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 retrospect 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).Ministerio de Economía y Competitividad REIPI RD12/001

Infections simulating immune checkpoint inhibitor toxicities: uncommon and deceptive

Use of immune checkpoint inhibitors (ICIs), a revolutionary treatment in modern oncology, is frequently complicated by immune-related adverse events (irAEs), which can be confused with infections, and vice versa, thus complicating management decisions. In this study, we review the published cases of infections as simulators of irAEs in cancer patients

Co-infections and superinfections complicating COVID-19 in cancer patients: A multicentre, international study

Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Complicacions infeccioses; CàncerCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Complicaciones infecciosas; CáncerCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Infectious complications; CancerBackground We aimed to describe the epidemiology, risk factors, and clinical outcomes of co-infections and superinfections in onco-hematological patients with COVID-19. Methods International, multicentre cohort study of cancer patients with COVID-19. All patients were included in the analysis of co-infections at diagnosis, while only patients admitted at least 48 h were included in the analysis of superinfections. Results 684 patients were included (384 with solid tumors and 300 with hematological malignancies). Co-infections and superinfections were documented in 7.8% (54/684) and 19.1% (113/590) of patients, respectively. Lower respiratory tract infections were the most frequent infectious complications, most often caused by Streptococcus pneumoniae and Pseudomonas aeruginosa . Only seven patients developed opportunistic infections. Compared to patients without infectious complications, those with infections had worse outcomes, with high rates of acute respiratory distress syndrome, intensive care unit (ICU) admission, and case-fatality rates. Neutropenia, ICU admission and high levels of C-reactive protein (CRP) were independent risk factors for infections. Conclusions Infectious complications in cancer patients with COVID-19 were lower than expected, affecting mainly neutropenic patients with high levels of CRP and/or ICU admission. The rate of opportunistic infections was unexpectedly low. The use of empiric antimicrobials in cancer patients with COVID-19 needs to be optimized.This study was supported by the Spanish Plan Nacional de IDi 2013-2016, Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, and the Spanish Network for Research in Infectious Diseases (REIPI grant: RD16/0016/0001). It was also co-financed by the European Development Regional Fund ‘A Way to Make Europe’, Operational Programme Smart Growth 2014-2020

Risk Factors for Nosocomial Bacterremia Due to Methicillin-Resistant Staphylococcus Aureus

In a prospective surveillance study (February 1990–December 1991) performed at a 1000-bed teaching hospital to identify risk factors for nosocomial methicillin-resistantStaphylococcus aureus (MRSA) bacteremia, 309 patients were found to be colonized (n=103; 33 %) or infected (n=206; 67 %) by MRSA. Sixty-three of them developed bacteremia. Compared with 114 patients who had nosocomial bacteremia caused by methicillin-sensitiveStaphylococcus aureus during the same period of time, MRSA bacteremic patients had more severe underlying diseases (p<0.01), were more often in intensive care units (p<0.01) and had received prior antibiotic therapy more frequently (p<0.01). To further identify risk factors for MRSA bacteremia, univariate and multivariate analyses of this series of 309 patients were performed using the occurrence of MRSA bacteremia as the dependent variable. Among 14 variables analyzed, intravascular catheterization, defined as one or more intravascular catheters in place for more than 48 h, was the only variable selected by a logistic regression model as an independent risk factor (OR=2.7, CI=1.1–6.6). The results of this study reinforce the concept that recent antibiotic therapy may predispose patients to MRSA infection and suggest that among patients colonized or infected by MRSA, those with intravascular catheters are at high risk of developing MRSA bacteremia

Nosocomial Staphylococcus Aureus Bacterimia among Nasal Carriers of Methicillin- Resistant and Methicillin-Susceptible Strains

Objectives To determine the relevance of nasal carriage of Staphylococcus aureus, either methicillin-sensitive (MSSA) or methicillinresistant (MRSA), as a risk factor for the development of nosocomial S aureus bacteremia during an MRSA outbreak. patients and methods: In this prospective cohort study, 488 patients admitted to an intensive care unit (ICU) during a 1-year period were screened with nasal swabs within 48 hours of admission and weekly thereafter in order to identify nasal S aureus carriage. Nasal staphylococcal carriers were observed until development of S aureus bacteremia, ICU discharge, or death. Results One hundred forty-seven (30.1%) of 488 patients were nasal S aureus carriers; 84 patients (17.2%) harbored methicillin-sensitive S aureus; and 63 patients (12.9%) methicillinresistant S aureus. Nosocomial S aureus bacteremia was diagnosed in 38 (7.7%) of 488 patients. Rates of bacteremia were 24 (38%) of the MRSA carriers, eight (9.5%) of the MSSA carriers, and six (1.7%) of noncarriers. After adjusting for other predictors of bacteremia by means of a Cox proportional hazard regression model, the relative risk for S aureus bacteremia was 3.9 (95% confidence interval, 1.6–9.8; P = 0.002) for MRSA carriers compared with MSSA carriers. Conclusions Among ICU patients, nasal carriers of S aureus are at higher risk for S aureus bacteremia than are noncarriers; in the setting of an MRSA outbreak, colonization by methicillin-resistant strains represents a greater risk than does colonization by MSSA and strongly predicts the occurrence of MRSA bacteremia

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

The emerging problem of bacterial resistance in cancer patients; proceedings of a workshop held by MASCC “Neutropenia, Infection and Myelosuppression” Study Group during the MASCC annual meeting held in Berlin on 27–29 June 2013

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

A Phase I/II Clinical Trial to evaluate the efficacy of baricitinib to prevent respiratory insufficiency progression in onco-hematological patients affected with COVID19: a structured summary of a study protocol for a randomised controlled trial

Objectives: Baricitinib is supposed to have a double effect on SARS-CoV2 infection. Firstly, it reduces the inflammatory response through the inhibition of the Januse-Kinase signalling transducer and activator of transcription (JAK-STAT) pathway. Moreover, it reduces the receptor mediated viral endocytosis by AP2-associated protein kinase 1 (AAK1) inhibition. We propose the use of baricinitib to prevent the progression of the respiratory insufficiency in SARS-CoV2 pneumonia in onco-haematological patients. In this phase Ib/II study, the primary objective in the safety cohort is to describe the incidence of severe adverse events associated with baricitinib administration. The primary objective of the randomized phase (baricitinib cohort versus standard of care cohort) is to evaluate the number of patients who did not require mechanical oxygen support since start of therapy until day +14 or discharge (whichever it comes first). The secondary objectives of the study (only randomized phase of the study) are represented by the comparison between the two arms of the study in terms of mortality and toxicity at day+30. Moreover, a description of the immunological related changes between the two arms of the study will be reported. Trial design: The trial is a phase I/II study with a safety run-in cohort (phase 1) followed by an open label phase II randomized controlled trial with an experimental arm compared to a standard of care arm

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

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 beta-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