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Didactic SeriesDidactic Series

Managing Common Complaints: Diarrhea

Daniel Lee, MDUCSD Medical Center – Owen Clinic

October 10, 2013

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Learning Objectives

1) To review the definition of diarrhea

2) To identify some common infectious causes of diarrhea in HIV

3) To discuss diagnosis and treatment options for various infectious causes of diarrhea in HIV

Outline

• Definition of diarrhea

• Case Study

• Infectious pathogens– Viral– Protozoal– Bacterial– Mycobacterial

• Diagnosis

• Treatment

Diarrheal Illnesses

• Second leading cause of morbidity and mortality worldwide1

• In the United States:– 211-375 million diarrheal illnesses (>1 day)– 73 million physician consultations– 1.8 million hospitalizations– 3100 deaths– $23 billion spent– 10 to 15 million Americans suffer from chronic

diarrhea2

1. Guerrant R. IDSA Practice Guidelines. Clinical Infectious Diseases, 2001; 32: 331-50.2. AGA Technical Review on the Evaluation and Management of Chronic Diarrhea, Gastroenterology, 1999

Definition of Diarrhea

• “Diarrhea” – the alteration in the normal bowel movement characterized by an increase in the water content, volume, or frequency of stools

• “Infectious diarrhea” – diarrhea due to an infectious etiology, often accompanied by symptoms of nausea, vomiting, abdominal cramps

• “Acute diarrhea” – diarrhea of 14 days duration• “Persistent diarrhea” – diarrhea of >14 days duration• “Chronic diarrhea” – diarrhea of >30 days duration

Guerrant R. IDSA Practice Guidelines. Clinical Infectious Diseases, 2001; 32: 331-50.

Managing Diarrheal Illnesses:Basic Principles

Managing Diarrheal Illnesses:Basic Principles

• Adequate fluid and electrolyte replacement• Thorough clinical and epidemiological

evaluation• Selective approach to diagnosis and treatment• Avoid antimotility agents if concern about

infectious diarrhea• Advise bland diet and avoidance of fat, dairy,

and complex carbohydrates

• Adequate fluid and electrolyte replacement• Thorough clinical and epidemiological

evaluation• Selective approach to diagnosis and treatment• Avoid antimotility agents if concern about

infectious diarrhea• Advise bland diet and avoidance of fat, dairy,

and complex carbohydrates

Clinical EvaluationClinical Evaluation

• Clinical features– Onset

– Duration

– Stool characteristics

– Frequency

– Volume of stool

– Volume depletion

• Clinical features– Onset

– Duration

– Stool characteristics

– Frequency

– Volume of stool

– Volume depletion

Guerrant RL et al, Practice Guidelines for the Management of Infectious Diarrhea. Clinical Infectious Diseases, 2001; 32:331-51.

Epidemiological EvaluationEpidemiological Evaluation

Guerrant RL et al, Practice Guidelines for the Management of Infectious Diarrhea. Clinical Infectious Diseases, 2001; 32:331-51.

• Epidemiologic risk factors– Daycare– Contact with ill persons– Travel– Recent hospital stay– Unsafe foods– Animals– Medications– Underlying medical conditions

• Epidemiologic risk factors– Daycare– Contact with ill persons– Travel– Recent hospital stay– Unsafe foods– Animals– Medications– Underlying medical conditions

Case Study• 35 y.o. male w/AIDS (CD4 = 40, VL = 255,000)

presents w/5 day h/o nonbloody, watery diarrhea with 10 episodes/day– Denies any fever, chills, night sweats

– + weight loss of 10 lbs

– Mild nausea, vomiting, and abdominal cramping

– PMH: HIV+ diagnosed 10 years ago

– Meds: None

– Vitals: T = 99.0°F, BP = 100/60, P = 110, R = 18

– PE: NAD, abdomen w/mild diffuse TTP w/o rebound or guarding, NABS, guaiac negative

– Xray of abdomen: Nonspecific bowel gas pattern

What is your differential diagnoses?

Causes of Infectious Diarrhea in an HIV-Infected Patient

• Viral– Cytomegalovirus (CMV)

– Adenovirus

– Herpes simplex virus (HSV)

• Protozoal– Cryptosporidium parvum

– Giardia lamblia

– Entamoeba histolytica

– Isospora belli

– Cyclospora cayetanensis

– Microsporidium

• Enterocytozoon bieneusi

• Encephalitozoon intestinalis

• Bacterial– Salmonella sp

– Shigella sp

– Campylobacter jejuni

– Clostridium difficile

– Yersinia enterocolitica

– Escherichia coli

• Mycobacterial– Mycobacterium avium-

intracellulare/complex (MAI/MAC)

– Mycobacterium bovis

– Mycobacterium tuberculosis

Workup of Infectious Diarrheain HIV-Infected Patients

• Stool cultures for– Salmonella, Shigella, Campylobacter, Vibrio, Yersinia,

E. coli O157, C. Diff toxin– O&P examination + AFB (Cryptosporidia, Cyclospora,

Isospora), trichrome or other stain for Microsporidia and antigen detection (Giardia)

• If stool cultures are negative– Consider flexible sigmoidoscopy (or colonoscopy)

with biopsies– Consider upper endoscopy with duodenal biopsies for

electron and light microscopyGuerrant R. IDSA Practice Guidelines. Clinical Infectious Diseases. 2001; 32: 331-50.Cohen J, et al. Gastroenterology Clinics. 2001; 30(3):

Cytomegalovirus (CMV)

• Most frequently causes colonic disease• Presentation: fever, crampy abdominal pain,

and frequent (often bloody) stools• Diagnosis

– Must be made on a colonoscopic biopsy (intranuclear (“owl’s eye”) and intracytoplasmic inclusions)

– Stool cultures are useless

• Treatment– Induction w/IV ganciclovir, foscarnet, cidofovir for several weeks

along with long-term maintenance– Effective HAART will often reduce need for maintenance

Cryptosporidium parvum• Infects enterocytes of the proximal small

intestine• May also cause gastric infections, which are

commonly associated w/duodenal involvement• Tends to be self-limited in non-HIV infected pts,

but severe and chronic in HIV-infected pts (with lower CD4 counts)

• Presentation:– profuse watery diarrhea, dull, crampy abdominal

pain, nausea, vomiting, anorexia, low-grade fever– may lead to severe dehydration, malabsorption,

electrolyte abnormalities, and wasting

Diagnosis and Treatment of Cryptosporidium parvum

• Diagnosis:– Cryptosporidium smear (modified acid-fast stain or Kinyoun

stain)– AFB smear– Direct fluorescent-antibody (DFA)– Enzyme immunoassay (EIA)– Not usually seen on O&P

• Treatment1:– Highly Active Antiretroviral Therapy (HAART)– Nitazoxanide 500-1000 mg PO BID– Paromomycin 1000 mg PO BID– Azithromycin 600 mg PO QD

1. Sande MA, et al. Sanford Guide to HIV/AIDS Therapy. 2003: 90.

Prevention ofCryptosporidium parvum

• Large-scale water purification systems for city water supplies (including filtration and chlorination) have not eliminated cryptosporidiosis

• Drink only bottled water that has undergone one of the following processes:– Reverse Osmosis– Filtered through an absolute pore size of 1 micron or smaller– Tested and certified by NSF Standard 53 for cyst removal or

reduction

• Consider boiling water that could be ingested, including water used for brushing teeth, making ice cubes, and washing fruits or vegetables

Ball S. AIDS Reader. 1998; 8(1): 4-6.

Giardia lamblia• Flagellated enteric protozoan• Up to 2.5 million cases of giardia annually in

U.S.• Transmission: via cysts

– Waterborne (usually) – mountain stream water/camping– Person-to-person

• Daycare settings– Fecal-oral

• Homosexual men

• Presentation:– Profuse, watery diarrhea, cramps, bloating, flatulence– Chronic infection can lead to greasy or foul-smelling stools,

malaise, weight loss, abd pain, malabsorption

Giardia lamblia• Diagnosis: presence of cysts/trophozoites

– Ova & Parasites (O&P)• Detection rate from 1 stool = 67%1

• Detection rate from 3 stools on 3 separate days = 85%2-4

– Direct fluorescent-antibody (DFA)– Enzyme immunoassay (EIA)

• Detection rate from 1 stool = 80%1

• Detection rate from 2 stools = >90%1

• Treatment:– Metronidazole 500-750 mg PO TID x 5 days– Nitazoxanide 500 mg PO BID x 3 days– Tinidazole 2 gm PO x 1

1. Hansen KL and Cartwright CP. J Clin Microbiol. 2001; 39: 474-7.2. Turgeon DK, et al. Gastroenterol Clin North Am. 2001; 30: 693-707.3. Goka AKJ, et al. Trans R Soc Trop Med Hyg. 1990; 84: 66-7.4. Katz DE, et al. Gastroenterol Clin North Am. 2001; 30: 797-815.

Isospora belli

• Endemic in tropical and subtropical areas• Hardy oocysts, resist chlorination• Transmission via contaminated food or water1

• Presentation:– High volume watery diarrhea, crampy abdominal pain, steatorrhea,

low-grade fever, malabsorption, weight loss

– Only protozoa that causes eosinophilia

• Diagnosis: O+P, modified acid-fast stain (Kinyoun stain)• Treatment2: will need chronic suppression after acute Rx

– TMP/SMX 1 DS QID x 10 days, then 1 DS BID x 3 weeks

– Pyrimethamine 75 mg QD + Folinic Acid 10 mg QD x 14d

– Ciprofloxacin 500 mg BID x 7 days

1. Lee SD, et al. Gastroenterol Clin North Am. 2001; 30: 679-92.2. Sande MA, et al. Sanford Guide to HIV/AIDS Therapy. 2003: 91.

Salmonella Shigella

Salmonella• Presentation:

– Diarrhea (may be bloody), fever, nausea, vomiting, and abdominal cramping 12-72 hrs after infection

– If severe, may cause dehydration or require hospitalization

• Diagnosis: routine stool culture• Treatment: Ciprofloxacin 500-750 mg PO (or 400 mg IV) q12hrs x 7 days

• Optimal duration of therapy not defined– Gastroenteritis without bacteremia

• CD4 count ≥200 cells/µL: 7-14 days• CD4 count <200 cells/µL: 2-6 weeks

– Gastroenteritis with bacteremia• CD4 count ≥200 cells/µL:14 days, longer if persistent bacteremia

or complicated infection• CD4 count <200 cells/µL: 2-6 weeks

• If bacteremia, monitor closely for recurrence• If recurrent, consider secondary prophylaxis with cipro or TMP/SMX

Shigella• Presentation:

– Abdominal discomfort, abdominal cramps, fever, vomiting diarrhea that is bloody, watery, and/or mucousy

• Diagnosis: routine stool culture• Treatment: to shorten duration and possibly prevent

transmission– Ciprofloxacin 500-750 mg PO or 400 mg IV Q12H

• Duration of therapy– Gastroenteritis: 7-10 days– Bacteremia ≥14 days– Recurrent infection: up to 6 weeks

• High rate of TMP-SMX resistance in infections acquired outside the United States

Mycobacterium avium complex (MAC)

• Group of nontuberculous mycobacteria including M. avium and M. intracellulare

• Ubiquitous, found in soil, fresh and salt water• Presentation:

– Diarrhea, abdominal pain, weight loss, anemia, night sweats, fever

• Diagnosis: AFB smear, AFB culture• Treatment:

– Clarithromycin 500 mg BID (or Azithromycin 600 mg QD) + Ethambutol 15-25 mg/kg/day + Rifabutin 300 mg QD

– May add Ciprofloxacin 750 mg BID, Ofloxacin 400 mg BID, or Amikacin 7.5-15 mg/kg IV QD

– Length of treatment varies, likely need to start HAART

Case Study (continued)

• Stool cultures revealed Cryptosporidium

• Patient was started on nitazoxanide 500 mg BID

Diarrhea improved … but not resolved after 1 week

Colonoscopy was performed showing …

Concurrent CMV Colitis

Patient was treated with IV Ganciclovir with resolution of diarrhea

Summary/Conclusions

• Infectious diarrhea is a significant cause of morbidity in HIV-infected patients

• In most cases of chronic diarrhea, a specific pathogen can be identified by a thorough diagnostic evaluation

• The treatment of various pathogens is very individual

• HAART may also be helpful to prevent recurrences of infections

• HIV-infected patients can often have more than one active infection at the same time