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Introduction Pseudomonas aeruginosa (PA) has historically been one of the major causes of severe sepsis and death among neutropenic cancer patients. There has been a recent increase of multidrug-resistant PA (MDRPA) isolates that may determine a worse prognosis, particularly in immunosuppressed patients. The aim of this study is to establish the impact of antibiotic resistance on the outcome of neutropenic onco-haematological patients with PA bacteraemia, and to identify the risk factors for MDRPA bacteraemia and mortality. Methods and analysis This is a retrospective, observational, multicentre, international study. All episodes of PA bacteraemia occurring in neutropenic onco-haematological patients followed up at the participating centres from 1 January 2006 to 31 May 2018 will be retrospectively reviewed. The primary end point will be overall case-fatality rate within 30 days of onset of PA bacteraemia. The secondary end points will be to describe the following: the incidence and risk factors for multidrug-resistant and extremely drug-resistant PA bacteraemia (by comparing the episodes due to susceptible PA with those produced by MDRPA), the efficacy of ceftolozane/tazobactam, the rates of persistent bacteraemia and bacteraemia relapse and the risk factors for very early (48 hours), early (7 days) and overall (30 days) case-fatality rates. Ethics and dissemination The Clinical Research Ethics Committee of Bellvitge University Hospital approved the protocol of the study at the primary site. To protect personal privacy, identifying information of each patient in the electronic database will be encrypted. The processing of the patients’ personal data collected in the study will comply with the Spanish Data Protection Act of 1998 and with the European Directive on the privacy of data. All data collected, stored and processed will be anonymised. Results will be reported at conferences and in peer-reviewed publications.

Background We aimed to describe the current rates of inappropriate empirical antibiotic treatment (IEAT) in oncohematological patients with febrile neutropenia (FN) and its impact on mortality. Methods This was a multicenter prospective study of all episodes of bloodstream infection (BSI) in high-risk FN patients (2006–2017). Episodes receiving IEAT were compared with episodes receiving appropriate empirical therapy. Adherence to Infectious Diseases Society of America (IDSA) recommendations was evaluated. Multivariate analysis was performed to identify independent risk factors for mortality in Pseudomonas aeruginosa episodes. Results Of 1615 episodes, including Escherichia coli (24%), coagulase-negative staphylococci (21%), and P. aeruginosa (16%), 394 (24%) received IEAT despite IDSA recommendations being followed in 87% of cases. Patients with multidrug-resistant gram-negative bacilli (MDR-GNB), accounting for 221 (14%) of all isolates, were more likely to receive IEAT (39% vs 7%, P < .001). Overall mortality was higher in patients with GNB BSI who received IEAT (36% vs 24%, P = .004); when considering individual microorganisms, only patients with infection caused by P. aeruginosa experienced a significant increase in mortality when receiving IEAT (48% vs 31%, P = .027). Independent risk factors for mortality in PA BSI (odds ratio [95% confidence interval] were IEAT (2.41 [1.19–4.91]), shock at onset (4.62 [2.49–8.56]), and pneumonia (3.01 [1.55–5.83]). Conclusions IEAT is frequent in high-risk patients with FN and BSI, despite high adherence to guidelines. This inappropriate treatment primarily impacts patients with P. aeruginosa–related BSI mortality and in turn is the only modifiable factor to improve outcomes.

Alemtuzumab, a humanized monoclonal antibody for the treatment of relapsing-remitting multiple sclerosis, produce the rapid depletion of all mature lymphocytes. For this reason, patients are at an increased risk of developing infections due to the reactivation of latent agents or acquired microorganisms. Most infections reported during the phase III trials were mild or moderate in severity, while serious infections were surprisingly uncommon.1 However, during the postmarketing use of alemtuzumab, several opportunistic infections have been reported.2–5 We describe a patient who presented simultaneous cytomegalovirus (CMV) reactivation and Listeria meningitis promptly following the first course of alemtuzumab.

Introduction: Pseudomonas aeruginosa (PA) has historically been one of the major causes of severe sepsis and death among neutropenic cancer patients. There has been a recent increase of multidrug-resistant PA (MDRPA) isolates that may determine a worse prognosis, particularly in immunosuppressed patients. The aim of this study is to establish the impact of antibiotic resistance on the outcome of neutropenic onco-haematological patients with PA bacteraemia, and to identify the risk factors for MDRPA bacteraemia and mortality. Methods and analysis: This is a retrospective, observational, multicentre, international study. All episodes of PA bacteraemia occurring in neutropenic oncohaematological patients followed up at the participating centres from 1 January 2006 to 31 May 2018 will be retrospectively reviewed. The primary end point will be overall case-fatality rate within 30 days of onset of PA bacteraemia. The secondary end points will be to describe the following: the incidence and risk factors for multidrugresistant and extremely drug-resistant PA bacteraemia (by comparing the episodes due to susceptible PA with those produced by MDRPA), the efficacy of ceftolozane/ tazobactam, the rates of persistent bacteraemia and bacteraemia relapse and the risk factors for very early (48 hours), early (7 days) and overall (30 days) case-fatality rates. Ethics and dissemination: The Clinical Research Ethics Committee of Bellvitge University Hospital approved the protocol of the study at the primary site. To protect personal privacy, identifying information of each patient in the electronic database will be encrypted. The processing of the patients’ personal data collected in the study will comply with the Spanish Data Protection Act of 1998 and with the European Directive on the privacy of data. All data collected, stored and processed will be anonymised. Results will be reported at conferences and in peerreviewed publications.

A high degree of vigilance and appropriate diagnostic methods are required to detect Clostridioides difficile infection (CDI). We studied the effectiveness of a multimodal training program for improving CDI surveillance and prevention. Between 2011 and 2016, this program was made available to healthcare staff of acute care hospitals in Catalonia. The program included an online course, two face-to-face workshops and dissemination of recommendations on prevention and diagnosis. Adherence to the recommendations was evaluated through surveys administered to the infection control teams at the 38 participating hospitals. The incidence of CDI increased from 2.20 cases/10 000 patient-days in 2011 to 3.41 in 2016 (P < 0.001). The number of hospitals that applied an optimal diagnostic algorithm rose from 32.0% to 71.1% (P = 0.002). Hospitals that applied an optimal diagnostic algorithm reported a higher overall incidence of CDI (3.62 vs. 1.92, P < 0.001), and hospitals that were more active in searching for cases reported higher rates of hospital-acquired CDI (1.76 vs. 0.84, P < 0.001). The results suggest that the application of a multimodal training strategy was associated with a significant rise in the reporting of CDI, as well as with an increase in the application of the optimal diagnostic algorithm.

Increased microvessel density in atherosclerotic plaques plays a major role in promoting plaque destabilization resulting in increased risk of stroke and myocardial infarction. Previously we have shown that expression of the inflammatory cytokine, Oncostatin-M (OSM), in human atherosclerotic plaques correlated with increased microvessel density, indicating a role for OSM in promoting plaque angiogenesis. The purpose of this study was to determine the mechanism by which OSM regulates Vascular Endothelial Growth Factor (VEGF) expression in human coronary artery smooth muscle cells. Using shRNA and overexpression studies, we have shown that the transcription factor, STAT-1 inhibited VEGF expression, while STAT-3 promoted the expression of VEGF. We further show that the mechanism by which STAT-1 and STAT-3 regulates VEGF expression is through modulation of Hypoxia Inducible Factor-1α (HIF-1α). STAT-1 suppresses HIF-1α expression, whereas STAT-3 positively regulates HIF-1α expression. These results provide evidence that activated STAT-1 and STAT-3 regulate VEGF expression indirectly, by modulating HIF-1α activity.

Objective Chronic inflammation plays a pivotal role in the development and progression of atherosclerosis. The inflammatory response is mediated by cytokines. The aim of this study was to determine if Oncostatin M (OSM), a monocyte and T-lymphocyte specific cytokine is present in atherosclerotic lesions. We also investigated the roles of signal transducer and activator of transcription (STAT)-1 and STAT-3 in regulating OSM-induced smooth muscle cell (SMC) proliferation, migration and cellular fibronectin (cFN) synthesis. Methods and results Immunostaining of atherosclerotic lesions from human carotid plaques demonstrated the expression of OSM antigen in both macrophages and SMCs. Explanted SMCs from human carotid plaques expressed OSM mRNA and protein as determined by RT-PCR and Western blotting. Using the chow-fed ApoE −/− mouse model of atherosclerosis, we observed that OSM was initially expressed in the intima at 20 weeks of age. By 30 weeks, OSM was expressed in both the intima and media. In vitro studies show that OSM promotes SMC proliferation, migration and cFN synthesis. Lentivirus mediated-inhibition of STAT-1 and STAT-3 prevented OSM-induced SMC proliferation, migration and cellular fibronectin synthesis. Conclusions These findings demonstrate that OSM is expressed in atherosclerotic lesions and may contribute to the progression of atherosclerosis by promoting SMC proliferation, migration and extracellular matrix protein synthesis through the STAT pathway.