Unresolved issues in the diagnosis of catheter related candidemia: A position paper.

The incidence and recent trends of candidemia and the contribution of the COVID-19 pandemic to its evolution are not well documented. The catheter is a major focus of Candida spp. infections, but the methods used to confirm the origin of candidemia are still based on the data generated for bacterial infection. The presence of Candida spp. on the tip of a removed catheter is the gold standard for confirmation but it is not always possible to remove it. Conservative methods, without catheter removal, have not been specifically studied for microorganisms whose times of growth are different from those of bacteria and therefore these results are not applicable to candidemia. The different Candida species do not have a particular tropism for catheter colonization and fungal biomarkers have not yet been able to contribute to the determination of the origin of candidemia. Techniques such Candida T2 Magnetic Resonance (T2MR) has not yet been applied for this purpose. Finally, there is not yet a consensus of how to proceed when Candida spp. is isolated from an extracted catheter and blood cultures obtained from simultaneous peripheral veins are negative. In this lack of firm data, a group of experts has formulated a series of questions trying to answer them based on the literature, indicating the current deficiencies and offering their own opinion. All authors agree with the conclusions of the manuscript and offer it as a position and discussion paper.

Fragmentomic analysis of circulating tumor DNA-targeted cancer panels.

BACKGROUND: The isolation of cell-free DNA (cfDNA) from the bloodstream can be used to detect and analyze somatic alterations in circulating tumor DNA (ctDNA), and multiple cfDNA-targeted sequencing panels are now commercially available for Food and Drug Administration (FDA)-approved biomarker indications to guide treatment. More recently, cfDNA fragmentation patterns have emerged as a tool to infer epigenomic and transcriptomic information. However, most of these analyses used whole-genome sequencing, which is insufficient to identify FDA-approved biomarker indications in a cost-effective manner. PATIENTS AND METHODS: We used machine learning models of fragmentation patterns at the first coding exon in standard targeted cancer gene cfDNA sequencing panels to distinguish between cancer and non-cancer patients, as well as the specific tumor type and subtype. We assessed this approach in two independent cohorts: a published cohort from GRAIL (breast, lung, and prostate cancers, non-cancer, n = 198) and an institutional cohort from the University of Wisconsin (UW; breast, lung, prostate, bladder cancers, n = 320). Each cohort was split 70%/30% into training and validation sets. RESULTS: In the UW cohort, training cross-validated accuracy was 82.1%, and accuracy in the independent validation cohort was 86.6% despite a median ctDNA fraction of only 0.06. In the GRAIL cohort, to assess how this approach performs in very low ctDNA fractions, training and independent validation were split based on ctDNA fraction. Training cross-validated accuracy was 80.6%, and accuracy in the independent validation cohort was 76.3%. In the validation cohort where the ctDNA fractions were all <0.05 and as low as 0.0003, the cancer versus non-cancer area under the curve was 0.99. CONCLUSIONS: To our knowledge, this is the first study to demonstrate that sequencing from targeted cfDNA panels can be utilized to analyze fragmentation patterns to classify cancer types, dramatically expanding the potential capabilities of existing clinically used panels at minimal additional cost.

The largest prehistoric mound in Europe is the Bronze-Age Hill of Udine (Italy) and legend linked its origin to Attila the Hun.

Prehistoric monuments often constitute evident landmarks and sometimes, after falling into disuse, fascinated local people enough to stimulate speculations about their origin over time. According to legend, the Hill of Udine (NE Italy) was built by Attila the Hun's soldiers, but its origin (natural or anthropogenic) has been debated until now. Our research analyzed five new 40-m long stratigraphic cores, investigating for the first time the total thickness of the hill and compared the data with the available archaeological information. Moreover, we considered other hills and mounds in northern Italy and other European regions where folklore traditions relate their origin to Attila. The geoarchaeological and ethnographic data prove that the Hill of Udine is a Bronze Age anthropogenic mound erected between 1400 and 1150 BCE and that, later, folklore has transformed the ancestral memory of its origin into legend. By measuring 30 m in height and over 400,000 m3 in volume, the flat-topped hill is the largest prehistoric mound in Europe. This discovery reveals unprecedented skills in earth construction and confirms significant anthropogenic modifications of the environment during Bronze Age.

International Validation of a Methicillin-Resistant Staphylococcus aureus Risk Assessment Tool for Skin and Soft Tissue Infections.

INTRODUCTION: To promote judicious prescribing of methicillin-resistant Staphylococcus aureus (MRSA)-active therapy for skin and soft tissue infections (SSTI), we previously developed an MRSA risk assessment tool. The objective of this study was to validate this risk assessment tool internationally. METHODS: A multicenter, prospective cohort study of adults with purulent SSTI was performed at seven international sites from July 2016 to March 2018. Patient MRSA risk scores were computed as follows: MRSA infection/colonization history (2 points); previous hospitalization, previous antibiotics, chronic kidney disease, intravenous drug use, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), diabetes with obesity (1 point each). Predictive performance of MRSA surveillance percentage, MRSA risk score, and estimated MRSA probability (surveillance percentage adjusted by risk score) were quantified using the area under the receiver operating characteristic curves (aROC) and compared. Performance characteristics of different risk score thresholds across varying baseline MRSA prevalence were examined. RESULTS: Two hundred three patients were included. Common SSTI were wounds (28.6%), abscess (25.1%), and cellulitis with abscess (20.7%). Patients with higher risk scores were more likely to have MRSA (P < 0.001). The MRSA risk score aROC (95%CI) [0.748 (0.678-0.819)] was significantly greater than MRSA surveillance percentage [0.646 (0.569-0.722)] (P = 0.016). Estimated MRSA probability aROC [0.781 (0.716-0.845)] was significantly greater than surveillance percentage (P < 0.001) but not the risk score (P = 0.192). The estimated negative predictive value (NPV) of an MRSA score ≥ 1 (i.e., a score of 0) was greater than 90% when MRSA prevalence was 30% or less. CONCLUSION: The MRSA risk score and estimated MRSA probability were significantly more predictive of MRSA compared with surveillance percentage. An MRSA risk score of zero had high predictive value and could help avoid unnecessary empiric MRSA coverage in low-acuity patients. Further study, including impact of such risk assessment tools on prescribing patterns and outcomes are required before implementation.

Development of an integrated environmental monitoring protocol for SARS-CoV-2 contamination. Applications at the IRCSS San Martino Polyclinic Hospital in Genoa, Italy.

SCIENTIFIC BACKGROUND: Environmental sampling of SARS-CoV-2 is a fundamental tool for evaluating the effectiveness of non-specific prophylaxis measures in counteracting virus spread. The purpose of our work was to evaluate the effectiveness of the different sampling methods in the hospital setting to assess their correlation with the structural, functional, and operational situation of the monitored departments and to define the dynamics of the spread of the virus in indoor environments. METHODS: The monitoring (air bubbling sampling, surface wipe test) was carried out at the San Martino Polyclinic Hospital (Genoa, Italy) in the period since April 2020 to June 2021. The presence of viral RNA in the collected samples was evaluated by qPCR. The infection capacity of the samples collected was also evaluated by an in vitro challenge test on cells sensitive to SARS-CoV-2 infection. RESULTS: The percentage of positivity with respect to the number of tests performed (sensitivity) were air bubbler 50%, wipe test 17%, and challenge test 11%. Only 20% of the samples tested positive in the wipe test and 43% of the samples tested positive in the bubbler sampling were also positive in the challenge test. All the positivity obtained was detected at a distance of less than 2 m and height of less than 1.5 from COVID-19 patients. CONCLUSIONS: Environmental contamination from SARS-CoV-2 detected at the San Martino Polyclinic Hospital is found lower than similar assessments performed in other hospitals both in Italy and abroad. Our study predicted that environmental monitoring of SARS-CoV-2 must be carried out in an integrated way by not using a single sampling method, as each individual test has a different biological significance and performance. However, the virus detected by wipe test only is often a degraded viral fragment and not an intact infecting virion.

Debridement, antibiotics and implant retention (DAIR): An effective treatment option for early prosthetic joint infections.

INTRODUCTION: Debridement, antibiotics and implant retention (DAIR) is an attractive treatment option for prosthetic joint infections (PJIs). However, reported success rates and predictors of DAIR failure vary widely. The primary aim of this study is to report the outcome of DAIR in patients with hip and knee PJIs receiving short course of antibiotic therapy. The secondary aim is to identify risk factors for DAIR failure. METHODS: We performed a retrospective analysis of prospectively collected data of all hip and knee PJIs consecutively diagnosed at Quadrante Orthopedic Center, an Italian orthopedic hospital highly specialized in prosthetic surgery, from January 1, 2013 to January 1, 2019, and we analyzed those treated with DAIR. RESULTS: Forty-seven PJIs occurred after 5102 arthroplasty procedures. Twenty-one patients (45%) aged 71 years were treated with DAIR for hip (62%) and knee (38%) PJIs. These were classified as early PJIs in 76% cases, delayed in 19% and late in 5%. Median time from PJI-related symptoms onset to implant revision surgery was 12 days (IQR, 7-20 days). The median duration of antibiotic treatment after surgery was 63 days (IQR, 53-84 days). Sixteen (76%) patients were cured after a median follow-up of 2197 days (IQR, 815-2342 days), while 5 (24%) experienced failure. At multivariate analysis, delayed/late PJIs were significantly associated with failure (OR = 12.51; 95% CI 1.21-129.63, p = 0.03). CONCLUSIONS: DAIR represents an effective strategy for the treatment of early PJIs in spite of short course of antibiotic therapy.

Risk factors for candidaemia in hospitalized patients with liver cirrhosis: a multicentre case-control-control study.

OBJECTIVES: The aim of this study was to evaluate the risk factors for candidaemia in patients with liver cirrhosis. METHODS: This was a case-control-control (1:2:2) study performed in four Italian tertiary centres from 2006 to 2015. Cases were patients with liver cirrhosis developing candidaemia. For every case of candidaemia we enrolled two additional patients undergoing blood cultures for suspected infection yielding isolation of a bacterial pathogen (control A) and two additional patients undergoing blood cultures for suspected infection yielding negative results (control B). Patients were matched according to age, sex and model for end stage liver disease at hospital admission. RESULTS: During the study period 90 cases, 180 controls A and 180 controls B were included. At multivariate analysis assessed by means of multinomial conditional regression models, factors independently associated with candidaemia were previous (<30 days) acute-on-chronic liver failure (relative risk ratio (RRR) 2.22 (95% confidence interval (CI) 1.09-4.54), p = 0.046), previous(<30 days) gastrointestinal endoscopy (RRR 2.38 (95% CI 1.19-4.78) p = 0.014), previous(<30 days) antibiotic treatment for at least 7 days (RRR 2.74 (95% CI 1.00-7.48), p = 0.049), presence of central venous catheter (RRR 2.77 (95% CI 1.26-6.09, p = 0.011), total parenteral nutrition (RRR 3.90 (95% CI 1.62-9.40), p = 0.002) at infection onset and length of in-hospital stay >15 days (RRR 4.63 (95% CI 2.11-10.18), p <0.001] Conversely, rifaximin treatment was associated with lower rate of candidaemia (RRR 0.38 (95% CI 0.19-0.77), p = 0.007). Multivariable analysis for 30-day mortality showed that patients with isolation of Candida spp. from blood cultures had worse outcome when compared with controls even though the difference did not reach a statistical significance (hazard ratio 1.64 (95% 0.97-2.75) p = 0.06). CONCLUSIONS: We identified previous antibiotic use, gastrointestinal endoscopy or acute-on-chronic liver failure and presence of central venous catheter especially for parenteral nutrition as independent factors associated with candidaemia. Surprisingly, chronic rifaximin use was a protective factor.

Association Between Minimum Inhibitory Concentration, Beta-lactamase Genes and Mortality for Patients Treated With Piperacillin/Tazobactam or Meropenem From the MERINO Study.

INTRODUCTION: This study aims to assess the association of piperacillin/tazobactam and meropenem minimum inhibitory concentration (MIC) and beta-lactam resistance genes with mortality in the MERINO trial. METHODS: Blood culture isolates from enrolled patients were tested by broth microdilution and whole genome sequencing at a central laboratory. Multivariate logistic regression was performed to account for confounders. Absolute risk increase for 30-day mortality between treatment groups was calculated for the primary analysis (PA) and the microbiologic assessable (MA) populations. RESULTS: In total, 320 isolates from 379 enrolled patients were available with susceptibility to piperacillin/tazobactam 94% and meropenem 100%. The piperacillin/tazobactam nonsusceptible breakpoint (MIC >16 mg/L) best predicted 30-day mortality after accounting for confounders (odds ratio 14.9, 95% confidence interval [CI] 2.8-87.2). The absolute risk increase for 30-day mortality for patients treated with piperacillin/tazobactam compared with meropenem was 9% (95% CI 3%-15%) and 8% (95% CI 2%-15%) for the original PA population and the post hoc MA populations, which reduced to 5% (95% CI -1% to 10%) after excluding strains with piperacillin/tazobactam MIC values >16 mg/L. Isolates coharboring extended spectrum ß-lactamase (ESBL) and OXA-1 genes were associated with elevated piperacillin/tazobactam MICs and the highest risk increase in 30-day mortality of 14% (95% CI 2%-28%). CONCLUSIONS: After excluding nonsusceptible strains, the 30-day mortality difference from the MERINO trial was less pronounced for piperacillin/tazobactam. Poor reliability in susceptibility testing performance for piperacillin/tazobactam and the high prevalence of OXA coharboring ESBLs suggests that meropenem remains the preferred choice for definitive treatment of ceftriaxone nonsusceptible Escherichia coli and Klebsiella.

Assessment of the impact of clinical recommendations on antibiotic use for CAP and HCAP: results from an implementation program in an Academic Hospital.

BACKGROUND: Local guidelines and recommendations to treat common infectious diseases are a cornerstone of most Antimicrobial Stewardship programs. The evaluation of the adherence to guidelines is an effective quality measure of the programs themselves; the proposed evaluation model aimed at examining antibiotic treatment for pneumonia. STUDY DESIGN: A retrospective pre-post intervention study was conducted in a North-Eastern Italian Academic Hospital. METHODS: 231 patients with Community-Acquired Pneumonia and 95 with Healthcare-Associated Pneumonia were divided into pre- and post-intervention groups (188 and 138, respectively). A course and a pocket summary of Pneumonia Regional Recommendations were the stewardship activities adopted. The compliance degree of prescriptions with Regional Recommendations was tested for drug(s), dosage and duration of treatment in both groups for Community-Acquired and Healthcare-Associated Pneumonia and a comparison with International guidelines was performed. RESULTS: A significant improvement in the compliance with Regional Recommendations for the variable drug emerged for Community-Acquired (38.8% vs 52.2%), but not for Healthcare-Associated Pneumonia; no significant variation in compliance was registered for dosage and duration of treatment. The significant decrease in consumption of levofloxacin showed the positive impact of the Regional Antimicrobial Stewardship programs. A high level of adherence to International Guidelines for the variable drug for Community-Acquired Pneumonia was found in both groups (75.5% and 77.2%, respectively). CONCLUSIONS: Our study highlighted that room for improvement in antibiotic prescription in Community-Acquired and Healthcare-Associated Pneumonia currently remains. New strategies for a better use of the adopted tools and definition of new antimicrobial stewardship initiatives are needed to improve compliance to Regional Recommendations.

Balancing evidence and frontline experience in the early phases of the COVID-19 pandemic: current position of the Italian Society of Anti-infective Therapy (SITA) and the Italian Society of Pulmonology (SIP).

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19), which has rapidly become epidemic in Italy and other European countries. The disease spectrum ranges from asymptomatic/mildly symptomatic presentations to acute respiratory failure. At the present time the absolute number of severe cases requiring ventilator support is reaching or even surpassing the intensive care unit bed capacity in the most affected regions and countries. OBJECTIVES: To narratively summarize the available literature on the management of COVID-19 in order to combine current evidence and frontline opinions and to provide balanced answers to pressing clinical questions. SOURCES: Inductive PubMed search for publications relevant to the topic. CONTENT: The available literature and the authors' frontline-based opinion are summarized in brief narrative answers to selected clinical questions, with a conclusive statement provided for each answer. IMPLICATIONS: Many off-label antiviral and anti-inflammatory drugs are currently being administered to patients with COVID-19. Physicians must be aware that, as they are not supported by high-level evidence, these treatments may often be ethically justifiable only in those worsening patients unlikely to improve only with supportive care, and who cannot be enrolled onto randomized clinical trials. Access to well-designed randomized controlled trials should be expanded as much as possible because it is the most secure way to change for the better our approach to COVID-19 patients.

Performance of existing definitions and tests for the diagnosis of invasive aspergillosis in critically ill, adult patients: A systematic review with qualitative evidence synthesis.

OBJECTIVES: To summarize the available evidence on the diagnostic performance for invasive aspergillosis (IA) in non-hematological, non-solid organ transplantation critically ill patients of the following: (i) existing definitions of IA (developed either for classical immunocompromised populations or for non-immunocompromised critically ill patients); (ii) laboratory tests; (iii) radiology tests. METHODS: A systematic review was performed by evaluating studies assessing the diagnostic performance for IA of a definition/s and/or laboratory/radiology test/s vs. a reference standard (histology) or a reference definition. RESULTS: Sufficient data for evaluating the performance of existing definitions and laboratory tests for the diagnosis of IA in critically ill patients is available only for invasive pulmonary aspergillosis. Against histology/autopsy as reference, the AspICU definition showed a promising diagnostic performance but based on small samples and applicable only to patients with positive respiratory cultures. Studies on laboratory tests consistently indicated a better diagnostic performance of bronchoalveolar lavage fluid (BALF) galactomannan (GM) than serum GM, and a suboptimal specificity of BALF and serum (1,3)-ß-D-glucan. CONCLUSIONS: Evidence stemming from this systematic review will guide the discussion for defining invasive aspergillosis within the FUNDICU project. The project aims to develop a standard set of definitions for invasive fungal diseases in critically ill, adult patients.

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.

Rapid microbiological tests for bloodstream infections due to multidrug resistant Gram-negative bacteria: therapeutic implications.

BACKGROUND: Treating severe infections due to multidrug-resistant Gram-negative bacteria (MDR-GNB) is one of the most important challenges for clinicians worldwide, partly because resistance may remain unrecognized until identification of the causative agent and/or antimicrobial susceptibility testing (AST). Recently, some novel rapid test for identification and/or AST of MDR-GNB from positive blood cultures or the blood of patients with bloodstream infections (BSIs) have become available. OBJECTIVES: The objective of this narrative review is to discuss the advantages and limitations of different rapid tests for identification and/or AST of MDR-GNB from positive blood cultures or the blood of patients with BSI, as well as the available evidence on their possible role to improve therapeutic decisions and antimicrobial stewardship. SOURCES: Inductive PubMed search for publications relevant to the topic. CONTENT: The present review is structured in the following way: (a) rapid tests on positive blood cultures; (b) rapid tests directly on whole blood; (c) therapeutic implications. IMPLICATIONS: Novel molecular and phenotypic rapid tests for identification and AST show the potential for favourably influencing patients' outcomes and results of antimicrobial stewardship interventions by reducing both the time to effective treatment and the misuse of antibiotics, although the interpretation about their impact on actual therapeutic decisions and patients' outcomes is still complex. Factors such as feasibility and personnel availability, as well as the detailed knowledge of the local microbiological epidemiology, need to be considered very carefully when implementing novel rapid tests in laboratory workflows and algorithms. Providing high-level, comparable evidence on the clinical impact of rapid identification and AST is becoming of paramount importance for MDR-GNB infections, since in the near future rapid identification of specific resistance mechanisms could be crucial for guiding rapid, effective, and targeted therapy against specific resistance mechanisms.

Qualitative and quantitative change of the tolerance to liposomal amphotericin B triggered by biofilm maturation in C. parapsilosis.

Candida parapsilosis is an emerging opportunistic pathogen present in both clinical and natural environment, with a strong frequency of biofilm forming strains. While the drugs active against biofilm are rare, liposomal amphotericin B is credited with an antibiofilm activity in some opportunistic species of the genus Candida. Using freshly isolated strains from hospital environment, in this paper we could show the prevalence of biofilm forming vs. nonbiofilm forming strains. The former displayed a large variability in terms of biofilm biomass and metabolic activity. Liposomal amphotericin B minimum inhibitory concentration (MIC) of planktonic cells was below the breakpoint, whereas the sessile cells MIC (SMIC) was 1 or 2 orders of magnitude above the planktonic MIC. When the drug was applied to freshly attached cells, that is, biofilm in formation, the MIC (called SDMIC) was even below the MIC value. All resistance metrics (MIC, SMIC, and SDMIC) were quite variable although no correlation could be detected between them and the metrics used to quantify biofilm activity and biomass production. These findings demonstrate that young biofilm cells are even more susceptible than planktonic cells and that early treatments with this drug can be beneficial in cases of prosthesis implantation or especially when there is the necessity of a CVC reimplantation during a sepsis.

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.

Intensive care management of influenza-associated pulmonary aspergillosis.

BACKGROUND: Severe pulmonary infections are among the most common reasons for admission to intensive care units (ICU). Within the last decade, increasing reports of severe influenza pneumonia resulting in acute respiratory distress syndrome (ARDS) complicated by Aspergillus infection were published. OBJECTIVES: To provide a comprehensive review of management of influenza-associated pulmonary aspergillosis in patients with ARDS. SOURCES: Review of the literature pertaining to severe influenza-associated pulmonary aspergillosis. PubMed database was searched for publications from the database inception to January 2019. CONTENT: In patients with lower respiratory symptoms, development of respiratory insufficiency should trigger rapid and thorough clinical evaluation, in particular in cases of suspected ARDS, including electrocardiography and echocardiography to exclude cardiac dysfunction, arrhythmias and ischaemia. Bronchoalveolar lavage should obtain lower respiratory tract samples for galactomannan assay, direct microscopy, culture, and bacterial, fungal and viral PCR. In case of positive Aspergillus testing, chest CT is the imaging modality of choice. If influenza pneumonia is diagnosed, neuraminidase inhibitors are the preferred approved drugs. When invasive aspergillosis is confirmed, first-line therapy consists of isavuconazole or voriconazole. Isavuconazole is an alternative in case of intolerance to voriconazole, drug-drug interactions, renal impairment, or if a spectrum of activity including the majority of Mucorales is desired. Primary anti-mould prophylaxis with posaconazole is recommended in haematology patients at high-risk. It may be considered in newly diagnosed influenza and ARDS, but ideally in clinical trials. IMPLICATIONS: The rising reports of influenza-associated pulmonary aspergillosis in patients with ARDS, who are otherwise not considered at risk for fungal pneumonia demands heightened clinical awareness. Tracheobronchitis and Aspergillus in respiratory tract samples should prompt suspicion of invasive fungal infection and further work-up. The management algorithm should comprise bronchoalveolar lavage, CT imaging, sophisticated ventilator-management, rescue extracorporeal membrane oxygenation, and antifungal and antiviral therapy. To decrease the burden of influenza-related illness, vaccination is of utmost importance, specifically in patients with co-morbidities.

Persistent hematogenous dissemination in pulmonary P. jiroveci infection.

Pneumocystis jiroveci pneumonia in non-HIV patients is infrequent and characterized by atypical presentations and increased severity. Although hematogenous dissemination from the lungs can lead to extrapulmonary infections, isolation of oocysts from blood in human subjects has not been documented. We report a case of P. jiroveci pneumonia with persistent isolation of oocysts from blood and positivity of P. jiroveci polymerase chain reaction. The patient presented with bilateral diffuse pulmonary nodules and received prolonged treatment with trimethoprim/sulfamethoxazole.