Transcript - PAETC | Pacific AIDS Education and Training Center

Didactic Series
Managing Common Complaints: Diarrhea
Daniel Lee, MD
UCSD Medical Center – Owen Clinic
October 10, 2013
ACCREDITATION STATEMENT: University of California, San Diego School of Medicine is accredited by the Accreditation Council for Continuing Medical Education
to provide continuing medical education for physicians. The University of California, San Diego School of Medicine designates this educational activity for a maximum
of one credit per hour AMA PRA Category 1 Credits™.
Physicians should only claim credit commensurate with the extent of their participation in the activity.
1
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
2
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:
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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
• 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 Evaluation
• 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 Evaluation
• Epidemiologic risk factors
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Daycare
Contact with ill persons
Travel
Recent hospital stay
Unsafe foods
Animals
Medications
Underlying medical conditions
Guerrant RL et al, Practice Guidelines for the Management of Infectious Diarrhea. Clinical
Infectious Diseases, 2001; 32:331-51.
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
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Cryptosporidium parvum
Giardia lamblia
Entamoeba histolytica
Isospora belli
Cyclospora cayetanensis
Microsporidium
• Enterocytozoon bieneusi
• Encephalitozoon
intestinalis
• Bacterial
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Salmonella sp
Shigella sp
Campylobacter jejuni
Clostridium difficile
Yersinia enterocolitica
Escherichia coli
• Mycobacterial
– Mycobacterium aviumintracellulare/complex
(MAI/MAC)
– Mycobacterium bovis
– Mycobacterium tuberculosis
Workup of Infectious Diarrhea
in 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 microscopy
Guerrant 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:
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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 of
Cryptosporidium 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.
2.
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Hansen KL and Cartwright CP. J Clin Microbiol. 2001; 39: 474-7.
Turgeon DK, et al. Gastroenterol Clin North Am. 2001; 30: 693-707.
Goka AKJ, et al. Trans R Soc Trop Med Hyg. 1990; 84: 66-7.
Katz DE, et al. Gastroenterol Clin North Am. 2001; 30: 797-815.
Isospora belli
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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)
Diarrhea improved … but
not resolved after 1 week
Colonoscopy was
performed showing …
• Stool cultures revealed
Cryptosporidium
• Patient was started on
nitazoxanide 500 mg BID
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