Effects of Broad Spectrum Antibiotics on Measurement of Immunosuppressant Drugs

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Antibiotics used parenterally can affect blood drug level measurements, as measured in diagnostic tests. To investigate the effect of six different antibiotics commonly used in intensive care units on tacrolimus, sirolimus, everolimus and cyclosporin A levels measured by mass spectrometry. Ampicillin + sulbactam (AB1, IV, 1 g), imipenem + cilastatin sodium (AB2, IV, 500 mg), piperacillin + tazobactam (AB3, 4.5 g, IV), ertapenem (AB4, IV, 1 g), meropenem trihydrate (AB5, 500 mg, IV) and ceftriaxone (AB6, 1 g, IV) antibiotics were used for the interference assay. Measurements were performed on the Shimadzu 8045 (Japan) LC-MS/MS instrument. Bias values were calculated. The least affected immunosuppressant was cyclosporine A (between -6.88% and 3.40%). The most affected were everolimus and sirolimus. Ertapenem caused negative interference on the level of everolimus at the rate of -27.34% and sirolimus at the rate of -26.79%. Piperacillin + tazobactam and imipenem + cilastatin sodium caused positive interferences on sirolimus at the rate of 24.24% and 22.73%, respectively. Ampicillin + sulbactam, meropenem trihydrate and ceftriaxone affected the sirolimus levels at lower rates (-4.49%, 5.93% and 9.86%). Everolimus levels deviated at the rate of -11.21% to -16.99% due to imipenem + cilastatin sodium, meropenem trihydrate and ceftriaxone. This study demonstrated the potential of antibiotic use affecting immunosuppressant levels. Antibiotic interference, especially in transplant patients, may cause erroneous immunosuppression, increasing the likelihood of rejection.