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

BACKGROUND: 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.

Antifungal susceptibility testing in Candida, Aspergillus and Cryptococcus infections: are the MICs useful for clinicians?

BACKGROUND: Invasive fungal infections (IFIs) represent a global issue and affect various patient populations. In recent years, resistant fungal isolates showing increased azole or echinocandin MICs have been reported, and their potential clinical impact has been investigated. AIMS: To provide an update on the epidemiology of resistance among fungi (e.g., Candida spp., Aspergillus spp., and Cryptococcus spp.) and to offer a critical appraisal of the relevant literature regarding the impact of MICs on clinical outcome in patients with IFI. SOURCES: PubMed search with relevant keywords along with a personal collection of relevant publications. CONTENT: Although antifungal resistance has been associated with a poorer response to antifungal therapy in various studies, other factors such as comorbidities, septic shock and source of infection appear to be key determinants affecting the clinical outcome of patients with IFI. IMPLICATIONS: Future international collaborative studies are required to tease out the relative contribution of in vitro antifungal resistance on patient outcomes, thus enabling the optimization of IFI management.

Clinical Predictive Model of Multidrug Resistance in Neutropenic Cancer Patients with Bloodstream Infection Due to Pseudomonas aeruginosa.

We aimed to assess the rate and predictive factors of bloodstream infection (BSI) due to multidrug-resistant (MDR) Pseudomonas aeruginosa in neutropenic cancer patients. We performed a multicenter, retrospective cohort study including oncohematological neutropenic patients with BSI due to P. aeruginosa conducted across 34 centers in 12 countries from January 2006 to May 2018. A mixed logistic regression model was used to estimate a model to predict the multidrug resistance of the causative pathogens. Of a total of 1,217 episodes of BSI due to P. aeruginosa, 309 episodes (25.4%) were caused by MDR strains. The rate of multidrug resistance increased significantly over the study period (P = 0.033). Predictors of MDR P. aeruginosa BSI were prior therapy with piperacillin-tazobactam (odds ratio [OR], 3.48; 95% confidence interval [CI], 2.29 to 5.30), prior antipseudomonal carbapenem use (OR, 2.53; 95% CI, 1.65 to 3.87), fluoroquinolone prophylaxis (OR, 2.99; 95% CI, 1.92 to 4.64), underlying hematological disease (OR, 2.09; 95% CI, 1.26 to 3.44), and the presence of a urinary catheter (OR, 2.54; 95% CI, 1.65 to 3.91), whereas older age (OR, 0.98; 95% CI, 0.97 to 0.99) was found to be protective. Our prediction model achieves good discrimination and calibration, thereby identifying neutropenic patients at higher risk of BSI due to MDR P. aeruginosa The application of this model using a web-based calculator may be a simple strategy to identify high-risk patients who may benefit from the early administration of broad-spectrum antibiotic coverage against MDR strains according to the local susceptibility patterns, thus avoiding the use of broad-spectrum antibiotics in patients at a low risk of resistance development.

The burden of severe cases of Influenza disease: the Friuli Venezia Giulia Region experience.

INTRODUCTION: Influenza is a matter of serious concern for clinicians, in both outpatient and in-hospital settings. Worldwide, the 2017-18 epidemic proved to be the most severe since 2003-04. We report a real-world experience regarding the management of patients with influenza admitted to a large teaching hospital in the Friuli Venezia Giulia region during the 2017-2018 influenza season. We also provide a practical guide for the management of hospitalized influenza patients. METHODS: A retrospective observational analysis was conducted among all influenza patients requiring admission to our center during the 2017-18 season. RESULTS: Overall, 29 patients were admitted to the University Hospital of Udine during the 2017-18 season with a diagnosis of influenza. B virus was responsible for the majority of cases. More than 65.5% of the subjects presented with a complication. We estimated that 41.4% of the patients admitted were affected by a "severe form". All these cases required admission to the Intensive Care Unit, with 27.6% and 10.3% needing Orotracheal Intubation and Extracorporeal Membrane Oxygenation, respectively. The fatality rate was 24.1%. Notably, only 9 subjects in our cohort had been vaccinated. Based on the experience acquired during the past season, we propose a practical guide to the management of influenza cases in everyday hospital practice. CONCLUSION: The cornerstones of the management of all hospitalized influenza patients are the rapid identification and treatment of severe forms. Timely and strict adherence to contact and respiratory precautions are also fundamental to reducing the risk of intra-hospital outbreaks. Despite improvements in antiviral therapies and supportive measures, influenza-related morbidity and mortality remain high. In our opinion, a universal vaccination program is the only safe and effective method of filling the gap.

The changing epidemiology of spinal tuberculosis: the influence of international immigration in Catalonia, 1993-2014.

The overall incidence of spinal tuberculosis (TB) appears to be stable or declining in most European countries, but with an increasing proportion of cases in the foreign-born populations. We performed a retrospective observational study (1993-2014), including all cases of spinal TB diagnosed at a Barcelona hospital to assess the epidemiological changes. Fifty-four episodes (48·1% males, median age 52 years) of spinal TB were diagnosed. The percentage of foreign-born residents with spinal TB increased from 14% to 45·2% in the last 10 years (P = 0·017). Positive Mycobacterium tuberculosis testing in vertebral specimens was 88·2% (15/17) for GeneXpert MTB/RIF. Compared with natives, foreign-born patients were younger (P < 0·01) and required surgery more often (P = 0·003) because of higher percentages of paravertebral abscess (P = 0·038), cord compression (P = 0·05), and persistent neurological sequelae (P = 0·05). In our setting, one-third of spinal TB cases occurred in non-native residents. Compared with natives, foreign-born patients were younger and had greater severity of the disease. The GeneXpert MTB/RIF test may be of value for diagnosing spinal TB.

Clinical efficacy of ß-lactam/ß-lactamase inhibitor combinations for the treatment of bloodstream infection due to extended-spectrum ß-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 ß-lactamase-producing Gram-negative bacilli (ESBL-GNB) is increasing at an alarming pace worldwide. Although ß-lactam/ß-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).

Epidemiology and Immediate Indirect Effects of Respiratory Viruses in Lung Transplant Recipients: A 5-Year Prospective Study.

The epidemiology of respiratory viruses (RVs) in lung transplant recipients (LTRs) and the relationship of RVs to lung function, acute rejection (AR) and opportunistic infections in these patients are not well known. We performed a prospective cohort study (2009-2014) by collecting nasopharyngeal swabs (NPSs) from asymptomatic LTRs during seasonal changes and from LTRs with upper respiratory tract infectious disease (URTID), lower respiratory tract infectious disease (LRTID) and AR. NPSs were analyzed by multiplex polymerase chain reaction. Overall, 1094 NPSs were collected from 98 patients with a 23.6% positivity rate and mean follow-up of 3.4 years (interquartile range 2.5-4.0 years). Approximately half of URTIDs (47 of 97, 48.5%) and tracheobronchitis cases (22 of 56, 39.3%) were caused by picornavirus, whereas pneumonia was caused mainly by paramyxovirus (four of nine, 44.4%) and influenza (two of nine, 22.2%). In LTRs with LRTID, lung function changed significantly at 1 mo (p = 0.03) and 3 mo (p = 0.04). In a nested case-control analysis, AR was associated with RVs (hazard ratio [HR] 6.54), Pseudomonas aeruginosa was associated with LRTID (HR 8.54), and cytomegalovirus (CMV) replication or disease was associated with URTID (HR 2.53) in the previous 3 mo. There was no association between RVs and Aspergillus spp. colonization or infection (HR 0.71). In conclusion, we documented a high incidence of RV infections in LTRs. LRTID produced significant lung function abnormalities. Associations were observed between AR and RVs, between P. aeruginosa colonization or infection and LRTID, and between CMV replication or disease and URTID.

Epidemiology of invasive respiratory disease caused by emerging non-Aspergillus molds in lung transplant recipients.

OBJECTIVES: Our aim was to assess the impact of positive cultures for non-Aspergillus molds on the risk of progression to invasive fungal infection (IFI), and the effect of prophylactic nebulized liposomal amphotericin B (n-LAB) on these pathogens. METHODS: This was an observational study (2003-2013) including lung transplant recipients (LTR) receiving lifetime n-LAB prophylaxis, in whom non-Aspergillus molds were isolated on respiratory culture before and after transplantation (minimum 1-year follow-up). RESULTS: We studied 412 patients, with a mean postoperative follow-up of 2.56 years (interquartile range 1.01-4.65). Pre- and post-transplantation respiratory samples were frequently positive for non-Aspergillus molds (11.9% and 16.9% of LTR respectively). Post transplantation, 10 (2.42%) patients developed non-Aspergillus mold infection (4 Scedosporium species, 4 Purpureocillium species, 1 Penicillium species, and 1 Scopulariopsis species); 5 (1.21%) had IFI, with 60% IFI-related mortality. Non-Aspergillus molds with intrinsic amphotericin B (AB) resistance were more commonly isolated in bronchoscopy samples than AB-variably sensitive or AB-sensitive molds (54.5% vs. 25%, P = 0.04) and were associated with a higher risk of infection (56.3% vs. 1.3%%, P < 0.01). CONCLUSIONS: In LTR undergoing n-LAB prophylaxis, pre- and post-transplantation isolation of non-Aspergillus molds is frequent, but IFI incidence (1.21%) is low. Purpureocillium is an emerging mold. AB-resistant non-Aspergillus species were found more often in bronchoscopy samples and were associated with a higher risk of infection.

Influenza vaccination during the first 6 months after solid organ transplantation is efficacious and safe.

Preventing influenza infection early after transplantation is essential, given the disease's high mortality. A multicentre prospective cohort study in adult solid organ transplant recipients (SOTR) receiving the influenza vaccine during four consecutive influenza seasons (2009-2013) was performed to assess the immunogenicity and safety of influenza vaccination in SOTR before and 6 months after transplantation. A total of 798 SOTR, 130 of them vaccinated within 6 months of transplantation and 668 of them vaccinated more than 6 months since transplantation. Seroprotection was similar in both groups: 73.1% vs. 76.5% for A/(H1N1)pdm (p 0.49), 67.5% vs. 74.1% for A/H3N2 (p 0.17) and 84.2% vs. 85.2% for influenza B (p 0.80), respectively. Geometric mean titres after vaccination did not differ among groups: 117.32 (95% confidence interval (CI) 81.52, 168.83) vs. 87.43 (95% CI 72.87, 104.91) for A/(H1N1)pdm, 120.45 (95% CI 82.17, 176.57) vs. 97.86 (95% CI 81.34, 117.44) for A/H3N2 and 143.32 (95% CI 103.46, 198.53) vs. 145.54 (95% CI 122.35, 174.24) for influenza B, respectively. After adjusting for confounding factors, time since transplantation was not associated with response to vaccination. No cases of rejection or severe adverse events were detected in patients vaccinated within the first 6 months after transplantation. In conclusion, influenza vaccination within the first 6 months after transplantation is as safe and immunogenic as vaccination thereafter. Thus, administration of the influenza vaccine can be recommended as soon as 1 month after transplantation.

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.

Immunogenicity of pandemic influenza A H1N1/2009 adjuvanted vaccine in pediatric solid organ transplant recipients.

The aim of this study was to assess the immunogenicity of a vaccine against this virus in a prospective cohort of transplanted pediatric patients without previous influenza infection who received one dose of MF59®-adjuvanted pandemic H1N1/2009 vaccine. Seventeen patients who were being regularly followed up at the Outpatient Clinic of the Children's Transplant Unit (liver and kidney transplantation) in Hospital Universitari Vall d'Hebron (Barcelona) were included. Seroconversion was demonstrated in 15 of 17 (88.2%) vaccinated children. There were no rejection episodes or major adverse events. The MF59(®) -adjuvanted pandemic H1N1/2009 vaccine was safe and elicited an adequate response.

Cystic dystrophy of the pancreas in patient with only one previous cyst.

CASE REPORT: we describe the case of a 46-year-old patient with cystic dystrophy of the pancreas admitted for alcoholic pancreatitis in a state of alcohol deprivation. The patient's background includes two cases of acute pancreatitis and a computed tomography taken 18 months prior to admittance reveals a 9 mm cyst in the first duodenal portion. Magnetic resonance imaging and endoscopic ultrasonography were consistent with cystic dystrophy of the pancreas without stenosis, for which reason treatment with octreotide was initiated. DISCUSSION: it is believed to be a disease caused by obstruction of the ducts of the heterotopic pancreas and is associated with alcoholic pancreatitis. Its treatment is still under debate, but it requires pancreatectomy as a last option. CONCLUSION: cystic dystrophy of the pancreas is a rare disease and an effort should be made to bring together all of the described cases to increase our understanding of the disease.

Distrofia quística de páncreas en paciente con un solo quiste previo / No disponible

Introducción: la distrofia quística de páncreas en una enfermedad rara. Su diagnóstico es difícil y su tratamiento se halla en debate. Caso clínico: describimos el caso de un paciente de 46 años con distrofia quística de páncreas que ingresa por pancreatitis alcohólica en estado de deprivación alcohólica. Entre sus antecedentes destaca dos pancreatitis agudas y en un TC de 18 meses previo al ingreso un quiste de 9 mm en primera porción duodenal. Se realizó resonancia magnética y ecoendoscopia hallando imagen compatible con distrofia quística de páncreas sin estenosis, por lo que se inició tratamiento con octreótido. Discusión: se cree que se trata de una enfermedad causada por la obstrucción de los ductos del páncreas heterotópico y se asocia a pancreatitis alcohólica. Su tratamiento se encuentra todavía en debate pero requiere en última instancia de pancreatectomía. Conclusión: la distrofia quística de páncreas es una enfermedad rara y se debe intentar aunar todos los casos descritos para incrementar nuestro conocimiento sobre la enfermedad(AU)

Case report: we describe the case of a 46-year-old patient with cystic dystrophy of the pancreas admitted for alcoholic pancreatitis in a state of alcohol deprivation. The patient’s background includes two cases of acute pancreatitis and a computed tomography taken 18 months prior to admittance reveals a 9 mm cyst in the first duodenal portion. Magnetic resonance imaging and endoscopic ultrasonography were consistent with cystic dystrophy of the pancreas without stenosis, for which reason treatment with octreotide was initiated. Discussion: it is believed to be a disease caused by obstruction of the ducts of the heterotopic pancreas and is associated with alcoholic pancreatitis. Its treatment is still under debate, but it requires pancreatectomy as a last option. Conclusion: cystic dystrophy of the pancreas is a rare disease and an effort should be made to bring together all of the described cases to increase our understanding of the disease(AU)