From the FDA Drug Label
The mechanism of action of levofloxacin and other fluoroquinolone antimicrobials involves inhibition of bacterial topoisomerase IV and DNA gyrase (both of which are type II topoisomerases), enzymes required for DNA replication, transcription, repair and recombination Fluoroquinolones, including levofloxacin, differ in chemical structure and mode of action from aminoglycosides, macrolides and β-lactam antibiotics, including penicillins Fluoroquinolones may, therefore, be active against bacteria resistant to these antimicrobials.
Alternative antibiotics for patients with kanamycin-induced nephrotoxicity may include levofloxacin, as it has a different mechanism of action and may be active against bacteria resistant to aminoglycosides like kanamycin 1.
- Key points:
- Levofloxacin has in vitro activity against Gram-negative and Gram-positive bacteria
- It may be effective against bacteria resistant to other antimicrobials, including aminoglycosides
- However, the safety and effectiveness of levofloxacin in treating clinical infections due to these bacteria have not been established in adequate and well-controlled clinical trials.
From the Research
For patients with kanamycin-induced nephrotoxicity, alternative antibiotics such as linezolid, daptomycin, ceftaroline, carbapenems, and tigecycline can be used, with consideration of the specific pathogen, infection site, and patient's renal function status. When selecting an alternative antibiotic, it is essential to consider the severity of the nephrotoxicity and the patient's overall clinical condition.
- Linezolid (600 mg IV/oral twice daily) is an excellent alternative for gram-positive infections, including MRSA, with no dose adjustment needed in renal impairment 2.
- Daptomycin (4-6 mg/kg IV once daily, adjusted for renal function) is effective against resistant gram-positive organisms but should be avoided in pneumonia.
- Ceftaroline (600 mg IV every 12 hours, reduced in renal impairment) provides coverage against MRSA and other gram-positives.
- For broader coverage, carbapenems like meropenem (1 g IV every 8 hours, adjusted for renal function) can be used.
- Tigecycline (100 mg IV loading dose, then 50 mg every 12 hours) doesn't require dose adjustment in renal impairment but has limitations, including FDA warnings about mortality. It is crucial to monitor the patient's renal function and adjust the antibiotic dose accordingly to prevent further kidney damage, as gentamicin and amikacin have been shown to be nephrotoxic in several studies 3, 4, 5, 6. The most recent and highest quality study should be prioritized when making a definitive recommendation, and in this case, the study by 5 provides valuable insights into the comparative nephrotoxicity of gentamicin and amikacin. In clinical practice, the choice of alternative antibiotic should be guided by the patient's specific needs and the potential risks and benefits of each option.