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Fluoroquinolones

By

Brian J. Werth

, PharmD, University of Washington School of Pharmacy

Last full review/revision May 2020| Content last modified May 2020
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Fluoroquinolones (see table 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: Ciprofloxacin, norfloxacin, and ofloxacin

  • Newer group: Delafloxacin, gemifloxacin, levofloxacin, and moxifloxacin

Many newer fluoroquinolones have been withdrawn from the US market because of toxicity; they include trovafloxacin (because of severe hepatic toxicity), gatifloxacin (because of hypoglycemia and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.

Table
icon

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

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 (including Streptococcus pneumoniae with reduced penicillin sensitivity) and some anaerobes; 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 Enterobacteriaceae, P. aeruginosa, S. pneumoniae, and Neisseria species. Nonetheless, fluoroquinolones have many clinical uses (see table Some Clinical Uses of Fluoroquinolones).

Fluoroquinolones are no longer recommended for treatment of gonorrhea because of increasing resistance worldwide.

Table
icon

Some Clinical Uses of Fluoroquinolones

Drug

Use

Comments

Fluoroquinolones except moxifloxacin

Urinary tract infections when Escherichia coli resistance to trimethoprim/sulfamethoxazole is > 15%

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

Fluoroquinolones

Bacterial prostatitis

Usually effective

Infectious diarrhea

Effective against most bacterial causes (Campylobacter species, salmonellae, shigellae, vibrios, Yersinia enterocolitica); however, increasing resistance of Campylobacter jejuni in some regions

Not used for E. coli 0157:H7 or other enterohemorrhagic E. coli

Not effective against Clostridioides difficile (formerly Clostridium difficile)

Ofloxacin

7-day course

Newer fluoroquinolones

Other drugs preferred if patients have taken fluoroquinolones recently

Drugs of choice (or azithromycin)

Ciprofloxacin

Used empirically because it is effective against Pseudomonas aeruginosa

Usually used with another antipseudomonal drug

Long-term oral treatment of gram-negative bacillaryosteomyelitis

Because fluoroquinolones have high oral bioavailability and good bone penetration, useful for osteomyelitis

Used extensively during 2001 after bioterrorist attack in US

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, 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

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

  • Upper gastrointestinal adverse effects occur in about 5% of patients because of direct gastrointestinal irritation and central nervous system (CNS) effects.

  • CNS adverse effects (eg, mild headache, drowsiness, insomnia, dizziness, mood alteration) occur in < 5%. Nonsteroidal anti-inflammatory drugs 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 Clostridioides (formerly 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 week and is more likely to develop in women < 40 years of age. Nephrotoxicity is rare.

Dosing Considerations

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.

Ciprofloxacin raises theophylline levels, sometimes resulting in theophylline-related adverse effects.

Drugs Mentioned In This Article

Drug Name Select Trade
REGLAN
BIAXIN
CILOXAN, CIPRO
IQUIX, LEVAQUIN, QUIXIN
No US brand name
ERY-TAB, ERYTHROCIN
ZYMAR
ELIXOPHYLLIN
FACTIVE
ZITHROMAX
Delafloxacin
AVELOX
NOROXIN
PROPULSID
FLOXIN OTIC
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