Insulin Therapy, C. Diff Update, LMWH or UFH for Acute Coronary Syndrome

C. Difficile Update

1. Loo VG, Poirier L, Miller MA, et al. A Predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality. N Engl J Med. 2005 Dec 8;353(23):2442-2449.
2. McDonald LC, Killgore GE, Thompson A, et al. An epidemic, toxin gene-variant strain of Clostridium difficile. N Engl J Med. 2005 Dec 8;353(23):2433-2441.
3. Warny M, Pepin J, Fang A, et al. Toxin production by an emerging strain of Clostridium difficile associated with outbreaks of severe disease in North American and Europe. Lancet. 2005 Sep 24-30;366(9491):1079-1084.

In 1978, Clostridium difficile was linked to antibiotic-associated diarrhea and pseudomembranous colitis. This spore-forming gram-positive rod causes disease through two toxins—A and B—which can be detected with cytotoxin assays. It colonizes a significant proportion of hospitalized patients, but causes disease in less than 1%. The primary risk factor for developing disease is antibiotic exposure, presumably through disruption of normal gut flora. Outcomes range from mild diarrhea to life-threatening pseudomembranous colitis requiring colectomy.

Since 2000 a number of hospitals in the United States and Canada have witnessed outbreaks of C. difficile characterized by increases in both the incidence and severity of disease. Three recent publications have shed light on the changes in microbiology that have contributed to those findings. All of the studies characterized C. difficile isolates from these outbreaks, and one included information about patient outcomes.

When isolates from the outbreaks were collected, all three studies identified a predominant strain of C. difficile known as NAP1/027. It accounted for 50%-82% of isolates from the outbreaks in these studies. In contrast, NAP1/027 was present in only 14 isolates from a database of more than 6,000 strains isolated in the United States prior to 2001.

NAP1/027 has a number of concerning microbiologic characteristics. It contains a deletion in the gene tcdC, which normally suppresses the production of toxins A and B. Warny, et al. found that the NAP1/027 strain produces levels of toxins A and B that are 16 and 23 times higher, respectively, than a historically dominant strain. NAP1/027 also produces a binary toxin previously uncommon in C. difficile isolates. The role of binary toxin is not well understood, but it may mediate increased pathogenicity. Finally, the NAP1/027 strain displays high levels of fluoroquinolone resistance, which is uncommon in previous strains of C. difficile.

Loo, et al. also studied patient outcomes in 1,703 patients with C. difficile disease outbreaks in 12 Canadian hospitals. The 30-day mortality rate attributable to C. difficile infection was 6.9%, compared with 0.5-5.5% in previous studies. Patients older than 80 had a higher risk of developing C. difficile infection. For those who did, the 30-day mortality rate attributable to C. difficile was more than 10%.

The discovery of the NAP1/027 strain should strengthen our resolve to use antibiotics judiciously, to recognize and treat C. difficile infections promptly, and to implement strict isolation when cases are discovered. Special attention should be given to elderly patients, who may be at higher risk. Finally, it stresses the importance of hospital epidemiology and infection control, areas in which hospitalists can take an active role.—SM

The Controversy of Thrombolytic Therapy in Hemodynamically Stable Patients with Acute PE

Söhne M, Ten Wolde M Boomsma F, et al. Brain natriuretic peptide in hemodynamically stable acute pulmonary embolism. J Thromb Haemost. 2006 Mar;4(3):552-526.

The role of thrombolytic therapy in hemodynamically stable patients with acute pulmonary embolism is controversial. Right ventricular dysfunction can be an indication for thrombolytics in some patients, but clinical examination is limited and emergent echocardiography is unavailable in many institutions. Rapid measurement of brain natriuretic peptide (BNP) as a marker of right ventricular strain may assist with decision-making in the management of acute PE. Söhne, et al, hypothesized that BNP at presentation would predict the risk of recurrent venous thromboembolism (VTE), including fatal pulmonary embolism.