ID Week 2013

October 2-6, 2013; San Francisco; CA

Focus on Clostridium difficile

Hand Washing Effective in Reducing Clostridium difficile Spores on Hands of Colonized Patients

It has been shown that hand washing with soap and water is more effective than alcohol hand rub for removing artificially applied Clostridium difficile spores from the hands of volunteers (www.ncbi.nlm.nih.gov/pubmed/20429659); however, limited data are available on the level of spore contamination on the hands of colonized patients. In addition, there have been no studies to evaluate the effectiveness of hand washing with soap and water by these patients. To see if the results found in volunteers also applies to colonized patients, researchers from Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH, and Case Western Reserve University, Cleveland, OH, conducted a randomized trial comparing the effectiveness of hand washing and alcohol hand rub for removing spores from the hands of individuals with C difficile infection and asymptomatic carriers of toxigenic C difficile. The results were reported during an oral abstract session (https://idsa.confex.com/idsa/2013/webprogram/Paper41087.html) at ID Week 2013.

The study included 44 patients; 28 had C difficile infection and 16 were asymptomatic carriers. During the study, 62 hand washes with soap and water and 59 alcohol rubs were performed, with each patient receiving between two and four hand hygiene assessments. Swabs from whole hands were taken before and after hand washing or use of alcohol hand rub, and the number of colony-forming units (CFUs) was quantified.

Before hand hygiene was undertaken, 60 of 121 hand cultures tested positive for C difficile and contained an average of 12 CFUs. There was no significant difference in the number of colonies recovered from patients with C difficile infection and asymptomatic carriers (mean, 11.5 vs 11.9 CFU). The researchers found that hand washing significantly reduced the percentage of positive cultures, from about 48% to 11%, whereas alcohol rub did not achieve similar results, only reducing the percentage from approximately 51% to 47%. In addition, hand washing reduced the number of colonies recovered from contaminated hands from about 13 CFUs to less than 2 CFUs, whereas alcohol hand rub barely reduced CFU counts from their baseline levels of about 11 CFUs. The researchers conducted interviews with participants at the time of enrollment and found that 32 (73%) were unaware that alcohol is ineffective for removing C difficile spores. 

Patients colonized with C difficile often have spore contamination on their hands, increasing their risk of spreading infection. Because soap and water washing was effective in significantly reducing the number of spores on patients’ hands, the investigators conclude that these individuals should receive proper education on the importance of hand washing for spore removal. Such measures may be particularly important in long-term care settings, where patients are mobile and frequently leave their rooms.—Christina T. Loguidice

Fecal Microbiome Transplantation Continues to Show Success for Treating Recurrent and Severe Clostridium difficile Infections

Cases of severe and recurrent Clostridium difficile infection have markedly increased. When these infections occur in patients older than 60 years and with multiple comorbidities, outcomes are generally poor, particularly when antibiotic treatments fail. Two studies presented during an oral abstract session at ID Week 2013 show that fecal microbiome transplantation (FMT) may be an efficacious treatment for these patients.

The first study (https://idsa.confex.com/idsa/2013/webprogram/Paper42434.html), which was conducted by researchers from Southern Illinois Healthcare, Carbondale and Herrin, IL, evaluated FMT in 21 hospitalized patients failing C difficile antibiotic treatment. All patients had more than three watery stools or more than 200 mL output from their ostomy daily, were deteriorating clinically while on oral vancomycin with or without intravenous metronidazole, and were not neutropenic or receiving chemotherapy or radiation therapy. Fresh, filtered stool from thoroughly screened donors was used for transplantation, and was introduced via nasogastric tube followed by two rectal retention enemas. The researchers reported no adverse events related to transplantation, and 20 patients (95.2%) were cured at 30 days.

In the second study (https://idsa.confex.com/idsa/2013/webprogram/Paper41627.html), conducted by researchers at the University of Calgary, Calgery, Alberta, Canada, FMT occurred via an oral capsule procedure, rather than via enema, jejunal catheter placement, or colonscopy, which are the usual modes of administration. The oral capsule procedure was developed to account for patients who could not tolerate a jejunal catheter or nasogastric tube and/or were unable to retain fecal enemas due to anal incontinence and failed arrest of recurrent C difficile infection. On the day of the procedure, previously screened donors provided approximately 100 g of freshly passed feces, which was processed and put through a centrifuge multiple times to isolate the fecal microbes, which were placed into gelatin capsules. The day before receiving the capsule, the recipient stopped vancomycin, and on the day of the procedure, he/she received colonic cleansing 8 hours before being provided with the freshly assembled capsules, which were administered over 5 to 15 minutes without any antacids and taken on an empty stomach. The researchers reported that all 27 patients who received the oral capsule procedure to date have arrested their recurrent C difficile infections. In addition, the treatment was well tolerated, with no patients vomiting after ingestion of the capsules.

Based on their findings, both study researchers indicate that fecal microbiome transplantation is a viable and efficacious treatment. In addition, the US researchers suggest that FMT should be evaluated as a primary treatment for patients with severe C difficile infections. As FMT evolves to include less invasive modes of administration, such as through the use of oral capsules, as outlined by the Canadian researchers, it is plausible that it will also become a more viable primary treatment for these patients.—Christina T. Loguidice  

Prevalence of Clostridium difficile Underestimated in Long-Term Care

Although Clostridium difficile is the most common cause of diarrhea in long-term care (LTC) facilities, there is a paucity of data on the true prevalence of C difficile infections in this setting. Subsequently, the burden of these infections is difficult to quantify, and many LTC facilities may rely on positive C difficile tests to estimate the burden; however, as shown by two studies presented during poster abstract sessions at ID Week 2013, this may not be an accurate measure for several reasons, including underutilization of tests (https://idsa.confex.com/idsa/2013/webprogram/Paper40825.html) and a discrepancy between test results and actual prevalence (https://idsa.confex.com/idsa/2013/webprogram/Paper40306.html)

Underutilization of Testing

Investigators at Detroit Medical Center, a tertiary care center in metropolitan Detroit with a centralized microbiology laboratory, assessed stool samples from surrounding acute care hospitals (total bed count, 1200), LTC facilities (median bed count, 115), and outpatient clinics. Examination of the microbiology data for all patients at these facilities who received a nucleic acid amplification test (NAAT) for C difficile between January 2011 and January 2013 showed that LTC facilities had the highest prevalence of infection at 31.2% (total NAATs performed, 1031; average, 2 per month per facility), followed by acute care hospitals at 15% (total NAATs performed, 13,970; average, 50-100 per month) and outpatient clinics at 12.8% (total NAATs performed, 1091). Despite a low volume of testing for C difficile infection at LTC facilities, their prevalence of C difficile infection was twice as high as that found in acute care hospitals. In addition, among the LTC facilities, there was one with 40 beds that had a surprisingly low prevalence of infection at 13.1%. The investigators found that this facility was physically located within an acute care hospital and managed by the same staff.

Based on these findings, the investigators conclude that there is “a critical need for educating healthcare workers, including nurses, nurse practitioners, nurse aids, and physicians at LTC facilities to send diarrheal stool for C difficile testing,” noting that “early diagnosis can help decrease C difficile infection–related morbidity and mortality and transmission opportunities in older adults.”

Calculation Discrepancies

Investigators at University Hospitals Case Medical Center, Cleveland, OH, and Case Western Reserve University, Cleveland, OH, compared the rates of positive C difficile tests with the prevalence of actual C difficile infections at four Veterans LTC facilities by using structured query language to collect data on a retrospective cohort of patients admitted to these facilities between 2009 and 2010. They determined the rate of positive C difficile tests among these residents by calculating the number of positive tests per month, and they determined the prevalence of C difficile infection by using an algorithmic approach that evaluated C difficile test outcomes and administration of metronidazole or oral vancomycin and examined electronic medical records to calculate the number of C difficile infections per month. The investigators found that the average number of positive C difficile tests per month was 5.8 ± 2.6 compared with 8.2 ± 3.7 cases of C difficile infections per month (P=.01). Based on their findings, the authors conclude that relying on positive C difficile tests might underestimate the prevalence of C difficile infections, noting their results “[have] implications for infection control measures within long-term care facilities,” and “may also influence interpretation of national surveillance data used to estimate the burden of C difficile infection in LTC facilities.”
—Christina T. Loguidice  

Fidaxomicin May Prevent Clostridium difficile Relapse and Reinfection

Recurrent Clostridium difficile infection is reported to occur in 25% of patients treated with metronidazole or vancomycin, and patients may experience several episodes of recurrent colitis. These episodes generally manifest within 1 to 3 weeks after discontinuing antibiotic therapy, but may occur as late as 2 to 3 months thereafter. A study (https://idsa.confex.com/idsa/2013/webprogram/Paper40383.html) presented during a poster abstract session at ID Week 2013 revealed that the incidence of C difficile infection recurrence is reduced following initial treatment with fidaxomicin compared with vancomycin. The investigators speculate this may be attributable to fidaxomicin potentially causing less disruption of the intestinal microbiome.

The investigators used whole genome sequencing (WGS) to assess whether fidaxomicin reduced C difficile recurrence in two pivotal multicenter, double-blinded, randomized phase 3 trials by preventing relapse of the same infection, reinfection, or both. Isolates were sequenced using Illumina HiSeq 2000, and sequence reads were mapped to the C difficile 630 reference genome. Paired isolates were available from 93 of 199 participants (47%); 28 of 68 (41%) were on fidaxomicin and 65 of 131(50%) were on vancomycin (P=.29). Single nucleotide variants (SNVs) were determined between each isolate pair. Recurrences within two or fewer SNVs of the first sample were considered a relapse, samples more than 10 SNVs apart were considered reinfection, and samples with three to 10 SNVs or no available isolate were considered indeterminate.

Overall, 54 (58%) of 93 participants had no SNVs between randomization and recurrence strains, whereas 16 (17%) had one SNV, four (4%) had two SNVs, and one participant each had four, six, eight, 11, and 13 SNVs. When classifying same-strain relapse as two or fewer SNVs and reinfection as more than 10 SNVs, two of 494 participants (4%) versus 52 of 496 participants (10%) relapsed on fidaxomicin versus vancomycin, respectively (95% confidence interval, 0.25-0.66; P=.0003), and four (0.8%) versus 12 (2%), respectively, had reinfection with a new strain. These effects of fidaxomicin versus vancomycin remained similar when adjusted for age, prior C difficile infection, number of unformed bowel movements, albumin levels, white blood cell counts, and creatinine levels (relapse, P<.001; reinfection, P<.07).

In addition to the primary finding that fidaxomicin was associated with a 2.5 times lower cumulative risk of relapse and a three times lower cumulative risk of reinfection up to 28 days following therapy compared with vancomycin, the authors suggest that WGS may be a valuable tool in C difficile antimicrobial resistance surveillance. They note that this modality detected mutations that conferred reduced susceptibility to fidaxomicin.—Christina T. Loguidice