Fungal Respiratory Infections Research Articles

Predictive Factors of In-Hospital Mortality in Older Adults with Community-Acquired Bloodstream Infection.

To assess the prevalence of intra-hospital mortality and associated risk factors in older people aged 75+, admitted with blood stream infections (BSI). Single center retrospective study performed in an 850-bed of the academic hospital of the Université Libre de Bruxelles. From January 2015 to December 2017, all inpatients over 75 years old admitted with BSI were included. Demographical, clinical and microbiological data were collected. 212 patients were included: median age was 82 [79-85] years and 60 % were female. The in-hospital mortality rate was 19%. The majority of microorganisms were Gram-negative strains, of which Escherichia coli was the most common, and urinary tract infection was the most common origin of BSI. Compared to patients who survived, the non-survivor group had a higher SOFA score (6 versus 3, p<0.0001), a higher comorbidity score (5 versus 4, p<0.0001), more respiratory tract infections (28 vs 6 %, p < 0.0001) and fungal infections (5 vs 1 %, p = 0.033), bedridden status (60 vs 25 %, p < 0.0001), and healthcare related infections (60 vs 40 %, p = 0.019). Using Cox multivariable regression analysis, only SOFA score was independently associated with mortality (HR 1.75 [95%IC 1.52-2.03], p<0.0001). BSI in older people are severe infections associated with a significant in-hospital mortality. Severity of clinical presentation at onset remains the most important predictor of mortality for BSI in older people. BSI originating from respiratory source and bedridden patients are at greater risk of intra-hospital mortality. Further prospective studies are needed to confirm these results.

First isolation of voriconazole-resistant Candida albicans, C. tropicalis, and Aspergillus niger from the blowholes of bottlenose dolphins (Tursiops truncatus).

Pulmonary mycosis is a fungal disease that commonly affects bottlenose dolphins (Tursiops truncatus) and is generally treated by the oral administration of azoles, such as itraconazole (ITZ) and voriconazole (VRZ). However, antifungal susceptibility testing of clinical isolates has not been well performed as a routine clinical examination in aquaria. In this study, we collected fungal species from the blowholes of 14 bottlenose dolphins, of which 12 were treated with ITZ or VRZ. All dolphins were housed in the Port of Nagoya Public Aquarium. The fungal species Candida albicans, C. tropicalis, C. glabrata, Aspergillus fumigatus, and A. niger were isolated. E-tests were performed to determine the minimum inhibitory concentrations (MICs) of ITZ and VRZ on these isolates. VRZ-resistant C. tropicalis (MIC: >32 µg/ml) and A. niger (MIC: >32 µg/ml) were isolated from three dolphins treated with ITZ or VRZ. Additionally, azole-resistant isolates of C. albicans and C. glabrata were collected from two dolphins that had never received azole therapy. To the best of our knowledge, our study is the first to report the isolation of VRZ-resistant C. albicans, C. tropicalis, and A. niger from the blowholes of bottlenose dolphins. Thus, antifungal susceptibility testing is a crucial strategy for selecting antifungal agents to treat respiratory fungal infections in bottlenose dolphins in aquaria.

Epicoccum nigrum-induced respiratory infection in a wild Eurasian scops owl (Otus scops).

A wild adult Eurasian scops owl (Otus scops), which was unable to fly, was rescued. Physical examination revealed a sticky exudate around the glottis. Heterophilic leukocytosis was identified through complete blood count, and radiography revealed a marked elevated density of posterior air sacs and inner cavities in both sides of the humerus and femur. Fungal cultures of samples taken from the owl suggested a respiratory fungal infection. Through molecular typing, the fungus was identified as Epicoccum nigrum. The owl was treated with oral itraconazole and broad-spectrum antibiotics. After one month, the inner cavities of pneumatic bones were slightly distinguishable by radiography and the owl started to fly well. Two months later, the air sac and all pneumatic bones displayed normal appearance.

Eltrombopag for Enhancement of Platelet Engraftment in Patients Undergoing Allogeneic Cord Blood Transplantation

BackgroundUmbilical cord blood (UCB) is an important alternative graft source for allogeneic hematopoietic cell transplantation (HCT) for patients without a HLA - matched donor. However, platelet recovery is significantly hampered following UCB transplantation, and patients remain platelet transfusion-dependent for prolonged periods of time. In the largest registry study to date, median time to platelet recovery over 20K/µL was over 70 days, and at 6 months only 50% of the patients had platelet engraftment. We hypothesized that eltrombopag (Revolade, GSK/Novartis), a thrombopoietin-receptor agonist, would enhance platelet engraftment after UCB transplantation.MethodsThis was a pilot multicenter open label single arm phase 2a study, in both adults and children (NCT01757145, NCT01940562). Oral eltrombopag was given from day +1 until platelet count exceeded 50K/µL for 14 consecutive days without platelet transfusion. Starting dose was 100 mg/d for adults and children weighing >40 kg and 50 mg/d for children weighing 20-40 kg. Based upon platelet response dosage was modified, with a maximal dose of 300mg/d for adults and 200mg/d for children. Study endpoints included safety, time to non-transfused platelet counts >20K/µL and >50K/µL, and platelet engraftment rate by day +50.ResultsBetween February 2013 and July 2016, 12 patients with hematological malignancies in complete remission were enrolled. The study cohort included 10 adults and 2 children, with a median age at transplantation of 50 (range 6-74) years (Table 1). Conditioning regimen was reduced-intensity in 7 patients and myeloablative in the remainder. Four patients received a single UCB unit, and 8 patients were given 2 units. The median total collected total nucleated cells (TNCs) *10^7/kg was 5.9 (range 2.7-8.6), and the median total collected CD34+ cells *10^5/kg was 3.1 (range 1.7-7.8).Patients received eltrombopag for a median of 76 days (range 15-175). Overall, eltrombopag was well tolerated even at maximal doses, and there was no need for dose reduction due to toxicity. No clinically significant side effects related to the study drug were reported. Of note, two patients developed mild, asymptomatic and transient indirect hyperbilirubinemia. No patient developed sinusoidal obstructive syndrome. No patient developed a thrombotic event while receiving eltrombopag. There was one case of lower extremity deep vein thrombosis, 6 months post-transplant (#03). No significant bone marrow fibrosis was documented even after prolonged eltrombopag administration.One patient (#07) died due to fungal respiratory infection on day +15 prior to engraftment. One patient (#01) had primary graft failure and autologous reconstitution, and is still alive in complete remission (CR) 5 years post-transplant. Among the 10 evaluable patients, median time to neutrophil engraftment was 23 (range 16-40) days. Median time to platelets>20K/µL and platelets>50K/µL was 55 (range 25-199) and 66 (range 31-230) days, respectively. Median time to RBC transfusion independence was 39 (range 13-157) days.Overall, 4 patients developed grade 2 (n=2) or grade 3 (n=2) acute graft versus host disease (GVHD), and 4 patients developed chronic GVHD (mild, n=3; moderate, n=1). There was no death attributable to GVHD.The median follow up time was 20 months (range 15 days - 61 months). At last follow up, 7 patients were alive, all still in CR at a median of 3.5 years post-transplant (range 1-5 years). Two patients died of relapse of their primary disease (#05, 7 months after transplant; #02, 29 months after transplant), for both these patients the UCB transplantation was the second transplant. Three patients died of infectious complications (#07, early death due to fungal respiratory infection on day +15; #08, pneumonia on day +157; #06 sepsis on day +153).ConclusionsIn the present study, eltrombopag was safe in the context of UCB transplantation. With the limitation of our small sample size, the use of eltrombopag was associated with enhanced platelet recovery time compared to published data. Further prospective studies are warranted to confirm these results. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Pulmonary Aspergillus fumigatus infection in rats affects gastrointestinal homeostasis

Microbiota inhabiting mucosal tissues is involved in maintenance of their immune homeostasis. Growing body of evidence indicate that dysbiosis in gut influence immune responses at distal sites including lungs. There are also reports concerning gut involvement with pulmonary injury/inflammation in settings of respiratory viral and bacterial infections. The impact of infections with other microorganisms on gut homeostasis is not explored. In this study, the rat model of sublethal pulmonary infection with Aspergillus fumigatus was used to investigate the effect of fungal respiratory infection on gut immune-mediated homeostasis. Signs of intestinal damage, intestinal and gut-draining lymphoid tissue cytokine responses and gut bacterial microbiota diversity were examined. Intestinal injury, inflammatory cell infiltration, as well as increased levels of intestinal interferon-γ (IFN-γ) and interleukin-17 (IL-17) (as opposed to unchanged levels of anti-inflammatory cytokine IL-10) during the two-week period depict intestinal inflammation in rats with pulmonary A. fumigatus infection. It could not be ascribed to the fungus as it was not detected in the intestine of infected rats. Increased production of pro-inflammatory cytokines by major gut-draining mesenteric lymph nodes point to these lymphoid organs as places of generation of cytokine-producing cells. No changes in spleen or systemic cytokine responses was observed, showing lack of the effects of pulmonary A. fumigatus infection outside mucosal immune system. Drop of intestinal bacterial microbiota diversity (disappearance of several bacterial bands) was noted early in infection with normalization starting from day seven. From day three, appearance of new bacterial bands (unique to infected individuals, not present in controls) was seen, and some of them are pathogens. Alterations in intestinal bacterial community might have affected intestinal immune tolerance contributing to inflammation. Disruption of gut homeostasis during pulmonary infection might render gastrointestinal tract more susceptible to variety of physiological and pathological stimuli. Data which showed for the first time gut involvement with pulmonary infection with A. fumigatus provide the baseline for future studies of the impact of fungal lung infections to gut homeostasis, particularly in individuals susceptible to these infections.

Iron restriction inside macrophages regulates pulmonary host defense against Rhizopus species

Mucormycosis is a life-threatening respiratory fungal infection predominantly caused by Rhizopus species. Mucormycosis has incompletely understood pathogenesis, particularly how abnormalities in iron metabolism compromise immune responses. Here we show how, as opposed to other filamentous fungi, Rhizopus spp. establish intracellular persistence inside alveolar macrophages (AMs). Mechanistically, lack of intracellular swelling of Rhizopus conidia results in surface retention of melanin, which induces phagosome maturation arrest through inhibition of LC3-associated phagocytosis. Intracellular inhibition of Rhizopus is an important effector mechanism, as infection of immunocompetent mice with swollen conidia, which evade phagocytosis, results in acute lethality. Concordantly, AM depletion markedly increases susceptibility to mucormycosis. Host and pathogen transcriptomics, iron supplementation studies, and genetic manipulation of iron assimilation of fungal pathways demonstrate that iron restriction inside macrophages regulates immunity against Rhizopus. Our findings shed light on the pathogenetic mechanisms of mucormycosis and reveal the role of macrophage-mediated nutritional immunity against filamentous fungi.

The myriad challenges of respiratory fungal infection in cystic fibrosis.

Fungal infection in cystic fibrosis (CF) is a recognized challenge, with many areas requiring further investigation. Consensus definitions exist for allergic bronchopulmonary aspergillus in CF, but the full scope of clinically relevant non-allergic fungal disease in CF-asymptomatic colonization, transient or chronic infection localized to endobronchial mucus plugs or airway tissue, and invasive disease-is yet to be clearly defined. Recent advances in mycological culture and non-culture identification have expanded the list of both potential pathogens and community commensals in the lower respiratory tract. Here we aim to outline the current understanding of fungal presence in the CF respiratory tract, risk factors for acquiring fungi, host-pathogen interactions that influence the role of fungi from bystander to pathogen, advances in the diagnostic approaches to isolating and identifying fungi in CF respiratory samples, challenges of classifying clinical phenotypes of CF patients with fungi, and current treatment approaches. Development and validation of biomarkers characteristic of different fungal clinical phenotypes, and controlled trials of antifungal agents in well-characterized target populations, remain central challenges to surmount and goals to be achieved.

Fungi Identified in Patients with Recurrent Lung Disorders

Background: Clinical and radiological features of fungal respiratory infections are nonspecific and have overlap with other respiratory diseases. A definitive diagnosis requires laboratory identification of the causative agents, of which the most frequent ones are Candida species, Aspergillus species, and Pneumocystis jirovecii. Objectives: The aim of this study was to evaluate the rate of fungi identified from the respiratory tract system of patients suffering from recurrent lung disorders (lung cancer or mycobacterial infections) by culture and real-time PCR. Methods: One hundred and ninety-two bronchoalveolar lavage and sputum samples from 96 patients with clinical and radiological signs and symptoms of lung diseases were collected and cultured. The identification of fungi was made by the macroscopic and microscopic examination of the isolates and yeasts were identified by the API 20 C AUX system. Pneumocystis jirovecii was detected by the microscopic examination of the samples through immunofluorescence staining and real-time PCR. Results: Fungi identification was successful in 49/96 (51%) patients. The Candida species growth was observed in the culture of 28/96 (29.2%). Aspergillus species were isolated from 7 patients (7.3%). The most frequent species identified were Candida albicans, C. glabrata, C. krusei, Aspergillus flavus, and A. fumigatus. Pneumocystis jirovecii immunofluorescence staining was positive in 23.9% of the patients with more than five cysts and 42.7% of the patients with less than five cysts. By real time-PCR, P. jirovecii was detected in 54.2% of the patients. Conclusions: A high frequency of identified fungi may be present as documented infection or colonization of the airways in pulmonary diseases. The management of high risk and immunosuppressed patients requires special attention to fungi identified from them.

Comparing the Profile of Respiratory Fungal Pathogens amongst Immunocompetent and Immunocompromised Hosts, their Susceptibility Pattern and Correlation of Various Opportunistic Respiratory Fungal Infections and their Progression in Relation to the CD4+T-cell Counts

Introduction: Invasive fungal infections are increasingly common in the nosocomial setting. Materials and Methods: The patients were divided into two groups immunocompetent and immunocompromised that is, patients with significant neutropenia <500 neutrophils/μl for longer than 10 days. microscopy, culture, identification of isolates were done and some specilised tests on serum and BAL for antigen detection were performed. Results: Majority of the patients were young adult males in this study. A higher prevalence of 26.7% was seen in immunocompromised patients. Amongst yeasts, Candida albicans was the predominant species followed by the National AIDS Control that is, Candida glabrata, Candida dubliniensis, Candida parapsilosis and Candida tropicalis in the same order. Amongst moulds, Aspergillus fumigatus was the most common species followed by Aspergillus flavus and Aspergillus niger. Mucor and Penicillium marneffei were seen in a lower prevalence. By Broth microdilution method, isolates of Candida spp. were most sensitive to caspofungin, amphotericin B, ketoconazole and fluconazole in the same order. Isolates of Aspergillus spp. were most sensitive to caspofungin, amphotericin B and itraconazole in the same order. By disc diffusion method, resistance to fluconazole was observed in 6.9% isolates of C. albicans. 50% of C. dubliniensis and 20% of C. glabrata showed resistance to fluconazole. A total mortality of 27.7% was observed during this study. This was distributed as 24.1%, 26.7%, 50%, 50%, 100% and 0% among by patients of candidiasis, aspergillosis, cryptococcosis, pneumocystosis, mucormycosis and penicilliosis. Fifteen per cent were lost to follow-up. Conclusion: Patterns of invasive fungal infections are changing in many ways. In the midst of these evolving trends, IFI of the respiratory tractcontinue to remain important causes of morbidity and mortality. Diagnostic tools can be adequately used only if the treating physician is aware of the propensity of patients to acquire a fungal infection. Thus, continuous awareness and education is crucial for successful management of patients. Judicious use of antifungal medications as prophylactic measures must be employed, particularly in the critically ill and patients of HIV.

Aspergillus and other respiratory fungal infections in the ICU: diagnosis and management.

Filamentous fungi respiratory infections, namely because of Aspergillus, Mucorales, Fusarium, or Scedosporium, show rising incidence and occur more in populations which are not classically immunosuppressed. This and their persistent dismal prognosis are the focus of this review. Both an early diagnosis, rooted on a high level of suspicion and based on clinical picture, radiology, cultural microbiological exams, fungal biomarkers, PCR and biopsy, and an early therapy, including immunorecovery, whenever possible, good antifungal selection, and surgery for source control, are paramount to maximize the outcome in these diseases. An evolving antifungal armamentarium and a more Pharmacokinetics/Pharmacodynamics-based antifungal prescription may help to improve the prognosis. Improved awareness of these infections may increase the level of suspicion, promoting early diagnosis and treatment, ideally supported with expert stewardship.

The diagnosis and management of respiratory tract fungal infection in cystic fibrosis: A UK survey of current practice.

Aspergillus fumigatus is commonly found in the airways of patients with cystic fibrosis (CF), and allergic bronchopulmonary aspergillosis (ABPA) is the most recognized associated clinical condition. However, accurate diagnosis remains challenging, and there is a paucity of clinical trials to guide clinical management of fungal disease. The aim of this survey was to assess the variability in current practice across the UK in diagnosis and management of fungal lung disease in CF patients. A 21 question anonymous online survey was sent to 94 paediatric and adult CF consultants in the UK. The response rate was 60.6% (32 adult physicians, 25 pediatricians) with 55 full and 2 partially completed surveys. For a first diagnosis of ABPA 20 (35.1%) treat with prednisolone alone, 38 (66.7%) use prednisolone with itraconazole and 2 (3.5%) choose voriconazole. Only 5 (8.8%) treat with prednisolone alone for a 1st relapse, 33 (58%) used prednisolone with itraconazole. To reduce treatment, 21 (36.8%) decrease steroids to zero over time and maintain azole therapy, 18 (31.6%) stop the azole and steroid after a fixed time, and 5 (8.8%) stop the azole after a fixed time and maintain a small steroid dose. Thirty-eight (66.7%) respondents believe Aspergillus colonization of the airway can cause clinical deterioration, and 37 (66.1%) would treat this. Scedosporium apiospermum infection has been diagnosed and treated by 35 (61.4%) of respondents. Results of this survey highlight the variance in clinical practice and the limited evidence available to guide management of fungal infection in CF.

Developing collaborative works for faster progress on fungal respiratory infections in cystic fibrosis.

Cystic fibrosis (CF) is the major genetic inherited disease in Caucasian populations. The respiratory tract of CF patients displays a sticky viscous mucus, which allows for the entrapment of airborne bacteria and fungal spores and provides a suitable environment for growth of microorganisms, including numerous yeast and filamentous fungal species. As a consequence, respiratory infections are the major cause of morbidity and mortality in this clinical context. Although bacteria remain the most common agents of these infections, fungal respiratory infections have emerged as an important cause of disease. Therefore, the International Society for Human and Animal Mycology (ISHAM) has launched a working group on Fungal respiratory infections in Cystic Fibrosis (Fri-CF) in October 2006, which was subsequently approved by the European Confederation of Medical Mycology (ECMM). Meetings of this working group, comprising both clinicians and mycologists involved in the follow-up of CF patients, as well as basic scientists interested in the fungal species involved, provided the opportunity to initiate collaborative works aimed to improve our knowledge on these infections to assist clinicians in patient management. The current review highlights the outcomes of some of these collaborative works in clinical surveillance, pathogenesis and treatment, giving special emphasis to standardization of culture procedures, improvement of species identification methods including the development of nonculture-based diagnostic methods, microbiome studies and identification of new biological markers, and the description of genotyping studies aiming to differentiate transient carriage and chronic colonization of the airways. The review also reports on the breakthrough in sequencing the genomes of the main Scedosporium species as basis for a better understanding of the pathogenic mechanisms of these fungi, and discusses treatment options of infections caused by multidrug resistant microorganisms, such as Scedosporium and Lomentospora species and members of the Rasamsonia argillacea species complex.

Clinical Vignettes/Case Reports-Obesity.

Bariatric surgeries of all types, including laparoscopic adjustable gastric band (LAGB), have gained large popularity in the past few decades as an effective method of weight loss in morbidly obese patients. Such procedures carry multiple short and long term complications. Rare and difficult to recognize surgical complications may have a significant impact on patient's quality of life and health-care cost. We report a case of a 62 year-old woman who presented to the hospital seven years after successful LAGB surgery with several months of cough, shortness of breath, and episodes of nausea associated with vomiting. She is a non-smoker and has a history of obstructive sleep apnea. Recent history is pertinent for multiple episodes of pneumonia treated with antibiotics in the outpatient. CT chest revealed extensive innumerable tiny nodular bilateral infiltrates with no significant adenopathy. It also showed distended esophagus with fluid content. Patient subsequently got admitted for further evaluation and management of her worsening symptoms. Initial workup for possible respiratory bacterial, fungal and mycobacterium infections were negative. Patient underwent extensive work up with bronchoscopy which showed erosive inflammation in various stages in the posterior oropharynx. Trans-bronchial biopsy from the right lower lobe showed inflammatory cells with no malignant cells. It also showed the presence of Enterobacter Cloacae (gut flora) on the bronchoalveolar lavage, suggestive of aspiration pneumonia. Esophagogastroduodenoscopy (EGD) showed distal migration of the gastric band, resulting in gastric retention (See image 1 & 2). Patient was then transferred to a tertiary care center where she underwent uncomplicated surgical removal of the gastric band with complete resolution of her symptoms. There have been only few reported cases of chronic cough as a long term complication of gastric band surgery. Chronic cough associated recurrent aspiration pneumonia in a patient with history of gastric band surgery should raise the suspicion of band slippage. Pathophysiology suspected is micro aspiration of acid leading to pneumonitis eventually predisposing to recurrent pneumonia and chronic cough. Early suspicion can help recognize the condition as removal of the band can result in complete resolution of symptoms.Figure: Distal esophageal dilatation with fluid stasis.Figure: Slipped band with errosions into the mid body part of the stomach.

Volatile Organic Compounds: Upcoming Role in Diagnosis of Invasive Mould Infections

Purpose of Review Breath testing for fungal respiratory infections has great promise as samples can be obtained by non-invasive, repeatable techniques that can be done on a wide range of patients including children, the confused and from those in the intensive care unit (ICU). We have reviewed progress toward development of test applicable to clinical practice.

In vitro activity of a novel compound, Mul-1867, against clinically significant fungi Candida spp. and Aspergillus spp.

There is an urgent need for new antifungal compounds to treat various types of fungal infections, including pulmonary infections. This study was designed to investigate the potency of a novel compound (Mul-1867) against Candida spp. and Aspergillus spp. isolated from patients with fungal pneumonia, cystic fibrosis and chronic obstructive pulmonary disease. Mul-1867 was highly effective against susceptible control strains as well as resistant clinical isolates, with minimum fungicidal concentrations (MFCs) varying from 0.06 µg/mL to 0.5 µg/mL. It was also highly effective against pre-formed 48-h-old biofilms formed by yeasts and moulds. The half-minimal biofilm eradication concentration (MBEC50) was equal to the MFC. The minimum biofilm eradication concentration to eliminate 90% of biofilms (MBEC90) varied from 1 × to 4 × MFC. Scanning electron microscopy revealed morphological changes accompanied by the release of intracellular material from the fungal cells following exposure to Mul-1867. Furthermore, an increased concentration of nucleic acids was found in the medium after 5 min and 20 min of Mul-1867 treatment, indicating leakage of cytoplasmic contents. Overall, these data indicate that Mul-1867 may be a promising inhaled antifungal agent for the treatment and prevention of fungal respiratory infections.

Contribution of the qPCR for the Diagnosis of Pneumocystosis

Background Pneumocystis jirovecii pneumonia (PCP) is an opportunistic fungal respiratory infection. The incidence of PCP has decreased among HIV patients, however among non HIV-negative patients on immunosuppressive drugs; an increase in incidence is noted. In this population, the diagnosis of PCP is difficult because the clinical presentation is atypical and the direct examination (DE) of the respiratory secretions is often negative. In this context, detection of Pneumocystis jirovecii DNA in respiratory secretions by real-time quantitative chain reaction (qPCR) should be usefull.MethodsIn order to evaluate the usefulness of qPCR, all patients hospitalized in medicine or intensive care unit (ICU) in a university hospital and having a positive qPCR in respiratory secretions were included in a retrospective study conducted between 2013 and 2016. Based on clinical data, respiratory secretions, imaging and treatment, patients were classified into three groups: certain PCP, possible, or colonization, irrespective of the value of qPCR.ResultsOne hundred and fifty patients, including 38 infected with HIV, were included: 75 in medicine and 75 in intensive care. Ninety patients (60%) had bronchoalveolar lavage. The diagnosis of PCP was considered certain or possible for 52 and 77 patients respectively and rejected (colonization) for 21 patients. DE was negative for 78% of non-HIV patients and 29% of HIV patients. Among the 129 patients with PCP, the hospital mortality was 35.9% in ICU and 21.5% in medicine. The median value of qPCR was 76,650 copies/mL among patients with PCP and 3,220 copies/mL among colonized patients (P < 0.001) with no significant difference in type of respiratory specimen or place of hospitalization. The optimal threshold value of qPCR determined from the ROC curve was 10,100 copies/mL with a sensitivity of 76.6% and a specificity of 86%. Specificity was 100% at the threshold of 59,250 copies/mL.ConclusionIf qPCR alone is imperfect for the differential diagnosis between colonization and infection, it has the merit of guiding the clinician towards the diagnosis of PCP especially for non-HIV patients whose DE of the respiratory secretions is negative in nearly 80% of cases, both in medicine and ICU.Disclosures All authors: No reported disclosures.

Surfactant proteins, SP-A and SP-D, in respiratory fungal infections: their role in the inflammatory response.

Pulmonary surfactant is a complex fluid that comprises phospholipids and four proteins (SP-A, SP-B, SP-C, and SP-D) with different biological functions. SP-B, SP-C, and SP-D are essential for the lungs’ surface tension function and for the organization, stability and metabolism of lung parenchyma. SP-A and SP-D, which are also known as pulmonary collectins, have an important function in the host’s lung immune response; they act as opsonins for different pathogens via a C-terminal carbohydrate recognition domain and enhance the attachment to phagocytic cells or show their own microbicidal activity by increasing the cellular membrane permeability. Interactions between the pulmonary collectins and bacteria or viruses have been extensively studied, but this is not the same for fungal pathogens. SP-A and SP-D bind glucan and mannose residues from fungal cell wall, but there is still a lack of information on their binding to other fungal carbohydrate residues. In addition, both their relation with immune cells for the clearance of these pathogens and the role of surfactant proteins’ regulation during respiratory fungal infections remain unknown. Here we highlight the relevant findings associated with SP-A and SP-D in those respiratory mycoses where the fungal infective propagules reach the lungs by the airways.

EPS03.9 Novel approaches for CF associated respiratory fungal infections

ePS03.9 Novel approaches for CF associated respiratory fungal infections

Mycological Profile of Sputum of HIV Positive Patients with Lower Respiratory Tract Infection and its Correlation with CD4+ T Lymphocyte Count.

Fungal respiratory infections are important cause of mortality and morbidity among HIV positive individuals. They account for up to 70% of illness in Acquired Immunodeficiency Disease Syndrome cases (AIDS). The range of illness varies from asymptomatic mucosal candidiasis to overwhelming disseminated infections. In these patients dissemination of fungus leads to very serious outcomes hence, it is important to have the knowledge of prevailing profile of fungus causing infections, so that it can be treated at the onset. Low CD4+ T lymphocyte count is an excellent indicator of decreased immunity and can also be helpful to predict opportunistic fungal respiratory infections and other complications. To define the fungal aetiology of lower respiratory tract infections in HIV positive patients and to correlate the occurrence of different fungi with CD4+ T lymphocyte count. This was a cross sectional study conducted between May 2014 to April 2015, on 180 treatment naive HIV seropositive patients with lower respiratory tract infections attending the Integrated Counselling and Testing Centre, SMS Medical College, Jaipur, Rajasthan. Early morning expectorated and induced sputum samples were collected and processed for isolation and identification of fungal species. CD4+ T lymphocyte count estimation was done by BD FACS Calibur. Fungal species were isolated from 155 (86.1%) patients. The most common isolate was Candida albicans (31.7%), followed by Aspergillus niger (17.7%) and Aspergillus flavus (10%). The fungal species were most commonly isolated from patients with CD4+ T lymphocyte cell less than 200 cells/μl. Fungal infections were seen in 86.1% of HIV positive patients with lower respiratory tract infections hence, high level of clinical suspicion for fungal aetiology of respiratory infections in HIV positive patients should be kept in mind.

Single-lung transplantation in emphysema: Retrospective study analyzing survival and waiting list mortality.

To performed remains a subject of debate and is the principal aim of the study. This retrospective analysis included 73 patients with emphysema (2000-2012). The outcomes of patients undergoing single-lung transplantation (SL) (n = 40) or double-lung transplant (DL) (n = 33) were compared in a Cox multivariate analysis to study the impact of the technique, postoperative complications and acute and chronic rejection on survival rates. Patients were selected for inclusion in the waiting list according to the International Society of Heart Lung Transplantation criteria. Pre and postoperative rehabilitation and prophylaxis, surgical technique and immunosuppressive treatment were similar in every patients. Lung transplantation waiting list information on a national level and retrospective data on emphysema patient survival transplanted in Spain during the study period, was obtained from the lung transplantation registry managed by the National Transplant Organization (ONT). Both groups were comparable in terms of gender and clinical characteristics. We found significant differences in the mean age between the groups, the DL patients being younger as expected from the inclusion criteria. Perioperative complications occurred in 27.6% SL vs 54% DL (P = 0.032). Excluding perioperative mortality, median survival was 65.3 mo for SL and 59.4 mo for DL (P = 0.96). Bronchiolitis obliterans and overall 5-year survival were similar in both groups. Bacterial respiratory infection, cytomegalovirus and fungal infection rates were higher but not significant in SL. No differences were found between type of transplant and survival (P = 0.48). To support our results, national data on all patients with emphysema in waiting list were obtained (n = 1001). Mortality on the waiting list was 2.4% for SL vs 6.2% for DL. There was no difference in 5 year survival between 235 SL and 430 DL patients transplanted (P = 0.875). Our results suggest that SL transplantation in emphysema produce similar survival than DL with less postoperative complication and significant lower mortality in waiting list.