GI Rx of C. dif

Question 1

a. Which 3 drugs are used in the Rx of C. difficile?

b. What other method is used to Rx C. dif infections?

Answer 1

“See (C) Different “Meteors Vanish Fast as Shit”
(C dif→tx w/ M, V, F, S)
a. Abx agents
1. Metronidazole
2. Vancomycin
3. Fidaxomicin
b. Stool Transplant→Fecal Microbiota Transplantation

Question 2

C. dif is the leading cause of _________ diarrhea?

Answer 2

Antibiotic-induced diarrhea

Question 3

T/F: C dif is now the 2nd most commonly hospital-acquired (aka nosocomial) infection behind MRSA.

Answer 3

False, it has overtaken MRSA and is now the mc hospital-acquired infection

Question 4

Recently a new hypervirulent C dif has emerged? What is it and what is it associated with?

Answer 4

NAP1/Ribotype 027 (NAP1/027) which is associated w/ increased disease severity and mortality

Question 5

How does C dif result in pathogenesis/damage?

Answer 5

They produce Toxins A and B that give rise to the pathogenesis.

Question 6

What makes NAP1/027 hypervirulent compared to most other strains of C dif?

Answer 6

a. Most strains of C. dif express tcdC, a protein that inhibits (negatively regulates) toxin gene transcription and therefore, also reduced toxin production.
b. NAP1/027: Mutated tcdC gene→decreased/no expression of tcdC→increased toxin production→increased virulence.

Question 7

Risk factors for C dif infection (CDI)? (4+1 maybe)

Answer 7

1. Exposure to antibiotics (create niche), especially use of multiple Abx→kill normal flora→C dif comes in and grow
2. Hospitalization and other healthcare settings
3. Age→mc in elderly (65-84 y.o.)
4. IBD
   (5. PPIs/H2 blockers/gastric acid suppression not a risk factor but may be associated w/ increase recurrence in AA, elderly, or comorbidities, but not significantly)

Question 8

Use of which antibiotics is most commonly associated w/ development of CDI?

Answer 8

a. Clindamycin
b. Penicillins (ampicillin and amoxicillin??)
c. Cephalosporins
d. Fluoroquinolones (occasionally)

Question 9

Dx of C. dif? (2)

Answer 9

Clinical Suspicion + Specific Immunoassays

1. Clinical Suspicion→diarrhea in pt w/ current/recent Abx use. Supported by presence of C dif bugs or toxin in stool
2. Immunoassays (EIAs) to detect C dif toxins A and B→rapid, inexpensive, convienent but limited due to frequent false negatives

Question 10

Which three antibiotics are used in the Rx of CDI?

Answer 10

1. Metronidazole
2. Vancomycin
3. Fidaxomicin

Question 11

When is oral Metronidazole used (1)?

Answer 11

a. DOC for mild to moderate CDI

do NOT use it if PREGNANT/BREASTFEEDING

Question 12

When is oral Vancomycin the DOC? (2)

Answer 12

1. Severe CDI

2. CDI in pregnant/lactating women

Question 13

How is complicated CDI treated?

Answer 13

Oral Vancomycin + IV Metronidazole

Question 14

How can CDI’s in pt’s with ileus, abdominal distention, or surgical/anatomical abnormalities that prevent oral Abx from reaching the colon be treated?

Answer 14

Rectal Vancomycin Enemas

Question 15

How are CDI recurrences treated?

Answer 15

a. 1st recurrence→same protocol

b. 2nd recurrence→extended course of oral vancomycin

Question 16

What are the indications/treatment recommendations for Fidaxomicin?

Answer 16

there are NONE

Question 17

Contraindications/ADEs of Metronidazole? (3)

Answer 17

Please Never Taste Pregnant-Milk

1. P: Peripheral Neuropathy (numbness and paresthesias of extremities) w/ prolonged use or high doses→therefore, you don’t continue using it w/ multiple recurrences
2. Nausea and Metallic Taste in 10%
3. P-M: contraindicated inPregnancy and Breastfeeding (it crosses placenta and is expressed in breast milk→fetal facial anomalies)

Question 18

MoA of Fidaxomicin?

Answer 18

Macrolide Abx: bactericidal to C dif, including some hypervirulent strains
Unique inhibition of RNA Polymerases (therefore, no cross resistance b/c it acts at a unique site)

Question 19

Is Fidaxomixin broad-spectrum?

Answer 19

No, it has minimal/no activity against gram negative anaerobes, facultative aerobes, or enterobacteriaceaea, and a limited/minimal effect on normal colon/fecal flora.

Question 20

Does Fidaxomixin have cross-resistance with Rifamycins?

Answer 20

No, it has NO cross-resistance with any other anti-microbials, including Rafamycins b/c it has a different/unique site of action on RNA polymerases.

Question 21

Is Fidaxomicin systematized with oral administration? How is it eliminated?

Answer 21

No, there is minimal systematization of after oral administration (it remains in the GI tract) and is almost completely eliminated in stool.

Question 22

ADEs of Fidaxomicin?

Answer 22

Comparable to ADEs of Vancomycin:
NAGging GI toxicity of Fidaxomicin
1. N/V
2. Abdominal pain
3. GI bleeding

Question 23

In pt’s w/ high risk for CDI recurrence how does Fidaxomicin compare to Vancomycin?

Answer 23

Fidaxomicin provides a superior clinical response and lower incidence of recurrence

Question 24

If so good, why is fidaxomicin not commonly used yet?

Answer 24

Much more expensive:
Fidaxomicin»>Vancomycin>Metronidazole

However, in the long run it could be worth it due to decreased expenses of hospitalizations for recurrence.

Question 25

In addition to Abx, how else can CDI be treated?

Answer 25

Fecal Microbiotal Transplant (Stool Transplant)

Question 26

How can fecal tranplant be done?

Answer 26

1. Installation into colon (lower GI tract) via colonoscopy

2. Nasogastric (NG) tube or gastroscopy

Question 27

Is Stool transplant effective?

Answer 27

90% of patients with lower GI (colonic) instillation experience clinical resolution following fecal transplant w/ no evidence of adverse effects from the procedure.