Determination of Mutational Timing of Colistin-Resistance Genes through Klebsiella pneumoniae Evolution.

The emergence and dissemination of carbapenem-resistant Klebsiella pneumoniae (KP), one of the carbapenem-resistant Enterobacteriaceae (CRE), is now an emerging cause of antibiotic-resistant nosocomial infections associated with high rates of morbidity and mortality. Colistin, or polymyxin E, is a last-resort peptide antibiotic used to treat multidrug-resistant (MDR) Gram-negative bacterial infections including KP. Unfortunately, resistance to colistin is rising with increasing use in the clinical setting. Although clinical evidence links certain mutations to colistin resistance (COL-R) in KP, the origination and association of the mutations remain unclear. We hypothesize that the timing of COL-R mutations influences the development and progression of KP resistance to colistin. We performed planktonic and biofilm in vitro experimental evolutions of KP strain ATCC 43816 under increasing colistin concentrations to characterize the temporal regulation of critical COL-R mutations throughout COL-R progression. The resistance generation and mutation profiles of independently evolved bacterial populations with different lifestyles were compared. Genes with various functions theorize the timeline in which key mutations are generated and their roles in the progression of COL-R. Our results aim to advance the research and development of effective therapeutics to treat MDR bacterial infection as the dissemination of CRE continues to be a severe public health threat.

Comprehensive assessment of mechanical behavior of an extremely long stent graft to control hemorrhage in torso.

Traumatic vascular injuries, resulting from either civilian accidents or wounded soldiers, require new endovascular devices (i.e., stent graft) to rapidly control the excessive internal hemorrhage in torso region. Current stent designs are limited by their permanent nature, which is note well suited for emergent placement. A retrievable stent graft could regulate the internal bleeding temporarily, as fast as possible with the most feasible performance, until the patients arrive the hospital to receive the proper treatment. The novel endovascular device of this study is designed according to the anatomy of a porcine model with plans to transition to a human model in the future. The stent graft is manufactured using a substantially long nitinol backbone and covered selectively based on anatomic measurements, with highly stretchable expanded-polytetrafluoroethylene (ePTFE). In this study, our group comprehensively explored designing and manufacturing methods, and their impact on the stent graft performance. Geometric parameters and heat treatment conditions were investigated to show their effect on the radial force of the metallic backbone. As a retrievable device, the resistance force for retrieval as well as deployment were measured, and analyzed to be manipulated through ePTFE covering configurations. In vitro measurements for bleeding were measured using swine aorta to show the functionality of the stent graft under the simulated pulsatile flow circulation. Finally, the stent graft showed substantial effectiveness for hemorrhage control in vivo, using swine model. The new design and fabrication methods enable rapid hemorrhage control that can be removed at the time of a dedicated surgical repair.

Damage control of caval injuries in a porcine model using a retrievable Rescue stent.

OBJECTIVE: Early hemorrhage control before the operating room is essential to reduce the significant mortality associated with traumatic injuries of the vena cava. Conventional approaches present logistical challenges on the battlefield or in the trauma bay. A retrievable stent graft would allow rapid hemorrhage control in the preoperative setting when endovascular expertise is not immediately available and without committing a patient to the limitations of current permanent stents. This study details a refined retrievable Rescue stent for percutaneous delivery that was examined in a porcine survival model of penetrating caval hemorrhage. METHODS: A retrievable caval stent was reduced in delivery profile to a 9F sheath using finite element analysis. The final stent was constructed with a "petal and stem" design using nitinol wire followed by covering with polytetrafluoroethylene. Seven Yorkshire pigs (79-86 kg) underwent 22F injury of the infrarenal vena cava with intentional class II hemorrhage (1200 mL). Percutaneous deployment of the Rescue stent was used to temporize hemorrhage for 60 minutes, followed by resuscitation with cell saver blood and permanent caval repair. Hemorrhage control was documented with photography and angiography. Vital signs were recorded and laboratory values were measured out to 48 hours postoperatively. Data were examined with a repeated-measures analysis of variance. RESULTS: The profile of the caval Rescue stent was successfully reduced from 16F to 9F while remaining within fracture and shape memory limits for nitinol. In addition, both rapid deployment and recapture were preserved. Following intentional hemorrhage after caval injury, animals revealed a significant drop in mean arterial pressure (average, 30 mm Hg), acidosis, and elevated lactate level compared with before injury. Compared with uncontrolled hemorrhage, which resulted in death in <9 minutes, the Rescue stent achieved hemorrhage control in <1 minute after venous access in all seven animals. All animals were successfully recovered after permanent repair. There was no significant change in levels of transaminases, bilirubin, creatinine, or hemoglobin at 48 hours compared with preinjury baseline. CONCLUSIONS: A retrievable Rescue stent achieved rapid percutaneous hemorrhage control after a significant traumatic injury of the vena cava and allowed successful recovery of all injured animals. Further development of this approach may have utility in preoperative damage control of caval injuries.