INFECTIOUS DIARRHEA IN THE ELDERLY

INFECTIOUS DIARRHEA 0889-8553/01 $15.00 + .OO

INFECTIOUS DIARRHEA IN THE ELDERLY

Peter K. Slotwiner-Nie, MD, and Lawrence J. Brandt, MD

Infectious diarrhea is an important cause of morbidity and mortality among the elderly in the United States. The full scope of its impact has been recognized more in recent years: in part perhaps because of better recognition of secondary hemodynamic consequences from acute diarrhea. Because atherosclerosis is so common in the elderly, complications that are uncommon in younger individuals are seen more frequently in the elderly, including myocardial, renal, cerebrovas- cular, and intestinal ischemia. This article reviews the epidemiology of infectious diarrhea in the elderly, age-related changes in intestinal physiology and immune system function, and some of the causative agents most commonly associated with infectious diarrhea in elderly patients. Although not classically considered to be infectious diarrhea, bacterial overgrowth is another cause of diarrhea in the elderly and is discussed.

EPIDEMIOLOGY

Life expectancy in the United States has risen from an average of 45 years in 1900 to 75 years at present. By the year 2025, 22% of the US population will be older than age 65.5 Gastrointestinal function is altered in many ways with aging: and the elderly are at an increased risk for certain illnesses, among which are various diarrheal diseases, including infectious diarrhea.4

Infectious diarrhea is an important cause of morbidity and mortality in the elderly. Although there is extensive literature about morbidity and mortality from infectious diarrhea in children, little has been published specifically about these issues in elderly patients except for Closfridium dificile colitis and Esche-

From the Division of Gastroenterology, Department of Medicine, Albert Einstein College of Medicine (PKSN, LJB) and Montefiore Medical Center (LJB), Bronx, New York

GASTROENTEROLOGY CLINICS OF NORTH AMERICA

VOLUME 30 * NUMBER 3 * SEMEMBER 2001 625

626 SLOTWINER-NIE & BRANDT

richiu coli 0157H7. One large analysis by Lew et alZ1 reviewed 28,538 diarrheal deaths (cases in which diarrhea was listed as either an immediate or an underlying cause of death) between 1979 and 1987. Lew et alZ1 found that most deaths from diarrhea occurred in individuals who were older than 74 years (51%); mortality was less among adults aged 55 to 74 years (27%) and least in children younger than 5 years (ll?'~).

In a later study addressing the incidence and complications of gastroenteritis, Gangarosa et all6 analyzed 4.06 million hospitalizations in the McDonnell- Douglas Health Information System database from 1985. Gastroenteritis was recorded as a discharge diagnosis in 98,185 hospitalizations and led to 1130 deaths. Gangarosa et all6 analyzed 87,181 hospitalizations (89%) and 514 deaths (45%) for which gastroenteritis was one of the top 3 diagnoses. Gastroenteritis was among the top 3 diagnoses in 9% of all hospitalizations of children 1 to 4 years old compared with 1.5% of hospitalizations throughout adulthood (220 years old). Only 0.05% of hospitalizations involving gastroenteritis were fatal for children younger than 5 years, compared with a 3% fatality rate in individuals 80 years of age or older. The older group represented 85% of all deaths from diarrhea. Age was the most important risk factor for death consequent to a hospitalization involving gastroenteritis. The authors of this study concluded that gastroenteritis is a large, underemphasized public health problem among the elderly, and that the case-fatality ratio is higher in the elderly than in children.

In parallel with the increasing age of the population, more elderly Ameri- cans live in group settings, a situation that could promote person-to-person spread of infectious diarrhea. Recognition of this problem was heightened after the report of a deadly outbreak of salmonella infection in a Maryland nursing home in 1970.13 A total of 104 of 145 (72%) residents and 19 of 66 (29%) staff members were infected during a 9-day period. Of the infected residents, 25 (24%) died. The 9 early deaths were attributed to acute dehydration, whereas the later deaths presumably were due to organ infarction and failure related to dehydration; this delayed mechanism of death was proven in one of the cases for which autopsy data were available.

IMMUNOSENESCENCE

The phenomenon of immunosenescence, or an overall decline in immune function as a consequence of advancing age, is supported by many observations. Infection-related mortality increases with age, and the elderly undergo a progres- sive decline in their ability to react to environmental stresses, such as exposure to new strains of infectious organisms. Several animal and human studies have provided evidence for specific immune system alterations with age that may lead to increased susceptibility to gastrointestinal infections?, 33, Evidence for age-related immune dysfunction is as follows:

400-fold increase in mortality from gastrointestinal infections among Japa-

Many elderly have debilitating diseases that compound immunosenes-

Age-related decline in helper T-cell numbers Age-related decline in T-cell function secondary to reduced intracellular

Mucous membranes of older individuals have an increased susceptibility

nese patients older than age 75

cence

calcium

INFECTIOUS DIARRHEA IN THE ELDERLY 627

to infection (possibly owing to decreased IgA on mucous membrane surface) Age-related increase in serum IgA may reflect a secretory defect that leads to reduced IgA levels on mucous membrane surfaces Decreased antibody-forming potential in elderly subjects Decreased efficacy of vaccines for influenza viruses and pneumococcal

Alteration in gut flora populations (eg , increased coliforms) Increased rate of progression of human immunodeficiency virus (HIV)

infections

infection in elderly

Systemic Immune System

The thymus gland reaches its peak mass at puberty and thereafter begins a process of involution. Only 5% to 10% of the original thymic mass remains by age 50.5 Absolute numbers of systemic, circulating T cells may be preserved, but there are changes in T-cell subset distributions, such as a reduction in the number of immature, autorosette-forming T cells and CD4 (helper) T cells. Flow of calcium into T cells of an aged person is impaired, leading to T-cell inactiva- tion and reduced cytokine ~ecreti0n.l~

B-cell function is aberrant in older subjects, as evidenced by high titers of autoantibodies and nonspecific circulating immunoglobulins. Despite such high titers, production of specific antibodies in response to antigens, such as pneumo- coccus and influenza vaccines is impaired.

Mucosal Immune System

Although there has been much investigation regarding age-related dysfunction of the systemic immune system, little specific work has been done to investigate such alterations in the secretory immune system of the intestinal mucosa. Finkelstein et all5 reported elevated serum levels of IgA in elderly subjects. Some authors speculated that this elevation may reflect a defect in the intestine's ability to secrete IgA into the gut lumen and that this in turn may lead to increased susceptibility to gastrointestinal infection^.^^ In contrast to this belief, Arranz et all showed that although there are elevated IgA concentrations in the serum and parotid gland secretions of the elderly compared with the same fluids of younger subjects, the amount of IgA secreted into the gut lumen, as measured by whole-gut lavage, was equal in both groups.

Physiologic Changes

Gastric acid provides a protective barrier that prevents many microorgan- isms from gaining systemic access through the gastrointestinal tract. It is be- lieved by many that a reduction in acid secretion accompanies aging; however, this belief has been proven to be untrue. Peak and basal acid secretion remain intact in healthy elderly subjects.", l4 Many elderly patients are hypochlorhydric or achlorhydric because of chronic atrophic gastritis, post-gastric surgical changes, degenerative systemic illness, or the use of potent medications that inhibit acid secretion.


Environmental Factors

Environmental factors play a role in the prevalence and spread of intestinal infections among the elderly. Greater numbers of elderly people now reside in group homes, a situation facilitating the spread of infectious agents. In a study from Great Britain, Ryan et a132 reported that 22% of all outbreaks of infectious intestinal diseases were associated with residence in an institution and that 95% of these institutions were for elderly patients ( eg , skilled nursing facilities and nursing homes). In their series, 71% of the outbreaks were attributed to person- to-person contact, and 21% were attributed to ingestion of contaminated food. How any of these observed and sometimes conflicting alterations in immune function specifically relate to the incidence of and morbidity and mortality from infectious diarrhea remains to be proven.

Clostridium difficile

In the 1970s, C. dificile was identified as the major cause of antibiotic- associated diarrhea. Infection with C. dificile is characterized by fever, nonbloody diarrhea, lower abdominal cramps, and marked leukocytosis. The spectrum of clinical disease severity is wide and includes asymptomatic carriage, mild diarrhea, and death secondary to toxic megacolon. There is a perception that C. dificile infection is commoner among the elderly and that it is associated with excess morbidity and mortality in the elderly. Although the former is true, the latter statement is based largely on anecdote and has been disproven (see later).8

Karlstrom et all9 looked at all cases of C. dificile-associated diarrhea oc- curring in Sweden during 1995 and reported a more than 10-fold increase in the incidence of C. dificile-associated diarrhea in persons 60 to 98 years old compared with the incidence in younger subjects. These investigators found that the incidence of C. dificile-associated diarrhea was significantly higher in rehabilita- tion and geriatric wards compared with other types of wards within the hospitals they surveyed.

Elderly patients are probably at more risk for acquiring nosocomial C. dificile infection than are other groups simply because they are more likely to spend more time in long-term and short-term care facilities. Several studies have documented the risk of acquisition of C. dificile infection in institutionalized patients. McFarland et a P reported that 83 of 399 (21%) C. dificile-negative patients admitted to a general medical ward acquired C. dificile infection and that 37% of those who acquired C. dificile infection developed symptomatic diarrhea. Rudensky et alm reported a 12.2% acquisition rate among 98 initially C. dificile-negative patients admitted to an acute-care geriatric ward.

In a study by Walker et a1,4* 7.1% of asymptomatic long-term care facility residents had stool cultures that were positive for C. dificile. The use of antibiotics, particularly cephalosporins and trimethoprim-sulfamethoxazole, and the use of H2-blockers were identified as risk factors for a C. dificile-positive stool culture. Other factors reported to increase the spread and acquisition of C. dificile in elderly patients include bowel incontinence, laxative use, and use of other medications that alter bowel flora."

Ramaswamy et alB reported on several factors that heralded increased mortality in the elderly: a serum albumin less than 2.5 g/dL on admission, a decrease in serum albumin of more than 1.1 g/dL at the onset of symptoms, the use of 3 or more antibiotics, and a persistently positive stool assay for C. dificile toxin after 7 days of therapy. There was no relation between mortality and a


variety of factors, such as age, sex, residence, past medical history, presenting complaints, or history of prior episodes or recurrent episodes of C. dificile colitis.

Not only is the incidence of C. dificile infection increased in elderly persons, but also the immune response of elderly individuals to this organism may be different than the immune response of younger people. C. dificile elaborates 2 toxins that work through different mechanisms to cause diarrhea in an infected host: Toxin A, an enterotoxin, causes fluid secretion and inflammation that leads to mucosal damage in rodent models; toxin B is a cytotoxin and exerts its effect through the disruption of the actin cytoskeleton. A study by Triadafilopoulos et al4I showed that compared with younger subjects, granulocytes harvested from subjects 65 years old or older, have an increase in vitro migratory response when exposed to purified C. dificile toxin A. These authors speculated that this enhanced chemotactic effect in the elderly might result in a heightened inflammatory response and more severe colitis. Bassaris et a12 investigated gran- ulocyte function in elderly patients between 69 and 82 years old and showed that polymorphonuclear leukocytes from elderly patients had a reduced ability to phagocytose C. dificile organisms in comparison with the white blood cells of younger subjects.

Despite the existing epidemiologic data, in vitro studies, and the theoretical reasons to suspect a worse clinical course of C. dificile-associated diarrhea in the elderly, this belief has been challenged. In a report from this institution, Brandt et a19 prospectively studied 89 patients with C. dificile colitis. Patients were divided by age into 2 groups. Patients at least 60 years old comprised the elderly subgroup. There was no statistically significant difference in mortality from C. dificile-associated diarrhea between the 2 groups (1 death in the young patient group versus 4 deaths in the elderly group, P = NS). Although fever occurred equally in both groups, white blood cell counts were more likely to be elevated in the elderly group (P<.05). One striking difference between the 2 age groups was the timing of diagnosis. Young patients were much more likely to be diagnosed with C. dificile colitis during the first 5 days of hospitalization compared with elderly patients, whose diagnosis usually was made after 2 weeks of hospitalization (P<.OOOl). This observation is consistent with the belief that most elderly patients develop infection with C. dificile through nosocomial spread.

Therapy for C. dificile colitis in elderly patients is based on the same principles as in other groups. Adequate hydration must be administered, and the offending antibiotics should be removed, if possible. Metronidazole or, if necessary, oral vancomycin should be given. For chronic relapses, therapy with probiotic agents may be beneficiaLZ7

C. dificile colitis is commoner among the elderly; usually it is acquired through nosocomial spread. Decreasing serum albumin levels and persistence of toxin in stool samples may be predictive of increased severity of illness. Al- though there is alteration of some in vitro measures of immune function and inflammatory reaction in elderly subjects, reports do not show any increased morbidity and mortality from C. dificile colitis in elderly individuals.

Escherichia coli 0157:H7

In 1982, E. coli 0157H7 was identified as the causative agent of an outbreak of hemorrhagic colitis.z9 Since then, this organism has emerged as an increasingly identified cause of sporadic and clustered outbreaks of infectious diarrhea and postdiarrheal hemolytic-uremic syndrome (HUS). Most reports of clusters, in-


cluding those in elderly patients, have implicated undercooked beef as the initial source of infection. In addition to undercooked beef, other meats, cheeses, person-to-person contact? lo, 35 water s~pplies,3~ and unpasteurized apple cider have been implicated.

The mechanism by which E. coli 0157H7 causes diarrhea and HUS is not understood fully. The organism can adhere to the mucosal surface, where it produces Shiga-like toxins. These toxins can damage intestinal vessels and ultimately result in increased translocation of bacterial lipopolysaccharide from the intestinal lumen into the systemic circulation.6 On the basis of experimental evidence and clinical, microbiologic, and epidemiologic studies, toxinemia has been implicated as the inciting pathogenic event in the spectrum of illnesses associated with E. coli 0157H7 (e.g., diarrhea, hemorrhagic colitis, and HUS). A wealth of evidence suggests the following series of pathologic events after infection with E. coli 0157H7 and release of Shiga-like toxins.38 Vascular endo- thelium is damaged, and the subendothelium beneath the disrupted surface is exposed; prostacyclin synthesis is decreased, and platelet agglutination ensues, followed by a cascade of coagulative events leading to intravascular thrombi formation. Ischemic changes are precipitated by platelet-fibrin thrombi in the colonic microvasculature with resultant hemorrhagic colitis. Patients who develop HUS or thrombotic thrombocytopenic purpura represent a clinical spectrum arising from the same underlying disease process but differing mainly in the location of thrombotic lesions.

Patients at the extremes of life are most susceptible to infection with E. coli 0157H7 and the development of HUS.6 As alluded to earlier, several authors reported clustered outbreaks in nursing home facilities,’O< 31, 36 highlighting the importance of considering this diagnosis in elderly patients and the need to implement infection control measures promptly to avoid widespread infection.

A broad spectrum of presentations can be seen with E. coli 0157H7. Patients can be asymptomatic; have diarrhea that can be bloody or nonbloody; or develop HUS, thrombocytopenic purpura, and death. Typically, elderly patients initially present with watery diarrhea followed by the development of grossly bloody stools within hours to a few days. Fever is not a prominent feature of infection with E. coli 0157H7. Nausea and vomiting can be seen in about half of patients. Radiographs may show ascending and transverse colonic thickening and thumb- printing suggestive of ischemic colitis. Among the elderly, 22% may go on to develop HUS. Of patients who develop HUS, an 88% case-fatality rate has been reported.10 In addition to extremes of age, other risk factors for development of HUS include the presence of bloody diarrhea, fever, an elevated leukocyte count, and therapy with antimotility agents?

Diagnosis requires clinical suspicion of E. coli 0157H7 or recognition of one of the associated complicating syndromes of infection with E. coli 0157H7, followed by appropriate stool cultures. Because E. coli 0157H7 ferments D-sorbitol relatively slowly, it appears colorless on sorbitol-MacConkey agar culture plates, in contrast to other species of E. coli. These sorbitol-negative strains can be screened for reactivity with 0157 and H7 antisera for definitive identification.

In a novel approach to diagnosing E. coli 0157:H7 infection, Su et a137 evaluated archived pathology specimens taken from 2 cases of proven E. coli 0157H7 colitis and 11 cases of ischemic colitis using an E. coli 0157H7-specific immunoperoxidase staining technique. Three of the 11 (27%) biopsy samples from the ischemic colitis patients tested positive, as did both cases of E. coli 0157H7 colitis. The authors hypothesized that E. coli 0157H7 may have a causative role in some cases of ischemic colitis and suggested use of this tech-


nique to establish the diagnosis of E. coli 0157H7 infection retrospectively when stools have not been cultured, but paraffin blocks of biopsy specimens are available. ~~ ~

There is no specific therapy for infectious diarrhea resulting from E. coli 0157:H7. Supportive care with early hydration is the mainstay of therapy. Some authors have noted worse outcomes in patients treated with antibiotics; however, this may be due to a selection bias whereby sicker patients are more likely to receive antibiotics. Currently, most authors do not recommend therapy with antimicrobial agents. Antimotility agents are contraindicated because this is a toxin-mediated disease.

NONTYPHOIDAL SALMONELLOSIS

Salmonella is one of the most deadly causes of gastroenteritis in the elderly. Several authors reported that Salmonella is the cause of most deaths attributed to outbreaks of infectious intestinal disease in nursing 32 In a survey of infectious intestinal disease among institutionalized individuals in England and Wales, Salmonella infection accounted for 170/0 of all identified cases, second in frequency only to small round structured viruses.32 Levine et alZ0 reported that Salmonella accounted for most (52%) food-borne outbreaks in nursing homes and 81% of deaths secondary to food-borne disease outbreaks. These reports of nursing home outbreaks attest to the importance of environmental factors that favor person-to-person spread and the hazards of food prepared at a central sta- tion.

Elderly individuals can present with classic symptoms of Salmonella gastroenteritis-nausea and vomiting followed by abdominal cramps and diarrhea. In contrast to younger subjects, however, the elderly are less likely to develop gastrointestinal symptoms and are more likely to develop invasive salmonellosis with bacteremia.40

The increased rate of complications among elderly individuals infected with Salmonella is probably due to a number of factors, including age-related immunosenescence and underlying chronic disease. Bradley and Kauffman7 showed that senescent rats have a diminished febrile response to infection with Salmonella typhimurium that is associated with increased bacterial counts in the liver and spleen. The rate of Salmonella bacteremia as a complication of intestinal infection increases with age in experimental model^.^ Other factors that predis- pose to Salmonella septicemia that are seen more commonly in the elderly include previous gastric surgery, hypochlorhydria, gastric atrophy, malignant disease, and chronic cardiopulmonary disease.40

In adults who are not elderly and who have no underlying disease, the routine use of antibiotics is not recommended for uncomplicated Salmonella gastroenteritis because it has not been shown to alter the clinical duration of illness, and it can prolong the duration of intestinal carriage. In contrast to other age groups, the routine application of antibiotic therapy is recommended for individuals at the extreme ages of life40 because of the high rate of complications seen in these individuals.

Shigella

There are 4 groups of Shigella: (1) S. dysenteriae, (2) S. flexneui, (3) S. boydii, and (4) S . sonnei. Most infections in Western countries are due to S. sonnei. S.

632 S L 0 " E R - M E & BRANDT

flexneri usually causes more severe disease. Shigellu is spread through fecal-oral contamination and requires a relatively small inoculum. Typical .presentations include fever, malaise, lower abdominal cramping, diarrhea, and tenesmus. Initially, Shiga toxin produces watery small-bowel diarrhea. Tissue invasion in the colon 48 to 72 hours later results in dysentery.12

Most of the available literature regarding Shigellu concerns children because infection in healthy adults is usually subclinical and does not require medical attention. Halpem et alls studied 116 hospitalized Israeli adults during a 10-year period. Because hospitalization selected for sicker patients, these investigators saw more S. flexneri than ordinarily would be expected. Halpem et alls found that infection severity with S. flexneri (but not S. sonnei) increased with age as measured by duration of diarrhea, fever, and hospital stay. Adult patients were more likely than children to have a leukocytosis, and elderly patients were more likely to have an elevated blood urea nitrogen and liver enzyme abnormalities. Age greater than 65 years has been reported as a risk factor for developing Shigellu ba~teremia?~ which carries a higher mortality rate than uncomplicated intestinal infection.

Therapy consists of hydration and supportive care. Antibiotics are not always necessary in healthy adults with uncomplicated disease. Elderly or debilitated patients with underlying disease should be treated with appropriate antibiotics.

VIRAL GASTROENTERITIS

The true incidence of viral gastroenteritis among the elderly is not known because routine stool tests do not detect viral pathogens. Rotavirus and Nor- walk-like virus are the pathogens most commonly identified as the causative agents in outbreaks of viral gastroenteritis among the elderly. Features of viral gastroenteritis outbreaks among the elderly that are in contrast to bacterial outbreaks include (1) sudden and rapid onset of nausea and vomiting, (2) higher attack rates in general, and (3) higher attack rates among women compared with

' Lewis et al" reported an outbreak of viral gastroenteritis characterized by 2 waves of infection in an inpatient geriatric ward. Using electron microscopy and latex agglutination assays of stool samples, Rotavirus was identified as the causative agent in the first wave of infection. The attack rate of the first wave among residents and staff was 68%. In contrast to other reports of viral gastro-

the attack rate among men and women was the same. In the second wave approximately 1 month later, 50% of individuals infected with rotavirus went on to develop gastroenteritis secondary to astrovirus. As in other age groups, therapy for elderly persons with viral gastroenteritis primarily consists of supportive care with attention to adequate volume resuscitation.

BACTERIAL OVERGROWTH

Although not classically considered to be an infectious cause of diarrhea, bacterial overgrowth is an important consideration when evaluating an elderly patient with diarrhea. In contrast to diarrhea caused by bacterial and viral gastroenteritis, diarrhea caused by bacterial overgrowth usually has a subacute or chronic presentation. The elderly are at increased risk for bacterial overgrowth for many reasons. Hypochlorhydria or achlorhydria is commoner among the


elderly because of post-gastric surgical changes and the common use of potent antisecretory medications. Other noniatrogenic anatomic and physiologic alterations seen among the elderly, such as jejunal diverticulosis and intestinal dysmotility, favor bacterial overgrowth and can lead to diarrhea.

When diarrhea secondary to bacterial overgrowth is suspected, the diagnosis can be supported by hydrogen breath testing, by elevated serum folate levels, or indirectly by response to a trial of empirical therapy with antibiotics. Rarely are quantitative cultures performed on small intestinal aspirates.

Therapy usually consists of a course of antibiotics. Tetracycline is used most commonly. In patients with frequent relapses, a schedule of rotating antibiotics may be necessary. Rarely the correction of an intestinal anatomic abnormality, such as a blind loop or intestinal stricture, is required. In patients with diarrhea from bacterial overgrowth, micronutrient malabsorption should be sought out and treated if found.

SUMMARY

Infectious diarrhea is an important disease in the elderly. Some basic princi-

Infectious diarrhea is an underappreciated health problem. There is a higher mortality rate and case-fatality rate compared with

Infectious diarrhea is most often associated with group settings (e.g.,

Infectious diarrhea may be associated with abnormal immune function

Certain bacterial infections are commoner (e.g., C. dificile, E. coli 0157H7,

Some infections behave differently (e.g., Salmonella). Prompt and adequate rehydration measures are crucial. The institution of appropriate contact isolation and infection control mea-

ples have been outlined, as follows. In the elderly:

younger persons.

nursing homes and skilled nursing facilities) or antibiotic use.

(i.e., immunosenescence).

and Salmonella).

sures is crucial in group settings.

References

1. Arranz E, OMahony S, Barton JR, et a1 Immunosenescence and mucosal immunity: Significant effects of old age on secretory IgA concentrations and intraepithelial lym- phocyte counts. Gut 33:882-886, 1992

2. Bassaris HP, Lianou FE, Legakis NJ, et al: Interaction between Clostridium difficile and polymorphonuclear leukocytes from the elderly and postoperative cancer patients: Phagocytosis and bactericidal function. Med Microbiol Immunol 173:49-55, 1984

3. Belongia EA, Osterholm MT, Soler JT, et a1 Transmission of Escherichia coli 0157:H7 in Minnesota child day-care facilities. JAMA 269:883-888, 1993

4. Bennett RG, Greenough WB: Approach to acute diarrhea in the elderly. Gastroenterol Clin North Am 22:517-533. 1993

5. Blechman MB, Gelb AM:’Aging and gastrointestinal physiology. Clin Geriatr Med 15:429438, 1999

6. Boyce TG, Swerdlow DL, Griffin P M Escherichia coli 0157H7 and the hemolytic-

7. Bradley SF, Kauffman C A Aging and the response to Salmonella infection. Exp Gerontol

8. Brandt LJ: Gastrointestinal Disorders of the Elderly. New York, Raven Press, 1984

uremic syndrome. N Engl J Med 333:364-368, 1995

25:75-80, 1990


9. Brandt LJ, Kosche KA, Greenwald DA, et al: Clostridium dzfftcile-associated diarrhea in

10. Carter AO, Borczyk AA, Carlson JA, et al: A severe outbreak of Escherichia coli the elderly. Am J Gastroenterol94326S3266, 1999

0157H7-associated hemorrhagic colitis in a nursing home. N Engl J Med 3171496- 1500, 1987

11. Collen MJ, Abdulian JD, Chen M(: Age does not affect basal gastric acid secretion in normal subjects or in patients with acid-peptic disease. Am J Gastroenterol 89:712- 716,1994

12. Du'Pont HL, Hornick RB, Dawkins AT, et al: The response of man to virulent Shigella flexnevi 2a. J Infect Dis 119:296-299, 1969

13. Farber RE, Solomon N, Garber HJ, et al: Salmonellosis-Baltimore, Maryland. MMWR Morb Mortal Wkly Rep 19314,1970

14. Feldman M, Cryer B, McArthur KE, et a1 Effects of aging and gastritis on gastric acid and pepsin secretion in humans: A prospective study. Gastroenterology 1101043- 1052, 1996

15. Finkelstein MS, Tanner M, Freedman ML: Salivary and serum IgA levels in a geriatric outpatient population. J Clin Immunol4:85-91,1984

16. Gangarosa RE, Glass RI, Lew JF, et al: Hospitalizations involving gastroenteritis in the United States, 1985: The special burden of the disease among the elderly. Am J Epidemiol 135:281-290, 1992

17. Gelb AM The aged in general. In Gelb AM (ed): Clinical Gastroenterology of the Elderly. New York, Marcel Dekker, 1996, pp 1-6

18. Halpem Z, Dan M, Giladi M, et al: Shigellosis in adults: Epidemiologic, clinical and ' laboratory features. Medicine (Baltimore) 68210-217, 1989 19. Karlstrom 0, Fryklund B, Tullus K, et a1 A prospective nationwide study of Clostridium

difficile-associated diarrhea in Sweden. Clin Infect Dis 26:141-145. 1998 20.

21.

22.

23.

24.

25.

26.

27.

28.

29.

30.

31.

32.

33.

L k n e WC, Smart JF, Archer DL, et al: Foodbome disease outbreaks in nursing homes,

Lew JF, Glass RI, Gangarosa RE, et al: Diarrheal deaths in the United States, 1979 through 1987 A special problem for the elderly. JAMA 265:3280-3284, 1991 Lewis DC, Lightfoot NF, Cubitt WD, et a1 Outbreaks of astrovirus type 1 and rotavirus gastroenteritis in a geriatric in-patient population. J Hosp Infect 14:9-14,1989 McFarland LV, Mulligan ME, Kwok RY, et a1 Nosocomial acquisition of Clostridium dzfftcile infection. N Engl J Med 3203204-210, 1989 Morduchowicz G, Huminer D, Siegman-Igra Y, et al: Shigella bacteremia in adults: A report of five cases and a review of the literature. Arch Intem Med 14732034-2037,1987 Pavia AT, Nicholas CR, Green DP, et al: Hemolytic-uremic syndrome during an outbreak of Escherichia coli 0157H7 infections in institutions for mentally retarded persons: Clinical and epidemiological observations. J Pediatr 116544-551, 1990 Pegues DA, Woemle C H An outbreak of acute nonbacterial gastroenteritis in a nursing home. Infect Control Hosp Epidemiol 1487-94,1993 Pochapin M: The effect of probiotics on Clostridium dzfftcile diarrhea. Am J Gastroenterol

Ramaswamy R, Grover H, Corpuz M, et a1 Prognostic criteria in Clostridium difftcile colitis. Am J Gastroenterol 9L460-464, 1996 Riley LW, Remis RS, Helgerson SD, et al: Hemorrhagic colitis associated with a rare Escherichia coli serotype. N Engl J Med 308:681485, 1983 Rudensky B, Rosner S, Sonnenblick M, et al: The prevalence and nosocomial acquisition of Clostridium dificile in elderly hospitalized patients. Postgrad Med J 69:4547, 1993 Ryan CA, Tauxe RV, Hosek GW, et a1 Escherichia coli 0157H7 diarrhea in a nursing home: Clinical, epidemiological and pathological findings. J Infect Dis 154:631-638, 1986 Ryan MJ, Wall PG, Adak GK, et al: Outbreaks of infectious disease in residential institutions in England and Wales 1992-1994. J Infect 3449-54,1997 Schmucker DL, Daniels CK Aging, gastrointestinal infections, and mucosal immunity. J Am Geriatr SOC 34377-384,1986

1975 through 1987. JAMA 266:2105-2109, 1991

95:S11-13,2000


34. Schmucker DL, Heyworth MF, Owen RL, et a1 Impact of aging on gastrointestinal mucosal immunity. Dig Dis Sci 41:1183-1193, 1996

35. Spika JS, Parsons JE, Nordenberg D, et a1 Hemolytic uremic syndrome and diarrhea associated with Escherichiu coli 0157H7 in a day care center. J Pediatr 109287-291,1986

36. Stewart PJ, Desormeaw W, Chene J: Hemorrhagic colitis in a home for the a g e d a t a r i o . Can Dis Wkly Rep 929-32, 1983

37. Su C, Brandt LJ, Sigal S, et a1 The immunohistological diagnosis of E. coli 0157H7 colitis: Possible association with colonic ischemia. Am J Gastroenterol 93:1055-1059, 1998

38. Su C, Brandt LJ: Escherichiu coli 0157H7 infection in humans. Ann Intern Med 123:698- 714, 1995

39. Swerdlow DL, Woodruff BA, Brady FC, et a1 A waterborne outbreak in Missouri of Escherichiu coli 0157H7 associated with bloody diarrhea and death. Ann Intern Med 117812-819, 1992

40. Thuluvath PJ, McKendrick Mw: Salmonella and complications related to age- Sheffield experience. OJM 67497-503, 1988

41. Triadafilopoulos G, Shah MH, Pothoulakis C: The chemotactic response of human granulocytes to Clostridium dzfflcile toxin A is age dependent. Am J Gastroenterol

42. Walker KJ, Gilliland SS, Vance-Bryan K, et al: Clostridium dzfflcile colonization in residents of long-term care facilities: Prevalence and risk factors. J Am Geriatr SOC 41:940-946, 1993

86:1461-1465, 1991

Address reprint requests to Peter Slotwiner-Nie, MD

Division of Gastroenterology Department of Medicine

Montefiore Medical Center 111 E 210th Street Bronx, NY 10467

Documents

INFECTIOUS DIARRHEA IN THE ELDERLY