From the Guidelines
Polymyxin B should be administered at a dose of 1.5–3 mg/kg/day, with a loading dose of 2–2.5 mg/kg, while ofloxacin dosing varies by infection type, but generally ranges from 200-400 mg orally twice daily for urinary tract infections to 400 mg twice daily for respiratory and skin/soft tissue infections. When considering the treatment of bacterial infections with polymyxin or ofloxacin, it is crucial to prioritize the most effective and safest dosing regimen to minimize morbidity, mortality, and improve quality of life. The recommended dosing frequency for polymyxin B is based on the study by the task force on management and prevention of Acinetobacter baumannii infections in the ICU 1, which suggests a dose of 1.5–3 mg/kg/day, with a loading dose of 2–2.5 mg/kg. For ofloxacin, the dosing frequency varies by infection type, but common regimens include 200-400 mg orally twice daily for urinary tract infections, 400 mg twice daily for respiratory infections, and 400 mg twice daily for skin/soft tissue infections. Key considerations in dosing these medications include monitoring renal function due to the nephrotoxicity risk associated with polymyxin B and adjusting ofloxacin dosage in patients with renal impairment, as noted in the context of treating bacterial infections 1. Some important points to consider when administering these medications include:
- The importance of maintaining therapeutic drug concentrations while minimizing toxicity
- The mechanism of action of polymyxin B, which disrupts bacterial cell membranes, and ofloxacin, which inhibits bacterial DNA gyrase
- The need to continue both medications for the full prescribed course even if symptoms improve to prevent recurrence and antimicrobial resistance.
From the FDA Drug Label
Adults and children 15,000 to 25,000 units/kg body weight/day in individuals with normal kidney function. Infusions may be given every 12 hours; however, the total daily dose must not exceed 25,000 units/kg/day. The dosage may be divided and given at either 4 or 6 hour intervals.
The recommended dosing frequency for polymyxin B is:
- Every 12 hours for intravenous administration
- Every 4 or 6 hours for intramuscular administration There is no information about ofloxacin in the provided drug label 2.
From the Research
Dosing Frequency of Polymyxin B
- The recommended dosing frequency for polymyxin B is typically 1.5-2.5 mg/kg daily, administered in two divided doses 3.
- However, the dosing frequency may need to be adjusted based on the patient's renal function, as polymyxin B is primarily eliminated by the kidneys 3.
- A study published in 2017 found that polymyxin B exposures in patients with normal and impaired renal function were comparable, suggesting that dosing adjustments may not be necessary in patients with renal insufficiency 4.
Dosing Frequency of Ofloxacin
- The recommended dosing frequency for ofloxacin is 300 mg orally every 12 hours 5.
- Ofloxacin has been shown to be effective in preventing gram-negative bacillary infections in granulocytopenic patients, with a lower number of acquired gram-negative bacillary organisms per patient and fewer cases of gram-negative septicemia compared to vancomycin/polymyxin 5.
Comparison of Polymyxin B and Ofloxacin
- Polymyxin B and ofloxacin have different mechanisms of action and spectrums of activity, with polymyxin B being effective against multidrug-resistant Gram-negative bacteria and ofloxacin being effective against a broader range of gram-negative and gram-positive bacteria 3, 5.
- The choice of antibiotic will depend on the specific infection being treated and the susceptibility of the causative organism to the antibiotic 3, 5.
Global Usage and Guidelines
- A global survey of polymyxin use found that there is a wide variation in dosing and clinical use of polymyxins, with a need for international guidelines to improve clinical outcomes and delay the emergence of resistance 6.
- The survey also found that colistin, a polymyxin antibiotic, is commonly underdosed, highlighting the need for clear guidance on indications, dosing, and antibiotic combinations 6.