Dr. Cluck Non Beta-Lactams (FQ, Aminoglycosides, Metronidazolide)EXAM 2 Flashcards
Important FQs
Ciprofloxacin 2nd (Cipro)
Levofloxacin 2nd (Levaquin)
Moxifloxacin 4th (Avelox, Vigamox)
Newer: Delafloxacin (Saxdela)
What is special about Delafloxacin?
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
Spectrum of activity FQ
-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)
Why is Ciprofloxacin considered Gen 2.5
-Because 2nd Gen covers MSSA and Cipro does NOT
What would be DOC for Strep pneumo (gram-positive)
-Levofloxacin or Moxifloxacin
-Ciprofloxacillin could work but it is not a respiratory FQ and not the best choice
Spectrum of activity 3rd/4th FQ
-Braod gram-positive
-EXCELLENT gram-negative-
-Broad anaerobic (Moxifloxacin PO option would be okay - there are better options)
-activity against Mycobacterium
Pharmacokinetics of FQ
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
What is the IV to PO conversion for Cipro?
Example:
IV 400 mg –> PO 500 mg
Which FQs need renal adjustment?
Cipro and Levofloxacin
-Moxifloxacin doesn’t need renal adjustment
Which FQ can NOT be used for UTIs?
Moxifloxacin
Contraindications and Warnings of FQ
-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)
Adverse effects for FQ
-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
Drug Interactions of FQs
Antacids/Iron/Zinc
Milk
Theophylline
Corticosteroids - work synergistically
Warfarin - reduce Vitamin K production -> bleeding
Antipsychotics/TCAs - QTc effect
Tizanidine + ciprofloxacin -> Category X, hypotension
Mechanism of Resistance
-Point mutation altering binding site of DNA Gyrase or topoisomerase IV
-Decreased permeability
-Efflux pumps
Clinical Pearls FQ
-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
Important Aminoglycosides
-Amikacin
-Gentamicin (does NOT cover Pseudomonas)
-Tobramycin (covers Pseudomonas)
PO option for Aminoglycoside
Neomycin
MOA for Aminoglycosides
-Blocks initiation
-promotes premature termination
-incorporates incorrect amino acids
Are Aminoglycosides Bacteriostatic or Bacteriocidal?
-Bacteriocidal
(while other protein synthesis inhibitors like tetracycline, and macrolides are static)
Spectrum of activity Aminoglycosides
-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
Pharmacokinetics of Aminoglycoside
Absorption: Absorbed parenterally only
Distribution: Wide distribution, very poor CSF penetration
Metabolism/Excretion: Essentially no metabolism and excreted via glomerular filtration (kidneys)
Adverse effects of Aminoglycosides
-Nephrotoxicity
-Ototoxicity (Can be irreversible)
-Neuromuscular blockade (don’t dose high in patients with myasthenia gravis (muscle weakness))
Drug Interactions Aminoglycosides
Augmented toxicity with concurrent use of Vancomycines and loop diuretics
Example: Which drugs are used for gram-negative and gram-positive coverage in a critically ill patient?
Gram-negative: Penicillin (Cephalosporin late GEN?)
Gram-positive: Vancomycin
2nd Gram-negative: Aminoglycoside (covers aerobic gram-negative)
Why do Aminoglycosides cover AEROBIC Gram-positives?
Because they require an O2 pump to enter the cell
Mechanisms of Resistance Aminoglycosides
Anaerobics are resistant bc they don’t use an O2 pump
-Altered ribosomal-binding
-decreased permeability
-production of inactivating enzymes
-efflux pumps
Clinical Pearls Aminoglycosides
-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
Which Aminoglycoside covers Pseudomonas?
Tobramycin
(Gentamycin does not cover Pseudomonas)
Flagyl (metronidazole)
-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)
Profound MOA
-nitro group serves as an electron acceptor
-> forms compound that binds and breaks DNA
Adverse Effects Metronidazole
-N/V/D
-Disulfiram reaction when taken with alcohol (controversial)
-Peripheral neuropathy (long-term use)
-Urine discoloration
-Taste perversion (metallic)
