C.18. Metronidazole. Fidaxomicin. Rifaximin. Pharmacotherapy of abdominal infections

Question 1

mechanism of action of metronidazole

Answer 1

ferredoxin present in anaerobes causes reductive bioactivation of metronidazole–> forming free radicals –> interfere with the nucleic acid synthesis
bactericidal effect

Question 2

what is the spectrum and clinical use of metronidazole?

Answer 2

1. Anaerobic gram -
2. clostridium difficile (pseudomembranous colitis)
3. Gardnerella vaginalis
4. H. pylori
5. intra-abdominal infections
6. brain abscesses
7. antiprotozoal: giardia, trichomonas vaginalis, entamoeba

Question 3

where does metronidazole achieve high concentration?

Answer 3

CSF

Question 4

what drugs have negligible SE due to limited absorption?

Answer 4

Fidaxomicin and Rifaximin

Question 5

how is metronidazole given?

Answer 5

oral or parenterally

Question 6

how are fidaxomicin and rifaximin given?

Answer 6

orally

Question 7

properties of metronidazole

Answer 7

• hepatic metabolism (dose reduction may be required in liver dysfunction)
• inhibitor of CYP450 enzymes

Question 8

how is the systemic absorption of Fidaxomicin and Rifaximin?

Answer 8

poor. reaches high luminal concentration

Question 9

side effects of metronidazole

Answer 9

GI distress
Leukopenia
CNS effects (neuropathy)
dark urine discoloration 
metallic taste
Disulfiram-like reaction with ethanol (nausea. vomiting, headache, hypotension)

Question 10

what is the difference between metronidazole and Tinidazole?

Answer 10

Tinidazole has a longer T1/2 (allows once-daily dosing)

*Tinidazole shares many common properties and indications as metronidazole

Question 11

mechanism of action of Fidaxomicin

Answer 11

inhibits bacterial RNA polymerase (transcription)

bactericidal effect

Question 12

what is the clinical use of fidaxomicin?

Answer 12

narrow-spectrum
gram-positive anaerobes
C. difficile

Question 13

what is Rifaximin and what is it’s mechanism of action?

Answer 13

Derivative of rifampicin

inhibits DNA- dependent RNA polymerase (transcription)

Question 14

what is the spectrum and clinical use of rifaximin

Answer 14

1. gram + and -
2. aerobes and anaerobes
3. management of IBS
4. diverticular disease
5. management of hepatic encephalopathy (↓ ammonia production)
6. travelers diarrhea

Question 15

what is the 1st line treatment for appendicitis?

Answer 15

ceftriaxone IV and metronidazole PO/IV

Question 16

what is the 2nd line treatment for appendicitis?

Answer 16

gentamycin IV and metronidazole PO/IV

Question 17

what is the 1st line treatment for cholecystitis?

Answer 17

ceftriaxone IV and Ampicillin IV

Question 18

what is the 2nd line treatment for cholecystitis?

Answer 18

ciprofloxacin PO/IV and Vancomycin IV

Question 19

Ab given in uncomplicated diverticular disease

Answer 19

Rifaxamin

Question 20

what is the 1st line treatment for diverticulitis (mild to moderate)?

Answer 20

TMP-SMX PO

Question 21

what is the 1st line treatment for diverticulitis (severe)?

Answer 21

piperacillin/tazobactam IV or Imipenem/Cilastatin IV

Question 22

what is the 2nd line treatment for diverticulitis (mild to moderate)?

Answer 22

ciprofloxacin PO and Metronidazole PO

Question 23

what is the 2nd line treatment for diverticulitis (severe)?

Answer 23

Ticarcillin/Clavulanate IV or Ertapenem

Question 24

what is the 1st line treatment for peritonitis (spontaneous bacterial)?

Answer 24

Ceftriaxone IV

Question 25

what is the 2nd line treatment for peritonitis (spontaneous bacterial)?

Answer 25

Levofloxacin IV

Question 26

what is the 1st line treatment for peritonitis (acute perforation)?

Answer 26

Ceftriaxone IV and Metronidazole PO/IV

Question 27

what is the 2nd line treatment for peritonitis (acute perforation)?

Answer 27

Gentamicin IV and Metronidazole PO/IV