Drug-related problems in patients admitted for SARS-CoV-2 infection during the COVID-19 pandemic.

Introduction: Drug-related problems (DRP) are events or circumstances in which drug therapy does or could interfere with desired health outcomes. In December 2019, a new coronavirus, SARS-CoV-2, appeared. Little knowledge about this type of infection resulted in the administration of various drugs with limited use in other pathologies. Evidence about DRP in patients with COVID-19 is lacking. Objective: The aim of the present study is to describe identified cases of DRP and those drugs involved in the first wave of patients with COVID-19, and evaluate associated risk factors. Material and methods: Observational, retrospective study performed in a tertiary university hospital between 14th March 2020 and 31 May 2020 (corresponding to the first COVID-19 wave). We recruited patients admitted during the study period. Exclusion criteria included age < 18 years; admission to critically ill units; and care received either in the emergency room, at-home hospitalization or a healthcare center. Results: A total of 817 patients were included. The mean age was 62.5 years (SD 16.4) (range 18-97), and 453 (55.4%) were male. A total of 516 DRP were detected. Among the patients, 271 (33.2%) presented at least one DRP. The mean DRP per patient with an identified case was 1.9. The prevailing DRPs among those observed were: incorrect dosage (over or underdosage) in 145 patients (28.2%); wrong drug combination in 131 (25.5%); prescriptions not in adherence to the then COVID-19 treatment protocol in 73 (14.1%); prescription errors due to the wrong use of the computerized physician order entry in 47 (9.2%); and incorrect dosage due to renal function in 36 (7%). The logistic regression analysis showed that patients who received only prescriptions of antibacterials for systemic use (J01 ATC group) faced a higher likelihood of experiencing a DRP (OR 2.408 (1.071-5.411), p = 0.033). Conclusion: We identified several factors associated with an increased risk of DRPs, similar to those reported in other pre-pandemic studies, including a prolonged length of stay, higher number of prescribed drugs and antimicrobial administration. The relevance of pharmacists and tools like pharmacy warning systems can help prevent, identify and resolve DRP efficiently.

Dosage Individualization of Linezolid: Precision Dosing of Linezolid To Optimize Efficacy and Minimize Toxicity.

The high interindividual variability in the pharmacokinetics (PK) of linezolid has been described, which results in an unacceptably high proportion of patients with either suboptimal or potentially toxic concentrations following the administration of a fixed regimen. The aim of this study was to develop a population pharmacokinetic model of linezolid and use this to build and validate alogorithms for individualized dosing. A retrospective pharmacokinetic analysis was performed using data from 338 hospitalized patients (65.4% male, 65.5 [±14.6] years) who underwent routine therapeutic drug monitoring for linezolid. Linezolid concentrations were analyzed by using high-performance liquid chromatography. Population pharmacokinetic modeling was performed using a nonparametric methodology with Pmetrics, and Monte Carlo simulations were employed to calculate the 100% time >MIC after the administration of a fixed regimen of 600 mg administered every 12 h (q12h) intravenously (i.v.). The dose of linezolid needed to achieve a PTA ≥ 90% for all susceptible isolates classified according to EUCAST was estimated to be as high as 2,400 mg q12h, which is 4 times higher than the maximum licensed linezolid dose. The final PK model was then used to construct software for dosage individualization, and the performance of the software was assessed using 10 new patients not used to construct the original population PK model. A three-compartment model with an absorptive compartment with zero-order i.v. input and first-order clearance from the central compartment best described the data. The dose optimization software tracked patients with a high degree of accuracy. The software may be a clinically useful tool to adjust linezolid dosages in real time to achieve prespecified drug exposure targets. A further prospective study is needed to examine the potential clinical utility of individualized therapy.

Population Pharmacokinetics of Anidulafungin in Critically Ill Patients.

A two-compartment pharmacokinetic (PK) population model of anidulafungin was fitted to PK data from 23 critically ill patients (age, 65 years [range, 28 to 81 years]; total body weight [TBW], 75 kg [range, 54 to 168 kg]). TBW was associated with clearance and incorporated into a final population PK model. Simulations suggested that patients with higher TBWs had less-extensive MIC coverage. Dosage escalation may be warranted in patients with high TBWs to ensure optimal drug exposures for treatment of Candida albicans and Candida glabrata infections.

Infectious postoperative endophthalmitis after cataract surgery performed over 7 years. The role of azithromycin versus ciprofloxacin eye drops.

OBJECTIVE: Although topical antibiotics have been used as antimicrobial prophylaxis after ocular surgery, recent studies have determined that intracameral cefuroxime at the end of surgery significantly reduce the risk to suffer an infection and suggest that the use of topical antibiotics in the prophylaxis of infectious postoperative endophthalmitis (IPOE) is controversial. Moreover, there is no evidence to confirm the higher effectiveness of topical ciprofloxacin, considered the standard of care, or topical azithromycin in preventing IPOE of cataract surgeries. METHODS: IPOE topical prophylaxis was performed with two different strategies: with azithromycin from January 1st, 2010 to December 31st, 2014 (group I) and with ciprofloxacin from January 1st, 2015 to January 31st, 2017 (group II). Patient characteristics and clinical signs and symptoms of IPOE from all consecutive cataract surgeries performed over a 7-year period were collected. RESULTS: A total of 15,146 cataract surgeries were conducted; 10,756 in group I and 4,390 in group II. Two cases of IPOE in each group were diagnosed, showing a 0.019% and 0.046% rate respectively, with no statistically significance. IPOE cases were related with aging, systemic and ocular comorbidities or with a complicated cataract surgery. CONCLUSIONS: The benefit of the application of topical antibiotics after cataract surgery is questionable when intracameral cefuroxime prophylaxis is performed and no better effectiveness with ciprofloxacin or azithromycin was observed.