Innate aminoglycoside resistance of Achromobacter xylosoxidans is due to AxyXY-OprZ, an RND-type multidrug efflux pump.

Achromobacter xylosoxidans is an innately multidrug-resistant pathogen which is emerging in cystic fibrosis (CF) patients. We characterized a new resistance-nodulation-cell division (RND)-type multidrug efflux pump, AxyXY-OprZ. This system is responsible for the intrinsic high-level resistance of A. xylosoxidans to aminoglycosides (tobramycin, amikacin, and gentamicin). Furthermore, it can extrude cefepime, carbapenems, some fluoroquinolones, tetracyclines, and erythromycin. Some of the AxyXY-OprZ substrates are major components widely used to treat pulmonary infections in CF patients.

Experimental investigation of MRgHIFU sonication with interleaved electronic and mechanical displacement of the focal point for transrectal prostate application.

High intensity focused ultrasound (HIFU) under MRI guidance may provide minimally invasive treatment for localized prostate cancer. In this study, ex vivo and in vivo experiments were performed using a prostate-dedicated endorectal phased array (16 circular elements arranged on a truncated spherical cap of radius 60 mm) and a translation-rotation mechanical actuator in order to evaluate the lesion formation and the potential interest of dual-modality (electronic and mechanical) interleaved displacement of the focus for volumetric sonication paradigms. Different sonication sequences, including elementary lesions, line scan, slice sweeping and volume sonications, were investigated with a clinical 1.5 T MR scanner. Two orthogonal planes (axial and sagittal) were simultaneously monitored using rapid MR thermometry (PRFS method) and the temperature and thermal dose maps were displayed in real time. No RF interferences were detected in MR acquisition during sonications. The shape of the thermal lesions in vivo was examined at day 5 post-treatment by MRI follow-up (T2w sequence and Gd-T1w-TFE) and postmortem histological analysis. This study suggests that electronic displacement of the focus (along the ultrasound propagation axis) interleaved with mechanical X-Z translations and rotation around B(0) can be a suitable modality to treat patient-specific sizes and shapes of a pathologic tissue. The electronic displacement of focus (achieved in less than 0.1 s) is an order of magnitude faster than the mechanical motion of the HIFU device (1 s latency). As an example, for an in vivo volumetric sonication with foci between 32 and 47 mm (7 successive line scans, 11 lines/slice, 4 foci/line) with applied powers between 17.4 and 39.1 Wac, a total duration of sonication of 408.1 s was required to ablate a volume of approximately 5.7 cm(3) (semi-chronic lesion measured at day 5), while the maximum temperature elevation reached was 30 °C. While electronic focusing is necessary to speed up the procedure, one should consider as a potential drawback the non-negligible risk for generating secondary lobes with full steering in 3D. Reference-free PRFS thermometry accurately removed the effects of B(o) dynamic perturbation in the vicinity of the moving transducer. Therefore, the dual-modality volumetric sonication paradigm represents a cost-effective technological compromise to induce the desired shape of the lesion in the prostate through the limited endorectal space, in a reasonable period of time and without side effects.