outline! - ucsf medical education engel.gastroenteritis.pdf · amoebic dysentery?" ... •...
TRANSCRIPT
Approach to Infec.ous Diarrhea
Joanne Engel, M.D., Ph.D. Professor
Depts of Medicine and Microbiology/Immunology
UCSF
"What the?...This is lemonade!Where's my culture ofamoebic dysentery?"
Outline
• Overview of diarrhea/gastroenteri4s • Viral diarrhea incl norovirus • Bacterial diarrhea • Traveler’s diarrhea • C. difficile
Diarrhea: a global cause of disease
• 2nd leading cause of morbidity/mortality worldwide
• In the US – 200-‐375 million episodes/year
– 73 million physician visits
– 1.8 million hospitaliza4ons
– 5000 deaths – Each person has 1-‐2 diarrheal illnesses/yr
Case I • 32 yo female calls your office c/o diarrhea x 2 days. She notes 8 loose stools in the past 24 hrs. She has a low grade temp, mild nausea, and has vomited x 2. She denies bloody stools, recent travel, inges4on of unsual foods. No sick contacts.
Issues
• Differen4al diagnosis? • Does the pa4ent need to be seen? • Should abx be given? • Is it safe to give an4-‐mo4lity agents? • Should stool tests be sent? • For which organisms?
Differen4al Dx
• Infec4ous • Ischemic
• IBD • Iatrogenic/Osmo4c • Malabsorp4on
The players aka “The dirty laundry list” Viral Bacterial Protozoal Calicivirus (Norwalk, Norovirus,Sapovirus)
Salmonella 16.1* Giardia
Rotavirus Campylobacter 13.4* E. histoly4ca
Adenovirus Shigella 10.3* Cryptosporidium 1.4*
CMV Yersinia Microsporidium
Astrovirus E. Coli 1.7* Cyclospora
Small round virus C. difficile
Corona virus C. perfringens
HSV S. aureus
Bacillus
Vibrio
Listeria
Chlamydia *cases per 100,000
N. gonorrhea
Who should be seen: Inflammatory vs non-‐inflammatory?
Take a good history! • When & how illness began • Stool characteris4cs • Frequency & quan4ty • Presence of dysenteric symptoms • Symptoms of volume deple4on
• Associated symptoms • Epidemiologic clues
Be a Sherlock Holmes • Travel to developing area • Day-‐care center ahendance or employment • Consump4on of raw meats, eggs, unpasteurized milk/cheese, swimming in or drinking from untreated fresh water
• Farm or zoo animals, rep4les • Exposure to other ill persons • Medica4ons, esp an4bio4cs • Underlying medical condi4ons • Recep4ve anal intercourse or oral/anal contact • Food-‐handler or caregiver
Norwalk Rotavirus
Viral diarrhea
• Usually resolves ≤ 3 days
Norovirus
Rotavirus • Rotavirus
– Infants protected up to age 3 mos by maternal an4bodies – Usually affects children age 6-‐24 mos – At least once before age 5 – Mul4ple serotypes – Immunity incomplete
• Morbidity and Mortality – 25 million clinic visits – 2 million hospitaliza4ons (60,000 in US) – Kills ~ 600,000 children annually in developing countries (37 in
US) – Most disease caused by 4 serotypes
• Dx: stool rapid an4gen
Two new vaccines NEJM Jan 2006
• Both are live oral vaccines intended to be given to infants at same 4me as DPT – Rotateq (Merck): age 2m 4m 6 mos
– Rotarix (GSK): age 2, 4 mos
• ACIP recommends rou4ne vaccina4on of infants w/either vaccine
Just a lihle stomach flu…
Norovirus
• Single stranded, noneveloped RNA virus • Caliciviridae family
• Genogroups-‐>genotypes-‐>strains • Replicates only in GI tract • Persists in environment
• Humans are the only reservoir
Glass et al, NEJM, 2009" Sx
• Diarrhea, vomi4ng, abd pain, malaise, low grade fever
• Usually self-‐limited, resolves ≤ 3 d – Prolonged and severe sx in elderly, very young – Prolonged asymptoma4c shedding
• Up to 8 wks in healthy pts • Up to 1 yr in severely IC pts
Dx
• Not culturable • Older techniques: EM, stool ELISA
• Gold standard: RT-‐PCR (since early 1990’s) – 68% sensi4ve – 99% specific – Only avail at public health depts, state, na4onal labs
Evolving epidemiology • Most common cause of gastroenteri4s • 35% of cases of sporadic gastroenteri4s of known cause • 5-‐31% of pts hospitalized for gastroenteri4s • 5-‐36% of clinic visits for gastroenteri4s
• Greatly under-‐reported – Only 1/1562 cases iden4fied
• Increasing outbreaks • An4genic shir and drir (like influenza) – Change in viral capsid affects binding to GI tract oligosaccharides
– New variant-‐>new epidemic wave – New pandemic strain every 2-‐4 yrs
Increasing outbreaks
Unit closed"
Unit re-opened"
Evolving epidemiology
• Increased outbreaks in nursing homes and long-‐term care facili4es – 30-‐50% of outbreaks occur in closed facili4es – 28% in restaurants/catered meals – 16% cruise ships – 8% day care centers – Commonly cause by GII.4 strain
• Increased illness severity – Associated with poor outcome in older pts
• Longer illness • Acute renal failure, arrhythmias, hypokalemia, chronic diarrhea
Why is norovirus so difficult to contain?
• Highly transmissable: a lihle goes a long way… – ID50: 10-‐100 virions
– Facile 2˚ spread • Viral shedding precedes clinical illness in >30% of pts • Prolonged shedding
– Up to 8 wks in healthy hosts – Up to 1 yr in IC hosts
• Asymptoma4c shedders
– Withstands wide range of temps and persists in environment
– Immunity is short-‐lived and not cross-‐protec4ve against an4genic variants
Why is norovirus so difficult to contain?
• Mul4ple modes of transmission – Food
• Globaliza4on of food distribu4on • Increased # of people who handle the food we eat • Increased consump4on of food at risk of contamina4on (fresh vegetables and
fruit)
– Water
– Airborne via vomitus • Suscep4bility correlates w/distance from vomi4ng event
– Contact w/contaminated surfaces
– Fomites – Person-‐person contact – Resistant to many disinfectants
Interrup4ng transmission
• Disinfec4on – Wipe surface w/detergent to remove par4cle debris followed by hypochlorite bleach (5000 ppm) as disinfectant
– Other disinfectants less efficient: (quanternary ammonium compounds, alcohols)
– Alcohol-‐based disinfectants are insufficient • Wash hands for 1 min w/soap & water, rinse for 20 sec, dry w/disposable towels
Planning your next cruise…. Cdc vessel sanitation site!
Case IIa • 32 yo female calls your office c/o diarrhea x 4 days. She notes 8 loose stools in the past 24 hrs. She has a low grade temp, mild nausea, and has vomited x 2. She denies bloody stools, recent travel, inges4on of unsual foods. No sick contacts.
What would you do? 1. Tell her to drink plenty of fluids, take lomo4l as
needed, and that her sx will likely resolve on their own
2. Treat her empirically with a 3 day course of levofloxicin
3. Treat her empirically with a single dose of azithromycin
4. Have her come into your office with plans to send stool for culture, O&P, with plans to start her on levofloxicin
Major bacterial pathogens in the US
Campylobacter Salmonella Shigella
E. coli O157:H7
Dis<nguish from viral diarrhea by dura<on of sx (> 3 days)
• Obtain cultures early in illness (1st 3 days) • Up to 2 cultures cost-‐effec4ve – Diagnos4c yield 1.5-‐5.6% – Cost ~$1000/posi4ve culture – Be selec4ve-‐
• limit to > 1d dura4on of symptoms • Definitely get for inflammatory diarrhea
• Send to lab ASAP (prevent prolifera4on of normal flora)
• Negligible yield if pt hospitalized > 3 days – Except if HIV+, immunocompromised, age >65, +comorbid illness (Annals of Internal Med 2006)
Bacterial Stool cultures
• Special requests for – Vibrio (TCBS media)
– Yersinia – EHEC – Aeromonas
– Pleisiomonas
– C. diff Vibrio
Tests for parasites Branda et al, CID, 2006
• Negligible yield if hospitalized > 3d prior to onset of diarrhea
• Par4cularly relevant if sx > 7 d, camping, exposure history • DFA for Giardia and Cryptosporidium faster, but misses
other pathogens seen by O&P; 95% sensi4vity • O&P
– Send up to 3 specimens (1 specimen: 71% Sensi4vity) – Send or run 2nd specimen if pt s4ll sx or high index of suspicion
• 2nd specimen adds ~6% sensi4vity • 3rd specimen adds ~3% sensi4vity
– Consider if HIV+ or if cyclospora or microsporidium a serious considera4on
Treatment
• Fluids, Fluids, Fluids • Abx-‐only under special circumstances – Diarrhea will resolve on its own
• An4mo4lity agents (loperamide) – Risk of exacerba4ng disease
• Bismuth subsalicylate • BRAT diet
Role of An4bio4cs • Decrease fecal excre4on (ie Shigella, Giardia, Cholera) – Prolongs excre4on of Salmonella?
• Prevent bacteremia in suscep4ble groups (neonates, IC, HIV, age > 50 ASHD, joint disease, cardiac valvular or endovasc abnl)
• Resolve persistent or life-‐threatening infec4ons – Giardia, amebiasis, cholera
• Hasten recovery 1-‐2 days – Traveler’s diarrhea – “Domes4cally acquired” diarrhea
• Weigh benefits vs drug resistance issues
Which an4bio4cs? • Fluoroquinolones
– Persistent or extra-‐intes4nal salmonella
– Shigella – E. coli (ETEC) in travelers – Prolonged campylobacter – Yersinia – Aeromonas – Pleisiomonas – Vibrio (some4mes) – Resistance increasing
• Azithromycin
• TMP-‐sulfa (kids) – Bacterial, cyclospora,
microsporidium – Resistance is problema4c
• Metronidazole – Persistent giardia – E. histoly4ca – C. difficile
• STD-‐assoc diarrhea
Drug resistance • Mul4drug resistance – Common in Salmonella DT104 (CAM, Septra, Tet, Amp) – Recently reported for Shigella (MMWR 2010 59:1619)
• 3 cases of Shigella in a family that was resistant to ceraz, cefepime, Amp, aztreonam, cefotaxime, cerriaxone, CAM, cipro, NA, strept, sulfisozazole, tet, TMS/Sulfa involving interna4onal adop4on
• Cephalosporin resistance – Salmonella (<0.5%)
• Cipro resistance – Salmonella enterica serotype Kentucky ST198 (Africa-‐>middle
east-‐>European and US travelers (JID 2011)
–
Drug resistance • Quinolone resistance – Campylobacter-‐longer dura4on of infec4on, greater risk of death or invasive disease
– Salmonella spp • Non-‐typhoidal isolates in US:nalR Incr from 1.6% to >2.3% 1996-‐2003
• Typhoidal isolates in US (travelers): 40-‐90% nalR • Most nalR isolates showed decr suscep4bility to ciprofloxicin • Unknown if all ciproR isolates are nalR • Many studies show increased morbidity/mortality in drug resistant salmonella typhimurium infec4ons
– Shigella • 20 cases reported (80% with travel to southeast asia, south asia) • An4microbial Agents and Chemotherapy, April 2011, p. 1758-‐1760, Vol. 55, No. 4
Salmonella outbreaks
Case IIB • 32 yo female calls your office c/o diarrhea x 3 days. She notes 8 loose stools in the past 24 hrs. She has a low grade temp, mild nausea, and has vomited x 2. She denies bloody stools. She returned 2 days ago from a 2 week trip to India.
What would you do 1. Tell her to drink plenty of fluids, take lomo4l as
needed, and that her sx will likely resolve on their own
2. Treat her empirically with a 3 day course of levofloxicin
3. Treat her empirically with a single dose of azithromycin
4. Have her come into your office with plans to send stool for culture including Cholera, O&P, with plans to start her on azithromycin
Traveler’s diarrhea • Most common illness in travelers
• Onset usually 5-‐15 days arer arrival • Usually resolves spontaneously 3-‐5 d • 40-‐60% incidence during 2-‐3 wk vaca4on in persons from industrialized countries-‐>developing regions
Traveler’s diarrhea:crihers • Occurs in naïve/non-‐immune hosts – ETEC most common
– Also enteroaggrega4ve E. coli – Campylobacter>Shigella, Salmonella
• Incr FQ resistance in Campylobacter
– Aeromonas, Pleisiomonas, V. cholera, V. parahaemoly4cus
– Rotavirus – Parasites (prolonged diarrhea: E. histoly4ca, Giardia, Cryptosporidium)
– Blastocys4s hominus unlikely to be a pathogen
– 20-‐30% have no iden4fiable cause
Traveler’s diarrhea: Px
• Avoid tap water, ice, bohled noncarbonated beverages
• Avoid raw veggies, unpeeled fruits, raw meat, and seafood
• Ab prophylaxis rarely required
Prophylaxis op4ons • If traveler cannot tolerate few days of illness
• Achlorhydria, IC, underlying chronic GI disease, CRF, DM, ostomies
• Rifamixin-‐effec4ve against ETEC • Peptobismol 2 tabs QID effec4ve in preven4ng ETEC (bacteriosta4c) – ~60% efffec4ve – Side effects: black tongue & stool, mild 4nnitus – Avoid if allergic to salicylates or on salicylates or an4-‐coagulants
– Not to exceed 3 weeks
Traveler’s diarrhea: Rx • Oral rehydra4on usually sufficient • An4mo4lity agents – Loperamide 4 mg followed by 2 mg q loose stool (<16 mg/day) – Not recommended if sx of dysentery (high fever, bloody stool)
• Dysentery: – Levofloxicin 500 mg qd un4l sx resolve or 3 days – Azithro (1000 mg) or 500 mg qd x 3d (preferable in SE & India 2/2 high rate of Cipro-‐R Campylobacter • Tribble et al CID 2007: • 96% cure single dose azithro • 95% cure 3D azithro • 71% cure levo • Cure rate related to levo resistant Campy
– Reduce dura4on of sx ~1 d
Prac4cal approach:
• Have pt fill prescrip4on for quinolone or azithro prior to travel – take if pt gets mod-‐severe diarrheal illness
• Have pt bring loperamide – take if pt has mild diarrheal illness or more severe illness if NO bloody diarrhea
Ini4al management (prior to culture results)
• Mild sx: Non-‐inflammatory diarrhea – Developed country: hydrate & observe, ±an4mo4lity agent – Traveler’s diarrhea: hydra4on, an4-‐mo4lity agent, single dose of levofloxicin or azithromycin
• Mod Sx: Inflammatory diarrhea – Levofloxicin or Azithromycin 1-‐3 d unless C. diff suspected – Loperamide if no bloody diarrhea – Flagyl if C. difficile or E. histoly4ca suspected – If no improvement in 48 hrs, seek medical evalua4on
• To culture or not to culture…that is the ques4on
What about EHEC?
• 95% of pts have bloody stools at least some 4me during their illness
• Abx shown to exac illness (Wong et al NEJM 2000) – Likely by decreasing nl flora and/or enhancing toxin produc4on
• How to dis4nguish dysentry from EHEC – Rely on case epidemiology-‐if returning travel to 3rd world countries, more likely shigella
– If domes4cally acquired, concern for EHEC • Send stool cultures if in first 6 d of illness and await results before prescribing abx
What would you do 1. Tell her to drink plenty of fluids, take lomo4l as
needed, and that her sx will likely resolve on their own
2. Treat her empirically with a 3 day course of levofloxicin (not good for travel to India or SE asia 2˚ to increasing resistance in Campylobacter)
3. Treat her empirically with a single dose of azithromycin
4. Have her come into your office with plans to send stool for culture, O&P, with plans to start her on levofloxicin
Case IIc • 32 yo female calls your office c/o diarrhea x 3 days. She notes 8 loose stools in the past 24 hrs. She has a low grade temp, mild nausea, and has vomited x 2. She denies bloody stools. She returned 2 days ago from a 2 week trip to Hai4.
Vibrio cholera: a life threatening illness in travelers
• Suspect V. cholera in all travelers with severe diarrhea in or returning from 3rd world
• Death can occur within 24 hrs due to profound dehydra4on
• Massive fluid replacement required
• An4bio4cs are an adjunct
Advice for pts w/diarrhea returning from cholera-‐epidemic countries
• Obtain travel hx!!! • If cholera suspected, aggressive rehydra4on • Doxycycline or azithromycin for hospitalized pts • Report to DPH • While risk of person-‐person transmission is low, do not return to work un4l sx subside if food handler, involved in child care, or HCW
Probio4cs • Beneficial microorganisms (lactobacillus or S. boulardii)
• Possible mechanisms – Lactose diges4on – Produc4on of an4-‐microbial agents – Compe44on for space or nutrients – Immune modula4on
• Possible uses-‐no clear indica4ons – Pediatric viral gastroenteri4s – C. difficile & an4bio4c associated diarrhea – Traveler’s diarrhea???
Main refs
• Said et al, CID 2008:47:1202-‐1208 • Glass et al, NEJM 361:18, 2009
hhp://www.cdc.gov/ncidod/dvrd/revb/gastro/norovirus.htm
Diarrhea in a hospitalized pt
• ID is a 64 yo male who underwent a CABG procedure that was complicated by a prolonged intuba4on, fevers, and a possible nosocomial pneumonia. The pt was extubated recently and just completed a 10 d course of Zosyn. He now has low grade temps and watery diarrhea. His abdominal exam is unremarkable. His WBC is 10.2 with a slight ler shir. His Cr is stable at 1.3. His stool for C. diff toxin is posi4ve.
What is the appropriate treatment
1. Stop all an4bio4cs and see if pa4ent improves
2. PO flagyl 500 mg TID x 10-‐14 d
3. PO vancomycin 125 mg PO QID x 10-‐14 d
Diarrhea in hospitalized pts
• Rarely caused by enteric bacteria, parasites, candida • Abx-‐associated diarrhea – ~20% caused by C. difficile • Clostridium difficile iden4fied as an the e4ologic agent of AAB (N Engl J Med 1978; 298: 531-‐534)
– Cytotoxin-‐producing Klebsiella oxytoca is newly recognized cause of hemorrhagic coli4s in pts w/suspected C. diff (Hogenauer et al, NEJM, 2006)
• Drugs • Iatrogenic
Clostridium difficile Kelly, JAMA, 2009; IDSA guidelines May 2010
• Gram posi4ve spore-‐forming rod – Persists in environment; resistant to alcohol and acid
– 3-‐5% of healthy adults are colonized • Disease is caused by Toxins A & B
• No 4ssue invasion, no bacteremia, only causes disease in the colo)n (very rarely terminal ileum in pts w/inflammatory bowel disease
– More likely to be asymptoma4c if culture + but Toxin -‐) – Recent severe outbreaks associated with an addi4onal toxin (Ctd-‐
unclear role in disease) and increased produc4on of toxins A & B – Toxins A&B disrupt the ac4n cytoskeleton-‐likely how they cause
diarrhea
• Responsible for ~20% AAD diarrhea – 300,000-‐cases/yr in US – Increasing incidence (doubled between 2001-‐2005) and severity
Pathophysiology
Pseudo-‐membranous
coli4s
Healthy colon
Clinical Signs/Sx
• Sx range from asymptoma4c to severe – Mild-‐mod disease: <10 stools/day, no fever, WBC<15K, Cr <1.5x nl,
minimal abd pain
– Severe disease: fever, severe abd pain, WBC>15-‐20K, Cr >1.5x nl, hypoalbumenemia, sep4c shock, hypotension, toxic megacolon, or colonic perfora4on
• 90-‐95% have watery diarrhea; 5-‐10% bloody diarrhea • 80% have abd pain, leukocytosis, fever • 50% have +Fecal WBC’s
– Not a useful test!
• May progress to toxic megacolon/perfora4on
Diagnosis: Toxin-‐mediated disease • Test only symptoma4c pts – Diarrheal stools unless pt has ileus
• Toxin tests: No false posi4ves – Tissue culture cytotoxicity assay for Toxin B (95% sensi4ve)
• Filtrate of diarrhea causes cells to round up in 12-‐24 hrs
– Elisa for Toxins A and/or B (70-‐95% sensi4ve) • Up to 1000X less sensi4ve but results avail within 2 hrs
• Test that detects both toxins (A & B) is more sensi4ve (1-‐2% of isolates are toxin A neg)
Dx (con4nued) • 2-‐stage tes4ng -‐faster – Test for presence of bacterium (C. diff an4gen test)
• Does not indicate whether strain is toxin producing • Useful 1˚ screening test (if neg, no need to test for toxin)
– PCR for Toxin B or cytotoxicity test • CT scan: colonic thickening • Flex sigmoidoscopy: pseudomembranes • If ini4al test neg, sx persist, and high suspicion, reasonable to repeat test if >48 hrs elapsed
Risk factors • An4bio4cs
– Usually develops arer 5-‐10 d of abx, can can occur arer 1 dose or as late as 4-‐6 wks arer discon4nua4on of abx
– 96% of pts have h/o abx exposure in prior 2 wks – 100% have h/o exposure to abx in prior 3 mos
• Chemotherapy – Some agents have an4-‐bacterial ac4vity
• PPI • Health care facility • New exposure to C.diff
– Coloniza4on and development of an4bodies to toxins may be protec4ve
• Community acquired cases without abx exposure reported
An4bio4cs Associated With C. difficile
Frequent Infrequent Rare
Cephalosporins (especially 2nd & 3rd gen agents)
Tetracyclines Aminoglycosides
Ampicillin & amoxicillin Trimethoprim-‐sulfamethoxazole
Metronidazole
Clindamycin Macrolides
Fluoroquinolones Vancomycin
Rifampin
Emergence of more virulent strain(s) • 2000: Emergence of B1/NAP1/027,
– fluoroquinolone resistant – hyperproducer of Toxins A&B – Produces addi4onal toxin (Binary toxin)
• ~ 1/3 isolates B1/NAP1 in some loca4ons • US: incidence 2x and mortality 4x
• ?reduced suscep4bility to metronidazole
Infec4on control measures: prevent person-‐person spread of this spore former
1. Pa4ent isola4on in a single room, preferably with a bathroom
2. Strict contact precau4ons 3. Terminal room cleansing with 1:10 bleach 4. Avoidance of rectal thermometers 5. Soap and water for hand washing 6. An4bio4c control (clindamycin, 3rd genera4on
cephalosporins)
Treatment of C. diff • Discon4nue all unnecessary an4bio4cs. If
possible, switch to more “low risk” an4bio4cs
• Avoid narco4cs and other agents known to reduce peristalsis
• Infec4on control measures
• Oral an4bio4c treatment – Non-‐severe cases: PO flagyl (500 mg TID x 10-‐14 d) – Severe cases: PO vanco (125 mg PO QID x 10-‐14 d)
– NPO pt: IV flagyl, if severe, consider vanco PR
• Probio4cs?
• Ini4al episode and first recurrence – Mild –to-‐moderate: metronidazole 500 mg PO TID for 10-‐14 days
– Severe or unresponsive to Metronidazole: vancomycin 125 mg PO QID for 10-‐14 days
Suggested approach NEJM Kelly & LaMont 359:1932, 2008
Flagyl vs Vanco Zar et al, CID 2007 45:302
• 69 severe cases – 97% of pts treated with vanco cured; 10% relapse – 76% treated with Flagyl cured: 21% relapse
• 81 mild cases – No difference in vanco vs flagyl rx
Treatment in NPO Pa4ent With Severe Disease
• IV or PO metronidazole re-‐enters small bowel via hepa4c re-‐circula4on, delivers ac4ve agent intraluminally.
• IV metronidazole never compared with PO vancomycin or PO metronidazole, but recommended in the pa4ent with ileus or toxic megacolon
• Vancomycin 500 mg QID by reten4on enema or NG tube • Intravenous immune globulin (IVIG) • Monoclonal ab • Tigecycline • Colectomy
Recurrent C. difficile • Incidence: 20% – Higher risk in pts w/ h/o relapse
• 50% have same organism, 50% have new strain
• Not related to severity of ini4al C. diff disease, inci4ng abx, Vancomycin vs Metronidazole rx, or persistence of C. diff within 72 hrs post ini4al rx – No role to reculture or retest at end of Rx – Carriage 3-‐4 wks arer ini4al rx was assoc with recurrent disease
• Usually occurred within 2 wks of discon4nua4on of Metronidazole or Vancomycin
• Probably a result of failure to develop ab response to toxins rather than drug failure
Relapse and Recurrence • Single recurrence: Rx w/ standard course PO metronidazole or
PO vancomycin • Recurrent disease: PO vancomycin in tapering dose over 4
weeks or 125 mg PO QOD for 6 weeks • Immune globulin 400 mg/Kg and consider repeat in 3 weeks • Monoclonal Ab in conjunc4on w/flagyl or vanco (7% recurrence
vs 25% in controls) (Lowry et al, NEJM, 2010). • Rifamicin: 2 wks arer comple4ng PO Vanco course
– Resistance does develop (Johnson et al, CID, 2007) • Fecal transplant using spousal donors • Probio4cs: Lactobacillus or Saccharomyces boulardii
Fidaxomicin v Vancomycin
• Prospec4ve, randomized, double-‐blind, controlled study
• Compare fidaxomicin 200 mg orally twice daily (287 pa4ents) and vancomycin 125 mg orally four 4mes daily (309 pa4ents)
• Exclusions – Severe disease(megacolon) – IBD – More than one recurrence
Role of Fidaxomicin in Therapy
• Use in recurrences? • COST IS AN ISSUE – Fidaxomicin is $1200 for 10 days
– Metronidazole and vancomycin are a frac4on of the cost
Probio4cs may have a place…
• Probio4cs are considered very safe – However, ingredients, dosing, ac4vity of probio4cs not regulated
• Cochrane review 2008: ¼ trials showed a benefit • McFarland, Anaerobe, 2009
– Pts must be followed up for 4-‐6 wks to adequately assess influence on recurrence
– Differences in probio4c prepara4ons – Meta-‐analyses should be viewed w/cau4on because they lump
together different probio4c preps
• McFarland 2006 meta-‐analysis found benefit for preven4ng recurrence in CDAD
What is the appropriate treatment
1. Stop all an4bio4cs and see if pa4ent improves
2. PO flagyl 500 mg TID x 10-‐14 d
3. PO vancomycin 125 mg PO QID x 10-‐14 d
Hospital Acquisi4on of C. difficile
• Prospec4ve study of 428 pa4ents admihed to a medical ward over an 11 month period – 7% (29 ) +ve on admission – Of the ini4ally 399 –ve pa4ents, 83 or 21% acquired C.difficile • 63% (52) remained asymptoma4c • 37% (31) developed C. difficile diarrhea
– Median 4me to acquisi4on—12days (range 3-‐98 days)
Hospital Acquisi4on of C. difficile N Engl J Med 1989;320:204-‐210
• Pa4ent-‐to-‐pa4ent transmission of C. difficile was evidenced by:
• 4me-‐space clustering of cases • Iden4cal immunoblot types • More frequent and earlier acquisi4on of C. difficile among pa4ents exposed to roommates with +ve cultures
Clinical Implica4ons—Unsehled Issues
• Recent descrip4on of airborne dispersal of C. difficile (CID 2010;50(11):1450-‐57)
• Spores isolated from air of 70% of pa4ents • “Fecal Cloud” surrounding symptoma4c pa4ents – ??? Airborne precau4ons
Other (Second-‐Line) Therapies for C. difficile
• Nitazoxanide (Alinia®)—500 mg BID X 7-‐10 days (Clin Infect Dis 2006;43:421)
• Rifaximin 400 mg QID X 10-‐14 days – Used as a “chaser” for therapy of recurrent disease (Clin Infect Dis 2007;44:846)
• Toxin binding agents—cholestyramine/Tolevamer 2 gm TID X 14 days (Clin Infect Dis 2006;43:411)
• Probio4cs—no good data to support the use for preven4on of C difficile disease