Pulmonary Fungal Infection Research Articles

Cerebral and pulmonary aspergillosis, treatment and diagnostic challenges of mixed breakthrough invasive fungal infections: case report study

BackgroundBreakthrough invasive fungal infections (bIFIs) are an area of concern in the scarcity of new antifungals. The mixed form of bIFIs is a rare phenomenon but could be potentially a troublesome challenge when caused by azole-resistant strains or non-Aspergillus fumigatus. To raise awareness and emphasize diagnostic challenges, we present a case of mixed bIFIs in a child with acute lymphoblastic leukemia.Case presentationA newly diagnosed 18-month-old boy with acute lymphoblastic leukemia was complicated with prolonged severe neutropenia after induction chemotherapy. He experienced repeated episodes of fever due to extended-spectrum beta-lactamase-producing Escherichia coli bloodstream infection and pulmonary invasive fungal infection with Aspergillus fumigatus (early-type bIFIs) while receiving antifungal prophylaxis. Shortly after pulmonary involvement, his condition aggravated by abnormal focal movement, loss of consciousness and seizure. Cerebral aspergillosis with Aspergillus niger diagnosed after brain tissue biopsy. The patient finally died despite 108-day antifungal therapy.ConclusionsMixed bIFIs is a rare condition with high morbidity and mortality in the patients receiving immunosuppressants for hematological malignancies. This case highlights the clinical importance of Aspergillus identification at the species level in invasive fungal infections with multiple site involvement in the patients on antifungal prophylaxis.

Conidiobolus pachyzygosporus invasive pulmonary infection in a patient with acute myeloid leukemia: case report and review of the literature

BackgroundConidiobolus spp. (mainly C. coronatus) are the causal agents of rhino-facial conidiobolomycosis, a limited soft tissue infection, which is essentially observed in immunocompetent individuals from tropical areas. Rare cases of invasive conidiobolomycosis due to C. coronatus or other species (C.incongruus, C.lamprauges) have been reported in immunocompromised patients. We report here the first case of invasive pulmonary fungal infection due to Conidiobolus pachyzygosporus in a Swiss patient with onco-haematologic malignancy.Case presentationA 71 year-old female was admitted in a Swiss hospital for induction chemotherapy of acute myeloid leukemia. A chest CT performed during the neutropenic phase identified three well-circumscribed lung lesions consistent with invasive fungal infection, along with a positive 1,3-beta-d-glucan assay in serum. A transbronchial biopsy of the lung lesions revealed large occasionally septate hyphae. A Conidiobolus spp. was detected by direct 18S rDNA in the tissue biopsy and subsequently identified at species level as C. pachyzygosporus by 28S rDNA sequencing. The infection was cured after isavuconazole therapy, recovery of the immune system and surgical resection of lung lesions.ConclusionsThis is the first description of C. pachyzygosporus as human pathogen and second case report of invasive conidiobolomycosis from a European country.

Saliva-controlled sputum culture (SSC) – A high value diagnostic tool for deep pulmonary infections

A major obstacle to prompt diagnosis of fungal pulmonary infections is that deep sputum samples are scarce, yet are frequently rejected if they contain saliva. We show that including saliva controls unfailingly distinguishes oropharyngeal flora from pulmonary fungi, thus preserving valuable samples for analysis, expediting diagnoses and improving patient care.

Fungal Isolates of the Respiratory Tract in Symptomatic Patients Hospitalized in Pulmonary Units: A Mycological and Molecular Epidemiologic Study.

IntroductionFungal respiratory infections are being recognized with increasing frequency in parallel with an expanding population of immunocompromised patients. In most cases, colonization is the first step in the progression to pulmonary fungal infection. This study was designed to evaluate the distribution of fungal elements in the respiratory tract of symptomatic patients hospitalized in pulmonary units.MethodsThis descriptive cross-sectional study was carried out over a period of two years, from October 2017 to October 2019 in Guilan province, located in Iran’s northern region. In the current study, bronchoalveolar lavage or sputum specimens were collected. All samples were analyzed by direct microscopy using KOH 10% and culture. Fungal identification was accomplished by internal transcribed spacer (ITS) and beta-tubulin sequencing. Also, in patients suspected of invasive pulmonary aspergillosis, BAL specimens were tested for galactomannan (GM) antigen.ResultsA total of 384 lung specimens (192 bronchoalveolar lavage (BAL) and 192 sputum samples) were obtained from symptomatic patients hospitalized in pulmonary units. Of these, 137 (35.67%) were positive in direct examination and culture. Among the 137 positive cases, most isolates were from male patients 86 (62.77%) and most of them were between 46 and 72 years. Candida albicans (37.22%) and Candida tropicalis (21.89%) represent the two most commonly isolated species in the current study. Cough (94.16%), dyspnea (81.02%), purulent sputum (62.04%) and weight loss (56.2%) were the predominant symptoms and tuberculosis (24.81%), chemotherapy (21.89%) and diabetes mellitus (19.70%) were the predominant underlying conditions. Also, 5 cases of invasive pulmonary aspergillosis and 1 case of mucormycosis were diagnosed.ConclusionCandida albicans was the most common fungal species isolated from symptomatic patients hospitalized in pulmonary units. Tuberculosis, chemotherapy and diabetes mellitus were important underlying conditions for pulmonary fungal colonization and/or infection.

English

English

Clinical Analysis of Allogeneic Hematopoietic Stem Cell Transplantation for Treatment of 12 Patients with Acute Leukemia in Tropical Area

To analyze the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for treatment of acute leukemia in the tropical area. Twelve acute leukemia patients who were underwent allo-HSCT from April 2013 to November 2018 in Hainan Hospital of Chinese PLA General Hospital were selected, including 5 cases of acute lymphoblastic leukemia (ALL) and 7 case of acute myeloid leukemia (AML). Three cases received HLA matched sibling hematopoietic stem cell transplantation, 8 cases received haploidentical hematopoietic stem cell transplantation, 1 cases received partially mismatched unrelated hematopoietic stem cell transplantation. Pretreatment regimen: 9 cases received modified BU/CY+ATG pretreatment regimen, 3 cases received BU/CY pretreatment regimen. Graft-versus-host disease (GVHD) prevention regimen: all patients received cyclosporine A, mycophenolate mofetil combined with short-term methotrexate regimen. The clinical efficacy of allo-HSCT in treatment of acute leukemia in the tropical area was analyzed by detecting hematopoietic reconstitution, GVHD, infection, relapse and survival after transplantation. All the 12 patients achieved granulocyte reconstruction and megakaryocyte reconstruction. The median time of granulocyte reconstruction was 11.5 (6-14) days, and the median time of megakaryocytic reconstruction was 12.5 (10-22) days. Within 100 days after transplantation, the acute GVHD occurved in 8 cases, including 6 cases of Ⅱ-Ⅳ degree acute GVHD and 2 cases of Ⅲ-Ⅳ degree acute GVHD, 11 cases survived more than 100 days after transplantation, and the chronic GVHD occurred in 1 case, which was mildly limited. Pulmonary infection occurred in 7 cases, cytomegaloviremia occurred in 6 cases, EB viremia occurred in 6 cases, and hemorrhagic cystitis occurred in 5 cases. 2 cases relapsed and eventually died, and the remaining 10 patients survived without disease until the date of follow-up. The median follow-up time was 4 (1-68) months, 83.3% (10/12) survived without disease, and 16.7% (2/12) relapsed. Allo-HSCT is an effective method for the treatment of acute leukemia in adults. Leukemia patients should be transplanted as soon as possible after remission. The incidence of pulmonary fungal infection in transplanted patients in tropics is high, therefore the prevention and treatment of fungal infection should be strengthened.

Computed tomography of lung infections in patients with lymphoproliferative diseases after chemotherapy

Objective : to determine CT features of pneumonia depending on the etiological agent in patients with LHP after chemotherapy. Materials and methods. 52 patients with LPD, who developed pneumonia, underwent chest CT. In all patients, the causative agent of lower respiratory tract infection was verified by microbiological diagnostic methods. Results . In the first 48 hours from the onset of the viral pneumonia, thickening of the interlobular septa and of peribronchial interstitium, part-solid and solid nodules, and hydropericardium (p < 0.01) were detected. After 48 hours, ground glass opacity, Intralobular septal thickening, “crazy-paving” pattern and hydropericardium were more often detected (p < 0.001). In the first 48 hours from the onset of invasive pulmonary mycosis, a halo sign (p < 0.01) and the prevalence of changes in the upper parts of the lungs (p < 0.05) were detected. After 48 hours, halo sign (p <0.01), a random distribution of nodules and solid nodules (p < 0.05) were detected. Conclusion . Viral or fungal etiology of lower respiratory tract infection can be excluded according to CT data with sufficient certainty, and that is undoubtedly a fundamental reason for changing further treatment tactics in such patients.

Hypercalcemia as an Early Finding of Opportunistic Fungal Pneumonia in Renal Transplantation: A Case Series Report

BackgroundPneumonia caused by opportunistic fungi is a serious complication in immunocompromised patients. Hypercalcemia has been described in renal transplantation associated with Pneumocystis jirovecii (PJP) or Histoplasma capsulatum (HCP) pneumonia. MethodsWe describe 5 patients who underwent kidney transplant between 2014 and 2019 and developed hypercalcemia before the diagnosis of pulmonary fungal infection: 4 patients with PJP and 1 with HCP. We assessed calcium metabolism and kidney function by total and ionized calcium, phosphorus, intact parathormone (iPTH), 25-OH vitamin D, 1,25(OH)2 vitamin D, and serum creatinine levels. ResultsMean albumin-corrected calcium and ionized calcium were 12.56 mg/dL (range, 10.8-13.8 mg/dL) and 1.57 mmol/L (range, 1.43-1.69 mmol/L). Patients were normocalcemic, at 10.12 mg/dL (range, 9.6-10.5 mg/dL), before diagnosis and resolved hypercalcemia after antifungal treatment, at 8.86 mg/dL (range, 8.0-9.5 mg/dL). All patients had low or normal iPTH values, at 29.1 pg/mL (range, <3-44 pg/mL), with higher PTH levels 3 months before diagnosis and after treatment, at 147.3 pg/mL (range, 28.1-479 pg/mL) and 117.5 pg/mL (range, 18.2-245 pg/mL), respectively. The mean value for 25-OH vitamin D was 30.8 ng/mL (range, 14.6-62.8 ng/mL). This supports a PTH-independent mechanism, and we postulated an extrarenal production of 1,25(OH)2 vitamin D. ConclusionIn kidney transplant patients, hypercalcemia independent of PTH and refractory to treatment should alert for the possibility of opportunistic fungal pneumonia.

Micosis pulmonares en pacientes con diabetes mellitus. Características clínicas y factores de riesgo

BackgroundDiabetes mellitus is a public health problem in Mexico, and the trend of the disease is increasing. From 2000 to 2017, 7.32 million new cases were diagnosed, with pulmonary mycoses being one of the most serious complications. AimsTo describe the frequency and the clinical characteristics of patients diagnosed with pulmonary mycoses, and to identify the risk factors associated with this entity. MethodsCase–control study, paired by gender (1:1-3) and age (± 5 years), that analyzed patients with pulmonary mycosis (mucormycosis, histoplasmosis, coccidioidomycosis, blastomycosis, aspergillosis, cryptococcosis, paracoccidioidomycosis) and studied the risk factors present in each patient. ResultsFrom the 162 patients studied, 56 suffered pulmonary mycosis and 106 were controls. The median of the age was 51 and 50 years for the cases and for the controls, respectively. Multiple logistic regression analysis showed that patients with diabetes mellitus had an odds ratio of 8,3 (p < 0.001), and patients with a history of tuberculosis had an odds ratio of 8,8 (p < 0.001). ConclusionsOur results show that 52% of the patients with pulmonary mycoses had a history of diabetes mellitus. Diabetes mellitus is a relevant risk factor for pulmonary mycoses, which are usually diagnosed in advanced stages and have a high mortality.

Management of Pulmonary Mycoses

Management of Pulmonary Mycoses

Pulmonary and Invasive Fungal Infections.

Pulmonary and Invasive Fungal Infections.

Pulmonary infections in patients with myelodysplastic syndromes receiving frontline azacytidine treatment.

Pulmonary infections (PIs) are a major complication of patients with myelodysplastic syndromes (MDS). We retrospectively evaluated 234 MDS patients treated with azacytidine (AZA). The total number of AZA cycles was 2886 (median 8 cycles per patient). There were 111 episodes of PI (3.8% of AZA cycles) in 81 patients (34.6%). PIs were considered of fungal origin in 27 cases (24.3%), associated to bacteremia in 11 cases (9.9%), to influenza infection in two cases (1.8%) and of unknown origin in the remaining 71 cases (64.0%). Forty-five PI episodes were documented in cycles 1 to 4 of AZA (5.1% of 875 cycles) and the remaining 66 episodes beyond the fourth cycle (3.2% of 2011 cycles) (P = .017). Overall, a fungal PI was documented in 13/875 (1.5%) cycles 1 to 4 and in 13/2011 (0.6%) cycles beyond the fourth cycle (P = .001). A baseline chronic pulmonary disease was significantly associated to a higher risk of severe PIs. In the survival analysis, cases of PI in patients who progressed to acute leukemia (PAL) were excluded, in view of the predominant influence of PAL on the outcome of the patients. A PI unrelated to PAL documented during the first 4 AZA cycles was an independent factor predicting lower survival (OR, 2.13; 95% CI, 1.37-3.33; P = .001). In conclusion, PIs are common in MDS patients receiving AZA, in particular during the first cycles of treatment and are associated with an unfavorable outcome. The results of our study raise the issue of the need of a tailored infection prevention strategy.

Antigen discovery unveils resident memory and migratory cell roles in antifungal resistance.

Priming at the site of natural infection typically elicits a protective T cell response against subsequent pathogen encounter. Here, we report the identification of a novel fungal antigen that we harnessed for mucosal vaccination and tetramer generation to test whether we can elicit protective, antigen-specific tissue resident memory (Trm) CD4+ T cells in the lung parenchyma. In contrast to expectations, CD69+, CXCR3+, CD103− Trm cells failed to protect against a lethal pulmonary fungal infection. Surprisingly, systemic vaccination induced a population of tetramer+ CD4+ T cells enriched within the pulmonary vasculature, and expressing CXCR3 and CX3CR1, that migrated to the lung tissue upon challenge and efficiently protected mice against infection. Mucosal vaccine priming of Trm may not reliably protect against mucosal pathogens.

Pulmonary mycoses treated by topical amphotericin B

Since its discovery, amphotericin B (AmB) became a key management because it is the most common antifungal drug with activity to disrupt the fungal cell wall. Furthermore, it is the first-choice treatment in pulmonary mycoses that may consider lethal infection; the difference in lipid structure between fungal and mammalian cell membranes determines the effect of AmB. However, some fungal pulmonary diseases such as aspergillomas are partially contact with the blood and narrow touch the walls of the lung cavities, thus administration of systemic antifungal agents may be ineffective to eliminate these infections. Tissue penetration of systemic antifungal agents must be evaluated to get a proper appreciation of their antifungal activity, which may differ even within the same antifungal class. So, topical administration considered necessity in these situations. AmB belongs to the polyene group has a wide-spectrum in vitro and in vivo antifungal activity. All of the known available formulas of AmB are administrated through intravenous injection to treat severe systemic fungal infections, while the development of the topical formula of AmB is still under preliminary development, including topical pulmonary AmB. Due to the revealing of antimicrobial-resistant fungi in recent years and ineffective systemic management of pulmonary fungi, this study explains the role of topical AmB in treating refractory lung fungi that not response to other drugs that may help researchers to develop an effective topical formula of AmB regarding pulmonary mycosis.

Spectrum of pulmonary fungal pathogens, associated risk factors, and anti-fungal susceptibility pattern among persons with presumptive tuberculosis at Gombe, Nigeria.

Pulmonary mycosis (PM) poses a great diagnostic challenge due to the lack of pathognomonic and radiological features, especially in the absence of mycology laboratory tests. This study was aimed to isolate, phenotypically identify, determine the prevalence of pulmonary fungal pathogens and antifungal susceptibility pattern of isolates of presumptive tuberculosis (PTB) patients attending Federal Teaching Hospital (FTH) Gombe, Nigeria. After ethical approval, three consecutive early morning sputa were collected from 216 participants with presumptive of PTB attending FTH Gombe, between May 2, 2017 and May 30, 2018. Samples were processed using standard mycological staining, microscopy, sugar biochemistry, and antifungal susceptibility test protocols. Sociodemographic variables and risk factors of pulmonary fungal infection were assessed through structured questionnaires. Pulmonary fungal infection was defined by the positive culture in at least two sputa. PTB was defined by Genexpert® nested polymerase chain reaction. Of the 216 participants, 19.9% had PTB and 73.6% had pulmonary fungal pathogens. Among the isolated pulmonary fungal pathogens, Aspergillus fumigatus made the highest occurrence, while 6.5% had PTB-fungal co-infection. No significant association existed between the prevalence of PM with age and sex of participants (P < 0.05). Cigarette smoking (adjusted odds ratio [aOR] = 15.9 [95% confidence interval (CI): 0.9-268.8]), prolong antibiotic use (aOR = 77.9 [95% CI: 4.7-1283]) and possession of domestic pet (aOR = 77.9 [95% CI: 4.7-1283]) were significant risk factors of PM (P < 0.05). Penicillium citrinum, Mucor spp. and Aspergillus flavus are more susceptible to voriconazole, and Candida albicans was found to be more susceptible to Nystatin. Of the 159 fungal isolates, 92.5% were resistant to fluconazole. Findings from this study revealed high level pulmonary fungal pathogens, especially among PTB patients. A majority of fungal isolates were resistant to fluconazole. It's recommended that persons should do away with or minimize risk factors for pulmonary fungal pathogens identified in this study.

Мультидисциплинарный подход к диагностике и лечению сочетанной микобактериальной и грибковой инфекции легких у больного с ANCA-ассоциированным системным васкулитом на заместительной почечной терапии. Случай из практики

Мультидисциплинарный подход к диагностике и лечению сочетанной микобактериальной и грибковой инфекции легких у больного с ANCA-ассоциированным системным васкулитом на заместительной почечной терапии. Случай из практики

Spectrum of Filamentous Fungi from Sputum of Tuberculosis Relapse and Retreatment Patients in Tuberculosis Reference Facilities

Background: Fungal infections represent a significant cause of morbidity and mortality among immunocompromised individuals. Pulmonary fungal infection may be missed or misdiagnosed as tuberculosis (TB) hence complicating management of these patients. The current study reports the spectrum of filamentous fungi isolated from sputum of TB relapse and retreatment cases at selected reference facilities in Kenya. Methods: A total of 340 sputum samples collected during the period of June 2018 to June 2019 were subjected to mycological investigations. The samples were mucolysed and inoculated on sabourauds dextrose agar (SDA) and incubated at 30°C for 7 days and checked daily for fungal growth. Moulds were identified by macroscopic and microscopic morphological features and the species were confirmed by sequencing. Results: The diversity of fungi out of the 340 sputum samples analyzed was as follows; 16% (n = 53) were positive for moulds with Aspergillus species being the predominant constituting 68 % (n = 36). Among the Aspergilli, A. flavus and A. niger were the most frequently isolated adding up to 23%, (n = 12) and 15% (n = 8) respectively. Additionally, Paecillomyces variotii (9%, n = 5), Scedosporium aspiospermum (6%, n = 3), Mucor racemosus (8%, n = 4) and Penicillium spp. (9%, n = 5) were also recovered. Conclusion: The isolated fungi represented potential respiratory pathogens that could be responsible for persistent TB like symptoms despite treatment that could be misdiagnosed as relapse requiring treatment. Fungal investigation of all presumptive TB relapse cases should be advocated before treatment. This will reduce unnecessary retreatment, delayed antifungal intervention and unwarranted morbidity and mortality associated with misdiagnosis.

Pulmonary actinomycosis presenting as a pleural tumour

Pulmonary actinomycosis is a rare gram positive higher prokaryotic bacterial infection. We hereby present a case of 78-year old male presented with non-specific symptoms like cough, shortness of breath (SOB) and chest pain mimicking as pulmonary tuberculosis, fungal infection and lung cancer but was diagnosed to have pulmonary actinomycosis. From this, we want to emphasize that pulmonary actinomycosis should be evaluated in all patients that are not responding to anti-tubercular and lung cancer treatment.

Clinical Usefulness of Fungal Culture of EBUS-TBNA Needle Rinse Fluid and Core Tissue.

PurposeThe diagnosis of pulmonary fungal infections is challenging due to the difficulty of obtaining sufficient specimens. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) needle rinse fluid has become an emerging diagnostic material. This study evaluated the role of routine fungal culture from EBUS-TBNA needle rinse fluid, in addition to histopathologic examination and fungal culture of EBUS-TBNA core tissue, in the diagnosis of pulmonary fungal infections.Materials and MethodsAmong patients who underwent EBUS-TBNA, those with results for at least one of three tests (histopathologic examination, fungal culture of EBUS-TBNA core tissue or needle rinse fluid) were included. Patients with a positive test were divided into two groups (clinical fungal infection and suspected fungal contamination) according to their clinical assessment and therapeutic response to antifungal.ResultsOf 6072 patients, 41 (0.7%) had positive fungal tests and 9 (22%) were diagnosed as clinical fungal infection. Of the 5222 patients who were evaluated using a fungal culture from EBUS-TBNA needle rinse fluid, 35 (0.7%) had positive results. However, only 4 out of 35 (11.4%) were classified as clinical fungal infection. Positive results were determined in 4 of the 68 (5.9%) evaluated by a fungal culture of EBUS-TBNA core tissue, and all were diagnosed as clinical fungal infection.ConclusionRoutine fungal culture of EBUS-TBNA needle rinse fluid is not useful due to the low incidence of fungal infection and high rate of contamination. However, fungal culture of EBUS-TBNA core tissue and needle rinse fluid should be considered in patients with clinically suspected fungal infection.

Pulmonary Fungal Co-Infection Prevalence among Iranian Patients with Pulmonary Tuberculosis: A Systematic Review and Meta-Analysis

Tuberculosis (TB) is further aggravated if it is accompanied with fungal co-infection. This study aimed to evaluate the prevalence of pulmonary fungal co-infection among Iranian patients with pulmonary TB using a systematic review and meta-analysis. The present study was a review of cross-sectional studies on the prevalence of pulmonary fungal co-colonization among Iranian patients with pulmonary TB with regard to the PRISMA Protocol. To this end, the articles published online in English and Persian were searched on the main databases and gateways such as Google Scholar, Science Direct, Web of Science, MEDLINE, PubMed, SCOPUS, Cochrane Library, Magiran, Irandoc, and Scientific Information Databases. The reviews of the literatures published online from 2000 to the end of 2018 were included in the study. The keywords used for searching through the databases were pulmonary fungal co-infection with pulmonary TB, pulmonary mycosis co-infection with pulmonary TB, pulmonary fungal colonization/agents with pulmonary TB, AND Iran. Finally, the collected data were analyzed by Comprehensive Meta-Analysis software. The analyses showed that the prevalence of fungal co-infection among patients with pulmonary TB varied from 12.3-68.8, and that the combined prevalence of fungal co-infection among patients with pulmonary TB was 17.4. Amongst the fungi involved in co-infection with TB, Candida spp. was the most predominant with the prevalence of 6.9, followed by Aspergillus spp. (3.2). Moreover, the highest prevalence of Aspergillus spp. was observed for Aspergillus fumigatus (1.6). The most frequent Candida spp. was Candida albicans with a frequency of 6. The findings showed that the combined prevalence of fungal co-infection among Iranian patients with pulmonary TB was high. In this regard, among the fungi involved in co-infection with TB, Candida spp. was the most frequent. © 2019 Penerbit Universiti Kebangsaan Malaysia. All rights reserved.