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By Hans P. Schlecht, MD, MSc, Assistant Professor of Medicine, Department of Medicine, Division of Infectious Diseases & HIV Medicine, Drexel University College of Medicine ; Christopher Bruno, MD, Assistant Professor of Medicine, Division of infectious Diseases & HIV Medicine, Drexel University College of Medicine

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Fluoroquinolones (see Table: Fluoroquinolones) exhibit concentration-dependent bactericidal activity (see Effectiveness) 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: Ciprofloxacin, norfloxacin, and ofloxacin

  • Newer group: Gemifloxacin, levofloxacin, and moxifloxacin

Many newer fluoroquinolones have been withdrawn because of toxicity; they include trovafloxacin (because of severe hepatic toxicity), gatifloxacin (because of hypoglycemia and hyperglycemia), grepafloxacin (because of cardiac toxicity), temafloxacin (because of acute renal failure, hepatotoxicity, hemolytic anemia, coagulopathy, and hypoglycemia), and lomefloxacin, sparfloxacin, and enoxacin.





Oral or parenteral




Oral or parenteral


Oral or parenteral




Oral or parenteral

*Several fluoroquinolones are also available as otic and ophthalmic formulations.


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. Moxifloxacin is eliminated primarily in bile.


Fluoroquinolones are active against the following:

  • Haemophilus influenzae

  • Moraxella catarrhalis

  • Mycoplasma sp

  • Chlamydia sp

  • Chlamydophila sp

  • Legionella sp

  • Enterobacteriaceae

  • Pseudomonas aeruginosa (particularly ciprofloxacin)

  • 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; moxifloxacin in particular is active against most clinically significant obligates 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: Some Clinical Uses of Fluoroquinolones).

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

Some Clinical Uses of Fluoroquinolones




Fluoroquinolones except moxifloxacin

UTIs when Escherichia coliresistance to trimethoprim/sulfamethoxazole is > 15%

Drugs of choice; however, increasing resistance of E. coli in some communities


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 or other enterohemorrhagic E. coli

Not effective against Clostridium difficile


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 azithromycin)


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


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, metoclopramide, cisapride, erythromycin, clarithromycin, classes Ia and III antiarrhythmics, tricyclic antidepressants)

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.

  • Peripheral neuropathy may occur soon after taking the drug and may be permanent. If symptoms occur (eg, pain, burning, tingling, numbness, weakness, change in sensation), use of the fluoroquinolone should be stopped to prevent irreversible damage.
  • 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 gemifloxacin is used for > 1 wk and is more likely to develop in women < 40. Nephrotoxicity is rare.

Dosing Considerations

Dose reduction, except for moxifloxacin, is required for patients with renal insufficiency. Older fluoroquinolones are normally given twice/day; newer ones and an extended-release form of ciprofloxacin are given once/day.

Ciprofloxacin raises theophylline levels, sometimes resulting in theophylline-related adverse effects (see Treatment of Stable COPD : Theophylline).

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