Fluoroquinolones Flashcards
Fluoroquinolones
Ciprofloxacin
Levofloxacin
Moxifloxacin
Gemifloxacin
Near ideal antibiotics from spectrum and PK standpoint
Broad spectrum; Gram+ and -, atypicals
Excellent oral bioavailability
Distribute widely into tissues
Overuse has led to resistance in some geographical regions and patient populations (enteric Gram- such as E. coli and Klebsiella)
No longer recommended 1st line in US for uncomplicated UTIs
Newer drugs gain increasing Gram+ (mostly pneumococcal) activity at expense of Gram- (mostly Pseudomonas) activity
Fluoroquinolones MOA
Inhibit DNA topoisomerases (enzymes involved in winding and unwinding DNA) which can lead to breaks in the DNA and death of the cell
Ciprofloxacin Spectrum
Good Enteric GNRs (E. coli, Proteus, Klebsiella, etc), H. influenzae
Moderate
Pseudomonas
Atypicals (Mycoplasma, Chlamydia, Legionella)
Poor Staph S. pneumoniae Anaerboes Enterococci
Other FQ Spectrum
Good Enteric Gram- S. pneumoniae Atypicals H. influenzae
Moderate
Pseudomonas (Levofloxacin)
MSSA
Poor
anaerobes (except Moxifloxacin which is moderate)
Enterococci
Fluoroquinolones Adverse Effects
Nervous system
Can cause CNS adverse effects (dizziness, confusion, hallucinations); elderly particularly susceptible
Younger patients may develop insomnia
Peripheral neuropathy can occur
Cardiovascular
Prolongation of QT interval possible; arrhythmias more likely in patients with other risk factors (underlying arrhythmia, on proarrhythmic drug, excessive dose)
Musculoskeletal
Arthralgias (uncommon)
Achilles’ tendon rupture (very rare)
Tendon rupture more common in elderly, renal dysfunction, also taking corticosteroids)
Tendonitis usually precedes rupture
Exacerbations of myasthenia gravis (less common)
Dermatologic Photosensitivity (avoid sun or use sunscreen)
Developmental
Contraindicated in pregnant women and relatively contraindicated in children due to toxicities in juvenile beagle dogs (there is some experience in children and may be used)
Fluoroquinolones Important Facts
MICs for Pseudomonas higher than for other susceptible organisms
Must use higher antipseudomonal doses
Ciprofloxacin: 400mg IV q8h; 750 PO q12h
Levofloxacin: 750mg IV/PO daily
Bioavailability is 80-100% so oral dose = IV dose (except Ciprofloxacin: PO ~ 1.25x IV)
Chelate cations; oral bioavailability significantly decreased when given with calcium, iron, antacids, milk, or multivitamins
Separate by at least 2 hours or take a week off
Oral administration with tube feedings is problematic
Cleared renally and require dose reduction in dysfunction (except Moxifloxacin- is not excreted into the urine and should not be used for UTIs)
Gemifloxacin has dual elimination- uncertain if effective for UTIs; does require dose adjustment in renal failure; best to avoid for UTIs until there is more evidence
FDA boxed warning for possibility of tendon rupture
In 2016, FDA added warning that risks outweigh benefits for more cases of sinusitis, bronchitis, and uncomplicated UTIs unless other options are not available due to possibility of rare but serious adverse effects
Ciprofloxacin Indications
CAP, sinusitis, AECB: - UTI: + Intra-abdominal infection: + Systemic Gram- infections: + Skin/soft tissue infection: - Pseudomonas (+/- beta lactam): + Treatment/prophylaxis in bioterrorism scenario (active vs anthrax, plague, tularemia): +
Levofloxacin Indications
CAP, sinusitis, AECB: + UTI: + Intra-abdominal infection: + Systemic Gram- infections: + Skin/soft tissue infection: + Pseudomonas (+/- beta lactam): + Treatment/prophylaxis in bioterrorism scenario (active vs anthrax, plague, tularemia): +
Moxifloxacin Indications
CAP, sinusitis, AECB: + UTI: - Intra-abdominal infection: + Systemic Gram- infections: + Skin/soft tissue infection: + Pseudomonas (+/- beta lactam): - Treatment/prophylaxis in bioterrorism scenario (active vs anthrax, plague, tularemia): ?
Gemifloxacin Indications
CAP, sinusitis, AECB: + UTI: ? Intra-abdominal infection: ? Systemic Gram- infections: ? Skin/soft tissue infection: + Pseudomonas (+/- beta lactam): - Treatment/prophylaxis in bioterrorism scenario (active vs anthrax, plague, tularemia): ?
