Data on fungemia epidemiology and antifungal susceptibility of isolates from children are scarce, leading frequently to pediatric empirical treatment based on available adult data. The present study was designed to update the epidemiological, mycological, and in vitro susceptibility data on fungal isolates from children with fungemia in Spain. All fungemia episodes were identified prospectively by blood culture over 13 months at 30 hospitals. Tests of susceptibility to amphotericin B, flucytosine, fluconazole, itraconazole, posaconazole, voriconazole, anidulafungin, caspofungin, and micafungin were performed at participant institutions by a microdilution colorimetric method. New species-specific clinical breakpoints for fluconazole, voriconazole, and echinocandins were also applied. A total of 203 episodes of fungemia in 200 children were identified. A higher proportion of fungal isolates was from general wards than intensive care units (ICU). Candida parapsilosis (46.8%), Candida albicans (36.5%), Candida tropicalis (5.9%), Candida glabrata (3.9%), and Candida guilliermondii (2.5%) were the leading species. C. parapsilosis was the predominant species except in neonates. C. albicans was the most frequent in neonatal ICU settings (51.9%). Intravascular catheter (79.3%), surgery (35%), prematurity (30%), and neutropenia (11%) were the most frequent predisposing factors. Most Candida isolates (95.1%) were susceptible to all antifungals. When the new species-specific clinical breakpoints were applied, all C. parapsilosis isolates were susceptible to echinocandins except one, which was micafungin resistant. This is the largest published series of fungemia episodes in the pediatric setting. C. parapsilosis is the most prevalent species in Spain, followed by C. albicans and C. tropicalis. Resistance to azole and echinocandin agents is extremely rare among Candida species. The fluconazole resistance rate in Spain has decreased in the last 10 years.

In the absence of clinical breakpoints (CBP), epidemiological cutoff values (ECVs) are useful to separate wild-type (WT) isolates (without mechanisms of resistance) from non-WT isolates (those that can harbor some resistance mechanisms), which is the goal of susceptibility tests. Sensititre YeastOne (SYO) is a widely used method to determine susceptibility of Candida spp. to antifungal agents. The CLSI CBP have been established, but not for the SYO method. The ECVs for four azoles, obtained using MIC distributions determined by the SYO method, were calculated via five methods (three statistical methods and based on the MIC50 and modal MIC). Respectively, the median ECVs (in mg/liter) of the five methods for fluconazole, itraconazole, posaconazole, and voriconazole (in parentheses: the percentage of isolates inhibited by MICs equal to or less than the ECVs; the number of isolates tested) were as follows: 2 (94.4%; 944), 0.5 (96.7%; 942), 0.25 (97.6%; 673), and 0.06 (96.7%; 849) for Candida albicans; 4 (86.1%; 642), 0.5 (99.4%; 642), 0.12 (93.9%; 392), and 0.06 (86.9%; 559) for C. parapsilosis; 8 (94.9%; 175), 1 (93.7%; 175), 2 (93.6%; 125), and 0.25 (90.4%; 167) for C. tropicalis; 128 (98.6%; 212), 4 (95.8%; 212), 4 (96.0%; 173), and 2 (98.5; 205) for C. glabrata; 256 (100%; 53), 1 (98.1%; 53), 1 (100%; 33), and 1 (97.9%; 48) for C. krusei; 4 (89.2%; 93), 0.5 (100%; 93), 0.25 (100%; 33), and 0.06 (87.7%; 73) for C. orthopsilosis. All methods included ≥94% of isolates and yielded similar ECVs (within 1 dilution). These ECVs would be suitable for monitoring emergence of isolates with reduced susceptibility by using the SYO method.

ALT), gamma glutamyl transferase (GGT), alkaline phosphatase (ALP) and total bilirubin (TB)), dose, diagnosis, age and sex were registered.Microsoft Excel was used for the statistics calculation. Results 68 determinations in 38 patients (73.75% men; aged 64.84 ±11.29 years).Diagnosis: probable disease 21 (55.28%), possibility 12 (31.57%), prophylaxis 5 (13.15%).6 (15.8%) patients needed a change in treatment. 5 (83.33%) had the dose changed in order to maintain plasma levels between 1 and 5.5 mg/mL. In 1 patient (16.66%) voriconazole was substituted.28 (73.7%) started treatment with the dose of 200 mg/12 hours, whereas the rest (26.3%) has a higher dose. 60% of dose changes were in patients taking 200 mg/12 hours.A positive correlation existed between plasma levels of voriconazole and liver enzymes as well as with cholestasis markers (AST: r 2 =0.1817; ALT: r 2 =0.1118; GGT: r 2 =0.2528; PA: r 2 =0.2444 and TB: r 2 =0.4637).The Chi-square statistic was significant at p<0.05 for plasmatic levels over 3 mg/mL and AST/ALT over physiological range (35 U/L).The relative risk of presenting ALT over the physiological range is 3.12 and for AST 2.31 in patients with plasmatic levels of voriconazole >3 mg/mL respects the ones whose plasmatic levels were <3 mg/mL. Conclusion and relevanceVoriconazole TDM is a tool that can help to avoid treatment failure and adverse events. Its relationship with liver toxicity, which shows our data, TDM would help to prevent these side effects.

Results 200 patients (54% males and 46% females) admitted to HED were evaluated by the pharmacy team. Mean age was 75 (31-99) years. 66 interventions were proposed in 54 patients (27%). 55% were accepted and 22% rejected. The remaining 23% could not be appraised as patients had been discharged prior to the medical team evaluation of the suggestions.Drug-related problems found were: 45% related to reconciliation (overdosing, underdosing, posology disparities, absence or no longer taking medicine prescription); 13% overdosing according to renal function or indication; 10% excessive anticholinergic burden that may have contributed to the current clinical problem; 9% underdosing for the indication; 8% lack of indication; 6% lack of prescription of a highly likely needed drug; 4% duplicities; 3% not optimal drug for the indication and 2% allergy-related problems.Proposed actions were: dosing adjustments (50%), prescription (20%), discontinuation (20%), posology modification (7%) and alternative drug selection (3%).Affected drug families were: antibiotics (22%), antidepressants, antipsychotics and anxiolytics (15%), antithrombotics (14%), blood pressure lowering agents (9%), vitamin and electrolytes supplements (9%), antiepileptics (7%), immunosupressors (4%) and others below 3% of incidence (painkillers, statins, antiretrovirals, antiarrhythmics, anti-gouts, thyroid hormones and eye-drops). Conclusion and relevanceMultidisciplinary teams are beneficial to patients' care. Incorporating a pharmacist in a HED reduces the incidence of medication errors and can positively contribute to the management of patients. Medicines reconciliation, dosing and indication checking and pharmacotherapy optimisation are actions in which the pharmacy team is capable of actively contributing for patients' best outcomes.

2021). Persistence after the first year of treatment was also assesed.Sociodemographic and clinical factors (age, age of diagnosis, DM phenotype, baseline Expanded Disability Status Scale (EDDS), treatment with disease-modifying therapies (DMTs) and anti-spasticity agents and walking support request) were collected from medical record. Persistence and adherence (measured as medication possession ratio (MPR)) data were collected from drug dispensation records (FarmaTools).For the analysis of persistence a survival analysis with the Kaplan-Meier estimator was performed. Influence of covariates was evaluated according to a Cox regression model. All statistical analyses were performed using SPSS V24.0. Significance level was 0.05. Results Fifty-one patients were included. Mean±SD age of MS diagnosis was 37.3±12.6 years. 62.7% female. At the start of the treatment, mean±SD age was 49.7±10.0 years. Phenotypes were relapsing-remitting (49%), secondary progressive (41.2%) and primary progressive (9.8%). 68.6% were on treatment with DMTs and 60.8% with anti-spasticity agents. 58.8% required support to walk. Baseline EDDS was 5±1.3. Median adherence in first year was 98.5±4.5%.Median persistence duration was 1.756 days (95% CI 1.405 to 2.107). Median time to suspension was 84 days . Medication suspension rate in first year was 31.4% and overall medication suspension rate was 13/100 patients-year (95% IC 8.1 to 17.9). Discontinuation reasons were lack of efficacy (57.9%), adverse effects (23.1%) or both (14.3%). Cox model showed only influence of age of DM diagnosis HR=1.05 (95% CI 1.01 to 1.07; p=0.007). Conclusion and relevance A high percentage of patients abandon treatment with fampridine, mainly due to lack of efficacy. Most discontinuations occur in the first year of treatment.