Ampicillin-resistant and vancomycin-susceptible Enterococcus faecium bacteremia: a clinical narrative review.

INTRODUCTION: Enterococcus faecium is a commensal microorganism that can cause infections such as bacteremia. Incidence of ampicillin-resistant and vancomycin-susceptible E. faecium (EfARSV) bacteremia is on the rise, and the mortality rate is high. Despite much data, the most appropriate treatment remains a question. AREAS COVERED: This article mostly reviews the relevant aspects of EfARSV bacteremia: microbiology, gastrointestinal tract colonization and invasion, antibiotic resistance, epidemiology, risk factors, mortality, and treatment, including pharmacologic components of employed agents and related clinical evidence. A literature search was conducted on PubMed on 31 July 2022, which was updated on 15 November 2022. EXPERT OPINION: EfARSV bacteremia presents high mortality. However, it is uncertain whether mortality is attributable to or a marker of severity/comorbidities. Considering its antibiotic resistance pattern, EfARSV is considered a difficult-to-treat microorganism. Glycopeptides have been used to treat EfARSV, with linezolid and daptomycin serving as potential alternative agents. Yet, the use of daptomycin is controversial due to a higher risk of treatment failures. Clinical evidence on this issue is scarce, unfortunately, and subject to many limitations. Despite increased incidence and mortality, EfARSV bacteremia presents multiple aspects to be addressed in well-conducted studies.

Antibiotic desensitization as a potential tool in antimicrobial stewardship programs: retrospective data analysis and systematic literature review.

OBJECTIVES: Antibiotic allergy labels (AAL) are related to worse therapeutic results. Strategies to improve the management of these patients, such as the implementation of antibiotic desensitization, are essential for Antimicrobial Stewardship Programs (ASP). The aim of our study is to evaluate the efficacy and safety of antibiotic desensitization procedures for the management of patients with AAL. METHODS: A retrospective study from 2015 to 2022 was performed to describe all antibiotic desensitization conducted in our institution, within the framework of ASP. A systematic literature review using electronic databases, such as PubMed, was also done to identify studies describing antibiotic desensitization between 2000 and 2022. RESULTS: Sixteen antibiotic desensitization protocols were carried out in our institution. In fourteen cases, the desensitization was successfully completed, and the antibiotic could be used to treat the infection. In the systematic review, twenty-two studies were included, with a total of 202 desensitization episodes . In 97% of them, the desensitization was completed successfully. No desensitization-related mortality was observed neither in our cohort nor in literature review. CONCLUSIONS: Antibiotic desensitization strategies should be considered a safe and effective tool that can be included in ASP for patients with a high risk of or confirmed allergy to penicillin.

Pharmacological management of antifungal agents in pulmonary aspergillosis: an updated review.

INTRODUCTION: Aspergillus may cause different types of lung infections: invasive, chronic pulmonary or allergic bronchopulmonary aspergillosis. Pharmacological management with antifungals poses as a challenge. Patients diagnosed with pulmonary aspergillosis are complex, as well as the problems associated with antifungal agents. AREAS COVERED: This article reviews the pharmacology of antifungal agents in development and currently used to treat pulmonary aspergillosis, including the mechanisms of action, pharmacokinetics, pharmacodynamics, dosing, therapeutic drug monitoring and safety. Recommendations to manage situations that arise in daily clinical practice are provided. A literature search of PubMed was conducted on November 15th, 2020 and updated on March 30th, 2021. EXPERT OPINION: Recent and relevant developments in the treatment of pulmonary aspergillosis have taken place. Novel antifungals with new mechanisms of action that extend antifungal spectrum and improve pharmacokinetic-related aspects, drug-drug interactions and safety are under current study. For those antifungals already marketed, new data related to pharmacokinetics, pharmacodynamics, dose adjustments in special situations, therapeutic drug monitoring and safety are available. To maximize efficacy and reduce the risk of associated toxicities, it is essential to choose the most appropriate antifungal; optimize its dose, interval, route of administration and length of treatment; and prevent side effects.

Eficacia y seguridad de una nueva formulación de enjuague bucal de dexametasona para el manejo de la estomatitis en pacientes con cáncer / Effectiveness and safety of a novel dexamethasone mouthwash formulation in managing stomatitis in cancer patients

OBJETIVO: Describir una nueva formulación de enjuague bucal con dexametasona y analizar su efectividad y seguridad en pacientes que reciben agentes antineoplásicos que producen estomatitis. MÉTODO: Estudio observacional prospectivo realizado en un hospital universitario entre marzo de 2017 y noviembre de 2019. Se incluyeron los pacientes que iniciaron everolimus. El tratamiento consistió en enjuagar con solución oral de dexametasona dos veces al día hasta la interrupción del tratamiento con everolimus. Se reclutó una segunda cohorte de pacientes con estomatitis inducida por otros agentes antineoplásicos con alta probabilidad de provocar estomatitis. Se evaluó la efectividad y seguridad del enjuague bucal con dexametasona. RESULTADOS: Se reclutaron nueve pacientes en profilaxis con formulación de enjuague bucal con dexametasona; seis pacientes presentaban un diagnóstico de cáncer de mama, dos de tumor neuroendocrino y uno de carcinoma renal. Cuatro pacientes desarrollaron estomatitis leve (grado 1-2) y tres pacientes descontinuaron everolimus por otros eventos adversos relacionados con el tratamiento. Se prescribió enjuague bucal con dexametasona en cinco pacientes con estomatitis existente como tratamiento. Todos los pacientes lograron una reducción significativa de la gravedad de la estomatitis tras iniciar el enjuague bucal con dexametasona. En general, el nuevo enjuague bucal con dexametasona fue bien tolerado y no se requirieron reducción de dosis ni interrupción debido a estomatitis. CONCLUSIONES: La nueva formulación de enjuague bucal con dexametasona podría considerarse una alternativa adecuada para el manejo de la estomatitis

OBJECTIVE: To present a new dexamethasone mouthwash formulation and analyze its effectiveness and safety among patients receiving stomatitis-producing antineoplastic agents. METHOD: Prospective observational study conducted in a university hospital between March 2017 and November 2019. Consecutive patients starting everolimus were enrolled. Patients were instructed to rinse dexamethasone mouthwash formulation twice daily until discontinuation of everolimus. A second cohort of patients with existing stomatitis induced by high probability of producing stomatitis chemotherapy therapies was also recruited to assess treatment effectiveness. Effectiveness and safety of dexamethasone mouthwash formulation was assessed. RESULTS: Dexamethasone mouthwash formulation was prescribed in nine patients as prophylaxis. Six patients were diagnosed with breast cancer, two with neuroendocrine tumor and one with renal cell carcinoma. Four patients developed mild stomatitis (grade 1-2) and three patients discontinued everolimus due to other treatment-related adverse events. In addition, dexamethasone mouthwash formulation was prescribed as treatment in five patients with existing stomatitis. All patients achieved a significant reduction in the severity of stomatitis after starting the dexamethasone mouthwash formulation. In both cohorts, dexamethasone mouthwash formulation was well tolerated and neither dose reduction nor discontinuation related to stomatitis was required. CONCLUSIONS: Dexamethasone mouthwash formulation could be considered as a suitable alternative for stomatitis management

Impact of non-formulary drugs on pharmacological prescription in hospitalised patients.

OBJECTIVES: The growing number of drugs on the market makes it necessary to adapt hospital formularies in order to ensure consistent drug coverage. The aim of this study was to evaluate the impact of the prescription of non-formulary drugs (NFD) on the therapeutic management of admitted patients. METHODS: This retrospective observational study included NFD prescriptions in patients hospitalised in a tertiary university hospital during the period 2012-2015. NFD prescriptions are displayed on the computerised medical order as a pending alert to be reviewed by the clinical pharmacists, who make a notation to the clinical course that includes a recommendation for an available therapeutic alternative when available in the hospital formulary. The degree of acceptance of the recommendation by physicians is recorded. RESULTS: Approximately 0.5% of patients hospitalised during the study period were affected by an NFD prescription. A total of 52 (9.5%) NFD were of doubtful therapeutic efficacy, five (0.9%) were non-replaceable drugs and 490 (89.4%) were prescriptions for drugs with an alternative available in the hospital formulary. The acceptance rate for the recommended alternative was 34.9% in the evaluable NFD prescriptions. No correlation was observed between the number of NFD prescriptions or the number of NFD and the availability index (drugs included in the hospital formulary in relation to the total number of drugs marketed). CONCLUSIONS: The number of patients with a NFD prescription was very low. The lack of correlation between the number of NFD or NFD prescriptions and the availability index demonstrated that the hospital formulary covers practically all therapeutic needs.

Effectiveness and safety of a novel dexamethasone mouthwash formulation in managing stomatitis in cancer patients.

OBJECTIVE: To present a new dexamethasone mouthwash formulation and  analyze its effectiveness and safety among patients receiving stomatitis-producing antineoplastic agents. METHOD: Prospective observational study conducted in a university hospital between March 2017 and November 2019. Consecutive patients starting everolimus were enrolled. Patients were instructed to rinse dexamethasone mouthwash formulation twice daily until discontinuation of everolimus. A second cohort of patients with existing stomatitis induced by  high probability of producing stomatitis chemotherapy therapies was also  recruited to assess treatment effectiveness. Effectiveness and safety of dexamethasone mouthwash formulation was assessed. RESULTS: Dexamethasone mouthwash formulation was prescribed in nine patients as prophylaxis. Six patients were diagnosed with breast cancer, two with neuroendocrine tumor and one with renal cell carcinoma. Four patients developed mild stomatitis (grade 1-2) and three patients  discontinued everolimus due to other treatment-related adverse events. In  addition, dexamethasone mouthwash formulation was prescribed as treatment in five patients with existing stomatitis. All patients achieved a significant reduction in the severity of stomatitis after starting the  dexamethasone mouthwash formulation. In both cohorts, dexamethasone  mouthwash formulation was well tolerated and neither dose reduction nor  discontinuation related to stomatitis was required. CONCLUSIONS: Dexamethasone mouthwash formulation could be considered as a  suitable alternative for stomatitis management.

Objetivo: Describir una nueva formulación de enjuague bucal con dexametasona y analizar su efectividad y seguridad en pacientes que reciben agentes antineoplásicos que producen estomatitis.Método: Estudio observacional prospectivo realizado en un hospital universitario entre marzo de 2017 y noviembre de 2019. Se incluyeron los pacientes que  iniciaron everolimus. El tratamiento consistió en enjuagar con solución oral de  dexametasona dos veces al día hasta la interrupción del tratamiento con  everolimus. Se reclutó una segunda cohorte de pacientes con estomatitis  inducida por otros agentes antineoplásicos con alta probabilidad de provocar  estomatitis. Se evaluó la efectividad y seguridad del enjuague bucal con  dexametasona.Resultados: Se reclutaron nueve pacientes en profilaxis con formulación de  enjuague bucal con dexametasona; seis pacientes presentaban un diagnóstico  de cáncer de mama, dos de tumor neuroendocrino y uno de carcinoma renal.  Cuatro pacientes desarrollaron estomatitis leve (grado 1-2) y tres pacientes  descontinuaron everolimus por otros eventos adversos relacionados con el  tratamiento. Se prescribió enjuague bucal con dexametasona en cinco pacientes  con estomatitis existente como tratamiento. Todos los pacientes lograron una  reducción significativa de la gravedad de la estomatitis tras iniciar el enjuague  bucal con dexametasona. En general, el nuevo enjuague bucal con  dexametasona fue bien tolerado y no se requirieron reducción de dosis ni  interrupción debido a estomatitis.Conclusiones: La nueva formulación de enjuague bucal con dexametasona podría considerarse una alternativa adecuada para el manejo de la estomatitis.

Propensity-Score Matched Comparative Study on Effects of Intravenous Human Serum Albumin Administration in Critically Ill Adult Patients Receiving Parenteral Nutrition.

BACKGROUND: The objective of this study was to assess the effect of intravenous human serum albumin administration (IV HSA) on nutrition markers, including non-serum-albumin plasma protein levels, in adult critically ill patients receiving parenteral nutrition (PN). METHODS: This was a retrospective study of prospectively collected data. Patients included in an initial cohort were patients who initiated IV HSA within 24 hours of start of PN. A second cohort who did not received IV HSA during PN was manually selected, matching several variables. Subsequently, both cohorts were propensity-score matched, resulting in 2 final cohorts: the cohort receiving IV HSA (ALB) and the cohort not receiving IV HSA (NOALB). RESULTS: A total of 42 patients, 21 in each cohort, entered the study. Both cohorts were similar in demographics, anthropometrics, comorbidities, diagnoses, PN composition, and severity of the disease, biochemistry, and nutrition markers. Patients in the ALB cohort received IV HSA at a dose of 30.0 g/day during 5 days. The ALB cohort presented higher values of final serum albumin level and serum albumin level change from baseline, but also presented lower values of final non-serum-albumin plasma protein levels and their change and lower final prealbumin. In addition, bilirubin in the ALB cohort increased, whereas it decreased in the NOALB cohort. CONCLUSION: Patients receiving IV HSA and PN for several days increased serum albumin level, but decreased non-serum-albumin plasma protein levels. In addition, bilirubin clearance could be slightly impaired in these patients.

Extremely high levels of vancomycin can cause severe renal toxicity.

Vancomycin has usually been associated with nephrotoxicity. Generally, this toxicity is presented as proximal tubular cells injury with or without necrosis and as acute interstitial nephritis. However, development of both lesions is uncommonly described in literature. We present a case of vancomycin-induced nephrotoxicity resulting in both acute interstitial nephritis and tubular cells damage confirmed by renal biopsy. Peak and trough levels of 77.11 and 63.60 µg/mL, respectively, were obtained at the first plasma determination. After 8 more plasma determinations and several hemodialysis sessions, vancomycin levels were undetectable 1 month after therapy was stopped. To our knowledge, this is the case report with the highest vancomycin trough levels developing both lesions and describing total vancomycin washout after a biopsy-proven vancomycin toxicity. In conclusion, early vancomycin therapeutic drug monitoring should be performed in order to avoid toxicities where, as seen in our patient, antibiotic exposure could last around 1 month after last dose administration.