Stability of Reconstituted Cloxacillin in Infusion
Reconstituted cloxacillin is not stable at room temperature and should be used immediately or refrigerated, with limited data supporting storage beyond 24 hours under refrigeration.
Stability at Room Temperature (20-25°C)
The available guideline evidence does not provide specific stability data for cloxacillin at room temperature. However, the IDSA guidelines for outpatient parenteral antimicrobial therapy indicate that oxacillin (a closely related penicillinase-resistant penicillin) maintains stability for only 1 day at 25°C 1. Given the structural similarity between cloxacillin and oxacillin, this limited room-temperature stability likely applies to cloxacillin as well.
Practical implication: Reconstituted cloxacillin infusions should not be stored at room temperature for more than 24 hours, and ideally should be prepared fresh or used within several hours of reconstitution 1.
Stability Under Refrigeration (2-8°C)
According to IDSA guidelines, oxacillin demonstrates stability for 7 days when refrigerated at 5°C 1. This represents a significant improvement over room-temperature storage and suggests that cloxacillin, if refrigerated immediately after reconstitution, may remain stable for up to one week.
Key caveat: The concentration matters significantly. The IDSA data show that oxacillin at optimal dilutions of 10-100 mg/mL maintains this 7-day refrigerated stability 1. More dilute or more concentrated solutions may have different stability profiles.
Comparison with Related Beta-Lactams
To contextualize cloxacillin's stability, consider these related antibiotics from the same guidelines 1:
- Nafcillin (another penicillinase-resistant penicillin): 3 days refrigerated, 1 day at room temperature
- Ampicillin: 48 hours refrigerated, 8 hours at room temperature
- Cefazolin: 10 days refrigerated, 1 day at room temperature
Cloxacillin's stability profile likely falls between nafcillin and oxacillin, given their structural similarities.
Critical Considerations for Beta-Lactam Stability
Recent French guidelines on beta-lactam optimization emphasize that continuous or prolonged infusion of beta-lactams must account for chemical stability over time, which is particularly important for drugs with short half-lives 1. The guidelines specifically note that some beta-lactams require administration of the daily dose in several divided portions prepared just before infusion due to limited stability 1.
For cloxacillin specifically: Given its use in treating methicillin-sensitive staphylococcal infections at doses of 2g per day (as two infusions) or 3g four times daily 2, and considering the stability limitations, prepare each dose fresh or store refrigerated for no more than 7 days, using the solution within 24 hours once brought to room temperature 1.
Practical Algorithm for Cloxacillin Infusion Preparation
Immediate use (preferred): Reconstitute and administer within 1-2 hours at room temperature 1
Short-term storage: Refrigerate immediately after reconstitution; stable up to 7 days at 2-8°C (based on oxacillin data) 1
Before administration: Allow refrigerated solution to reach room temperature, but use within 24 hours of removal from refrigeration 1
Discard if: Solution shows visible particulates, discoloration, or has exceeded storage timeframes 1
Common Pitfalls to Avoid
Do not assume all beta-lactams have similar stability—carbapenems like imipenem have stability of only 2-3 hours at 25°C, while others like cefazolin remain stable for 30 days refrigerated 1
Do not store diluted cloxacillin at room temperature overnight—the 24-hour room-temperature limit is a maximum, not a recommendation 1
Do not freeze cloxacillin solutions—freezing data is not available for cloxacillin, and related compounds show variable stability when frozen 1
Verify the concentration—stability is concentration-dependent, with optimal dilutions (10-100 mg/mL for oxacillin) showing better stability than very dilute or highly concentrated solutions 1