Post-CART-T Cell Infection: Etiology, pathogenesis, and therapeutic approaches.

Chimeric antigen receptor (CAR) T cell therapy targeting CD-19 has revolutionized the treatment of refractory B-cell malignancies. However, patients undergoing this therapy face an increased risk of infections due to compromised immune function, lymphodepleting chemotherapy, hospitalization, and therapy-related complications such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome. Patients with systemic corticosteroid use, low immunoglobulin levels, and severe CRS, are at higher risk of infection. This review article highlights the spectrum of infections encountered in CAR T cell therapy, including bacterial, viral, and fungal infections. Following consensus guidelines for vaccination and immunoglobulin replacement is recommended. Clear criteria for antibiotic usage and vaccinating household members against respiratory viruses are crucial. Understanding the risk factors, spectrum of infections, and implementing appropriate prophylactic measures are essential to optimize outcomes in patients undergoing CAR T cell therapy. By prioritizing infection prevention strategies, healthcare professionals can effectively improve patient care.

Recommendations on the use of azole antifungals in hematology-oncology patients.

The administration of antifungals for therapeutic and, especially, prophylactic purposes is virtually a constant in patients requiring hematology-oncology treatment. Any attempt to prevent or treat Aspergillus or Mucor infections requires the administration of some drugs in the azole group, which include voriconazole, posaconazole and isavuconazole, noted for their activity against these pathogens. One very relevant aspect is the potential risk of interaction when associated with one of the antineoplastic drugs used to treat hematologic tumors, with serious complications. In this regard, acalabrutinib, bortezomib, bosutinib, carfilzomib, cyclophosphamide, cyclosporine A, dasatinib, duvelisib, gilteritinib, glasdegib, ibrutinib, imatinib, nilotinib, ponatinib, prednisone, ruxolitinib, tacrolimus, all-transretinoic acid, arsenic trioxide, venetoclax, or any of the vinca alkaloids, are very clear examples of risk, in some cases because their clearance is reduced and in others because of increased risk of QTc prolongation, which is particularly evident when the drug of choice is voriconazole or posaconazole.

Early Stepdown From Echinocandin to Fluconazole Treatment in Candidemia: A Post Hoc Analysis of Three Cohort Studies.

BACKGROUND: There are no clear criteria for antifungal de-escalation after initial empirical treatments. We hypothesized that early de-escalation (ED) (within 5 days) to fluconazole is safe in fluconazole-susceptible candidemia with controlled source of infection. METHODS: This is a multicenter post hoc study that included consecutive patients from 3 prospective candidemia cohorts (2007-2016). The impact of ED and factors associated with mortality were assessed. RESULTS: Of 1023 candidemia episodes, 235 met inclusion criteria. Of these, 54 (23%) were classified as the ED group and 181 (77%) were classified as the non-ED group. ED was more common in catheter-related candidemia (51.9% vs 31.5%; P = .006) and episodes caused by Candida parapsilosis, yet it was less frequent in patients in the intensive care unit (24.1% vs 39.2%; P = .043), infections caused by Nakaseomyces glabrata (0% vs 9.9%; P = .016), and candidemia from an unknown source (24.1% vs 47%; P = .003). In the ED and non-ED groups, 30-day mortality was 11.1% and 29.8% (P = .006), respectively. Chronic obstructive pulmonary disease (odds ratio [OR], 3.97; 95% confidence interval [CI], 1.48-10.61), Pitt score > 2 (OR, 4.39; 95% CI, 1.94-9.20), unknown source of candidemia (OR, 2.59; 95% CI, 1.14-5.86), candidemia caused by Candida albicans (OR, 3.92; 95% CI, 1.48-10.61), and prior surgery (OR, 0.29; 95% CI, 0.08-0.97) were independent predictors of mortality. Similar results were found when a propensity score for receiving ED was incorporated into the model. ED had no significant impact on mortality (OR, 0.50; 95% CI, 0.16-1.53). CONCLUSIONS: Early de-escalation is a safe strategy in patients with candidemia caused by fluconazole-susceptible strains with controlled source of bloodstream infection and hemodynamic stability. These results are important to apply antifungal stewardship strategies.

Experience with the use of siltuximab in patients with SARS-CoV-2 infection.

OBJECTIVE: The study aims to describe characteristics and clinical outcome of patients with SARS-CoV-2 infection that received siltuximab according to a protocol that aimed to early block the activity of IL-6 to avoid the progression of the inflammatory flare. METHODS: Retrospective review of the first 31 patients with SARS-CoV-2 treated with siltuximab, in Hospital Clinic of Barcelona or Hospital Universitario Salamanca, from March to April 2020 with positive polymerase-chain reaction (PCR) from a nasopharyngeal swab. RESULTS: The cohort included 31 cases that received siltuximab with a median (IQR) age of 62 (56-71) and 71% were males. The most frequent comorbidity was hypertension (48%). The median dose of siltuximab was 800 mg ranging between 785 and 900 mg. 7 patients received siltuximab as a salvage therapy after one dose of tocilizumab. At the end of the study, a total of 26 (83.9) patients had been discharged alive and the mortality rate was 16.1% but only 1 out of 24 that received siltuximab as a first line option (4%). CONCLUSIONS: Siltuximab is a well-tolerated alternative to tocilizumab when administered as a first line option in patients with COVID-19 pneumonia within the first 10 days from symptoms onset and high C-reactive protein.

Real-life use of remdesivir in hospitalized patients with COVID-19.

OBJECTIVE: Controversial results on remdesivir efficacy have been reported. We aimed to report our real-life experience with the use of remdesivir from its availability in Spain. METHODS: We performed a descriptive study of all patients admitted for ≥48 hours with confirmed COVID-19 who received remdesivir between the 1st of July and the 30th of September 2020. RESULTS: A total of 123 patients out of 242 admitted with COVID-19 at our hospital (50.8%) received remdesivir. Median age was 58 years, 61% were males and 56.9 % received at least one anti-inflammatory treatment. No adverse events requiring remdesivir discontinuation were reported. The need of intensive care unit admission, mechanical ventilation and 30-days mortality were 19.5%, 7.3% and 4.1%, respectively. CONCLUSIONS: In our real-life experience, the use of remdesivir in hospitalized patients with COVID-19 was associated with a low mortality rate and good safety profile.

Healthcare-associated pneumonia: a prospective study in Spain.

OBJECTIVE: The aim of the study was to describe the epidemiological characteristics and factors related to outcome in Streptococcus pneumoniae and methicillin-resistant Staphylococcus aureus (MRSA) healthcare-associated pneumonia (HCAP). METHODS: A 3-year prospective observational epidemiological case study of HCAP was conducted in seven Spanish hospitals. Microbiological and patient characteristics and outcomes were collected and classified by causative pathogen into 4 categories: "S. pneumoniae", "MRSA", "Others" and "Unknown". Patients were followed up 30 days after discharge. RESULTS: A total of 258 (84.6%) patients were enrolled (170 were men [65.9%]). Mean age was 72.4 years ± 15 years (95% CI [70.54-74.25]). The etiology of pneumonia was identified in 73 cases (28.3%): S. pneumoniae in 35 patients (13.6%), MRSA in 8 (3.1%), and other microorganisms in 30 patients (11.6%). Significant differences in rates of chronic obstructive pulmonary disease (p < 0.05), previous antibiotic treatment (p<0.05), other chronic respiratory diseases, inhaled corticosteroids (p <0.01), and lymphoma (p < 0.05) were observed among the four groups. Patients with MRSA pneumonia had received more previous antibiotic treatment (87.5%). Thirty-three (12.8%) patients died during hospitalisation; death in 27 (81.2%) was related to pneumonia. CONCLUSIONS: The etiology of HCAP was identified in only one quarter of patients, with S. pneumoniae being the most prevalent microorganism. Patients with chronic respiratory diseases more frequently presented HCAP due to MRSA than to S. pneumoniae. Death at hospital discharge was related in most cases to pneumonia.

Combination antifungal therapy for breakthrough invasive mould disease in patients with haematological malignancies: when management reasoning eclipses evidence-based medicine.

Timely diagnosis and treatment of invasive mould disease is challenging in severely immunocompromised patients, particularly for patients who develop breakthrough infections while on antifungal prophylaxis. Currently, there are no high-quality data on how to best diagnose and treat these infections. Many essential decisions affecting the management of breakthrough mould disease are made before a definitive diagnosis is established. In this scenario, sound management reasoning often favours the use of combination antifungal therapy, especially when antifungal resistance, suspicion of undetected sites of infection or pharmacokinetic/pharmacodynamic limitations at the site of infection are likely. In these scenarios, pre-emptive use of antifungal combination therapy with frequent re-evaluation with an aim of de-escalation could be justified for many high-risk patients.

Efficacy of extended infusion of ß-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 ß-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.

Predictors of multidrug-resistant Pseudomonas aeruginosa in neutropenic patients with bloodstream infection.

OBJECTIVES: To assess risk factors for multidrug-resistant Pseudomonas aeruginosa (MDR-PA) infection in neutropenic patients. METHODS: Single-centre retrospective analysis of consecutive bloodstream infection (BSI) episodes (2004-2017, Barcelona). Two multivariate regression models were used at BSI diagnosis and P. aeruginosa detection. Significant predictors were used to establish rules for stratifying patients according to MDR-PA BSI risk. RESULTS: Of 661 Gram-negative BSI episodes, 190 (28.7%) were caused by P. aeruginosa (70 MDR-PA). Independent factors associated with MDR-PA among Gram-negative organisms were haematological malignancy (OR 3.30; 95% CI 1.15-9.50), pulmonary source of infection (OR 7.85; 95% CI 3.32-18.56), nosocomial-acquired BSI (OR 3.52; 95% CI 1.74-7.09), previous antipseudomonal cephalosporin (OR 13.66; 95% CI 6.64-28.10) and piperacillin/tazobactam (OR 2.42; 95% CI 1.04-5.63), and BSI occurring during ceftriaxone (OR 4.27; 95% CI 1.15-15.83). Once P. aeruginosa was identified as the BSI aetiological pathogen, nosocomial acquisition (OR 7.13; 95% CI 2.87-17.67), haematological malignancy (OR 3.44; 95% CI 1.07-10.98), previous antipseudomonal cephalosporin (OR 3.82; 95% CI 1.42-10.22) and quinolones (OR 3.97; 95% CI 1.37-11.48), corticosteroids (OR 2.92; 95% CI 1.15-7.40), and BSI occurring during quinolone (OR 4.88; 95% CI 1.58-15.05) and ß-lactam other than ertapenem (OR 4.51; 95% CI 1.45-14.04) were independently associated with MDR-PA. Per regression coefficients, 1 point was assigned to each parameter, except for nosocomial-acquired BSI (3 points). In the second analysis, a score >3 points identified 60 (86.3%) out of 70 individuals with MDR-PA BSI and discarded 100 (84.2%) out of 120 with non-MDR-PA BSI. CONCLUSIONS: A simple score based on demographic and clinical factors allows stratification of individuals with bacteraemia according to their risk of MDR-PA BSI, and may help facilitate the use of rapid MDR-detection tools and improve early antibiotic appropriateness.

Prophylaxis of mould infections.

Invasive fungal infection continues to be an important cause of morbidity and mortality in haematological patients. Antifungal prophylaxis in these patients has remarkably increased survival since its introduction. In recent years, new antifungals have been on the rise, being more effective and having less toxicity than previous ones. Nonetheless, the number of patients at risk of fungal infection has also been increasing due to the continuous appearance of new immunosuppressive treatments. As a result of such, we face a changing situation that requires constant updating.

Current time-to-positivity of blood cultures in febrile neutropenia: a tool to be used in stewardship de-escalation strategies.

OBJECTIVES: We aimed to describe the current time-to-positivity (TTP) of blood cultures in individuals with onco-haematological diseases with febrile neutropenia. We assessed the probability of having a multidrug-resistant Gram-negative bacilli (MDR-GNB) bloodstream infection (BSI) 24 h after cultures were taken, to use this information for antibiotic de-escalation strategies. METHODS: BSI episodes were prospectively collected (2003-2017). When a patient experienced more than one BSI, only one episode was randomly chosen. Time elapsed from the beginning of incubation to a positive reading was observed; TTP was recorded when the first bottle had a positive result. RESULTS: Of the 850 patient-unique episodes, 323 (38%) occurred in acute leukaemia, 185 (21.8%) in non-Hodgkin's lymphoma and 144 (16.9%) in solid neoplasms. Coagulase-negative staphylococci (225; 26.5%), Escherichia coli (207; 26.1%), Pseudomonas aeruginosa (136; 16%), Enterococcus spp. (81; 9.5%) and Klebsiella pneumoniae (67; 7.9%), were the most frequent microorganisms isolated. MDR-GNB were documented in 126 (14.8%) episodes. Median TTP was 12 h (interquartile range 9-16.5 h). Within the first 24 h, 92.1% of blood cultures were positive (783/850). No MDR-GNB was positive over 24 h. Of the 67 (7.9%) episodes with a TTP ≥24 h, 25 (37.3%) occurred in patients who were already receiving active antibiotics against the isolated pathogen. Most common isolations with TTP ≥24 h were coagulase-negative staphylococci, candidaemia and a group of anaerobic GNB. CONCLUSIONS: Currently, the vast majority of BSI in individuals with onco-haematological diseases with febrile neutropenia have a TTP <24 h, including all episodes caused by MDR-GNB. Our results support reassessing empiric antibiotic treatment in neutropenic patients at 24 h, to apply antibiotic stewardship de-escalation strategies.

Factors influencing mortality in neutropenic patients with haematologic malignancies or solid tumours with bloodstream infection.

The purpose of this study was to identify factors influencing mortality in neutropenic patients with haematologic malignancies or solid tumours with bloodstream infection (BSI). All episodes of BSI occurring in adult neutropenic patients with haematologic malignancies or solid tumours were prospectively recorded from January 2006 to December 2013. We analysed the factors influencing mortality in both groups of patients. We documented 602 consecutive episodes of BSI; 510 occurred in patients with haematologic malignancies and 92 in patients with solid tumours. The overall case-fatality rates were 12% and 36%, respectively. Independent risk factors associated with a higher case-fatality rate in patients with haematologic malignancies were: intensive care unit admission (odds ratio (OR), 15.2; 95% confidence interval (CI), 5.4-42.7), advanced neoplasm (OR, 8.7; 95% CI, 2.9-25.7), corticosteroid therapy (OR, 7.0; 95% CI, 3-16.4), multidrug-resistant Gram-negative BSI (OR, 3.8; 95% CI, 1.2-11.8) and a Multinational Association for Supportive Care in Cancer risk score of <21 (OR, 3.1; 95% CI, 1.3-7.4). By contrast, coagulase-negative staphylococci BSI (OR, 0.04; 95% CI, 0.004-0.5) and empirical antibiotic combination therapy (OR, 0.1; 95% CI, 0.05-0.3) were found to be protective. Independent risk factors for overall case-fatality rate in patients with solid tumours were: shock at presentation (OR, 14.3; 95% CI, 3.2-63.8), corticosteroid therapy (OR, 10; 95% CI, 2.3-44) and advanced neoplasm (OR, 7.8; 95% CI, 1.4-41.4). Prognostic factors identified in this study may help to detect those patients at higher risk of death in each group. Medical intervention addressing some of these factors might improve the outcome of BSI in neutropenic patients with haematologic malignancies or solid tumours.

Unusual forms of subacute invasive pulmonary aspergillosis in patients with solid tumors.

OBJECTIVES: Aspergillus spp. can cause acute invasive disease in severely immunocompromised patients. Nonetheless, there are few reports of solid tumors complicated with subacute invasive pulmonary aspergillosis (subacute IPA). METHODS: Retrospective observational cohort study, performed in patients with primary lung cancer or secondary lung metastasis complicated with subacute IPA in three referral hospitals. RESULTS: From 2008 to 2011, 14 episodes of subacute IPA were diagnosed, including 11 (78.6%) probable and 3 proven (21.4%). Nine patients (64.3%) had primary lung cancer. Thirteen patients (92.9%) had more than one local or systemic predisposing factor for subacute IPA. No patient had previous fungal colonization. Aspergillus spp. was isolated in 6 specimens of bronchoalveolar lavage, 6 sputum, 2 biopsies, and 1 percutaneous lung puncture. At the time Aspergillus spp. was isolated, the most common radiologic findings on chest computed tomography (CT) were cavitary masses, and development or expansion of cavitation in existing masses or nodules (10/14, 71.4%). On CT follow-up, most patients (8/12, 66.7%) had new cavity formation or expansion of one or more existing cavities. All patients were treated with azoles and two underwent surgery. Ten (71.4%) patients died after Aspergillus spp. was detected (median time 73 days, IQR 33-243): 2 (20%) deaths were subacute IPA-attributable and 6 (60%) were related. CONCLUSIONS: Primary lung cancer and secondary lung metastasis seem to be triggering factors for Aspergillus spp. implantation, and predispose to subacute IPA. Once localized in the damaged lung, the mold can grow and cause or expand cavities. In lung cancer patients, Aspergillus spp. detection is associated with a very poor prognosis.

Environmental variables associated with an increased risk of invasive aspergillosis.

Information on the environmental variables that may affect the incidence of invasive aspergillosis (IA) is scarce. We sought to determine the relationship between airborne spore counts, climatic conditions and IA. We also examined whether circulating respiratory viruses predispose patients to IA in a multicentre cohort study of hospitalized adults with IA. Data on environmental mould spores, climatic conditions and circulating respiratory viruses were obtained from the Environmental Department of the Autonomous University of Barcelona, the Meteorological Service of Catalonia and the Acute Respiratory Infection Surveillance Project in Catalonia, respectively. Between 2008 and 2011, 165 patients with IA were identified. Diagnosis was based on one or more of the following: culture (125 cases), galactomannan antigen (98) and histology (34). One hundred and twenty-seven cases (77%) had criteria for probable IA and the remainder for proven IA. Environmental mould spore counts from the period 28-42 days preceding infection presented significant associations with admissions due to IA. None of the climatic conditions were associated with an increased risk of IA, but the presence of circulating respiratory viruses was associated with a higher risk of infection: the most strongly associated viruses were respiratory syncytial virus, influenza A(H1N1)pdm09 and adenovirus. In conclusion, the presence of high numbers of spores in the air increases the risk of admission due to IA. Circulating respiratory viruses appear to be associated with a higher risk of developing IA. Physicians should be aware of this association in order to optimize prevention and diagnosis strategies for IA during viral epidemic periods.

Etiology, clinical features and outcomes of pre-engraftment and post-engraftment bloodstream infection in hematopoietic SCT recipients.

We conducted an observational study to assess the etiology, clinical features and outcomes of bloodstream infection (BSI) in 172 hematopoietic SCT (HCST) recipients. One hundred episodes of BSI in the pre-engraftment period (early onset) were compared with 89 episodes in the post-engraftment phase (late onset). More patients with late-onset BSI received an allogeneic HSCT, had GVHD and had received corticosteroids, whereas patients with early-onset BSI were more likely to have neutropenia, severe mucositis and a central venous catheter (CVC) in place. CVC was the most frequent site of infection, followed by an endogenous source. Pneumonia and gastrointestinal infection were particularly frequent in late-onset BSI, whereas mucositis was more frequent in the early-onset group. Gram-positive organisms predominated over Gram negatives. Streptococcus pneumoniae was more frequent in patients with late-onset BSI. Patients with late-onset BSI presented worse outcomes regarding septic shock, intensive care unit admission and early and overall case-fatality rates. Early-onset BSI was mainly related to the presence of neutropenia, mucositis and CVC, whereas late-onset BSI mainly affected severely immunosuppressed allogeneic HSCT recipients with GVHD and corticosteroids. Late-onset BSI caused high case-fatality rates. BSI due to S. pneumoniae was especially frequent late after transplantation. The development of better vaccination strategies is needed.

Bacteraemia due to multidrug-resistant Gram-negative bacilli in cancer patients: risk factors, antibiotic therapy and outcomes.

OBJECTIVES: To assess the risk factors, antibiotic therapy and outcomes of multidrug-resistant Gram-negative bacilli (MDRGNB) bacteraemia in hospitalized patients with cancer. METHODS: Episodes of MDRGNB bacteraemia were compared with a susceptible control group in a 4 year prospective study. RESULTS: Of 747 bacteraemias, 372 (49.7%) were caused by a Gram-negative bacilli (GNB). Fifty-one of these (13.7%) were caused by a multidrug-resistant (MDR) strain. Previous antibiotics [odds ratio (OR) 3.57; 95% confidence interval (CI) 1.63-7.80] and urinary catheter (OR 2.41; 95% CI 1.01-5.74) were identified as independent risk factors for MDRGNB acquisition. The most frequent mechanism of resistance was extended-spectrum ß-lactamase (ESBL) production (45%), mainly by Escherichia coli, followed by Amp-C cephalosporinase hyperproduction (24%). Patients with MDRGNB bacteraemia more frequently received inadequate initial antibiotic therapy (69% versus 9%; P < 0.001) and time to adequate therapy was longer in this group (41% versus 4%; P < 0.001). Patients in the resistant group more frequently required intensive care unit (ICU) admission (14% versus 5%; P = 0.023), had greater need for mechanical ventilation (14% versus 3%; P = 0.005) and had a higher overall case-fatality rate (41% versus 21%; P = 0.003). Risk factors for mortality were solid tumour (OR 5.04; 95% CI 2.49-10.19), current corticosteroid use (OR 4.38; 95% CI 2.39-8.05), ICU admission (OR 11.40; 95% CI 3.19-40.74) and MDRGNB bacteraemia (OR 3.52; 95% CI 1.36-9.09). CONCLUSIONS: MDRGNB bacteraemia was common among cancer patients, especially in those exposed to antibiotics and urinary catheter. The most frequent mechanism of resistance was ESBL production. Patients with MDRGNB more frequently received inadequate empirical antibiotic therapy and presented poorer outcomes with a higher overall case-fatality rate (within 30 days).

Effect of statins on outcomes in immunosuppressed patients with bloodstream infection.

Although it has been suggested that statins have a beneficial effect on the outcome of bloodstream infection (BSI) in immunosuppressed patients, prospective studies testing this hypothesis are lacking. We performed an observational analysis of consecutive cancer patients and transplant recipients hospitalized at two tertiary hospitals in Spain (2006-2009). The first episode of BSI occurring in statin users was compared with those occurring in non-statin users. During the study period, 668 consecutive episodes of BSI in 476 immunosuppressed patients were recorded. Underlying diseases were solid tumor (46.2%), hematologic malignancy (35.1%), and transplantation (18.7%). Fifty-nine (12.4%) patients were receiving statins at the onset of BSI. Comparing with statin non-users, patients on statin treatment were older (67.3 vs. 58.7 years; p < 0.001) and had higher frequency of comorbidities (74.6% vs. 40.6%; p < 0.001). There were no significant differences in intensive care unit admission (6.8% vs. 7.7%; p = 1) and overall mortality (15.3% vs. 24%; p = 0.13) between groups. In a multivariate analysis, prior statin use was not associated with increased survival (odds ratio [OR], 0.52; 95% confidence interval [CI], 0.22-1.23; p = 0.14). In conclusion, prior statin use is not associated with increased survival in immunosuppressed patients with BSI. Caution is warranted in attributing beneficial effects to statin use in infections among immunocompromised patients.

Recent improvement in long-term survival after a COPD hospitalisation.

BACKGROUND: Evidence-based international guidelines on chronic obstructive pulmonary disease (COPD), and their corresponding recommendations, were established to improve individual COPD prognosis, and ultimately to improve survival. The aim of this study was to determine whether the long-term mortality after discharge from a COPD hospitalisation has improved recently, and the effect of co-morbidity treatment in improving COPD prognosis. METHODS: In a prospective cohort study design of two cohorts 7 years apart, patients discharged from the same university hospital after a COPD exacerbation were followed-up, and their outcomes compared. Demographic and clinical variables, as well as lung function, were collected with the same protocol by the same investigators. Comprehensive assessments of co-morbidities and treatments were undertaken. Kaplan-Meier survival curves were estimated, and outcomes were compared by means of Cox regression methods. RESULTS: Overall, 135 participants in the 1996-7 cohort and 181 participants in the 2003-4 cohort were studied. Both cohorts were comparable in their baseline demographic and clinical variables, and median follow-up was 439 days. The 3-year mortality was lower in the 2003-4 cohort (38.7%) than in the 1996-7 cohort (47.4%) (p=0.017), and the RR of death after adjustment for gender, age, body mass index, co-morbidities, lung function and mMRC (modified Medical Research Council scale) dyspnoea was 0.66 (95% CI 0.45 to 0.97). Long-term survival improved in the second cohort for patients with COPD with heart failure or cancer (p<0.001). CONCLUSIONS: A recent trend towards better prognosis of patients with COPD after hospital discharge is described and is likely to be associated with better management and treatment of COPD and co-morbidities.

Pneumococcal pneumonia presenting with septic shock: host- and pathogen-related factors and outcomes.

BACKGROUND: Host- and pathogen-related factors associated with septic shock in pneumococcal pneumonia are not well defined. The aim of this study was to identify risk factors for septic shock and to ascertain patient outcomes. Serotypes, genotypes and antibiotic resistance of isolated strains were also analysed. METHODS: Observational analysis of a prospective cohort of non-severely immunosuppressed hospitalised adults with pneumococcal pneumonia. Septic shock was defined as a systolic blood pressure of <90 mm Hg and peripheral hypoperfusion with the need for vasopressors for >4 h after fluid replacement. RESULTS: 1041 patients with pneumococcal pneumonia diagnosed by Gram stain and culture of appropriate samples and/or urine antigen test were documented, of whom 114 (10.9%) had septic shock at admission. After adjustment, independent risk factors for shock were current tobacco smoking (OR, 2.11; 95% CI, 1.02 to 4.34; p = 0.044), chronic corticosteroid treatment (OR, 4.45; 95% CI, 1.75 to 11.32; p = 0.002) and serotype 3 (OR, 2.24; 95% CI, 1.12 to 4.475; p = 0.022). No significant differences were found in genotypes and rates of antibiotic resistance. Compared with the remaining patients, patients with septic shock required mechanical ventilation more frequently (37% vs 4%; p<0.001) and had longer length of stay (11 vs 8 days; p<0.001). The early (10% vs 1%; p<0.001) and overall case fatality rates (25% vs 5%; p<0.001) were higher in patients with shock. CONCLUSIONS: Septic shock is a frequent complication of pneumococcal pneumonia and causes high morbidity and mortality. Current tobacco smoking, chronic corticosteroid treatment and infection caused by serotype 3 are independent risk factors for this complication.

Risk factors for opportunistic infections in infliximab-treated patients: the importance of screening in prevention.

We sought to determine factors associated with opportunistic infections (OI) in infliximab-treated patients. A retrospective study cohort (1999-2004) was examined. Nine OI were diagnosed in 94 infliximab-treated patients: tuberculosis (four), visceral leishmaniasis (one), pyogenic muscular abscess (one Salmonella spp. and one Streptococcus pneumoniae), and two viral infections (hepatitis B virus [HBV] and zoster ophthalmicus). The risk for OI was significantly higher in the first year of treatment (odds ratio [OR] 8; 95% confidence interval [CI] 2-50). Previous treatment with more than two immunosuppressive drugs was the only factor related to OI (OR 8.686; 95% CI 1.889-39.943). We identified the subset of patients treated with infliximab who had a higher risk for OI. The screening of latent infections is key to diminishing the incidence of these infections.