ABX for Diarrhea

Question 1

Drugs for Infectious Diarrhea

Answer 1

Fluoroquinolones (-oxacin)
Trimethoprim-Sulfamethoxazole
Antiprotozoal (Metronidazole)
Others (Vancomycin)
Symptomatic Therapy- Bismuth subsalicylate, opioid agonists

Question 2

bacterial meningitis, gram-positive diplococci- what is it?

Answer 2

strep pneumo

Question 3

agent that inhibits the enzyme responsible for bacterial cell wall transpeptidation. Choose from below:

Azithromycin 
Ceftriaxone
Doxycycline
Levofloxacin
Trimethoprim-sulfamethoxazole

Answer 3

Answer: Ceftriaxone (3rd gen cephalosporin)

azithromycin is a macrolide
doxycycline is a tetracycline
levofloxacin is a fluoroquinolone
trimeth is a sulfonamide

Question 4

On ceftriaxone for bacterial meningitis, now diarrhea with cramping pain, mucoid, greenish foul-smelling watery stools. Temp 101.3, stool sample positive for fecal leukocytes.

What is this? Best management?

Answer 4

c. diff (antibiotic-associated)
gram-positive, spore forming bacillus

begin directed therapy for C. diff but do not discontinue the ceftriaxone (meningitis!)

Question 5

antimicrobials that may induce C diff diarrhea

Answer 5

Frequently: fluoroquinolones, clindamycin, cephalosporins, penicillins

occasionally: macrolides, trimethoprim-sulfamethoxazole

Rarely: aminoglycosides, tetracyclines, metronidazole, vancomycin

Question 6

Appropriate initial treatment for c diff associated diarrhea?

Answer 6

vancomycin and metronidazole
(vanco binds D-Ala-D-Ala and inhibits bacterial cell wall synthesis)
(metronidazole damages bacterial DNA via nitro radical groups)

For severe and complicated, can combine the two drugs

Question 7

what ginds DNA gyrase?

Answer 7

fluoroquinolone

Question 8

What prevents folic acid synthesis?

Answer 8

sulfa drugs

Question 9

how do we choose between metronidazole and vancomycin for c diff?

Answer 9

can they handle oral? (vanco can be given IV)

They are equally efficacious in mild, but for severe, vanco is superior

vanco is also super expensive, so for mild (leukocytosis of 15,000 cells/ microLiter or lower and creatinine 1.5 times the premorbid level) we use metronidazole

Question 10

other ways to get c diff besides abx

Answer 10

c diff spores (nosocomial)

Question 11

ADR of fluoroquinolones

Answer 11

achilles tendon rupture

Question 12

ADR of tetracyclines

Answer 12

photosensitivity

Question 13

ADR of macrolides

Answer 13

QT prolongation

Question 14

ADR of vancomycin

Answer 14

ab pain, bad taste, nausea

metronidazole can also cause bad taste.

Question 15

IV antibiotics and diarrhea?

Answer 15

not appropriate; doesn’t get to the GI tract

if oral won’t work, let’s do rectal or through ileostomy

Question 16

traveler’s diarrhea treatment

Answer 16

often e coli

management: oral rehydration would be critical
fluoroquinolones to shorten the diarrhea from 3-4 days to 1-2 days

Question 17

symptomatic therapy for diarrhea hat works by inhibiting intestinal prostaglandin and chloride secretion

Answer 17

bismuth subsalicylate

Question 18

How does aprepitant work?

Answer 18

NK-1 receptor antagonist, for nausea and vomiting

Question 19

bisacodyl works how?

Answer 19

stimulant laxative

Question 20

diphenoxylate is what?

Answer 20

opioid agonist

Question 21

loperamide is what?

Answer 21

opioid agonist

Question 22

gal with traveler’s diarrhea

The decision is made to begin antibiotic therapy.  Which of the following agents would be most appropriate in this case? 
Azithromycin
Ciprofloxacin
Metronidazole
Trimethoprim-sulfamethoxazole
Vancomycin

Answer 22

ciprofloxacin

Question 23

undercooked chicken. What diarrhea?

Answer 23

campylobacter

Question 24

Which of the following would be most appropriate for campylobacter? An agent which inhibits: 
Cell wall synthesis
DNA gyrase
DNA synthesis
Folic acid synthesis
Protein synthesis

Answer 24

Azythromycin or Erythromycin

protein synthesis inhibitor belonging to the macrolide class

campylobacter is resistant to fluoroquinolones (chicken feed?)

Question 25

sick drinking alcohol, treated with abx.

Answer 25

probably it’s metronidazole

more clues– he had been backpacking and drinking stream water (giardia)

Question 26

therapy for giardiasis, does what? Inhibits…

Cell wall synthesis
DNA gyrase
DNA synthesis
Folic acid synthesis
Protein synthesis

Answer 26

inhibits DNA synthesis (metronidazole!)

don’t take with alcohol!

Question 27

popular mexican grill, now bloody diarrhea, abdominal tenderness, no fever. What diarrhea?

Answer 27

E Coli (hemorrhagic)

Question 28

A 50 y/o female with Shiga toxin-producing E. coli (STEC).

The best management for this patient would include:
Azithromycin – to reduce duration of diarrhea from 3-4 to 1-2 days
Ciprofloxacin – to reduce duration of illness 2.4 days
Loperamide – to reduce patient symptoms
Metronidazole – to treat diarrhea if persistent
Supportive care – antibiotics will not affect illness duration

Answer 28

Supportive care!

ABX can make it worse

Question 29

Glycopeptides MOA, ADRs

Answer 29

Vancomycin (PO, IV)
MOA: * inhibits cell wall synthesis binding with high affinity to D-Ala-D-Ala terminal of cell wall precursor units.
Spectrum: broad gram-positive coverage – S. aureus (including MRSA), S. epidermidis (including MRSE), Streptococci, Bacillus, Corynebacterium spp., Actinomyces, * Clostridium
Therapeutic Use: osteomyelitis, endocarditis, MRSA, Streptococcus, enterococci, CNS infections, bacteremia, * orally for C. difficile
ADRs:
Macular skin rash, chills, fever, rash
Red-man syndrome (histamine release): extreme flushing, tachycardia, hypotension
Ototoxicity, nephrotoxicity (33% with initial trough > 20 mcg/mL)

Question 30

Fluoroquinolones MOA, ADRs

Answer 30

MOA: concentration-dependent; targets bacterial DNA gyrase & topoisomerase IV.
Spectrum: * E. coli, * Salmonella, * Shigella, Enterobacter, * Campylobacter, Neisseria, Pseudomonas aeruginosa, S. aureus (not MRSA), limited coverage of Streptococcus spp.
Therapeutic Use: UTI, prostatitis, STI (chlamydia, Neisseria gonorrhoeae), * traveler’s diarrhea, * shigellosis, bone, joint, SSTI infections, diabetic foot infections
ADRs:
GI 3-17% (mild nausea, vomiting, abdominal discomfort)
CNS 0.9-11% (mild headache, dizziness, delirium, rare hallucinations)
Rash, photosensitivity, Achilles tendon rupture (CI in children)

Question 31

Metronidazole MOA, ADRs

Answer 31

MOA: prodrug, requires reductive activation of nitro groups by susceptible organisms. Highly reactive nitro radical anions kill organisms by * targeting DNA
Spectrum: anaerobic cocci and both anaerobic gram-negative bacilli (including Bacteroides) and anaerobic spore forming gram-positive bacilli * (Clostridium), trichomoniasis, * amebiasis, * giardiasis. Helicobacter and Campylobacter.
Therapeutic Use: anaerobic bacterial infections. * Clostridium difficile
ADRs:
Headache, nausea, dry mouth, metallic taste
Vomiting, diarrhea, abdominal distress
Well-reported disulfiram effect
DDIs: induced metabolism of phenobarbital, prednisone, rifampin. Prolongs prothrombin time in those receiving warfarin.

Question 32

Sulfonamides & Trimethoprim MOA, ADRs

Answer 32

MOA: sulfonamides = bacteriostatic, competitive *inhibitors of dihyropteroate synthase. Synergistic trimethoprim = * inhibition of microbial dihydrofolate reductase.
Spectrum: Broad! * E. coli, Proteus mirabilis, Proteus morgannii, Enterobacter, * Salmonella, * Shigella, Serratia, Brucella abortus, Yersinia pseudotuberculosis, T. enterocolitical, Norcardia asteroids
Therapeutic Use: UTI, bacterial prostatitis, bronchitis, * Shigellosis, * Traveler’s diarrhea, * Salmonella, Pneumocystis jiroveci (fungus) prophylaxis in neutropenia, Nocardia, Stenotrophomonas maltophilia.
ADRs: allergic skin rashes, nausea, vomiting, CNS (headache, depression), photosensitivity, renal dysfunction, Stevens-Johnson syndrome.