Gi_Pm_Micro&pharma_Abx-Assoc-Colitis

Front 1

Describe the outcomes of Antibiotic Therapy (ABTx) leading to coitis

Back 1

ABTx -->
Disruption of Colonic Microflora --> C. difficile exposure and colonization-->
Release of Toxin A (enterotoxin) & Toxin B (Ctyotoxin) -->
Mucosal Injury and Inflammation

Front 2

What do the C. diff bacts do?

Back 2

Produce small amounts of A & B toxins once bug is predominate in colon
-Gastric epi cell skilled and Pseudomembrane forms

Front 3

Incidence in US per year

Transmission

Back 3

3 million
--30% of Hospital Pts with diarrhe

Normal Flora PLUS Fecal Oral

Front 4

Character of C. diff.
Gram
Spore?
Air?
Toxins?

Back 4

Gram Positive
Rod
Spore Forming
Anaerobic
Toxins A (more active) & B

Front 5

What causes diarrhea in C. Diff?

Back 5

ABTx reduce normal flora, interferes with bacterial breakdown of CHOs.
inc CHOs causes Osmotic Diarrhea

Front 6

Describe the Infection?

Back 6

C Diff overgrows
-_Acute inflammation with pus and mucus results in Pseudomembrane

Front 7

What is the epidemic strain of C. diff

Back 7

NAP1/027

Front 8

Which Toxin primarily acts as an enterotoxin

Back 8

Toxin A

Front 9

Effects of Toxin A

Back 9

ALters memrbane perm
-cels die by stimulation of host cell mitogen activating protein kinaases (MAK Kinases
-kills cells in colon

Front 10

Toxin B

Back 10

Toxin B

Front 11

Clinical Sx of c. diff?

Back 11

Varies: Asympto to Fulminant colitis
--Severity related ot toxin actiev and presence of receptors
--Most common is 5-15 stools per day
--Begins 5010 days post AbTx, but can be up to 10 weeks later

Front 12

2-3% peeps develop what

Back 12

Fulminant Colitis-
severe morbidity and mortality
Diarrhea + Constipation
-Seve. Abd pain
-Toxic MEgacolon + Perforation
-Hyperactive bowel sounds

Front 13

Diagnosis

Back 13

Hx of ABTx in past month
-Culture diffiuclt at they're anaerobes
-ELISA on feces for A an B-- 70-90senstitive
-Stool positive for Heme
-Stools contain WBCs about half the time
--Careful endoscopy if no stool produced

Front 14

Prevention of C diff?

Back 14

No vaccine
-Humoral immune response is important
-Vac developing in France for Toxin A and B

Front 15

Deliberate maipulatio of intestinal microflora with Tx intention

Back 15

Probiotics
--Can reduce frequency and or duration of gastroenteriits

Front 16

Evidence ofr PRobiotic benefit in what?

Back 16

ABTx diarrhea
C diff toxin induced colitis
Infectious diarrhea
Hepatic Encephalopathy
IBS
Allergy

Front 17

Contents of Probiotics

Back 17

-Lactic Acid Bacilli (ie, Lactobacillus sp. & Bifidobacterium sp.)
-Non-Path E. Coli, Clostridum butryicum
-Genetic engineered bacteria with immunomodulators

Front 18

What in probiotics is used to modulate immune system

Back 18

Induce protective cytokines (IL-10 and TGF-Betat)
-Suppress Proinflammatory Cytokines (TNF)

Front 19

Secondary effect of Probiotics

Back 19

Modulation of pain perception

Front 20

End of Micro Part of Lecture

Back 20

Beginning Pharma Part of Lecture

Front 21

Which ABs frequently cause Antiobiotic Assoc Colitis (AAC)

Back 21

Frequent:
Fluoroquins (cipros / floxacins)
Clindamycin
BS Pens
BS Cephs

-BS = broad spec

Front 22

Which ABs have Occasional AAC incidence?

Back 22

Macrolides
TMP/SMX (bactrim)

Front 23

Which ABs have Selmdom AAC incidence?

Back 23

Amionglycosides
TCN
Chloramphenical
Metronidazole
Vancomyocin

Front 24

Note:

Back 24

C diff is now #1 Nosocomial infection

Front 25

What is rule for AAC incidence

Back 25

The broader the Spectrum, the greater the incidence

ie, Pen G <<< Amoxicliin << Piperaciliin in terms of causing C diff

Front 26

With mild infection, what is best drug for C diff?

Back 26

Vanco just slightly better than Metron.

If Severe! Vanco is MUCH better

Front 27

What are preventative measures for C diff?

Back 27

Avoid ABTx
C Diff exposure
Vaccine??
Soap and Water (alcohol doesn't kill the spores)

Front 28

MEasures for Suspected or confirmed C diff?

Back 28

Contact Precautions
Hand Hygiene
Hospital (home) cleaning with Weak Bleach

Front 29

Tx for C Diff

Back 29

Stop ABTx if possible
Begin Appr Tx (Vanc or Metro)
Fluid Electrolytes
Antidiarrheal Agents--Loperamide--generally NOT recommended

Front 30

What are several Experimental Agents

Back 30

Fidaxomicin
Rifaximin
Tolevamer

Front 31

Which is shown in one study to be superior and or equivalent to vancomycin in C diff Tx

Back 31

Fidaxomycin

Front 32

How long are drugs administered

Back 32

10-14 Days for Metro and Vanc

Note: this is one of few times Vanc is given orally---it is NOT absorbed

Front 33

What are primary AE for Metro

Back 33

Mainly GI
N&V, Xerostomia
Metallic Taste, Anorexia, Ab pain

CNS: seriuos ones--go away with D/C drug

Disulfiram-Like Reaction

Front 34

drug interaction with Metro
(main 2)

Back 34

Warfarin
-Increased Levels, INR, bleeding

Phenobarbitol-?

Front 35

What is MOA for Metronidazole?

Back 35

Disrupts DNAs helical structure

Front 36

Which bacteria are covered by Metro

Back 36

Bacteroides fragilis
C. diff and C. perfringens
Gardnerella vaginalis
H. Pylori

Front 37

What PRots are covered by Metro

Back 37

Entamoeba histolytica
giardia lamblia
Trichomonas vaginalis

__ONE of thses IS NOT covered by Metro maybe)

Front 38

Metro with Preggers?

Back 38

Categroy B: many do not recommend using, esp in 1st trimester
--Most do NOT recommend breast feeding

Front 39

Moving onto Vancomycin

Back 39

Disrupts cell wall synthesis
--Doesn't Rapidly Kill---rather its a SLOW onset ABTx
--intereferes with other shit/ multiple MOAs
--GIven orally ONLY for GI tract issues

Front 40

Drug Interactions
--think of the NO in vaNcO

Back 40

Nephrotoxic
Ototoxic

-Redneck Syndrome/ Redman from Nipple line on Up

Front 41

Drug interactions
--think vaNcO

Back 41

Other drugs with Nephro or OTO toxicities

Loop Diuretics