fluoroquinolones Flashcards
Ciprofloxacin (CIPRO)
oral, IV, ophthalmic
Levofloxacin (LEVAQUIN)
oral, IV, ophthalmic
Moxifloxacin (AVELOX)
oral, IV
Early fluoroquinolones are largely ?? in spectrum, while subsequent generations widen to include more ??
G-
G+s, anaerobes, and some atypicals such as Mycobacterium
MOA: FQs target ??
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)
FQs selective for bacteria??
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)
?? appears to be the more important target in G-s
while in G+s ?? is more important.
Fluoroquinolones accumulate rapidly inside bacteria via ??
DNA gyrase
topoisomerase IV
porins
incorporation of ?? improves lipid solubility and bacterial accumulation, and also increases affinity for the DNA enzymes
fluorine atoms
FQ absorption: good or bad???
good to excellent
inhibited by polyvalent cations typical of antacid and supplement formulations, including calcium, magnesium, aluminum, iron and zinc
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 ??.
macrophages, neutrophils, kidney, urine, prostate, lung, stool, and bile
bone and prostatic fluid
CNS infections, CSF accumulation is unreliable
FQ half-life ??
how cleared??
which one depends on hepatic metabolism, so use with caution in hepatic failure??
3-10 hrs.
cleared by renal mechanisms (dosage adjustment in renal impairment)
Moxifloxacin
FQ uses: GU tract infections
-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)
FQ uses: diarrhea caused by
Salmonella typhi, Shigella species, and E. coli.
respiratory FQs??
effective against pneumonia-causing pathogens including ??
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)
Oral ?? is also used for Pseudomonas aeruginosa in cystic fibrosis and, despite growing resistance
ciprofloxacin
FQs are the only abx class with oral formulations that are reliably active against Pseudomonas
Among FQs ?? is the best choice for anaerobic infection.
moxifloxacin
In a trial of patients with complicated intra-abdominal infections, moxifloxacin outcomes were comparable to piperacillin-tazobactam or amoxicillin-clavulanate
FQs also used in ??
bone, joint and soft tissue infections, including chronic osteomyelitis and diabetic foot infections.
FQs can be used in atypical scenarios, including ??
multidrug treatment of TB and Mycobacterium avium in AIDS patients.
-infections caused by Francisella tularensis and Anthraces bacillus
Resistance to FQs: quick and widespread
most rapidly developing resistance results from ??
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
Resistance to FQs can also occur via ??
chromosomal point mutations in the quinolone binding site.
Cross-resistance to FQs and other agents is common: For example ??
Enterobacter spp and Kleb are often resistant to both FQs and beta-lactams
FQs used to tx MRSA??
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?
SEs that caused FQ withdrawal
highest offender??
QT prolongation, hypoglycemia, immune hemolytic anemia, hepatotoxicity, and phototoxicity
moxifloxacin
most common FQ SE
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)
about 10% of patients receiving FQs experience ??
CNS disturbances: ha, dizzy (hallucinations, delirium, seizures- rare)
epileptogenic: displacement of GABA from its receptors, can be exacerbated by theophylline and NSAIDs
FQs: 2 boxed warnings!!
- 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
FQs: safe for pregnancy??
No, pregnancy category C: associated with etabolic acidosis and hemolytic anemia in pregnancy
Up to about 2% of pts taking FQs experience ??
rash or sensitivity reactions.
-FQs also assoc. w. with peripheral neuropathy
take care when combining FQs with other drugs that cause Q-T prolongation including ??
?? can exacerbate the seizure-inducing potential of FQs
SSRIs, tricyclic antidepressants (TCAs), antipsychotics and diuretics
NSAIDs and theophylline
