fluoroquinolones

Question 1

Ciprofloxacin (CIPRO)

Answer 1

oral, IV, ophthalmic

Question 2

Levofloxacin (LEVAQUIN)

Answer 2

oral, IV, ophthalmic

Question 3

Moxifloxacin (AVELOX)

Answer 3

oral, IV

Question 4

Early fluoroquinolones are largely ?? in spectrum, while subsequent generations widen to include more ??

Answer 4

G-

G+s, anaerobes, and some atypicals such as Mycobacterium

Question 5

MOA: FQs target ??

Answer 5

two DNA synthesis enzymes: DNA gyrase and DNA topoisomerase IV
-fix supercoiling that results from the unwinding of helical strands necessary for replication (so this is inhibited in bacteria)

Question 6

FQs selective for bacteria??

Answer 6

Eukaryotes lack DNA gyrase, but do possess a topoisomerase II that is vaguely similar to bacterial topoisomerase IV (only affected by extremely high FQ concentrations)

Question 7

?? appears to be the more important target in G-s

while in G+s ?? is more important.

Fluoroquinolones accumulate rapidly inside bacteria via ??

Answer 7

DNA gyrase

topoisomerase IV

porins

Question 8

incorporation of ?? improves lipid solubility and bacterial accumulation, and also increases affinity for the DNA enzymes

Answer 8

fluorine atoms

Question 9

FQ absorption: good or bad???

Answer 9

good to excellent
inhibited by polyvalent cations typical of antacid and supplement formulations, including calcium, magnesium, aluminum, iron and zinc

Question 10

Fluoroquinolones distribute widely and penetrate many tissues and fluids. They exceed serum concentration in ??. Penetration to ?? is lower but still effective.
not regularly used for ?? in part because ??.

Answer 10

macrophages, neutrophils, kidney, urine, prostate, lung, stool, and bile

bone and prostatic fluid

CNS infections, CSF accumulation is unreliable

Question 11

FQ half-life ??
how cleared??

which one depends on hepatic metabolism, so use with caution in hepatic failure??

Answer 11

3-10 hrs.
cleared by renal mechanisms (dosage adjustment in renal impairment)

Moxifloxacin

Question 12

FQ uses: GU tract infections

Answer 12

-UTIs and bacterial prostatitis; E. coli is the most common pathogen in both
-Chlamydial trachomatis and chancroid resulting from Haemophilus ducreyi.
NOT used:
-Treponema pallidum however is unaffected
-N. gonorrhoeae is v. commonly resistant (use ceftriaxone)

Question 13

FQ uses: diarrhea caused by

Answer 13

Salmonella typhi, Shigella species, and E. coli.

Question 14

respiratory FQs??

effective against pneumonia-causing pathogens including ??

Answer 14

levofloxacin, moxifloxacin, and gemifloxacin
G+: S. pneumo, S. aureus
atypicals: Mycoplasma pneumoniae and Legionella pneumophila
(prominent but not necessarily first-line role in tx CAP in adults, less in HCAP, and in kiddos)

Question 15

Oral ?? is also used for Pseudomonas aeruginosa in cystic fibrosis and, despite growing resistance

Answer 15

ciprofloxacin

FQs are the only abx class with oral formulations that are reliably active against Pseudomonas

Question 16

Among FQs ?? is the best choice for anaerobic infection.

Answer 16

moxifloxacin

In a trial of patients with complicated intra-abdominal infections, moxifloxacin outcomes were comparable to piperacillin-tazobactam or amoxicillin-clavulanate

Question 17

FQs also used in ??

Answer 17

bone, joint and soft tissue infections, including chronic osteomyelitis and diabetic foot infections.

Question 18

FQs can be used in atypical scenarios, including ??

Answer 18

multidrug treatment of TB and Mycobacterium avium in AIDS patients.
-infections caused by Francisella tularensis and Anthraces bacillus

Question 19

Resistance to FQs: quick and widespread

most rapidly developing resistance results from ??

Answer 19

plasmid factors:

• Quinolone resistance (Qnr) proteins that protect bacterial DNA gyrase
• production of an aminoglycoside acetyltransferase that can also modify ciprofloxacin, yielding cross-resistance
• efflux pumps

Question 20

Resistance to FQs can also occur via ??

Answer 20

chromosomal point mutations in the quinolone binding site.

Question 21

Cross-resistance to FQs and other agents is common: For example ??

Answer 21

Enterobacter spp and Kleb are often resistant to both FQs and beta-lactams

Question 22

FQs used to tx MRSA??

Answer 22

NO!
resistance in MRSA is widespread, and even in isolates that are initially FQ-sensitive, resistance is very likely to emerge during the course of tx
FQ resistance is also a concern in Pseudomonas?

Question 23

SEs that caused FQ withdrawal

highest offender??

Answer 23

QT prolongation, hypoglycemia, immune hemolytic anemia, hepatotoxicity, and phototoxicity

moxifloxacin

Question 24

most common FQ SE

Answer 24

GI disturbance, upwards of 20% of patients experiencing N/V/D
usually mild, one of the most common causes of C. diff colitis (selection for v. toxic strain)

Question 25

about 10% of patients receiving FQs experience ??

Answer 25

CNS disturbances: ha, dizzy (hallucinations, delirium, seizures- rare)

epileptogenic: displacement of GABA from its receptors, can be exacerbated by theophylline and NSAIDs

Question 26

FQs: 2 boxed warnings!!

Answer 26

• Achilles tendon rupture, especially in the elderly, in patients receiving corticosteroids, and those with organ transplants (can be used in kids, but typ. avoided)
• NM blocking and exacerbation of myasthenia gravis

Question 27

FQs: safe for pregnancy??

Answer 27

No, pregnancy category C: associated with etabolic acidosis and hemolytic anemia in pregnancy

Question 28

Up to about 2% of pts taking FQs experience ??

Answer 28

rash or sensitivity reactions.

-FQs also assoc. w. with peripheral neuropathy

Question 29

take care when combining FQs with other drugs that cause Q-T prolongation including ??

?? can exacerbate the seizure-inducing potential of FQs

Answer 29

SSRIs, tricyclic antidepressants (TCAs), antipsychotics and diuretics

NSAIDs and theophylline