Prevalence of co-existent COVID-19-associated pulmonary aspergillosis (CAPA) and its impact on early mortality in patients with COVID-19-associated pulmonary mucormycosis (CAPM).

BACKGROUND: Data on mixed mould infection with COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated pulmonary mucormycosis (CAPM) are sparse. OBJECTIVES: To ascertain the prevalence of co-existent CAPA in CAPM (mixed mould infection) and whether mixed mould infection is associated with early mortality (≤7 days of diagnosis). METHODS: We retrospectively analysed the data collected from 25 centres across India on COVID-19-associated mucormycosis. We included only CAPM and excluded subjects with disseminated or rhino-orbital mucormycosis. We defined co-existent CAPA if a respiratory specimen showed septate hyphae on smear, histopathology or culture grew Aspergillus spp. We also compare the demography, predisposing factors, severity of COVID-19, and management of CAPM patients with and without CAPA. Using a case-control design, we assess whether mixed mould infection (primary exposure) were associated with early mortality in CAPM. RESULTS: We included 105 patients with CAPM. The prevalence of mixed mould infection was 20% (21/105). Patients with mixed mould infection experienced early mortality (9/21 [42.9%] vs. 15/84 [17.9%]; p = 0.02) and poorer survival at 6 weeks (7/21 [33.3] vs. 46/77 [59.7%]; p = 0.03) than CAPM alone. On imaging, consolidation was more commonly encountered with mixed mould infections than CAPM. Co-existent CAPA (odds ratio [95% confidence interval], 19.1 [2.62-139.1]) was independently associated with early mortality in CAPM after adjusting for hypoxemia during COVID-19 and other factors. CONCLUSION: Coinfection of CAPA and CAPM was not uncommon in our CAPM patients and portends a worse prognosis. Prospective studies from different countries are required to know the impact of mixed mould infection.

Has the mortality from pulmonary mucormycosis changed over time? A systematic review and meta-analysis.

OBJECTIVES: Pulmonary mucormycosis (PM) is increasingly being reported in immunocompromised patients and has a high mortality. Our aim was to assess the mortality of PM and its trend over time. We also evaluated the role of combined medical-surgical therapy in PM. METHODS: We performed a systematic review of Pubmed, Embase, and Cochrane central databases. Studies were eligible if they described at least five confirmed cases of PM and reported mortality. We also assessed the effect of combined medical-surgical therapy versus medical treatment alone on PM mortality. We used a random-effects model to estimate the pooled mortality of PM and compared it across three time periods. The factors influencing mortality were assessed using meta-regression. We evaluated the risk difference (RD) of death in the following: subjects undergoing combined medical-surgical therapy versus medical therapy alone, subjects with isolated PM versus disseminated disease, and PM in diabetes mellitus (DM) versus non-DM as a risk factor. RESULTS: We included 79 studies (1544 subjects). The pooled mortality of PM was 57.1% (95% confidence interval [CI] 51.7-62.6%). Mortality improved significantly over time (72.1% versus 58.3% versus 49.8% for studies before 2000, 2000-2009, and 2010-2020, respectively, p 0.00001). This improved survival was confirmed in meta-regression after adjusting for the study design, the country's income level, and the sample size. Combined medical-surgical therapy was associated with a significantly lower RD (95%CI) of death: -0.32 (-0.49 to -0.16). The disseminated disease had a higher risk of death than isolated PM, but DM was not associated with a higher risk of death than other risk factors. CONCLUSIONS: While PM is still associated with high mortality, we noted improved survival over time. Combined medical-surgical therapy improved survival compared to medical treatment alone.

Autopsy findings after long-term treatment of COVID-19 patients with microbiological correlation.

Between April and June 2020, i.e., during the first wave of pandemic coronavirus disease 2019 (COVID-19), 55 patients underwent long-term treatment in the intensive care unit at the University Hospital of Regensburg. Most of them were transferred from smaller hospitals, often due to the need for an extracorporeal membrane oxygenation system. Autopsy was performed in 8/17 COVID-19-proven patients after long-term treatment (mean: 33.6 days). Autopsy revealed that the typical pathological changes occurring during the early stages of the disease (e.g., thrombosis, endothelitis, capillaritis) are less prevalent at this stage, while severe diffuse alveolar damage and especially coinfection with different fungal species were the most conspicuous finding. In addition, signs of macrophage activation syndrome was detected in 7 of 8 patients. Thus, fungal infections were a leading cause of death in our cohort of severely ill patients and may alter clinical management of patients, particularly in long-term periods of treatment.

Invasive Pulmonary Aspergillosis in Chronic Obstructive Pulmonary Disease Exacerbations.

Nowadays, reports in the literature support that patients with severe chronic obstructive pulmonary disease (COPD) are at higher risk to develop invasive pulmonary aspergillosis (IPA). However, the interpretation of Aspergillus-positive cultures from the airways in critically ill COPD is still a challenge. Indeed, as the patient could be merely colonized, tissue samples are required to ascertain IPA diagnosis but they are rarely obtained before death. Consequently, diagnosis is often only suspected on the basis of a combination of three elements: clinical characteristics, radiological images (mostly thoracic CT scan), and microbiological, and occasionally serological, results. To facilitate the analysis of these data, several algorithms have been developed, and the best effectiveness has been demonstrated by the Clinical algorithm. This is of importance as IPA prognosis in these patients remains presently very poor and using such an algorithm could promote prompter diagnosis, early initiation of treatment, and subsequently improved outcome.While the most classical presentation of IPA in critically ill COPD patients features a combination of obstructive respiratory failure, antibiotic-resistant pneumonia, recent or chronic corticosteroid therapy, and positive Aspergillus cultures from the lower respiratory tract, the present article will also address less typical presentations and discuss the most appropriate treatments which could alter prognosis.

Cryptococcus neoformans Evades Pulmonary Immunity by Modulating Xylose Precursor Transport.

Cryptococcus neoformans is a fungal pathogen that kills almost 200,000 people each year and is distinguished by abundant and unique surface glycan structures that are rich in xylose. A mutant strain of C. neoformans that cannot transport xylose precursors into the secretory compartment is severely attenuated in virulence in mice yet surprisingly is not cleared. We found that this strain failed to induce the nonprotective T helper cell type 2 (Th2) responses characteristic of wild-type infection, instead promoting sustained interleukin 12p40 (IL-12p40) induction and increased IL-17A (IL-17) production. It also stimulated dendritic cells to release high levels of proinflammatory cytokines, a behavior we linked to xylose expression. We further discovered that inducible bronchus-associated lymphoid tissue (iBALT) forms in response to infection with either wild-type cryptococci or the mutant strain with reduced surface xylose; although iBALT formation is slowed in the latter case, the tissue is better organized. Finally, our temporal studies suggest that lymphoid structures in the lung restrict the spread of mutant fungi for at least 18 weeks after infection, which is in contrast to ineffective control of the pathogen after infection with wild-type cells. These studies demonstrate the role of xylose in modulation of host response to a fungal pathogen and show that cryptococcal infection triggers iBALT formation.

Risk factors and mortality in invasive Rasamsonia spp. infection: Analysis of cases in the FungiScope® registry and from the literature.

BACKGROUND: The new Rasamsonia spp. complex can develop invasive infection in immunosuppression or chronic pulmonary disease. It has potential to be misidentified as other genera due to morphological similarities. Nowadays, there is a gap of knowledge on this fungi. OBJECTIVES: To provide knowledge base of risk factors and therapeutic decisions in invasive Rasamsonia spp. complex infection. PATIENTS/METHODS: Cases of invasive infection due to Rasamsonia spp. (formerly Geosmithia/Penicillium spp.) from FungiScope® registry and all reported cases from a literature were included. RESULTS: We identified 23 invasive infections due to Rasamsonia spp., six (26.1%) in the FungiScope® registry. Main risk factors were chronic granulomatous disease (n = 12, 52.2%), immunosuppressive treatment (n = 10, 43.5%), haematopoietic stem cell transplantation (n = 7, 30.4%), graft-versus-host disease and major surgery (n = 4, 17.4%, each). Predominantly affected organs were the lungs (n = 21, 91.3%), disease disseminated in seven cases (30.4%). Fungal misidentification occurred in 47.8% (n = 11), and sequencing was used in 69.6% of the patients (n = 16) to diagnose. Breakthrough infection occurred in 13 patients (56.5%). All patients received antifungal treatment, mostly posaconazole (n = 11), caspofungin (n = 10) or voriconazole (n = 9). Combination therapy was administered in 13 patients (56.5%). Susceptibility testing showed high minimum inhibitory concentrations for azoles and amphotericin B, but not for echinocandins. No preferable treatment influencing favourable outcome was identified. Overall mortality was 39% (n = 9). CONCLUSION: Rasamsonia spp. are emerging fungi causing life-threatening infections, especially in immunocompromised and critically ill patients. Mortality is high. Treatment is challenging and clinicians dealing with this patient population should become aware of this infection constituting a medical emergency.

Characteristics and risk factors for mortality of invasive non-Aspergillus mould infections in patients with haematologic diseases: A single-centre 7-year cohort study.

Since mould-active azole prophylaxis has become a standard approach for patients with high-risk haematologic diseases, the epidemiology of invasive fungal infections (IFIs) has shifted towards non-Aspergillus moulds. It was aimed to identify the epidemiology and characteristics of non-Aspergillus invasive mould infections (NAIMIs). Proven/probable NAIMIs developed in patients with haematologic diseases were reviewed from January 2011 to August 2018 at Catholic Hematology hospital, Seoul, Korea. There were 689 patients with proven/probable invasive mould infections; of them, 46 (47 isolates) were diagnosed with NAIMIs. Fungi of the Mucorales order (n = 27, 57.4%) were the most common causative fungi, followed by Fusarium (n = 9, 19.1%). Thirty-four patients (73.9%) had neutropenia upon diagnosis of NAIMIs, and 13 (28.3%) were allogeneic stem cell transplantation recipients. The most common site of NAIMIs was the lung (n = 27, 58.7%), followed by disseminated infections (n = 8, 17.4%). There were 23.9% (n = 11) breakthrough IFIs, and 73.9% (n = 34) had co-existing bacterial or viral infections. The overall mortality at 6 and 12 weeks was 30.4% and 39.1%, respectively. Breakthrough IFIs (adjusted hazards ratio [aHR] = 1.99, 95% CI: 1.3-4.41, P = .031) and surgical treatment (aHR = 0.09, 95% CI: 0.02-0.45, P = .003) were independently associated with 6-week overall mortality. NAIMIs were not rare and occur as a complex form of infection often accompanied by breakthrough/mixed/concurrent IFIs and bacterial or viral infections. More active diagnostic efforts for NAIMIs are needed.

A multicentre observational study on the epidemiology, risk factors, management and outcomes of mucormycosis in India.

OBJECTIVES: To describe the epidemiology, management and outcome of individuals with mucormycosis; and to evaluate the risk factors associated with mortality. METHODS: We conducted a prospective observational study involving consecutive individuals with proven mucormycosis across 12 centres from India. The demographic profile, microbiology, predisposing factors, management and 90-day mortality were recorded; risk factors for mortality were analysed. RESULTS: We included 465 patients. Rhino-orbital mucormycosis was the most common (315/465, 67.7%) presentation followed by pulmonary (62/465, 13.3%), cutaneous (49/465, 10.5%), and others. The predisposing factors included diabetes mellitus (342/465, 73.5%), malignancy (42/465, 9.0%), transplant (36/465, 7.7%), and others. Rhizopus species (231/290, 79.7%) were the most common followed by Apophysomyces variabilis (23/290, 7.9%), and several rare Mucorales. Surgical treatment was performed in 62.2% (289/465) of the participants. Amphotericin B was the primary therapy in 81.9% (381/465), and posaconazole was used as combination therapy in 53 (11.4%) individuals. Antifungal therapy was inappropriate in 7.6% (30/394) of the individuals. The 90-day mortality rate was 52% (242/465). On multivariate analysis, disseminated and rhino-orbital (with cerebral extension) mucormycosis, shorter duration of symptoms, shorter duration of antifungal therapy, and treatment with amphotericin B deoxycholate (versus liposomal) were independent risk factors of mortality. A combined medical and surgical management was associated with a better survival. CONCLUSIONS: Diabetes mellitus was the dominant predisposing factor in all forms of mucormycosis. Combined surgical and medical management was associated with better outcomes. Several gaps surfaced in the management of mucormycosis. The rarer Mucorales identified in the study warrant further evaluation.

Scedosporium spp lung infection in immunocompetent patients: A systematic review and MOOSE-compliant meta-analysis.

Scedosporium genus as a significant emerging opportunist causes a broad spectrum of disease in not only immunosuppressed but also immunocompetent patients. The lung is one of the most commonly encountered sites of Scedosporium infection. Due to its very high levels of antifungal resistance, surgery has been recommended as an important part in the treatment of pulmonary Scedosporium spp infection, even in immunocompetent cases. However, whether lung surgery could help to reduce the risk of death in immunocompetent patients is not clear.We retrospectively retrieved the records of pulmonary infections with Scedosporium species in immunocompetent patients through a comprehensive literature search. The association of surgery on all-cause mortality was explored using binary logistic regression (BLR). Receiver operating characteristic (ROC) curve analysis was carried out to evaluate the capability of the model.The comprehensive searching strategy yielded 33 case reports and 3 case series in total, with 40 individual patients being included. The overall mortality was 12.50%. The fatality rate was 9.09% (2/22) in cases with surgery and 16.67% (3/18) in cases without surgery (odds ratio, 0.50; 95% confidence interval, 0.07-3.38; P = .48). Consistently, BLR analysis identified no statistical association between surgery and reduced mortality (odds ratio, 1.19; 95% confidence interval, 0.09-15.64; P = .89), after adjusting for age, gender, and antifungal chemotherapy. The area under the ROC curve was 0.88.For immunocompetent patients with pulmonary Scedosporium spp infection, surgical therapy may not be associated with reduced mortality. Surgical excision could be considered but is not imperative in this group of patients.

Characteristics of pulmonary mucormycosis and predictive risk factors for the outcome.

PURPOSE: Little is known about risk factors for the outcome of pulmonary mucormycosis. We summarized characteristics of this rare disease, and systemically explored risk factors for the outcome. METHODS: Ninety-two patients with pulmonary mucormycosis, including 12 patients at Peking Union Medical College Hospital and 80 patients published in 62 articles between 2006 and 2016, were retrospectively analyzed. RESULTS: The median age was 47.5 years, and the male to female ratio was 2.8:1. Hematological disorders, diabetes mellitus, renal insufficiency and organ transplantation were main underlying conditions. Twelve percent of patients had no underlying diseases. A predilection for involvement of upper lobes was noted, and thick-walled cavity was described in 37.0% of patients on chest computed tomography. Most of the patients were diagnosed by microscopic analysis (95.7%), mainly histopathology; and only a minority were diagnosed by culture of sterile materials (28.3%). The overall mortality rate was 30.4%. Four independent determinants were associated with a better prognosis: hemoptysis (adjusted OR 7.910; 95% CI 1.411-44.342), chronic onset (adjusted OR 25.269, 95% CI 1.654-385.993), treated with medicine (adjusted OR 53.896, 95% CI 3.072-945.561), and treated with surgery (adjusted OR 5.983, 95% CI 1.497-23.918). CONCLUSIONS: Pulmonary mucormycosis is a rare infection with a high mortality. Invasive approach for histopathology and culture are crucial for a definite diagnosis. Acute onset patients had a poorer prognosis, and early treatment with antifungal therapy is imperative. Surgical approach is recommended in appropriate patients for a better outcome.

The role of extracorporeal membrane oxygenation in severe pulmonary coccidioidomycosis.

BACKGROUND: Severe coccidioidal pneumonia with acute respiratory distress syndrome (ARDS) is associated with high mortality. Extracorporeal membrane oxygenation (ECMO) has been applied successfully to other severe fungal pneumonia associated with ARDS. We review our experience with the use of ECMO in severe coccidioidal ARDS. OBJECTIVES: To review indications and outcome of ECMO in severe pulmonary coccidioidomycosis. METHODS: Three cases of severe ARDS caused by coccidioidomycosis are presented. All were managed with ECMO. Clinical course, complications, antifungal therapy and outcome are reviewed. RESULTS: Three cases of severe coccidioidal ARDS survived after treatment with ECMO. Common complications included bacterial pneumonia, encephalopathy and critical illness myopathy. They received liposomal amphotericin during ECMO, and transitioned to azole therapy. All required prolonged hospitalization and rehabilitation. CONCLUSIONS: ECMO was life-saving in cases of coccidioidal ARDS. Common complications included pneumonia, encephalopathy and critical illness myopathy. All cases were successfully managed with liposomal amphotericin followed by azole therapy. They required prolonged hospitalization and rehabilitation.

Pneumonia in Renal Transplant Recipients: A Single-Center Study.

OBJECTIVES: Pulmonary infections are a significant cause of morbidity and mortality in solid-organ transplant recipients despite enhanced facilities for perioperative care. The aim of this study was to evaluate the demographic characteristics, clinical course, and outcomes of renal transplant recipients with pneumonia. MATERIALS AND METHODS: The medical records of all renal transplant recipients from January 2010 to December 2014 were retrospectively reviewed, and patients diagnosed with pneumonia according to Centers for Disease Control and Prevention criteria were evaluated. Pneumonia was classified as community acquired or nosocomial. Patient demographics, microbiologic findings, need for intensive care/mechanical ventilation over the course of treatment, and information about clinical follow-up and mortality were all recorded. RESULTS: Eighteen (13.4%) of 134 renal transplant recipients had 25 pneumonia episodes within the study period. More than half (56%) of the pneumonia episodes developed within the first 6 months of transplant, whereas 44% developed after 6 months (all > 1 year). Eight cases (32%) were considered nosocomial pneumonia, and 17 (68%) were considered community-acquired pneumonia. Bacteria were the most common cause of pneumonia (28%), and fungi ranked second (8%). No viral or mycobacterial agents were detected. No patients required prolonged mechanical ventilation. No statistically significant difference was found in the need for intensive care or regarding mortality between patients with nosocomial and community-acquired pneumonia. Two patients (11%) died, and all remaining patients recovered. CONCLUSIONS: The present study confirmed that pneumonia after renal transplant is not a rare complication but a significant cause of morbidity. Long-term and close follow-up for pneumonia is necessary after renal transplant.

Values of radiological examinations for the diagnosis and prognosis of invasive bronchial-pulmonary aspergillosis in critically ill patients with chronic obstructive pulmonary diseases.

INTRODUCTION: The important role of radiological examinations of invasive pulmonary aspergillosis (IPA) in patients with neutropenia has been well studied; however, little is known about IPA in critically ill chronic obstructive pulmonary disease (COPD) patients. OBJECTIVES: To evaluate the value of radiological examinations in the diagnosis and prognosis of invasive bronchial-pulmonary aspergillosis (IBPA) in critically ill COPD patients. METHODS: We included 61 critically ill COPD patients in the intensive care unit (ICU) in a retrospective, single-center cohort study. RESULTS: All of the patients were classified as IBPA group (n = 21) or non-IBPA group (n = 40). The chest computed tomography (CT) image analysis showed that the IBPA group had the highest percent of patchiness (76.2%), followed by multiple nodules (33.3%), angio-invasive patterns (including halo sign, wedge consolidation and air-crescent sign/cavity with a relatively low percent of 19%, 19% and 28.5%, respectively), and the multiple nodules that were distributed along the airway provided the most specific image, with the highest specificity of 92.5%. Compared to the survivors in the IBPA group, non-surviving patients had a higher percent of large consolidation (0% vs. 45.5%, P = .035). When the new effusions appeared on a chest x-ray (CXR), the creatinine (140.4 µmol/L vs. 64.0 µmol/L, P = .010) and PaO2 /FiO2 (188 mm Hg vs. 222 mm Hg, P = .034) rate deteriorated. CONCLUSIONS: Multiple nodules that were distributed along with broncho-vascular bundles were relatively common and specific in critically ill COPD patients with IBPA. Deteriorated CXR combined with specific laboratory examinations, even when appropriate antibiotics were used, could indicate a diagnosis of IBPA. Large consolidations might be considered as poor prognostic indicators.

Risk and outcomes of pulmonary fungal infection after pediatric lung transplantation.

BACKGROUND: Prospective studies to determine associated risk factors and related outcomes for pulmonary fungal infection (PFI) after pediatric lung transplant (PLT) are lacking. METHODS: NIH-sponsored Clinical Trials in Organ Transplantation in Children enrolled PLT candidates, collecting data prospectively for 2 years post-transplant. Demographics, signs/symptoms, radiology, pathology and microbiology were collected. Analyses evaluated for PFI-related risks and outcomes. RESULTS: In 59 PLT, pre-transplant fungal colonization occurred in 6 donors and 15 recipients. Cystic fibrosis (CF) was associated with pre-transplant colonization (P < .01). Twenty-five (42%) PLT had 26 post-transplant colonizations (median = 67 days, range = 0-750 days) with Candida (13), Aspergillus (4), mold (6) or yeast (3). Post-PLT colonization was not associated with CF, age, or pre-PLT colonization. Thirteen PFIs occurred in 10 (17%) patients, 3 proven (Candida species) and 10 probable (Candida [3], Aspergillus [3], Penicillium [3], and mold [1]). Pulmonary fungal infection was preceded by post-PLT colonization with the same organism in 4 of 13 PFI, but post-PLT colonization did not predict subsequent PFI (P = .87). Older age at transplant was a risk for PFI (P < .01). No mortality was attributed to PFI. Prophylaxis use was not associated with decreased post-PLT colonization (P = .60) or PFI (P = .48). CONCLUSION: In PLT, PFI and fungal colonization are common but without associated mortality. Post-PLT colonization did not predict PFI. Optimal prevention strategies require additional study.

Early-Onset Pneumonia After Liver Transplant: Microbial Causes, Risk Factors, and Outcomes, Mansoura University, Egypt, Experience.

OBJECTIVES: Pneumonia has a negative effect on the outcome of liver transplant. Our aim was to analyze early-onset pneumonia that developed within the first month after transplant. MATERIALS AND METHODS: This prospective single-center study included 56 adult living-donor liver transplant recipients; those who developed early-onset pneumonia based on clinical and radiologic criteria were investigated as to causative pathogens and then followed up and compared with other recipients without pneumonia to illustrate risk factors, outcomes, and related mortality of posttransplant pneumonia. RESULTS: Twelve patients (21.4%) developed early-onset pneumonia with mortality rate of 75% (9 of 12). Sixteen pathogens were isolated; extended spectrum beta-lactamase producing Enterobacteriaceae were the most common (31.2%) followed by carbapenem-producing Enterobacteriaceae and methicillin-resistant Staphylococcus aureus (18.8%). Fungi were isolated in 3 cases that were also coinfected with bacteria. Diabetes mellitus (P = .042), liberal postoperative fluid therapy (P = .028), prolonged posttransplant intensive care unit stay (P = .01), atelectasis grade ≥ 2 (P ≤ .001), and calcineurin inhibitor-induced neurotoxicity (P = .04) were risk factors for early posttransplant pneumonia. CONCLUSIONS: Pneumonia is the leading cause of early mortality after liver transplant. The emergence of multidrug-resistant bacteria is major issue associated with a high rate of treatment failure.

Respiratory Tract Infection Caused by Fonsecaea monophora After Kidney Transplantation.

Fonsecaea spp. are melanized fungi which cause most cases of chromoblastomycosis. The taxonomy of this genus has been revised, now encompassing four species, with different pathogenic potential: F. pedrosoi, F. nubica, F. pugnacius, and F. monophora. The latter two species present wider clinical spectrum and have been associated with cases of visceral infection, most often affecting the brain. To our knowledge, this is the first report of proven case of F. monophora respiratory tract infection. A Brazilian 57-year-old-female patient underwent kidney transplantation on January 12, 2013. On the fourth postoperative month, the patient presented with fever, productive cough, and pleuritic pain in the right hemithorax. A thoracic CT scan showed a subpleural 2.2-cm nodular lesion in the right lung lower lobe, with other smaller nodules (0.5-0.7 cm) scattered in both lungs. Bronchoscopy revealed a grayish plaque on the right bronchus which was biopsied. Microscopic examination demonstrated invasion of bronchial mucosa by pigmented hyphae. Culture from the bronchial biopsy and bronchoalveolar lavage samples yielded a melanized mold, which was eventually identified as F. monophora. She started treatment with voriconazole (400 mg q.12h on the first day, followed by 200 mg q.12h). After 4 weeks of therapy, voriconazole dose was escalated to 200 mg q.8h and associated with amphotericin B (deoxycolate 1 mg/kg/day) because of a suspected dissemination to the brain. The patient eventually died of sepsis 8 weeks after the start of antifungal therapy. In conclusion, F. monophora may cause respiratory tract infection in solid organ transplant recipients.

Challenges and opportunities in the treatment of ventilator-associated pneumonia.

INTRODUCTION: Ventilator-associated pneumonia (VAP) is a distinct clinical entity characterized by an onset after 48 hours of the application of mechanical ventilation (MV). Protocols exist to aid in the prevention of VAP, but this infection carries a devastating impact on patient morbidity and potentially mortality. Areas covered: In this review we present key concepts from existing guidelines to aid clinicians. Challenges remain in defining this disease and, most importantly appropriate empiric antimicrobial treatment is the main determinant of outcome. We highlight that the selection of initial antibiotics is critical, as VAP can by caused by a broad array of drug resistant organisms (DROs), the appropriate duration of treatment for VAP is an evolving concept, but may, in part, be guided by biomarkers, and provide focus on diagnostic challenges, initial therapies and treatment strategies for VAP. Both traditional and novel antimicrobials are presented, including developments in the modes of delivery. Expert commentary: The clinical approach to VAP continues to evolve. Recent evidence regarding the changes in microbiology, diagnostics approaches, and treatment strategies for VAP are important for clinicians to remain informed of to provide optimal patient care.

Emergency and elective pulmonary surgical resection in haematological patients with invasive fungal infections: a report of 50 cases in a single centre.

Invasive fungal infections (IFI) remain life-threatening complications in haematological patients. The aim of the study was to present the experience of a single centre in the surgical treatment of pulmonary IFI. Between 1992 and 2014, 50 haematological patients with IFI underwent pulmonary resection. In 27 cases it was an emergency procedure to avoid haemoptysis (if the lesion threatened pulmonary vessels). The remaining 23 patients underwent elective surgery before new chemotherapy or stem-cell transplantation. Among these patients (median age: 54 years; range: 5-70 years), 92% had acute leukaemia and 68% were on haematological first-line therapy (receiving induction or consolidation chemotherapies). Invasive pulmonary aspergillosis and pulmonary mucormycosis were diagnosed in 37 and 12 patients, respectively. One patient had IFI due to Trichoderma longibrachiatum. All of the patients received antifungal agents. In the month preceding IFI diagnosis, 94% of patients had been neutropenic. At the time of surgery, 30% of patients were still neutropenic and 54% required platelet transfusions. Lobectomy or segmentectomy were performed in 80% and 20% of cases, respectively. Mortality at 30 and 90 days post-surgery was 6% and 10%, respectively. After surgery, median overall survival was 21 months; median overall survival was similar between patients with emergency or elective surgery and between the types of IFI (invasive pulmonary aspergillosis or pulmonary mucormycosis). However, overall survival was far better in haematological first-line patients or in those achieving a haematological complete response than in other patients (p <0.001). In pulmonary IFI, lung resection could be an effective complement to medical treatment in selected haematological patients.

Cryptococcal heat shock protein 70 homolog Ssa1 contributes to pulmonary expansion of Cryptococcus neoformans during the afferent phase of the immune response by promoting macrophage M2 polarization.

Numerous virulence factors expressed by Cryptococcus neoformans modulate host defenses by promoting nonprotective Th2-biased adaptive immune responses. Prior studies demonstrate that the heat shock protein 70 homolog, Ssa1, significantly contributes to serotype D C. neoformans virulence through the induction of laccase, a Th2-skewing and CNS tropic factor. In the present study, we sought to determine whether Ssa1 modulates host defenses in mice infected with a highly virulent serotype A strain of C. neoformans (H99). To investigate this, we assessed pulmonary fungal growth, CNS dissemination, and survival in mice infected with either H99, an SSA1-deleted H99 strain (Δssa1), and a complement strain with restored SSA1 expression (Δssa1::SSA1). Mice infected with the Δssa1 strain displayed substantial reductions in lung fungal burden during the innate phase (days 3 and 7) of the host response, whereas less pronounced reductions were observed during the adaptive phase (day 14) and mouse survival increased only by 5 d. Surprisingly, laccase activity assays revealed that Δssa1 was not laccase deficient, demonstrating that H99 does not require Ssa1 for laccase expression, which explains the CNS tropism we still observed in the Ssa1-deficient strain. Lastly, our immunophenotyping studies showed that Ssa1 directly promotes early M2 skewing of lung mononuclear phagocytes during the innate phase, but not the adaptive phase, of the immune response. We conclude that Ssa1's virulence mechanism in H99 is distinct and laccase-independent. Ssa1 directly interferes with early macrophage polarization, limiting innate control of C. neoformans, but ultimately has no effect on cryptococcal control by adaptive immunity.

Role of bronchoalveolar lavage in diagnosis of fungal infections in liver transplant recipients.

OBJECTIVES: Pulmonary fungal infections remain the most important cause of morbidity and mortality in liver transplant recipients. Fast and accurate causative diagnoses are essential for a good outcome. Bronchoscopy with bronchoalveolar lavage frequently is performed to diagnose pulmonary infections in immunocompromised patients. The aim of this study was to evaluate the diagnostic use of bronchoalveolar lavage in liver transplant recipients with pulmonary infections. MATERIALS AND METHODS: We retrospectively analyzed the data of 408 patients who underwent liver transplant from January 1990 to December 2012. Patients who underwent bronchoalveolar lavage after transplant were included in this study. RESULTS: There were 18 of 408 liver transplant recipients (4.41%) who underwent bronchoalveolar lavage after transplant. The mean age was 49.5 ± 18 years. In 5 patients (27.8%), fungal microorganisms were observed in the cytology of bronchoalveolar lavage specimens, including Aspergillus fumigatus in 3 patients and Candida albicans in 2 patients. Death occurred in 4 of 5 patients (80%) with fungal infections. No association was observed between the presence of fungal infection and clinical and radiographic findings of the patients. CONCLUSIONS: Bronchoscopy with bronchoalveolar lavage is a useful, noninvasive diagnostic tool for the rapid diagnosis of infections in solid-organ transplant recipients.