside the hospital. According to an analysis of 2010 data from the Centers for Disease Control and Prevention (CDC), 75% of C. difficile patients were not hospitalized at infection onset.
“Only about 20% to 25% of all C. difficile cases have their onset in the acute care hospital. About that proportion again have their onset in nursing homes. But the rest have their onset in the community,” said L. Clifford McDonald, MD, FACP, senior advisor for science and integrity in the Division of Healthcare Quality Promotion at the CDC and lead author of the analysis, which was published in the March 9, 2012, Morbidity and Mortality Weekly Report.
Those community-onset infections can often be successfully diagnosed and treated by general internists, and experts in the field had some tips and tricks on ridding infected outpatients of C. difficile and reducing the risk that others will develop it.
The biggest risk factor for C. difficile is the same in and out of the hospital: antibiotic use. The primary symptom is pretty obvious, too. But many more patients have antibiotic-associated diarrhea than are actually infected with C. difficile.
This micrograph depicts gram-positive C. difficile bacteria from a stool sample culture obtained using a 0.1-µm filter. Photo from CDC/Janice Carr
Timing is one key to differentiating the conditions. Antibiotic-associated diarrhea occurs while patients are taking antibiotics. “If [the diarrhea] has its onset or clearly worsens after the person stops taking antibiotics, that’s a sign it could be C. difficile,” said Dr. McDonald. Accompanying fever or abdominal pain is also a diagnostic indicator.
If a patient shows some of these signs and has three or more unformed stools on sequential days, it may be time for a C. difficile test. But be careful with testing. “The biggest mistake [physicians make] is [interpreting] the test,” said Dr. Bartlett. “There are two tests—one overcalls and one undercalls.”
The overcalling, or less specific, test is the newer option, the polymerase chain reaction (PCR) test. “The big strength of the PCR is that they are so very sensitive. A negative result says that the person does not have C. difficile,” said Dr. McDonald. Of course, the downside is that some patients will test positive when, in fact, they are not infected.
The CDC encourages use of this newer test, but many hospitals and labs are still using the less-sensitive enzyme immunoassay test, which is more likely to underdiagnose C. difficile.
It’s important to know which test your patients are given and weigh the results accordingly, the experts advised. “When somebody says, ‘I had a positive test,’ the next question is ‘What test?’” said Dr. Bartlett.
In the Netherlands, a beagle was trained to identify C. difficile by sniffing stool samples and even patients themselves. Photo from iStockphoto
The very newest test for C. difficile is noteworthy for its novelty, but unlikely to be available at a hospital near you (Dr. Bartlett was unable to get his administrators to implement it). In the Netherlands, a beagle was trained to identify C. difficile by sniffing stool samples and even patients themselves. The dog scored 100% on sensitivity and specificity with the samples and did well with the patients, too, according to results published by BMJ on Dec. 13, 2012.
Until you have a C. difficile-detecting dog, though, keep in mind that neither of the two existing tests can distinguish between colonization and actual infection, an important consideration in both initial diagnosis and follow-up. “There is no test of cure,” said Dr. Bartlett. “[Physicians] want to do a C. diff test to make sure it’s gone. Once it’s positive, it’s just going to stay positive.”
Choices have to be made in the treatment of C. difficile, as well. Two drugs, vancomycin and the newer fidaxomicin, have been FDA-approved for the infection, but metronidazole is actually the guideline-recommended treatment for mild or moderate cases. The other drugs are typically reserved for severe or recurrent cases.
“Fidaxomicin is probably the drug of choice for C. diff,” said Dr. Bartlett. “If the price was competitive, that would be definite. ... It has the best overall cure rates.” Currently, with the other drugs being significantly less expensive, fidaxomicin is most useful for patients particularly at risk of relapse, he added.
Relapse is a major concern in C. difficile, occurring in 20% of patients after initial treatment. Discontinuing and then avoiding the antibiotics that led to the initial infection reduces risk, if that course of action is clinically feasible. “Other steps to try to reduce recurrence include always using at least 10 days of therapy and using the therapy by mouth whenever possible,” said Dr. McDonald.
One relapse is not too bad a sign for patients’ future health, and patients on their first relapse can be treated with the same drug they received as initial therapy. But an additional recurrence is an ominous sign.
“If someone recurs, their risk for a subsequent recurrence is still only 20%,” said Dr. McDonald. “If they recur a second time, then their risk of recurrence is about 50% or even higher. People can go on with multiply recurrent C. difficile.” Multiple recurrences should be the trigger for referring patients to specialty care, experts said.
Patients who see a specialist may be offered a donor feces transplant, a treatment option that made headlines for its superiority to vancomycin in a randomized trial published in the Jan. 31, 2013, New England Journal of Medicine. C. difficile experts have been using this technique successfully for many years, but the study’s publication may lead to wider acceptance, Dr. Bartlett predicted.
“If they’ve had three or four or five or six relapses, which some of them do, then we say it’s time for a stool transplant,” he said. “It’s the perfect treatment. After patients get past the ‘yuck’ stage, they say ‘I wish I’d done this earlier.’”
Earlier this year, the FDA announced plans to regulate fecal transplants as an investigational new drug, potentially limiting access to the procedure, but the agency backed off plans to enforce that regulation after protest by physician groups.
While providing enemas or infusions of feces may be the yuckiest task associated with treatment of C. difficile, some scrubbing of dirty surfaces should also be on outpatient practices’ to-do lists.
Epidemiologic research has shown that people are more likely to develop C. difficile after visiting their outpatient physicians, even if they’re not on antibiotics. That finding raises concerns about the need for better infection control measures.
“We don’t have anything that says this is an important form of transmission, but the fact that so many of these patients have recently been in their doctor’s office suggests that we need to look at this further,” said Dr. McDonald.
Because antibiotic use significantly raises the risk of C. difficile infection, practices where a lot of patients take those meds—oncology offices, dialysis clinics—might be particular targets for investigation and prevention, he speculated.
Previous research has shown that C. difficile patients have been found to contaminate examination tables, so all offices might want to consider cleaning such likely spots for contamination.
“If they have a patient that they know has C. diff, they should be doing the typical things to decrease transmission—cleaning the bathroom with chlorine-based disinfectants, for example,” said Jon-Mark Hirshon, MD, MPH, PhD, an associate professor in the departments of emergency medicine and epidemiology and public health at the University of Maryland, Baltimore. The need for further action is uncertain, he said. “Do you sterilize the entire waiting room? We don’t know.”
Dr. Bartlett, who has an outpatient C. difficile clinic, hasn’t found it necessary to go that far. “We don’t have a fetish about it,” he said. “We wear gloves. We do the things that make sense.”
The spore structure of C. difficile does make it harder to kill than some other bugs, he noted. “They’ve found Clostridia that have been on a surface for 100 years,” Dr. Bartlett said. The spores also make alcohol rubs less effective as a hand hygiene tool, so clinicians should wash their hands with soap and water after examining a patient with C. difficile.
Patients should engage in some extra cleaning, too, if possible. “We’ve said, if someone does have C. difficile diarrhea and is managed at home, try to use a separate bathroom from other family members or [have] the bathroom be cleaned between uses by others,” said Dr. McDonald.
Spread among family members is one of the theories to explain C. difficile infections in patients who haven’t had any recent contact with health care (which made up only 6% of the total in the CDC analysis).
“There are a couple of epidemiologic studies to suggest that people are at increased risk if a family member has C. difficile,” said Dr. McDonald. “There’s also a suggestion that people who are around infants might be more likely to develop C. difficile.”
No one is sure why these nonhospital cases appear to be on the rise and how much concern is warranted about the increase.
“We looked at incidence of community-acquired infection and the incidence was increasing,” Dr. Hirshon said. “Some of that is almost certainly diagnostic detection bias. People are thinking about it more in the outpatient setting so they’re testing for it more.”
Other trends in health care may also contribute to driving C. difficile into the community settings, according to Jennifer Kuntz, PhD, an assistant investigator with the Kaiser Permanente Northwest Center for Health Research in Portland, Ore.
“There is a shift in the identification of C. diff in the outpatient setting as patients are getting discharged from hospitals sooner and more medical issues are being handled exclusively in the outpatient setting. If this trend continues, identification and management of C. diff by primary care clinicians will be of great importance,” she said.
Dr. Kuntz recently led an analysis of outpatient C. difficile infections, published in the October 2012 Infection Control Hospital Epidemiology. More than 50% of the recorded infections were identified in outpatient settings, and, echoing the thoughts of all the C. difficile experts, the authors concluded that the infection “demands greater attention in the outpatient setting.”
Pearls about C. diff from an infectious diseases doctor
It should come as little surprise that some of the most common questions asked of infectious diseases specialist Carlos Isada, MD, deal with Clostridium difficile.
Dr. Isada, vice chairman of the department of infectious diseases at Cleveland Clinic, offered insight on these and other topics during a session at the Society of Hospital Medicine’s 2013 annual meeting, held in National Harbor, Md., in May.
Severe Clostridium difficile (C. diff) can be difficult to treat because it is often complicated by ileus, which significantly decreases the delivery of oral antibiotics to the colon, and the main treatment for C. diff is oral vancomycin. What to do?
IV vancomycin and metronidazole by themselves don’t work, Dr. Isada said. Vancomycin enemas have shown some promise, but the research is based on a small number of case reports. Current recommendations by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America from 2010 suggest simultaneously attacking the problem three different ways:
- 500 mg of oral vancomycin four times a day, plus
- 500 mg of vancomycin in 100 mL saline by rectum every six hours as retention enema, plus
- 500 mg of IV metronidazole every eight hours.
Another treatment for severe C. diff is colectomy. Patients should be considered for this option if their serum lactate level is rising to 5 mmol/L or their white blood count is 50,000 cells/µL, Dr. Isada said.
Probiotics and C. diff in elderly patients
A multistrain preparation of lactobacilli and bifidobacteria failed to prevent antibiotic-associated diarrhea and/or Clostridium difficile diarrhea in elderly patients, a study found.
In a randomized, double-blind, placebo-controlled trial, researchers assigned inpatients to receive either placebo, or the multi-strain preparation with a total of 6 × 1010 organisms, one per day for 21 days.
Antibiotic-associated diarrhea (AAD) (including C. difficile diarrhea [CDD]) occurred in 10.8% of the inpatients in the microbial preparation group (n=1,470) and 10.4% of the inpatients in the placebo group (n=1,471); the difference was not significant between groups.
CDD was an uncommon cause of AAD and occurred in 12 (0.8%) inpatients in the microbial preparation group and 17 (1.2%) inpatients in the placebo group. About 20% of participants had one or more serious adverse events, and the frequency of these events didn’t differ by group, nor were they attributed to study factors.
This trial indicates there is insufficient evidence to support routinely using probiotics to prevent AAD in older inpatients, the authors wrote.
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