Fluoroquinolones (see table Fluoroquinolones Fluoroquinolones ) exhibit concentration-dependent bactericidal activity 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Many newer fluoroquinolones have been withdrawn from the US market because of toxicity; they include trovafloxacin (because of severe hepatic toxicity), gatifloxacin (because of hypoglycemia and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 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:
Some atypical mycobacteria
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 (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
Gram-positive bacteria including MRSA, as well as atypical respiratory tract pathogens
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 Some Clinical Uses of Fluoroquinolones ).
Fluoroquinolones are no longer recommended for treatment of gonorrhea because of increasing resistance worldwide.
Contraindications to Fluoroquinolones
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
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 Clostridioides (formerly Clostridium) difficile–Induced Diarrhea Toxins produced by Clostridioides difficile strains in the gastrointestinal tract cause pseudomembranous colitis, typically after antibiotic use. Symptoms are diarrhea, sometimes bloody... read more (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 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.
Ciprofloxacin raises theophylline Theophylline Chronic obstructive pulmonary disease (COPD) management involves treatment of chronic stable COPD and treatment of exacerbations. Treatment of chronic stable COPD aims to prevent exacerbations... read more levels, sometimes resulting in theophylline-related adverse effects.