scholarly journals 1736. Evaluation of Targeted vs. Universal Antifungal Prophylaxis (AP) for Invasive Fungal Infections (IFI) After Lung Transplant (LTx)

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S636-S636
Author(s):  
Kathleen A Linder ◽  
Twisha S Patel ◽  
Carol A Kauffman ◽  
Linda J Fitzgerald ◽  
Marisa H Miceli ◽  
...  
Keyword(s):  
Lung Transplant ◽  
Fungal Infections ◽  
Invasive Pulmonary Aspergillosis ◽  
Antifungal Prophylaxis ◽  
Mortality Data ◽  
Pulmonary Aspergillosis ◽  
Increased Risk ◽  
History Of ◽  
Candida Infections ◽  
Research Grant

Abstract Background LTx patients (pt) are at increased risk for IFI. Systemic AP is widely used, but the optimal strategy remains unclear. Our LTx program changed from universal to targeted AP in July 2016; we compared outcomes between the 2 strategies. Methods All adult pt who underwent LTx at U. Michigan from July 1, 2014 to December 31, 2017 were studied for 18 mo post-LTx. Universal AP consisted of itraconazole (itra) ± inhaled liposomal amphotericin-B (iAmB) for 6 months. Pt received targeted AP with voriconazole for 3 months if they had a history of pre-LTx Aspergillus colonization or invasive pulmonary aspergillosis (IPA); 14 days of a yeast-active azole was given if donor or recipient had Candida colonization at the time of LTx. All other pt received no AP. Demographics, LTx characteristics, occurrence of proven/probable IFI defined by EORTC/MSG criteria, and mortality data were recorded. Results Of 105 LTx patients, 73 (70%) were men and 84 (80%) received a double LTx. The most common indication for LTx was idiopathic pulmonary fibrosis (38, 36%). Of 59 pt receiving universal AP, 36 (61%) received itra, and 23 (39%) received itra+iAmB; outcomes did not differ between these 2 regimens. Of 46 patients in the targeted AP cohort, 10 (22%) received antifungals based on predefined criteria. Overall, 19 proven/probable IFI occurred: 14 IPA, 3 invasive Candida infections, 1 Cryptococcus pneumonia, and 1 mold wound infection. IFI occurred in 5 patients (8%) in universal AP group vs. 13 patients (28%) in targeted AP group, P = .008. All but 1 IFI in the targeted AP group occurred among pt for whom antifungals were not recommended or given. IPA occurred in 4 patients (7%) in universal AP group and 9 patients (20%) in targeted AP group, P = 0.05; Candida infections occurred only among patients in the targeted AP cohort. Time to IFI was similar between the 2 AP strategies with the majority occurring <180 days post-LTx (median 109 days). Death occurred in 11 patients (8 in the universal AP cohort and 3 in the targeted AP cohort, P = .34); no deaths were related to IFI. Conclusion When compared with universal AP, targeted AP strategy was associated with a significant increase in IFI post-LTx. Universal AP for 6 months appears to be more effective than our targeted AP strategy for prevention of IFI post-LTx. Disclosures Marisa H. Miceli, MD, FIDSA, Astellas: Advisory Board, Research Grant; Scynexis: Research Grant.

scholarly journals Proven pulmonary aspergillosis in a COVID-19 patient: A case report

2021 ◽  
Author(s):  
Sadegh Khodavaisy ◽  
Nasim Khajavirad ◽  
Seyed Jamal Hashemi ◽  
Alireza Izadi ◽  
Seyed Ali Dehghan Manshadi ◽  
...  
Keyword(s):  
Case Report ◽  
Fungal Infections ◽  
Left Lung ◽  
Aspergillus Species ◽  
Pulmonary Aspergillosis ◽  
Biopsy Material ◽  
Cavitary Lesion ◽  
Healthcare Settings ◽  
Increased Risk ◽  
History Of

Background and Purpose: Coronavirus disease 2019 (COVID-19) has become a significant clinical challenge in healthcare settings all over the world. Critically ill COVID-19 patients with acute respiratory distress syndrome may be at increased risk of co-infection with pulmonary aspergillosis. This study aimed to describe a clinical case of proven pulmonary aspergillosis caused by Aspergillus tubingensis in a 59-year-old man with a history of hospitalization due to COVID-19 infection. Case report: The Covid-19 infection was confirmed by positive nasopharyngeal polymerase chain reaction. He had a cavitary lesion measured 20 mm in diameter with intracavitary soft tissue density in the left lung in the first chest computerized tomography scan. After 25 days, he showed two cavitary lesions in both lungs which raised suspicion of fungal infection; hence, the patient underwent a trans-thoracic biopsy of the cavitary lesion. The direct examination and culture of the biopsy material revealed Aspergillus species. To confirm the Aspergillus species identification, the beta-tubulin region was sequenced. The patient was treated with oral voriconazole. Conclusion: This report underlined the importance of early diagnosis and management of invasive fungal infections in severe COVID-19 patients

Therapeutic Granulocyte Transfusions in Neutropenic Patients with Invasive Pulmonary Aspergillosis,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3372-3372
Author(s):  
Kathrin Drognitz ◽  
Michael Lubbert ◽  
Gerald Illerhaus ◽  
Frank Gartner ◽  
Hartmut Bertz
Keyword(s):  
Antifungal Therapy ◽  
Hematological Malignancies ◽  
Fungal Infections ◽  
Invasive Pulmonary Aspergillosis ◽  
Severe Neutropenia ◽  
Conventional Chemotherapy ◽  
Pulmonary Aspergillosis ◽  
Septic Complications ◽  
Increased Risk ◽  
Neutropenic Patients

Abstract Abstract 3372 Background: Granulocyte transfusions (GTX) are used as an additional therapeutic option in patients with severe neutropenia following chemotherapy constituting an increased risk for life-threatening bacterial and fungal infections. We hypothesized that interventional GTX would provide a clinical benefit for neutropenic patients with invasive pulmonary aspergillosis (IPA). Methods: We reviewed the clinical outcome of 44 patients with severe neutropenia (46 cases) and underlying hematological malignancies suffering from IPA unresponsive to standard antifungal therapy. They received a total of 181 human recombinant granulocyte colony-stimulating factor (rh G-CSF) stimulated GTX at Freiburg University medical center from 1996 – 2009. Neutropenias were caused by conventional chemotherapy (n=38), conditioning chemotherapy for allogeneic (n=4) and autologous (n=2) hematopoietic cell transplantation (HCT), aplastic anemia (n=1) and by intense immunosuppressive (n=1). Donors were exclusively relatives and acquaintances of the recipients. IPA was diagnosed by clinic, computed tomography (CT) scan, serological or microbiological measures. Response of GTX was evaluated by repeated CT, decreasing C-reactive protein (CRP) levels, hematopoietic regeneration and clearance of serum galactomannan antigen. Results: A median of 3 GTX (range 1–25) containing a median total of 59.4×109 (range 3–170) white blood cells per GTX were administered. All but five (3%) transfusions were well tolerated. Median duration of neutropenia proceeding GTX was 15.5 d (range 4–70). Resolution of infection or clinical improvement was achieved in 29 (63%) patients with IPA and haematopoietic recovery has been assumed within 10 days after the last GTX in 34 patients (74%). Thirty-three (72%) patients were alive one month after the first GTX. Overall, progressive malignant disease was the main cause of death. Patients not responding to GTX died without on septic complications despite appropriate antibacterial and antifungal treatment. Nine out of 26 neutropenic patients receiving GTX after conventional chemotherapy underwent allogeneic HCT later on after control of IPA. Conclusions: Rh G-CSF stimulated GTX are a safe and effective therapeutic tool for patients with hematological malignancies suffering from profound neutropenia and antifungal-therapy resistant IPA. GTX may serve as a bridging therapy in severe neutropenic patients with IPA scheduled for allo-HCT. Disclosures: Bertz: GILEAD: Research Funding; MSD: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Antifungal Prophylaxis Is Effective against Murine Invasive Pulmonary Aspergillosis

2006 ◽  
Vol 50 (8) ◽  
pp. 2895-2896 ◽  
Author(s):  
Gunter Rieg ◽  
Brad Spellberg ◽  
Julie Schwartz ◽  
Yue Fu ◽  
John E. Edwards ◽  
...  
Keyword(s):  
Invasive Pulmonary Aspergillosis ◽  
Antifungal Prophylaxis ◽  
Pulmonary Aspergillosis

Invasive pulmonary aspergillosis/pseudomonas

2021 ◽  
Vol 14 (7) ◽  
pp. e236887
Author(s):  
Menaka Mahendran ◽  
Daniel Urbine
Keyword(s):  
Antifungal Therapy ◽  
High Mortality ◽  
Surgical Intervention ◽  
Main Pulmonary Artery ◽  
Invasive Pulmonary Aspergillosis ◽  
Chest Discomfort ◽  
Pulmonary Aspergillosis ◽  
Extensive Disease ◽  
Massive Haemoptysis ◽  
History Of

A 47-year-old Caucasian man on long-standing antifungal therapy for chronic necrotising aspergillosis and a history of recurrent pseudomonas pneumonias presented to the outpatient pulmonary clinic with dyspnoea and chest discomfort for 3 days. A CT angiography of the chest demonstrated angioinvasion from the previously noted left upper lobe cavitary lesion into the left main pulmonary artery, along with new consolidating lesions. Due to the high risk for massive haemoptysis, he was evaluated by thoracic surgery and underwent a successful left pneumonectomy. As invasive pulmonary aspergillosis is associated with high mortality, surgical intervention should always be considered, especially in those who develop extensive disease, despite being on aggressive antifungal therapy. Though minimally described in literature, invasive pulmonary pseudomonas also carries a high mortality risk. In our patient, cultures from the resected lung only demonstrated Pseudomonas aeruginosa.

scholarly journals Isavuconazole Is as Effective as and Better Tolerated Than Voriconazole for Antifungal Prophylaxis in Lung Transplant Recipients

2020 ◽  
Author(s):  
Palash Samanta ◽  
Cornelius J Clancy ◽  
Rachel V Marini ◽  
Ryan M Rivosecchi ◽  
Erin K McCreary ◽  
...  
Keyword(s):  
Risk Factors ◽  
Lung Transplantation ◽  
Lung Transplant ◽  
Fungal Infections ◽  
Oral Intake ◽  
Antifungal Prophylaxis ◽  
Red Blood Cell Transfusion ◽  
Transplant Recipients ◽  
Independent Risk Factors ◽  
Lung Transplant Recipients

Abstract Background Invasive fungal infections (IFIs) are common following lung transplantation. Isavuconazole is unstudied as prophylaxis in organ transplant recipients. We compared effectiveness and tolerability of isavuconazole and voriconazole prophylaxis in lung transplant recipients. Methods A single-center, retrospective study of patients who received isavuconazole (September 2015–February 2018) or voriconazole (September 2013–September 2015) for antifungal prophylaxis. IFIs were defined by EORTC/MSG criteria. Results Patients received isavuconazole (n = 144) or voriconazole (n = 156) for median 3.4 and 3.1 months, respectively. Adjunctive inhaled amphotericin B (iAmB) was administered to 100% and 41% of patients in the respective groups. At 1 year, 8% of patients receiving isavuconazole or voriconazole developed IFIs. For both groups, 70% and 30% of IFIs were caused by molds and yeasts, respectively, and breakthrough IFI (bIFI) rate was 3%. Outcomes did not significantly differ for patients receiving or not receiving iAmB. Independent risk factors for bIFI and breakthrough invasive mold infection (bIMI) were mold-positive respiratory culture and red blood cell transfusion &gt;7 units at transplant. Bronchial necrosis &gt;2 cm from anastomosis and basiliximab induction were also independent risk factors for bIMI. Isavuconazole and voriconazole were discontinued prematurely due to adverse events in 11% and 36% of patients, respectively (P = .0001). Most common causes of voriconazole and isavuconazole discontinuation were hepatotoxicity and lack of oral intake, respectively. Patients receiving ≥90 days prophylaxis had fewer IFIs at 1 year (3% vs 9%, P = .02). IFIs were associated with increased mortality (P = .0001) and longer hospitalizations (P = .0005). Conclusions Isavuconazole was effective and well tolerated as antifungal prophylaxis following lung transplantation.

scholarly journals Primary or Secondary Prophylaxis with Voriconazole Compared with Posaconazole for Prevention of Invasive Fungal Infections After Hematopoietic Stem Cell Transplantation

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S75-S75
Author(s):  
Jeffrey W Jansen ◽  
Anupam Pande ◽  
Rizwan Romee ◽  
Steven J Lawrence ◽  
William Powderly
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Fungal Infections ◽  
Antifungal Prophylaxis ◽  
Invasive Fungal Infections ◽  
Hematopoietic Stem ◽  
Research Grant

Abstract Background Invasive fungal infections (IFI) remain a serious complication in hematopoietic stem cell transplantation (HSCT) patients and are associated with increased costs, morbidity, and mortality. Posaconazole (PCZ) and voriconazole (VCZ) are frequently utilized as antifungal prophylaxis in this population. To date, no direct comparison between PCZ and VCZ exists for the prevention of IFI in adult HSCT patients. Methods A retrospective cohort analysis of HSCT patients aged ≥18 years who received ≥28 continuous days of primary (PPPx) or secondary (SPPx) antifungal prophylaxis with either VCZ or PCZ between February 26, 2003 and September 30, 2015 at Barnes-Jewish Hospital was conducted. Patients who received PPPx or SPPx with both VCZ and PCZ were analyzed following intention to treat of the initial agent received. Patients who received both PPPx and SPPx were included once for both PPPx and SPPx. The primary outcome of interest was development of possible, probable, or proven IFI as defined by EORTC/MSG guidelines. In the SPPx patients, development of IFI was confirmed as a distinct event from primary IFI based on manual chart review and radiographic evidence. Results Overall, there were 472 patients included; 402 in the VCZ group and 70 in the PCZ group. At baseline, patients in the PCZ group had more graft vs. host disease (GVHD) prior to prophylaxis (27.1% vs. 16.7%, P = 0.04) and were more likely to be on SPPx (60% vs. 41%, P &lt; 0.01). There were 22 and 1 IFI events in the VCZ and PCZ groups, respectively, which corresponded to a crude incidence rate of 0.345 and 0.077 per 1000 person-days of prophylaxis. Figure 1 displays the Cox proportional hazard model which was completed in the backwards stepwise method accounting for gender, transplant type, GVHD prior to prophylaxis, disease remission, and PPPx or SPPX. The hazard ratio for development of IFI while on prophylaxis between VCZ and PCZ was 5.22 (95% CI: 0.69–39.4; P = 0.11) after controlling for PPPx or SPPx. Conclusion There was not a significant difference between rates of IFI in HSCT patients who received antifungal prophylaxis with VCZ compared with PCZ. Our data trends towards favoring PCZ but is limited by low rates of IFI. Larger, prospective analyses are necessary to confirm our findings. Disclosures W. Powderly, Merck: Grant Investigator and Scientific Advisor, Consulting fee and Research grant. Gilead: Scientific Advisor, Consulting fee. Astellas: Grant Investigator, Research grant

scholarly journals A Case of Chronic Granulomatous Disease with a Necrotic Mass in the Bronchus: A Case Report and a Review of Literature

2012 ◽  
Vol 2012 ◽  
pp. 1-4
Author(s):  
Ali Cheraghvandi ◽  
Majid Marjani ◽  
Saeid Fallah Tafti ◽  
Logman Cheraghvandi ◽  
Davoud Mansouri
Keyword(s):  
Case Report ◽  
Chronic Granulomatous Disease ◽  
Medical Therapy ◽  
Unusual Case ◽  
Fungal Infections ◽  
Invasive Pulmonary Aspergillosis ◽  
Granulomatous Disease ◽  
Review Of Literature ◽  
Pulmonary Aspergillosis ◽  
The Right

Chronic granulomatous disease is a rare phagocytic disorder with recurrent, severe bacterial and fungal infections. We describe an unusual case of chronic granulomatous disease manifesting as an invasive pulmonary aspergillosis with an obstructive necrotic mass at the right middle bronchus. The patient was successfully treated with a bronchoscopic intervention for the removal of the obstructive mass and a medical therapy.

scholarly journals Aspergillus niger causing tracheobronchitis and invasive pulmonary aspergillosis in a lung transplant recipient: case report

2008 ◽  
Vol 41 (2) ◽  
pp. 200-201 ◽  
Author(s):  
Melissa Orzechowski Xavier ◽  
Maria da Penha Uchoa Sales ◽  
José de Jesus Peixoto Camargo ◽  
Alessandro Comarú Pasqualotto ◽  
Luiz Carlos Severo
Keyword(s):  
Case Report ◽  
Aspergillus Niger ◽  
Transplant Recipient ◽  
Cytomegalovirus Infection ◽  
Lung Transplant ◽  
Invasive Pulmonary Aspergillosis ◽  
Invasive Disease ◽  
Fungal Species ◽  
Lung Transplant Recipient ◽  
Pulmonary Aspergillosis

A case of invasive aspergillosis caused by Aspergillus niger in a lung transplant recipient is described. The patient presented hyperglycemia starting postoperatively, with other complications such as cytomegalovirus infection. The associated predisposing factors and other implications are discussed. Aspergillus niger seems to be a fungal species of low virulence that requires the presence of a severely immunosuppressed host to cause invasive disease.

scholarly journals Antifungal effect of all-trans retinoic acid against Aspergillus fumigatus in vitro and in a pulmonary aspergillosis in vivo model

2020 ◽  
Author(s):  
Elena Campione ◽  
Roberta Gaziano ◽  
Elena Doldo ◽  
Daniele Marino ◽  
Mattia Falconi ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Aspergillus Fumigatus ◽  
Rat Model ◽  
Fungal Infections ◽  
Invasive Pulmonary Aspergillosis ◽  
Antifungal Drugs ◽  
Pulmonary Aspergillosis ◽  
Fungistatic Activity

AIM: Aspergillus fumigatus is the most common opportunistic fungal pathogen and causes invasive pulmonary aspergillosis (IPA), with high mortality among immunosuppressed patients. Fungistatic activity of all-trans retinoic acid (ATRA) has been recently described in vitro. We evaluated the efficacy of ATRA in vivo and its potential synergistic interaction with other antifungal drugs. MATERIALS AND METHODS: A rat model of IPA and in vitro experiments were performed to assess the efficacy of ATRA against Aspergillus in association with classical antifungal drugs and in silico studies used to clarify its mechanism of action. RESULTS: ATRA (0.5 and 1 mM) displayed a strong fungistatic activity in Aspergillus cultures, while at lower concentrations, synergistically potentiated fungistatic efficacy of sub-inhibitory concentration of Amphotericin B (AmB) and Posaconazole (POS). ATRA also enhanced macrophagic phagocytosis of conidia. In a rat model of IPA, ATRA reduced mortality similarly to Posaconazole. CONCLUSION: Fungistatic efficacy of ATRA alone and synergistically with other antifungal drugs was documented in vitro, likely by inhibiting fungal Hsp90 expression and Hsp90-related genes. ATRA reduced mortality in a model of IPA in vivo. Those findings suggest ATRA as suitable fungistatic agent, also to reduce dosage and adverse reaction of classical antifungal drugs, and new therapeutic strategies against IPA and systemic fungal infections.

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