Clinical outcomes of an innovative cefazolin delivery program for MSSA infections in OPAT

Cefazolin is a recommended treatment for methicillin-susceptible Staphylococcus aureus (MSSA) infections that has been successfully used in outpatient parenteral antibiotic therapy (OPAT) programs. The aim of this study was to assess the clinical outcomes of cefazolin delivered each day (Group 24) vs. every two days (Group 48) for MSSA infections in OPAT programs. It was a prospective observational study with retrospective analysis of a cohort of MSSA infections attended in OPAT. The primary outcome was treatment success, defined as completing the antimicrobial regimen without death, treatment discontinuation, or readmission during treatment and follow-up. A univariate and multivariate logistic regression model was built. A two-sided p < 0.05 was considered statistically significant. Of the 149 MSSA infections treated with cefazolin 2 g/8 h in OPATs, 94 and 55 patients were included in the delivery Group 24 and Group 48, respectively. Treatment failure and unplanned readmission rates were similar in both groups (11.7% vs. 7.3% p = 0.752 and 8.5% vs. 5.5% p = 0.491). There was a significant increase in vascular access complications in Group 24 (33.0%) with respect to Group 48 (7.3%) (p < 0.001). Treating uncomplicated MSSA infection with cefazolin home-delivered every two days through an OPAT program is not associated with an increased risk of treatment failure and entails a significant reduction in resource consumption compared to daily delivery

AMP-activated kinase in human spermatozoa: Identification, intracellular localization, and key function in the regulation of sperm motility

AMP‑activated kinase (AMPK), a protein that regulates energy balance and metabolism, has recently been identified in boar spermatozoa where regulates key functional sperm processes essential for fertilization. This work’s aims are AMPK identification, intracellular localization, and their role in human spermatozoa function. Semen was obtained from healthy human donors. Sperm AMPK and phospho‑Thr172‑AMPK were analyzed by Western blotting and indirect immunofluorescence. High‑ and low‑quality sperm populations were separated by a 40%–80% density gradient. Human spermatozoa motility was evaluated by an Integrated Semen Analysis System (ISAS) in the presence or absence of the AMPK inhibitor compound C (CC). AMPK is localized along the human spermatozoa, at the entire acrosome, midpiece and tail with variable intensity, whereas its active form, phospho‑Thr172‑AMPK, shows a prominent staining at the acrosome and sperm tail with a weaker staining in the midpiece and the postacrosomal region. Interestingly, spermatozoa bearing an excess residual cytoplasm show strong AMPK staining in this subcellular compartment. Both AMPK and phospho‑Thr172‑AMPK human spermatozoa contents exhibit important individual variations. Moreover, active AMPK is predominant in the high motility sperm population, where shows a stronger intensity compared with the low motility sperm population. Inhibition of AMPK activity in human spermatozoa by CC treatment leads to a significant reduction in any sperm motility parameter analyzed: percent of motile sperm, sperm velocities, progressivity, and other motility coefficients. This work identifies and points out AMPK as a new molecular mechanism involved in human spermatozoa motility. Further AMPK implications in the clinical efficiency of assisted reproduction and in other reproductive areas need to be studied.Trabajo patrocinado por: Mutua Madrileña. Beca Junta de Extremadura y Fondos FEDER. Ayudas JUEX‑IBI13121, PCJ1008, GR10125, y GR10156 Fundación Tatiana Pérez Guzmán el Bueno. Beca para Violeta Calle Guisado Ministerio de Educación y Ciencia. Beca Predoctoral FPU para Violeta Calle GuisadopeerReviewe

Prevalence and Risk Factors for Multidrug-Resistant Organisms Colonization in Long-Term Care Facilities Around the World: A Review

Elderly people confined to chronic care facilities face an increased risk of acquiring infections by multidrug-resistant organisms (MDROs). This review presents the current knowledge of the prevalence and risk factors for colonization by MDROs in long-term care facilities (LTCF), thereby providing a useful reference to establish objectives for implementing successful antimicrobial stewardship programs (ASPs). We searched in PubMed and Scopus for studies examining the prevalence of MDROs and/or risk factors for the acquisition of MDROs in LTCF. One hundred and thirty-four studies published from 1987 to 2020 were included. The prevalence of MDROs in LTCF varies between the different continents, where Asia reported the highest prevalence of extended-spectrum ß-lactamase (ESBL) Enterobacterales (71.6%), carbapenem resistant (CR) Enterobacterales (6.9%) and methicillin-resistant Staphylococcus aureus (MRSA) (25.6%) and North America the highest prevalence to MDR Pseudomonas aeruginosa (5.4%), MDR Acinetobacter baumannii (15.0%), vancomycin-resistant Enterococcus spp. (VRE) (4.0%), and Clostridioides difficile (26.1%). Furthermore, MDRO prevalence has experienced changes over time, with increases in MDR P. aeruginosa and extended spectrum ß-lactamase producing Enterobacterales observed starting in 2015 and decreases of CR Enterobacterales, MDR A. baumannii, VRE, MRSA and C. difficile. Several risk factors have been found, such as male sex, chronic wounds, the use of medical devices, and previous antibiotic use. The last of these aspects represents one of the most important modifiable factors for reducing colonization with MDROs through implementing ASPs in LTCF.The study was funded by the Instituto de Salud Carlos III, the Spanish Ministry of Economy, Industry, and Competitiveness (grant number: PI17-02195) and was partially funded by the European Development Regional Fund “A way to achieve Europe”. A.R.V. and A.B.G.G. are supported by the Subprograma Río Hortega, Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spain. A.R.V. grant number: CM18/00122. A.B.G.G. grant number: CM19/00029. C.M.G. and J.C.C.R. are supported by the Instituto de Salud Carlos III (grant number: PI17-02195) and co-financed by European Development Regional Fund ‘A way to achieve Europe’ ERDF, Spanish Network for the Research in Infectious Diseases (REIPI RD16/0016/0009).G.P. is supported by the Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0001)- co-financed by European Development Regional Fund “A way to achieve Europe”, Operative program Intelligent Growth 2014–2020. M.E.P.I. is a postdoctoral researcher belonging to the program “Nicolás Monardes” (C1-0038-2019), Servicio Andaluz de Salud, Junta de Andalucía, Spain. J.M.C. received funding for research from Plan Nacional de I+D+i 2013–2016 and Instituto de Salud Carlos III, Subdireccion General de Redes y Centros de InvestigacionCooperativa, Ministry of Economy, Industry and Competitiveness, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0001, RD16/0016/0009), co-financed by the European Development Regional Fund “A way to achieve Europe”.Ye

Application of new indicators to assess the quality of antimicrobial use in intensive care units

This study explored the feasibility of a bundle of indicators aimed at assessing the quality of antimicrobial use in intensive care units (ICUs) through an observational prospective study spanning 12 quarters (January 2019-December 2021) in a 1290-bed teaching hospital in Spain. Members of the antimicrobial stewardship programme team selected the indicators to analyse the quality of antimicrobial use based on consumption data from a list proposed in a previous study. Antimicrobial use in the ICU was measured as defined daily dose (DDD) per 100 occupied bed-days. Trends and points of change were analysed with segmented regression. The intravenous macrolides/intravenous respiratory fluoroquinolones ratio in the ICU increased progressively, although not significantly, by 11.14% per quarter, likely related to prioritization of the use of macrolides in serious community-acquired pneumonia and the coronavirus disease 2019 pandemic. A remarkable upward trend of 2.5% per quarter was detected in the anti-methicillin-susceptible Staphylococcus aureus/anti-methicillin-resistant S. aureus agents ratio in the ICU, which could be explained by the low prevalence of methicillin-resistant S. aureus at the study centre. Patterns of amoxicillin-clavulanic acid/piperacillin-tazobactam ratio and diversification of anti-pseudomonal beta-lactams showed an increment in use over the study. The use of these novel indicators provides additional information for the current analysis of DDD. Implementation is feasible, and led to the detection of patterns that agree with local guidelines and cumulative antibiogram reports, and foster targeted improvement actions within antimicrobial stewardship programmes.A.B.G. receives financial support from Subprograma Juan Rodés, Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spain (JR21/00017). G.P. receives a grant from the Plan Andaluz de Investigación, Desarrollo e Innovación, Consejería de Transformación Económica, Industria, Conocimiento y Universidades, Junta de Andalucía, Spain (Grant PAIDI2020/POSTDOC_21_00831). L.H. and M.M. receive financial support from Subprograma Río Hortega, Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spain (CM19/00152 and CM21/00115).Peer reviewe

The effect of an online exercise programme on bone health in paediatric cancer survivors (iBoneFIT): study protocol of a multi-centre randomized controlled trial

Background: New approaches on paediatric cancer treatment aim to maintain long-term health. As a result of radiotherapy, chemotherapy or surgery, paediatric cancer survivors tend to suffer from any chronic health condition. Endocrine dysfunction represents one of the most common issues and affects bone health. Exercise is key for bone mass accrual during growth, specifically plyometric jump training. The iBoneFIT study will investigate the effect of a 9-month online exercise programme on bone health in paediatric cancer survivors. This study will also examine the effect of the intervention on body composition, physical fitness, physical activity, calcium intake, vitamin D, blood samples quality of life and mental health. Methods: A minimum of 116 participants aged 6 to 18 years will be randomized into an intervention (n = 58) or control group (n = 58). The intervention group will receive an online exercise programme and diet counselling on calcium and vitamin D. In addition, five behaviour change techniques and a gamification design will be implemented in order to increase the interest of this non-game programme. The control group will only receive diet counselling. Participants will be assessed on 3 occasions: 1) at baseline; 2) after the 9 months of the intervention; 3) 4 months following the intervention. The primary outcome will be determined by dual energy X-ray absorptiometry (DXA) and the hip structural analysis, trabecular bone score and 3D-DXA softwares. Secondary outcomes will include anthropometry, body composition, physical fitness, physical activity, calcium and vitamin D intake, blood samples, quality of life and mental health. Discussion: Whether a simple, feasible and short in duration exercise programme can improve bone health has not been examined in paediatric cancer survivors. This article describes the design, rationale and methods of a study intended to test the effect of a rigorous online exercise programme on bone health in paediatric cancer survivors. If successful, the iBoneFIT study will contribute to decrease chronic health conditions in this population and will have a positive impact in the society.The iBoneFIT project is funded by a fellowship from 'la Caixa' Foundation (ID 100010434). The fellowship code is LCF/BQ/PR19/11700007. This study has been partially supported by the University of Granada, Plan Propio de Investigación 2016, Excellence actions: Units of Excellence; Unit of Excellence on Exercise and Health (UCEES), and by the Junta de Andalucía, Consejería de Conocimiento, Investigación y Universidades and European Regional Development Fund (ERDF), ref. SOMM17/6107/UGR

Statistical analysis plan. Study protocol for a randomized clinical trial to assess 7 versus 14-days of treatment for Pseudomonas aeruginosa bloodstream infections (SHORTEN-2 trial)

Efficacy and safety of 7 versus 14 days of antibiotic treatment for Pseudomonas aeruginosa bacteraemia: a multicentre, randomized clinical trial (SHORTEN-2) with a DOOR/RADAR analysis.Peer reviewe

Full-length study protocol (Spanish). Study protocol for a randomized clinical trial to assess 7 versus 14-days of treatment for Pseudomonas aeruginosa bloodstream infections (SHORTEN-2 trial)

Eficacia y seguridad de 7 versus 14 días de tratamiento antibiótico para la bacteriemia producida por Pseudomonas aeruginosa: un ensayo clínico multicéntrico, aleatorizado (SHORTEN-2) con un análisis DOOR/RADAR.Peer reviewe

Results of the survey among participating centers regarding diagnostic and clinical routines for the management of BSI-PA

S4 File. Results of the survey among participating centers regarding diagnostic and clinical routines for the management of BSI-PAPeer reviewe

Full-length study protocol (English). Study protocol for a randomized clinical trial to assess 7 versus 14-days of treatment for Pseudomonas aeruginosa bloodstream infections (SHORTEN-2 trial)

Efficacy and safety of 7 versus 14 days of antibiotic treatment for Pseudomonas aeruginosa bacteraemia: a multicentre, randomized clinical trial (SHORTEN-2) with a DOOR/RADAR analysis.Peer reviewe

List of participating centers. Study protocol for a randomized clinical trial to assess 7 versus 14-days of treatment for Pseudomonas aeruginosa bloodstream infections (SHORTEN-2 trial)

S1 File. List of participating centers.Peer reviewe