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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., Instituto de Salud Carlos III (ISCIII)/ Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Depto. de Medicina, Fac. de Medicina, TRUE, pub

Introduction Intra-abdominal infections represent the second most frequently acquired infection in the intensive care unit (ICU), with mortality rates ranging from 20% to 50%. Candida spp. may be responsible for up to 10-30% of cases. This study assesses risk factors for development of intra-abdominal candidiasis (IAC) among patients admitted to ICU. Methods We performed a case-control study in 26 European ICUs during the period January 2015-December 2016. Patients at least 18 years old who developed an episode of microbiologically documented IAC during their stay in the ICU (at least 48 h after admission) served as the case cohort. The control group consisted of adult patients who did not develop episodes of IAC during ICU admission. Matching was performed at a ratio of 1:1 according to time at risk (i.e. controls had to have at least the same length of ICU stay as their matched cases prior to IAC onset), ICU ward and period of study. Results During the study period, 101 case patients with a diagnosis of IAC were included in the study. On univariate analysis, severe hepatic failure, prior receipt of antibiotics, prior receipt of parenteral nutrition, abdominal drain, prior bacterial infection, anastomotic leakage, recurrent gastrointestinal perforation, prior receipt of antifungal drugs and higher median number of abdominal surgical interventions were associated with IAC development. On multivariate analysis, recurrent gastrointestinal perforation (OR 13.90; 95% CI 2.65-72.82, p = 0.002), anastomotic leakage (OR 6.61; 95% CI 1.98-21.99, p = 0.002), abdominal drain (OR 6.58; 95% CI 1.73-25.06, p = 0.006), prior receipt of antifungal drugs (OR 4.26; 95% CI 1.04-17.46, p = 0.04) or antibiotics (OR 3.78; 95% CI 1.32-10.52, p = 0.01) were independently associated with IAC. Conclusions Gastrointestinal perforation, anastomotic leakage, abdominal drain and prior receipt of antifungals or antibiotics may help to identify critically ill patients with higher probability of d

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.

Alvisa Palese,1 Stefania Chiappinotto,1 Maddalena Peghin,2 Meri Marin,3 David Turello,3 Denis Caporale,3 Carlo Tascini2 1Department of Medical Science, University of Udine, Udine, Italy; 2Division of Infectious Diseases, Department of Medicine, University of Udine, Udine, Italy; 3Azienda Sanitaria Universitaria Friuli Centrale, Udine, ItalyCorrespondence: Alvisa Palese, Department of Medical Sciences, University of Udine, Udine, 33100, Italy, Tel +39(0)432 590926, Fax +39(0)432 507715, Email alvisa.palese@uniud.itPurpose: To identify interventions implemented during the first, second and third waves of the Coronavirus disease 2019 (COVID-19) among Italian Nursing Homes (NHs).Patients and Methods: A descriptive qualitative design according to COnsolidated criteria for REporting Qualitative (COREQ) guideline. A purposeful sample of five public NHs, located in the north-east of Italy, equipped with from 60 to 151 beds, participated. Six nurse managers, four clinical nurses and one NH director were interviewed in depth at the end of 2021. These interviews were audio-recorded and then transcribed verbatim. A qualitative content analysis was performed to identify effective interventions as perceived by participants to protect facilities and residents from the pandemic.Results: Three main sets of interventions have been applied, at the environmental, nurse staff and at the resident levels. Some have been enacted in all facilities, others in a few but in a homogeneous fashion, while other interventions have been implemented in some NHs also in contrast with available national or local recommendations.Conclusion: Despite their documented frailty and precarious system, NHs implemented several interventions to protect their residents from the COVID-19. All interventions have been designed and implemented during the event, suggesting the need to increase the NHs’ preparedness to face future disasters. Regarding those interventions enacted in contrast to the recommendations or

Background: A growing body of observational evidence supports the value of ceftazidime-avibactam (CAZ-AVI) in managing infections caused by carbapenem-resistant Enterobacteriaceae. Methods: We retrospectively analyzed observational data on use and outcomes of CAZ-AVI therapy for infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) strains. Multivariate regression analysis was used to identify variables independently associated with 30-day mortality. Results were adjusted for propensity score for receipt of CAZ-AVI combination regimens versus CAZ-AVI monotherapy. Results: The cohort comprised 577 adults with bloodstream infections (n = 391) or nonbacteremic infections involving mainly the urinary tract, lower respiratory tract, and intra-abdominal structures. All received treatment with CAZ-AVI alone (n = 165) or with ≥1 other active antimicrobials (n = 412). The all-cause mortality rate 30 days after infection onset was 25% (146/577). There was no significant difference in mortality between patients managed with CAZ-AVI alone and those treated with combination regimens (26.1% vs 25.0%, P =. 79). In multivariate analysis, mortality was positively associated with presence at infection onset of septic shock (P =. 002), neutropenia (P <. 001), or an INCREMENT score ≥8 (P =. 01); with lower respiratory tract infection (LRTI) (P =. 04); and with CAZ-AVI dose adjustment for renal function (P =. 01). Mortality was negatively associated with CAZ-AVI administration by prolonged infusion (P =. 006). All associations remained significant after propensity score adjustment. Conclusions: CAZ-AVI is an important option for treating serious KPC-Kp infections, even when used alone. Further study is needed to explore the drug's seemingly more limited efficacy in LRTIs and potential survival benefits of prolonging CAZ-AVI infusions to ≥3 hours.

Matteo Bassetti,1,2 Maddalena Peghin,1 Alessio Mesini,3 Elio Castagnola3 1Infectious Diseases Clinic, Department of Medicine University of Udine and Azienda Sanitaria Universitaria Integrata, Udine, Italy; 2Department of Health Sciences, University of Genoa, Genoa, Italy; 3Division of Infectious Diseases, IRCCS Istituto Giannina Gaslini, Genoa, ItalyCorrespondence: Matteo BassettiClinica Malattie Infettive, Azienda Ospedaliera Universitaria Santa Maria Della Misericordia, Piazzale Santa Maria Della Misericordia 15, Udine 33100, ItalyTel +39 0432 559355Fax +39 0432 559360Email matteo.bassetti@asuiud.sanita.fvg.itAbstract: Antimicrobial resistance poses a substantial threat to global public health. The pursuit of new antibiotics has decreased and very few options have been investigated for the treatment of complicated multidrug-resistant Gram-negative (MDR-GN) infections in adult population and even less in pediatric patients. Ceftazidime-avibactam (CAZ-AVI) is novel cephalosporin/β-lactamase inhibitor (BL-BLI) combination with broad antibacterial spectrum. The aim of this review is to describe the current and future role CAZ-AVI in the pediatric population with suspected or confirmed MDR-GN infections.Keywords: pediatric, infections, multidrug-resistant Gram-negative, ceftazidime/avibactam

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.

BackgroundThe objective of this study was to assess the cumulative incidence of invasive candidiasis (IC) in intensive care units (ICUs) in Europe.MethodsA multinational, multicenter, retrospective study was conducted in 23 ICUs in 9 European countries, representing the first phase of the candidemia/intra-abdominal candidiasis in European ICU project (EUCANDICU).ResultsDuring the study period, 570 episodes of ICU-acquired IC were observed, with a cumulative incidence of 7.07 episodes per 1000 ICU admissions, with important between-center variability. Separated, non-mutually exclusive cumulative incidences of candidemia and IAC were 5.52 and 1.84 episodes per 1000 ICU admissions, respectively. Crude 30-day mortality was 42%. Age (odds ratio [OR] 1.04 per year, 95% CI 1.02-1.06, p<0.001), severe hepatic failure (OR 3.25, 95% 1.31-8.08, p 0.011), SOFA score at the onset of IC (OR 1.11 per point, 95% CI 1.04-1.17, p 0.001), and septic shock (OR 2.12, 95% CI 1.24-3.63, p 0.006) were associated with increased 30-day mortality in a secondary, exploratory analysis.ConclusionsThe cumulative incidence of IC in 23 European ICUs was 7.07 episodes per 1000 ICU admissions. Future in-depth analyses will allow explaining part of the observed between-center variability, with the ultimate aim of helping to improve local infection control and antifungal stewardship projects and interventions.

BackgroundThe objective of this study was to assess the cumulative incidence of invasive candidiasis (IC) in intensive care units (ICUs) in Europe.MethodsA multinational, multicenter, retrospective study was conducted in 23 ICUs in 9 European countries, representing the first phase of the candidemia/intra-abdominal candidiasis in European ICU project (EUCANDICU).ResultsDuring the study period, 570 episodes of ICU-acquired IC were observed, with a cumulative incidence of 7.07 episodes per 1000 ICU admissions, with important between-center variability. Separated, non-mutually exclusive cumulative incidences of candidemia and IAC were 5.52 and 1.84 episodes per 1000 ICU admissions, respectively. Crude 30-day mortality was 42%. Age (odds ratio [OR] 1.04 per year, 95% CI 1.02-1.06, p<0.001), severe hepatic failure (OR 3.25, 95% 1.31-8.08, p 0.011), SOFA score at the onset of IC (OR 1.11 per point, 95% CI 1.04-1.17, p 0.001), and septic shock (OR 2.12, 95% CI 1.24-3.63, p 0.006) were associated with increased 30-day mortality in a secondary, exploratory analysis.ConclusionsThe cumulative incidence of IC in 23 European ICUs was 7.07 episodes per 1000 ICU admissions. Future in-depth analyses will allow explaining part of the observed between-center variability, with the ultimate aim of helping to improve local infection control and antifungal stewardship projects and interventions.

[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.

Introduction. Influenza represents a matter of serious concern for clinicians, both for outpatient and in hospital setting. The 2017-18 epidemic represented the highest in terms of severity since 2003-04 worldwide. Overall, in Italy 764 cases was classified as “severe form”, with 173 influenza-attributed deaths . The majority of the fatal cases were recorded in the elderly and in patients with multiple comorbidities. However, some sporadic cases were also described in previously healthy people. We report a real-world experience about the management of cases of influenza admitted in 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 cases.Methods. A retrospective observational analysis wasbconducted among all influenza cases requiring admission in our Center during the 2017-18 season.Results. Overall, 29 patients were admitted at the University Hospital of Udine during the 2017-18 season with a diagnosis of influenza. B virus was responsible for the majority of the cases. More than 65.5% of the subjects presented with a complication. We estimated that 41.4% of the admitted cases were affected by a “severe form”. All these cases required admission in Intensive Care Unit, 27.6% and 10.3% of them needing Oral-Tracheal Intubation and Extracorporeal Membrane Oxygenation, respectively. Fatality rate was 24.1%. Noteworthy, only 9 subjects of our cohort had received vaccination. On the basis of the experience acquired during the past season, we propose a practical guide to approach influenza cases in everyday hospital practice.Conclusion. The cornerstones of the management of all hospitalized influenza cases are the rapid identification and treatment of severe forms. Timely and strictly adherence to contact and respiratory precautions are also fundamental to reduce the risk of intra-hospital outbreaks. Despite the improvements of antiviral

Introduction. Influenza represents a matter of serious concern for clinicians, both for outpatient and in hospital setting. The 2017-18 epidemic represented the highest in terms of severity since 2003-04 worldwide. Overall, in Italy 764 cases was classified as “severe form”, with 173 influenza-attributed deaths . The majority of the fatal cases were recorded in the elderly and in patients with multiple comorbidities. However, some sporadic cases were also described in previously healthy people. We report a real-world experience about the management of cases of influenza admitted in 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 cases.Methods. A retrospective observational analysis wasbconducted among all influenza cases requiring admission in our Center during the 2017-18 season.Results. Overall, 29 patients were admitted at the University Hospital of Udine during the 2017-18 season with a diagnosis of influenza. B virus was responsible for the majority of the cases. More than 65.5% of the subjects presented with a complication. We estimated that 41.4% of the admitted cases were affected by a “severe form”. All these cases required admission in Intensive Care Unit, 27.6% and 10.3% of them needing Oral-Tracheal Intubation and Extracorporeal Membrane Oxygenation, respectively. Fatality rate was 24.1%. Noteworthy, only 9 subjects of our cohort had received vaccination. On the basis of the experience acquired during the past season, we propose a practical guide to approach influenza cases in everyday hospital practice.Conclusion. The cornerstones of the management of all hospitalized influenza cases are the rapid identification and treatment of severe forms. Timely and strictly adherence to contact and respiratory precautions are also fundamental to reduce the risk of intra-hospital outbreaks. Despite the improvements of antiviral

Matteo Bassetti,1,2 Nadia Castaldo,1 Alessia Carnelutti,1 Maddalena Peghin,1 Daniele Roberto Giacobbe21Infectious Diseases Division, Department of Medicine, University of Udine and Azienda Sanitaria Universitaria Integrata di Udine, Udine, Italy; 2Department of Health Sciences, University of Genoa, Genoa, ItalyIntroduction: Tedizolid phosphate is an oxazolidinone approved for the treatment of acute bacterial skin and skin-structure infections (ABSSSIs) and active against methicillin-resistant Staphylococcus aureus.Aims: The objective of this article was to review the evidence for the efficacy and safety of tedizolid phosphate for the treatment of ABSSSI.Evidence review: Approval of tedizolid phosphate for the treatment of ABSSSI was based on the results of two phase III randomized controlled trials, ESTABLISH-1 (NCT01170221) and ESTABLISH-2 (NCT01421511), comparing 6-day once-daily tedizolid vs 10-day twice-daily linezolid. In ESTABLISH-1, noninferiority was met with early clinical response rates of 79.5% and 79.4% in tedizolid and linezolid groups, respectively (difference 0.1%, 95% CI –6.1% to 6.2%, with a 10% noninferiority margin). In ESTABLISH-2, noninferiority was met with 85% and 83% rates of early clinical response in tedizolid and linezolid groups, respectively (difference 2.6%, 95% CI –3.0% to 8.2%). Pooled data from ESTABLISH-1 and ESTABLISH-2 indicated a lower frequency of thrombocytopenia in tedizolid-treated than in linezolid-treated patients.Conclusion: Tedizolid offers the option of an intravenous to oral switch, allows once-daily administration, and presents lower risk of myelotoxicity when a 6-day course is used for the treatment of ABSSSI. Greater economic cost associated with this antibiotic could be offset by its shorter treatment duration and possibility of oral administration in routine clinical practice, although either sponsored or nonsponsored postmarketing observational experience remains essential for ultimate

Skin and soft-tissue infections (SSTIs) encompass a variety of pathological conditions that involve the skin and underlying subcutaneous tissue, fascia, or muscle, ranging from simple superficial infections to severe necrotizing infections. SSTIs are a frequent clinical problem in surgical departments. In order to clarify key issues in the management of SSTIs, a task force of experts met in Bertinoro, Italy, on June 28, 2018, for a specialist multidisciplinary consensus conference under the auspices of the World Society of Emergency Surgery (WSES) and the Surgical Infection Society Europe (SIS-E). The multifaceted nature of these infections has led to a collaboration among general and emergency surgeons, intensivists, and infectious disease specialists, who have shared these clinical practice recommendations.

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We aimed to describe the characteristics of patients with Staphylococcus aureus bacteremia and to evaluate the risk factors associated with early (7-day) and late (30-day) mortality. We performed an observational study including all consecutive episodes of Staphylococcus aureus bacteremia diagnosed at two Italian university hospitals during 2010±2014. A total of 337 patients were included. Mean age was 69 years (range, 57±78) and 65% were males. Methicillin-resistant S. aureus (MRSA) was identified in 132/337 (39%)cases. Overall 7-And 30-day mortality were 13% and 26%, respectively. Early mortality was associated with increased Charlson scores (OR 1.3, 95% CI 1.1±1.5), MRSA bacteremia (OR 3.2, 95% CI 1.4±8.1), presentation with septic shock (OR 13.5, 95% CI 5.4±36.4), and occurrence of endocarditis (OR 4.5, 95%CI 1.4±14.6). Similar risk factors were identified for late mortality, including increased Charlson scores (OR 1.2, 95% CI 1.1±1.4), MRSA bacteremia (OR 2.1, 95% CI 1.2±3.9), presentation with septic shock (OR 4, 95%CI 1.7±9.7), occurrence of endocarditis (OR 3.8, 95% CI 1.4±10.2) as well as Child C cirrhosis (OR 3.9, 95% CI 1.1±14.4) and primary bacteremia (OR 2.5, 95%CI 1.3±5). Infectious disease consultation resulted in better outcomes both at 7 (OR 0.1, 95% CI 0.05±0.4) and at 30 days (OR 0.4, 95% CI 0.2± 0.7). In conclusion, our study highlighted high rates of MRSA infection in nosocomial Staphylococcus aureus bacteremia. Multiple comorbidities, disease severity and methicillin-resistance are key factors for early and late mortality in this group. In patients with Staphylococcus aureus bacteremia, infectious disease consultation remains a valuable tool to improve clinical outcome.

Premi Extraordinari de Doctorat concedit pels programes de doctorat de la UAB per curs acadèmic 2017-2018, En la última década, las infecciones fúngicas invasoras (IFI) siguen aumentando su incidencia en pacientes inmunodeprimidos u hospitalizados. Estas infecciones presentan elevadas tasas de morbilidad y mortalidad, originando un consumo elevado de recursos. Además, la población de pacientes susceptibles a desarrollar IFI se ha ampliado de forma importante y han surgido nuevos grupos de riesgo. Por tanto, se ha modificado la visión clásica de la IFI y ahora sabemos que los diversos síndromes clínicos pueden ser vistos como un espectro continuo de la enfermedad, dependiendo de la interacción entre el patógeno y el huésped. Finalmente, se han identificado cambios en la cronología de estas infecciones, debido a los avances médicos contra las enfermedades subyacentes clásicas, la presencia de nuevas estrategias profilácticas y terapéuticas, la aparición de resistencias antifúngicas y de nuevas herramientas diagnósticas. Este trabajo muestra que en la IFI causada por hongos filamentosos la relación entre patógeno y huésped se modifica constantemente debido a los cambios epidemiológicos y a los clínicos del propio paciente. En el primer estudio hemos observado que en los pacientes con neoplasia de pulmón primaria o metastásica, la presencia de cambios anatómicos pulmonares debidos a la neoplasia, asociados a alteraciones locales y sistémicas que comprometen la respuesta inmune, parecen ser factores que predisponen a la aspergilosis pulmonar crónica (APC). En la actualidad, esta entidad poco conocida se encuentra en la frontera entre la enfermedad saprofítica e invasiva y puede ser infradiagnosticada, debido a que sus síntomas pueden estar enmascarados por los de la la enfermedad de base. El aislamiento de Aspergillus spp. en muestras respiratorias debe inducir un elevado nivel de sospecha de infección en estos pacientes vulnerables en los que la APC se asocia con un mal pronóstico. En el segundo estudio hemos descrito que la profilaxis con anfotericina B nebulizada (n-LAB) e, Over the last decade, the incidence of invasive fungal infections (IFI) is increasing in immunocompromised or hospitalized patients. These infections have high morbidity and mortality, resulting in a high consumption of resources. In addition, the population of patients susceptible to developing IFI has expanded significantly and new groups at risk have emerged. Therefore, the classic view of IFI has changed and, now, we know that different clinical syndromes can be seen as a continuum of the same disease, depending on the interaction between the fungi and the host. Finally, we have identified changes in the timing of these infections due to medical advances against the traditional underlying disease, the presence of new prophylactic and therapeutic strategies, the emergence of antifungal resistances and new diagnostic tools. This work shows that in the IFI caused by filamentous fungi the relationship between pathogen and host is constantly changing due to epidemiological and clinical changes of the patient. In the first study we found that in patients with primary lung neoplasia or metastatic lung cancer, the presence of pulmonary anatomical changes due to the cancer, associated with local and systemic disorders that compromise the immune response, appear to be factors that predispose to chronic pulmonary aspergillosis (CPA). Today, this entity, which is on the border between saprophytic and invasive disease, may be underdiagnosed because the underlying disease can mask its symptoms. Isolation of Aspergillus spp. in respiratory specimens should induce a high level of suspicion in these vulnerable patients in whom CPA is associated with a poor prognosis. In the second study, we have described that prophylaxis with nebulized liposomal amphotericin B (n-LAB) has proved to be safe, tolerable and can be used for preventing Aspergillus spp. infection in lung transplant recipients (LTR). Over the last years, the incidence of Aspergillus spp. colonization and infection has

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