Minimum inhibitory concentrations (MIC) determination of TB drugs and broad-spectrum antibiotics inM.tuberculosiswith M/X/TDR

The problem of justifying the choice of the most effective regimens for TB with MDR, XDR and to all 1 st - and 2 nd -line (TDR- total drug resistance) is very urgent. This is due to that conventional DSTs based on critical concentrations (CC) do not fully correspond to the main pharmacokinetic parameters (PP) of drugs used in the forced modes of such patients9 treatment. Aim: Estimation MTB drug susceptibility polymorphism in linking with PP as an aid for MDR TB treatment. Method: 108 MTB M/X/TDR clinical strains were selected by testing on solid LJ medium. MICs were tested in liquid culture medium Middlebrook 7H9/OADC in a 96-well plate (Sensititre) for TB drugs and additive antibiotics. MIC results were corresponded with the basic drug pharmacokinetic parameters (Cmax and T1/2). Results: The distribution of MIC (mg/l): 12.5% Str MIC≤8; 5% H MIC≤2; 100% Rif≥8; 52% Rifab MIC≤1.0; 78% E MIC≤8; 35% Km MIC≤5; 58% Am MIC≤2; 62% Cs MIC≤64; 25% MIC Ofl≤4; 25% MIC Ciprofl≤2; 78% MIC Mox≤4; 55% MIC Ethio≤10; 78% MIC PAS≤4; 98% MIC Lz≤2; 38% MIC Clarithromycin≤1; 74% MIC Co-trimoxazole≤1.9/65; 66% MIC Doxycycline-Dox≤4; 18% MIC Imip≤8; 12.5% MIC Augmentin≤4/2; 42% MIC Minocycline-Min≤4. MIC breakpoints were corresponded to the maximum permissible doses of drugs. MTB resistance often were to Cephalosporins. Promising may be Co-trimoxazole, Dox, Min as an additive drugs. MIC determination for Cycloserine, Augmentin apparently require the other design of a test system. Conclusion: Using the MIC and PP for drugs helped to justify the appointment of the most effective drugs, their dosage and mode of administration in the intensive phase of M/X/TDR TB treatment.