RESUMO
The use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) is increasing rapidly for patients with diabetes, heart failure, and chronic kidney disease. These medications can cause euglycemic diabetic ketoacidosis in the perioperative period, and the Food and Drug Administration recently updated their recommendations that they be held for at least 3-to-4 days preoperatively. There is a paucity of guidelines for the perioperative management of patients taking SGLT2i who present for emergent surgery or elective surgery having not held the medications per Food and Drug Administration guidelines. At the University of Pennsylvania, a multidisciplinary team from the Departments of Anesthesiology, Endocrinology, and Pharmacy has developed comprehensive guidelines detailing preoperative, intraoperative, and postoperative management for patients using these medications. In this article, the authors present these guidelines and discuss challenges encountered while implementing them at a large academic medical center with satellite hospitals and surgery centers with varying resources and patient populations.
Assuntos
Diabetes Mellitus Tipo 2 , Cetoacidose Diabética , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Cetoacidose Diabética/tratamento farmacológico , Glucose , SódioRESUMO
BACKGROUND: Voriconazole is an azole antifungal utilized for prophylaxis and treatment of invasive fungal infections in hematologic patients. Previous studies have revealed decreased efficacy and increased toxicity with subtherapeutic <1 mcg/mL and supratherapeutic > 4 mcg/mL levels. A voriconazole dose modification guideline was introduced in July 2014 based on a retrospective analysis. OBJECTIVE: The primary objective was to evaluate the voriconazole dose modification guideline. Secondary objectives were to identify patient-specific characteristics that contribute to inadequate levels, adverse effects, and breakthrough invasive fungal infections. METHODS: This prospective study included 128 patients with 250 admissions who received voriconazole from July 2014 to February 2016. Eligible adult patients receiving voriconazole for prophylaxis or treatment with at least one trough level, drawn appropriately, were included. Demographics, adverse effects, and breakthrough invasive fungal infections were documented. RESULTS: Voriconazole use was categorized as: new start, new start with loading dose, or continuation of home therapy. The median initial levels were 1.5, 3.5, and 1.7 mcg/mL with 62% (73/119), 55% (6/11), and 60% (72/120) within the therapeutic range, respectively. Using the voriconazole dose modification guideline, 80% were within goal by the second dose adjustment. Age ≤ 30 and BMI ≤ 25 kg/m2 had higher rates of subtherapeutic levels in the new start cohorts (p = 0.024 and p = 0.009). Approximately 7.6% of patients experienced an adverse effect with neurologic/psychological being the most common. A total of 8.5% of patients had a possible, probable or proven breakthrough invasive fungal infections while on voriconazole. CONCLUSION: Using the voriconazole dose modification guideline, the number of patients that reached therapeutic range improved from 36% to 80% by the second dose adjustment (p = 0.007). This voriconazole dose modification guideline can be utilized to help dose and adjust voriconazole in order to achieve therapeutic levels.
Assuntos
Antifúngicos/administração & dosagem , Neoplasias Hematológicas/complicações , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/prevenção & controle , Voriconazol/administração & dosagem , Adulto , Fatores Etários , Idoso , Antifúngicos/efeitos adversos , Antifúngicos/sangue , Índice de Massa Corporal , Feminino , Humanos , Infecções Fúngicas Invasivas/etiologia , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Estudos Prospectivos , Voriconazol/efeitos adversos , Voriconazol/sangue , Adulto JovemRESUMO
BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and infective endocarditis (IE) have become increasingly difficult to treat over the past decade, with suboptimal response rates of less than 50%. Although vancomycin and daptomycin are standard therapeutic options, treatment failures with either or both agents are common. Telavancin is a lipoglycopeptide antibiotic with activity against MRSA. In vitro, telavancin displays bactericidal activity and has lower minimum inhibitory concentrations to MRSA than vancomycin. METHODS: We present a retrospective, case-series report of 14 patients treated with telavancin for refractory MRSA bacteremia with and without IE at our institution from 9 September 2010 to 2 April 2012. RESULTS: Of the 14 patients who received telavancin for refractory MRSA bacteremia and IE, eight survived their inpatient admission and were able to be followed for 30 days. The overall survival rate was 57% (n = 8). Of the eight surviving patients, five were diagnosed with MRSA IE and the remaining three were diagnosed with complicated MRSA bacteremia. All six patients who did not survive the inpatient admission were diagnosed with left-sided IE involving the mitral valves. CONCLUSIONS: This retrospective case series provides clinical evidence for the use of telavancin as a treatment option for refractory MRSA bacteremia and IE. With limited effective agents in the treatment of MRSA-complicated bacteremia and IE, telavancin represents a potential treatment option. Further randomized, controlled trials are necessary to define the optimal role of telavancin in the treatment of MRSA bacteremia and IE.
Assuntos
Aminoglicosídeos/uso terapêutico , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Endocardite Bacteriana/tratamento farmacológico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológico , Adulto , Idoso , Aminoglicosídeos/administração & dosagem , Bacteriemia/microbiologia , Bacteriemia/mortalidade , Endocardite Bacteriana/microbiologia , Endocardite Bacteriana/mortalidade , Feminino , Humanos , Lipoglicopeptídeos , Masculino , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Pessoa de Meia-Idade , Estudos Retrospectivos , Terapia de Salvação , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/mortalidade , Taxa de Sobrevida , Fatores de Tempo , Adulto JovemRESUMO
Vancomycin is a glycopeptide antibiotic used in the treatment of gram-positive infections including methicillin-resistant Staphylococcus aureus (MRSA). The most common adverse reaction to vancomycin is red man syndrome, which is a histaminergic reaction causing a rash on the upper torso, neck, and face after rapid infusion of the drug. Less commonly, vancomycin has been associated with thrombocytopenia. The etiology is believed to be the induction of drug-dependent antibodies, which in turn cause immune-mediated destruction of platelets. We describe a 41-year-old man who received two courses of vancomycin for the treatment of MRSA pneumonia and then experienced a decline in platelet count to a nadir of 15 x 10³/mm³. Vancomycin was discontinued, doxycycline was started, and the patient's platelet count rebounded over the next 6 days. The patient was readmitted to the hospital 2 months later for MRSA bacteremia and was rechallenged with vancomycin. He again experienced a decline in platelet count. Vancomycin was discontinued, and daptomycin was started. The patient's platelet count rebounded to normal levels over the next 5 days. Although the patient experienced acute thrombocytopenia after vancomycin exposure, no bleeding complications occurred, and the patient's platelet count rebounded to normal after the discontinuation of vancomycin. The patient had no other known risk factors for the development of rapid thrombocytopenia. Use of the Naranjo adverse drug reaction probability scale indicated a definite relationship (score of 9) between the patient's development of thrombocytopenia and vancomycin therapy. Although vancomycin was the presumed cause of thrombocytopenia in this patient, no drug-dependent antibody was isolated from blood samples collected after both exposures to vancomycin (analyzed by using a screening assay to identify drug-dependent antibodies to vancomycin [developed by the BloodCenter of Wisconsin]). Although the evidence supporting vancomycin induction of antibody-mediated destruction of platelets was lacking, further studies delineating alternate mechanisms of platelet destruction are warranted. Therefore, even in the absence of a positive antibody test, vancomycin should still be considered in the differential diagnosis as a cause of drug-induced thrombocytopenia.