Fluoroquinolones (see Table 10: 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:
Some newer fluoroquinolones have been withdrawn because of toxicity; they include trovafloxacin (because of severe hepatic toxicity) and gatifloxacinSome Trade Names ZYMAR Click for Drug Monograph (because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).
*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:
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: Some Clinical Uses of Fluoroquinolones).
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
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
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.
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) exhibit concentration-dependent bactericidal activity by inhibiting the activity of DNA gyrase and topoisomerase, enzymes essential for bacterial DNA replication. 
