Background: The first generic PPI was introduced in Spain in 2001, and since then their prescriptions have increased steadily by about 200%. Aim: To evaluate the frequency of use and the appropriateness of indications of PPIs in hospitalised patients, and possible factors predicting their use. We also evaluated relevant PPI-drug interactions and serious adverse drug reactions (SADRs). Methods: This was a cross-sectional, prescription-indication drug-utilisation study in hospitalised patients with follow-up until discharge. Sampling was random and stratified by services, and was calculated to obtain an error in the precision of prescription of ±4% with a 95% confidence interval with maximum variability (50%). Results: 328 patients were included; 28.65% were prescribed a PPI at admission, 82.62% were prescribed a PPI during hospitalisation, and 54.75% at discharge, with inappropriate indications in 74.47%, 61.25% and 80.24% respectively. The OR of being discharged with PPIs was 3.01(95% CI:2.17 – 4.18, p=0.000). The inappropriate indication most frequently seen at admission and at discharge was antiplatelet therapy. During hospitalisation it was prophylaxis for stress ulcer in patients at low risk. PPI prescription at admission remained at discharge in 75.90% of cases, 73.02% without an acceptable indication. Being > 64 years old, taking > 4 drugs, co-medication (NSAIDs, antiaggregation and anticoagulation), certain hospital departments and length of stay > 15 days predicted 83.7% of prescriptions at discharge. Four relevant PPIdrug interactions were found, and 2 resulted in SADRs, thus the incidence per 1, 000 patients was 2.66 (Poisson 95% CI:0.62-7.23). Conclusions: There was a very high frequency of overuse of PPIs in inpatients and outpatients. Hospitalisation did not represent an opportunity for better prescription of PPIs.

Plitidepsin, a marine-derived cyclic-peptide, inhibits SARS-CoV-2 replication at nanomolar concentrations by targeting the host protein eukaryotic translation elongation factor 1A. Here, we show that plitidepsin distributes preferentially to lung over plasma, with similar potency against across several SARS-CoV-2 variants in preclinical studies. Simultaneously, in this randomized, parallel, open-label, proof-of-concept study (NCT04382066) conducted in 10 Spanish hospitals between May and November 2020, 46 adult hospitalized patients with confirmed SARS-CoV-2 infection received either 1.5 mg (n = 15), 2.0 mg (n = 16), or 2.5 mg (n = 15) plitidepsin once daily for 3 d. The primary objective was safety; viral load kinetics, mortality, need for increased respiratory support, and dose selection were secondary end points. One patient withdrew consent before starting procedures; 45 initiated treatment; one withdrew because of hypersensitivity. Two Grade 3 treatment-related adverse events were observed (hypersensitivity and diarrhea). Treatment-related adverse events affecting more than 5% of patients were nausea (42.2%), vomiting (15.6%), and diarrhea (6.7%). Mean viral load reductions from baseline were 1.35, 2.35, 3.25, and 3.85 log₁₀ at days 4, 7, 15, and 31. Nonmechanical invasive ventilation was required in 8 of 44 evaluable patients (16.0%); six patients required intensive care support (13.6%), and three patients (6.7%) died (COVID-19-related). Plitidepsin has a favorable safety profile in patients with COVID-19.

A 55-year-old woman was diagnosed with pneumonia and was treated with meropenem; 5 days later she developed epileptic seizures. She had been treated with valproic acid for 16 years to control her epileptic seizures. Her serum valproic acid concentration was low during treatment with meropenem than previously recorded despite an increase of valproic dose. As soon as administration of meropenem was withdrawn, valproic acid concentration increased to previous levels and her seizures stopped. Meropenem decreases valproic acid concentration, and may promote the development of epileptic seizures in previously controlled epileptic patients. The acute lowering of serum valproate produced by meropenem probably precludes their concomitant use.