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Fluoroquinolones

By

Brian J. Werth

, PharmD, University of Washington School of Pharmacy

Last full review/revision May 2022| Content last modified May 2022
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Fluoroquinolones exhibit concentration-dependent bactericidal activity Time vs concentration of a single dose of a theoretical antibiotic Time vs concentration of a single dose of a theoretical antibiotic 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: Delafloxacin, gemifloxacin, levofloxacin, and moxifloxacin

Many newer fluoroquinolones have been withdrawn from the US market because of toxicity when given systemically; they include trovafloxacin (because of severe hepatic toxicity), gatifloxacin (because of hypoglycemia and hyperglycemia; it is still available in the US as an ophthalmic preparation), grepafloxacin (because of cardiac toxicity), temafloxacin (because of acute renal failure, hepatotoxicity, hemolytic anemia, coagulopathy, and hypoglycemia), and lomefloxacin, sparfloxacin, and enoxacin.

Table

Fluoroquinolones

Drug

Route*

Ciprofloxacin

Oral or parenteral

Delafloxacin

Oral or parenteral

Gemifloxacin

Oral

Levofloxacin

Oral or parenteral

Moxifloxacin

Oral or parenteral

Norfloxacin

Oral

Ofloxacin

Oral or parenteral

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

Pharmacokinetics

Oral absorption is diminished by coadministration of polyvalent cations (aluminum, magnesium, calcium, 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.

Indications for Fluoroquinolones

Fluoroquinolones are active against the following:

Nosocomial methicillin-resistant staphylococci (MRSA) are usually resistant. Older fluoroquinolones have poor activity against streptococci and anaerobes. Newer fluoroquinolones have reliable activity against streptococci Streptococcal Infections Streptococci are gram-positive aerobic organisms that cause many disorders, including pharyngitis, pneumonia, wound and skin infections, sepsis, and endocarditis. Symptoms vary with the organ... read more Streptococcal Infections (including Streptococcus pneumoniae with reduced penicillin sensitivity) and some anaerobes Overview of Anaerobic Bacteria Bacteria can be classified by their need and tolerance for oxygen: Facultative: Grow aerobically or anaerobically in the presence or absence of oxygen Microaerophilic: Require a low oxygen concentration... read more ; moxifloxacin in particular is active against most clinically significant obligate anaerobes.

Delafloxacin, the most recently approved fluoroquinolone, is the most broad-spectrum fluoroquinolone with activity against

As fluoroquinolone use has increased, resistance, particularly to older fluoroquinolones, is developing among Enterobacterales, P. aeruginosa, S. pneumoniae, and Neisseria species. Nonetheless, fluoroquinolones have many clinical uses (see table Some Clinical Uses of Fluoroquinolones Some Clinical Uses of Fluoroquinolones Some Clinical Uses of Fluoroquinolones ).

Fluoroquinolones are no longer recommended for empiric treatment of gonorrhea because of increasing resistance worldwide. However, a single dose of ciprofloxacin is highly effective in treating gonococcal infections caused by strains of N. gonorrhoeae that are susceptible to the drug.

Table

Contraindications to Fluoroquinolones

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)

Delafloxacin does not appear to cause significant prolongation of the QT interval.

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 gastrointestinal tract infections.

Use During Pregnancy and Breastfeeding

Animal reproduction studies with fluoroquinolones show some risk. Data related to pregnancy in humans are limited. Fluoroquinolones should be used in pregnancy only if clinical benefit exceeds risk and a safer alternative is not available.

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

Adverse Effects of Fluoroquinolones

Fluoroquinolones have black box warnings because they have been associated with disabling and potentially irreversible serious adverse reactions that have occurred together including

  • Tendinopathy, including rupture of the Achilles tendon, may occur even after short-term use of fluoroquinolones.

  • Peripheral neuropathy may occur soon after taking the drug and may be permanent. If symptoms (eg, pain, burning, tingling, numbness, weakness, change in sensation) occur, use of the fluoroquinolone should be stopped to prevent irreversible damage.

  • Central nervous system (CNS) adverse effects include seizures, increased intracranial pressure (including pseudotumor cerebri), and toxic psychosis. Other CNS adverse effects include nervousness, anxiety, agitation, insomnia, nightmares, dizziness, mood alteration, paranoia, confusion, tremors, hallucinations, and depression. Seizures are rare, but fluoroquinolones should not be used in patients with CNS disorders.

  • Muscle weakness may be exacerbated in patients with myasthenia gravis, so fluoroquinolones should be avoided in these patients.

Other adverse effects include

Diarrhea, leukopenia, anemia, and photosensitivity are uncommon. Rash is uncommon unless gemifloxacin is used for > 1 week and is more likely to develop in women < 40 years of age. Nephrotoxicity is rare.

Dosing Considerations for Fluoroquinolones

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

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