case records of the massachusetts general hospital n engl j med 366;11 nejm.org march 15, 2012 1041 The patient’s white-cell count and differential count are normal and are not highly suggestive of a bac- terial process. Could this be a usual community- acquired viral illness such as enterovirus or noro- virus infection? Might it be cytomegalovirus (CMV) or adenovirus infection related to immunosup- pression? The abrupt onset of the patient’s illness is consistent with norovirus infection, which is characterized by vomiting, diarrhea, and moder- ate fever in about half of cases. Most patients make a rapid and complete recovery in 1 to 2 days. This virus is usually associated with large outbreaks of illness, and at the time of this patient’s presen- tation, it was not known to be circulating within our community, although there was a spike in norovirus activity in the previous year. The patient is at considerable risk for CMV infection, although his illness seems somewhat acute for reactivation of CMV, which is usually more gradual in onset and often causes leukope- nia. He had received therapy with natalizumab, a biologically active agent approved for treatment of refractory multiple sclerosis and Crohn’s dis- ease. Natalizumab has been associated with pro- gressive multifocal leukoencephalopathy, a poten- tially fatal neurologic infection caused by JC virus, a human polyomavirus, but it usually occurs much later in the course of therapy (after many monthly infusions). JC virus does not cause gastrointesti- nal symptoms or diarrhea and therefore is not a consideration in this case. Finally, enterovirus in- fections can have protean manifestations beyond gastrointestinal symptoms, including neurologic, pleural, cardiac, ocular, and cutaneous manifes- tations, and they can be especially severe and po- tentially fatal in persons who have agammaglo- bulinemia, who have undergone bone marrow transplantation, who have B-cell defects, or who are receiving rituximab therapy. Enteroviruses would be worthy of consideration in this patient. This patient’s blood cultures were reported to be positive for bacteria after 1 day. When consider- ing bacterial infections that cause gastrointesti- nal disease, one must first think about foodborne illnesses mediated by toxins such as preformed Bacillus cereus toxin, staphylococcal toxins, or even toxins transmitted by fish or shellfish. Such ma- rine toxins are unlikely in this case, since our pa- tient had a high fever and an absence of other char- acteristic symptoms, such as flushing, headache, and neurologic symptoms. Nontyphoidal salmonellae and campylobacter are the most common causes of bacterial enteritis in the United States and are serious considerations in this patient. Both organisms are associated with poultry, and salmonellae are also associated with eggs. Salmonella serotypes vary considerably by location, but Salmonella enterica serotype Enteritidis and S. enterica serotype Typhimurium are the most common and may cause systemic illness with bacteremia. This patient is an ideal candidate for infection with salmonella, which is by far the most likely cause of enteritis with bacteremia, since it commonly contaminates the worldwide food chain. Campylobacter jejuni and C. coli are the most com- mon of the campylobacter species, which are less likely than salmonellae to cause bacteremia. There are other less common campylobacter species, such as C. fetus, which has a vascular tropism and may cause vascular infection, endocarditis, or sep- tic thrombophlebitis, sometimes in immunocom- promised hosts. Could this be a case of Clostridium difficile in- fection or possibly infection with C. difficile and another secondary bacteremia of intestinal origin in an immunocompromised host? Community- acquired C. difficile infection in the absence of pre- vious antibiotic therapy is possible but not likely. People with impaired antibody-based immunity, including the generally ill and the elderly, may be more likely to acquire C. difficile infection. It is also important to remember that bacteremias with staphylococci or pneumococci may present with nonspecific diarrheal symptoms, so it is always important to look carefully for other sites of in- fection or portals of entry that might not be obvi- ous in an immunocompromised host. When considering foodborne illnesses, obtain- ing a careful history of exposures to food and animals can be helpful. Each year, one of six per- sons in the United States has a foodborne illness and about 3000 persons die from the foodborne diseases (www.cdc.gov/foodborneburden). Infec- tion with Shiga-toxin–producing Escherichia coli characteristically causes bloody diarrhea and no fever and sometimes toxin-mediated renal failure. The recent outbreak in Europe of a toxigenic E. coli, non-O157 serotype, 1 reminds us that several ap- parently fresh and healthful foods, such as bean sprouts, are prime suspects in outbreaks of food- borne illness and also highlights the fact that
