Recommended doses of endovenous vancomycin are insufficient to achieve therapeutic concentrations in paediatric patients.

OBJECTIVES: Vancomycin therapeutic drug monitoring is challenging, especially in the paediatric population where evidence is scarce. The main objective of this study was to analyse the achievement of therapeutic concentrations of vancomycin in paediatric patients and to evaluate the current monitoring method (trough levels), doses used, and the time required to achieve target concentrations. METHODS: Paediatric patients on treatment and monitored with vancomycin from November 2019 to December 2021 were included. Those with only one determination of serum vancomycin concentration were excluded. Demographic variables, analytical and microbiological parameters and toxicity data were collected. Pharmacokinetic parameters were assessed at baseline and during treatment. RESULTS: 225 patients (40.9% female; 108 neonates, 49 infants and 68 children or adolescents) were included in the study. The main indications for vancomycin treatment were sepsis (33.9%) and fever of unknown origin (29.3%). Microbiological cultures were positive in 71.1%, mostly with Gram-positive bacteria (60.4%). Therapeutic levels of vancomycin were reached in only 20.1% of the participants in the first determination. After pharmacokinetic monitoring, 81.7% of patients reached therapeutic concentrations, requiring a 23% increase in the initial dose, a 2-day lag time and 1-2 dosage adjustments until the therapeutic concentration was reached. Of the total patients, 13 developed nephrotoxicity, nine neutropenia and one patient developed red man syndrome. CONCLUSIONS: In our sample of paediatric patients, the recommended doses of vancomycin were insufficient to achieve therapeutic concentrations. Revision of the recommendations and/or a change in the method of pharmacokinetic monitoring is crucial to optimise treatment in this population.

[Translated article] Paradoxical interaction between nirmatrelvir/ritonavir and voriconazole in a patient with COVID-19.

This case is based on a drug interaction between nirmatrelvir/ritonavir (approved drug for COVID-19) and voriconazole is presented, possibly derived from the bidirectional effect of ritonavir on the 2 main voriconazole metabolizing enzymes (cytochrome P450 3A and 2C19) ritonavir inhibits the former and induces the latter respectively. According to the main pharmacotherapeutic information databases, in the interaction between both drugs, a decrease in the area under the curve of voriconazole is expected due to the inducing effect of its metabolism; however, in the case we present, unexpectedly, a paradoxical effect occurs, according to what is described in literature, with the result of sustained supratherapeutic levels of voriconazole. Given the short treatment period with nirmatrelvir/ritonavir (5 days), the induction effect of ritonavir proposed in the studies on which the recommendations are based, where treatment with ritonavir is longer, does not occur.

Paradoxical interaction between nirmatrelvir/ritonavir and voriconazole in a patient with COVID-19. / Interacción paradójica entre nirmatrelvir/ritonavir y voriconazol en un paciente con COVID-19.

This case is based on a drug interaction between nirmatrelvir/ritonavir (approved drug for COVID-19) and voriconazole is presented, possibly derived from the bidirectional effect of ritonavir on the 2 main voriconazole metabolising enzymes (cytochrome P450 3A and 2C19) ritonavir inhibits the former and induces the latter respectively. According to the main pharmacotherapeutic information databases, in the interaction between both drugs, a decrease in the area under the curve of voriconazole is expected due to the. inducing effect of its metabolism; however, in the case we present, unexpectedly, a paradoxical effect occurs, according to what is described in literature, with the result of sustained supratherapeutic levels of voriconazole. Given the short treatment period with nirmatrelvir/ritonavir (5 days), the induction effect of ritonavir proposed in the studies on which the recommendations are based, where treatment with ritonavir is longer, does not occur.

Survival of Patient With Hemorrhagic Meningitis Associated With Inhalation Anthrax.

This report describes a 49-year-old male construction worker who acquired a Bacillus anthracis infection after working on a sheep farm. He experienced a severe respiratory infection, septic shock, and hemorrhagic meningoencephalitis with severe intracranial hypertension. After several weeks with multiple organ dysfunction syndrome, he responded favorably to antibiotic treatment. Three weeks into his hospitalization, an intracranial hemorrhage and cerebral edema led to an abrupt deterioration in his neurological status. A single dose of raxibacumab was added to his antimicrobial regimen on hospital day 27. His overall status, both clinical and radiographic, improved within a few days. He was discharged 2 months after admission and appears to have fully recovered.

[Echinocandins: searching for differences. The example of their use in patients requiring continuous renal replacement therapy]. / Equinocandinas: buscando diferencias. El ejemplo de su uso en pacientes sometidos a técnicas continuas de reemplazamiento renal.

The echinocandins have a growing role in the treatment of fungal infections because of their novel mechanism of action. This is reflected in recently published management guidelines, but available in vitro data, animal studies, and clinical studies do not clearly differentiate the three agents in class. Comparative clinical efficacy among agents within the class, pharmacokinetic profiles in special populations, pharmacoeconomics justifications, and place in therapy have been largely unanswered. They share many common properties but marketing strategies of drug manufacturers are engaged in product differentiation. Although exist similarities in the pharmacokinetic (PK) profiles of the echinocandins, limited data have been published regarding their pharmacokinetics in continuous renal replacement therapy (CRRT) patients. The pharmacokinetics of drug removal in critically ill patients receiving CRRT is very complex, with multiple variables affecting clearance. This review outlines the basic principles that determine whether a dose adjustment is required. Two studies with data on PK parameters of micafungin and anidulafungin in CRRT patients have been published and are compared following that basic principles in the review.

[Assessment of the effectiveness and safety of ranibizumab in neovascular age-related macular degeneration]. / Efectividad y seguridad de ranibizumab en degeneración macular neovascular asociada a la edad.

BACKGROUND AND OBJECTIVES: Neovascular Age Related Macular Degeneration (ARMD) is a chronic and degenerative disease. Current treatment options are limited and have shown to slow disease progression. The aim of this study was to assess Ranibizumab effectiveness and safety and to describe patients' demographic and clinical characteristics. PATIENTS AND METHOD: We conducted a retrospective observational study including all patients who had started treatment between 1/12/2006 and 31/12/2008, and were followed up until 31/03/2009. A bivariate analysis on months 4, 12 and 18 and two logistic regression models were performed to analyze the influence of demographic and clinical factors on the effectiveness and durability of treatment. Adverse reactions were collected as described in the medical records to assess safety. RESULTS: A total of 126 eyes of 112 patients were recruited. The mean age was 77.7 (± 6.0) years. The mean durability of treatment was 18.2 months, and it was higher in the group of patients who started treatment with visual acuity (VA) > 0.1 (p<0.001). Ranibizumab therapy maintained AV over baseline at 18 months. None of the studied variables showed any influence on treatment effectiveness. However, baseline visual acuity influenced on treatment duration, being higher in the group of patients with AV > 0.1. CONCLUSIONS: Ranibizumab was shown to be effective until 18 months. Early diagnosis of AMD could lead to an earlier treatment start, when patients present a higher AV, in order to optimize the benefits of treatment. Ranibizumab was well tolerated and safe in most patients.