C. diff. Risk in Veteran’s Long-term Care

SOURCE: Brown KA, Jones M, Daneman N, et al. Importation, antibiotics, and Clostridium difficile infection in veteran long-term care: A multi-level case-control study. Ann Intern Med 2016;164:787-794.

While the risks for Clostridium difficile infection (CDI) are well-recognized, the basis for the significant variation in CDI incidence found in long-term care across the United States is poorly understood. These authors examined regional risk factors for CDI across Veteran Health Administration long-term care facilities (LTCF) from 2006 to 2012. VHA is divided into 86 different regions, and there are significant differences between them in the risk of CDI.

Cases of CDI were defined by a positive toxin test three or more days after admission to LTCF or a positive toxin test eight or more weeks after a previous positive result. Various risk factors were included in the analysis, including patient age and comorbidities, use of antibiotics within 28 days, and use of proton pump inhibitors. Estimates of importation of cases were based on the prevalence of CDI within the local acute care facility within the previous eight weeks.

A total of 6,012 CDI were identified across the VHA regions, ranging from a minimum of 0.6 cases per 10,000 days to a maximum of 31.0 cases per 10,000 days. In unadjusted analyses, the strongest predictors for CDI were total antibiotic use within an LTCF (incidence risk ratio [IRR] 2.86, R2 = 0.63) and importation of cases from the acute care setting (IRR 1.59, R2 = 0.5). Both of these factors varied considerably: Estimated importation of cases varied 100-fold and antibiotic use varied six-fold across regions. Not surprisingly, individual use of antibiotics within the previous 28 days also was a significant risk factor. Other risk factors examined, including age, comorbidity, and proton pump inhibitor use, had little effect on the variability of CDI across regions.

In complex weighted analyses, antibiotic use and importation of cases explained 75% of the regional variability in the incidence of CDI in LTCF. Regional differences in antibiotic use suggested that not only was antibiotic use associated with an increased risk of CDI, but with an increased risk of spreading CD. The authors surmised that the remaining 25% of geographic variability, which was unexplained by their data, may be due to factors such as improved infection control practices and environmental measures at specific facilities.

Certainly a “community burden” of CD must play a significant role in the risk of active CDI within a facility. Our acute care hospital, with two campuses located 17 miles apart, screens all high-risk hospital admissions with rectal swabs for CD PCR (e.g., admissions from SNF or other facilities, dialysis patients, anyone with a history of CDI). The prevalence of CD colonization on admission between the two campuses is 19% vs. 9.7%, and the difference in CD colonization for SNF admissions between the two campuses is 18% vs. 6%. Despite the use of the same infection control and environmental procedures at both facilities, significant differences in CD rates between the two facilities are frequently observed.

Survival in Acute Liver Failure

SOURCE: Reuben A, Tillman H, Fontana RJ, et al. Outcomes in adults with acute liver failure between 1998 and 2013: An observational cohort study. Ann Intern Med 2016:164:724-732.

As infectious disease consultants, we are frequently involved in cases of severe liver failure (ALF). My recent experience, involving a young Asian Indian man with acute severe hepatitis E virus infection, who required formal consultation with a liver transplant service but was not placed on the transplant list and survived, was more positive than others. Patients with acute hepatic deterioration from acute injury receive the most urgent ranking for organ transplantation, and it’s important to know when and whom to call when such events occur. Fortunately, infectious causes of acute liver failure are responsible for a minority of cases, although antimycobacterial and antifungal medications may contribute.

From 1998 to 2005 and from 2006 to 2013, these authors examined the U.S. experience with ALF patients enrolled in the Acute Liver Failure Study Group (ALFSH), including the severity of liver failure, patient characteristics, and the transplant-free and transplant-related outcomes at 21 days. During this 16-year period, 2,070 patients (median age, 39 years) were enrolled in the registry, 461 (22%) of whom received a liver transplant. Of these, there were sufficient data to examine characteristics and outcomes in 1,410 individuals.

During the 16-year study period, causes of ALF did not significantly differ. Acetaminophen (AC) toxicity remained the leading cause of ALF in nearly half of the cases, although the majority of these cases were from unintentional overuse rather than suicidal overdose. Other causes included other non-AC drug-induced ALF (10.8%), auto-immune hepatitis (7%), ischemia (5.7%), and mushroom toxicity (0.6%); hepatitis B virus infection (7.2%) and hepatitis A virus (1.8%) were less common — and ALF due to other viruses even less common (0.9%). Only three cases were due to HCV infection and three due to HEV infection. Only the role of hepatitis A appeared to decrease over time, from 2.8% during the first eight years to 0.8% during the second eight-year study period, probably from improved immunity from vaccination.

Most of the patients registered on the transplant list had critical liver failure, and 50% had grade 3 or 4 hepatic encephalopathy. Even though the causes for ALF did not significantly differ between the two study periods, both transplant-free and transplant survival significantly improved. Overall survival steadily improved during the 16-year study period from 58.8% in 1998 to 75% in 2013 (P < 0.001). Transplant-free survival improved from 32.9% in 1998 to 61% in 2013 (P < 0.001). Overall survival for AC-related ALF with grade 1 or 2 hepatic encephalopathy improved from 34.5% to 43.7% (P = 0.019), although there was no significant change in mortality with more severe AC-related injury. This was believed to be related to improvements in critical care and the administration of N-acetylcysteine. The 21-day transplant survival improved from 88.3% in 1998 to 96.3% in 2013 (P = 0.002).

Causes of death included multi-organ system failure (20%), neurologic causes (13.9%), multifactorial causes (10.8%), general “liver-related causes” (10.8%), sepsis and infection (7.9%), and cardiac causes (5.3%). Thirty-one liver transplant centers participate in the ALFSH project, five of which have been operating for the entire 16 years. There were no apparent differences in survival between those five transplant centers and the remaining facilities.