The Resurgence of Polymyxins
Polymyxins, including Polymyxin B and Polymyxin E (colistin), are a class of polypeptide antibiotics that have seen a resurgence in use due to the increasing prevalence of infections caused by multidrug-resistant (MDR) Gram-negative bacteria [1.5.2]. These powerful antibiotics are often the last line of defense against organisms like Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae [1.2.1]. Given their potency and potential for toxicity, particularly nephrotoxicity (kidney damage) and neurotoxicity, their correct preparation and administration are of paramount importance for patient safety and therapeutic success [1.8.1].
A fundamental step in this process is the reconstitution of the lyophilized (powdered) drug and its subsequent dilution for infusion. The fluid used for this dilution, known as the diluent, can significantly impact the drug's stability. Clinicians frequently question the compatibility of these drugs with common intravenous fluids. Specifically, can Polymyxin be given in normal saline (0.9% sodium chloride)?
Diluent Options: Normal Saline vs. Dextrose 5% in Water (D5W)
Both 0.9% sodium chloride (normal saline) and 5% dextrose in water (D5W) are commonly used as diluents for intravenous medications. For polymyxins, the choice can be nuanced.
Polymyxin B and Normal Saline
Studies have confirmed that Polymyxin B is administered by intravenous infusion and requires reconstitution with solutions like 0.9% saline or 5% glucose [1.2.3]. Research has evaluated the stability of Polymyxin B in both solutions. One study found that Polymyxin B diluted in both 0.9% saline and 5% glucose solution remains stable for 24 hours at both room temperature (25°C) and at 40°C [1.2.3]. After this 24-hour period, significant degradation was observed [1.2.3]. Another study concluded that Polymyxin B diluted in 0.9% sodium chloride injection was stable for at least one day when stored at either 4°C or 25°C [1.5.1]. This supports the safe use of normal saline for infusions completed within a 24-hour timeframe [1.2.3].
For specific routes of administration, normal saline is explicitly recommended:
- Intrathecal: For meningitis treatment, Polymyxin B is dissolved in 10 mL of sterile physiologic saline [1.2.2].
- Inhalation: For respiratory infections, inhaled Polymyxin B is often diluted with 5 mL of 0.9% saline solution before being aerosolized [1.2.1].
- Topical Irrigation: Solutions for bladder irrigation are prepared by diluting polymyxin in 1 liter of normal saline [1.3.2, 1.6.3].
Colistimethate Sodium (CMS) and Normal Saline
Colistimethate sodium (CMS) is a prodrug that is converted into the active form, colistin (Polymyxin E), in the body [1.7.3]. CMS is compatible with a wide range of intravenous fluids, including normal saline, D5W, and Lactated Ringer's solution [1.4.1, 1.7.5]. For intravenous infusion, reconstituted CMS can be diluted in 50mL of 0.9% sodium chloride [1.7.6]. Final infusion solutions of CMS should be freshly prepared and used within 24 hours [1.7.1].
Comparison of Diluents for Polymyxin Administration
| Feature | Normal Saline (0.9% NaCl) | Dextrose 5% in Water (D5W) |
|---|---|---|
| Polymyxin B Stability | Stable for at least 24 hours after dilution [1.5.1, 1.5.5]. | The manufacturer-recommended diluent, with stated stability up to 72 hours under refrigeration [1.3.1, 1.5.4]. |
| Colistin (CMS) Stability | Compatible and commonly used for dilution [1.4.1, 1.7.5]. Freshly prepared infusions should be used within 24 hours [1.7.1]. | Compatible for dilution [1.4.1, 1.7.5]. |
| Clinical Preference | May be preferred in patients where dextrose administration is a concern (e.g., hyperglycemia) [1.5.2]. | Often the standard recommended diluent for IV Polymyxin B infusions [1.6.1, 1.3.5]. |
| pH Considerations | The pH of 0.9% NaCl is typically around 5.6 [1.5.4]. Polymyxins are more susceptible to degradation at neutral or basic pH values (above 7.0) [1.2.3]. | D5W has a more acidic pH range (3.2–6.5), which may contribute to its longer stated shelf life for Polymyxin B [1.5.4]. |
Administration and Safety Considerations
Proper administration technique is crucial to minimize the risks associated with polymyxin therapy.
Preparation and Dosing
- Reconstitution: The lyophilized powder is first reconstituted with a small volume of a suitable liquid like Sterile Water for Injection or 0.9% Sodium Chloride Injection [1.6.2].
- Dilution: The reconstituted drug is then added to a larger volume of infusion fluid (e.g., 300-500 mL of D5W or normal saline) for intravenous drip [1.3.1, 1.2.2].
- Dosing: Doses are calculated based on body weight (mg/kg) and renal function. A loading dose is often recommended to quickly achieve therapeutic drug levels [1.8.3].
Minimizing Nephrotoxicity
Nephrotoxicity is the most significant dose-limiting side effect of polymyxins [1.8.5]. Studies suggest that Polymyxin B may be associated with a lower incidence of acute kidney injury (AKI) compared to colistin [1.8.1, 1.8.5]. Key strategies to mitigate this risk include:
- Monitoring Renal Function: Close monitoring of serum creatinine and urine output is essential [1.8.1].
- Avoiding Concomitant Nephrotoxins: Use of other drugs that can harm the kidneys should be avoided whenever possible [1.8.1].
- Appropriate Dosing: Adhering to recommended dosing guidelines, especially in patients with pre-existing renal impairment, is critical. Dosing for colistin is adjusted for renal function, while guidelines often recommend not adjusting Polymyxin B doses for renal impairment [1.8.1, 1.8.4].
Conclusion
Yes, Polymyxin B and colistin (CMS) can be given in normal saline. For Polymyxin B, solutions diluted in normal saline are considered stable for at least 24 hours, making it a viable option for intravenous, intrathecal, and inhaled administration [1.2.3, 1.5.1]. While D5W is frequently cited as the manufacturer-recommended diluent for IV Polymyxin B with a longer stability profile, normal saline is a safe and effective alternative, particularly when infusions are completed within 24 hours or when dextrose solutions are contraindicated. For colistin, normal saline is one of several compatible diluents for IV administration [1.7.5]. The final choice of diluent rests on drug stability data, route of administration, and patient-specific factors, always guided by institutional protocols and pharmaceutical guidelines.
Authoritative Link: Polymyxin B Sulfate Monograph - Drugs.com [1.3.2]
