Usage
Levonadifloxacin is a broad-spectrum antibiotic primarily prescribed for bacterial skin and soft tissue infections, including diabetic foot infections with concurrent bacteremia. It is particularly effective against Methicillin-resistant Staphylococcus aureus (MRSA). It is classified as a fluoroquinolone antibiotic and a beta-lactamase inhibitor.
Levonadifloxacin exerts its bactericidal effect by inhibiting bacterial DNA gyrase and topoisomerase IV, enzymes essential for bacterial DNA replication, repair, and transcription. By inhibiting these enzymes, levonadifloxacin disrupts bacterial DNA synthesis, leading to bacterial cell death. As a beta-lactamase inhibitor, it overcomes bacterial resistance mechanisms that involve the production of beta-lactamase enzymes, which inactivate certain antibiotics.
Alternate Names
Levonadifloxacin is also known as (S)-(-)-Nadifloxacin and WCK 771. Brand names include Emrok and Emrok O.
How It Works
Pharmacodynamics: Levonadifloxacin exerts its bactericidal action through the dual inhibition of bacterial DNA gyrase and topoisomerase IV. This inhibition disrupts bacterial DNA replication, repair, and transcription, resulting in bacterial cell death. It exhibits enhanced activity in acidic environments, making it effective against bacteria residing in abscesses or infected tissues. Its efficacy is also attributed to its ability to circumvent common bacterial resistance mechanisms, such as efflux pumps and beta-lactamase production.
Pharmacokinetics: Levonadifloxacin is available in both intravenous and oral formulations. Following administration, it is metabolized primarily to levonadifloxacin sulfate, an inactive metabolite. Levonadifloxacin demonstrates linear pharmacokinetics, meaning that its concentration in the body increases proportionally with the administered dose. It has a half-life that allows for twice-daily dosing. Excretion of levonadifloxacin and its metabolites is primarily through renal and hepatic pathways, with the majority being excreted in the urine. It achieves high concentrations in lung epithelial lining fluid (ELF), which is advantageous in the treatment of respiratory infections.
Mode of Action: Levonadifloxacin targets bacterial topoisomerases, specifically DNA gyrase and topoisomerase IV. It primarily binds to DNA gyrase in Staphylococcus aureus and other bacteria. This binding disrupts the supercoiling and decatenation of bacterial DNA, hindering DNA replication and transcription, ultimately leading to bacterial cell death.
Elimination Pathways: Primarily renal and fecal elimination. Levonadifloxacin sulfate, the major metabolite, is excreted in both urine and feces.
Dosage
Standard Dosage
Adults:
The recommended dose for adults is 800 mg intravenously every 12 hours or 500-750mg orally once daily for 5-14 days depending on the infection.
Children:
Levonadifloxacin is not recommended for use in children under 18 years of age.
Special Cases:
- Elderly Patients: No specific dose adjustment is necessary unless renal function is impaired.
- Patients with Renal Impairment: Dose adjustment may be required based on creatinine clearance.
- Patients with Hepatic Dysfunction: Dose adjustments for patients with hepatic impairment are generally not needed.
- Patients with Comorbid Conditions: Close monitoring of blood glucose is recommended for patients with diabetes.
Clinical Use Cases
Dosage guidelines should follow standard recommendations for ABSSSI. While data might exist regarding specific clinical situations (Intubation, Surgical Procedures, Mechanical Ventilation, Intensive Care Unit (ICU) Use, Emergency Situations), it is not commonly utilized in such contexts and would warrant further investigation before employing it for such conditions.
Dosage Adjustments
Dose modifications are necessary based on creatinine clearance for patients with renal impairment.
Side Effects
Common Side Effects
Constipation, vomiting, cough, nausea, diarrhea, headache, and dizziness.
Rare but Serious Side Effects
Tendinitis, tendon rupture, peripheral neuropathy, Clostridium difficile-associated diarrhea, hypoglycemia, hyperglycemia, allergic reactions, photosensitivity, QT prolongation, and CNS effects (confusion, tremors, hallucinations, seizures).
Long-Term Effects
Potential long-term effects may include peripheral neuropathy and tendon disorders with prolonged use.
Adverse Drug Reactions (ADR)
Severe hypoglycemia, anaphylaxis, angioedema, Stevens-Johnson Syndrome, and toxic epidermal necrolysis are rare but require immediate medical attention.
Contraindications
Hypersensitivity to levonadifloxacin or other quinolones, history of tendon disorders related to quinolone use, patients under 18 years of age, pregnancy, and breastfeeding.
Drug Interactions
Antacids containing magnesium or aluminum, sucralfate, multivitamins containing iron or zinc, didanosine, corticosteroids, NSAIDs, theophylline, and other drugs that prolong the QT interval.
Pregnancy and Breastfeeding
Levonadifloxacin is not recommended during pregnancy and breastfeeding due to limited safety data.
Drug Profile Summary
- Mechanism of Action: Inhibits bacterial DNA gyrase and topoisomerase IV, disrupting DNA replication and transcription. Also acts as a beta-lactamase inhibitor.
- Side Effects: Constipation, vomiting, cough, nausea, diarrhea, headache, dizziness (common); tendinitis, tendon rupture, peripheral neuropathy, C. difficile infection, hypoglycemia, hyperglycemia, allergic reactions, photosensitivity, QT prolongation, CNS effects (rare but serious).
- Contraindications: Hypersensitivity to levonadifloxacin or other quinolones, history of tendon disorders related to quinolone use, age under 18, pregnancy, breastfeeding.
- Drug Interactions: Antacids, sucralfate, metal cations, multivitamins, didanosine, corticosteroids, NSAIDs, theophylline, QT interval prolonging drugs.
- Pregnancy & Breastfeeding: Not recommended.
- Dosage: Adults: 800 mg IV every 12 hours or 500-750 mg oral once daily; Children: Not recommended.
- Monitoring Parameters: Blood glucose, renal function, liver function, signs of tendonitis, ECG for QT prolongation.
Popular Combinations
No established clinically popular combinations have been mentioned in the sources. Combination therapy would be guided by the specific infectious organism and clinical scenario.
Precautions
Screen for allergies, renal/hepatic dysfunction, diabetes, and history of tendon disorders. Closely monitor for adverse reactions, especially in elderly patients and those on concomitant corticosteroids. Advise patients to avoid prolonged sun exposure.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Levonadifloxacin?
A: Adults: 800 mg IV every 12 hours or 500-750 mg oral once daily; children: not recommended. Dosage adjustment is needed for patients with renal impairment.
Q2: What are the common side effects?
A: Common side effects include constipation, vomiting, cough, nausea, diarrhea, headache, and dizziness.
Q3: What are the serious side effects?
A: Tendinitis, tendon rupture, peripheral neuropathy, C. difficile infection, hypoglycemia, allergic reactions, photosensitivity, QT prolongation, CNS effects (confusion, tremors, hallucinations, seizures).
Q4: Is Levonadifloxacin safe in pregnancy?
A: No, Levonadifloxacin is not recommended during pregnancy and breastfeeding.
Q5: What is the mechanism of action of Levonadifloxacin?
A: Inhibits bacterial topoisomerases DNA gyrase and topoisomerase IV, disrupting DNA replication and transcription. Also acts as a beta-lactamase inhibitor.
Q6: What are the contraindications to using Levonadifloxacin?
A: Hypersensitivity to Levonadifloxacin or other quinolones, history of tendon disorders related to quinolone use, patients under 18 years old, pregnancy, and breastfeeding.
Q7: Does Levonadifloxacin interact with other medications?
A: Yes, it interacts with antacids, sucralfate, multivitamins with minerals, didanosine, corticosteroids, NSAIDs, theophylline, and drugs that prolong the QT interval.
Q8: What infections is Levonadifloxacin used to treat?
A: Primarily bacterial skin and soft tissue infections, including diabetic foot infections with concurrent bacteremia, and infections caused by MRSA.
Q9: Are there any precautions for patients with renal impairment?
A: Yes, dose adjustment is necessary based on creatinine clearance.
Q10: How should blood glucose be monitored in patients with diabetes taking Levonadifloxacin?
A: Close monitoring of blood glucose is recommended due to the risk of hypoglycemia and hyperglycemia.
