Pulmonary Zygomycosis Research Articles

Report of a Successful Treatment of Pulmonary Cunninghamella bertholletiae Infection With Liposomal Amphotericin and Posaconazole in a Child With GvHD and Review of the Literature

Zygomycosis is an emerging, opportunistic fungal infection particularly affecting immunocomprised patients. We report the case of a 10-year-old girl who developed pulmonary zygomycosis because of Cunninghamella bertholletiae 1 year after undergoing bone marrow transplantation complicated with severe cutaneous and digestive graft-versus-host disease. Treatment with surgery and liposomal amphotericin B followed by posaconazole successfully treated the infection.

Capítulo 7 - Zigomicose

Zygomycosis (mucormycosis) is a rare but highly invasive infection caused by fungi belonging to the order Mucorales, which includes the genera Rhizopus, Mucor, Rhizomucor, Absidia, Apophysomyces, Saksenaea, Cunninghamella, Cokeromyces and Syncephalastrum. This type of infection is usually associated with hematologic diseases, diabetic ketoacidosis and organ transplantation. The most common form of presentation is rhinocerebral mucormycosis, with or without pulmonary involvement. Pulmonary zygomycosis is more common in patients with profound, prolonged neutropenia and can present as segmental or lobar infiltrates, isolated nodules, cavitary lesions, hemorrhage or infarction. The clinical and radiological manifestations are often indistinguishable from those associated with invasive aspergillosis. This article describes the general characteristics of pulmonary zygomycosis, emphasizing laboratory diagnosis, and illustrates the morphology of some lesions.

Pharmacokinetics of Liposomal Amphotericin B in Pleural Fluid

We report the penetration of liposomal amphotericin B into the pleural fluid of a patient with pulmonary zygomycosis and empyema. The ratio of area under the concentration-versus-time curve in pleural fluid (AUC(pleural fluid)) to that in serum (AUC(serum)) for liposomal amphotericin B over 24 h was 9.4%, with pleural fluid concentrations of 2.12 to 4.91 microg/ml. Given the relatively low level of intrapleural penetration of liposomal amphotericin B, chest tube drainage may be warranted for successful treatment of zygomycotic empyema.

Pulmonary Zygomycosis in Solid Organ Transplant Recipients in the Current Era

Fifty-eight solid organ transplant recipients with zygomycosis were studied to assess the presentation, radiographic characteristics, risks for extra-pulmonary dissemination and mortality of pulmonary zygomycosis. Pulmonary zygomycosis was documented in 31 patients (53%) and developed a median of 5.5 months (interquartile range, 2-11 months) posttransplantation. In all, 74.2% (23/31) of the patients had zygomycosis limited to the lungs and 25.8% (8/31) had lung disease as part of disseminated zygomycosis; cutaneous/soft tissue (50%, 4/8) was the most common site of dissemination. Pulmonary disease presented most frequently as consolidation/mass lesions (29.0%), nodules (25.8%) and cavities (22.6%). Patients with disseminated disease were more likely to have Mycocladus corymbifer as the causative pathogen. The mortality rate at 90 days after the treatment was 45.2%. In summary, pulmonary zygomycosis is the most common manifestation in solid organ transplant recipients with zygomycosis, and disseminated disease often involves the cutaneous/soft tissue sites but not the brain.

Deposition of calcium salts in a case of pulmonary zygomycosis: histopathologic and chemical findings

We report a case of pulmonary zygomycosis associated with unusual deposition of calcium salt crystals. The patient was a 75-year-old female who had onset of cough and shortness of breath. She was treated for community-acquired pneumonia but died despite intensive therapy. Postmortem examination revealed diffuse alveolar damage and multifocal necrotizing pneumonia associated with herpes simplex infection and invasive zygomycosis. Birefringent particles were seen associated with fungal elements in the lung parenchyma, within bronchial cartilage, and in blood vessel walls. By infrared spectroscopy, the birefringent particles in the pulmonary parenchyma and within bronchial cartilage had spectral characteristics of calcium oxalate dihydrate and calcium oxalate monohydrate, respectively. The birefringent crystals within vascular walls were identified as calcium carbonate. This case documents the chemical composition and location of 3 different calcium salt crystals in pulmonary zygomycosis. It also shows that among pulmonary fungal infections, calcium oxalate deposition is not restricted to aspergillosis.

152: Amphotericin B for Treatment of Concurrent Pulmonary Zygomycosis and Aspergillus in Kidney Transplant Recepient

152: Amphotericin B for Treatment of Concurrent Pulmonary Zygomycosis and Aspergillus in Kidney Transplant Recepient

Vesicular thick‐walled swollen hyphae in pulmonary zygomycosis

An autopsy case of pulmonary zygomycosis in a patient with rheumatoid arthritis on immunosuppressive therapy is presented herein. There was a pulmonary cavitated infarct caused by mycotic thrombosis. Thin-walled narrow hyphae and vesicular thick-walled swollen hyphae were found on the pleural surface and in the necrotic tissue at the periphery of the cavity. Findings of such shaped fungal elements may cause erroneous histopathological diagnosis because pauciseptate broad thin-walled hyphae are usually the only detectable fungal elements in zygomycosis tissue. Although immunohistochemistry confirmed these unusual elements to be zygomycetous in the present case, it is important for the differential diagnosis to be aware that zygomycetes can form thin narrow hyphae and vesicular thick-walled swollen hyphae.

Successful treatment of pulmonary zygomycosis in two transplant recipients with liposomal amphotericin B and partial surgical resection followed by posaconazole

Summary Pulmonary zygomycosis is a relatively uncommon complication of solid organ or peripheral blood stem cell transplantation and has a high associated mortality. Optimal therapy consists of complete resection of infected tissue and treatment with amphotericin B (AmB). We describe two patients, one of whom underwent orthotopic heart transplantation and the other who received a peripheral blood stem cell transplant, who were diagnosed with invasive pulmonary zygomycosis. Both patients were treated with a liposomal preparation of AmB and early partial resection of the infected structures followed by prolonged posaconazole maintenance therapy. Despite incomplete resection, this treatment regimen resulted in a favourable outcome in both patients, including survival of more than 17 months in one patient at last follow up. For patients in whom complete resection of pulmonary zygomycosis is not possible, subtotal resection and treatment with liposomal AmB followed by therapy with posaconazole may be an effective treatment option.

Simultaneous mold infections in an orthotopic heart transplant recipient

Simultaneous mold infections in heart transplant recipients have not been previously reported. Here we describe early onset post-transplant pulmonary aspergillosis and cutaneous zygomycosis in a 46-year-old heart transplant recipient who was also treated with basiliximab. Along with surgical debridement, medical treatment of his cutaneous abdominal wall zygomycosis at the former left ventricular assist device driveline site with liposomal amphotericin B and voriconazole also led to cure of his pulmonary aspergillosis.

A Case of Pulmonary Angioinvasive Zygomycosis in a Patient with Acute Promyelocytic Leukemia successfully treated with Surgical Resection and Posaconazole

A Case of Pulmonary Angioinvasive Zygomycosis in a Patient with Acute Promyelocytic Leukemia successfully treated with Surgical Resection and Posaconazole

Concurrent pulmonary zygomycosis and Mycobacterium tuberculosis infection: a case report

A non-smoking 77-year old gentleman of Indian origin was admitted with a 4-month history of intermittent night sweats, haemoptysis and 6 kg of weight loss. CT scan of thorax demonstrated a 2.5 cm mass in the right middle lobe with multiple small nodules within the right lung and confirmed the presence of mediastinal and hilar lymph nodes.Fibreoptic bronchoscopy demonstrated a distorted right main bronchus, anterior shift of the right upper lobe and occlusion of the right middle lobe bronchus with a black necrotic ulcer. Mycobacterium tuberculosis was found in the bronchoalveolar lavage and histology demonstrated numerous fungal hyphae with a morphological appearance of zygomycetes within necrotic areas of tissue. Medical management with anti-fungal and anti-mycobacterial treatment was instigated as the patient's pre-existing IHD did not permit surgical intervention. Subsequently CT imaging following completion of therapy demonstrated improvement of the mass and a resolution of the associated nodules. The patient has been followed for 6 months to date and there has been no recurrence of symptoms. Recent bronchoalveolar lavage cultures have been negative for M. tuberculosis and zygomycetes.

Treatment of Cavitary Pulmonary Zygomycosis With Surgical Resection and Posaconazole

We describe a 57-year-old woman with acute lymphoblastic leukemia who had a cavitary lesion develop in the right upper lobe caused by Cunninghamella bertholletiae, a zygomycete. The infection was resistant to both high-dose liposomal amphotericin B and voriconazole. The current report demonstrates successful treatment, even in the setting of subsequent bone marrow transplantation and immunosuppression, using a combination of surgical resection and posaconazole therapy.

Favourable outcome of pulmonary zygomycosis in haematological malignancy

Sir,Zygomycosis is a rare fungal infection occurring in immunosuppressed patients. The infections are acute, rapidly developing and often fulminant with a high mortality. Diagnosis is often difficu...

The rising trend of invasive zygomycosis in patients with uncontrolled diabetes mellitus

Zygomycosis is an emerging infection worldwide. A study was conducted to understand its spectrum in the Indian scenario. All patients diagnosed for invasive zygomycosis at a tertiary care center in north India from 2000-2004, were retrospectively analyzed. A total of 178 cases (mean average of 35.6 cases/year) of zygomycosis were diagnosed. Rhino-orbito-cerebral type (54.5%) was the commonest presentation followed by cutaneous (14.6%), disseminated (9.0%), and gastrointestinal (8.4%) zygomycosis. Renal and pulmonary zygomycosis were seen in 6.7% patients each. Uncontrolled diabetes mellitus (in 73.6% of cases) was the significant risk factor in all types (Odds Ratio 1.5-8.0) except renal zygomycosis. Breach of skin was the risk factor in 46.2% patients with cutaneous zygomycosis. However, no risk factor could be detected in 11.8% patients. Antemortem diagnosis was possible in 83.7% cases. The commonest (61.5%) isolate was Rhizopus oryzae followed by Apophysomyces elegans in 27% patients. Combination of debridement surgery and amphotericin B therapy was significantly better in survival of the patients (P<0.005) than amphotericin B alone (79.6% vs. 51.7% survival). Thus, a rising trend of invasive zygomycosis was observed in patients with uncontrolled diabetes mellitus in India. Consistent diagnosis of renal zygomycosis in apparently healthy hosts and the emergence of A. elegans in India demand further study.

Mucormycose pulmonaire

Mucormycosis is a rare, devastating, opportunistic fungal infection, which occurs principally in some particular conditions, specially in non-controlled diabetic patients, notably during keratoacidosis. We report two cases in 62 and 72 year-old diabetic women. In both cases, histologic examination of endobronchial biopsies showed tissue invasion by hyphae with characteristic morphology leading to the diagnosis of pulmonary zygomycosis. This difficult diagnosis must be evoked in diabetic patients with non-responsive lung infections in order to apply early aggressive therapy.

A Case of Gastrointestinal Zygomycosis in a Patient With Gastric Adenocarcinoma

Zygomycosis, in particular, infection due to fungi of the order Mucorales, is typically found in patients with diabetes, solid organ transplants, hematologic malignancies, or those treated with deferoxamine. Recently, with increased myleosuppressive chemotherapy regimens, more cases of pulmonary or disseminated zygomycosis have been reported in neutropenic patients than in the past. We present a white man diagnosed with gastric adenocarcinoma who presented with a small bowel perforation due to gastrointestinal zygomycosis. He was not significantly neutropenic, however, his risk for development of this unusual fungal infection was malnutrition, acidosis, and leukopenia.

Successful treatment of pulmonary zygomycosis with posaconazole in a recipient of a haploidentical donor stem cell transplant

We report the clinical course of a patient who developed a Rhizopus infection of his right lung and pleural cavity, 11 months after receiving a T-cell-depleted, haploidentical donor peripheral blood stem cell transplant. Thoracotomy was performed to remove the pulmonary lesion, but residual disease in the pleural cavity was noted. Treatment with amphotericin B was complicated by the development of severe renal dysfunction, necessitating alternative antifungal therapy. Treatment was initiated with the investigational triazole posaconazole. Despite concurrent treatment with corticosteroids for graft-versus-host disease (GVHD), the patient had a complete response and remains well 4 years later.

Predictors of Pulmonary Zygomycosis versus Invasive Pulmonary Aspergillosis in Patients with Cancer

Pulmonary zygomycosis (PZ), an emerging mycosis among patients with cancer, has a clinical manifestation similar to that of invasive pulmonary aspergillosis (IPA). Most cases of PZ in such patients develop as breakthrough infections if treatment with antifungal agents effective against Aspergillus species is administered. However, clinical criteria to differentiate PZ from IPA are lacking. We retrospectively reviewed the clinical characteristics and computed tomography (CT) findings for 16 patients with cancer and PZ and for 29 contemporaneous patients with cancer and IPA at the time of infection onset (2002-2004). Patients with mixed infections were excluded. Parameters predictive of PZ by univariate analysis were included in a logistic regression model. Almost all patients with PZ (15 of 16) and IPA (28 of 29) had underlying hematological malignancies and typical risk factors for invasive mold infections. In logistic regression analysis of clinical characteristics, concomitant sinusitis (odds ratio [OR], 25.7; 95% confidence interval [CI], 1.47-448.15; P = .026) and voriconazole prophylaxis (OR, 7.76; 95% CI, 1.32-45.53; P = .023) were significantly associated with PZ. The presence of multiple (> or = 10) nodules (OR, 19.8; 95% CI, 1.94-202.29; P = .012) and pleural effusion (OR, 5.07; 95% CI, 1.06-24.23; P = .042) at the time that the patient underwent the initial CT were both independent predictors of PZ in the logistic regression analysis of radiological parameters. No difference occurred in the frequency of other CT findings suggestive of pulmonary mold infections (e.g., masses, cavities, halo sign, or air-crescent sign) between the 2 patient groups. PZ in immunocompromised patients with cancer could potentially be distinguished from IPA on the basis of clinical and radiological parameters; prospective validation is needed.

Pulmonale Zygomykose – eine seltene angioinvasive Pilzinfektion

Zusammenfassung Rhizopus‐Arten sind Pilze, die Zygomykosen verursachen. Die Zygomykose umfasst mukokutane, rhinocerebrale, pulmonale, urogenitale und disseminierte Infektionen. Prädisponierende Faktoren sind eine Immunsuppression infolge von schweren Erkrankungen, Immundefekte oder Störungen des Stoffwechsels wie die diabetische Ketoazidose. Rhizopus‐Infektionen sind charakterisiert durch ein angioinvasives Wachstum der Pilze, eine perineurale Invasion und Nekrosen des infizierten Gewebes. Bemerkenswert ist die histopathologisch nachweisbare Invasion von Blutgefässen. Zygomykosen verlaufen häufig letal. Wir berichten über zwei Patienten mit einer pulmonalen Zygomykose, hervorgerufen durch Rhizopus spp.: Pat. 1, weibl. 73 Jahre: Protrahierter Verlauf nach infizierter Hüft‐TEP (abkurtzung für Totalendoprothese) und Infektion eines femoropoplitealen Bypasses des rechten Beines, schließlich Hüftgelenksexartikulation rechts, Pseudomonas‐Pneumonie, Staphylokokkensepsis, schweres septisches Schockgeschen mit akutem Lungen‐ und Nierenversagen, Zustand nach multimodaler Antibiotikatherapie. In der Folge Nachweis von Rhizopus spp. in der BAL, antimykotische Therapie mit Amphotericin B. Pat. 2, männl., 68 Jahre: Zustand nach Nierentransplantation, aktuell Transplantatversagen. Multiple abgelaufene Infektionen. In der Folge abszedierende Pneumonie rechts mit Entwicklung eines Pleuraempyems, darin Nachweis von Rhizopus spp., deshalb Unterlappenresektion und Transplantatnephrektomie wegen Rejektion. Protrahierter septischer Verlauf. Behandlung mit Caspofungin. Beide Verläufe endeten trotz aller intensivmedizinischer Bemühungen letal. Die seltene pulmonale Zygomykose infolge einer Infektion mit Rhizopus spp. entstand bei unseren Patienten infolge einer Immunsuppression, bei einem aufgrund einer Organtransplantation iatrogen induziert, beim anderen infolge einer protrahiert verlaufenden schweren Sepsis. Im Vergleich zu anderen Pilzinfektionen bleibt die Therapie von Rhizopus‐Infektionen schwierig. Ihre starke Affinität zu Gefäßen, in denen sie sich vermehren und ihre Eigenschaft, im Rahmen der vaskulären Invasion eine Thrombosierung und anschließende Infarktbildung herbeizuführen, erschweren die Therapie.

Lipid‐based amphotericin in pulmonary zygomycosis: safety and efficacy of high exposure in a renal allograft recipient

Zygomycosis is associated with a high mortality in immunosuppressed patients. Treatment typically includes surgical resection and administration of intravenous amphotericin B. Success of treatment may require withdrawal of immunosuppression, with risk of graft loss. We report the successful treatment of invasive pulmonary zygomycosis, following initial surgical resection, using very high doses of lipid-based amphotericin B without withdrawal of immunosuppression. The patient received daily doses up to 10 mg/kg/day (51 g cumulatively) of lipid-based amphotericin B along with a brief course of intrapleural amphotericin. Despite immunosuppression not being withdrawn, the patient's kidney allograft function remained stable. We conclude that high doses of lipid-based amphotericin B can be safe and effective as part of the treatment regimen for pulmonary zygomycosis.