Safety analysis of fidaxomicin in comparison with oral vancomycin for Clostridium difficile infections.

Fidaxomicin is a novel macrocyclic antibiotic recently approved by the US Food and Drug Administration for the treatment of Clostridium difficile-associated diarrhea in adults. We reviewed safety data from nonclinical studies and clinical trials (phases 1, 2A, and 3) with fidaxomicin. In nonclinical studies, fidaxomicin was administered orally at approximately 1 g/kg/d to dogs for up to 3 months with no significant target-organ toxicities observed. A total of 728 adults have received oral fidaxomicin in clinical trials to date: 116 healthy volunteers and 612 patients with C. difficile infection. In phase 3 clinical trials, fidaxomicin was well tolerated, with a safety profile comparable with oral vancomycin. There were no differences in the incidence of death or serious adverse events between the 2 drugs. Fidaxomicin appears to be well tolerated. Continued monitoring of adverse events in the postmarketing setting will provide additional information about the full safety profile of fidaxomicin.

Intravascular Cooling in the Treatment of Stroke (ICTuS): early clinical experience.

We sought to evaluate the safety and feasibility of mild therapeutic hypothermia using an endovascular temperature management system in awake acute ischemic stroke patients. The Intravascular Cooling in the Treatment of Stroke (ICTuS) study was an uncontrolled, multicenter development and feasibility study of conscious patients (n = 18) presenting within 12 hours of onset of an acute ischemic stroke at 5 clinical sites in the United States. Enrolled patients were to undergo core temperature management using an endovascular cooling system to induce and maintain mild, therapeutic hypothermia (target temperature of 33.0 degrees C) for a period of either 12 or 24 hours, followed by controlled rewarming to 36.5 degrees C over the subsequent 12-hour period. Nine patients underwent 12 hours of cooling followed by 12 hours of controlled rewarming, and 6 patients underwent 24 hours of cooling followed by 12 hours of controlled rewarming. Three patients underwent <1.5 hours of hypothermia due to clinical or technical issues. We also developed an antishivering regimen using buspirone and meperidine administered prophylactically to suppress shivering. The endovascular cooling catheter was well tolerated, with acceptable adverse event rates. Increasing the duration of hypothermia administration from 12 hours to 24 hours did not appear to increase the incidence or severity of adverse effects. Endovascular cooling with a proactive antishivering regimen can be accomplished in awake stroke patients. Further studies are needed to establish the safety and efficacy of this approach.

Comparison of endovascular and surface cooling during unruptured cerebral aneurysm repair.

OBJECTIVE: To compare endovascular versus surface methods for the induction and reversal of hypothermia during neurosurgery in a multicenter, prospective, randomized study. METHODS: Patients undergoing elective open craniotomy for repair of an unruptured cerebral aneurysm (n = 153) were randomly assigned (2:1) to undergo whole-body hypothermia to 33 degrees C, either with an endovascular cooling device placed in the inferior vena cava via the femoral vein (n = 92) or with a surface convective air blanket (n = 61). Active rewarming was accomplished using the same devices. RESULTS: Cooling rates in endovascular and surface blanket groups averaged 4.77 and 0.87 degrees C/h, respectively (P < 0.001). When the first temporary arterial or aneurysm clip was placed, 99% of endovascular patients and 20% of surface blanket patients had reached the target of 33 degrees C (P < 0.001). Obese patients were cooled efficiently with the endovascular approach (3.56 degrees C/h). Rewarming rates averaged 1.88 degrees C/h for endovascular patients and 0.69 degrees C/h for surface blanket patients (P < 0.001). By the end of surgery, 89 and 53% of these patients, respectively, had rewarmed to at least 35 degrees C (P < 0.001). On leaving the operating room, 14% of endovascular patients and 28% of surface blanket patients were still intubated (P = 0.035). The overall safety of the two procedures was comparable. No clinically significant catheter-related thrombotic, bleeding, or infectious complications were reported in the endovascular group. CONCLUSION: Endovascular cooling provided superior induction, maintenance, and reversal of hypothermia compared with the surface blanket, without an increase in complications. Endovascular cooling may have clinical benefit for patients undergoing cerebrovascular surgery, as well as patients with acute stroke, head injury, or acute myocardial infarction.