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IDSA: Vincent T. Andriole ID Board Review Course
10/19/2011
1
GASTROINTESTINAL INFECTIONS
John G. BartlettJohns Hopkins University
School of Medicine
Conflicts: None
GI INFECTIONS
H. pyloriAgents of diarrhea• Secretary vs. inflammatory• Norovirus• Major bacterial agents• Outbreaks• Clostridium difficile
IDSA: Vincent T. Andriole ID Board Review Course
10/19/2011
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HELICOBACTER PYLORI
HELIOBACTER PYLORI1979: R. Warren – chronic gastritis1982: B. Marshall (registrar) results
of 100 biopsies presented at AGA1987: A. Morris drank H. pylori
sequential endoscopy studies1992: D. Graham – Controlled Abx
trial1992-present: peptic ulcer, gastric
cancer, gastric lymphoma, etc.2005: Nobel Prize – Warren and
Marshall
IDSA: Vincent T. Andriole ID Board Review Course
10/19/2011
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HELICOBACTER PYLORI:Ingestion by a healthy volunteer
Day Observation-17 to –2 Gastric pH 1 – 1.7 (23x)0 Ingestion H. pylori1 pH 1, asymptomatic3 – 12 Epig pain + vomiting8 Gastric biopsy8 – 27 pH 6 – 8 (7x)25 – 50 Doxycycline61 H. pylori present
*Morris A: Am J Gastro. 82:192, 1987
IDSA: Vincent T. Andriole ID Board Review Course
10/19/2011
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IDSA: Vincent T. Andriole ID Board Review Course
10/19/2011
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HELICOBACTER PYLORI
Causes: PUD, gastric ca, gastric lymphoma (dyspepsia?, GERD?)
Diagnosis: 90-95% sensitiveGastric bx; Urease test;Breath test; stool antigen
Reinfection common
IDSA: Vincent T. Andriole ID Board Review Course
10/19/2011
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HELIOBACTER PYLORI: TREATMENT
Standard: PPI/clari/amox (Prevpac)Pen allergy: PPI/clari/metroSequential: Clari/amox → PPI/tinid/clariQuad: Bis/tetra/metro/rinitidineSalvage: New regimen; FQ, rifabutinNote: PI + 2-3 Abx – clari, metro, amox,
tetra (levo, moxi) x 1-2 wks
Which of the following is characteristic of norovirus infection?
1. Bloody diarrhea2. Fever3. Fecal leukocytes4. Vomiting5. Duration 4-7 days
IDSA: Vincent T. Andriole ID Board Review Course
10/19/2011
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Which of the following is characteristic of
norovirus infection?
23%
20%
13%
20%
23% 1. Bloody diarrhea2. Fever3. Fecal leukocytes4. Vomiting5. Duration 4-7 days
NOROVIRUS (former Norwalk agent)
Frequency: Most common cause of infectious diarrhea in US
Settings: Restaurants, picnics, cruise ships, schools, hospitals, nursing homes
Infectious dose: 10-100 particlesSx: Watery diarrhea + vomiting x 24-48
hoursDx: RT-PCRMultiple strains: No cross immunity
IDSA: Vincent T. Andriole ID Board Review Course
10/19/2011
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NOROVIRUS ON AN AIRPLANE
Flight – Boston → LA15 in tour group had norovirus → flightdiverted due to widespread vomit and stool – (Kirking H. CID 2010;50:1216)
Recurring norovirus on an airplane –(Thornley CN. CID 2011;53:515)
Passenger with norovirus; 27/66 (43%) of flight attendants on this airplane over the next 5 days were infected
NOROVIRUS: KAPLAN’S CRITERIA
Vomiting: >50%Incubation period: 24-48 hrsDuration of illness: 12-60 hrsNo bacterial pathogen
IDSA: Vincent T. Andriole ID Board Review Course
10/19/2011
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NOROVIRUS: DIFFERENTIAL DIAGNOSIS
Bacillus cereusStaphylococcus aureusC. perfringensEnterotoxigenic E. coliCampylobacterViruses: Rotavirus, Calicivirus
adenovirus, etc.
APPROACH TO INFECTIOUS DIARRHEA
Small bowel Colon
Prototype ETEC/cholera Shigella
Appellation Secretory Inflammatory
Endoscopy Normal Colitis
Diarrhea Watery Bloody flux
Lab-WBC Negative Positive
Volume Large Moderate
IDSA: Vincent T. Andriole ID Board Review Course
10/19/2011
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DIARRHEA:E. COLI
AbxEnterotoxigenic (ETEC) – travelers* YEntreadherent (EAEC) – travelers YEnteroinvasive (EIEC) – like Shigella NEntro-pathogenic (EPEC) – infants NEnteroaggregative (EAEC) – Persistent sx YE. coli 0157:H7 (EHEC) – HUS N
*Hydration, loperamide; severe – FQ or Rifaximin (Azithromycin)
SHIGELLA
Sx: watery diarrhea – dysentery ID: 10 microbesDx: CultureRx: Abx – always; rehydration
Sulfa sensitive – TMP/SMXFluoroquinoloneMisc: Ceftriaxone, azithromycin,
Nalidixic acid
IDSA: Vincent T. Andriole ID Board Review Course
10/19/2011
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SHIGELLA DYSENTERIAE
Epidemiology• Travelers• PandemicsComplications• Shiga toxin HUS• Reiter syndrome (HLA-B27)Abx: ↑ FQ resistance – SE Asia
CAMPYLOBACTER JEJUNI
Frequency: #1 or 2 (Salmonella)Dx: Stool cultureSx: Diarrhea, fever, crampsSource: Raw meat, poultry or cutting
boards (not person-person)Complications: GBS, pseudo-appendicitisRx: Sx <1 week and not severe – no Abx
Severe: Erythromycin, azithromycin; ciprofloxacin (resistance 10%)
IDSA: Vincent T. Andriole ID Board Review Course
10/19/2011
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SALMONELLA SPECIES
Typhoid fever: Developing countriesUS: 400 cases/year
Non-typhoid: Second most common bacterial cause of diarrhea in US
Source: Foodborne – meat, eggs, poultry, dairy products (peanut paste 2008-09)
Sx: Gastroenteritis – watery diarrheaEnteric fever – blood, crampsOther: vascular, bone, joint, valve
SALMONELLOSIS:TREATMENT
What: Ceftriaxone, cefotaxime, cipro, cefixime
Who: Gastroenteritis -- ?/severe or risk – yes• HIV/AIDS -- #1 cause GN bacteremia• High risk: age >50, prosthesis, valve
disease, uremia, cancer• Carrier – TMP/SMX, cipro, amox +
cholecystectomy if gall stones• Concern – Abx resistance
IDSA: Vincent T. Andriole ID Board Review Course
10/19/2011
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SALMONELLA: PREVENTION
• Avoid raw or undercooked eggs• Temperature standards – food
preparation• Surveillance food handlers• Large outbreaks – contaminated
food – eggs, ice cream , peanut paste
IDSA: Vincent T. Andriole ID Board Review Course
10/19/2011
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NATIONWIDE SALMONELLA OUTBREAKS(Maki D. NEJM 2009;360:949)
Date: April-August 2008Agent: Salmonella Saint PaulNumber: 1407 persons, 43 states
282 hospitalized, 2 deathsEstimated number: >20,000Source: Jalapeno and serrano peppers,
Mexico farmEconomic cost: $200 million - tomatoes
IDSA: Vincent T. Andriole ID Board Review Course
10/19/2011
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OUTBREAK #2
Date: September 1, 2008Agent: Salmonella TyphimuriumNumber: 529 pts, 43 states
116 hospitalized and 8 deathsEstimated number: >20,000Source: Peanut butter in >400 food
products
FOODBORNE DISEASE: US
No. affected: 76 millionHospitalization: 350,000
Deaths: 5,000Healthcare cost: $7 billion
Why
IDSA: Vincent T. Andriole ID Board Review Course
10/19/2011
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FOODBORNE DISEASE: US
No. affected: 76 millionHospitalization: 350,000
Deaths: 5,000Healthcare cost: $7 billion
Why
Industrial scale productionMuch imported
Mass transportation of goodsEating out
FOOD IRRADIATION*
Irradiation kills pathogens without change in taste, loss of nutrition or risk
Endorsements: WHO, CDC, FDA, AMA, European Commission on Food
*Osterholm M: Role of irradiation in food safety. (NEJM 2004;350:1898)
IDSA: Vincent T. Andriole ID Board Review Course
10/19/2011
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BOTTLED WATER
Cost: $4.00/gallon – Gasoline/$3.50/gallonSafety regulations: FDA
Tap water: EnvironmentalProtection Agency (more stringent)
Consumer: Cannot tell (easily) where it came from, safety or pollutants
Comments: “No simple way to know about bottled water” (Jane Houlihan)“Bottled water is as safe as tap” (JK Doss, President of the International Water Association)
Which of the following drugs is a concern for resistance when used to treat C. difficile?
1. Metronidazole2. Vancomycin3. Fidaxomicin4. Rifaximin5. Tigecycline
IDSA: Vincent T. Andriole ID Board Review Course
10/19/2011
18
Which of the following drugs is a concern for
resistance when used to treat C. difficile?
20%
27%
17%
30%
7% 1. Metronidazole2. Vancomycin3. Fidaxomicin4. Rifaximin5. Tigecycline
CLOSTRIDIUM DIFFICILEINFECTION
• NAP-1 strain: epidemic in US, Canada and Europe 2000-04
• Risks: Elderly (immunosenesence)Antibiotic exposure (colonic microbiome) hospital (spore contamination)
• Expression: Inflammatory diarrhea• Pathology: Colitis/PMC• Dx: Toxin or microbe• Treatment: Oral vancomycin,
metronidazole, fidaxomicin• Complication: Mortality – 6%, relapse –
20%
IDSA: Vincent T. Andriole ID Board Review Course
10/19/2011
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0
10
20
30
40
50
60
70
80
90
1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005
0
5
10
15
20
25
Principal Diagnosis All Diagnoses Mortality
1. Elixhauser A, et al. Healthcare Cost and Utilization Project: Statistical Brief #50. April 2008. Available at: http://www.hcup-us.ahrq.gov/reports/statbriefs/sb50.pdf. Accessed March 10, 2010. 2. Redelings MD, et al. Emerg Infect Dis. 2007;13:1417-1419.
Incidence and Mortality Increasing in US
Annual M
ortality Rate
per Million Population
# of
CD
I C
ases
per
100
,000
Dis
char
ges
NAP-1: EPIDEMIC STRAIN*
Characteristic Comment
Toxin A & B Produces 16-23 x more toxin in vitro**
tcdC deletion Represses productionToxin A & B
FQ resistance Rare in historic strains
*McDonald C. NEJM 2005;353:2433**Warny M. Lancet 2005;366:1079
IDSA: Vincent T. Andriole ID Board Review Course
10/19/2011
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IDSA: Vincent T. Andriole ID Board Review Course
10/19/2011
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CDI: SPECIFIC CLUES
Leukocytosis: Leukemoid reactionHypoalbuminemiaDistinctive stool odorCT scan findingsPseudomembranous colitisAntibiotic connection
SEVERE C. difficile INFECTION(Lamontagne F. Ann Surg 2007;245:267)
Method: Retrospective analysis of 165 patients admitted to ICU for C. difficileinfection 2003-05
Results: Mortality (30 day): 87/165 (53%)Risks: OR
WBC >50K 18Age >75 yrs 7Immunosuppression 9Lactate >5 12Colectomy 0.2
IDSA: Vincent T. Andriole ID Board Review Course
10/19/2011
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WHERE IS C. DIFFICILE?Gastrointestinal tract• Healthy neonates 2-40%• Healthy adults 2-3%• Hospitalized pts 20-40%• Dogs and cats 2-10%Environment• Humus soil 5-22%• Homes 2-5%• Hospital rooms 30-50%• Hospital air 10% (1 hr)Food (salad, meat) 2-20%
LAB TEST INTERPRETATION
Test Pos Neg ConclusionPCR + ColonizedToxigenic C. diff ▬ No CDIEIA + CDIToxin ▬ False Neg 20%Combo +/+ CDI EIA for GDH + Toxin -/- No CDI
+/- = Need alternative toxin test
Note: Test only diarrhea stools. No repeat test --No test of cure
IDSA: Vincent T. Andriole ID Board Review Course
10/19/2011
23
TREATMENT GUIDELINES 2010:IDSA/SHEA
Mild/moderate disease*: Metronidazole 500 mg po qid x 10-14/d
Severe/complicated**: Vancomycin 500 mg po qid + metronidazole 500 mg IV q 8/h
Multiple relapses: Vancomycin –standard regimen → taper → pulse
*Severe = WBC >15,000/mm3Creatinine >1.5 x baseline
**Toxic megacolon, ICU shock, pancolitis (CT)
IDSA: Vincent T. Andriole ID Board Review Course
10/19/2011
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WHAT’S NEW WITH CDI
Host: Outpatients, pregnant woman, no antibiotic exposure, pediatric patients
NAP-1: Uncertain significanceTests: Multiple options for rapid testsTreatment: Fidaxomicin
Relapsing disease – (50-80% same strain), pulse vanco/transplant
Surgery: Colon-sparing surgery –(ileostomy)
C. DIFFICILE SUMMARY
NAP-1: Epidemic in US; Canada and Europe 2000-04
Risks: Age, Abx, HospitalsRx: Oral vanco, metronidazole, fidaxomycinComplications:
Toxic megacolon → colectomyRelapse (20%): Vanco taper → pulse or
stool transplant Healthcare Reform: “Never event” 2013
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