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Effect of metronidazole use on tacrolimus concentrations in transplant patients treated for C lostridium difficile
Author(s) -
Early C.R.,
Park J.M.,
Dorsch M.P.,
Pogue K.T.,
Hanigan S.M.
Publication year - 2016
Publication title -
transplant infectious disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.69
H-Index - 67
eISSN - 1399-3062
pISSN - 1398-2273
DOI - 10.1111/tid.12588
Subject(s) - metronidazole , medicine , vancomycin , confidence interval , tacrolimus , gastroenterology , trough level , pharmacokinetics , antibiotics , transplantation , microbiology and biotechnology , genetics , bacteria , biology , staphylococcus aureus
Background Two case reports suggest that metronidazole treatment for C lostridium difficile infections ( CDI ) increases tacrolimus ( TAC ) trough levels. The primary objective of this study was to determine the clinical significance of this potential interaction in transplant patients receiving CDI treatment. Currently, no robust literature exists to estimate a magnitude of pharmacokinetic interaction between metronidazole and TAC . Methods In this retrospective study, the effects of CDI and metronidazole treatment on TAC levels in 52 adult solid organ transplant patients were investigated. The primary outcome was to determine the difference in dose‐normalized TAC levels between baseline and symptom resolution in patients treated with metronidazole or vancomycin. The secondary outcome was to determine the difference in dose‐normalized TAC levels at baseline and CDI diagnosis. Results The average change in log‐transformed dose‐normalized TAC levels from baseline to symptom resolution was 0.99 for metronidazole ( n = 35) and 1.04 for vancomycin ( n = 17) treatment. The mean difference between the groups was 0.96 (95% confidence interval: 0.74–1.24). No significant difference was found between dose‐normalized TAC levels at CDI diagnosis and baseline ( P = 0.37). Conclusion CDI treatment with metronidazole was not associated with a >30% increase in TAC levels compared with vancomycin. Both treatment groups required TAC dose adjustments to maintain goal TAC levels and those treated with metronidazole did not require a significantly greater dose adjustment.