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Stool examination: Culture versus gram stain
SPECIAL CONTRIBUTION cost effectiveness, culturing, stool; culturing, stool; stool culturing, cost effectiveness
Stool Examination: Culture Versus Gram Stain Presented is a methodology for efficient, cost-effective collection, transport, culture, and microscopic examination of infectious diarrhea. A critical review of the literature is included, as are guidelines for workup and management of the disease complex in the emergency department. [Adler P: Stool examination: Culture versus Gram stain. Ann Emerg Med March 1986; 15:337-341.] INTRODUCTION Diarrheal disease in the ambulatory patient has been studied since World War I. I Many of the studies were done in areas of the world in which the incidence of the disease is high. However, the results of studies from Bangladesh and other underdeveloped areas may not be applicable to a busy emergency department practice, and probably do not represent high-quality, cost-effective medical care techniques for the 1980s.2 Questions of concern to the emergency physician include when to do a culture or microscopic examination of stool; how many stool samples are needed; which medium of transport should be used; which patients are at high risk for colon cancer and should have their stool tested for blood; and which situations do not require definitive diagnosis. The indications for stool examination in the emergency department are the following:3 1) Diarrhea for more than 72 hours; 2) Change in stool consistency, odor, or color for more than 72 hours; 3) Blood in stool or rectum; 4) Itching in rectum; 5) Diarrhea in a patient on antibiotics or antimetabolites; and 6) Diarrhea in a toxic patient. Emergency physicians often function as primary care providers, and thus have responsibility for preventive and cost-effective care. Cancer of the colon is one of the most common cancers in men and women. A history of diarrhea in the following high-risk groups mandates examination of stool for blood: 4 1) Previous history of colon cancer; 2) History of ulcerative colitis; 3) Symptoms suggestive of colorectal cancer; 4) Familial polyposis or Gardner's syndrome; 5) Family history of cancer of the colon; and 6) History of adenoma of the colon. If a n y of these risk factors is present, the patient should be referred for outpatient radiological examination and follow-up. Significant numbers of cases of parasitic or infectious diarrhea are seen in the male and female homosexual populations and in a segment of the heterosexual population. The primary mode of transmission of the disease in these populations is unhygienic sexual practice, including analingus and anal coitus followed by fellatio. Some investigators recommend culturing all homosexual patients, even ff they are asymptomatic, because more than onefourth of homosexual patients have parasitic infestation (Entamoeba histolytica and Giardia lamblia), s Another group that is at risk for parasitic diarrhea is international travelers 15:3 March 1986
Annals of Emergency Medicine
Paul M Adler, DO Philadelphia, Pennsylvania From the Department of Emergency Medicine, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania. Presented at the Winter Symposium Advances Track of the American College of Emergency Physicians in San Diego, California, April 1985. Address for reprints: Paul M Adler, DO, Thomas Jefferson University Hospital, 111 South 11th Street, Room 252, Thompson Building, Philadelphia, Pennsylvania 19107.
337/163
STOOL EXAMINATION Adler
to endemic areas in the third world. Included are places we think of as developed nations, such as southern Europe, especially Italy from Naples to Sicily and the South of France. Louisiana and parts of Florida may be considered endemic areas as well. In our larger cities, the recent influx of immigrants from endemic areas has increased the clinical pool. In the hospital w i t h o u t a parasitology referral service, the emergency physician should consider performing the procedures shown (Figure). Some of these procedures should be done only in specific situations (eg, Cryptosporidium ssp in an AIDS victim who is toxic or Vibrio ssp seasonally in areas in which shellfish are harvested.
REVIEW OF THE LITERATURE Collection and Transport Examination and collection of stool is optimally done within 30 minutes of passage. 6 Specimens should be collected in a container, not taken from diapers or by rectal swab. z Transport depends on the climate and type of organism sought. At high ambient temperatures, results usually are unsatisfactory. Competition between pathogenic and nonpathogenic bacteria may be such that internal isolation of pathogens is impossible. 8 Although refrigeration would appear to be the answer, low temperature harms shigellae and, to a lesser extent, salmonella. Enteropathic Escherichia coli and other enteric nonpathogenic bacteria are not inhibited by low temperatures. Quick freezing with liquid nitrogen until transport to the laboratory is optimal in tropical climates. The use of two samples with different preservatives is optimal for parasites. The specimens should be placed in polyvinyl alcohol (PVA) preservatives and a 5% or 10% formalin compound. Many hospitals use a onecontainer technique with PVA alone, but lower egg or cyst counts are encountered consistently.9 Urine contamination also lowers counts. Culture of bacteria is obviated by the parasitic preservatives. If parasites are a consideration, the Subcommittee on Laboratory Standards of the American Society of Parasitology recommends three samples for amoeba and one for helminths. The recovery rate for one specimen is 83%; for two, 95%; and for three, 100% .9 The microscopic examination 164/338
costs $40, and increases accuracy by only 5% if three specimens are sent. We recommend two specimens unless the laboratory analyzes stool for ovum and parasites only infrequently, in which case we recommend three samples to increase the accuracy. One sample should be a purged specimen if the clinician is looking for parasites, because most relevant parasites localize in the small intestine and cecum, m In the case of a presumed uncomplicated bacterial infection, we usually send off only one specimen. The infecting organism will appear in almost all specimens.
panied by leukocytes. 12 Campylobacter recently has been reputed to be the most common cause of acute diarrheal illness.13,14 A good quantitative study of leukocytes in Campylobacter infections has not been done. In view of these data, it appears that the absence of leukocytes does not preclude bacterial diarrhea. Not quantitated is the neutrophil response in ulcerative colitis and pseudomembranous enterocolitis. The literature says the response may be profuse, but no statistics are given.
Microscopic Examination
most common cause of diarrhea, has variable regional prevalence ranging from 1.2% to 9.3%, with a mean of 4.4%) s Campylobacter cultures are complex and are not done by all laboratories. Two studies, however, showed that Gram stain had a variable sensitivity of 43% and 80%, but each demonstrated 99.4% specificity for Campylobacter. 16 Yersinia, frequently mentioned in the mid-1970s, is now rarely mentioned in the enteric literature. Studies of both symptomatic and asymptomatic patients yielded incidence of the organism but not prevalence in clinical disease. As mentioned, Shigella has widely varying recovery rates, depending on the study. Enteropathic E coli testing is complex and expensive, is done only in reference laboratories, and only rarely is clinically useful in adults. 17 Bacterial cultures cost between $i5 and $35 per culture, should not be taken by rectal swab, and recover only three pathogenic organisms, Shigella, Salmonellae, and Campylobaeter. Organisms such as enteropathic E coli, Clostridium dificile, Yersinia, and Vibrio cholerae, unless specifically sought, will not be cultured in a general microbiology laboratory. Viral cultures cost $60, and have little clinical applicability. Microscopy versus culture for parasites has been poorly studied. One article 16 suggests that concentrating stool will double the yield for microscopy, and culturing the stool will quadruple the yield. Culturing stool is still a research tool. Giardia lamblia cannot be cultured. 16 Many laboratories will include pH and fat content as routine stool tests.
The examination of stool for leukocytes may be diagnostic and thus costeffective. When a "very large"* number of l e u k o c y t e s are seen, three etiologic bacterial organisms are implicated: Shigella, Entamoeba histolytica, and Campylobacter. No study to date has compared the relative number of leukocytes found with each type of infection. A prospective study at the International Center for Diarrheal Disease Research in Dacca, Bangladesh, examined 1,593 patients with diarrhea and a single pathogen. Clinical condition was not evaluated, but leukocytes alone were found to be very predictive. Only 8% of patients had > 50 PMN/HPF; of these, 39% (interpolated data) had Shigella and 7% had Entamoeba histolytica. In 44% of cases, a Shigella infection had between l0 and 50 PMN/HPE E histolytica had between 10 and 50 PMN/ HPF 61% of the time. A variety of other organisms infrequently (less than 5% of cases) had between 10 and 50 PMN/HPE The leukocyte count in Shigel]a may be clinically more relevant because recovery rates are widely distributed, from a low of 15% to a high of 80%. The literature concerning leukocytes in Shigella is contradictory; in one study, c o r r o b o r a t i n g the Bangladesh findings, 19 of 20 patients had some leukocytes, 11 yet a poorly controlled study from the Centers for Disease Control found that only five of 14 Shigella infections were accom* "Very large" is not well defined in the literature. Only Still's study from Bangladesh has specifically defined "very large" as more than 50 polymorphonuclear cells (PMN) per high-power field (HPF). Annals of Emergency Medicine
Culture Campylobacter, r e p o r t e d l y the
15:3 March 1986
Patient With Diarrhea I
Febrile No
I
I
Toxic*
Duration > 7 days
Yes I No
< 7 days
I
I I
Methylene blue smear
Immunocompromised I
]
High Risk
Low Risk
Yes
!
No
i
Supportive care
I
Methylene blue stain I
50 PMN/HPF
Include smear for
Bacterial culture
Crgptospofidium Bacterial culture
I
Exam for parasites
I
Consider need for special laboratoryt
Smear for ovum and parasites ]
I
I
One concentrated
One purged Over
Under
I
Clinical pictureShigella
Yes
I
One bacterial culture Two smears ovum and parasites
No
I Presume Shigella
I
Culture for bacteria and examine for Entamoeba histolytica
I
I
One concentrated
I
One purged
*Usually required hospital admission. 1-For example, C dificile, Enterotoxigenic, E coil, Yersinia, Vibrio cholerae.
Unless malabsorption is part of the differential diagnosis, however, these tests {which c o s t $18) probably will not add useful information. The examination for visible mucus and blood is downplayed in most studies, The exception is a well-done Campylobacter. study which found that bloody and watery diarrhea with leukocytes resulted from Shigella, Salmonellae, or Campylobacter 83% of 15:3 March 1986
the time. TM Sexually transmitted diseases cannot be cultured from stool, and are poorly retrieved from stool Gram stain. G o n o r r h e a and c h l a m y d i a , which cause mucopurulent proctitis, require a swab from the rectum. The literature is conflicting, but apparently Gram stain is as effective as culture. 19 If a cukure is sent, it should be placed directly on a selective mediAnnals
of Emergency
Medicine
FIGURE. Algorithm for diagnosis of infectious diarrhea. um and incubated as soon as possible.ZO C L I N I C A L DECISIONS The following are recommendations for optimal decisions in terms of rapid diagnosis and cost effectiveness. 339/165
STOOL EXAMINATION Adler
Mildly Febrile Patient With Diarrhea
Afebrile Patient With Diarrhea for Less Than One Week
It is most effective to begin with a t h i n - c o a t m e t h y l e n e blue stain. 3 If m o r e t h a n 50 l e u k o c y t e s per highpower field are seen and the clinical condition reflects infectious diarrhea, the clinician may presume that Shigella is the causative organism if t h e p a t i e n t h a s no h i s t o r y of ulcerative colitis and is n o t on antim e t a b o l i t e s or antibiotics k n o w n to cause pseudomembranous enterocolitis. 2 If the leukocyte smear is more than l0 but less t h a n 50, the p h y s i c i a n should send one culture for bacteria and two for parasites. If it is a parasite, the l i k e l y o r g a n i s m is Entamoeba. (Two rather than three smears are sent p r e s u m i n g the l a b o r a t o r y is experienced in performing stool examinations.) If there are m i n i m a l leukocytes, the physician should send one bacterial culture. If this is negative and there is no relief or slowing of the diarrhea in one week, one should consider ulcerative colitis or pseudomembranous enterocolitis. The literature is not clear concerning fewer than 10 leukocytes in the smear of a m i l d l y febrile patient. It makes sense to get a bacterial culture, a n d in t h e h i g h - r i s k groups to do ovum and parasite microscopy w i t h concentration techniques t i m e s two. If there is no relief or slowing of the diarrhea in one week, one should consider ulcerative colitis or pseudomembranous enterocolitis. In an endemic area, the appropriate culture should be done for treatable infections (eg, Vibrio I.
The afebrile patient w i t h diarrhea for less than one week and leukocytes in his stool probably has a self-limited condition. Supportive care usually is all that is n e c e s s a G Antibiotic therapy is not required, even ff an infectious agent is identified, unless the diarrhea lasts longer than one week. 3 The s a m e is true for the absence of leukocytes, suggesting that the causative agent is probably viral. If microscopic e x a m i n a t i o n shows eosinophils or Charcot-Leyden crystals, the patient probably has an infestation. 2~ Finding the parasitic agent will n e c e s s i t a t e o v u m and p a r a s i t e microscopy w i t h concentration techniques times two.
Diarrhea in a Toxic Patient A bacterial culture should be done regardless of the leukocyte count. Depending on the clinical situation, the physician should consider the need for a special l a b o r a t o ~ All these patients should have two smears for ovum and parasites, one purged and one regular, concentrated for a higher yield. In an i m m u n o c o m p r o m i s e d h o s t (eg, a homosexual when there is the p o s s i b i l i t y of AIDS), t h e c l i n i c i a n should search for cryptosporidium on smear. The last, and perhaps most important, thing to consider is an antibioticor antimetabolite-associated diarrhea. These patients should be hospitalized and medication should be stopped. 166/340
Afebrile Patient With Diarrhea for One W e e k The afebrile patient w i t h diarrhea for one week is diagnosed w i t h methylene blue stain and bacterial culture. Shigella is not presumed to be as likely w i t h o u t 50 P M N / H P E The cliniCian should consider having the laboratory look for Yersinia, E coli, and C dificile, for these organisms are not included routinely. A viral etiology can be verified only with cultures, and special techniques are needed. With this clinical picture it appears that parasites are as c o m m o n as bacteria, and thus microscopy w i t h concentration techniques times two is indicated. As noted, unless the leukocyte stain is highly positive (ie, 50 PMN/HPF) culture should be done. The clinician should culture, however, o n l y w h e n the results will change treatment. This is the major idea garnered from the literature: cultures are not read, a n d u s u a l l y do n o t c h a n g e t h e r apy 14,22
SUMMARY The emergency physician m u s t approach the patient with diarrhea in a logical, stepwise fashion. Two prime d i f f e r e n t i a t i n g p o i n t s are l e n g t h of time with s y m p t o m s and presence or absence of fever. The next point of differentiation, w i t h our current level of k n o w l e d g e , appears to be l e u k o c y t e count (ie, > 50 P M N / H P F or < 50 PMN/HPF). Finally, only one bacterial culture is necessary, viral culture rarely is useful, and two smears for parasites are mandatory. Annals of Emergency Medicine
Areas for further research appear to be the following: 1) A definitive study on how m u c h more effective culture is than G r a m stain for rectal gonorrhea; 2) T h e c l i n i c a l u t i l i t y of c u l t u r e c o m p a r e d to m i c r o s c o p i c v i s u a l i z a tion in the diagnosis of stool parasites; 3) Whether diagnostic accuracy can be a c h i e v e d u s i n g q u a n t i t a t i o n of stool l e u k o c y t e s in c o m m o n infectious diarrhea; 4) Yersinia's role as a stool pathogen; and 5) T h e i n c i d e n c e i n t h e U n i t e d States of Entamoeba histolytica cansing a leukocyte response.
REFERENCES 1. Graham D: Some points in the diagnosis and treatment of dysentery occurring in the British Salonika Force. Lancet 1918;2:200-206. 2. Stoll B, Glass R, Banu H, et al: Value of stool examination in patients with diarrhea. Br Med J 1983~286:2037-2040. 3. Satterwhite MD, Dupont HC: Infectious diarrhea in office practice. Med Clin North Am 1983;67:205-209. 4. Winawer S: Current status of fecal occult blood testing in screening for colorectal cancer. CA-A Cancer Journal for Clinicians 1982;32:100-Ii2. 5. Markely E: Intestinal protozoa in homosexual men of the San Francisco Bay Area: Prevalence and correlates of infection. Am J Trop Med Hyg 1984; 33:239245. 6. Garcia L, Ash L: Diagnostic Parasitology. St Louis, CV Mosby Co, 1975, p 1-21. 7. Korzeniowski O, Barada F, Rouse J: Value of examination for fecal leukocytes in the early diagnosis of shigellosis. Am J Trop Med Hyg 1979;28:1031-1035. 8. Wolff HL, Croon JJ: Acta Leidensia 1977;45:47-59. 9. Thompson J, Haas R: Intestinal parasites: The necessity of examining multiple stool specimens. Mayo Clin Proc 1984;5A:641-642. 10. Alicna A, Fadell E: Advantage of purgation in recovery of intestinal parasites or their eggs. Am J Clin Pathol 1959; 31:139-142. 11. Harris J, Dupont H, Hornick R: Fecal leukocytes in diarrheal illness. Ann Intern Med 1973;76:697-703. 12. Koplan J, Fineberg H, Ferrara M, et al: Values of stool cultures. Lancet 1980;2: 413-416. 13. Blaser MJ: Campylobacter enteritis in Denver. West J Med 1982;136:287-290. 15:3 March 1986
14. Pai C, Soryer S: Campylobacter gastroenteritis in children. J Pediatr 1979; 94:553-600. 15. Ho D, A u h M, Mufata G: Campylobacter enteritis: Early diagnosis with G r a m stain. A r c h I n t e r n M e d 1982; 142:1858-1860. 16. M c M i l l a n A: C o m p a r i s o n of sensitivity of microscopy or culture in the laboratory, Diagnosis of intestinal protozoal infection. J Clin Pathol 1984; 37:809-811.
15:3 March 1986
17. Sack RB, Tihon R: Laboratory diagnosis of bacterial diarrhea, Cumitech 12. Washington, DC, American Society for Microbiology, 1980, p 8. 18. Blaser M, Reller LB: Campylobacter e n t e r i t i s in the US. A n n I n t e r n M e d 1983;98:360-365. 19. Judson F: Transmitted viral hepatitis and enteric pathogen. Urol Clin North A m 1984;11:177-185. 20. Lebedeff D, H o c h m a n E: R e c t a l
Annals of Emergency Medicine
gonorrhea in men: Diagnosis and treatment Ann intern Med 1980;92:463-466. 21. Melvin D, Brooke M: Laboratory Procedures for the Diagnosis of Intestinal Parasites. Washington, DC, US Department of Health, Education and Welfare, PHS DHEW No 76-8282, p 23-25. 22. Edwards C, Levin S, Balagtas E: Ordering patterns and utilization of bacteriologic culture reports. Arch Intern Med 1973; 132:678-682.
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Stool Examination: Culture Versus Gram Stain Presented is a methodology for efficient, cost-effective collection, transport, culture, and microscopic examination of infectious diarrhea. A critical review of the literature is included, as are guidelines for workup and management of the disease complex in the emergency department. [Adler P: Stool examination: Culture versus Gram stain. Ann Emerg Med March 1986; 15:337-341.] INTRODUCTION Diarrheal disease in the ambulatory patient has been studied since World War I. I Many of the studies were done in areas of the world in which the incidence of the disease is high. However, the results of studies from Bangladesh and other underdeveloped areas may not be applicable to a busy emergency department practice, and probably do not represent high-quality, cost-effective medical care techniques for the 1980s.2 Questions of concern to the emergency physician include when to do a culture or microscopic examination of stool; how many stool samples are needed; which medium of transport should be used; which patients are at high risk for colon cancer and should have their stool tested for blood; and which situations do not require definitive diagnosis. The indications for stool examination in the emergency department are the following:3 1) Diarrhea for more than 72 hours; 2) Change in stool consistency, odor, or color for more than 72 hours; 3) Blood in stool or rectum; 4) Itching in rectum; 5) Diarrhea in a patient on antibiotics or antimetabolites; and 6) Diarrhea in a toxic patient. Emergency physicians often function as primary care providers, and thus have responsibility for preventive and cost-effective care. Cancer of the colon is one of the most common cancers in men and women. A history of diarrhea in the following high-risk groups mandates examination of stool for blood: 4 1) Previous history of colon cancer; 2) History of ulcerative colitis; 3) Symptoms suggestive of colorectal cancer; 4) Familial polyposis or Gardner's syndrome; 5) Family history of cancer of the colon; and 6) History of adenoma of the colon. If a n y of these risk factors is present, the patient should be referred for outpatient radiological examination and follow-up. Significant numbers of cases of parasitic or infectious diarrhea are seen in the male and female homosexual populations and in a segment of the heterosexual population. The primary mode of transmission of the disease in these populations is unhygienic sexual practice, including analingus and anal coitus followed by fellatio. Some investigators recommend culturing all homosexual patients, even ff they are asymptomatic, because more than onefourth of homosexual patients have parasitic infestation (Entamoeba histolytica and Giardia lamblia), s Another group that is at risk for parasitic diarrhea is international travelers 15:3 March 1986
Annals of Emergency Medicine
Paul M Adler, DO Philadelphia, Pennsylvania From the Department of Emergency Medicine, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania. Presented at the Winter Symposium Advances Track of the American College of Emergency Physicians in San Diego, California, April 1985. Address for reprints: Paul M Adler, DO, Thomas Jefferson University Hospital, 111 South 11th Street, Room 252, Thompson Building, Philadelphia, Pennsylvania 19107.
337/163
STOOL EXAMINATION Adler
to endemic areas in the third world. Included are places we think of as developed nations, such as southern Europe, especially Italy from Naples to Sicily and the South of France. Louisiana and parts of Florida may be considered endemic areas as well. In our larger cities, the recent influx of immigrants from endemic areas has increased the clinical pool. In the hospital w i t h o u t a parasitology referral service, the emergency physician should consider performing the procedures shown (Figure). Some of these procedures should be done only in specific situations (eg, Cryptosporidium ssp in an AIDS victim who is toxic or Vibrio ssp seasonally in areas in which shellfish are harvested.
REVIEW OF THE LITERATURE Collection and Transport Examination and collection of stool is optimally done within 30 minutes of passage. 6 Specimens should be collected in a container, not taken from diapers or by rectal swab. z Transport depends on the climate and type of organism sought. At high ambient temperatures, results usually are unsatisfactory. Competition between pathogenic and nonpathogenic bacteria may be such that internal isolation of pathogens is impossible. 8 Although refrigeration would appear to be the answer, low temperature harms shigellae and, to a lesser extent, salmonella. Enteropathic Escherichia coli and other enteric nonpathogenic bacteria are not inhibited by low temperatures. Quick freezing with liquid nitrogen until transport to the laboratory is optimal in tropical climates. The use of two samples with different preservatives is optimal for parasites. The specimens should be placed in polyvinyl alcohol (PVA) preservatives and a 5% or 10% formalin compound. Many hospitals use a onecontainer technique with PVA alone, but lower egg or cyst counts are encountered consistently.9 Urine contamination also lowers counts. Culture of bacteria is obviated by the parasitic preservatives. If parasites are a consideration, the Subcommittee on Laboratory Standards of the American Society of Parasitology recommends three samples for amoeba and one for helminths. The recovery rate for one specimen is 83%; for two, 95%; and for three, 100% .9 The microscopic examination 164/338
costs $40, and increases accuracy by only 5% if three specimens are sent. We recommend two specimens unless the laboratory analyzes stool for ovum and parasites only infrequently, in which case we recommend three samples to increase the accuracy. One sample should be a purged specimen if the clinician is looking for parasites, because most relevant parasites localize in the small intestine and cecum, m In the case of a presumed uncomplicated bacterial infection, we usually send off only one specimen. The infecting organism will appear in almost all specimens.
panied by leukocytes. 12 Campylobacter recently has been reputed to be the most common cause of acute diarrheal illness.13,14 A good quantitative study of leukocytes in Campylobacter infections has not been done. In view of these data, it appears that the absence of leukocytes does not preclude bacterial diarrhea. Not quantitated is the neutrophil response in ulcerative colitis and pseudomembranous enterocolitis. The literature says the response may be profuse, but no statistics are given.
Microscopic Examination
most common cause of diarrhea, has variable regional prevalence ranging from 1.2% to 9.3%, with a mean of 4.4%) s Campylobacter cultures are complex and are not done by all laboratories. Two studies, however, showed that Gram stain had a variable sensitivity of 43% and 80%, but each demonstrated 99.4% specificity for Campylobacter. 16 Yersinia, frequently mentioned in the mid-1970s, is now rarely mentioned in the enteric literature. Studies of both symptomatic and asymptomatic patients yielded incidence of the organism but not prevalence in clinical disease. As mentioned, Shigella has widely varying recovery rates, depending on the study. Enteropathic E coli testing is complex and expensive, is done only in reference laboratories, and only rarely is clinically useful in adults. 17 Bacterial cultures cost between $i5 and $35 per culture, should not be taken by rectal swab, and recover only three pathogenic organisms, Shigella, Salmonellae, and Campylobaeter. Organisms such as enteropathic E coli, Clostridium dificile, Yersinia, and Vibrio cholerae, unless specifically sought, will not be cultured in a general microbiology laboratory. Viral cultures cost $60, and have little clinical applicability. Microscopy versus culture for parasites has been poorly studied. One article 16 suggests that concentrating stool will double the yield for microscopy, and culturing the stool will quadruple the yield. Culturing stool is still a research tool. Giardia lamblia cannot be cultured. 16 Many laboratories will include pH and fat content as routine stool tests.
The examination of stool for leukocytes may be diagnostic and thus costeffective. When a "very large"* number of l e u k o c y t e s are seen, three etiologic bacterial organisms are implicated: Shigella, Entamoeba histolytica, and Campylobacter. No study to date has compared the relative number of leukocytes found with each type of infection. A prospective study at the International Center for Diarrheal Disease Research in Dacca, Bangladesh, examined 1,593 patients with diarrhea and a single pathogen. Clinical condition was not evaluated, but leukocytes alone were found to be very predictive. Only 8% of patients had > 50 PMN/HPF; of these, 39% (interpolated data) had Shigella and 7% had Entamoeba histolytica. In 44% of cases, a Shigella infection had between l0 and 50 PMN/HPE E histolytica had between 10 and 50 PMN/ HPF 61% of the time. A variety of other organisms infrequently (less than 5% of cases) had between 10 and 50 PMN/HPE The leukocyte count in Shigel]a may be clinically more relevant because recovery rates are widely distributed, from a low of 15% to a high of 80%. The literature concerning leukocytes in Shigella is contradictory; in one study, c o r r o b o r a t i n g the Bangladesh findings, 19 of 20 patients had some leukocytes, 11 yet a poorly controlled study from the Centers for Disease Control found that only five of 14 Shigella infections were accom* "Very large" is not well defined in the literature. Only Still's study from Bangladesh has specifically defined "very large" as more than 50 polymorphonuclear cells (PMN) per high-power field (HPF). Annals of Emergency Medicine
Culture Campylobacter, r e p o r t e d l y the
15:3 March 1986
Patient With Diarrhea I
Febrile No
I
I
Toxic*
Duration > 7 days
Yes I No
< 7 days
I
I I
Methylene blue smear
Immunocompromised I
]
High Risk
Low Risk
Yes
!
No
i
Supportive care
I
Methylene blue stain I
50 PMN/HPF
Include smear for
Bacterial culture
Crgptospofidium Bacterial culture
I
Exam for parasites
I
Consider need for special laboratoryt
Smear for ovum and parasites ]
I
I
One concentrated
One purged Over
Under
I
Clinical pictureShigella
Yes
I
One bacterial culture Two smears ovum and parasites
No
I Presume Shigella
I
Culture for bacteria and examine for Entamoeba histolytica
I
I
One concentrated
I
One purged
*Usually required hospital admission. 1-For example, C dificile, Enterotoxigenic, E coil, Yersinia, Vibrio cholerae.
Unless malabsorption is part of the differential diagnosis, however, these tests {which c o s t $18) probably will not add useful information. The examination for visible mucus and blood is downplayed in most studies, The exception is a well-done Campylobacter. study which found that bloody and watery diarrhea with leukocytes resulted from Shigella, Salmonellae, or Campylobacter 83% of 15:3 March 1986
the time. TM Sexually transmitted diseases cannot be cultured from stool, and are poorly retrieved from stool Gram stain. G o n o r r h e a and c h l a m y d i a , which cause mucopurulent proctitis, require a swab from the rectum. The literature is conflicting, but apparently Gram stain is as effective as culture. 19 If a cukure is sent, it should be placed directly on a selective mediAnnals
of Emergency
Medicine
FIGURE. Algorithm for diagnosis of infectious diarrhea. um and incubated as soon as possible.ZO C L I N I C A L DECISIONS The following are recommendations for optimal decisions in terms of rapid diagnosis and cost effectiveness. 339/165
STOOL EXAMINATION Adler
Mildly Febrile Patient With Diarrhea
Afebrile Patient With Diarrhea for Less Than One Week
It is most effective to begin with a t h i n - c o a t m e t h y l e n e blue stain. 3 If m o r e t h a n 50 l e u k o c y t e s per highpower field are seen and the clinical condition reflects infectious diarrhea, the clinician may presume that Shigella is the causative organism if t h e p a t i e n t h a s no h i s t o r y of ulcerative colitis and is n o t on antim e t a b o l i t e s or antibiotics k n o w n to cause pseudomembranous enterocolitis. 2 If the leukocyte smear is more than l0 but less t h a n 50, the p h y s i c i a n should send one culture for bacteria and two for parasites. If it is a parasite, the l i k e l y o r g a n i s m is Entamoeba. (Two rather than three smears are sent p r e s u m i n g the l a b o r a t o r y is experienced in performing stool examinations.) If there are m i n i m a l leukocytes, the physician should send one bacterial culture. If this is negative and there is no relief or slowing of the diarrhea in one week, one should consider ulcerative colitis or pseudomembranous enterocolitis. The literature is not clear concerning fewer than 10 leukocytes in the smear of a m i l d l y febrile patient. It makes sense to get a bacterial culture, a n d in t h e h i g h - r i s k groups to do ovum and parasite microscopy w i t h concentration techniques t i m e s two. If there is no relief or slowing of the diarrhea in one week, one should consider ulcerative colitis or pseudomembranous enterocolitis. In an endemic area, the appropriate culture should be done for treatable infections (eg, Vibrio I.
The afebrile patient w i t h diarrhea for less than one week and leukocytes in his stool probably has a self-limited condition. Supportive care usually is all that is n e c e s s a G Antibiotic therapy is not required, even ff an infectious agent is identified, unless the diarrhea lasts longer than one week. 3 The s a m e is true for the absence of leukocytes, suggesting that the causative agent is probably viral. If microscopic e x a m i n a t i o n shows eosinophils or Charcot-Leyden crystals, the patient probably has an infestation. 2~ Finding the parasitic agent will n e c e s s i t a t e o v u m and p a r a s i t e microscopy w i t h concentration techniques times two.
Diarrhea in a Toxic Patient A bacterial culture should be done regardless of the leukocyte count. Depending on the clinical situation, the physician should consider the need for a special l a b o r a t o ~ All these patients should have two smears for ovum and parasites, one purged and one regular, concentrated for a higher yield. In an i m m u n o c o m p r o m i s e d h o s t (eg, a homosexual when there is the p o s s i b i l i t y of AIDS), t h e c l i n i c i a n should search for cryptosporidium on smear. The last, and perhaps most important, thing to consider is an antibioticor antimetabolite-associated diarrhea. These patients should be hospitalized and medication should be stopped. 166/340
Afebrile Patient With Diarrhea for One W e e k The afebrile patient w i t h diarrhea for one week is diagnosed w i t h methylene blue stain and bacterial culture. Shigella is not presumed to be as likely w i t h o u t 50 P M N / H P E The cliniCian should consider having the laboratory look for Yersinia, E coli, and C dificile, for these organisms are not included routinely. A viral etiology can be verified only with cultures, and special techniques are needed. With this clinical picture it appears that parasites are as c o m m o n as bacteria, and thus microscopy w i t h concentration techniques times two is indicated. As noted, unless the leukocyte stain is highly positive (ie, 50 PMN/HPF) culture should be done. The clinician should culture, however, o n l y w h e n the results will change treatment. This is the major idea garnered from the literature: cultures are not read, a n d u s u a l l y do n o t c h a n g e t h e r apy 14,22
SUMMARY The emergency physician m u s t approach the patient with diarrhea in a logical, stepwise fashion. Two prime d i f f e r e n t i a t i n g p o i n t s are l e n g t h of time with s y m p t o m s and presence or absence of fever. The next point of differentiation, w i t h our current level of k n o w l e d g e , appears to be l e u k o c y t e count (ie, > 50 P M N / H P F or < 50 PMN/HPF). Finally, only one bacterial culture is necessary, viral culture rarely is useful, and two smears for parasites are mandatory. Annals of Emergency Medicine
Areas for further research appear to be the following: 1) A definitive study on how m u c h more effective culture is than G r a m stain for rectal gonorrhea; 2) T h e c l i n i c a l u t i l i t y of c u l t u r e c o m p a r e d to m i c r o s c o p i c v i s u a l i z a tion in the diagnosis of stool parasites; 3) Whether diagnostic accuracy can be a c h i e v e d u s i n g q u a n t i t a t i o n of stool l e u k o c y t e s in c o m m o n infectious diarrhea; 4) Yersinia's role as a stool pathogen; and 5) T h e i n c i d e n c e i n t h e U n i t e d States of Entamoeba histolytica cansing a leukocyte response.
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