I. Indications

  1. Cystic Fibrosis
  2. Complicated Urinary Tract Infection
  3. Enteric Fever
  4. Chronic Suppurative Otitis Media
  5. Multi-drug resistant Gram NegativeSepsis
  6. Multi-drug resistant Mycobacterium infection
  7. Skeletal infection caused by Gram Negatives
  8. Febrile neutropenic patients
  9. Bacterial Meningitis with resistant organisms
  10. Neisseria Meningitidis prophylaxis

II. Contraindications: Relative

  1. Not FDA approved for use under age 18 years
    1. Theoretical cartilage growth suppression
  2. Increasing use in pediatric patients
    1. Quinolones have a long track record of use in children with Cystic Fibrosis
    2. Despite cartilage effects in study young dogs, no strong evidence of similar effects in children
    3. May be considered in for specific infections (pseudomonas aeruginosa) or resistant infections (e.g. Pneumonia, Sinusitis)
    4. Transient myalgias and arthralgias may occur (however Quinolone induced Tendinopathy is rare in children)
    5. Bradley (2014) Pediatrics 134(1):e146-53 [PubMed] (or open in [QxMD Read])

III. Precautions

  1. Tendinopathy and tendon rupture risk (especially over age 60 years) is an FDA Black Box Warning
  2. Peripheral Neuropathy is a potentially long-lasting, disabling complication leading to FDA warning in 2013 (see below)

IV. Pharmacokinetics

  1. Oral dosing equivalent to intravenous
  2. Tissue penetration
    1. High tissue concentrations
      1. Stool and bile
      2. Prostate
      3. Lung
      4. White Blood Cells: Neutrophils, Macrophages
      5. Kidney and urine
    2. Low tissue concentrations (poor penetration)
      1. Poor cerebrospinal fluid penetration
  3. Excretion
    1. Renal excretion: Most Fluoroquinolones
    2. Hepatic excretion
      1. Sparfloxacin (Zagam)
      2. Moxifloxacin (Avelox)
      3. Trovafloxacin (Trovan)

V. Pathophysiology: Bacterial Resistance Mechanisms

  1. Mutations of A Subunits of DNA gyrase
  2. Alterations of outer membrane porins
    1. Affects organism permeability

VI. Mechanism

  1. Gram Negative activity
    1. Inhibits DNA gyrase resulting in dsDNA fragmentation
  2. Gram Positive activity
    1. Inhibits DNA type IV topoisomerase

VII. Mechanism: Fluoroquinolone classes

  1. First Generation Quinolones
    1. Good Gram Negative Rod efficacy
    2. Useful in Urinary Tract Infection
    3. Example: Nalidixic Acid (introduced in 1962)
  2. Second Generation Quinolones
    1. Most active on Aerobic Gram Negative Rods
    2. Some Gram Positive coverage
    3. Example: Ciprofloxacin (Cipro)
  3. Third Generation Quinolones
    1. Broad Spectrum
      1. Gram Negative Rod coverage as above
      2. Greater Gram Positive Cocci coverage
        1. Especially Pneumococcus coverage
    2. Example: Levofloxacin (Levaquin)
  4. Fourth Generation Quinolones
    1. Very Broad spectrum
      1. Gram Negative Rod coverage
      2. Gram Positive Cocci coverage
      3. Anaerobes
    2. Less resistance development
    3. Example: Trovafloxacin (Trovan)

VIII. Mechanism: Activity Spectrum

  1. Most Gram Negative Bacteria
    1. Best Fluoroquinolone Coverage
      1. Second Generation Fluoroquinolone
      2. Third Generation Fluoroquinolone
    2. Bacteria
      1. Enterobacteriaceae (Gram Negative Rods)
      2. Pseudomonas aeruginosa (especially Ciprofloxacin)
      3. HaemophilusInfluenzae
      4. Moraxella catarrhalis
  2. Gram Positive activity varies (4th generation is best)
    1. Best Fluoroquinolone coverage
      1. Moxifloxacin (strep activity 4-8 fold Levofloxacin)
      2. Trovafloxacin
      3. Levofloxacin (less active for Staph. and Strep.)
      4. Sparfloxacin (less active for Staph. and Strep.)
    2. Fluoroquinolones with minimal to no coverage
      1. First Generation Fluoroquinolones
      2. Second Generation Fluoroquinolones
    3. Bacteria
      1. Staphylococci
      2. Streptococci (Streptococcus Pneumoniae)
  3. Anaerobic Bacteria coverage
    1. Best Coverage
      1. Trovafloxacin
      2. Moxifloxacin (unlabeled use)
      3. Clinafloxacin (most potent against Anaerobes)
    2. Fluoroquinolones with no coverage
      1. First Generation Fluoroquinolones
      2. Second Generation Fluoroquinolones
  4. Atypical bacteria coverage
    1. Bacteria
      1. Legionella pneumophila
      2. Chlamydia pneumoniae
      3. Mycoplasma pneumoniae
      4. Ureaplasma
    2. Best Fluoroquinolone coverage
      1. Moxifloxacin
      2. Levofloxacin
      3. Gemifloxacin

IX. Adverse Effects

  1. Interferes with cartilage growth in animals
    1. Avoid in children under age 18 years (however see caveat under contraindications as above)
  2. Nausea
  3. Taste disturbance
  4. Diarrhea
  5. Photosensitivity
  6. Pruritus or dermatitis
  7. Glucose effects in Diabetes Mellitus
    1. May result in Hypoglycemia and Hyperglycemia
  8. Tendinopathy (black box warning)
    1. Onset at approximately day 13 of therapy
    2. Achilles Tendon Rupture increased risk (3.2 cases per 1000 patient treatment years)
    3. Higher risk patients
      1. Age over 60
      2. Concurrent Corticosteroid use
      3. Athletes
      4. Transplant recipients
    4. References
      1. (2005) Clin Infect Dis 41: 144 [PubMed] (or open in [QxMD Read])
      2. (2002) BMJ 324:1306 [PubMed] (or open in [QxMD Read])
  9. QTc Prolongation (risk of Torsades de Pointes)
    1. Grepafloxacin pulled from U.S. market in 1999
    2. Also may occur with Sparfloxacin and Moxifloxacin
  10. Peripheral Neuropathy
    1. Potentially long-lasting complication with serious Disability (led to FDA warning in 2013)
    2. http://www.fda.gov/Drugs/DrugSafety/ucm365050.htm
  11. Other neurologic effects
    1. Confusion or other mental status changes
      1. Most common in the elderly or those with decreased Renal Function
    2. Seizures (especially if concurrent NSAID use)
    3. Headache
    4. Dizziness
    5. Tremors

X. Drug Interactions

  1. Antiarrhythmics or Cisapride (risk QTc prolongation)
  2. NSAIDs (risk of Seizure)
  3. Increases level of other medications
    1. Increased Anticoagulation effect with Coumadin
    2. Increased Cyclosporine (also risks nephrotoxicity)
    3. Increased Caffeine level
    4. Increased Theophylline levels
    5. Increased Riluzole levels
  4. Chelates with cations (decreased Quinolone absorption)
    1. Avoid these agents within 2 hours of Quinolone
    2. Antacids containing Magnesium, Aluminum or Calcium
    3. Iron Sulfate
    4. Zinc
    5. Calcium
    6. Didanosine
    7. Sucralfate
  5. Decreases Norfloxacin activity
    1. Chloramphenicol
    2. Nitrofurantoin
    3. Rifampin
    4. Tetracycline

Images: Related links to external sites (from Google)

Ontology: Quinolones (C0034428)

Definition (MSH) A group of derivatives of naphthyridine carboxylic acid, quinoline carboxylic acid, or NALIDIXIC ACID.
Concepts Organic Chemical (T109)
MSH D015363
English Ketoquinolines, Oxoquinolines, Quinolinones, quinolones, Quinolones [Chemical/Ingredient], quinolone, quinolinone, Quinolones
Swedish Kinoloner
Czech chinolinony, chinolony, sparfloxacin
Finnish Kinolonit
Russian KHINOLINONY, KHINOLONY, KETOKHINOLINONY, OKSOKHINOLINONY, КЕТОХИНОЛИНОНЫ, ОКСОХИНОЛИНОНЫ, ХИНОЛИНОНЫ, ХИНОЛОНЫ
Japanese オキソキノリン, キノリノン, キノロン, ケトキノリン
Italian Chetochinoline, Chinolinoni, Ossochinoline, Chinoloni
Croatian KINOLONI
Polish Chinolonu pochodne, Chinolinony
French Quinolinone, Quinolone
German Chinolinone, Chinolone, Ketochinoline, Oxochinoline
Portuguese Cetoquinolinas, Oxoquinolinas, Quinolinonas, Quinolonas
Spanish Cetoquinolinas, Oxoquinolinas, Quinolinonas, Quinolonas

Ontology: Fluoroquinolones (C0949665)

Definition (MSH) A group of QUINOLONES with at least one fluorine atom and a piperazinyl group.
Concepts Organic Chemical (T109) , Pharmacologic Substance(T121)
MSH D024841
Swedish Fluorokinoloner
Czech fluorochinolony
Finnish Fluorokinolonit
Russian FTORKHINOLONY, FLUOROKHINOLONY, ФЛУОРОХИНОЛОНЫ, ФТОРХИНОЛОНЫ
Croatian Not Translated[Fluoroquinolones]
English Fluoroquinolones [Chemical/Ingredient], fluoroquinolones, fluoroquinolone, Fluoroquinolones
Polish Fluorochinolonu pochodne
French Fluoroquinolones
German Fluorchinolone
Italian Fluorochinoloni
Portuguese Fluoroquinolonas
Spanish Fluoroquinolonas