gastrointestinal infections - confex

IDSA: Vincent T. Andriole ID Board Review Course

10/19/2011

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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


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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


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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


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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


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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


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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


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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


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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


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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


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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%)


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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


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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


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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


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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


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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)


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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


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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%


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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


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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


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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


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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)


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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

gastrointestinal infections - confex

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