Erdman - Fluoroquinolones Flashcards
Why are fluoroquinolones a big deal?
-Broad spectrum of activity
-Excellent oral bioavailability
-Long half-lives
What are the fluoroquinolones?
-Ciprofloxacin (PO, IV)
-Levofloxacin (PO, IV)
-Moxifloxacin (PO, IV)
-Delafloxacin (PO, IV)
Fluoroquinolone mechanism of action
Bind to and inhibit topoisomerase 2 (primary gram-negative target) and topoisomerase 4 (primary gram-positive target)
What are the mechanisms of resistance for fluoroquinolones?
-Altered binding sites
-Expression of active efflux
-Altered cell wall permeability (decreased porin expression)
-Cross-resistance occurs between FQs
What are the older FQs?
Ciprofloxacin
What are the newer FQs (respiratory)?
-Levofloxacin
-Moxifloxacin
-Delafloxacin (not technically in this category but has similar activity)
Which FQs are best against gram-positive?
Newer/respiratory FQs
FQ activity against gram positive aerobes
-Group and viridans streptococci (limited activity)
-Streptococcus pneumoniae (including PRSP)*
-Enterococcus spp. (limited activity)
-MSSA* (never used)
-MRSA* (only delafloxacin but also never really used)
Which FQs are best against gram-negative?
-Cipro
-Dela
-Levo
FQ activity against gram negative aerobes
HENPECKSSS
-Pseudomonas aeruginosa - significant resistance has emerged (NOT moxi)
FQ activity against anaerobes
Moxi has limited activity against bacteroides spp.
Which FQs are best against atypical?
All FQs have excellent activity
FQ activity against atypical
-Legionella pneumophila (DOC)
-Chlamydia and chlamydia spp.
-Mycoplasma spp.
-Ureaplasma urealyticum
Other bacteria that FQs cover
-Mycobacterium tuberculosis
-Bacillus anthracis
What are FQs dependent on when killing bacteria
-Concentration dependent
-AUC/MIC
-Conc-time profile lower than beta-lactams
Which FQs can penetrate the CSF?
All have minimal penetration
Which FQs are not renally eliminated?
Moxifloxacin
Which FQs are removed during hemodialysis?
None
How fast do FQs kill bacteria?
Very rapid killers
What tissues do FQs penetrate?
-Lung
-Bone
-Urinary tract and prostate (cipro, levo, dela)
Which FQ does not penetrate into the urinary tract system or the prostate?
Moxifloxacin (not renally eliminated)
Are FQs good for treating meningitis?
No, they do not get into CSF
Which FQs require dosage adjustment in renal insufficiency?
-Levo
-Cipro
-Dela
Clinical uses of FQs
-Community acquired pneumonia (levo, moxi)
-Nosocomial pneumonia (cipro, levo)
-UTI (cipro, levo)
-Skin and skin structure infections (dela)
Which FQs are used for upper respiratory tract infections?
-Levo
-Moxi
-Cipro
Which FQs are used for community-acquired pneumonia?
-Levo
-Moxi
(respiratory FQs)
Which FQs are used for nosocomial pneumonia?
-Cipro
-Levo
(Want gram negative coverage)
Which FQs are used for cystitis, pyelonephritis, prostatitis, UTIs?
-Cipro
-Levo
Which FQs are used for skin infections?
Dela (MRSA coverage)
(Never used due to lack of studies and price)
FQ adverse effects
-Neurologic (peripheral neuropathy)
-Prolonged QTc interval (possible Torsades)
-Articular cartilage damage
-Tendonitis and tendon rupture
What is the black box warning on FQs?
Peripheral neuropathy
Who is at risk of TDP in patients taking FQs?
-Hypokalemia
-Preexisting QTc prolongation
-Concomitant antiarrhythmics
What patient population are FQs contraindicated in?
-Pediatric patients
-Pregnant/breastfeeding patients
Who is at risk of tendon rupture/tendonitis in patients taking FQs?
-Patients over 60 years old
-Patients on corticosteroids
-Transplant patients
What are potential drug interactions with FQs?
-Divalent and trivalent cations (all PO FQs)
-Warfarin (all FQs)
What are the effects of taking an oral FQ with a divalent or trivalent cation?
Impair absorption of FQ leading to clinical failure
Can you still give divalent or trivalent cations to a patient taking oral FQs?
Yes you must stagger the dose by 2-6 hours and preferably administer the FQ first
Which drugs interact with cipro?
-Theophylline
-Cyclosporine
