Clinical manifestations, associated risk factors and treatment outcomes of Chronic Pulmonary Aspergillosis (CPA): Experiences from a tertiary care hospital in Lahore, Pakistan.

BACKGROUND: Chronic pulmonary aspergillosis (CPA) has a wide spectrum of illnesses depending on the progression of the disease and comorbid conditions. However, there is an inadequacy of investigations regarding clinical, laboratory, risk factor and prognostic data on CPA. The current study is aimed to consider the clinical manifestations, risk factors and outcomes of CPA. METHODOLOGY: Retrospective records of all patients with a confirmed diagnosis of CPA who sought treatment at Gulab Devi Chest Hospital Lahore, Pakistan from January 2017 to December 2019 were evaluated. Data regarding demographics, clinical manifestations, comorbidities, radiographic and microbiological findings, length of hospital stay (LOS) and intensive care unit (ICU) admission was collected and analyzed to identify the factors associated with mortality. The independent factors associated with mortality were also identified by appropriate analyses. RESULTS: A total of 218 CPA patients were included in this study. The mean age was 45.75 ± 6.26 years. Of these, 160 (73.4%) were male, and 65 (29.8%) had diabetes. The mean LOS was 18.5 ± 10.9 days. The most common type of CPA was simple aspergilloma (56%) followed by chronic cavitary pulmonary aspergillosis (CCPA) (31.2%). About one half of the patients had a history of pulmonary tuberculosis (TB) and treatment response rates were low in patients with active TB. The overall mortality rate was 27.1%. ICU admission was required for 78 (35.8%) patients. Diabetes mellitus (DM), hematological malignancies and chronic kidney disease (CKD) were the common underlying conditions predicting a poor outcome. Mean LOS, hematological malignancies, consolidation and ICU admission were identified as the independent factors leading to mortality. CONCLUSIONS: CPA had a significant association with TB in the majority of cases. Treatment response rates in cases with active TB were comparatively low. Cases with high mean LOS, hematological malignancies, consolidation, ICU admission, CKD and DM experienced poor outcomes. High mean LOS, hematological malignancies, consolidation and ICU stay were identified as independent risk factors for mortality. Future large prospective studies, involving aspergillus specific immunoglobulin G (IgG) antibody testing, are required for a better understanding of CPA in Pakistan.

COVID-19-Associated Pulmonary Aspergillosis, Fungemia, and Pneumocystosis in the Intensive Care Unit: a Retrospective Multicenter Observational Cohort during the First French Pandemic Wave.

The aim of this study was to evaluate diagnostic means, host factors, delay of occurrence, and outcome of patients with COVID-19 pneumonia and fungal coinfections in the intensive care unit (ICU). From 1 February to 31 May 2020, we anonymously recorded COVID-19-associated pulmonary aspergillosis (CAPA), fungemia (CA-fungemia), and pneumocystosis (CA-PCP) from 36 centers, including results on fungal biomarkers in respiratory specimens and serum. We collected data from 154 episodes of CAPA, 81 of CA-fungemia, 17 of CA-PCP, and 5 of other mold infections from 244 patients (male/female [M/F] ratio = 3.5; mean age, 64.7 ± 10.8 years). CA-PCP occurred first after ICU admission (median, 1 day; interquartile range [IQR], 0 to 3 days), followed by CAPA (9 days; IQR, 5 to 13 days), and then CA-fungemia (16 days; IQR, 12 to 23 days) (P < 10-4). For CAPA, the presence of several mycological criteria was associated with death (P < 10-4). Serum galactomannan was rarely positive (<20%). The mortality rates were 76.7% (23/30) in patients with host factors for invasive fungal disease, 45.2% (14/31) in those with a preexisting pulmonary condition, and 36.6% (34/93) in the remaining patients (P = 0.001). Antimold treatment did not alter prognosis (P = 0.370). Candida albicans was responsible for 59.3% of CA-fungemias, with a global mortality of 45.7%. For CA-PCP, 58.8% of the episodes occurred in patients with known host factors of PCP, and the mortality rate was 29.5%. CAPA may be in part hospital acquired and could benefit from antifungal prescription at the first positive biomarker result. CA-fungemia appeared linked to ICU stay without COVID-19 specificity, while CA-PCP may not really be a concern in the ICU. Improved diagnostic strategy for fungal markers in ICU patients with COVID-19 should support these hypotheses. IMPORTANCE To diagnose fungal coinfections in patients with COVID-19 in the intensive care unit, it is necessary to implement the correct treatment and to prevent them if possible. For COVID-19-associated pulmonary aspergillosis (CAPA), respiratory specimens remain the best approach since serum biomarkers are rarely positive. Timing of occurrence suggests that CAPA could be hospital acquired. The associated mortality varies from 36.6% to 76.7% when no host factors or host factors of invasive fungal diseases are present, respectively. Fungemias occurred after 2 weeks in ICUs and are associated with a mortality rate of 45.7%. Candida albicans is the first yeast species recovered, with no specificity linked to COVID-19. Pneumocystosis was mainly found in patients with known immunodepression. The diagnosis occurred at the entry in ICUs and not afterwards, suggesting that if Pneumocystis jirovecii plays a role, it is upstream of the hospitalization in the ICU.

Prognostic factors of chronic pulmonary aspergillosis: A retrospective cohort of 264 patients from Japan.

BACKGROUND: Chronic pulmonary aspergillosis (CPA) develops in various underlying pulmonary conditions. There is scarce data evaluating interstitial lung disease (ILD)/abnormalities (ILA) as such conditions, and it has not been explored much whether non-tuberculous mycobacterial pulmonary disease (NTM-PD) is a prognostic factor for mortality in CPA patients. Few reports had investigated prognostic factors of CPA including underlying pulmonary conditions. OBJECTIVES: To explore prognostic factors of CPA including pulmonary conditions. METHODS: We conducted a retrospective cohort study of 264 CPA patients from a center for pulmonary aspergillosis in Japan. RESULTS: Survival rates were 78.7%, 61.0%, and 47.4% at 1, 3, and 5 years, respectively. Of 264 patients, 53 (20.1%) and 87 (33.1%) were complicated with ILA and NTM-PD. Several independent prognostic factors were identified by multivariate Cox proportional analysis: ILA (HR 1.76, 95%CI 1.06-2.92, p = 0.029), age (1.05, 1.02-1.08, p<0.001), male sex (2.48, 1.34-4.59, p = 0.004), body mass index of <18.5 kg/m2 (1,87, 1.20-2.90, p = 0.005), presence of aspergilloma (1.59, 1.04-2.45, p = 0.033), and lower serum albumin (0.56, 0.38-0.83, p = 0.004). NTM-PD was not associated with higher mortality (0.85, 0.52-1.38, p = 0.51). CONCLUSIONS: The poor prognosis of CPA and several prognostic factors were revealed. Early diagnosis and intervention is required with reference to such factors.

COVID-19-associated pulmonary aspergillosis: a prospective single-center dual case series.

BACKGROUND: COVID-19-associated pulmonary aspergillosis (CAPA) has emerged as an invasive fungal disease, often affecting previously immunocompetent, mechanically ventilated, intensive care unit (ICU) patients. Incidence rates of 3.8%-33.3% have been reported depending on the geographic area, with high (47%) mortality. OBJECTIVES: Here, we describe a single-centre prospective case series with CAPA cases from both the first (March-May, n = 5/33) and second (mid-September through mid-December, n = 8/33) COVID-19 wave at a 500-bed teaching hospital in the Netherlands. PATIENTS/METHODS: In the first COVID-19 wave, a total of 265 SARS-CoV-2 PCR-positive patients were admitted to our hospital of whom 33 needed intubation and mechanical ventilation. In the second wave, 508 SARS-CoV-2 PCR-positive patients were admitted of whom 33 needed mechanical ventilation. Data were prospectively collected. RESULTS: We found a significant decrease in COVID-19 patients needing mechanical ventilation in the ICU in the second wave (p < .01). From these patients, however, a higher percentage were diagnosed with CAPA (24.2% vs 15.2%), although not significant (p = .36). All CAPA patients encountered in the second wave received dexamethasone. Mortality between both groups was similarly high (40%-50%). Moreover, we found environmental TR34 /L98H azole-resistant Aspergillus fumigatus isolates in two separate patients. CONCLUSIONS: In this series, 19.7% (n = 13/66) of mechanically ventilated SARS-CoV-2 patients were diagnosed with CAPA. In addition, we found a significant reduction in COVID-19 patients needing mechanical ventilation on the ICU in the second wave. Numbers are too small to determine whether there is a true difference in CAPA incidence in mechanically ventilated patients between the two waves, and whether it could be attributed to dexamethasone SARS-CoV-2 therapy.

COVID-19-Associated Pulmonary Aspergillosis, March-August 2020.

Pneumonia caused by severe acute respiratory syndrome coronavirus 2 emerged in China at the end of 2019. Because of the severe immunomodulation and lymphocyte depletion caused by this virus and the subsequent administration of drugs directed at the immune system, we anticipated that patients might experience fungal superinfection. We collected data from 186 patients who had coronavirus disease-associated pulmonary aspergillosis (CAPA) worldwide during March-August 2020. Overall, 182 patients were admitted to the intensive care unit (ICU), including 180 with acute respiratory distress syndrome and 175 who received mechanical ventilation. CAPA was diagnosed a median of 10 days after coronavirus disease diagnosis. Aspergillus fumigatus was identified in 80.3% of patient cultures, 4 of which were azole-resistant. Most (52.7%) patients received voriconazole. In total, 52.2% of patients died; of the deaths, 33.0% were attributed to CAPA. We found that the cumulative incidence of CAPA in the ICU ranged from 1.0% to 39.1%.

Accuracy of galactomannan testing on tracheal aspirates in COVID-19-associated pulmonary aspergillosis.

OBJECTIVE: Our aim was to evaluate the performance of two galactomannan (GM) assays (Platelia Aspergillus EIA, Bio-Rad® , and Aspergillus GM LFA, IMMY® ) in tracheal aspirate (TA) samples of consecutive critically ill patients with COVID-19. METHODS: We included critically ill patients, performed GM-EIA and GM-Lateral Flow Assay (GM-LFA) in TA and followed them until development of COVID-19-associated pulmonary aspergillosis (CAPA) or alternate diagnosis. CAPA was defined according to the modified AspICU criteria in patients with SARS-CoV-2 infection. We estimated sensitivity, specificity, positive and negative predictive values for GM-EIA, GM-LFA, the combination of both or either positive results for GM-EIA and GM-LFA. We explored accuracy using different breakpoints, through ROC analysis and Youden index to identify the optimal cut-offs. We described antifungal treatment and 30-day mortality. RESULTS: We identified 14/144 (9.7%) patients with CAPA, mean age was 50.35 (SD 11.9), the median time from admission to CAPA was 8 days; 28.5% received tocilizumab and 30-day mortality was 57%. ROC analysis and Youden index identified 2.0 OD as the best cut-off, resulting in sensitivity and specificity of 57.1% and 81.5% for GM-EIA and 60% and 72.6% for GM-LFA, respectively. CONCLUSIONS: The diagnostic performance of GM in tracheal aspirates improved after using a cut-off of 2 OD. Although bronchoalveolar lavage testing is the ideal test, centres with limited access to bronchoscopy may consider this approach to identify or rule out CAPA.

Impact of Aspergillus precipitating antibody test results on clinical outcomes of patients with Mycobacterium avium complex lung disease.

BACKGROUND AND OBJECTIVE: Chronic pulmonary aspergillosis (CPA) is associated with mortality in patients with Mycobacterium avium complex lung disease (MAC-LD). However, the clinical significance of the positivity of Aspergillus precipitating antibody (APAb), a serodiagnostic test for pulmonary aspergillosis (PA), at the time of MAC-LD diagnosis is unknown. The objective of this study was to investigate the effects of APAb test results on the clinical outcomes of patients with MAC-LD. METHODS: We retrospectively analyzed patients who were newly diagnosed as having MAC-LD between 2007 and 2014 in our hospital and checked for APAb at the time of diagnosis. RESULTS: We enrolled 131 patients in this study. Of these patients, 20 (15.3%) tested positive for APAb at the diagnosis of MAC-LD. The APAb-positive patients were more frequently male (70.0% vs. 37.8%, P = 0.013) and more frequently had pulmonary emphysema (60.0% vs. 13.5%, P < 0.001) and interstitial pneumonia (15.0% vs. 1.8%, P = 0.025) compared with the APAb-negative patients. During a median follow-up period of 4.0 years, PA developed in 12 of the APAb-positive patients (60.0%, CPA: 9 and allergic bronchopulmonary aspergillosis: 3) and 12 APAb-negative patients (10.8%, CPA: 12) (P < 0.001). The APAb-positive patients had a significantly higher rate of mortality than did the APAb-negative patients (P = 0.004). A multivariate analysis indicated that older age, lower albumin, fibrocavitary or fibrocavitary and nodular/bronchiectatic radiographic features, and APAb positivity were negative prognostic factors. CONCLUSIONS: APAb-positive patients with MAC-LD more frequently develop PA and may have an unfavorable prognosis.

Fatal Invasive Aspergillosis and Coronavirus Disease in an Immunocompetent Patient.

Invasive pulmonary aspergillosis is a complication in critically ill patients with acute respiratory distress syndrome, especially those with severe influenza pneumonia. We report a fatal case of invasive pulmonary aspergillosis in an immunocompetent patient in France who had severe coronavirus disease-associated pneumonia.

Pulsed echinocandin therapy in azole intolerant or multiresistant chronic pulmonary aspergillosis: A retrospective review at a UK tertiary centre.

INTRODUCTION: Chronic pulmonary aspergillosis (CPA) is a fungal disease with high mortality and morbidity. Guidelines suggest treatment with azoles as first-line therapy. However, patients often develop treatment intolerance or increasingly azole resistance. OBJECTIVES: This retrospective review assesses outcomes in azole resistant or intolerant patients with CPA treated with cyclical echinocandin therapy. METHODS: We retrospectively examined records of 25 patients with CPA treated with cyclical caspofungin, 6 of whom were either azole-resistant or azole intolerant. Baseline characteristics, high-resolution computed tomography severity scores, forced expiratory volume after 1 minute (FEV1), forced vital capacity (FVC), body mass index and serology (Aspergillus fumigatus-specific IgG, Aspergillus fumigatus-specific IgE, total IgE and CRP) were assessed before and after caspofungin. RESULTS: Of the six patients, four (66%) started caspofungin due to intolerance and two (33%) due to pan-azole resistance. On treatment, there was stability in FEV1 with an overall mortality of 33% during the follow-up period with a median survival of 875.5 days (IQR 529-1024). No significant change in serology (A. fumigatus-specific IgG and CRP was seen. CONCLUSIONS: With pulsed echinocandin therapy, azole-intolerant or pan-resistant CPA patients have similar mortality rates to azole-naïve CPA patients. Pulsed echinocandin therapy may present a strategy to stabilize CPA in patients with pan resistance or intolerance to, azole therapy.

Pulmonary aspergillosis as a late complication after surgery for locally advanced non-small cell lung cancer treated with induction chemoradiotherapy.

PURPOSE: Some long-term survivors after surgery for locally advanced non-small cell lung cancer (NSCLC) treated with induction chemoradiotherapy (trimodality treatment) develop chronic pulmonary aspergillosis (CPA). The aim of our study was to assess the characteristics and outcomes of CPA that develops after trimodality treatment. METHODS: We retrospectively reviewed the data of 187 NSCLC patients who underwent trimodality treatment between 1999 and 2018. RESULTS: Six male ever-smoker patients developed CPA. All 6 patients had undergone extended resection for NSCLC and had a history of either adjuvant chemotherapy (n = 3) or radiation pneumonitis (n = 4). Among the 4 patients with CPA localized in a single lung, 3 patients were treated surgically (completion pneumonectomy or cavernostomy) and 1 patient was treated with antifungal therapy alone. Both treatments led to the improved control of CPA. In contrast, patients with CPA in both lungs were not candidates for surgery, and died of CPA. The survival rates after trimodality treatment in the CPA group and the group without CPA were comparable (10-year survival rate, 50.0% vs. 57.6%, P = 0.59). CONCLUSION: The early diagnosis of CPA localized in a single lung after NSCLC surgery is critical to improving control and survival in patients with CPA.

Chronic pulmonary aspergillosis in a tertiary care centre in Spain: A retrospective, observational study.

The aim of this study was to describe the characteristics of patients with chronic pulmonary aspergillosis (CPA) in a tertiary care centre in Spain. Retrospective cohort study of all patients diagnosed with CPA between January 2010 and December 2015. The patients were identified through the Microbiology Registry. Demographic, clinical, laboratory, radiological, microbiological and clinical data were recorded. Patients were followed up for 12 months. Fifty-three patients were included; median age was 61.5 years. Forty-seven had a lung condition, 25 suffered from COPD, 19 an active malignancy, 10 had previous pulmonary tuberculosis and 9 lung interstitial disease. Twenty-eight patients presented with chronic cavitary pulmonary form (CCPA) and 20 with subacute invasive aspergillosis (SAIA). Species identified were A fumigatus (34), A niger (5), A terreus (4) and A flavus (3). All-cause 1-year mortality was 56%. Predictors of mortality were cancer history (OR, 9.5; 95% CI, 2.54-35.51; P < 0.01) and SAIA (OR, 5.49; 95% CI, 1.49-19.82; P < 0.01). Previous pulmonary tuberculosis, surgery for the treatment of CPA and CCPA were found to be associated with lower mortality (OR, 0.05; 95% CI, <0.01-0.47; P < 0.01; OR, 0.16; 95% CI, 0.03-0.88; P = 0.035 and OR 0.2, 95% CI, 0.01-0.67; P = 0.01, respectively). This is the first study providing an overview of the features of CPA in patients from Spain. CCPA was the most frequent form of CPA and A fumigatus the most frequently isolated species. Patients with cancer history and SAIA had a worse prognosis.

Chronic pulmonary aspergillosis update: A year in review.

Chronic pulmonary aspergillosis (CPA) is an uncommon, slowly destructive pulmonary disease characterized by progressive cavitation, fibrosis, and pleural thickening. CPA is usually seen in immunocompetent individuals with underlying respiratory disorders. Estimates suggest that up to 3 million people are affected worldwide causing high rates of morbidity and mortality. Pulmonary tuberculosis (TB) seems to be the most relevant driver for the global burden of CPA with estimates suggesting about 1.2 million patients with CPA as a sequel to TB. Diagnosis of CPA is often challenging and delayed and should be based upon a combination of characteristics. The first guidelines for the diagnosis and management of CPA were published in 2016 jointly by the European Society for Clinical Microbiology and Infectious Diseases (ESCMID), the European Respiratory Society (ERS), and the European Confederation of Medical Mycology (ECMM). CPA continues to receive significant public attention, which resulted in almost 150 newly published papers during 2017. The aim of this mini-review is to highlight the most important published papers from January 2017 to April 2018 to provide an update on current developments in the field of CPA.

Epidemiology and clinical outcomes of invasive mould infections in Indian intensive care units (FISF study).

BACKGROUND AND AIM: Due to limited data on invasive mould infections (IMIs) in the intensive care units (ICUs) of developing countries, we ascertain epidemiology and management of IMIs at 11 ICUs across India. METHODS: Consecutive patients with proven or probable/putative IMIs were enrolled during the study period. Subjects were categorized into classical (neutropenia, malignancy, transplant recipients on immunosuppression) and non-classical (chronic obstructive pulmonary disease, diabetes, liver disease and glucocorticoids) risk groups. We analyzed the demographic, laboratory variables and outcomes of these patients. RESULTS: 398 patients with IMIs (96 proven, 302 probable) were identified, amounting to a prevalence of 9.5 cases/1000 ICU admissions. The mean ±â€¯SD age of the participants was 45.6 ±â€¯21.9 years. The mean ±â€¯SD APACHE II score was 14.3 ±â€¯11.4. The IMIs were diagnosed at a median of 4 days after ICU admission. There were 145 and 253 subjects with classical and non-classical risk groups, respectively. Although Aspergillus spp. were the commonest (82.1%) isolates, Mucorales were detected in 14.4% subjects. A high APACHE II score and IMI due to mucormycosis were significant predictors of mortality. CONCLUSIONS: The study highlights the distinct epidemiology of IMIs in India ICUs with high burden, new susceptible patient groups and considerable number of non-Aspergillus mould infections. [clinicaltrials.gov: NCT02683642].

Assessment of posaconazole salvage therapy in chronic pulmonary aspergillosis using predefined response criteria.

OBJECTIVES: Chronic pulmonary aspergillosis (CPA) is a progressive infection that destroys lung tissue in non-immunocompromised patients. First-line therapies for CPA (itraconazole and/or voriconazole) are often curtailed due to toxicity or the development of drug resistance. Posaconazole is a potential alternative for these patients. METHODS: Use of posaconazole was funded by the National Health Service Highly Specialised National Commissioners on an individual basis for patients who failed or did not tolerate first-line therapy; those who met predefined criteria for improvement at 4 and 6 months (weight gain and/or improvement in St George's Respiratory Questionnaire) continued posaconazole long-term. We recorded response, failure, discontinuation rates, and adverse events. RESULTS: Seventy-eight patients received posaconazole as salvage therapy. Thirty-four (44%) achieved targets for continuation of therapy. Fourteen (18%) failed therapy; five (36%) patients did not achieve clinical targets at 4 or 6 months of assessment and nine (64%) developed clinical and/or radiological failure. Twenty-eight (36%) discontinued their trial early; 8 (29%) died and 20 (71%) had significant side effects. One patient was non-compliant and another was lost to follow up. CONCLUSIONS: Establishing criteria for therapeutic success offered a clear, safe and sustainable method of identifying patients who benefit from additional therapy, and minimised continuation of ineffective therapy in those who did not.

Clinical significance of Aspergillus species isolated from respiratory specimens in patients with Mycobacterium avium complex lung disease.

Chronic pulmonary aspergillosis (CPA) is associated with mortality in patients with Mycobacterium avium complex lung disease (MAC-LD). An Aspergillus-positive respiratory specimen often reflects colonization, and thus the clinical significance of Aspergillus isolation in MAC-LD patients is not well understood. The objective of this study was to investigate the clinical characteristics and outcomes of MAC-LD patients in whom Aspergillus was isolated from respiratory specimens. We performed a retrospective review of the medical records of 329 MAC-LD patients. We compared the characteristics and mortality rates between patients with Aspergillus isolation and those without. All Aspergillus species detected from respiratory specimens within the follow-up period were reviewed. Aspergillus was detected in 40 (12.2%) of the 329 patients. There were no significant differences in the clinical characteristics and mortality rates between patients with and without Aspergillus isolation. Among the 40 patients with Aspergillus isolation, 9 (22.5%) developed CPA. CPA was most often caused by A. fumigatus. In the 40 Aspergillus-positive patients, patients with A. fumigatus isolation had a significantly higher mortality rate than those without (P < 0.001). The multivariate Cox proportional hazards model showed older age (P = 0.050), presence of respiratory comorbidities (P = 0.008), hypoalbuminemia (P < 0.001), and isolation of A. fumigatus (P = 0.005) to be prognostic factors for mortality in MAC-LD patients. There was no significant difference in the mortality rates between patients with Aspergillus isolation and those without. However, isolation of A. fumigatus may be associated with poor prognosis in MAC-LD patients.

Host immune status-specific production of gliotoxin and bis-methyl-gliotoxin during invasive aspergillosis in mice.

Delayed diagnosis in invasive aspergillosis (IA) contributes to its high mortality. Gliotoxin (GT) and bis-methyl-gliotoxin (bmGT) are secondary metabolites produced by Aspergillus during invasive, hyphal growth and may prove diagnostically useful. Because IA pathophysiology and GT's role in virulence vary depending on the underlying host immune status, we hypothesized that GT and bmGT production in vivo may differ in three mouse models of IA that mimic human disease. We defined temporal kinetics of GT and bmGT in serum, bronchoalveolar lavage fluid (BALF) and lungs of A. fumigatus-infected chronic granulomatous disease (CGD), hydrocortisone-treated, and neutropenic mice. We harvested lungs for assessment of fungal burden, histology and GT/bmGT biosynthetic genes' mRNA induction. GT levels were higher in neutropenic versus CGD or steroid-treated lungs. bmGT was persistently detected only in CGD lungs. GT, but not bmGT, was detected in 71% of sera and 50% of BALF of neutropenic mice; neither was detected in serum/BALF of CGD or steroid-treated mice. Enrichment of GT in Aspergillus-infected neutropenic lung correlated with fungal burden and hyphal length but not induction of GT biosynthetic genes. In summary, GT is detectable in mouse lungs, serum and BALF during neutropenic IA, suggesting that GT may be useful to diagnose IA in neutropenic patients.

Pulmonary co-infections by Pneumocystis jirovecii and Aspergillus fumigatus in non-HIV patients: A report of two cases and literature review.

Pneumocystis jirovecii is the causative agent of Pneumocystis pneumonia (PcP), a common and often life-threatening opportunistic infection in HIV-infected patients. However, non-HIV, immunocompromised patients are at risk of PcP as well, whereas the mortality appears to be higher among these patients. Pneumocystis co-infections with other microorganisms are less frequent and only sparse reports of combined PcP and invasive pulmonary fungal infections exist in the literature, especially in the non-HIV patients. Two cases of pulmonary co-infections by P. jirovecii and Aspergillus fumigatus are presented. Both patients were non-HIV infected, the first one was suffering from crescentic IgA nephropathy under immunosuppressive treatment and the second from resistant non-Hodgkin lymphoma under chemotherapy. Both patients were treated with intravenous trimethoprim/sulphamethoxazole (TMP/SMX) combined with voriconazole. The first patient showed gradual clinical improvement while the outcome for the second patient was unfavourable. In addition, a literature review of the previous published cases of co-infection by P. jirovecii and other fungi in non-HIV patients was performed. Our target was to provide comprehensive information on this kind of infections, highlighting the importance of clinical suspicion.

Culture-Positive Pulmonary Aspergillosis Infection: Clinical and Laboratory Features of Solid-Organ Transplant Recipients.

OBJECTIVES: Aspergillosis is a common fungal infection among solid-organ transplant recipients. Even after awareness of this infection occurs, there are still gaps in nonculture diagnostic tests, which can delay treatment initiation. Here, we aimed to define the common traits of pulmonary aspergillosis infection among solid-organ transplant recipients, thus shedding light on prevention and early diagnosis. MATERIALS AND METHODS: We conducted a database search of patients at Baskent University who had a positive aspergillosis culture between January 2010 and March 2016. Among 20 patients identified, 15 (mean age of 50.93 ± 11.17 y, 2 female and 13 male patients) with solid-organ transplant were included in the study. RESULTS: Of the 15 study patients, 7 were heart transplant, 6 were kidney transplant, and 2 were liver transplant recipients. Three patients had positive aspergillosis cultures from extrapulmonary specimens (1 brain biopsy and 2 wound swap cultures). Other patients with positive cultures were from bronchoalveolar lavage (6 patients), sputum (4 patients), both bronchoalveolar lavage and sputum (1 patient), and deep tracheal aspiration specimen (1 patient). Aspergillus fumigatus was the most common species. Mean hospitalization duration was 31.53 days (range, 2-135 d). Although all patients had positive culture results, 7 patients (46.7%) had negative galactomannan test results at the time of culture specimen collection. Positive galactomannan test results were statistically higher in 6 heart transplant patients (P = .045). All patients had fever at presentation, and 13 patients had been referred to the pulmonary disease department before positive culture results were obtained. CONCLUSIONS: Risk factors for pulmonary aspergillosis and its clinical presentation in solid-organ transplant recipients are still unclear. Although the expected time for aspergillosis infection in solid-organ transplant recipients is 6 months after transplant, clinicians must remember the nonspecific presentation of infections in these patients and be aware of the reliability of diagnostic tools.