Efficacy of extended infusion of β-lactam antibiotics for the treatment of febrile neutropenia in haematologic patients : Protocol for a randomised, multicentre, open-label, superiority clinical trial (BEATLE)

Altres ajuts: The BEATLE study is a non-commercial, investigator-driven clinical trial funded by the Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0005; RD16/0016/0010) The Spanish Clinical Research Network (SCReN) provides clinical trial data monitoring and oversees pharmacovigilance (PT17/0017/0010).Background: Febrile neutropaenia (FN) is a very common complication in patients with haematological malignancies and is associated with considerable morbidity and mortality. Broad-spectrum antipseudomonal β-lactam antibiotics (BLA) are routinely used for the treatment of cancer patients with FN. However, the clinical efficacy of BLA may be diminished in these patients because they present with pathophysiological variations that compromise the pharmacokinetic (PK) parameters of these antibiotics. Optimised administration of BLA in prolonged infusions has demonstrated better clinical outcomes in critically ill patients. However, there is a paucity of data on the usefulness of this strategy in patients with FN. The aim of this study is to test the hypothesis that the administration of BLA would be clinically more effective by extended infusion (EI) than by intermittent infusion (II) in haematological patients with FN. Methods: A randomised, multicentre, open-label, superiority clinical trial will be performed. Patients with haematological malignancies undergoing chemotherapy or haematopoietic stem-cell transplant and who have FN and receive empirical antibiotic therapy with cefepime, piperacillin-tazobactam or meropenem will be randomised (1:1) to receive the antibiotic by EI (during half the time of the dosing interval) in the study group, or by II (30 min) in the control group. The primary endpoint will be clinical efficacy, defined as defervescence without modifying the antibiotic treatment administered within the first 5 days of therapy. The primary endpoint will be analysed in the intention-to-treat population. The secondary endpoints will be pharmacokinetic/pharmacodynamic (PK/PD) target achievement, bacteraemia clearance, decrease in C-reactive protein, overall (30-day) case-fatality rate, adverse events and development of a population PK model of the BLA studied. Discussion: Data on the usefulness of BLA administration in patients with FN are scant. Only three clinical studies addressing this issue have been published thus far, with contradictory results. Moreover, these studies had some methodological flaws that limit the interpretation of their findings. If this randomised, multicentre, phase IV, open-label, superiority clinical trial validates the hypothesis that the administration of BLA is clinically more effective by EI than by II in haematological patients with FN, then the daily routine management of these high-risk patients could be changed to improve their outcomes. Trial registration: European Clinical Trials Database: EudraCT 2018-001476-37. ClinicalTrials.gov, ID: NCT04233996

Clinical efficacy of β-lactam/β-lactamase inhibitor combinations for the treatment of bloodstream infection due to extended-spectrum β-lactamase-producing Enterobacteriaceae in haematological patients with neutropaenia: a study protocol for a retrospective observational study (BICAR)

Introduction: Bloodstream infection (BSI) due to extended-spectrum β-lactamase-producing Gram-negative bacilli (ESBL-GNB) is increasing at an alarming pace worldwide. Although β-lactam/β-lactamase inhibitor (BLBLI) combinations have been suggested as an alternative to carbapenems for the treatment of BSI due to these resistant organisms in the general population, their usefulness for the treatment of BSI due to ESBL-GNB in haematological patients with neutropaenia is yet to be elucidated. The aim of the BICAR study is to compare the efficacy of BLBLI combinations with that of carbapenems for the treatment of BSI due to an ESBL-GNB in this population. Methods and analysis: A multinational, multicentre, observational retrospective study. Episodes of BSI due to ESBL-GNB occurring in haematological patients and haematopoietic stem cell transplant recipients with neutropaenia from 1 January 2006 to 31 March 2015 will be analysed. The primary end point will be case-fatality rate within 30 days of onset of BSI. The secondary end points will be 7-day and 14-day case-fatality rates, microbiological failure, colonisation/infection by resistant bacteria, superinfection, intensive care unit admission and development of adverse events. Sample size: The number of expected episodes of BSI due to ESBL-GNB in the participant centres will be 260 with a ratio of control to experimental participants of 2. Ethics and dissemination: The protocol of the study was approved at the first site by the Research Ethics Committee (REC) of Hospital Universitari de Bellvitge. Approval will be also sought from all relevant RECs. Any formal presentation or publication of data from this study will be considered as a joint publication by the participating investigators and will follow the recommendations of the International Committee of Medical Journal Editors (ICMJE). The study has been endorsed by the European Study Group for Bloodstream Infection and Sepsis (ESGBIS) and the European Study Group for Infections in Compromised Hosts (ESGICH)

The Impact of Culturing the Organ Preservation Fluid on Solid Organ Transplantation: A Prospective Multicenter Cohort Study

Background. We analyzed the prevalence, etiology, and risk factors of culture-positive preservation fluid and their impact on the management of solid organ transplant recipients. Methods. From July 2015 to March 2017, 622 episodes of adult solid organ transplants at 7 university hospitals in Spain were prospectively included in the study. Results. The prevalence of culture-positive preservation fluid was 62.5% (389/622). Nevertheless, in only 25.2% (98/389) of the cases were the isolates considered ?high risk? for pathogenicity. After applying a multivariate regression analysis, advanced donor age was the main associated factor for having culture-positive preservation fluid for high-risk microorganisms. Preemptive antibiotic therapy was given to 19.8% (77/389) of the cases. The incidence rate of preservation fluid?related infection was 1.3% (5 recipients); none of these patients had received preemptive therapy. Solid organ transplant (SOT) recipients with high-risk culture-positive preservation fluid receiving preemptive antibiotic therapy presented both a lower cumulative incidence of infection and a lower rate of acute rejection and graft loss compared with those who did not have high-risk culture-positive preservation fluid. After adjusting for age, sex, type of transplant, and prior graft rejection, preemptive antibiotic therapy remained a significant protective factor for 90-day infection. Conclusions. The routine culture of preservation fluid may be considered a tool that provides information about the contamination of the transplanted organ. Preemptive therapy for SOT recipients with high-risk culture-positive preservation fluid may be useful to avoid preservation fluid?related infections and improve the outcomes of infection, graft loss, and graft rejection in transplant patients

Pregnancy as a risk factor for severe influenza infection: an individual participant data meta-analysis

Background: WHO identifies pregnant women to be at increased risk for severe outcomes from influenza virus infections and recommends that they be prioritized for influenza vaccination. The evidence supporting this, however, is inconsistent. Ecologic studies in particular suggest more severe outcomes from influenza infection during pregnancy than studies based on individual patient data. Individual studies however may be underpowered and, as reported in a previous systematic review, confounding factors could not be adjusted for. We therefore conducted an individual participant data meta-analysis to assess the risk for severe outcomes of influenza infection in pregnant women while adjusting for other prognostic factors. Methods: We contacted authors of studies included in a recently published systematic review. We pooled the individual participant data of women of reproductive age and laboratory confirmation of influenza virus infection. We used a generalized linear mixed model and reported odds ratios (OR) and 95% confidence intervals (CI). Results: A total of 33 datasets with data on 186,656 individuals were available, including 36,498 eligible women of reproductive age and known pregnancy status. In the multivariable model, pregnancy was associated with a 7 times higher risk of hospital admission (OR 6.80, 95%CI 6.02–7.68), among patients receiving medical care as in- or outpatients, pregnancy was associated with a lower risk of admission to intensive care units (ICU; OR 0.57, 95%CI 0.48–0.69), and was not significantly associated with death (OR 1.00, 95%CI 0.75–1.34). Conclusions: Our study found a higher risk of influenza associated hospitalization among pregnant women as compared to non-pregnant women. We did not find a higher mortality rate or higher likelihood of ICU admission among pregnant women who sought medical care. However, this study did not address whether a true community based cohort of pregnant women is at higher risk of influenza associated complications.Fil: Mertz, Dominik. Mc Master University; CanadáFil: Lo, Calvin Ka Fung. Mc Master University; CanadáFil: Lytvyn, Lyubov. Mc Master University; CanadáFil: Ortiz, Justin R.. Organizacion Mundial de la Salud; ArgentinaFil: Loeb, Mark. Mc Master University; CanadáFil: Ang, Li Wei. Ministry of Health; SingapurFil: Anlikumar, Mehta Asmita. Amrita Vishwa Vidyapeetham; IndiaFil: Bonmarin, Isabelle. Santé publique; FranciaFil: Borja Aburto, Victor Hugo. Instituto Mexicano del Seguro Social; MéxicoFil: Burgmann, Heinz. Medical University Vienna; AustriaFil: Carratalà, Jordi. Universidad de Barcelona; España. Instituto de Investigación Biomédica de Bellvitge; España. Spanish Network for Research in Infectious Diseases; EspañaFil: Chowell, Gerardo. Georgia State University; Estados Unidos. National Institutes of Health; Estados UnidosFil: Cilloniz, Catia. Universidad de Barcelona; España. Instituto de Investigaciones Biomédicas August Pi i Sunyer; EspañaFil: Cohen, Jessica. Centers for Disease Control and Prevention; Estados UnidosFil: Cutter, Jeffery. Ministry of Health; SingapurFil: Filleul, Laurent. Santé publique; Francia. French National Public Health Agency; FranciaFil: Garg, Shikha. Centers for Disease Control and Prevention; Estados UnidosFil: Geis, Steffen. London School of Hygiene and Tropical Medicine; Reino UnidoFil: Helferty, Melissa. Public Health Agency; CanadáFil: Huang, Wan Ting. Taiwan Centers for Disease Control; ChinaFil: Jain, Seema. Centers for Disease Control and Prevention; Estados UnidosFil: Sevic, Biljana Joves. Institute for Pulmonary Diseases of Vojvodina; SerbiaFil: Kelly, Paul. Australian Capital Territory Health Directorate; Australia. Australian National University Medical School; AustraliaFil: Kusznierz, Gabriela. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorios e Instituto de Salud "Dr. C. G. Malbran". Instituto Nacional de Enfermedades Respiratorias; ArgentinaFil: Lehners, Nicola. Ruprecht Karls Universitat Heidelberg; AlemaniaFil: Lenzi, Luana. Universidade Federal do Paraná; BrasilFil: Ling, Ivan T.. Sir Charles Gairdner Hospital; AustraliaFil: Mitchell, Robyn. Public Health Agency; CanadáFil: Mulrennan, Siobhain A.. Sir Charles Gairdner Hospital; Canadá. University of Western Australia; AustraliaFil: Nishioka, Sergio A.. Ministerio de Salud de Brasil; BrasilFil: Norton, Robert. Townsville Hospital; AustraliaFil: Oh, Won Sup. Kangwon National University School of Medicine; Corea del SurFil: Orellano, Pablo Wenceslao. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Influence of socioeconomic status on community-acquired pneumonia outcomes in elderly patients requiring hospitalization: a multicenter observational study

The associations between socioeconomic status and community-acquired pneumonia outcomes in adults have been studied although studies did not always document a relationship. The aim of this multicenter observational study was to determine the association between socioeconomic status and community-acquired pneumonia outcomes in the elderly, in the context of a public health system providing universal free care to the whole population

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. © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ

Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances. These guidelines are intended for use by healthcare professionals who care for patients at risk for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), including specialists in infectious diseases, pulmonary diseases, critical care, and surgeons, anesthesiologists, hospitalists, and any clinicians and healthcare providers caring for hospitalized patients with nosocomial pneumonia. The panel's recommendations for the diagnosis and treatment of HAP and VAP are based upon evidence derived from topic-specific systematic literature reviews