Emerging issue of fluconazole-resistant candidemia in a tertiary care hospital of southern italy: time for antifungal stewardship program

An increased number of patients is at risk of Candida spp. bloodstream infection (CBSI) in modern medicine. Moreover, the rising of antifungal resistance (AR) was recently reported. All consecutive CBSI occurred in our Hospital (consisting of 1,370 beds) between 2015 and 2018, were reviewed. For each case, Candida species, AR pattern, ward involved and demographic data of patients were recorded. Overall, 304 episodes of CBSI occurred, with a median (q1:first-,q3:third quartile) of 77 (71-82) CBSI/year. Over the years, a significant increase of CBSI due to C. albicans compared to non-albicans strains was recorded in medical wards (from 65% to 71%, p=0.030), while this ratio remained stable in others. An increase of resistant strains to multiple antifungals such as C. guillermondii was noticed in recent years (from 0% to 9.8%, p=0.008). Additionally, from 2015 to 2018 an increase in fluconazole-resistance was recorded in our Hospital (from 7.4% to 17.4%, p=0.025) and a slight increase in voriconazole-resistance (from 0% to 7% in 2018, p=0.161) was observed, while resistance to echinocandin and amphotericin B remained firmly below 2%.This study suggests a rapid spread of antifungal resistance in our Hospital; therefore, an appropriate antifungal stewardship programs is urgently warranted.     

Cross-species comparison of the metabolism and excretion of selexipag

1. The metabolism of the prostacyclin receptor agonist selexipag (NS-304; ACT-293987) and its active metabolite MRE-269 (ACT-333679) has been investigated in liver microsomes and hepatocytes of rats, dogs, and monkeys. MRE-269 formation is the main pathway of selexipag metabolism, irrespective of species. Some interspecies differences were evident for both compounds in terms of both metabolic turnover and metabolic profiles. The metabolism of MRE-269 was slower than that of selexipag in all three species.

2. The metabolism of selexipag was also studied in bile-duct-cannulated rats and dogs after a single oral and intravenous dose of [¹⁴C]selexipag. MRE-269 acyl glucuronide was found in both rat and dog bile. Internal acyl migration reactions of MRE-269 glucuronide were identified in an experiment with the synthetic standard MRE-6001.

3. MRE-269 was the major component in the faeces of rats and dogs. In ex vivo study using rat and dog faeces, selexipag hydrolysis to MRE-269 by the intestinal microflora is considered to be a contributory factor in rats and dogs.

4. A taurine conjugate of MRE-269 was identified in rat bile sample. Overall, selexipag was eliminated via multiple routes in animals, including hydrolysis, oxidative metabolism, conjugation, intestinal deconjugation, and gut flora metabolism.     

Autonomic neuropathy as post-acute sequela of SARS-CoV-2 infection: a case report

Journal of NeuroVirology - Symptoms of autonomic dysfunction, particularly those of orthostatic intolerance, continue to represent a major component of the currently recognized post-acute sequelae...     

Sativex-induced neurobehavioral effects: causal or concausal? A practical advice!

Nabiximols (Sativex) is an oromucosal spray, containing delta-9 tetrahydrocannabinol (THC) and cannabidiol (CBD), used as treatment for unresponsive spasticity in multiple sclerosis (MS) patients. Sativex is thought to not affect cognition or induce any psychiatric problem at the doses generally used. Nonetheless, it is known that the concomitant use of more than one muscle-relaxant drugs can result in additive neuropsychiatric effects. Herein we describe a case of a woman affected by MS and treated with baclofen and methylprednisolone, who developed important behavioral changes, including suicidal ideation, after 4 weeks of Sativex administration. We are not completely able to state if Sativex alone was responsible for our patient’s psychiatric symptoms, in reason of the concomitant use of the other drugs.In conclusion, physicians should pay more attention when prescribing drugs to MS patients affected by spasticity, including Sativex, since neurobehavioral side effects may emerge especially in predisposed individuals.