Rabies encephalitis has plagued humankind for thousands of years. In developed countries, access to preventive care, both pre-exposure and post-exposure, has significantly reduced the burden of suffering and disease. However, around the world, rabies remains a neglected tropical disease, largely due to uncontrolled dog rabies, and tens of thousands perish each year. Currently, the standard of care for management of rabies encephalitis is palliation. Heroic attempts to treat human rabies patients over the last few decades have yielded glimpses into our understanding of pathophysiology, opening the door to the development of new antiviral therapies and modalities of treatment. Researchers continue to investigate new compounds and approaches to therapy, yet there remain real challenges given the complexity of the disease. We explore and review some of the promising therapies on the horizon in pursuit of a salvage treatment for rabies.

Bloodstream infections (BSI) are a common cause of morbidity and mortality in people with sickle cell disease (SCD). In children with SCD, BSI are most often caused by encapsulated organisms. There is a surprising paucity of medical literature that is focused on evaluating SCD adults with BSI. We reviewed the charts of adults with SCD and BSI who were admitted to our hospital between April 1999 and August 2003. During this period a total of 1,692 hospital admissions for 193 adults with SCD were identified and 28% of these patients had at least 1 episode of positive blood cultures, with 69 episodes (17%) considered true BSI. Nosocomial BSI occurred in 34 episodes (49%). Among community BSI, in contrast to BSI in children with SCD, Streptococcus pneumoniae was rarely encountered. A high incidence of staphylococcal BSI in adults with SCD was noted. Twenty‐eight percent of all BSI were caused by Staphylococcus aureus, and 15 of 22 isolates (68%) of these were methicillin‐resistant. Gram‐negative organisms, anaerobes, and yeast were found in 21 (27%), 3 (4%), and 4 isolates (5%) of BSI, respectively. Since over 80% of BSI were considered catheter‐related, the higher incidence of gram‐positive bacterial infections was likely due to the presence of indwelling central venous catheters. Empiric therapy for adults with SCD suspected of having BSI, especially in the presence of indwelling central venous catheters, should include antimicrobial therapy targeted at gram‐positive bacteria (especially MRSA) and gram‐negative bacteria. Also, if patients are critically ill, consideration should be made to include antifungal agents. Additional research into the adult SCD population appears necessary to further define this problem. Am. J. Hematol., 2006.

Acidovorax avenaeis a gram-negative rod in the familyComamonadaceaeand a phytopathogen found in the environment. Human infections caused by members of theComamonadaceaeare extremely rare. We report a case of implanted-port-catheter-related sepsis caused byAcidovorax avenaeand methicillin (meticillin)-sensitiveStaphylococcus aureus(MSSA).

Background: Clostridium difficile infection (CDI) is an increasing nosocomial problem. New, more-virulent strains of C. difficile have spread across North America and Europe. Health care institutions now face a greater incidence of disease, often with greater severity. A need for surgical management for control of infection is on the increase. The clinical appearance of CDI is changed. Methods: We report four unusual and severe cases of CDI in surgical patients with a review of the relevant literature. Results: One patient developed CDI and required a colectomy for a perforated viscus. He developed C. difficile ileitis 12 days later that responded to medical therapy. Another patient who underwent a colectomy for infrarenal aortic occlusion, later in his hospital course, developed C. difficile ileitis and died. The third patient was hospitalized for several months for hypertension and associated morbidities. Eventually he developed severe abdominal pain and was found to have a small bowel mural abscess that grew C. difficile on culture. A fourth patient, taking long-term antibiotics for a surgical site infection of the knee, developed unexplained leukocytosis without diarrhea. Colonoscopy revealed pseudomembranous colitis that advanced to toxic megacolon. She required a colectomy and ultimately died from the disease. Conclusions: Patients are at high risk from CDI in this modern era. Disease manifestations may differ from the typical presentation. A heightened awareness for diagnosing this dangerous, evolving disease is paramount.

Rabies is a devastating disease and affects millions of people globally, yet it is preventable with appropriate and timely postexposure prophylaxis (PEP). The current WHO exposure categories (Categories I, II, and III) need revision, with a special Category IV for severe exposures. Rare cases of PEP failure have occurred in severe bites to the head and neck. Multiple factors, including route, wound severity, depth, contamination, viral dose, proximity to highly innervated areas and the CNS, and the number of lesions, remain unconsidered. Injuries in areas of high neural density are the most significant considering lyssavirus pathophysiology. Current recommendations do not account for these factors. A Category IV designation would acknowledge the severity and the increased risk of progression. Subsequently, patient management would be optimized with wound care and the appropriate administration of rabies-immune globulin/monoclonal antibodies (RIG/MAbs). All Category IV exposures would be infiltrated with the full dose of intact RIG (i.e., human RIG or MAbs) if the patient was previously unvaccinated. More concentrated RIG/MAb formulations would be preferred. As a world rabies community, we cannot tolerate PEP failures. A fourth WHO categorization will improve the care of these high-risk patients and highlight the global health urgency of this neglected disease.