Erdman - Fluoroquinolones

Question 1

Why are fluoroquinolones a big deal?

Answer 1

-Broad spectrum of activity
-Excellent oral bioavailability
-Long half-lives

Question 2

What are the fluoroquinolones?

Answer 2

-Ciprofloxacin (PO, IV)
-Levofloxacin (PO, IV)
-Moxifloxacin (PO, IV)
-Delafloxacin (PO, IV)

Question 3

Fluoroquinolone mechanism of action

Answer 3

Bind to and inhibit topoisomerase 2 (primary gram-negative target) and topoisomerase 4 (primary gram-positive target)

Question 4

What are the mechanisms of resistance for fluoroquinolones?

Answer 4

-Altered binding sites
-Expression of active efflux
-Altered cell wall permeability (decreased porin expression)
-Cross-resistance occurs between FQs

Question 5

What are the older FQs?

Answer 5

Ciprofloxacin

Question 6

What are the newer FQs (respiratory)?

Answer 6

-Levofloxacin
-Moxifloxacin
-Delafloxacin (not technically in this category but has similar activity)

Question 7

Which FQs are best against gram-positive?

Answer 7

Newer/respiratory FQs

Question 8

FQ activity against gram positive aerobes

Answer 8

-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)

Question 9

Which FQs are best against gram-negative?

Answer 9

-Cipro
-Dela
-Levo

Question 10

FQ activity against gram negative aerobes

Answer 10

HENPECKSSS
-Pseudomonas aeruginosa - significant resistance has emerged (NOT moxi)

Question 11

FQ activity against anaerobes

Answer 11

Moxi has limited activity against bacteroides spp.

Question 12

Which FQs are best against atypical?

Answer 12

All FQs have excellent activity

Question 13

FQ activity against atypical

Answer 13

-Legionella pneumophila (DOC)
-Chlamydia and chlamydia spp.
-Mycoplasma spp.
-Ureaplasma urealyticum

Question 14

Other bacteria that FQs cover

Answer 14

-Mycobacterium tuberculosis
-Bacillus anthracis

Question 15

What are FQs dependent on when killing bacteria

Answer 15

-Concentration dependent
-AUC/MIC
-Conc-time profile lower than beta-lactams

Question 16

Which FQs can penetrate the CSF?

Answer 16

All have minimal penetration

Question 17

Which FQs are not renally eliminated?

Answer 17

Moxifloxacin

Question 18

Which FQs are removed during hemodialysis?

Answer 18

None

Question 19

How fast do FQs kill bacteria?

Answer 19

Very rapid killers

Question 20

What tissues do FQs penetrate?

Answer 20

-Lung
-Bone
-Urinary tract and prostate (cipro, levo, dela)

Question 21

Which FQ does not penetrate into the urinary tract system or the prostate?

Answer 21

Moxifloxacin (not renally eliminated)

Question 22

Are FQs good for treating meningitis?

Answer 22

No, they do not get into CSF

Question 23

Which FQs require dosage adjustment in renal insufficiency?

Answer 23

-Levo
-Cipro
-Dela

Question 24

Clinical uses of FQs

Answer 24

-Community acquired pneumonia (levo, moxi)
-Nosocomial pneumonia (cipro, levo)
-UTI (cipro, levo)
-Skin and skin structure infections (dela)

Question 25

Which FQs are used for upper respiratory tract infections?

Answer 25

-Levo -Moxi -Cipro

Question 26

Which FQs are used for community-acquired pneumonia?

Answer 26

-Levo -Moxi (respiratory FQs)

Question 27

Which FQs are used for nosocomial pneumonia?

Answer 27

-Cipro -Levo (Want gram negative coverage)

Question 28

Which FQs are used for cystitis, pyelonephritis, prostatitis, UTIs?

Answer 28

-Cipro -Levo

Question 29

Which FQs are used for skin infections?

Answer 29

Dela (MRSA coverage) (Never used due to lack of studies and price)

Question 30

FQ adverse effects

Answer 30

-Neurologic (peripheral neuropathy) -Prolonged QTc interval (possible Torsades) -Articular cartilage damage -Tendonitis and tendon rupture

Question 31

What is the black box warning on FQs?

Answer 31

Peripheral neuropathy

Question 32

Who is at risk of TDP in patients taking FQs?

Answer 32

-Hypokalemia -Preexisting QTc prolongation -Concomitant antiarrhythmics

Question 33

What patient population are FQs contraindicated in?

Answer 33

-Pediatric patients -Pregnant/breastfeeding patients

Question 34

Who is at risk of tendon rupture/tendonitis in patients taking FQs?

Answer 34

-Patients over 60 years old -Patients on corticosteroids -Transplant patients

Question 35

What are potential drug interactions with FQs?

Answer 35

-Divalent and trivalent cations (all PO FQs) -Warfarin (all FQs)

Question 36

What are the effects of taking an oral FQ with a divalent or trivalent cation?

Answer 36

Impair absorption of FQ leading to clinical failure

Question 37

Can you still give divalent or trivalent cations to a patient taking oral FQs?

Answer 37

Yes you must stagger the dose by 2-6 hours and preferably administer the FQ first

Question 38

Which drugs interact with cipro?

Answer 38

-Theophylline -Cyclosporine