Defining acute renal dysfunction as a criterion for the severity of Clostridium difficile infection in patients with community-onset vs hospital-onset infection.

BACKGROUND: Acute renal dysfunction can be used to define severe Clostridium difficile infection (CDI). The Society for Healthcare Epidemiology of America (SHEA) and Infectious Disease Society of America (IDSA) guidelines define acute renal dysfunction as serum creatinine (SrCr) ≥1.5 times the premorbid level. AIM: To determine the ability to assess premorbid SrCr in hospitalized patients with CDI, stratified into community-onset CDI (CO-CDI) and hospital-onset CDI (HO-CDI); and to evaluate differing definitions for premorbid SrCr as a criterion for acute renal dysfunction. METHODS: Hospitalized patients with CDI were stratified into CO-CDI and HO-CDI. The ability to assess premorbid SrCr was determined, and the incidence of acute renal dysfunction and the severity of CDI were compared using varying definitions of premorbid SrCr. FINDINGS: In total, 293 patients with CDI were evaluated; of these, 135 (46%) had CO-CDI and 158 (54%) had HO-CDI. Premorbid SrCr data were not available for 37 (27%) patients with CO-CDI and one (<1%) patient with HO-CDI (P < 0.0001). Depending on the definition of premorbid SrCr used, acute renal dysfunction ranged from 17% to 24% for patients with CO-CDI (P = 0.26), and from 13% to 14% for HO-CDI (P = 0.81). The severity of CDI could not be determined for 43 out of 293 (15%) patients, primarily due to the lack of premorbid SrCr data (N = 38). CONCLUSION: Assessment of acute renal dysfunction and the severity of CDI was not possible for many patients with CO-CDI using the current SHEA/IDSA guidelines. Given the increasing incidence of CO-CDI, an alternative definition of acute renal dysfunction may be required.

Alpha-actinin and calmodulin interact with distinct sites on the arms of the clathrin trimer.

In the present study, the interaction of alpha-actinin and calmodulin with clathrin heavy chain are demonstrated using Western blot analysis and rotary shadowing electron microscopy. The results show that alpha-actinin and calmodulin bind the clathrin heavy chain. The interaction is specific and affected by calcium. However, the interaction of both proteins with the clathrin heavy chain is distinct; the proteins do not block each other's ability to bind, and they interact with different protein fragments of the clathrin heavy chain. Furthermore, using rotary shadowing the results show that alpha-actinin differentially affected the terminal region of the clathrin trimer. Whereas, the effects of calmodulin were most noticeably detected along the length of trimer arms. The possible existence of distinct binding sites on the arms of the clathrin trimer for these cytosolic proteins supports the contention that these cytosolic proteins play an important role in cellular trafficking.