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To analyse the effectiveness and safety of daptomycin versus vancomycin on the management catheter-related bloodstream nfections in oncology patients.A retrospective study was carried out including all patients admitted at the Medical Oncology Unit between 2010 and 2018 with positive blood cultures confirmed catheter-related bloodstream infections due to gram- positive microorganism, who were treated with either vancomycin or daptomycin. The primary end point was all cause 30-days mortality, 30-days hospital readmission and length of hospital stay (length of hospital stay). Results: A total of 70 patients with catheter-related bloodstream infections were included in the present study: vancomycin was administered to 61.4% (n = 43) and daptomycin to 38.6% (n = 27) of patients. 78.5% (n = 55) of isolated bacteria showed a vancomycin minimum inhibitory concentration ≤ 1 μg/ml. No differences were observed between the two groups of patients regarding the 30-day mortality rate rate (32.6% [n = 14] versus 29.6% [n = 8]; p = 0.797), the 30-day re-admission rate (30.2% [n = 13] versus 29.6% [n = 8]; p = 0.957) or the length of hospital stay (18.9 versus 16.5 days; p = 0.562). Nephrotoxicity rate was equivalent in both groups: a 7% (n = 3) of vancomycin goup versus a 7.4% (n = 2) of daptomycin group (p = 0.946).Our results show that both antibiotics are equivalent in their safety and effectiveness. Therefore, vancomycin should continue being the treatment of chose for gram-positive catheter-related bloodstream infections, in particular at hospital centres with a low prevalence of strains that show diminished susceptibility to vancomycin.Analizar la eficacia y seguridad de la daptomicina frente a la vancomicina en el tratamiento de las infecciones del torrente sanguíneo asociadas a catéter vascular en pacientes oncológicos.Método: Se realizó un estudio retrospectivo que incluyó a los pacientes ingresados en la Unidad de Oncología-Médica entre 2010-2018 con infección del torrente sanguíneo asociada a catéter vascular causada por grampositivos, y que fueron tratados con vancomicina o daptomicina. Como objetivos principales se determinaron la tasa de mortalidad por todas las causas a los 30 días, el reingreso hospitalario a los 30 días y la duración de la estancia hospitalaria.El estudio incluyó 70 pacientes con infecciones del torrente sanguíneo asociadas a catéter vascular: el 61,4% (n = 43) recibió vancomicina y el 38,6% (n = 27) daptomicina. El 78,5% (n = 55) de las bacterias aisladas presentaron una concentración mínima inhibitoria de vancomicina ≤ 1 μg/ml. No se observaron diferencias entre ambos grupos de pacientes en cuanto a la tasa de mortalidad a 30 días (32,6% [n = 14] frente al 29,6% [n = 8]; p = 0,797), la tasa de reingreso a 30 días (30,2% [n = 13] frente al 29,6% [n = 8]; p = 0,957) o la duración de la hospitalización (18,9 frente a 16,5 días; p = 0,562). La tasa de nefrotoxicidad fue equivalente en ambos grupos: 7% (n = 3) para vancomicina frente al 7,4% (n = 2) para daptomicina (p = 0,946).Nuestros resultados muestran que ambos antibióticos son equivalentes en su seguridad y eficacia. Por ello, vancomicina debería seguir siendo el tratamiento de elección para la infección del torrente sanguíneo asociada a catéter vascular, especialmente en centros con una baja prevalencia de cepas con una susceptibilidad disminuida a ancomicina.

Introduction The addition of imatinib to the therapeutic arsenal for chronic myeloid leukaemia (CML) has changed the natural course of the disease, in such a way that it is now considered a chronic pathology. However, to achieve therapeutic success, it is necessary to reach adequate plasma concentrations to ensure efficacy and safety. In this study, we aimed to evaluate the plasma concentration of imatinib, analysing its influence on effectiveness and safety in patients with CML. Methods We performed a descriptive, multicentre study in which imatinib plasma levels from patients diagnosed with CML between 2019–2020 were analysed. An optimal therapeutic range of 750–1500 ng/mL was established for the stratification of patients, according to their minimum plasma concentrations measured at steady state (Cssmin). Results A total of 28 patients were included, of whom only 39.3% (n = 11) showed Cssmin within the therapeutic range. 100% of patients with Cssmin >750 ng/mL achieved an optimal molecular response, while only 50% of patients with Cssmin 1500 ng/mL and 5.9% for those with Cssmin Conclusions This study aimed to describe the correlation between the toxicity and effectiveness of imatinib according to its Cssmin in routine clinical practice conditions. Based on our findings, it would be certainly justified to monitor patient plasma concentrations of imatinib on a daily routine basis in our hospitals.

Introduction Trastuzumab is a monoclonal antibody which could induce the activation of a humoral immune response generating anti-drug antibodies (ADAs). Such response depends of the protein nature and the route of administration (intravenous or subcutaneous). The formation of these antibodies could block the action of trastuzumab (ADA-Tras) and forming immune complexes which decrease its efficacy, so it would be interesting to determine the presence of ADA-Tras in patients treated with trastuzumab. Material and methods The blood samples were centrifuged to separate the plasma. The presence of ADA-Tras in plasma was determined using an ELISA-type automated immunoassay. Results Fifty-one women with non-metastatic HER2-positive breast cancer treated with trastuzumab were included. Two groups were studied: patients treated intravenously and subcutaneously. In neither case was there any presence of ADA-Tras. Discussion This study may be the first ever conducted under usual clinical practice conditions to detect the presence of ADA-Tras in patients with non-metastatic HER2-positive breast cancer. We have wanted to show the antibodies anti-trastuzumab determination as a possible tool that would enable comparison of potential differences in immunogenic behavior between trastuzumab and its biosimilars.

Background: Subcutaneous trastuzumab (T-SC) administration does not allow the historical target concentration of 20 µg/mL for efficacy to be reached, from the start of treatment in patients with a body mass index (BMI) >30 kg/m2. Objectives: To analyze the influence of the strategy of dosification (fixed vs adjusted patient’s body weight dose) on the initial minimum plasma concentration ( Cmin) of trastuzumab in obese patients. Methods: This was an observational, prospective study, which included patients with HER2-positive nonmetastatic breast cancer treated with trastuzumab. The determination of the Cmin of trastuzumab was performed on day +21 of the first cycle using the ELISA technique. Patients were stratified according to the strategy of dosification and BMI. Results: A total of 50 patients were included; 16 patients received the drug intravenously and 34 in a fixed dosage subcutaneous (T-SC) regimen. The proportion of patients who achieved an adequate plasma concentration since the beginning of treatment was significantly higher when the drug was administered intravenously (93.8% vs 67.6%, P = 0.042). These differences are especially greater in T-SC patients with BMI >30 kg/m2, with only 20% of patients exceeding the pharmacokinetic target. Conclusion and Relevance: Our study suggests that trastuzumab SC fixed dose of 600 mg is not equivalent to IV administration, especially in obese patients. An adequate trastuzumab exposure in this population needs patient weight–adjusted IV dosage in the first administration. The clinical relevance of these findings remains to be elucidated, and further research, including larger controlled trials, is warranted.

Resumen Introduccion El manejo de las bacteriemias por Klebsiella pneumoniae productora de carbapenemasa del tipo OXA-48 (KPOXA-48) es complicado por las escasas opciones terapeuticas y la elevada mortalidad. El objetivo del estudio fue describir las caracteristicas clinicas de bacteriemia por KPOXA-48 entre octubre de 2013 y diciembre de 2016. Material y metodos Se recogieron retrospectivamente de las historias clinicas las variables para analizar. La produccion de carbapenemasas se confirmo por metodos fenotipicos y moleculares. Resultados Se incluyeron 38 pacientes con bacteriemia, mayoritariamente de origen nosocomial (n = 31). Un alto porcentaje de las bacteriemias (n = 26) fueron secundarias, principalmente de origen urinario (n = 11). Todos los aislamientos eran multirresistentes con produccion de la beta-lactamasa de espectro extendido CTX-M-15 y carbapenemasa del tipo OXA-48. La mortalidad bruta con antibioterapia dirigida adecuada fue del 0% y la inadecuada del 55% (p = 0,0015). Conclusiones Se pone de manifiesto la importancia de identificar este mecanismo de resistencia, los factores del paciente, el tipo de bacteriemia y la adecuacion de la estrategia terapeutica en la evolucion clinica.

The present work analyzed the stability of trastuzumab concentrations in blood and plasma samples stored at 4 °C and -20 °C.Blood samples of patients treated with trastuzumab (Herceptin ®) were analyzed. Stability of trastuzumab was analyzed under different conditions: whole blood stored at 4 °C during 72 hours, blood plasma stored at 4 °C during 120 hours and blood plasma stored at -20 °C during 365 days.In whole blood trastuzumab concentration at 72 hours was 99.01 ± 0.02%, and in plasma samples at 120 hours it was 98.6 ± 2.0%. The concentration of trastuzumab was 95.22 ± 3.20% after 12 months' storage at -20 ºC.The concentration of trastuzumab remains stable for at least 72 hours in whole blood stored at 4 °C, five days in plasma stored at 4 °C and one year in plasma stored at -20 °C.Objetivo: Analizar la estabilidad del trastuzumab en sangre y plasma a 4 °C y –20 °C.Método: Se determinó la concentración plasmática de trastuzumab en las muestras de sangre y plasma de pacientes con cáncer de mama HER2 positivo tratados con trastuzumab (Herceptin®). Se analizó la estabilidad del trastuzumab en sangre a 4 °C durante 72 horas. En el caso de las muestras de plasma, se estudió la estabilidad a 4 °C durante 72 y 120 horas, así como durante 365 días congeladas a –20 °C.Resultados: En sangre, la concentración de trastuzumab a las 72 horas fue de 99,01 ± 0,02%, y en las muestras de plasma a las 120 horas fue de 98,6 ± 2,0%. La concentración de trastuzumab fue de 95,22 ± 3,20% después de 12 meses de almacenamiento a –20 °C.Conclusiones: El trastuzumab permanece estable durante al menos 72 horas en sangre total almacenada a 4 °C, cinco días en plasma almacenado a 4 °C y un año en plasma almacenado a –20 °C.

Background: Plasma concentrations of trastuzumab min) of 20 µg/mL after first drug administration, established as therapeutically effective in clinical trials. The secondary objective was to identify the physiological and anthropometric characteristics that determine interindividual pharmacokinetic variability. Methods: Serum concentrations of trastuzumab were assessed by ELISA on day 1 of the second cycle before administration of the second dose ( Cmin). Results: Of 19 patients included, 9 (47.4%) had a mean Cmin of 19.0 µg/mL (±12.1) after the first administration. Body mass index (BMI) and weight was the main variable that determined the achievement of therapeutic levels after the first administration. Thus, the proportion of patients reaching the target concentration was 89% when BMI was ≤30 kg/m2 but only 11% when BMI was >30 kg/m2 ( P < 0.01). Conclusions: The standard dose of 600 mg subcutaneous trastuzumab did not ensure adequate pharmacodynamic exposure from the first administration in 52% of patients, with weight and BMI being related to the plasma levels obtained.

Introduction: Lung cancer is the third most frequent neoplastic tumour in Spain, with around 27 000 new cases diagnosed per year; 80-95% of these are non-small-cell cancer (NSCLC), and the majority of cases are diagnosed in advanced stages of the disease, and for this reason it is one of the oncologic conditions with higher mortality rates (21.4% mean survival at 5 years). The main treatment regimens used for first-line treatment of NSCLC are: isplatin/pemetrexed (cis/pem), cisplatin/gemcitabine/ bevacizumab (cis/gem/bev), and carboplatin/paclitaxel/ bevacizumab (carb/pac/bev). The objective of this study was to evaluate the cost-effectiveness ratio of antineoplastic 1st line NSCLC treatment regimens, from the point of view of hospital management. Methodology: A cost-efficacy mathematical model was prepared, based on a decision tree. The efficacy variable was Progression Free Survival, obtained from the PARAMOUNT, AVAIL and SAIL Phase III clinical trials. The study was conducted from the perspective of the hospital management, considering only the direct costs of drug acquisition. A deterministic sensitivity analysis was conducted to confirm the robustness of outcomes. Results: The PFS obtained in clinical trials with cis/pem, cis/ gem/bev and carb/pac/bev was: 6.9, 6.7 and 6.2 months, respectively. Based on our model, the mean cost of treatment per patient for these regimens was: 19 942 €, 15 594 € and 36 095 €, respectively. The incremental cost-effectiveness ratio per month of additional PFS between cis/pem and cis/gem/bev was 19 303 €. Estimating a 30% reduction in acquisition costs for pemetrexed (Alimta®Eli Lilly Nederland B.V.), due to the forthcoming launch of generic medications, the cis/pem treatment would become the predominant alternative for 1st line treatment of NSCLC patients, by offering the best health results at a lower cost.

Asymptomatic colonization of the gastrointestinal tract by carbapenemase-producing Enterobacteriaceae is an important reservoir for transmission that may precede infection. This prospective, observational, case–control study was designed to identify risk factors for carbapenemase-producing Klebsiella pneumoniae (CPKP) fecal carriage. This study included 87 cases and 200 controls. Multivariate analysis identified length of stay (odds ratio [OR], 1.02; 95% confidence interval [CI], 1.01-1.03; P = .03), previous hospitalization (OR, 5.89; 95% CI, 1.73-20.68; P = .01), antibiotic use (OR, 0.20; 95% CI, 0.65-0.62; P = .01), and corticosteroid use (OR, 0.33; 95% CI, 0.15-0.74; P = .007) as independent risk factors for CPKP rectal carriage. Length of hospital stay, previous hospitalization, corticosteroid use, and antimicrobial exposure are important risk factors for CPKP rectal colonization. Adherence to infection control practices and directed surveillance programs appear to be critical components for CPKP control programs.

Asparaginase (ASNase) use as a tumour-inhibitor drug has changed completely the natural course of paediatric acute lymphoblastic leukaemia (ALL) in such a way that it represents a paradigm shift in ALL management. ASNase treatment emergence has significantly improved pathologic responses and increased survival rates of ALL patients. Although different ASNase forms are currently available, only the pegylated form (PEG-ASNase) is recommended by relevant clinic guides. PEG-ASNase form shows longer elimination half-life, reducing the number of administrations, along with an enhanced safety profile. In spite of all of these advantages, PEG-ASNase elevated cost limits enormously its use. PEG-ASNase is commercialised as a lyophilised powder which according to the manufacturer it is stable for 24 hours once reconstituted, as a result, the leftover is usually discarded. In this study we analysed the enzymatic stability of reconstituted PEG-ASNase after conservation in three different temperature conditions for 5 and 14 days, aiming to take advantage of the remaining leftover for the subsequent administration. Our results have shown that PEG-ASNase is stable at 4°C, −20°C and −80°C for at least 14 days, retaining the 95% from the initial enzymatic activity in all three storage temperatures. According to our results, it is feasible to reuse the remaining content of PEG-ASNase vial after reconstitution, which means a 50% reduction of its cost for paediatric patient treatment and, consequently, removes the main barrier to use this drug in a wider population.

Introduction Limited therapeutic options and high mortality make the management of OXA-48-like carbapenemase-producing Klebsiella pneumoniae (KPOXA-48) bacteraemia complicated. The aim of the study was to describe the clinical characteristics of KPOXA-48 bacteraemia between October 2013 and December 2016. Material and methods The variables to analyse were retrospectively collected from medical records. Carbapenemase production was confirmed by phenotypic and molecular methods. Results A total of 38 patients with bacteraemia were included, mainly classified as hospital-acquired (n = 31). The majority of cases were secondary bacteraemia (n = 26), most commonly arising from the urinary tract (n = 11). All isolates presented a multidrug-resistant profile with the extended spectrum beta-lactamase CTX-M-15 and the carbapenemase OXA-48-like production. The crude mortality rate with adequate targeted antibiotic therapy was 0%, rising to 55% with inadequate treatment (p = 0.0015). Conclusions This study highlights the importance of identifying this resistance mechanism, the patient factors, type of bacteraemia and adequacy of antibiotic therapy in the outcome of bacteraemia.

Colorectal cancer is the second most common cancer in Europe. Most antineoplastic regimens in first-line treatment involve 5-fluorouracil or oral prodrug capecitabine, combined with other antineoplastic agents such as oxaliplatin or irinotecan. It is well known that 5-fluorouracil and capecitabine are agents that can be toxic in cases of decreased dihydropyrimidine dehydrogenase activity because this enzyme is the main limiting factor in the metabolism of both agents. In this paper, we describe the case of a patient who developed severe toxicity to 5-fluouracil and who had a mutation in the gene encoding the enzyme dihydropyrimidine dehydrogenase.

Introduction The advent of Luer-type needleless venous access catheters has been accompanied by a growing number of catheter-related bloodstream infections. Our main objective was to compare rates of colonisation and phlebitis between our standard of care and the new passive disinfection system, using a Luer SwabCap bearing a sponge impregnated with 70% isopropyl alcohol. Methods We performed a prospective experimental study involving patients attending our day hospital oncology unit, with central venous (CV) or peripheral venous (PV) access lines with needleless connectors for antineoplastic treatment delivery. We assessed the colonisation rate by culture of the inside of the hubs (qualitative culture) and also assessed the possible appearance of phlebitis and the extra cost of introducing the new system in our oncology day hospital; nurse satisfaction was evaluated by a questionnaire. The effectiveness of the isopropyl alcohol disinfection cap was evaluated by analysing rates of catheter colonisation and phlebitis between two groups: group 1 comprised of patients receiving the standard disinfection method and group 2 comprised of patients receiving SwabCaps on any venous access connectors. Samples were taken from the catheter lumen through a sterile swab seeded in Luria Bertani-rich broth and cultivated for at least 48 h at 37°C. We also assessed the extra cost of introducing the new system in our oncology day hospital, and nurse satisfaction was evaluated by a questionnaire. Results 29 patients were included (13 in group 1 and 16 in group 2). In group 1, 56% of the samples were taken from CV access connectors versus 40% in group 2. Bacterial growth was detected in 43.7% of group 1 samples versus 0% in group 2 (p=0.006). No differences in the degree of contamination were found between CV and PV access connectors. No cases of phlebitis were observed. Nurse satisfaction with the new system was 9.2 out of a maximum score of 10. The incremental cost of incorporating the new system in our oncology unit was estimated at €1.87 836. Conclusion Passive disinfection systems help reduce colonisation of venous access catheters without requiring large economic investment or special training of health personnel.