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Published on: May 24, 2024
Two suspected cases of immunoglobulin-mediated interference causing falsely low vancomycin concentrations with the
Mary Gunther1, Lynora Saxinger, Margaret Gray
1Pharmacy Services, University of Alberta Hospital, Edmonton, Alberta, Canada. mary.gunther@albertahealthservices.ca
Insights
High immunoglobulin levels can interfere with vancomycin measurements using the Beckman Coulter PETINIA assay, leading to falsely low results. Clinicians should consider assay interference when vancomycin levels don't match clinical expectations.
Area of Science:
- Clinical Chemistry
- Immunology
- Pharmacokinetics
Background:
- Vancomycin is a critical antibiotic for treating serious infections.
- Accurate therapeutic drug monitoring is essential for optimizing vancomycin efficacy and safety.
- Immunoassay interference can lead to misinterpretation of drug concentrations.
Observation:
- Two patients with immune-related comorbidities receiving vancomycin showed falsely low trough concentrations (<4 mg/L) via the Beckman Coulter particle-enhanced turbidimetric inhibition immunoassay (PETINIA).
- These low levels were inconsistent with appropriate vancomycin dosing regimens.
- Alternative testing methods confirmed expected vancomycin concentrations.
Findings:
- The Beckman Coulter PETINIA method for vancomycin measurement is susceptible to interference from high immunoglobulin levels.
- This interference results in a graded phenomenon, leading to falsely decreased serum vancomycin concentrations.
- Literature review identified two similar cases, supporting the hypothesis of immunoglobulin interference.
Implications:
- Clinicians must maintain a high index of suspicion for assay interference when measured vancomycin levels do not align with clinical presentation.
- Consideration of alternative immunoassay methods or direct measurement techniques may be necessary in patients with suspected immunoglobulin interference.
- This highlights the importance of understanding potential interferences in therapeutic drug monitoring assays.
Objective:
To describe 2 recent cases of suspected immunoglobulin-mediated interference with the Beckman Coulter particle-enhanced turbidimetric inhibition immunoassay (PETINIA) used to measure vancomycin serum or plasma concentrations and to review the existing literature.
Case Summary:
A 64-year-old woman with a history of multiple immune-related comorbidities received vancomycin for treatment of a prosthetic joint infection growing coagulase-negative Staphylococcus spp. A 33-year-old man with a history of Felty syndrome received vancomycin for the treatment of methicillin-resistant Staphylococcus aureus pneumonia. Both patients had multiple vancomycin trough concentrations determined using the Beckman Coulter PETINIA method and had measured concentrations reported as less than 4 mg/L despite appropriate vancomycin dosing for their size, age, and organ function. The patients' serum was then tested by alternative methods, which reported vancomycin concentrations consistent with those expected with the patients' dosing regimens.
Discussion:
Immunoglobulins are well known for interfering with chemistry assays. It is suspected that high levels of immunoglobulins in these 2 patients interfered with the accurate measurement of serum vancomycin concentrations. An objective causality assessment supported the interactions as being definite and probable, respectively. Two other cases of suspected immunoglobulin interference with vancomycin measurement have been reported in the literature when vancomycin concentrations were initially measured using the Beckman Coulter PETINIA method. In vitro studies support the hypothesis that immunoglobulin interference with vancomycin measurement by this method occurs and is a graded phenomenon.
Conclusions:
These cases suggest a high likelihood of immunoglobulin-mediated interference with the Beckman Coulter PETINIA method, which results in the reporting of falsely low vancomycin serum concentrations. When vancomycin concentrations do not correlate with what would be expected clinically, clinicians should have a high index of suspicion for potential assay interference.

