RESUMEN
BACKGROUND: Carbamazepine (CBZ) is an antiseizure medication known to induce the expression of cytochrome P4503A metabolic enzymes. Here, we describe a man living with HIV who underwent several changes in the daily dose of CBZ, which resulted in different induction effects on darunavir trough concentrations. METHODS: A 59-year-old man with HIV, successfully undergoing maintenance antiretroviral treatment with darunavir/cobicistat once daily (combined with raltegravir), was prescribed CBZ for recurrent trigeminal neuralgia. Over subsequent months, the patient underwent various changes in the doses (from 200 to 800 mg/d) and trough concentrations (from 3.6 to 18.0 mg/L) of CBZ, guided by clinical response to trigeminal neuralgia. RESULTS: A highly significant inverse association was observed between darunavir trough concentration and both CBZ dose or trough concentration (coefficient of determination >0.75, P < 0.0001). Ultimately, the darunavir dose was increased to 600 mg twice daily with ritonavir and dolutegravir to ensure optimal antiretroviral coverage, anticipating potential further uptitration of CBZ doses. CONCLUSIONS: The impact of CBZ on boosted darunavir exposure seemed to be dose- and concentration-dependent. The management of such drug-drug interactions in daily practice was facilitated through therapeutic drug monitoring. This case underscores the importance of a multidisciplinary approach that incorporates both antiretroviral and nonantiretroviral comedications contributing to the optimal management of polypharmacy in individuals living with HIV.
Asunto(s)
Carbamazepina , Darunavir , Interacciones Farmacológicas , Infecciones por VIH , Humanos , Darunavir/uso terapéutico , Darunavir/farmacocinética , Masculino , Persona de Mediana Edad , Carbamazepina/uso terapéutico , Carbamazepina/farmacocinética , Infecciones por VIH/tratamiento farmacológico , Neuralgia del Trigémino/tratamiento farmacológico , Ritonavir/uso terapéutico , Ritonavir/administración & dosificación , Anticonvulsivantes/farmacocinética , Anticonvulsivantes/uso terapéutico , Anticonvulsivantes/administración & dosificación , Piridonas/farmacocinética , Piridonas/uso terapéutico , Piridonas/sangre , Compuestos Heterocíclicos con 3 Anillos/farmacocinética , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/administración & dosificación , Piperazinas/uso terapéutico , Piperazinas/farmacocinética , Oxazinas/uso terapéutico , Oxazinas/farmacocinética , Relación Dosis-Respuesta a Droga , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/farmacocinética , Fármacos Anti-VIH/administración & dosificación , Monitoreo de Drogas/métodosRESUMEN
The humoral response to SARS-CoV-2 vaccination has shown to be temporary, although may be more prolonged in vaccinated individuals with a history of natural infection. We aimed to study the residual humoral response and the correlation between anti-Receptor Binding Domain (RBD) IgG levels and antibody neutralizing capacity in a population of health care workers (HCWs) after 9 months from COVID-19 vaccination. In this cross-sectional study, plasma samples were screened for anti-RBD IgG using a quantitative method. The neutralizing capacity for each sample was estimated by means of a surrogate virus neutralizing test (sVNT) and results expressed as the percentage of inhibition (%IH) of the interaction between RBD and the angiotensin-converting enzyme. Samples of 274 HCWs (227 SARS-CoV-2 naïve and 47 SARS-CoV-2 experienced) were tested. The median level of anti-RBD IgG was significantly higher in SARS-CoV-2 experienced than in naïve HCWs: 2673.2 AU/mL versus 610.9 AU/mL, respectively (p <0.001). Samples of SARS-CoV-2 experienced subjects also showed higher neutralizing capacity as compared to naïve subjects: median %IH = 81.20% versus 38.55%, respectively; p <0.001. A quantitative correlation between anti-RBD Ab and inhibition activity levels was observed (Spearman's rho = 0.89, p <0.001): the optimal cut-off correlating with high neutralization was estimated to be 1236.1 AU/mL (sensitivity 96.8%, specificity 91.9%; AUC 0.979). Anti-SARS-CoV-2 hybrid immunity elicited by a combination of vaccination and infection confers higher anti-RBD IgG levels and higher neutralizing capacity than vaccination alone, likely providing better protection against COVID-19.
Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/prevención & control , Inmunidad Humoral , Vacuna BNT162 , Vacunas contra la COVID-19 , Estudios Transversales , Pruebas de Neutralización , Anticuerpos Neutralizantes , Inmunoglobulina G , Anticuerpos Antivirales , VacunaciónRESUMEN
Staphylococcus aureus bacteraemia (SAB) is a life-threatening bloodstream infection. Improved adherence to quality-of-care indicators (QCIs) can significantly enhance patient outcomes. This quasi-experimental study evaluated the impact of a bundle of interventions on QCI adherence in adult patients with SAB. Additionally, a molecular rapid diagnostic test (mRDT) for S. aureus and methicillin resistance was introduced during weekdays. We compared pre-intervention (January-December 2022) and post-intervention (May 2023-April 2024) data on QCI adherence and time to appropriate treatment. A total of 56 and 40 SAB episodes were included in the pre- and post-intervention periods, respectively. Full QCI adherence significantly increased from 28.6% to 67.5% in the post-intervention period (p < 0.001). The mRDT diagnosed SAB in eight cases (26.6%), but the time to achieve appropriate target therapy did not improve in the post-intervention period (54 h (IQR 30-74) vs. 72 h (IQR 51-83), p = 0.131). The thirty-day mortality rate was comparable between the two periods (17.9% vs. 12.5%, p = 0.476). This study demonstrates that a bundle of interventions can substantially improve adherence to SAB management QCIs.
RESUMEN
INTRODUCTION: This paper describes how mortality among hospitalised COVID-19 patients changed during the first three waves of the epidemic in Italy. METHODS: This prospective cohort study used the Kaplan-Meier method to analyse the time-dependent probability of death of all of the patients admitted to a COVID-19 referral centre in Milan, Italy, during the three consecutive periods of: 21 February-31 July 2020 (first wave, W1), 1 August 2020-31 January 2021 (second wave, W2), and 1 February-30 April 2021 (third wave, W3). Cox models were used to examine the association between death and the period of admission after adjusting for age, biological sex, the time from symptom onset to admission, disease severity upon admission, obesity, and the comorbidity burden. RESULTS: Of the 2,023 COVID-19 patients admitted to our hospital during the study period, 553 (27.3%) were admitted during W1, 838 (41.5%) during W2, and 632 (31.2%) during W3. The crude mortality rate during W1, W2 and W3 was respectively 21.3%, 23.7% and 15.8%. After adjusting for potential confounders, hospitalisation during W2 or W3 was independently associated with a significantly lower risk of death than hospitalisation during W1 (adjusted hazard ratios [AHRs]: 0.75, 95% confidence interval [CI] 0.59-0.95, and 0.58, 95% CI 0.44-0.77). Among the patients aged >75 years, there was no significant difference in the probability of death during the three waves (AHRs during W2 and W3 vs W1: 0.93, 95% CI 0.65-1.33, and 0.88, 95% CI 0.59-1.32), whereas those presenting with critical disease during W2 and W3 were at significantly lower risk of dying than those admitted during W1 (AHRs 0.61, 95% CI 0.43-0.88, and 0.44, 95% CI 0.28-0.70). CONCLUSIONS: Hospitalisation during W2 and W3 was associated with a reduced risk of COVID-19 death in comparison with W1, but there was no difference in survival probability in patients aged >75 years.