Pharm
Fluoroquinolone
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Fluoroquinolone
, Quinolone, Nalidixic Acid, Delafloxacin, Baxdela
Indications
Cystic Fibrosis
Complicated
Urinary Tract Infection
Enteric Fever
Chronic Suppurative Otitis Media
Multi-drug resistant
Gram Negative
Sepsis
Multi-drug resistant
Mycobacterium
infection
Skeletal infection caused by
Gram Negative
s
Febrile neutropenic patients
Bacterial Meningitis
with resistant organisms
Neisseria Meningitidis
prophylaxis
Otitis Media
with patent
Tympanostomy Tube
s (drops)
Bacterial Conjunctivitis
(drops)
Otitis Externa
(drops)
Contraindications
Relative
Not FDA approved for use under age 18 years
Theoretical cartilage growth suppression
Increasing use in pediatric patients
Quinolones have a long track record of use in children with
Cystic Fibrosis
Despite cartilage effects in study young dogs, no strong evidence of similar effects in children
Consider for specific infections (
Pseudomonas
aeruginosa) or resistant infections (e.g.
Pneumonia
,
Sinusitis
)
Transient myalgias and
Arthralgia
s may occur (however Quinolone induced
Tendinopathy
is rare in children)
Bradley (2014) Pediatrics 134(1):e146-53 [PubMed]
Precautions
FDA Warnings
See adverse effects below
Informed Consent
regarding risk is recommended
Avoid high impact while taking Fluoroquinolones
Onset typically within first 1-2 weeks of exposure, but may be delayed up to 90 days
Tendinopathy
and tendon rupture risk (FDA Black Box Warning)
Highest risk in age >60 years, males,
Chronic Kidney Disease
, and especially
Corticosteroid
use (RR:46)
Peripheral Neuropathy
(FDA warning in 2013)
Potentially long-lasting, disabling complication
Aortic Complications (FDA warning in 2019)
Increased risk of
Aortic Dissection
, aortic aneurysm and
Aortic Rupture
Pharmacokinetics
Oral dosing equivalent to intravenous
Tissue penetration
High tissue concentrations
Stool
and bile
Prostate
Lung
White Blood Cell
s:
Neutrophil
s,
Macrophage
s
Kidney
and urine
Low tissue concentrations (poor penetration)
Poor cerebrospinal fluid penetration
Excretion
Renal excretion: Most Fluoroquinolones
Hepatic excretion
Sparfloxacin
(
Zagam
)
Moxifloxacin
(
Avelox
)
Trovafloxacin
(
Trovan
)
Pathophysiology
Bacteria
l Resistance Mechanisms
Mutations of A Subunits of DNA gyrase
Alterations of outer membrane porins
Affects organism permeability
Mechanism
Gram Negative
activity
Inhibits DNA gyrase resulting in dsDNA fragmentation
Gram Positive
activity
Inhibits DNA type IV topoisomerase
Mechanism
Fluoroquinolone classes
First
Gene
ration Quinolones
Good
Gram Negative Rod
efficacy
Useful in
Urinary Tract Infection
Example: Nalidixic Acid (introduced in 1962)
Second Generation Quinolone
s
Most active on
Aerobic Gram Negative Rod
s
Some
Gram Positive
coverage
Example:
Ciprofloxacin
(Cipro)
Third Generation Quinolone
s
Broad Spectrum
Gram Negative Rod
coverage as above
Greater
Gram Positive Cocci
coverage
Especially Pneumococcus coverage
Example:
Levofloxacin
(
Levaquin
)
Fourth Generation Quinolone
s
Very Broad spectrum
Gram Negative Rod
coverage
Gram Positive Cocci
coverage
Anaerobe
s
Less resistance development
Examples:
Trovafloxacin
(
Trovan
), Delafloxacin (Baxdela)
Other Quinolones
Delafloxacin (Baxdela)
Broad spectrum antibiotic FDA approved in 2017 for acute
Bacteria
l
Skin Infection
s
Increased
Gram Positive
coverage (including
MRSA
) over other Quinolones
However, should be reserved for resistant infections refractory to other agents
(2017) Presc Lett 24(11): 66
Mechanism
Activity Spectrum
Most
Gram Negative Bacteria
Best Fluoroquinolone Coverage
Second Generation Fluoroquinolone
Third Generation Fluoroquinolone
Bacteria
Enterobacteriaceae
(
Gram Negative Rod
s)
Pseudomonas
aeruginosa (especially
Ciprofloxacin
)
Haemophilus
Influenza
e
Moraxella catarrhalis
Gram Positive
activity varies (4th generation is best)
Best Fluoroquinolone coverage
Moxifloxacin
(strep activity 4-8 fold
Levofloxacin
)
Trovafloxacin
Levofloxacin
(less active for Staph. and Strep.)
Sparfloxacin
(less active for Staph. and Strep.)
Fluoroquinolones with minimal to no coverage
First
Gene
ration Fluoroquinolones
Second Generation Fluoroquinolone
s
Bacteria
Staphylococci
Streptococci (
Streptococcus Pneumoniae
)
Anaerobic Bacteria
coverage
Best Coverage
Trovafloxacin
Moxifloxacin
(unlabeled use)
Clinafloxacin (most potent against
Anaerobe
s)
Fluoroquinolones with no coverage
First
Gene
ration Fluoroquinolones
Second Generation Fluoroquinolone
s
Atypical
Bacteria
coverage
Bacteria
Legionella pneumophila
Chlamydia pneumoniae
Mycoplasma pneumoniae
Ureaplasma
Best Fluoroquinolone coverage
Moxifloxacin
Levofloxacin
Gemifloxacin
Adverse Effects
Interferes with cartilage growth in animals
Avoid in children under age 18 years (however see caveat under contraindications as above)
Nausea
Taste disturbance
Diarrhea
Photosensitivity
Pruritus
or dermatitis
Clostridium difficile
(esp.
Moxifloxacin
)
Retinal Detachment
Glucose
effects in
Diabetes Mellitus
May result in
Hypoglycemia
(esp. with sulonylurea) and
Hyperglycemia
Kabbara (2015) Ther Clin Risk Manag 11: 639–647 [PubMed]
Increased
Hypoglycemia
risk in elderly,
Renal Insufficiency
, especially if on
Insulin
or
Sulfonylurea
https://www.fda.gov/downloads/Drugs/DrugSafety/UCM612834.pdf
Aortic Complications (FDA warning in 2019)
Increased risk of
Aortic Dissection
, aortic aneurysm and
Aortic Rupture
(1 in 11,000)
May occur with short Quinolone course, but risk increases with duration, and risk may persist for months
Highest risk (1 in 300) in patients already at risk for aortic complications (Quinolones may double risk)
Elderly
History of aortic aneurysm
Tobacco Abuse
Vascular disease or risk factors (e.g.
Hypertension
)
Marfan Syndrome
Ehlers-Danlos Syndrome
References
(2019) Presc Lett 26(2): 7
FDA alert
https://www.fda.gov/Drugs/DrugSafety/ucm628753.htm
Tendinopathy
(black box warning)
Tendinopathy
risk with Fluoroquinolones is 4 fold higher than other antibiotics
Informed Consent
regarding risk (and avoiding high impact activities) is recommended
Onset typically within first 1-2 weeks of exposure, but may be delayed up to 90 days
Achilles Tendon Rupture
increased risk (3.2 cases per 1000 patient treatment years)
Higher risk patients
Age over 60 years
Chronic Kidney Disease
Concurrent
Corticosteroid
use (RR 46)
Athletes
Transplant recipients
References
Delaney in Herbert (2015) EM:Rap 15(9):11-2
(2005) Clin Infect Dis 41: 144 [PubMed]
(2002) BMJ 324:1306 [PubMed]
QTc Prolongation
(risk of
Torsades de Pointes
)
Grepafloxacin pulled from U.S. market in 1999
Also may occur with
Sparfloxacin
and
Moxifloxacin
Peripheral Neuropathy
Potentially long-lasting complication with serious
Disability
(led to FDA warning in 2013)
http://www.fda.gov/Drugs/DrugSafety/ucm365050.htm
Other neurologic effects (3% of patients)
Confusion,
Delirium
, impaired memory or other mental status changes
Most common in the elderly or those with decreased
Renal Function
Seizure
s (especially if concurrent
NSAID
use)
Myasthenia Gravis
exacerbation
Insomnia
Hallucination
s
Headache
Dizziness
Tremor
s
Drug Interactions
Antiarrhythmic
s or Cisapride (risk
QTc Prolongation
)
NSAID
s (risk of
Seizure
)
Increases level of other medications
Increased
Anticoagulation
effect with
Coumadin
Increased
Cyclosporine
(also risks nephrotoxicity)
Increased
Caffeine
level
Increased
Theophylline
levels
Increased Riluzole levels
Sulfonylurea
associated-
Hypoglycemia
Chelates with cations (decreased Quinolone absorption)
Avoid these agents within 2 hours of Quinolone
Antacid
s containing
Magnesium
, Aluminum or
Calcium
Iron Sulfate
Zinc
Calcium
Didanosine
Sucralfate
Decreases
Norfloxacin
activity
Chloramphenicol
Nitrofurantoin
Rifampin
Tetracycline
References
Mandell (2000) Infectious Disease, Churchill, p. 576
King (2000) Am Fam Physician 61(9):2741-8 [PubMed]
O'Donnell (2000) Infect Dis Clin North Am 14(2):489-513 [PubMed]
Oliphant (2002) Am Fam Physician 65(3):455-64 [PubMed]
Owens (2000) Med Clin North Am 84(6):1447-69 [PubMed]
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