Fluroquinolones

Question 1

MOA

Answer 1

Bactericidal
inhibition of DNA synthesis by binding to and inhibiting bacterial topoisomerases

DNA gyrase (topoisomerase II) - removes excess positive supercoiling in the DNA helix
Quinolones form a stable complex with DNA and DNA gyrase which blocks DNA replication
Primary target in gram negative bacteria

Topoisomerase IV - Essential for separation of interlinked daughter DNA molecules
Quinolones interfere with separation of daughter cells
Primairy target for many gram positive bacteria

Question 2

Mechanisms of resistance

Answer 2

1. Altered binding sites - chromosomal mutation that decreases binding affinity
2. Expression of active efflux
3. Altered cell wall permeability
4. Cross resistance occurs between quinolones

Question 3

Older fluroquinolone

Answer 3

Ciprofloxacin - PO,IV

Question 4

Newer Fluroquinolone

Answer 4

Levofloxacin - PO, IV
Moxifloxacin - PO, IV
Delafloxacin - PO, IV

Question 5

Spectrum of activity
Gram positive aerobes

Answer 5

Ciprofloxacin has poor activity

PRSP (only Newer agents) , MRSA (only Delafloxacin)

Question 6

Spectrum of activity
Gram negative aerobes

Answer 6

Cipro, Dela, Levo > Moxi

H. Influenzia
Moraxella catarrhalis
Enterobacteriaceae (klebsiella, Citrobacter, E. Coli, Enterobacter, Proteus, Salmonella, shigella, serratia, marcescens

Pseudomonas aeruginosa (Cipro> Levo> Dela)

Question 7

Spectrum of activity
Anaerobes

Answer 7

Bacteroides - Moxi has limited activity

Question 8

Spectrum of activity
Atypicals

Answer 8

ALL quinolones
Legionella Pneumophila
Chlamydophila
Mycoplasma
Ureaplasma

Question 9

Pharmacology

Answer 9

Consentration dependent
AUC/MIC
PAE against gram positive (2hours) and gram negative (2 to 4 hours)

Question 10

Absorption

Answer 10

Well absorbed after oral administration
except for delafloxacin 59%

Coadministration with food delays the peak concentration

Question 11

Distribution

Answer 11

Extensive tissue penetration - lung, prostate, bone, bronchial mucosa

Minimal CSF penetration

Question 12

Elimination

Answer 12

Renally eliminated

Hepatically eliminated: Moxifloxacin - does not need renal adjustment

NONE of the quinolones are removed during hemodialysis

Question 13

Clinical use

Answer 13

1.Community aquired pneumonia - levo, moxi
2.Nosocomial Pneumonia - cipro and levo
3.UTI (Cystitis, Pyelonephritis, Prostatitis) - cipro, levo
4.Skin and skin structure infections - delafloxacin
5.Acute exacerbation of chronic bronchitis and sinusitis - cipro, levo, moxifloxacin

Question 14

Adverse effects

Answer 14

Neurological - Peripheral neuropathy (BLACK BOX WARNING)

Cardiac toxicity - QTC prolongation (caution in those with hypokalemia, preexisting QT prolongation, concomitant anti-arrythmics (ex: Amiodarone))

Hepatotoxicity - LFT elevation, liver failure

Articular damage - contraindication in pediatric patient and avoid in pregnant or breast feeding women

Tendonitits and tendon rupture - especially in patients over 60 receiving corticosteroids

Gastrointestinal - N/V, Diarrhea, Dyspepsia

Question 15

Drug interactions
1. Divalent and trivalent cations

Answer 15

1. Divalent and trivalent cations - ALL PO FQs
   - Zinc, Mg, Calcium, aluminum, and iron (ZICAM)
   - Antacids, sucralfate, didanosine, enteral feedings, calcium rich foods (OJ)
   - Will impair absorption of oral FQs and can lead to clinical failure
   - administer doses 2 hours apart - always do FQ first

Question 16

Drug interaction
Warfarin

Answer 16

Idiosyncratic - leads to increased prothrombin time and potential bleeding - ALL FQs

Question 17

Drug interaction specific to Ciprofloxacin

Answer 17

Cyclosporine and Theophylline

Ciprofloxacin inhibits both of theses drugs metabolism and leads to increased levels of these drugs in the body