A study today confirms that antibiotic use is a primary risk factor for community-associated Clostridium difficile infection (CA-CDI), researchers from the US Centers for Disease Control and Prevention (CDC) report in Open Forum Infectious Diseases.
The results also suggest a visit to the emergency department (ED) may be a significant risk factor as well.
While the link between antibiotic use and CA-CDI comes as no surprise, the association between ED visits and increased risk for the infection indicates that C difficile bacteria may be as problematic in certain outpatient settings as it is in hospitals. And the findings underscore the growing burden of the pathogen in the community.
CDI is the leading causes of healthcare-associated diarrhea and one of the most common infections among hospital inpatients, with cases frequently occurring among older patients taking antibiotics for other infections. But community-associated cases have been on the rise, climbing from 35% of the total CDI burden in the United States in 2011 to 41% in 2014, the authors note.
Concerns about outpatient antibiotics
For the study, the largest case-control study to investigate CA-CDI risk factors to date, the investigators enrolled participants from 10 geographically diverse US locations over a 6-month period (October 2014 through March 2015). The case-patients were adults who had a positive C difficile stool specimen collected as an outpatient or within 3 days of a hospital visit but with no overnight stay in a healthcare facility during the previous 12 weeks and no prior CDI diagnosis. They were matched one-to-one with a randomly selected control with no history of CDI.
All 452 participants (226 matched pairs) were interviewed by phone for information about medication use, underlying conditions, outpatient healthcare visits, and diet. The exposure period of interest was the 12 weeks prior to the case-patient's illness-onset date.
The results showed that prior outpatient medical care and antibiotic therapy were more common among case-patients, with 82.1% reporting at least one outpatient visit in the previous 12 weeks and 62.2% reporting antibiotic use, compared with 57.9% and 10.3%, respectively, among the control group. The case-patients were also more likely to have had outpatient healthcare exposure within the 2 weeks preceding their illness (55.7% vs 37.7%), most commonly at a doctor's or dentist's office.
Multivariate analysis of the results indicated that exposure to the antibiotic classes commonly associated with CDI—cephalosporins (adjusted matched odds ratio [AmOR], 19.02), clindamycin (AmOR, 35.31), fluoroquinolones (AmOR, 30.71), and beta-lactam and/or beta-lactamase inhibitor combinations (AmOR, 9.87)—was a primary risk factor for CA-CDI infection among the case-patients. Other risk factors included white race (AmOR, 7.67), cardiac disease (AmOR, 4.87), chronic kidney disease (AmOR, 12.12), and inflammatory bowel disease (AmOR , 5.13).
These results, which were in line with previous studies on CA-CDI infection, highlight concerns about antibiotic use and misuse in outpatient settings. Among the participants, 22% reported taking antibiotics for ear, sinus, and upper respiratory conditions, which are frequently caused by viruses and don't require antibiotics. A 2016 CDC study estimated that half of the prescriptions written for acute respiratory conditions in ambulatory care settings were unnecessary.
Nearly 16% of the participants reported prophylactic antibiotic use for dental procedures, even though American Dental Association guidelines recommend prophylactic antibiotics for only a small number of patients with heart conditions. A recent study by the Minnesota Department of Health found that 15% of patients with CA-CDI had been prescribed antibiotics for a dental procedure.
Antibiotics can increase the risk of CDI by wiping out both good and bad bacteria in the gut and allowing C difficile, a common environmental bacterium, to flourish in the intestinal tract and cause severe diarrhea.
"There's a lot of work that needs to be done in terms of improving outpatient prescribing practices and making sure that providers are appropriately prescribing antibiotics," lead author Alice Guh, MD, MPH, a medical officer with the CDCs Division of Healthcare Quality Promotion, said in a news release from the Infectious Diseases Society of America (IDSA), publisher of the journal.
ED visit as primary risk factor
More surprising was the finding that an ED visit, independent of antibiotic use, was also a primary risk factor for CA-CDI (AmOR, 17.37) in multivariate analysis, even though it accounted for only 11% of the cases. This finding, the authors suggested, is an indication that EDs may serve as reservoirs for the pathogen, which is known to live for long periods on hospital surfaces and medical devices.
There are several factors that make EDs a potential source for C difficile. One is that they serve a high volume of patients, potentially including CDI patients who may shed spores into the environment and onto the hands of healthcare workers. In addition, the high rate of patient turnover means less opportunity for the type of thorough environmental cleaning needed to keep C difficile under control. Other outpatient settings that share similar characteristics may carry the same risks.
"In outpatient settings where procedures are performed or there is long duration and high frequency of patient contact with healthcare providers and the environment, such as EDs, outpatient procedure and surgical centers, hemodialysis, hospital-based outpatient settings, and urgent care, C difficile transmission might be more likely to occur," Guh and her colleagues wrote.
There might be other, unidentified risk factors as well. Thirty-eight percent of the case-patients reported no antibiotic use, and 36% of those patients also had no recent healthcare exposure. But diet, household exposures, and other medications were not found to be significantly associated with increased CA-CDI risk.
The CDC estimates that CDI was responsible for approximately half a million infections and 29,000 deaths in 2011. It costs the US healthcare system roughly $5 billion a year.
Oct 26 Open Forum Infect Dis study
Oct 26 IDSA news release