Fluoroquinolones (see Table 10: Bacteria and Antibacterial Drugs: Fluoroquinolones) exhibit concentration-dependent bactericidal activity by inhibiting the activity of DNA gyrase and topoisomerase, enzymes essential for bacterial DNA replication. Fluoroquinolones are divided into 2 groups, based on antimicrobial spectrum and pharmacology:

• Older group: CiprofloxacinSome Trade Names
  CILOXAN
  CIPRO
  Click for Drug Monograph
  , norfloxacinSome Trade Names
  NOROXIN
  Click for Drug Monograph
  , and ofloxacinSome Trade Names
  FLOXIN
  Click for Drug Monograph
  
• Newer group: GemifloxacinSome Trade Names
  FACTIVE
  Click for Drug Monograph
  , levofloxacinSome Trade Names
  IQUIX
  LEVAQUIN
  QUIXIN
  Click for Drug Monograph
  , and moxifloxacinSome Trade Names
  AVELOX
  Click for Drug Monograph
  

Some newer fluoroquinolones have been withdrawn because of toxicity; they include trovafloxacin (because of severe hepatic toxicity) and gatifloxacinSome Trade Names
ZYMAR
Click for Drug Monograph
(because of hypoglycemia and hyperglycemia).

Table 10
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Fluoroquinolones Drug Route* CiprofloxacinSome Trade Names CILOXAN CIPRO Click for Drug Monograph Oral or parenteral GemifloxacinSome Trade Names FACTIVE Click for Drug Monograph Oral LevofloxacinSome Trade Names IQUIX LEVAQUIN QUIXIN Click for Drug Monograph Oral or parenteral MoxifloxacinSome Trade Names AVELOX Click for Drug Monograph Oral or parenteral NorfloxacinSome Trade Names NOROXIN Click for Drug Monograph Oral OfloxacinSome Trade Names FLOXIN Click for Drug Monograph Oral or parenteral *Several fluoroquinolones are also available as otic and ophthalmic formulations.

Pharmacology

Oral absorption is diminished by coadministration of cations (aluminum, Mg, Ca, zinc, and iron preparations). After oral and parenteral administration, fluoroquinolones are widely distributed in most extracellular and intracellular fluids and are concentrated in the prostate, lungs, and bile.

Most fluoroquinolones are metabolized in the liver and excreted in urine, reaching high levels in urine. MoxifloxacinSome Trade Names
AVELOX
Click for Drug Monograph
is eliminated primarily in bile.

Indications

Fluoroquinolones are active against the following:

• Neisseria sp
• Haemophilus influenzae
• Moraxella catarrhalis
• Mycoplasma sp
• Chlamydia sp
• Chlamydophila sp
• Legionella sp
• Enterobacteriaceae
• Pseudomonas aeruginosa (particularly ciprofloxacinSome Trade Names
  CILOXAN
  CIPRO
  Click for Drug Monograph
  )
• Mycobacterium tuberculosis
• Some atypical mycobacteria
• Methicillin-sensitive staphylococci

Nosocomial methicillin-resistant staphylococci are usually resistant. Older fluoroquinolones have poor activity against streptococci and anaerobes. Newer fluoroquinolones have reliable activity against streptococci (including Streptococcus pneumoniae with reduced penicillin sensitivity) and some anaerobes. As use has increased, resistance, particularly to older fluoroquinolones, is developing among Enterobacteriaceae, P. aeruginosa, S. pneumoniae, and Neisseria sp. Nonetheless, fluoroquinolones have many clinical uses (see Table 11: Bacteria and Antibacterial Drugs: Some Clinical Uses of Fluoroquinolones).

Table 11
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Some Clinical Uses of Fluoroquinolones Drug Use Comments Fluoroquinolones except moxifloxacinSome Trade Names AVELOX Click for Drug Monograph UTIs when Escherichia coli resistance to trimethoprim/sulfamethoxazoleSome Trade Names BACTRIM SEPTRA Click for Drug Monograph is > 15% Drugs of choice; however, increasing resistance of E. coli in some communities Fluoroquinolones Bacterial prostatitis — Salmonella bacteremia — Typhoid fever Usually effective Infectious diarrhea Effective against most bacterial causes (Campylobacter sp, salmonellae, shigellae, vibrios, Yersinia enterocolitica); however, increasing resistance of C. jejuni in some regions Not used for E. coli 0157:H7 Not effective against Clostridium difficile OfloxacinSome Trade Names FLOXIN Click for Drug Monograph Chancroid 3-day course Chlamydia trachomatis infections 7-day course Newer fluoroquinolones Community-acquired pneumonia Other drugs preferred if patients have taken fluoroquinolones recently Legionella pneumonia Drugs of choice (or azithromycinSome Trade Names ZITHROMAX Click for Drug Monograph ) CiprofloxacinSome Trade Names CILOXAN CIPRO Click for Drug Monograph Hospital-acquired pneumonia Used empirically because it is effective against Pseudomonas aeruginosa Usually used with another antipseudomonal drug Long-term oral treatment of gram-negative bacillary or Staphylococcus aureus osteomyelitis — Meningococcal prophylaxis — Anthrax prophylaxis Used extensively during 2001 after bioterrorist attack in US Some Clinical Uses of Fluoroquinolones Drug Use Comments Fluoroquinolones except moxifloxacinSome Trade Names AVELOX Click for Drug Monograph UTIs when Escherichia coli resistance to trimethoprim/sulfamethoxazoleSome Trade Names BACTRIM SEPTRA Click for Drug Monograph is > 15% Drugs of choice; however, increasing resistance of E. coli in some communities Fluoroquinolones Bacterial prostatitis — Salmonella bacteremia — Typhoid fever Usually effective Infectious diarrhea Effective against most bacterial causes (Campylobacter sp, salmonellae, shigellae, vibrios, Yersinia enterocolitica); however, increasing resistance of C. jejuni in some regions Not used for E. coli 0157:H7 Not effective against Clostridium difficile OfloxacinSome Trade Names FLOXIN Click for Drug Monograph Chancroid 3-day course Chlamydia trachomatis infections 7-day course Newer fluoroquinolones Community-acquired pneumonia Other drugs preferred if patients have taken fluoroquinolones recently Legionella pneumonia Drugs of choice (or azithromycinSome Trade Names ZITHROMAX Click for Drug Monograph ) CiprofloxacinSome Trade Names CILOXAN CIPRO Click for Drug Monograph Hospital-acquired pneumonia Used empirically because it is effective against Pseudomonas aeruginosa Usually used with another antipseudomonal drug Long-term oral treatment of gram-negative bacillary or Staphylococcus aureus osteomyelitis — Meningococcal prophylaxis — Anthrax prophylaxis Used extensively during 2001 after bioterrorist attack in US

Fluoroquinolones are no longer recommended for treatment of gonorrhea in the US because of increasing resistance.

Contraindications

Contraindications include

• Previous allergic reaction to the drugs
• Certain disorders that predispose to arrhythmias (eg, QT-interval prolongation, uncorrected hypokalemia or hypomagnesemia, significant bradycardia)
• Use of drugs known to prolong the QT interval or to cause bradycardia (eg, metoclopramideSome Trade Names
  REGLAN
  Click for Drug Monograph
  , cisaprideSome Trade Names
  PROPULSID
  Click for Drug Monograph
  , erythromycinSome Trade Names
  ERY-TAB
  ERYTHROCIN
  Click for Drug Monograph
  , clarithromycinSome Trade Names
  BIAXIN
  Click for Drug Monograph
  , classes Ia and III antiarrhythmics, tricyclic antidepressants)

Clinical Calculator

Fluoroquinolones have traditionally been considered to be contraindicated in children because they may cause cartilage lesions if growth plates are open. However, some experts, who challenge this view because evidence is weak, have recommended prescribing fluoroquinolones as a 2nd-line antibiotic and restricting use to a few specific situations, including P. aeruginosa infections in patients with cystic fibrosis, prophylaxis and treatment of bacterial infections in immunocompromised patients, life-threatening multiresistant bacterial infections in neonates and infants, and Salmonella or Shigella GI tract infections.

Use During Pregnancy and Breastfeeding

Fluoroquinolones are in pregnancy category C (animal studies show some risk, evidence in human and animal studies is inadequate, but clinical benefit sometimes exceeds risk).

Fluoroquinolones enter breast milk. Use during breastfeeding is not recommended.

Adverse Effects

Serious adverse effects are uncommon; main concerns include the following:

• Upper GI adverse effects occur in about 5% of patients because of direct GI irritation and CNS effects.
• CNS adverse effects (eg, mild headache, drowsiness, insomnia, dizziness, mood alteration) occur in < 5%. NSAIDs may enhance the CNS stimulatory effects of fluoroquinolones. Seizures are rare, but fluoroquinolones should not be used in patients with CNS disorders.
• Tendinopathy, including rupture of the Achilles tendon, may occur even after short-term use of fluoroquinolones.
• QT-interval prolongation can occur, potentially leading to ventricular arrhythmias and sudden cardiac death.
• Fluoroquinolone use has been strongly associated with Clostridium difficile–associated diarrhea (pseudomembranous colitis), especially that due to the hypervirulent C. difficile ribotype 027.

Diarrhea, leukopenia, anemia, and photosensitivity are uncommon. Rash is uncommon unless gemifloxacinSome Trade Names
FACTIVE
Click for Drug Monograph
is used for > 1 wk and is more likely to develop in women < 40. Nephrotoxicity is rare.

Dosing Considerations

Dose reduction, except for moxifloxacinSome Trade Names
AVELOX
Click for Drug Monograph
, is required for patients with renal insufficiency. Older fluoroquinolones are normally given twice/day; newer ones and an extended-release form of ciprofloxacinSome Trade Names
CILOXAN
CIPRO
Click for Drug Monograph
are given once/day.

CiprofloxacinSome Trade Names
CILOXAN
CIPRO
Click for Drug Monograph
raises theophyllineSome Trade Names
ELIXOPHYLLIN
THEO-DUR
Click for Drug Monograph
levels, sometimes resulting in theophyllineSome Trade Names
ELIXOPHYLLIN
THEO-DUR
Click for Drug Monograph
-related adverse effects.

Last full review/revision July 2009 by Matthew E. Levison, MD

Content last modified April 2012