Is Levaquin (levofloxacin) effective against Methicillin-Sensitive Staphylococcus aureus (MSSA) infections?

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Last updated: June 4, 2025View editorial policy

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From the Guidelines

Levaquin (levofloxacin) is effective against Methicillin-Sensitive Staphylococcus aureus (MSSA) infections, but it is not the first-line treatment option. According to the most recent guidelines, levofloxacin has activity against MSSA, but resistance rates have increased over time, making it a less reliable choice compared to other antibiotics 1.

Key Points to Consider

  • First-line treatments for MSSA typically include beta-lactam antibiotics such as nafcillin, oxacillin, or cefazolin, which have better efficacy and lower resistance rates.
  • Levofloxacin might be used as an alternative when patients have allergies to preferred agents or in specific clinical scenarios where its broader spectrum of activity is beneficial.
  • The typical adult dose of levofloxacin for MSSA infections is 500-750 mg once daily, with treatment duration varying based on infection type and severity (typically 7-14 days) 1.
  • Fluoroquinolones like levofloxacin work by inhibiting bacterial DNA gyrase and topoisomerase IV, preventing DNA replication.
  • Due to concerns about resistance development and potential adverse effects, levofloxacin should generally be reserved for situations where first-line agents cannot be used.

Clinical Considerations

  • The guidelines recommend considering coverage for MSSA when MRSA coverage is not used, with options including piperacillin-tazobactam, cefepime, levofloxacin, imipenem, and meropenem 1.
  • Oxacillin, nafcillin, and cefazolin are preferred for the treatment of proven MSSA, but would ordinarily not be used in an empiric regimen for hospital-acquired pneumonia (HAP).
  • If a patient has a severe penicillin allergy and aztreonam is used instead of any β-lactam–based antibiotic, coverage for MSSA should be included 1.

From the FDA Drug Label

Clinical success and microbiological eradication rates by pathogen are detailed in Table 13.

The FDA drug label does not answer the question.

From the Research

Effectiveness of Levaquin against MSSA

  • Levaquin (levofloxacin) is a fluoroquinolone antibacterial agent with a broad spectrum of activity against Gram-positive and Gram-negative bacteria and atypical respiratory pathogens 2.
  • It is active against both penicillin-susceptible and penicillin-resistant Streptococcus pneumoniae, but its effectiveness against Methicillin-Sensitive Staphylococcus aureus (MSSA) is not explicitly stated in the study 2.
  • However, another study suggests that fluoroquinolones, such as levofloxacin, have bactericidal activity against MRSA, but their effectiveness against MSSA is not specified 3.
  • A study on once-daily treatments for MSSA bacteremia mentions that fluoroquinolones are effective in vitro against MSSA, but there is insufficient evidence to support their use for MSSA bacteremia 4.

Clinical Use of Levaquin

  • Levaquin is generally well tolerated, with the most frequently reported adverse events being nausea and diarrhea 2.
  • It has a pharmacokinetic profile that is compatible with once-daily administration and allows for sequential intravenous to oral therapy 2.
  • However, its use for MSSA infections is not well established, and more clinical studies are needed to determine its efficacy and safety in this context 4.

Comparison with Other Antibiotics

  • Other antibiotics, such as linezolid, TMP-SMX, and tetracyclines, have been shown to be effective against MRSA, but their effectiveness against MSSA is not well established 3.
  • A novel anti-MRSA agent, levonadifloxacin, has been approved for the treatment of complicated skin and soft-tissue infections and concurrent bacteremia, but its effectiveness against MSSA is not specified 5.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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