Background. The epidemiological and clinical characteristics of solid organ transplant (SOT) patients during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic remains unclear. We conducted a matched retrospective cohort study to compare clinical outcomes among SOT recipients with the general population and to assess immunosuppression management. Methods. Adult SOT recipients with laboratory polymerase chain reaction-confirmed SARS-CoV-2 infection admitted to a tertiary-care hospital in Barcelona, Spain, from March 11 to April 25, 2020, were matched to controls (1:4) on the basis of sex, age, and age-adjusted Charlson's Index. Patients were followed for up to 28 days from admission or until censored. Primary endpoint was mortality at 28 days. Secondary endpoints included admission to the intensive care unit and secondary complications. Drug-drug interactions (DDI) between immunosuppressants and coronavirus disease 2019 (COVID-19) management medication were collected. Results. Forty-six transplant recipients and 166 control patients were included. Mean (SD) age of transplant recipients and controls was 62.7 (12.6) and 66.0 (12.7) years, 33 (71.7%) and 122 (73.5%) were male, and median (interquartile range) Charlson's Index was 5 (3-7) and 4 (2-7), respectively. Mortality was 37.0% in SOT recipients and 22.9% in controls (P = 0.51). Thirty-three (71.7%) patients underwent transitory discontinuation of immunosuppressants due to potential or confirmed DDI. Conclusions. In conclusion, hospitalized SOT recipients with COVID-19 had a trend toward higher mortality compared with controls, although it was not statistically significant, and a notable propensity for DDI.

Background: Limited data regarding altered linezolid pharmacokinetics in patients with liver cirrhosis are available. The objective of this study was to evaluate the pharmacokinetics, efficacy and safety of linezolid in cirrhotic patients. Methods: A case–control 1:1 study of patients undergoing linezolid therapeutic drug monitoring was conducted between January 2015 and June 2017. Cases with liver cirrhosis were matched with controls by age, body weight, comorbidities, renal function, and intensive care unit (ICU) admission. Results: Fifty-two patients were included, 26 in each group. Patients with Child–Pugh Scores A, B, and C were 1 (3.8%), 13 (50.0%), and 12 (46.2%), respectively. Cases had higher median linezolid trough plasma concentrations than controls [20.6 (17.4) versus 2.7 (11.3); P < 0.001)] and more frequently achieved an optimal pharmacodynamic index [26 (100%) versus 16 (61.5%); P = 0.002]. In addition, potentially toxic concentrations and treatment discontinuation due to overexposure and hematological toxicity were also more frequently seen in cirrhotic patients. Overall clinical cure rate was high (67.4%), and in-hospital mortality was 28.8%. No differences in clinical outcomes were observed between both groups. Conclusions: Linezolid showed a high clinical cure rate. Nevertheless, plasma concentrations and treatment discontinuation due to hematological toxicity were higher in cirrhotic patients. Liver cirrhosis may influence linezolid pharmacokinetics and question the use of standard doses. Therapeutic drug monitoring of linezolid would be valuable in these patients.

Azole antifungals have frequently been linked to the presence of hepatotoxicity, but there is scarce information on cross-toxicity between these drugs or on the possibility of using some of them when this type of toxicity occurs. We report the case of a 64-year-old man with invasive aspergillosis (IA) leading to spondylodiscitis with neurological involvement. Early management included intravenous (iv) voriconazole, which had to be interrupted after 1 week due to liver damage. Therapeutic drug monitoring (TDM) of voriconazole showed that the plasma concentration was within the therapeutic range. However, it was replaced by a combination therapy of oral posaconazole plus iv caspofungin. Posaconazole allowed normalization of liver enzymes. After finishing posaconazole monotherapy on an outpatient basis, the patient made a full recovery. This case report provides further evidence that oral posaconazole is safe and effective as rescue therapy after the appearance of voriconazole-induced liver toxicity.

administration route (oral/injectable/intravenous), treatment satisfaction and treatment decision-making. This questionnaire was elaborated and validated by an MS expert committee (hospital pharmacists, neurologist, patients' associations: Fundación Esclerosis Múltiple Madrid (nurses) and Esclerosis Múltiple España (clinical psychologists). Results One-hundred and fifty-seven MS patients (44 males/ 113 females) were included. The adherence rate was 71% (Morisky-Green scale), and was associated with: older age (mean: 45.2 years compliance; 40.4 years non-compliance), better cognitive status, being married/in-union, more lines of prior treatments, time to diagnosis of 5-10 years, exacerbations absence, clear information about the disease and high treatment satisfaction (table ). There were no differences in the adherence rate between oral (63%) and injectable (77%) treatments. Analysing the injectable administration, there was greater adherence in patients with IV (100%) vs SC (68%). There was also a significant difference between IV (100%) vs oral (63%) (p=0.001). The main cause for non-compliance was forgetfulness (27%). Conclusion Adherence rate for the MS treatment is acceptable (71%). It is negatively affected by forgetfulness, lower cognitive status and lack of family support. The injectable route shows higher adherence than the oral route, although the latter show the highest patient satisfaction. REFERENCES AND/OR ACKNOWLEDGEMENTSStudy supported by Roche, Spain. We gratefully acknowledge AMBER for its contribution (data collection/statistical analysis).No conflict of interest.

Background: High rates of amoxicillin-clavulanate (AMC) resistance among Enterobacterales isolated from urinary tract infections (UTIs) were observed in our area. The aim of this study was to identify risk factors associated with AMC resistance in patients with community-onset UTI in emergency departments (EDs). Methods: A retrospective study was performed of all ED patients with positive urine cultures for Escherichia coli or Klebsiella pneumoniae in a Spanish tertiary-care hospital. Results: 330 urine cultures in all were included: 261 (79.1%) for E. coli and 69 (20.90%) for K. pneumonia. Rates of AMC resistance were 14.94% and 34.78%, respectively. UTI was clinically confirmed in 212 (64.24%) cases. Previous antimicrobial exposure was independently associated with AMC resistance development in E. coli and K. pneumoniae urinary isolates (OR = 2.94, 95% CI = 1.55–5.58). Analyses of infected patients revealed that previous exposure to fluoroquinolones (OR = 3.33, 95% CI = 1.10–10.12, p = 0.034) and to AMC (OR = 5.68, 95% CI = 1.97–16.44, p = 0.001) was significantly associated with isolation of AMC-resistant strains. Conclusions: Prior antibiotic exposure, particularly to AMC or fluoroquinolones, was the only independent risk factor associated with development of AMC resistance in E. coli and K. pneumoniae urinary isolates from patients attending the ED.

Critically ill patients undergo significant pathophysiological changes that affect antibiotic pharmacokinetics. Piperacillin/tazobactam administered by continuous infusion (CI) improves pharmacokinetic/pharmacodynamic (PK/PD) target attainment. This study aimed to characterize piperacillin PK after CI administration of piperacillin/tazobactam in critically ill adult patients with preserved renal function and to determine the empirical optimal dosing regimen. A total of 218 piperacillin concentrations from 106 patients were simultaneously analyzed through the population PK approach. A two-compartment linear model best described the data. Creatinine clearance (CLCR) estimated by CKD-EPI was the covariate, the most predictive factor of piperacillin clearance (CL) interindividual variability. The mean (relative standard error) parameter estimates for the final model were: CL: 12.0 L/h (6.03%); central and peripheral compartment distribution volumes: 20.7 L (8.94%) and 62.4 L (50.80%), respectively; intercompartmental clearance: 4.8 L/h (26.4%). For the PK/PD target of 100% fT>1×MIC, 12 g of piperacillin provide a probability of target attainment > 90% for MIC < 16 mg/L, regardless of CLCR, but higher doses are needed for MIC = 16 mg/L when CLCR > 100 mL/min. For 100% fT>4×MIC, the highest dose (24 g/24 h) was not sufficient to ensure adequate exposure, except for MICs of 1 and 4 mg/L. Our model can be used as a support tool for initial dose guidance and during therapeutic drug monitoring.

ObjectiveOur objective was to evaluate the prevalence of discrepancies between primary care electronic medication records (EMR) and patient reported medication (PRM) in ambulatory patients starting a hospital dispensing treatment (HDT) at a hospital-based ambulatory care pharmacy (HACPh). Our secondary aims were to analyse factors associated with the presence of discrepancies and their impact on the prevalence of potential drug–drug interactions (DDIs) with the HDT.MethodsRetrospective study including 230 patients starting a HDT at the HACPh. Pharmacists interviewed patients and PRM was compared with EMR. Discrepancies were classified as omissions (medication in the PRM not present in the EMR) and commissions (medication active in the EMR that the patients were not taking). Potential DDIs with the HDT were screened, and univariate and multivariate analyses were performed to detect factors associated with the presence of discrepancies.ResultsWe identified 221 discrepancies in 116 (50.4%) patients. Being visited by three or more medical specialties (OR 1.93, 95% CI 1.11 to 3.37) and attending private healthcare (OR 4.36, 95% CI 1.14 to 16.72) in the 12 months before the study inclusion were the factors independently associated with the presence of discrepancies. Among patients with commissions (n=91), 15.4% had a potential DDI between the HDT and one medication from the EMR that they were not taking at that moment. Among patients with omissions (n=45), 11.1% had a potential DDI between the HDT and a medication in the PRM not present in the EMR.ConclusionsAbout 40% of patients had one or more medications in the EMR which they were not taking and one fifth used medications that were not listed in the EMR. EMR should not be used as the only source of information when screening for DDIs, especially in patients followed by different medical specialties or combining private and public healthcare.

BackgroundLinezolid is used at a standard dose of 600 mg/12 hours regardless of renal or hepatic function but very little data concerning its pharmacokinetics (PK), efficacy and safety in patients with liver cirrhosis is available.PurposeThe objectives were to describe the PK, efficacy and safety of linezolid in cirrhotic patients.Material and methodsA prospective case-control 1:1 study conducted between January 2015 to June 2017. Cases were all cirrhotic patients treated with linezolid undergoing therapeutic drug monitoring (TDM). Controls were matched by age, actual bodyweight, comorbidities, renal function (glomerular filtration rate (GFR)) and severity. Subtherapeutic linezolid concentrations were defined as a through (Cmin) concentration <2 mg/L and supratherapeutic as a Cmin >10 mg/L. Thrombocytopaenia was defined as a decrease in platelet count to <75% and anaemia as an ≥2 g/dL decrease in haemoglobin, both from baseline. Data are described as the mean± (standard deviation SD). The Student’s t-test or Mann–Whitney U-test for continuous variables and the Chi-square or Fisher’s exact test for dichotomous variables were used.ResultsFifty-two patients were included. Mean age: 62 (±11. 9) years, males 66. 1%, without differences in baseline demographic and clinical characteristics excepting for low baseline platelet count (57.7% vs. 26.9%, p=0.025).Abstract 4CPS-059 Table 1 Cases (n= 26) Controls (n= 26) P value Baseline GFR (CKD-EPI, ml/min/1.73 m2) 75.0 (44.8) 70.1 (48.6) 0.709 Linezolid dose (mg/kg) 16.9 (2.8) 17.5 (3.3) 0.479 Cmin, ss (mg/L) 22.6 (14.7) 7.4 (9.0) < 0.001 Subtherapeutic concentrations 0 (0%) 9 (32.0%) 0.002 Supratherapeutic concentrations 20 (80%) 7 (28%) < 0.001 Clinical cure 19 (73.1%) 12 (46.1%) 0.348 Anaemia 7 (28.4%) 6 (24.2%) 0.747 Thrombocytopaenia 13 (52%) 8 (33.3%) 0.187 Final platelet count<100. 000/mm3 18 (69.2%) 4 (16.7%) < 0.001 Discontinuation due to haematological toxicity 5 (19.2%) 1 (3.8%) 0.083 ConclusionCirrhotic patients were more likely to have supratherapeutic concentrations of linezolid and a lower final platelet count, probably due to reduced non-renal clearance. Linezolid showed a good clinical response rate with no differences between patients with and without cirrhosis. These results question the use of standard doses of linezolid to this population and highlight the need to perform TDM to reduce toxicity.No conflict of interest