A hybrid of montmorillonite (Mnt) and rifampicin (RIF) was synthesized and the structure and stability of the drug carrier system clarified. Density functional theory calculations involving dispersion corrections (DFT-D3) were performed to characterize interactions acting in the interlayer space of montmorillonite intercalated with rifampicin. The structure and stability of the RIF-Mnt intercalated complex were determined. Calculations revealed the deformation of the molecular structure of rifampicin after intercalation into the Mnt interlayer space due to the clay environment. The ansa chain of RIF was bent in the interlayer space compared with the structure of the RIF molecule in the monocrystal. RIF was keyed into the Mnt surface by means of numerous hydrogen bonds of weak to moderate strength. The calculated vibrational spectrum from ab initio molecular dynamics (AIMD) was in good agreement with the FTIR measured spectra and helped to analyze the overlapped vibrational bands. Based on analysis of structural stability, theoretical calculations revealed that Mnt is a suitable drug carrier for delayed release of the RIF drug. Batch adsorption experiments showed the large adsorption capacity of montmorillonite for RIF.

We screened tuberculosis (TB) contacts as an outbreak investigation with tuberculin skin test (TST) and interferon-gamma release assay (IGRA). We evaluated adverse events and TB incidence in all persons screened after rifampicin (RFP) prophylaxis, and specifically assessed the new TB cases in relation to initial TST and IGRA results. The 180 contacts were divided into four groups: TST+/IGRA+ (n=101), TST+/IGRA− (n=22), TST−/IGRA+ (n=16), and TST–/IGRA– (n=41). RFP treatment (4 months) was prescribed only to the TST+/IGRA+ group. Of 87 contacts who initiated prophylaxis, adverse events occurred in 21 contacts (24·1%) including hepatotoxicity (11·5%), flu-like syndrome (5·7%), and thrombocytopenia (3·4%). TB developed in two TST+/IGRA+ subjects after completion of prophylaxis, including one multidrug-resistant (MDR)-TB case during 21·8 months of follow-up. Adverse events were frequent, and development of TB including MDR-TB occurred after RFP prophylaxis.