Continuing Education Activity
Levofloxacin is FDA-approved for the treatment of nosocomial pneumonia, community-acquired pneumonia, acute bacterial rhinosinusitis, acute bacterial exacerbation of chronic bronchitis, acute bacterial prostatitis, acute pyelonephritis, urinary tract infection, skin or skin structure infections, prophylaxis, and treatment of plaque due to Yersinia pestis, and to reduce the incidence of disease progression of inhalational anthrax. It is in the fluoroquinolone class of medications. This activity will highlight the indications, mechanism of action, adverse event profile, contraindication, monitoring, toxicity, and relevant interactions pertinent for healthcare team members in the treatment of patients with bacterial infections.
- Identify the mechanism of action of levofloxacin.
- Identify the indications of levofloxacin.
- Recognize the adverse effects of levofloxacin.
- Outline interprofessional team strategies for improving care coordination and communication to advance levofloxacin and improve outcomes.
Levofloxacin is a broad-spectrum, third-generation fluoroquinolone antibiotic used to treat bacterial infections. Levofloxacin is a safe and effective medicine on the World Health Organization's essential medicines list. It was patented in 1987 and subsequently received FDA approval in 1996 for medical use in the United States.
FDA-approved Indications of Levofloxacin
- Nosocomial Pneumonia
- Community-Acquired Pneumonia
- Skin and Skin Structure Infections Complicated and Uncomplicated
- Chronic bacterial prostatitis
- Acute Bacterial Exacerbation of Chronic Bronchitis
- Acute Bacterial Sinusitis
- Inhalational Anthrax, Post-Exposure in adult and pediatric patients
- Plague in adult and pediatric patients
- Urinary Tract Infections (UTI)
- Acute Pyelonephritis
- Bacterial conjunctivitis(Ophthalmic formulation)
Non-FDA Approved Indications
- Diabetic foot infection
Due to an increased risk of severe side effects (e.g., tendinitis and tendon rupture, peripheral neuropathy, and CNS effects), levofloxacin is used in patients with acute exacerbation of chronic bronchitis, acute bacterial sinusitis, and uncomplicated urinary tract infections who do not have alternative treatment options.
To decrease the development of drug-resistant bacteria, the FDA has recommended using levofloxacin only for strongly suspected bacterial infections. Also, levofloxacin should not be used empirically in patients at risk of multidrug-resistant Escherichia coli.
Mechanism of Action
Levofloxacin is a bactericidal antibiotic of the fluoroquinolone drug class that directly inhibits bacterial DNA synthesis. Levofloxacin promotes the breakage of DNA strands by inhibiting DNA-gyrase in susceptible organisms, which inhibits the relaxation of supercoiled DNA.
Of the fluoroquinolone class, levofloxacin has the most enhanced activity against gram-positive penicillin-sensitive and resistant organisms notably, Streptococcus pneumoniae) and reduced action against gram-negative bacilli notably, Pseudomonas aeruginosa compared to ciprofloxacin. Levofloxacin has effectiveness against other common respiratory organisms, notably Haemophilus influenzae, Moraxella catarrhalis, Legionella spp, Mycoplasma spp, and Chlamydia pneumoniae.Levofloxacin also has a higher in-vitro activity against mycobacterium tuberculosis and is preferred over the other fluoroquinolones as second-line antitubercular therapy.
There is a growing concern of drug resistance to fluoroquinolones worldwide, which can occur through chromosome-encoded or plasmid-mediated mechanisms. Levofloxacin is rapidly absorbed and widely distributed in the body. The bioavailability of levofloxacin is 99%; therefore, levofloxacin's intravenous and oral preparations are used interchangeably. Levofloxacin clearance is primarily via the renal route (87%).
Levofloxacin is available both for oral tablets and solution and intravenous administration. Levofloxacin is not available for administration through intramuscular, intrathecal, or subcutaneous routes. The marketed oral dosage strengths for levofloxacin are 250 mg, 500 mg, and 750 mg.
Oral dosing with tablets can be without regard to meals. However, the oral solution should be taken 1 hour before or 2 hours after meals. Patients should avoid using antacids, or levofloxacin should be administered two hours before or two hours after taking antacids containing magnesium or aluminum. It is essential to maintain proper hydration to prevent crystalluria.
- The recommended oral dose regimen is 750 mg once daily to treat nosocomial pneumonia, complicated skin and skin structure infections (7 to 14 days), community-acquired pneumonia, acute bacterial sinusitis, complicated urinary tract infection, or acute pyelonephritis (five days).
- The daily dosing of 500 mg once daily is recommended to treat nosocomial pneumonia (7 to 14 days), acute bacterial sinusitis (10 to 14 days), acute bacterial exacerbation of chronic bronchitis (seven days), uncomplicated skin and skin structure infections (7 to 10 days), chronic bacterial prostatitis (28 days), and post-exposure inhalational anthrax (60 days).
- The daily dosing of 250 mg once daily is recommended for patients with complicated urinary tract infections or acute pyelonephritis (10 days) or uncomplicated urinary tract infections (3 days).
Levofloxacin injection should be administered to both adult or pediatric patients by slow intravenous infusion over 60 minutes (for 250 to 500 mg) and over 90 minutes (for 750 mg). Due to an increased risk of hypotension, bolus or rapid intravenous administration should be avoided. In addition, the infusion should not use a solution containing multivalent cations. The ophthalmic solution is safe and an effective antibiotic used for seven days to treat bacterial conjunctivitis.
A 50% reduction in the total daily dosage is recommended in patients with renal impairment (glomerular filtration rate between 10 and 50 mL/min) and extended to every 48 hours if glomerular filtration rate falls less than 10 mL/min).
The primary adverse effects of levofloxacin include photosensitivity, nausea, diarrhea, headache, tendinitis, tendon rupture, hyper-hypoglycemia, seizures, prolonged QT interval, and peripheral neuropathy. Clinicians should prescribe levofloxacin to patients with a history of prolonged QT intervals carefully.
It is advisable to minimize or avoid exposure to natural or artificial sunlight while taking levofloxacin to reduce the occurrence of phototoxicity.
FDA has alerted a black box warning for using levofloxacin and other fluoroquinolones due to increased risk of disabling and irreversible side effects, including tendinitis and tendon rupture, peripheral neuropathy, and CNS effects (e.g., seizures, increased intracranial pressure) in all ages. However, older patients (older than 60 years), those patients taking corticosteroids and with kidney, heart, or lung transplants are at increased risk of severe tendon disorders.
Research has determined that prolonged use of levofloxacin is associated with an increased risk of fungal or bacterial superinfection (e.g., pseudomembranous colitis).
Due to the increased risk of hepatotoxicity, patients should be educated on signs or symptoms of liver injury so they can discontinue treatment.
The concurrent administration of levofloxacin with drugs that prolong the QT interval is contraindicated.
It is also contraindicated in patients with documented hypersensitivity to the drug or its components, in pregnancy, nursing mothers, and in children younger than 18 years of age due to the possible risk of cartilage damage.
It is recommended to avoid levofloxacin and other fluoroquinolone antibiotics in patients with myasthenia gravis due to an increased risk of exacerbating existing muscle weakness.
Unlike ciprofloxacin, levofloxacin does not inhibit the drug-metabolizing enzyme CYP1A2; however, due to its weak inhibiting potential on the CYP2C9 enzyme, bleeding can occur with concurrent administration of warfarin.
Careful monitoring of blood glucose is recommended for patients taking concurrent antidiabetic agents due to the risk of glucose dysregulation.
Providers should monitor patients who are taking levofloxacin for crystalluria, signs and symptoms of tendonitis and disordered glucose regulation, altered mental status, white blood cells, and signs of infections.
It is also essential to periodically evaluate organ system functions (hepatic, renal, hematopoietic) during treatment. It is also necessary to monitor for evidence of bleeding because of the drug interaction of levofloxacin with warfarin, which acts on the CYP2C9 enzyme and raises warfarin levels.
Unlike ciprofloxacin, monitoring patients concurrently taking theophylline is unnecessary as levofloxacin does not inhibit the enzyme CYP1A2.
The elimination half-life of levofloxacin ranges from 27 to 35 hours in adults with renal impairment, depending on severity, compared with six to eight hours in healthy adults. This prolonged half-life indicates that dosing adjustment is necessary for these patients. Levofloxacin has a low potential for acute toxicity; however, the stomach needs to be emptied during an acute overdose. The patient should be under observation with adequate maintenance of hydration. It is important to note that hemodialysis or peritoneal dialysis can not adequately remove levofloxacin. The role of enhancing drug elimination with forced dilution is not clear. Activated oral charcoal administration is also a recommended approach with appropriate conditions.
Clinical data indicate that breast milk has a low concentration of levofloxacin, which is unlikely to cause adverse effects in breastfed babies. The use of levofloxacin with breastfeeding mothers is acceptable with monitoring of the infant for possible GI adverse effects (diarrhea or candidiasis).
Enhancing Healthcare Team Outcomes
Levofloxacin is a widely prescribed respiratory fluoroquinolone by many healthcare professionals for a broad spectrum of bacterial infections. Levofloxacin is well-known to increase the risk of tendinitis and tendon rupture in all ages, especially in patients over 60 years old, taking corticosteroids, and with a history of kidney, heart, or lung transplants. It not only extends hospital stay but increases the cost of healthcare. All healthcare workers who prescribe this agent should stratify patients earlier for risk of these complications and should sparely use the drug for patients with acute sinusitis, acute bronchitis, and uncomplicated urinary tract infections. Healthcare staff should counsel patients to maintain adequate hydration to prevent crystalluria and avoid antacids to enhance bioavailability. As levofloxacin excretion is primarily via the kidney, providers should carefully adjust the dose in the presence of renal insufficiency to prevent levofloxacin accumulation.
Clinicians should monitor patients for changes in bowel frequency, fever, abdominal cramps, loss of appetite, nausea, vomiting, right upper quadrant tenderness, jaundice, dark-colored urine, or palpitations. Levofloxacin is well-known to cause pseudomembranous colitis, hepatotoxicity, and QT prolongation; therefore, patients should receive education to discontinue treatment when the clinical features develop. If diarrhea develops, it is essential to manage fluid and electrolyte replacement in this patient population adequately. Healthcare workers should limit the duration of levofloxacin therapy and abstain from the empirical prescribing of this agent due to the growing worldwide concern of drug resistance to levofloxacin and other fluoroquinolones.
Clear communication between physicians and nurses is necessary so that levofloxacin is administered by slow infusion to avoid the risk of hypotension. Pharmacists need to verify dosing and treatment duration, as well as to check for drug-drug interactions. Nursing is on the front lines to observe adverse effects and promptly report these to the rest of the team. A concerted and collaborative interprofessional team effort between patients, physicians, nurses, pharmacists, and other healthcare providers is necessary to achieve improved patient outcomes with reduced risk of side effects and increased patient satisfaction. [Level 5]