Ofloxacin

Second-generation fluoroquinolone antibiotic for bacterial infections

Ofloxacin is a second-generation fluoroquinolone antibiotic developed in the 1980s that has since been used in the treatment of various bacterial infections. It is a racemic mixture of two enantiomers; the laevorotatory enantiomer (S-ofloxacin) is known as levofloxacin and has greater antibacterial activity. Ofloxacin is available in Germany as tablets (under brand names such as Tarivid), infusion solution, and as eye drops and ear drops.

Ofloxacin is characterised by a broad antibacterial spectrum, good bioavailability after oral administration (nearly 100 percent), and good tissue penetration. It acts against a wide range of gram-negative and gram-positive bacteria as well as atypical pathogens such as chlamydia, mycoplasma, and legionella. Since 2019, systemically used ofloxacin has been subject to an EU-wide restriction by the European Medicines Agency due to serious, potentially long-lasting side effects, particularly affecting tendons, muscles, joints, and the nervous system.

Mechanism of Action

Ofloxacin inhibits two bacterial enzymes essential for DNA replication and cell division: DNA gyrase (topoisomerase II) and topoisomerase IV. Both enzymes are necessary for winding, uncoiling, and separating bacterial DNA during replication and transcription. By binding to the enzyme-DNA complex, ofloxacin stabilises a non-covalent complex and prevents the re-ligation of the DNA strand after cutting reactions. This leads to double-strand breaks in the bacterial DNA and ultimately to cell death.

Ofloxacin acts bactericidally and shows concentration-dependent efficacy: the higher the tissue concentration in relation to the minimum inhibitory concentration (MIC) of the pathogen, the more pronounced the bactericidal effect. As human topoisomerases have a different structure from bacterial enzymes, selectivity for bacterial targets is high; nonetheless, mutagenic effects on human cells cannot be entirely excluded at high concentrations.

Resistance development against ofloxacin arises primarily through point mutations in the genes for DNA gyrase and topoisomerase IV, as well as active efflux (efflux pumps) and porin loss in gram-negative bacteria. Cross-resistance within the fluoroquinolone class is common.

Indications

• Urinary tract infections: Uncomplicated and complicated urinary tract infections caused by susceptible pathogens (E. coli, Klebsiella spp.); today only used after resistance testing due to increasing resistance rates
• Respiratory tract infections: Community-acquired pneumonia (for specific indications), acute exacerbation of chronic bronchitis (only if other antibiotics are not suitable)
• Sexually transmitted infections: Gonorrhoea (after resistance testing; increasing resistance limits use), chlamydial infections, epididymitis, prostatitis
• Skin and soft tissue infections: For gram-negative pathogens or mixed infections; use after strict indication review
• Eye drops: Bacterial conjunctivitis, corneal infections (keratitis), perioperative prophylaxis in eye surgery
• Ear drops: Bacterial otitis externa, chronic suppurative otitis media (with intact or perforated eardrum)
• Tuberculosis: In combination for multi-resistant tuberculosis (off-label or within special programmes)

Dosage and Administration

Urinary tract infections (uncomplicated): 200 mg twice daily for 3 to 7 days. Urinary tract infections (complicated) and prostatitis: 200 to 400 mg twice daily for 10 to 28 days. Respiratory tract infections: 400 mg once to twice daily for 7 to 10 days. Gonorrhoea: 400 mg as a single dose (only after resistance testing; largely abandoned). Eye drops (0.3%): Initially 1 drop every 2 hours (during waking hours), after 2 days four times daily; total duration 5 to 10 days. Ear drops (0.3%): 5 to 10 drops once to twice daily, depending on the indication.

Ofloxacin should be taken independently of meals but with sufficient fluid (at least one glass of water). Dairy products, antacids, and iron or zinc supplements reduce absorption and should be taken at separate times (at least 2 hours apart). Direct sunlight and UV radiation should be avoided during therapy (photosensitisation).

Side Effects

Common: Gastrointestinal complaints (nausea, diarrhoea, vomiting, abdominal pain), headache, insomnia, dizziness, skin reactions.

Serious (class effects of fluoroquinolones):

• Tendon ruptures: Particularly the Achilles tendon; risk increases with concurrent corticosteroid use, in elderly patients, and in renal transplant recipients. Immediate discontinuation of treatment if tendon irritation or pain occurs
• Peripheral neuropathy: Tingling, burning, numbness, or weakness in extremities; may be permanent
• CNS toxicity: Seizures, psychotic reactions, hallucinations, confusion, anxiety disorders, depression; increased risk in epileptic patients
• QTc prolongation: Cardiac risk; critical in patients with known QTc prolongation or corresponding co-medication
• Aortic dissection and aortic aneurysm: Rare but serious association; particular caution with corresponding risk factors (hypertension, connective tissue diseases)
• Hepatotoxicity: Elevated liver values up to liver failure in individual cases
• Clostridioides difficile colitis: Like all systemic antibiotics, ofloxacin can trigger pseudomembranous colitis

Interactions

Antacids, sucralfate, iron, zinc, calcium, magnesium: Drastic reduction of ofloxacin absorption through chelation; intake at separate times (at least 2 hours) required.

QTc-prolonging medications: Antiarrhythmics (amiodarone, sotalol), antipsychotics, certain antidepressants; additive risk for life-threatening cardiac arrhythmias.

Corticosteroids: Increased risk of tendon ruptures in combination; especially in elderly patients.

Oral anticoagulants (warfarin, phenprocoumon): Enhanced anticoagulation possible; regular INR checks recommended.

Theophylline, NSAIDs: Increased risk of seizures through pharmacodynamic interaction.

Antidiabetic drugs: Blood glucose fluctuations (hypo- and hyperglycaemia) in combination with insulin or sulphonylureas; close blood glucose monitoring.

Special Notes

Restricted indication since 2019: The EMA has restricted the approval of systemic fluoroquinolones. Ofloxacin should only be used when no other antibiotics are suitable and after careful benefit-risk assessment. This restriction does not apply to topical use (eye drops, ear drops).

Pregnancy and breastfeeding: Ofloxacin is contraindicated during pregnancy. Animal studies showed damage to embryonic cartilage tissue. Ofloxacin passes into breast milk; breastfeeding should be interrupted during therapy.

Children and adolescents: Systemic ofloxacin is contraindicated in children and adolescents in the growth phase, as cartilage damage cannot be excluded. Eye drops may be used after medical assessment.

Photosensitisation: Avoid direct sunlight and UV radiation during therapy; sun protection recommended for up to several days after the end of therapy.

Driving ability: CNS side effects such as dizziness, confusion, or visual disturbances can impair driving ability.

Frequently Asked Questions

Why are fluoroquinolones like ofloxacin less recommended today?

Fluoroquinolones were restricted in their systemic use by the EMA and national authorities due to an increased risk of serious and potentially long-lasting or irreversible side effects (tendon ruptures, peripheral neuropathy, CNS effects, aortic aneurysms). Topical forms (eye drops, ear drops) are exempt from this restriction.

What is the difference between ofloxacin and levofloxacin?

Levofloxacin is the active laevorotatory enantiomer of racemic ofloxacin. Levofloxacin has twice the activity against most pathogens and is used at half the dose of ofloxacin. In systemic therapy, levofloxacin has largely replaced ofloxacin.

May ofloxacin be taken with milk?

No. Milk and dairy products contain calcium, which forms chelates with ofloxacin and considerably reduces absorption. Ofloxacin should be taken with water and with at least 2 hours' separation from calcium-rich foods.

References

• Product information Tarivid (Sanofi), as of 2023
• European Medicines Agency (EMA): Restriction of approval of systemic fluoroquinolones, 2019
• Federal Institute for Drugs and Medical Devices (BfArM): Dear Doctor Letter on fluoroquinolones, 2019
• Paul-Ehrlich-Gesellschaft (PEG): Antibiotic guidelines and resistance reports, 2023
• Andriole VT: The quinolones. 3rd edition. Academic Press, 2000