Cure of XXXX despite serum concentrations of antituberculosis drugs below published reference ranges.

@entity1 @entity3110 @entity5585 @entity17208 @entity3109 @entity1215 @entity378
PRINCIPLES: Therapeutic target serum concentrations of first-line antituberculosis drugs have not been well defined in clinical studies in @entity378 ( @entity378 ) @entity1 . METHODS: We retrospectively investigated the estimated maximum serum concentrations (eCmax) of antituberculosis drugs and clinical outcome of @entity378 @entity1 with therapeutic drug monitoring performed between 2010-2012 at our institution, and follow-up until March 2014. The eCmax was defined as the highest serum concentration during a sampling period (2, 4 and 6 hours after drug ingestion). We compared the results with published eCmax values, and categorised them as either "within reference range", "low eCmax", or "very low eCmax".Low/very low eCmax-levels were defined as follows: @entity3109 2-3/<2 mg/l, @entity1215 4-8/<4 mg/l, @entity17208 0.2-0.3/<0.2 mg/l, @entity3110 1-2/<0.1 mg/l and @entity5585 <20 mg/l. RESULTS: Concentrations of antituberculosis drugs in 175 serum samples of 17 @entity1 with @entity378 were analysed. In 12 (71%) @entity1 , multiple therapeutic drug monitoring samples were collected over time, in 5 (29%) @entity1 only one sample was available for therapeutic drug monitoring. Overall, 94% of all @entity1 had at least one low antituberculosis drug concentration. Overall, 64% of all eCmax levels were classified as "low" or "very low". The eCmax was below the relelvant reference range in 80% of @entity3109 , 95% of @entity1215 , 30% of @entity5585 , and 30% of @entity3110 measurements. All but one @entity1 were cured of @entity378 . CONCLUSIONS: Although many antituberculosis drug serum concentrations were below the widely used reference ranges, 16 of 17 @entity1 were cured of @entity378 . These results challenge the use of the published reference ranges for therapeutic drug monitoring.
