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PURPOSE: Post-neurosurgical intracranial infection caused by carbapenem-resistant gram-negative bacteria (CRGNB) is a life-threatening complication. This study aimed to assess the current practices and clinical outcomes of intravenous (IV) combined with intraventricular (IVT)/intrathecal (ITH) polymyxin B in treating CRGNB intracranial infection. METHODS: A retrospective study was conducted on patients with post-neurosurgical intracranial infection due to CRGNB from January 2013 to December 2020. Clinical characteristics and treatment outcomes were collected and described. Kaplan-Meier survival and multivariate logistic regression analyses were performed. RESULTS: The study included 114 patients, of which 72 received systemic antimicrobial therapy combined with IVT/ITH polymyxin B, and 42 received IV administration alone. Most infections were caused by carbapenem-resistant Acinetobacter baumannii (CRAB, 63.2%), followed by carbapenem-resistant Klebsiella pneumoniae (CRKP, 31.6%). Compared with the IV group, the IVT/ITH group had a higher cerebrospinal fluid (CSF) sterilization rate in 7 days (p < 0.001) and lower 30-day mortality (p = 0.032). In the IVT/ITH group, patients with CRKP infection had a higher initial fever (p = 0.014), higher incidence of bloodstream infection (p = 0.040), lower CSF sterilization in 7 days (p < 0.001), and higher 30-day mortality (p = 0.005) than those with CRAB infection. Multivariate logistic regression analysis revealed that the duration of IVT/ITH polymyxin B (p = 0.021) was independently associated with 30-day mortality. CONCLUSIONS: Intravenous combined with IVT/ITH polymyxin B increased CSF microbiological eradication and improved clinical outcomes. CRKP intracranial infections may lead to more difficult treatment and thus warrant attention and further optimized treatment.
Assuntos
Antibacterianos , Carbapenêmicos , Bactérias Gram-Negativas , Infecções por Bactérias Gram-Negativas , Polimixina B , Humanos , Polimixina B/uso terapêutico , Polimixina B/administração & dosagem , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/mortalidade , Bactérias Gram-Negativas/efeitos dos fármacos , Idoso , Adulto , Injeções Espinhais , Procedimentos Neurocirúrgicos/efeitos adversos , Resultado do Tratamento , Injeções IntraventricularesRESUMO
Background: The role of hospital pharmacists has shifted from primarily ensuring drug supply to providing comprehensive pharmaceutical care. To accommodate this shift, new positions are needed. The traditional training model for hospital pharmacists is no longer sufficient for the evolving demands of pharmaceutical care and these new roles. This study aimed to describe the development of a position-oriented learning system explicitly tailored for hospital pharmacists and to assess its impact on workforce development and pharmacy service. Methods: The position-oriented learning system for hospital pharmacists, aimed at enhancing training and workforce development, was evaluated based on two critical criteria: the completion rate of learning modules and the subsequent improvement in pharmaceutical care at the hospital. The completion rate assessed the engagement and effectiveness of the training content. At the same time, the improvement in pharmaceutical care evaluated practical outcomes such as percentages of patients who received pharmaceutical care and percentages of inappropriate medication orders intercepted. Results: In 2021, 218 employees participated in the learning system. The pharmacy department has identified 22 pharmacists for various positions through this system. The quantity and quality of pharmaceutical care have improved significantly. Conclusion: The position-oriented diversified learning system achieves the perfect combination of department development direction and individual career planning of employees. The learning system can significantly improve the learning efficiency of pharmacists, enhance the quality of various pharmaceutical care, and promote the development of disciplines.
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Histone deacetylase 9 (HDAC9) is implicated in ischemic stroke by genome-wide association studies. We conducted a series of experiments using a mouse model of ischemic stroke (middle cerebral artery occlusion followed by reperfusion) to examine the potential role of HDAC9. Briefly, HDAC9 was upregulated in the penumbra. Deletion of HDAC9 from neurons reduced infarction volume, inhibited neuronal apoptosis in the penumbra, and improved neurological outcomes. HDAC9 knockout from neurons in the penumbra upregulated cGMP-dependent kinase II (cGK II), blocking which abrogated the protective effects of HDAC9 deletion. Mechanistically, HDAC9 interacts with the transcription factor MEF2, thereby inhibiting MEF2's binding to the promoter region of the cGK II gene, which results in the suppression of cGK II expression. Inhibiting the interaction between HDAC9 and MEF2 by BML210 upregulated cGK II and attenuated ischemic injury in mice. These results encourage targeting the HDAC9-MEF2 interaction in developing novel therapy against ischemic stroke.