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Objectives: This study aimed to assess the real use of cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis (IE) in the Spanish National Endocarditis Database (GAMES) and to compare it with antistaphylococcal penicillin (ASP). Methods: Prospective cohort study with retrospective analysis of a cohort of MSSA IE treated with cloxacillin and/or cefazolin. Outcomes assessed were relapse; intra-hospital, overall, and endocarditis-related mortality; and adverse events. Risk of renal toxicity with each treatment was evaluated separately. Results: We included 631 IE episodes caused by MSSA treated with cloxacillin and/or cefazolin. Antibiotic treatment was cloxacillin, cefazolin, or both in 537 (85%), 57 (9%), and 37 (6%) episodes, respectively. Patients treated with cefazolin had significantly higher rates of comorbidities (median Charlson Index 7, P

This large, multicenter, retrospective cohort study including onco-hematological neutropenic patients with Pseudomonas aeruginosa bloodstream infection (PABSI) found that among 1213 episodes, 411 (33%) presented with septic shock. The presence of solid tumors (33.3% vs. 20.2%, p < 0.001), a high-risk Multinational Association for Supportive Care in Cancer (MASCC) index score (92.6% vs. 57.4%; p < 0.001), pneumonia (38% vs. 19.2% p < 0.001), and infection due to multidrug-resistant P. aeruginosa (MDRPA) (33.8% vs. 21.1%, p < 0.001) were statistically significantly higher in patients with septic shock compared to those without. Patients with septic shock were more likely to receive inadequate empirical antibiotic therapy (IEAT) (21.7% vs. 16.2%, p = 0.020) and to present poorer outcomes, including a need for ICU admission (74% vs. 10.5%; p < 0.001), mechanical ventilation (49.1% vs. 5.6%; p < 0.001), and higher 7-day and 30-day case fatality rates (58.2% vs. 12%, p < 0.001, and 74% vs. 23.1%, p < 0.001, respectively). Risk factors for 30-day case fatality rate in patients with septic shock were orotracheal intubation, IEAT, infection due to MDRPA, and persistent PABSI. Therapy with granulocyte colony-stimulating factor and BSI from the urinary tract were associated with improved survival. Carbapenems were the most frequent IEAT in patients with septic shock, and the use of empirical combination therapy showed a tendency towards improved survival. Our findings emphasize the need for tailored management strategies in this high-risk population.

Several genetic polymorphisms of the innate immune system have been described to increase the risk of cytomegalovirus (CMV) infection in transplant patients. The aim of this study was to assess the impact of a polygenic score to predict CMV infection and disease in high risk CMV transplant recipients (heart, liver, kidney or pancreas). On hundred and sixteen CMV-seronegative recipients of grafts from CMV-seropositive donors undergoing heart, liver, and kidney or pancreas transplantation from 7 centres were prospectively included for this purpose during a 2-year period. All recipients received 100-day prophylaxis with valganciclovir. CMV infection occurred in 61 patients (53%) at 163 median days from transplant, 33 asymptomatic replication (28%) and 28 CMV disease (24%). Eleven patients (9%) had recurrent CMV infection. Clinically and/or functionally relevant single nucleotide polymorphisms (SNPs) from TLR2, TLR3, TLR4, TLR7, TLR9, AIM2, MBL2, IL28, IFI16, MYD88, IRAK2 and IRAK4 were assessed by real time polymerase chain reaction (RT-PCR) or sequence-based typing (PCR-SBT). A polygenic score including the TLR4 (rs4986790/rs4986791), TLR9 (rs3775291), TLR3 (rs3775296), AIM2 (rs855873), TLR7 (rs179008), MBL (OO/OA/XAO), IFNL3/IL28B (rs12979860) and IFI16 (rs6940) SNPs was built based on the risk of CMV infection and disease. The CMV score predicted the risk of CMV disease with an AUC of the model of 0.68, with sensitivity and specificity of 64.3 and 71.6%, respectively. Even though further studies are needed to validate this score, its use would represent an effective model to develop more robust scores predicting the risk of CMV disease in donor/recipient mismatch (D+/R-) transplant recipients.

Invasive fusariosis (IF) is associated with severe neutropenia in patients with concurrent hematologic conditions. We conducted a retrospective observational study to characterize the epidemiology of IF in 18 Spanish hospitals during 2000–2015. In that time, the frequency of IF in nonneutropenic patients increased from 0.08 cases per 100,000 admissions in 2000–2009 to 0.22 cases per 100,000 admissions in 2010–2015. Nonneutropenic IF patients often had nonhematologic conditions, such as chronic cardiac or lung disease, rheumatoid arthritis, history of solid organ transplantation, or localized fusariosis. The 90-day death rate among nonneutropenic patients (28.6%) and patients with resolved neutropenia (38.1%) was similar. However, the death rate among patients with persistent neutropenia (91.3%) was significantly higher. We used a multivariate Cox regression analysis to characterize risk factors for death: persistent neutropenia was the only risk factor for death, regardless of antifungal therapy.

Abstract Background Almost one third of the patients with candidemia develop septic shock. The understanding why some patients do and others do not develop septic shock is very limited. The objective of this study was to identify variables associated with septic shock development in a large population of patients with candidemia. Methods A post hoc analysis was performed on two prospective, multicenter cohort of patients with candidemia from 12 hospitals in Spain and Italy. All episodes occurring from September 2016 to February 2018 were analyzed to assess variables associated with septic shock development defined according to The Third International Consensus Definition for Sepsis and Septic Shock (Sepsis-3). Results Of 317 candidemic patients, 99 (31.2%) presented septic shock attributable to candidemia. Multivariate logistic regression analysis identifies the following factors associated with septic shock development: age > 50 years (OR 2.57, 95% CI 1.03–6.41, p = 0.04), abdominal source of the infection (OR 2.18, 95% CI 1.04–4.55, p = 0.04), and admission to a general ward at the time of candidemia onset (OR 0.21, 95% CI, 0.12–0.44, p = 0.001). Septic shock development was independently associated with a greater risk of 30-day mortality (OR 2.14, 95% CI 1.08–4.24, p = 0.02). Conclusions Age and abdominal source of the infection are the most important factors significantly associated with the development of septic shock in patients with candidemia. Our findings suggest that host factors and source of the infection may be more important for development of septic shock than intrinsic virulence factors of organisms.

Objectives: To assess the clinical features and outcomes of Pseudomonas aeruginosa bloodstream infection (PA BSI) in neutropenic patients with hematological malignancies (HM) and with solid tumors (ST), and identify the risk factors for 30-day mortality. Methods: We performed a large multicenter, retrospective cohort study including onco-hematological neutropenic patients with PA BSI conducted across 34 centers in 12 countries (January 2006–May 2018). Episodes occurring in hematologic patients were compared to those developing in patients with ST. Risk factors associated with 30-day mortality were investigated in both groups. Results: Of 1217 episodes of PA BSI, 917 occurred in patients with HM and 300 in patients with ST. Hematological patients had more commonly profound neutropenia (0.1 × 109 cells/mm) (67% vs. 44.6%; p < 0.001), and a high risk Multinational Association for Supportive Care in Cancer (MASCC) index score (32.2% vs. 26.7%; p = 0.05). Catheter-infection (10.7% vs. 4.7%; p = 0.001), mucositis (2.4% vs. 0.7%; p = 0.042), and perianal infection (3.6% vs. 0.3%; p = 0.001) predominated as BSI sources in the hematological patients, whereas pneumonia (22.9% vs. 33.7%; p < 0.001) and other abdominal sites (2.8% vs. 6.3%; p = 0.006) were more common in patients with ST. Hematological patients had more frequent BSI due to multidrug-resistant P. aeruginosa (MDRPA) (23.2% vs. 7.7%; p < 0.001), and were more likely to receive inadequate initial antibiotic therapy (IEAT) (20.1% vs. 12%; p < 0.001). Patients with ST presented more frequently with septic shock (45.8% vs. 30%; p < 0.001), and presented worse outcomes, with increased 7-day (38% vs. 24.2%; p < 0.001) and 30-day (49% vs. 37.3%; p < 0.001) case-fatality rates. Risk factors for 30-day mortality in hematologic patients were high risk MASCC index score, IEAT, pneumonia, infection due to MDRPA, and septic shock. Risk factors for 30-day mortality in patients with ST were high risk MASCC index score, IEAT, persistent BSI, and septic shock. Therapy with granulocyte colony-stimulating factor was associated with survival in both groups. Conclusions: The clinical features and outcomes of PA BSI in neutropenic cancer patients showed some differences depending on the underlying malignancy. Considering these differences and the risk factors for mortality may be useful to optimize their therapeutic management. Among the risk factors associated with overall mortality, IEAT and the administration of granulocyte colony-stimulating factor were the only modifiable variables.

IntroductionOur goal was to study whether influenza vaccination induced antibody mediated rejection in a large cohort of solid organ transplant recipients (SOTR).MethodsSerum anti-Human Leukocyte Antigen (HLA) antibodies were determined using class I and class II antibody-coated latex beads (FlowPRATM Screening Test) by flow cytometry. Anti-HLA antibody specificity was determined using the single-antigen bead flow cytometry (SAFC) assay and assignation of donor specific antibodies (DSA) was performed by virtual-crossmatch.ResultsWe studied a cohort of 490 SOTR that received an influenza vaccination from 2009 to 2013: 110 (22.4%) received the pandemic adjuvanted vaccine, 59 (12%) within the first 6 months post-transplantation, 185 (37.7%) more than 6 months after transplantation and 136 (27.7%) received two vaccination doses. Overall, no differences of anti-HLA antibodies were found after immunization in patients that received the adjuvanted vaccine, within the first 6 months post-transplantation, or based on the type of organ transplanted. However, the second immunization dose increased the percentage of patients positive for anti-HLA class I significantly compared with patients with one dose (14.6% vs. 3.8%; P = 0.003). Patients with pre-existing antibodies before vaccination (15.7% for anti-HLA class I and 15.9% for class II) did not increase reactivity after immunization. A group of 75 (14.4%) patients developed de novo anti-HLA antibodies, however, only 5 (1.02%) of them were DSA, and none experienced allograft rejection. Only two (0.4%) patients were diagnosed with graft rejection with favorable outcomes and neither of them developed DSA.ConclusionOur results suggest that influenza vaccination is not associated with graft rejection in this cohort of SOTR.

Enterococcus faecalis infective endocarditis (EFIE) is a severe disease of increasing incidence. The objective was to analyze whether the outcome of patients with native valve EFIE (NVEFIE) treated with a short course of ampicillin plus ceftriaxone (4wAC) was similar to patients treated according to international guidelines (6wAC). Between January 2008 and June 2018, 1,978 consecutive patients with definite native valve IE were prospectively included in a national registry. Outcomes of patients with NVEFIE treated with 4wAC were compared to those of patients who received 6wAC. Three hundred and twenty-two patients (16.3%) had NVEFIE. One hundred and eighty-three (56.8%) received AC. Thirty-nine patients (21.3%) were treated with 4wAC for four weeks and 70 patients (38.3%) with 6wAC. There were no differences in age or comorbidity. Patients treated 6wAC presented a longer duration of symptoms before diagnosis (21 days, IQR 7-60 days vs. 7 days, IQR 1-22 days; p = 0.002). Six patients presented perivalvular abscess and all of these received 6wAC. Surgery was performed on 14 patients (35.9%) 4wAC and 34 patients (48.6%) 6wAC (p = 0.201). In-hospital mortality, one-year mortality and relapses among 4wAC and 6wAC patients were 10.3% vs. 11.4% (p = 0.851); 17.9% vs. 21.4% (p = 0.682) and 5.1% vs. 4.3% (p = 0.833), respectively. In conclusion, a four-week course of AC may be considered as an alternative regimen in NVEFIE, notably in patients with shorter duration of symptoms and those without perivalvular abscess. These results support the performance of a randomized clinical trial to evaluate the efficacy of this short regimen.

ObjetivesThe aim of this study was to identify CMV drug resistance mutations (DRM) in solid organ transplant (SOT) recipients with suspected resistance comparing next-generation sequencing (NGS) with Sanger sequencing and assessing risk factors and the clinical impact of resistance.MethodsUsing Sanger sequencing as the reference method, we prospectively assessed the ability of NGS to detect CMV DRM in the UL97 and UL54 genes in a nationwide observational study from September 2013 to August 2016.ResultsAmong 44 patients recruited, 14 DRM were detected by Sanger in 12 patients (27%) and 20 DRM were detected by NGS, in 16 (36%). NGS confirmed all the DRM detected by Sanger. The additional six mutations detected by NGS were present in ConclusionsNGS showed a higher yield than Sanger sequencing for detecting CMV resistance mutations in SOT recipients. The presence of DRM detected by NGS was independently associated with longer antiviral treatment.

The use of endovascular catheters is a routine practice in secondary and tertiary care level hospitals. The short-term use of peripheral catheters has been found to be associated with the risk of nosocomial bacteraemia, resulting in morbidity and mortality. Staphylococcus aureus is mostly associated with peripheral catheter insertion. This Consensus Document has been prepared by a panel of experts of the Spanish Society of Cardiovascular Infections, in cooperation with experts from the Spanish Society of Internal Medicine, Spanish Society of Chemotherapy, and the Spanish Society of Thoracic-Cardiovascular Surgery, and aims to define and establish guidelines for the management of short duration peripheral vascular catheters. The document addresses the indications for insertion, catheter maintenance, registering, diagnosis and treatment of infection, indications for removal, as well as placing an emphasis on continuous education as a drive toward quality. Implementation of these guidelines will allow uniformity in use, thus minimizing the risk of infections and their complications.

To assess the effect of combination antibiotic empirical therapy on 30-day case-fatality rate in neutropenic cancer patients with Pseudomonas aeruginosa (PA) bacteremic pneumonia. This was a multinational, retrospective cohort study of neutropenic onco-hematological patients with PA bloodstream infection (BSI) (2006–2018). The effect of appropriate empirical combination therapy, appropriate monotherapy and inappropriate empirical antibiotic therapy [IEAT] on 30-day case-fatality was assessed only in patients with PA bacteremic pneumonia. Among 1017 PA BSI episodes, pneumonia was the source of BSI in 294 (28.9%). Among those, 52 (17.7%) were caused by a multidrug-resistant (MDR) strain and 68 (23.1%) received IEAT, mainly when the infection was caused by an MDR strain [38/52 (73.1%) vs. 30/242 (12.4%); p < 0.001]. The 30-day case-fatality rate was higher in patients with PA bacteremic pneumonia than in those with PA BSI from other sources (55.1% vs. 31.4%; p < 0.001). IEAT was associated with increased 30-day case-fatality (aHR 1.44 [95%CI 1.01–2.03]; p = 0.042), whereas the use of appropriate combination empirical treatment was independently associated with improved survival (aHR 0.46 [95%CI 0.27–0.78]; p = 0.004). Appropriate empirical monotherapy was not associated with improved overall survival (aHR 1.25 [95%CI 0.76–2.05]; p = 0.39). Combination antibiotic empirical therapy should be administered promptly in febrile neutropenic patients with suspected pneumonia as the source of infection.