Impact of antimicrobial stewardship programs on antibiotic consumption and antimicrobial resistance in four Colombian healthcare institutions.

BACKGROUND: Antimicrobial stewardship programs (ASPs) have become a fundamental pillar in optimizing antimicrobial usage, improving patient care, and reducing antimicrobial resistance (AMR). Herein we evaluated the impact of an ASP on antimicrobial consumption and AMR in Colombia. METHODS: We designed a retrospective observational study and measured trends in antibiotic consumption and AMR before and after the implementation of an ASP using interrupted time series analysis over a 4-year period (24 months before and 24 months after ASP implementation). RESULTS: ASPs were implemented according to the available resources in each of the institutions. Before ASP implementation, there was a trend toward an increase in the antibiotic consumption of all measured antimicrobials selected. Afterward, an overall decrease in antibiotic consumption was observed. The use of ertapenem and meropenem decreased in hospital wards, while a decrease in the use of ceftriaxone, cefepime, piperacillin/tazobactam, meropenem, and vancomycin was observed in intensive care units. After ASP implementation, the trend toward an increase of oxacillin-resistant Staphylococcus aureus, ceftriaxone-resistant Escherichia coli, and meropenem-resistant Pseudomonas aeruginosa was reversed. CONCLUSIONS: In our study, we showed that ASPs are a key strategy in tackling the emerging threat of AMR and have a positive impact on antibiotic consumption and resistance.

Assessment of diarrhea as side effect of oral targeted antineoplastic agents in clinical practice.

BACKGROUND: Diarrhea is one of the most frequent class adverse events associated with targeted oral antineoplastic agents (OAAs). Our objective was to analyze the incidence, characteristics, and severity of diarrhea in cancer patients in clinical practice. METHODS: An observational, longitudinal, and prospective study of cancer outpatients treated with targeted OAAs was carried out in a tertiary hospital. Targed OAAs analyzed were anaplastic lymphoma kinase inhibitors, BCR-ABL inhibitors, cyclin-dependent kinase inhibitors, epidermal growth factor receptor inhibitors, mTOR inhibitors, poly (ADP-ribose) polymerase inhibitors, and vascular endothelial growth factor receptor inhibitors. Patients were given a data collection form to record daily the number, severity (CTCAE version 5.0), and characteristics of stools during the first 30 days of treatment with OAAs. Multivariate analysis was performed to identify risk factors associated with the incidence of diarrhea. RESULTS: We analyzed 240 patients, of whom 28.7% experienced diarrhea (25.4% grades 1-2 and 3.3% grades 3-4). Patients treated with EGFR and VEGFR inhibitors had a higher incidence of diarrhea. The multivariate analysis revealed that taking the OAA with food was associated with a lower risk of diarrhea (OR = 0.404 [0.205-0.956], p = 0.038). CONCLUSIONS: More than a third of patients in treatment with OAAs presented diarrhea (any grade), and 22.1% of stools were semi-liquid/liquid. In multivariate analysis, taking the OAA on an empty stomach was associated with a statistically significant increase in the incidence of diarrhea.

Effects of land use on taxonomic and functional diversity: a cross-taxon analysis in a Mediterranean landscape.

Land-use change is the major driver of biodiversity loss. However, taxonomic diversity (TD) and functional diversity (FD) might respond differently to land-use change, and this response might also vary depending on the biotic group being analysed. In this study, we compare the TD and FD of four biotic groups (ants, birds, herbaceous, woody vegetation) among four land-use types that represent a gradient of land-use intensity in a Mediterranean landscape (Mediterranean shrublands, dehesas, mixed-pine forests, olive groves). Analyses were performed separately at two different spatial scales: the sampling unit scale and the site scale. Land-use intensity effects on TD and FD were quite different and highly varied among the four biotic groups, with no single clear pattern emerging that could be considered general for all organisms. Additive partitioning of species diversity revealed clear contrasting patterns between TD and FD in the percentage of variability observed at each spatial scale. While most variability in TD was found at the larger scales, irregardless of organism group and land-use type, most variability in FD was found at the smallest scale, indicating that species turnover among communities is much greater than functional trait turnover. Finally, we found that TD and FD did not vary consistently, but rather followed different trajectories that largely depended on the biotic group and the intensity of land-use transformation. Our results highlight that the relationship of land use with TD and FD is highly complex and context-dependent.

Infectious diseases experts as part of the antibiotic stewardship team in primary care: protocol for a cluster-randomised blinded study (IDASP).

INTRODUCTION: Antibiotic overuse is directly related to antibiotic resistance, and primary care is one of the main reasons for this overuse. This study aims to demonstrate that including experts on infectious diseases (ID) within the antimicrobial stewardship (AMS) programme team in primary care settings achieves higher reductions in overall antibiotic consumption and increases the quality of prescription. METHODS AND ANALYSIS: A multicentre, cluster-randomised, blinded clinical trial will be conducted between 2021 and 2023. Six primary care centres will be randomly assigned to an advanced or a standard AMS programme. The advanced AMS programme will consist of a standard AMS programme combined with the possibility that general practitioners (GP) will discuss patients' therapies with ID experts telephonically during working days and biweekly meetings. The main endpoint will be overall antibiotic consumption, defined as daily defined dose per 1000 inhabitants per day (DHD). Secondary end-points will be: (1) unnecessary antibiotic prescriptions in patients diagnosed with upper respiratory tract or urinary tract infection, (2) adequacy of antibiotic prescription, (3) reattendance to GP or emergency room within 30 days after the initial GP visit and (4) hospital admissions for any reason within 30 days after the GP visit. Two secondary endpoints (unnecessary antibiotic therapy and adequacy of therapy) will be evaluated by blinded investigators.We will select three clusters (centres) per arm (coverage of 147 644 inhabitants) which will allow the rejection of the null hypothesis of equal consumption with a power of 80%, assuming a moderate intracluster correlation of 0.2, an intracluster variance of 4 and a mean difference of 1 DHD. The type I error will be set at 5%. ETHICS AND DISSEMINATION: The protocol was reviewed and approved by local ethics committees. The results of this study will be published in peer-reviewed journals and presented at medical conferences. TRIAL REGISTRATION NUMBER: NCT04848883.

Multicentre, randomised, open-label, phase IV-III study to evaluate the efficacy of cloxacillin plus fosfomycin versus cloxacillin alone in adult patients with methicillin-susceptible Staphylococcus aureus bacteraemia: study protocol for the SAFO trial.

INTRODUCTION: Methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia is a frequent condition, with high mortality rates. There is a growing interest in identifying new therapeutic regimens able to reduce therapeutic failure and mortality observed with the standard of care of beta-lactam monotherapy. In vitro and small-scale studies have found synergy between cloxacillin and fosfomycin against S. aureus. Our aim is to test the hypothesis that cloxacillin plus fosfomycin achieves higher treatment success than cloxacillin alone in patients with MSSA bacteraemia. METHODS: We will perform a superiority, randomised, open-label, phase IV-III, two-armed parallel group (1:1) clinical trial at 20 Spanish tertiary hospitals. Adults (≥18 years) with isolation of MSSA from at least one blood culture ≤72 hours before inclusion with evidence of infection, will be randomly allocated to receive either cloxacillin 2 g/4-hour intravenous plus fosfomycin 3 g/6-hour intravenous or cloxacillin 2 g/4-hour intravenous alone for 7 days. After the first week, sequential treatment and total duration of antibiotic therapy will be determined according to clinical criteria by the attending physician.Primary endpoints: (1) Treatment success at day 7, a composite endpoint comprising all the following criteria: patient alive, stable or with improved quick-Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA at day 7. (2) Treatment success at test of cure (TOC) visit: patient alive and no isolation of MSSA in blood culture or at another sterile site from day 8 until TOC (12 weeks after randomisation).We assume a rate of treatment success of 74% in the cloxacillin group. Accepting alpha risk of 0.05 and beta risk of 0.2 in a two-sided test, 183 subjects will be required in each of the control and experimental groups to obtain statistically significant difference of 12% (considered clinically significant). ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Ethics Committee of Bellvitge University Hospital (AC069/18) and from the Spanish Medicines and Healthcare Product Regulatory Agency (AEMPS, AC069/18), and is valid for all participating centres under existing Spanish legislation. The results will be presented at international meetings and will be made available to patients and funders. TRIAL REGISTRATION NUMBER: The protocol has been approved by AEMPS with the Trial Registration Number EudraCT 2018-001207-37. ClinicalTrials.gov Identifier: NCT03959345; Pre-results.

Endocrine therapy of metastatic breast cancer.

Breast cancer growth and dissemination is regulated by estrogen and different growth factor receptor signalling pathways. The increasing knowledge of the biology of breast cancer regarding the interaction of these signalling pathways provides a tool to understand endocrine therapies response and resistance mechanisms. In patients with slowly progressive disease, no visceral involvement, and minimal symptoms, endocrine therapy could be the strategy of choice, even if the tumor has low estrogen receptor expression. Ovarian suppression and tamoxifen are recommended for premenopausal patients whether aromatase inhibitors are the option for postmenopausal ones. Chemotherapy still remains as the right alternative for hormone unresponsive or resistant patients. This is a review focused on the different strategies and combinations of endocrine therapies for metastatic breast cancer patients considering the potential strategies clinically tested to overcome resistance and the different treatments of choice available for each scenario of disseminated disease.

Breast metastases as the first sign of recurrence of a cutaneous melanoma.

Malignant melanoma is the most rapidly increasing cancer in the world. Metastatic disease occurs in 20% of patients, and prognosis in these cases is poor. We report the case of a woman who presented breast metastasis as the first sign of recurrence of a melanoma.

Brain metastases in metastatic breast cancer patients receiving trastuzumab-based therapies.

INTRODUCTION: CNS metastases mean a great challenge. It has been suggested that the brain metastases incidence could be high in metastasic breast cancer patients receiving trastuzumab based-therapies. MATERIAL AND METHODS: We performed a descriptive analysis of our experience in this setting. 86 patients met the criteria (From Oct/99 to Oct/03). RESULTS: CNS progression occurred in 17 patients (19.5%). Mean age of CNS progression disease patients was 45.4 years while mean age for all the patients was 50.5 years. Response rate for the entire group of patients was: OR 39.7%; CB (OR + SD) 69%. Response rate to trastuzumab based-therapy was OR 82.4% and CB 88.2 at the time of CNS progression. Median time from the start of trastuzumab therapy up to the CNS progression was 10 months. OS was 23.4 weeks. CONCLUSIONS: The incidence of CNS involvement is high in young metastasic breast cancer women responding to trastuzumab-based therapies. This may lead to prophylactic cranial irradiation strategies or to the early detection in asymptomatic patients to improve surgery or radiosurgery results in these patients.

Could Adult European Pharmacoresistant Epilepsy Patients Be Treated With Higher Doses of Zonisamide?

OBJECTIVE: To examine the clinical effect (efficacy and tolerability) of high doses of zonisamide (ZNS) (>500 mg/d) in adult patients with pharmacoresistant epilepsy. METHODS: Between 2006 and 2013, all epileptic outpatients treated with high doses of ZNS were selected. Safety and efficacy were assessed based on patient and caregiver reports. Serum levels of ZNS and other concomitant antiepileptic drugs were evaluated if available. RESULTS: Nine patients (5 female): 8 focal/1 generalized pharmacoresistant epilepsy. Mean age: 34 years. Most frequent seizure type: complex partial seizures; other seizure types: generalized tonic-clonic, tonic, myoclonia. Zonisamide in polytherapy in all (100%), administered in tritherapy in 3 (33%) of 9 patients; mean dose: 633 (600-700) mg/d; efficacy (>50% seizure reduction) was observed in 5 (55%) of 9 patients. Five of 9 patients are still taking high doses of ZNS (more than 1 year). Adverse events were observed in 3 (37%) of 8 patients. Good tolerance to high doses of other antiepileptic drugs had been observed in 6 (66%) of 9 patients. Plasma levels of ZNS were only available in 2 patients; both were in the therapeutic range (34.95, 30.91) (10-40 mg/L). CONCLUSIONS: High doses of ZNS are effective and safe in pharmacoresistant epileptic patients. Therapeutic drug monitoring of ZNS may be considered at therapeutic failure.

Cuirasse skin metastases secondary to gastric adenocarcinoma.

Skin metastases are infrequent manifestations of solid tumours. However, it is important to recognize them since they may be the first evidence of a neoplasia, or a sign of tumour progression or recurrence. Skin metastases from gastric adenocarcinomas are particularly rare, and represent 6% of the total in males and 1% in females. We report, here, the case of a patient diagnosed with gastric adenocarcinoma with extensive subcutaneous infiltration of the abdominal wall, resulting in an abdominal cuirass.