Dr. Cluck Non Beta-Lactams (FQ, Aminoglycosides, Metronidazolide)EXAM 2

Question 1

Important FQs

Answer 1

Ciprofloxacin 2nd (Cipro)
Levofloxacin 2nd (Levaquin)
Moxifloxacin 4th (Avelox, Vigamox)

Newer: Delafloxacin (Saxdela)

Question 2

What is special about Delafloxacin?

Answer 2

Activity against MRSA !!! (important to know)

and Pseudomonas (but does not cover Pseudomonas better than Cipro)

-a good choice for diabetic foot infection, Pseudomonas or MRSA in a wound

-EXPENSIVE though

Question 3

Spectrum of activity FQ

Answer 3

-1st mostly gram-negative (like Aztreonam (which covers gram-negative only)

2nd GEN: activity against gram-positive (resistance rises); EXCELLENT activity against gram-negative
-> Levofloxacine (not Ciprofloxacine)

-Cipro is the DOC for Pseudomonas (Levofloxacin is also active against Pseudomonas)

Question 4

Why is Ciprofloxacin considered Gen 2.5

Answer 4

-Because 2nd Gen covers MSSA and Cipro does NOT

Question 5

What would be DOC for Strep pneumo (gram-positive)

Answer 5

-Levofloxacin or Moxifloxacin

-Ciprofloxacillin could work but it is not a respiratory FQ and not the best choice

Question 6

Spectrum of activity 3rd/4th FQ

Answer 6

-Braod gram-positive
-EXCELLENT gram-negative-
-Broad anaerobic (Moxifloxacin PO option would be okay - there are better options)
-activity against Mycobacterium

Question 7

Pharmacokinetics of FQ

Answer 7

Absorption: absorbed well
Distribution: Well throughout the body, gets to CSF and bones with limited accumulation

Metabolism/Excretion: GEN-dependent

-1:1 conversion from IV to PO for Levofloxacin and Moxifloxacin

Question 8

What is the IV to PO conversion for Cipro?

Answer 8

Example:
IV 400 mg –> PO 500 mg

Question 9

Which FQs need renal adjustment?

Answer 9

Cipro and Levofloxacin

-Moxifloxacin doesn’t need renal adjustment

Question 10

Which FQ can NOT be used for UTIs?

Answer 10

Moxifloxacin

Question 11

Contraindications and Warnings of FQ

Answer 11

-Hypersensitivity to quinolones
-Black box warning for tendinopathy and exacerbation of myasthenia gravis
-can lower the seizure threshold
-caution in kids: cartilage development abnormalities (treatment of last resort)

Question 12

Adverse effects for FQ

Answer 12

-N/V/D
-Photosensitivity
-QT prolongation (causes arrhythmias, dangerous in pt with history of heart problems)
-Clostridioides difficile infection - damages the gut flora
-Blood glucose abnormalities (high or low)
-Can make people crazy (like coffee - especially the elderly) -> not so often

Question 13

Drug Interactions of FQs

Answer 13

Antacids/Iron/Zinc
Milk
Theophylline
Corticosteroids - work synergistically
Warfarin - reduce Vitamin K production -> bleeding
Antipsychotics/TCAs - QTc effect
Tizanidine + ciprofloxacin -> Category X, hypotension

Question 14

Mechanism of Resistance

Answer 14

-Point mutation altering binding site of DNA Gyrase or topoisomerase IV
-Decreased permeability
-Efflux pumps

Question 15

Clinical Pearls FQ

Answer 15

-often prescribed by physicians due to broad coverage
-overuse leads to MRSA
-side effects are rare but should considered prior to use

not needed for basic diseases: UTIs, sinusitis,..
Legionella pneumonia or Mycoplasma pneumonia would be an example to give FQ

Question 16

Important Aminoglycosides

Answer 16

-Amikacin
-Gentamicin (does NOT cover Pseudomonas)
-Tobramycin (covers Pseudomonas)

Question 17

PO option for Aminoglycoside

Answer 17

Neomycin

Question 18

MOA for Aminoglycosides

Answer 18

-Blocks initiation
-promotes premature termination
-incorporates incorrect amino acids

Question 19

Are Aminoglycosides Bacteriostatic or Bacteriocidal?

Answer 19

-Bacteriocidal

(while other protein synthesis inhibitors like tetracycline, and macrolides are static)

Question 20

Spectrum of activity Aminoglycosides

Answer 20

-aerobic gram-negatives
-limited for gram-positives (not recommended for MSSA)
-> synergistic effect with a cell wall active agent (Ampicillin + Gentamycin) for Streptococci and Enterococcus

Question 21

Pharmacokinetics of Aminoglycoside

Answer 21

Absorption: Absorbed parenterally only
Distribution: Wide distribution, very poor CSF penetration

Metabolism/Excretion: Essentially no metabolism and excreted via glomerular filtration (kidneys)

Question 22

Adverse effects of Aminoglycosides

Answer 22

-Nephrotoxicity
-Ototoxicity (Can be irreversible)
-Neuromuscular blockade (don’t dose high in patients with myasthenia gravis (muscle weakness))

Question 23

Drug Interactions Aminoglycosides

Answer 23

Augmented toxicity with concurrent use of Vancomycines and loop diuretics

Question 24

Example: Which drugs are used for gram-negative and gram-positive coverage in a critically ill patient?

Answer 24

Gram-negative: Penicillin (Cephalosporin late GEN?)
Gram-positive: Vancomycin
2nd Gram-negative: Aminoglycoside (covers aerobic gram-negative)

Question 25

Why do Aminoglycosides cover AEROBIC Gram-positives?

Answer 25

Because they require an O2 pump to enter the cell

Question 26

Mechanisms of Resistance Aminoglycosides

Answer 26

Anaerobics are resistant bc they don’t use an O2 pump
-Altered ribosomal-binding
-decreased permeability
-production of inactivating enzymes
-efflux pumps

Question 27

Clinical Pearls Aminoglycosides

Answer 27

-Should NEVER be used as a Monotherapy (except UTIs)
-often as a 2nd Gram-negative drug
-for patients known to be colonized with multiresistant drugs

Question 28

Which Aminoglycoside covers Pseudomonas?

Answer 28

Tobramycin
(Gentamycin does not cover Pseudomonas)

Question 29

Flagyl (metronidazole)

Answer 29

-Available IV, PO, topically, vaginally
-narrow-spectrum: Covers anaerobes and protozoal infections -> so don’t give empirically
-Drug interactions: warfarin and alcohol (data weak, still counsel)

Question 30

Profound MOA

Answer 30

-nitro group serves as an electron acceptor
-> forms compound that binds and breaks DNA

Question 31

Adverse Effects Metronidazole

Answer 31

-N/V/D
-Disulfiram reaction when taken with alcohol (controversial)
-Peripheral neuropathy (long-term use)
-Urine discoloration
-Taste perversion (metallic)