Oral Gram-negative anaerobic bacilli as a reservoir of ß-lactam resistance genes facilitating infections with multiresistant bacteria.

Many ß-lactamases have been described in various Gram-negative bacilli (Capnocytophaga, Prevotella, Fusobacterium, etc.) of the oral cavity, belonging to class A of the Ambler classification (CepA, CblA, CfxA, CSP-1 and TEM), class B (CfiA) or class D in Fusobacterium nucleatum (FUS-1). The minimum inhibitory concentrations of ß-lactams are variable and this variation is often related to the presence of plasmids or other mobile genetic elements (MGEs) that modulate the expression of resistance genes. DNA persistence and bacterial promiscuity in oral biofilms also contribute to genetic transformation and conjugation in this particular microcosm. Overexpression of efflux pumps is facilitated because the encoding genes are located on MGEs, in some multidrug-resistant clinical isolates, similar to conjugative transposons harbouring genes encoding ß-lactamases. All these facts lead us to consider the oral cavity as an important reservoir of ß-lactam resistance genes and a privileged place for genetic exchange, especially in commensal strictly anaerobic Gram-negative bacilli.

Towards a real time release approach for manufacturing tablets using NIR spectroscopy.

The aim of this study was to use the near-infrared spectroscopy (NIRS) as a process analytical tool to evaluate the conformity of paracetamol tablets in terms of four Pharmacopoeia tests (content uniformity, hardness, disintegration time, friability) and to control in-line blend uniformity. Tablets were manufactured by direct compression. Three different active pharmaceutical ingredient (API) concentrations were manufactured and three different compaction pressures were used. Intact tablets were analysed by transmission mode with NIRS prior to European Pharmacopoeia tests that were used as reference methods. Partial least square (PLS) regression was selected to build the prediction NIR models for content uniformity, tablet hardness and disintegration time. The prediction of NIR content uniformity and tablet hardness methods were validated using the accuracy profile approach. The values of the root mean squared error of calibration (RMSEC) and the root mean squared error of prediction (RMSEP) for the disintegration time indicated the robustness and the global accuracy of the NIR model. Regarding the tablet friability test, the classification was based on K-nearest neighbours (KNN). Then tablet NIR analyses successfully allowed the prediction of their conformity. Compared to the time consuming Pharmacopoeia reference methods, the benefit of this nondestructive method is significant, especially for reducing batch release time.