Fluoroquinolones

Fluoroquinolones are antibiotic successors of nalidixic acid. They offer greater efficacy, a broader spectrum of activity, and are safer than their predecessors. They include;

• Ciprofloxacin
• Gemifloxacin
• Levofloxacin
• Moxifloxacin
• Norfloxacin
• Ofloxacin

Pregnancy Category: C

They can be used with caution if the benefits outweigh the risks

Mechanism of Action

Fluoroquinolones disturb DNA replication in susceptible gram-negative bacteria by exhibiting antimicrobial effects on bacterial DNA gyrase (bacterial topoisomerase II) and topoisomerase IV. Inhibition of DNA gyrase results in relaxation of the supercoiled DNA and DNA strand breakage. Inhibition of topoisomerase IV interferes with the separation of newly replicated DNA during cell division.

Pharmacokinetics

• Absorption: 80%-90% of orally absorbed fluoroquinolones are absorbed except for norfloxacin to which only 35% to 70% are absorbed. Concurrent ingestion of fluoroquinolones with sucralfate, aluminum- or magnesium containing antacids, or dietary supplements containing iron, calcium or zinc can reduce the absorption.
• Distribution: Fluoroquinolones distribute well into all tissues and body fluids. Levels are high in bone, urine (except moxifloxacin), kidney, and prostatic tissue (but not prostatic fluid), and concentrations in the lungs exceed those in serum. Only Ofloxacin has a high penetration level to the CSF. They also accumulate in macrophages and polymorphonuclear leukocytes, thus interfering with intracellular organisms.
• Elimination: Most fluoroquinolones are excreted renally and dosage adjustments are needed in renal dysfunction. Moxifloxacin is excreted primarily by the liver, and no dose adjustment is required for renal impairment.

Indications

• Treatment of infections caused by susceptible gram-negative bacteria, including Escherichia coli, Proteus mirabilis, Klebsiellapneumoniae, Enterobacter cloacae, Proteus vulgaris, Providencia rettgeri, Morganella morganii, Pseudomonas aeruginosa, Citrobacter freundii, Staphylococcusaureus, S. epidermidis, group D streptococci, Streptococcus pneumonia
• Unlabeled use: Treatment of patients with cystic fibrosis who have pulmonary exacerbations

Cautions and Contraindications

• Use cautiously with renal impairment,
• Contraindicated in patients with allergy to any fluoroquinolone; pregnancy; lactation; and history of myasthenia gravis.

Adverse Effects

• CNS: Headache, dizziness, insomnia, fatigue, somnolence, depression, blurred vision
• GI: Nausea, vomiting, dry mouth, diarrhea, and abdominal pain
• Hematologic: Elevated BUN, AST, ALT,serum creatinine and alkaline phosphatase;decreased WBC, neutrophil count, Hematocrit
• Other: Fever, rash, photosensitivity, QT interval prolongation, tendinitis, tendonrupture

Interactions

• Decreased therapeutic effectwith iron salts, and sucralfate
• Decreased absorption with antacids
• Increased serum levels andtoxic effects of theophylline with fluoroquinolones
• Risk of prolonged QT interval when combined with other drugs that prolong QT interval
• Increased photosensitivity reactions with St. John’s Wort

Nursing Considerations

Assessment

• Assess allergy to fluoroquinolones,
• Assess for renal impairment, seizures, lactation
• Assess skin color, lesions
• Orientation, reflexes, affect
• Mucous membranes, bowel sounds
• LFTs, renal function tests

Interventions

• Drug increases risk of tendinitis and tendon rupture, especially in older patients, patients with organ
  transplants, and patients on corticosteroids; may exacerbate weakness in patients with myasthenia gravis. Avoid use in these patients.
• Arrange for culture and sensitivity tests before beginning therapy.
• Continue therapy for 2 days after the signs and symptoms of infection have disappeared.
• Administer oral drug 1 hour before or 2 hours after meals with a glass of water.
• Ensure that patient is well hydrated during course of drug therapy.
• Administer antacids, if needed, at least 2 hours after dosing.
• Monitor clinical response; if no improvement is seen or a relapse occurs, repeat culture and sensitivity.
• Ensure ready access to bathroom if diarrhea occurs.
• Arrange for appropriate bowel training program if constipation occurs.
• Provide frequent small meals if GI upset occurs.
• Arrange for monitoring of environment (noise, temperature) and analgesics, for headache.
• Establish safety precautions if CNS, visual changes occur.
• Encourage patient to complete full course of therapy.

Patient/Family Teaching

• Take oral drugs on an empty stomach, 1 hour before or 2 hours after meals. If you need an antacid, do not take it within 2 hours of ciprofloxacin dose.
• Drink plenty of fluids.
• You may experience these side effects: Nausea, vomiting, abdominal pain (frequent small meals may help); diarrhea or constipation (consult your health care provider); drowsiness, blurring of vision dizziness (observe caution if driving or using hazardous equipment).
• Report rash, visual changes, severe GI problems, weakness, tremors.

References

• Karch M. (2014). Lippincott’s Nursing Drug Guide. Wolter’s Kluwer/Lippincott Williams and Wilkins. New York, USA.
• Vallerand A., Sanoski C., Deglin J. (2015). Davis’s Drug Guide for Nurses (14^th Ed). F.A Davis Company. Philadelphia, Pennsylvania, USA.
• Whalen K., Finkel R., Panavelil T. (2015). Lippincott Illustrated Reviews Pharmacology (6^th Ed). Wolter’s Kluwer. USA.