Fluoroquinolones – Dangerous Antibiotics

Fluoroquinolones – Infectious Diseases – Merck Manual Professional Edition

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Fluoroquinolones (see Table: Fluoroquinolones) exhibit concentration-dependent bactericidal activity (see Bacteria and Antibacterial Drugs: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Many newer fluoroquinolones have been withdrawn because of toxicity; they include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.

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. Moxifloxacin is eliminated primarily in bile.

Indications

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.

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)

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 gemifloxacin is used for > 1 wk and is more likely to develop in women < 40. Nephrotoxicity is rare.