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Updated: Aug 10, 2025
Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
Published on: August 30, 2018
Antimicrobial residual drug error in the intensive care unit; a single blinded prospective observational study
Paul Jarrett1, Samantha Keogh2, Jason A Roberts3
1Queensland University of Technology (QUT), School of Nursing, Kelvin Grove, Brisbane, Queensland 4059. Australia; Department of Intensive Care Services, Royal Brisbane & Women's Hospital, Herston, Brisbane, Queensland 4029, Australia.
Objective:
To determine the percentage of drug remaining in discarded antibiotic vials after use.
Design:
Blinded prospective observational trial.
Setting:
26-bed Australian metropolitan tertiary referral intensive care unit.
Main Outcome Measures:
Percentage of labelled dose remaining in the vial after discard.
Method:
Discarded antibiotic vials collected over a 7-day period in an adult intensive care unit were analysed. Each collected vial had any drug remnant washed out and made up to a known volume. A 1 ml aliquot of each vials washings was analysed using high performance liquid chromatography. From this concentration, the percentage of the drug remaining in the vial after discard was calculated. Additionally, each vial was weighed before and after washing to determine the weight of the remnant in each vial.
Results:
A total of 311 vials comprising of 11 different drugs and 14 individual vial types were collected. The median residual drug error across all vials was 3.7 %. The drug with the highest median was piperacillin at 6.1 % (IQR 4.3) and the lowest was amoxicillin 0.2 % (IQR 0.1). The single highest value for a given vial was vancomycin (500 mg) with 33.2 % and the lowest for a given vial was 0.1 % amoxicillin (1 g). These two drugs also exhibited the greatest range between the maximum and minimum value for any drug being 32 % and 0.9 % respectively.
Conclusions:
Our study shows that up to a third of the intended dose may fail to reach the patient, highlighting a significant factor in the administration of antibiotics to the critically ill population.
Implications For Clinical Practice:
Residual drug often remains in antibiotic vials meaning that drug is not reaching the patient. There is considerable variation in the method by which medications are reconstituted in clinical settings. Two person checks should be completed after reconstitution in order to ensure that the medication is fully reconstituted and extracted from the vial.
Insights
Significant antibiotic residue remains in discarded vials, potentially up to a third of the dose. This study highlights the need for improved antibiotic administration practices in intensive care units to ensure patients receive the full prescribed medication.
Area of Science:
- Pharmacology
- Clinical Pharmacy
- Drug Delivery
Background:
- Antibiotic administration in critically ill patients is crucial.
- Accurate dosing is essential for effective treatment and preventing resistance.
- Residual drug in vials may impact therapeutic outcomes.
Purpose of the Study:
- To quantify the percentage of antibiotic drug remaining in discarded vials.
- To identify variations in residual drug amounts across different antibiotics.
- To assess the implications for patient dosing in intensive care.
Main Methods:
- Prospective observational trial in an Australian tertiary referral intensive care unit.
- Collection and analysis of 311 discarded antibiotic vials over 7 days.
- High-performance liquid chromatography (HPLC) used to determine residual drug concentration.
Main Results:
- Median residual drug error across all vials was 3.7%.
- Piperacillin showed the highest median residual drug (6.1%), while amoxicillin had the lowest (0.2%).
- A single vancomycin vial contained 33.2% residual drug, indicating significant variability.
Conclusions:
- A substantial portion of prescribed antibiotic doses may not reach critically ill patients due to vial residue.
- Variability in drug reconstitution and extraction necessitates improved clinical practices.
- Implementing two-person checks after reconstitution is recommended to ensure complete medication extraction.
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