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Rocha MF, Bain HDC, Stone N, Meya D, Darie L, Toma AK, Lunn MPT, Mehta AR, Coughlan C. Reframing the clinical phenotype and management of cryptococcal meningitis. Pract Neurol 2025; 25:25-39. [PMID: 38997136 PMCID: PMC11877062 DOI: 10.1136/pn-2024-004133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/27/2024] [Indexed: 07/14/2024]
Abstract
Cryptococcal meningitis is an important global health problem, resulting from infection with the yeast Cryptococcus, especially Cryptococcus neoformans and Cryptococcus gattii, which cause a spectrum of disease ranging from pulmonary and skin lesions to life-threatening central nervous system involvement. The diagnosis and management of cryptococcal meningitis have substantially changed in recent years. Cryptococcal meningitis often occurs in people living with advanced HIV infection, though in high-income countries with robust HIV detection and treatment programmes, it increasingly occurs in other groups, notably solid-organ transplant recipients, other immunosuppressed patients and even immunocompetent hosts. This review outlines the clinical presentation, management and prognosis of cryptococcal meningitis, including its salient differences in people living with HIV compared with HIV-negative patients. We discuss the importance of managing raised intracranial pressure and highlight the advantages of improved multidisciplinary team working involving neurologists, infectious disease specialists and neurosurgeons.
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Affiliation(s)
- Maria Francisca Rocha
- National Hospital for Neurology and Neurosurgery, Queen Square, University College London Hospitals NHS Foundation Trust, London, UK
| | - Hamish D C Bain
- National Hospital for Neurology and Neurosurgery, Queen Square, University College London Hospitals NHS Foundation Trust, London, UK
| | - Neil Stone
- Hospital for Tropical Diseases, University College London Hospitals NHS Foundation Trust, London, UK
| | - David Meya
- Infectious Diseases Institute, Makerere University, Kampala, Uganda
| | - Lucia Darie
- Department of Neurosurgery, National Hospital for Neurology and Neurosurgery, Queen Square, University College London Hospitals NHS Foundation Trust, London, UK
| | - Ahmed K Toma
- Department of Neurosurgery, National Hospital for Neurology and Neurosurgery, Queen Square, University College London Hospitals NHS Foundation Trust, London, UK
| | - Michael P T Lunn
- National Hospital for Neurology and Neurosurgery, Queen Square, University College London Hospitals NHS Foundation Trust, London, UK
| | - Arpan R Mehta
- National Hospital for Neurology and Neurosurgery, Queen Square, University College London Hospitals NHS Foundation Trust, London, UK
- MRC Protein Phosphorylation & Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee, UK
| | - Charles Coughlan
- National Hospital for Neurology and Neurosurgery, Queen Square, University College London Hospitals NHS Foundation Trust, London, UK
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Chen CT, Ho MW, Chung WH. Disseminated Cryptococcal Gattii infection in a patient with anti-granulocyte-macrophage colony-stimulating-factor autoantibody: a case report. BMC Infect Dis 2024; 24:1413. [PMID: 39695975 DOI: 10.1186/s12879-024-10267-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2024] [Accepted: 11/25/2024] [Indexed: 12/20/2024] Open
Abstract
BACKGROUND Cryptococcosis is an opportunistic fungal infection in immunocompromised patients. The major species include Cryptococcus grubii, Cryptococcus neoformans, and rarely, Cryptococcus gattii. Here we present a disseminated Cryptococcus gattii infection in a patient with elevated granulocyte-macrophage colony-stimulating-factor autoantibody which was successfully treated with antifungal therapy. CASE PRESENTATION A 61-year-old healthy man presented with a 3-week history of blurred vision, low-grade fever, headache, and a one-year history of low back pain following a fall on his farm. Physical examination revealed lower back tenderness and diplopia. He was tested negative for hepatitis B, C, and human immunodeficiency virus. Chest X-ray revealed a focal opacity in the right retrocardiac paraspinal region and pleural effusion. Magnetic resonance imaging showed a mass located at the L1 prevertebral region and multiple rim-enhancing lesions in bilateral cerebral hemispheres. Thoracoscopy demonstrated cystic lesions at the right costopleural angle. Pathology and microbiology studies confirmed the diagnosis of disseminated Cryptococcus gatti infection. Autoantibodies to granulocyte-macrophage colony-stimulating factor were detected and were considered to cause disseminated cryptococcosis. The patient was started on amphotericin B followed by fluconazole treatment. One month later, the symptoms ameliorated and repeated image studies after 1 year of follow-up showed the resolution of lesions. CONCLUSION This report describes the first case of disseminated Cryptococcus gattii infection involving the musculoskeletal system, respiratory system, and central nervous system with granulocyte-macrophage colony-stimulating-factor autoantibody by evidence of histology and microbiology.
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Affiliation(s)
- Chi-Tung Chen
- Division of Cardiovascular Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Mao-Wang Ho
- Division of Infectious Disease, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Wei-Hsin Chung
- Division of Cardiovascular Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
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Barut D, Kunay B, Yıldırım Arslan S, Akkuş GK, Şahbudak Bal Z, Yazıcı P, Karakoyun M, Aydoğdu S. Disseminated cryptococcosis in a child with liver transplantation: a case report. Turk J Pediatr 2024; 66:499-504. [PMID: 39387422 DOI: 10.24953/turkjpediatr.2024.4817] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Accepted: 07/22/2024] [Indexed: 10/15/2024]
Abstract
BACKGROUND Cryptococcus neoformans causes cryptococcosis, primarily affecting immunocompromised individuals, including solid-organ transplant recipients, and, less frequently, immunocompetent people. CASE A 15-year-old male with congenital hepatic fibrosis, portal hypertension, and cirrhosis underwent orthotopic liver transplantation. He received perioperative antimicrobial and antifungal prophylaxis and continued immunosuppressive treatment. Thirty months post-transplant, he presented with fever, hypertension, and sacroiliac joint pain. Peripheral blood cultures showed C. neoformans, confirmed by pan-fungal polymerase chain reaction assay and latex agglutination tests. Despite initial treatment with intravenous (IV) fluconazole, his condition worsened, necessitating intubation for acute hypoxic respiratory failure. Magnetic resonance imaging and computed tomography scans indicated disseminated cryptococcosis with lymphadenitis, possible meningitis, and pneumonia. Treatment was escalated to IV liposomal amphotericin B and 5-flucytosine, while reducing immunosuppressive treatment. Despite negative fungal cultures on the tenth day, the patient deteriorated, developing pancreatitis, pneumonia, and massive gastrointestinal bleeding, leading to death on the 35th day of hospitalization. CONCLUSION This case shows the severity and complexity of managing disseminated cryptococcosis in pediatric liver transplant recipients. Aggressive therapy and early identification are essential for improving outcomes in these high-risk patients.
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Affiliation(s)
- Doğan Barut
- Division of Gastroenterology, Hepatology and Nutrition Disease, Department of Pediatrics, Medical School of Ege University, İzmir, Türkiye
| | - Bora Kunay
- Division of Gastroenterology, Hepatology and Nutrition Disease, Department of Pediatrics, Medical School of Ege University, İzmir, Türkiye
| | - Sema Yıldırım Arslan
- Division of Infectious Disease, Department of Pediatrics, Medical School of Ege University, İzmir, Türkiye
| | - Gözde Kayalı Akkuş
- Department of Microbiology, Medical School of Ege University, İzmir, Türkiye
| | - Zümrüt Şahbudak Bal
- Division of Infectious Disease, Department of Pediatrics, Medical School of Ege University, İzmir, Türkiye
| | - Pınar Yazıcı
- Division of Pediatric Intensive Care, Department of Pediatrics, Medical School of Ege University, İzmir, Türkiye
| | - Miray Karakoyun
- Division of Gastroenterology, Hepatology and Nutrition Disease, Department of Pediatrics, Medical School of Ege University, İzmir, Türkiye
| | - Sema Aydoğdu
- Division of Gastroenterology, Hepatology and Nutrition Disease, Department of Pediatrics, Medical School of Ege University, İzmir, Türkiye
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Lulic I, Fingler G, Lulic D, Pavicic Saric J, Mikulic D, Filipec Kanizaj T, Goluza E. Meningeal cryptococcosis in a pancreas transplant recipient requiring grafectomy: A case report. World J Gastrointest Surg 2024; 16:3032-3040. [PMID: 39351551 PMCID: PMC11438803 DOI: 10.4240/wjgs.v16.i9.3032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Revised: 07/17/2024] [Accepted: 07/22/2024] [Indexed: 09/18/2024] Open
Abstract
BACKGROUND Through continuous improvement in transplantation medicine, a wider range of solid organ transplant (SOT) recipients is considered suitable for complex procedures. Despite advances in modern transplantation practice, transpiring invasive fungal infections pose a substantial threat for SOT recipients. To our knowledge, cryptococcal infection confined amidst sole pancreas SOT recipients has not been described to date. Enforcement of a multidisciplinary transplant team approach in the management of pancreas SOT recipients presenting with complex cryptococcal complications is fundamental in improving patient outcomes. CASE SUMMARY We present the case of a female pancreas transplant recipient, with confirmed meningeal cryptococcosis, referred to our institution for further evaluation and treatment from the Regional Center for Infectious Diseases. On admission, the patient was weaned from the protocolized immunosuppression therapy for two consecutive weeks, in addition to tapering systemic corticosteroid remedial treatment. Our novel multidisciplinary transplant team approach embodied exhaustive discussions of possible complex and diverse multiple organ system physiologic and pathologic challenges associated with distinct management strategies in pancreas transplant recipients. Owing to the potentially devastating impact of invasive cryptococcosis in terms of morbidity and mortality, a definitive surgical intervention of pancreas transplant grafectomy was reinforced, as a pathway towards secure access to early meaningful expertise care. The patient was discharged to the Regional Center for Infectious Diseases 2 mo after the admittance further advancing to a clinical improvement. CONCLUSION The precision transplantation approach by tailoring complex medical interventions to individual needs proved indispensable in improving our patient's outcomes.
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Affiliation(s)
- Ileana Lulic
- Department of Anaesthesiology, Intensive Care and Pain Medicine, Clinical Hospital Merkur, Zagreb 10000, Croatia
| | - Gorana Fingler
- Department of Anaesthesiology, Intensive Care and Pain Medicine, Clinical Hospital Merkur, Zagreb 10000, Croatia
| | - Dinka Lulic
- Immediate Medical Care Unit, Saint James Hospital, Sliema SLM-1030, Malta
| | - Jadranka Pavicic Saric
- Department of Anaesthesiology, Intensive Care and Pain Medicine, Clinical Hospital Merkur, Zagreb 10000, Croatia
| | - Danko Mikulic
- Department of Surgery, Clinical Hospital Merkur, Zagreb 10000, Croatia
| | | | - Eleonora Goluza
- Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Center Zagreb, Zagreb 10000, Croatia
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Zhao M, Tan X, Wu X. The Role of Ficolins in Lung Injury. J Innate Immun 2024; 16:440-450. [PMID: 39159606 PMCID: PMC11521482 DOI: 10.1159/000540954] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 08/14/2024] [Indexed: 08/21/2024] Open
Abstract
BACKGROUND Respiratory diseases seriously threaten human health worldwide, and lung injury is an important component of respiratory disease. Complement activation is an important function of the innate immune system. Complement activation helps the body defend against invasion by external microorganisms, whereas excessive complement activation can exacerbate tissue damage or lead to unwanted side effects. Ficolins are a class of immune-related proteins in the lectin pathway that play important roles in the body's immune defense. Although individual ficolins are not well understood, current information suggests that ficolins may play an important regulatory role in lung injury. SUMMARY Several studies have shown that ficolins are involved in the immune response in the lung, particularly in the response to infectious and inflammatory processes. KEY MESSAGES This review summarizes the role of ficolins in lung injury. Ficolins may influence the development and repair of lung injury by recognizing and binding pathogenic microorganisms, modulating the inflammatory response, and promoting the clearance of immune cells. In addition, ficolins are associated with the development and progression of lung diseases (such as pneumonia and ARDS) and may have an important impact on the pathophysiological processes of inflammatory diseases.
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Affiliation(s)
- Meiyun Zhao
- Pulmonary and Critical Care Medicine, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China
| | - Xiaowu Tan
- Pulmonary and Critical Care Medicine, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China
| | - Xu Wu
- Pulmonary and Critical Care Medicine, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China
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Miwa T, Okamoto K, Ikeuchi K, Yamamoto S, Okugawa S, Ichida A, Akamatsu N, Hasegawa K, Tsutsumi T. The Role of Frequent Screening or Diagnostic Testing of Serum Cryptococcal Antigen in Liver Transplant Recipients: A Descriptive Epidemiology. Open Forum Infect Dis 2024; 11:ofae255. [PMID: 38774792 PMCID: PMC11108085 DOI: 10.1093/ofid/ofae255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Indexed: 05/24/2024] Open
Abstract
Background Cryptococcosis is a notable infectious complication of liver transplantation. Currently, there is no recommendation for screening serum cryptococcal antigen (CrAg) levels in solid organ transplant recipients. We aimed to explore the role of serum CrAg in liver transplant recipients at an institution where posttransplant serum CrAg has been widely tested. Methods This retrospective study was conducted at a tertiary care center in Japan. All liver transplant recipients with serum CrAg measured either for screening or for diagnostic testing at least once after transplantation between April 2005 and March 2022 were included. For participants with either a positive CrAg test result or positive culture for Cryptococcus, we manually reviewed clinical manifestations, management, and prognosis from the medical records. Results During the study period, 12 885 serum CrAg tests (median, 16 tests per patient) were performed in 468 liver transplant recipients. The 1-year posttransplant incidence of positive serum CrAg test results and culture-proven cryptococcosis was 1.9% (9/468) and 0.6% (3/468), respectively. No patient with persistently negative serum CrAg test results showed growth of Cryptococcus in culture. Four patients had clinical manifestations consistent with cryptococcosis, of whom 2 (50.0%) started antifungal therapy promptly based on a positive serum CrAg test result. In contrast, 5 patients had no clinical manifestations. Three of the 5 (60.0%) patients did not receive antifungal therapy and remained free of clinical manifestations. Conclusions Serum CrAg test was more sensitive than culture among liver transplant recipients and prompted early diagnosis and antifungal therapy in symptomatic patients. However, serial screening of serum CrAg in asymptomatic patients may be of little value, with the potential for false-positive results.
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Affiliation(s)
- Toshiki Miwa
- Department of Infectious Diseases, The University of Tokyo Hospital, Tokyo, Japan
| | - Koh Okamoto
- Department of Infectious Diseases, The University of Tokyo Hospital, Tokyo, Japan
- Department of Infectious Diseases, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
| | - Kazuhiko Ikeuchi
- Department of Infectious Diseases, The University of Tokyo Hospital, Tokyo, Japan
| | - Shinya Yamamoto
- Department of Infectious Diseases, The University of Tokyo Hospital, Tokyo, Japan
| | - Shu Okugawa
- Department of Infectious Diseases, The University of Tokyo Hospital, Tokyo, Japan
| | - Akihiko Ichida
- Artificial Organ and Transplantation Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Nobuhisa Akamatsu
- Artificial Organ and Transplantation Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kiyoshi Hasegawa
- Artificial Organ and Transplantation Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Takeya Tsutsumi
- Department of Infectious Diseases, The University of Tokyo Hospital, Tokyo, Japan
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de Sena ACVP, de Arruda JAA, Oliveira SR, Pereira NM, Faria LDS, Travassos DV, Silva TA. Orofacial Cryptococcosis: A Challenging Clinical Report and a Systematic Analysis of the Literature. Int J Surg Pathol 2024; 32:165-181. [PMID: 37143300 DOI: 10.1177/10668969231169048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/06/2023]
Abstract
Cryptococcosis is a neglected fungal disease. The scarcity of studies on oral cryptococcosis is certainly due to rarity and/or underreporting of the disease, especially in Brazil. We describe an example of orofacial cryptococcosis affecting a 57-year-old man after heart transplantation, who presented with multiple erythematous ulcers and erosions distributed in the chin, nasal cavity, labial mucosa, hard palate, and buccal vestibule. Computed tomography revealed opacities and micronodules in the lungs. Histopathological features of the oral and pulmonary lesions were compatible with Cryptococcus spp. Amphotericin B and fluconazole were used for treatment during hospitalization and itraconazole for prolonged therapy after hospital discharge. The patient has been under follow up for 6 months without signs of disease. According to a review conducted in PubMed, Web of Science, Scopus, Embase, and LILACS for data analysis of oral cryptococcosis, 26 reports were described in the literature. Predilection for men was observed (85%), with a male:female ratio of 5.5:1. The mean age of the individuals was 49 ± 15.3 years. Oral cryptococcosis mostly presented as an ulcer (n = 17). The palate and tongue were the most affected sites (n = 9 for each). Amphotericin B was the primary therapy utilized in most patients. Seventeen (65%) individuals survived. Knowledge of the clinicodemographic aspects of oral cryptococcosis is important for clinicians in decision making and surveillance.
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Affiliation(s)
- Ana Carolina Velasco Pondé de Sena
- Department of Oral Surgery, Pathology and Clinical Dentistry, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - José Alcides Almeida de Arruda
- Department of Oral Surgery, Pathology and Clinical Dentistry, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Sicília Rezende Oliveira
- Department of Oral Surgery, Pathology and Clinical Dentistry, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Nickolas Mendes Pereira
- Multiprofessional Integrated Residency in Health, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Larissa Dos Santos Faria
- Multiprofessional Integrated Residency in Health, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Denise Vieira Travassos
- Multiprofessional Integrated Residency in Health, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
- Department of Social and Preventive Dentistry, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Tarcília Aparecida Silva
- Department of Oral Surgery, Pathology and Clinical Dentistry, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
- Multiprofessional Integrated Residency in Health, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
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Barros K, Tepper JW, Ramchandani J, Kelley MK, Kussin ML, Israel EN, Tompkins MG, Alali M. Unusual presentation of disseminated cryptococcal infection complicated by myocarditis in a heart transplant recipient. Pediatr Transplant 2024; 28:e14585. [PMID: 37489596 DOI: 10.1111/petr.14585] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2022] [Revised: 06/21/2023] [Accepted: 07/10/2023] [Indexed: 07/26/2023]
Abstract
BACKGROUND Cryptococcus neoformans is the third most common cause of invasive fungal infection in solid organ transplant (SOT) recipients. While cryptococcal infection can involve any organ, cases of myocarditis are exceedingly rare. METHODS A retrospective chart review was completed for this case report. RESULTS We present the case of a 21-year-old heart transplant recipient who developed disseminated cryptococcal infection with biopsy-proven cryptococcal myocarditis. CONCLUSIONS Cryptococcal disease in SOT recipients poses diagnostic and therapeutic challenges. There are no current guidelines for the duration of cryptococcal myocarditis treatment. Repeat myocardial biopsy may play a role in guiding length of therapy.
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Affiliation(s)
- Kathryn Barros
- Ryan White Center for Pediatric Infectious Diseases & Global Health, Indiana University, Indianapolis, Indiana, USA
| | - John William Tepper
- Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Juhi Ramchandani
- Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Meagan Kristine Kelley
- Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Michelle L Kussin
- Pediatric Infectious Diseases, Department of Pharmacy, Riley Hospital for Children at Indiana University Health and Ryan White Center for Pediatric Infectious Diseases & Global Health, Indiana University, Indianapolis, Indiana, USA
| | - Emily N Israel
- Purdue College of Pharmacy, West Lafayette, Indiana, USA
- Department of Pharmacy, Riley Hospital for Children at Indiana University Health, Indianapolis, Indiana, USA
| | - Madeline G Tompkins
- Pediatric Cardiology, Department of Pharmacy, Riley Hospital for Children at Indiana University Health, Indianapolis, Indiana, USA
| | - Muayad Alali
- Ryan White Center for Pediatric Infectious Diseases & Global Health, Indiana University, Indianapolis, Indiana, USA
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Guan ST, Huang YS, Huang ST, Hsiao FY, Chen YC. The incidences and clinical outcomes of cryptococcosis in Taiwan: A nationwide, population-based study, 2002-2015. Med Mycol 2024; 62:myad125. [PMID: 38126122 PMCID: PMC10802930 DOI: 10.1093/mmy/myad125] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Revised: 10/28/2023] [Accepted: 12/19/2023] [Indexed: 12/23/2023] Open
Abstract
Large-scale epidemiological data on cryptococcosis other than cryptococcal meningitis (CM), human immunodeficiency virus (HIV)- or solid organ transplantation (SOT)-associated cryptococcosis are limited. This study investigated the disease burden of cryptococcosis in Taiwan over 14 years. Incident episodes of cryptococcosis, comorbidities, treatment, and outcomes were captured from Taiwan's National Health Insurance Research Database and National Death Registry between 2002 and 2015. Of 6647 episodes analyzed, the crude incidence rate per 100 000 population increased from 1.48 in 2002 to 2.76 in 2015, which was driven by the growing trend in the non-CM group (0.86-2.12) but not in the CM group (0.62-0.64). The leading three comorbidities were diabetes mellitus (23.62%), malignancy (22.81%), and liver disease (17.42%). HIV accounted for 6.14% of all episodes and was associated with the highest disease-specific incidence rate (269/100 000 population), but the value dropped 16.20% biennially. Within 90 days prior to cohort entry, 30.22% of episodes had systemic corticosteroid use. The in-hospital mortality of all episodes was 10.80%, which varied from 32.64% for cirrhosis and 13.22% for HIV to 6.90% for SOT. CM was associated with a higher in-hospital mortality rate than non-CM (19.15% vs. 6.33%). At diagnosis, only 48.53% of CM episodes were prescribed an amphotericin-based regimen. The incidence rate of cryptococcosis was increasing, especially that other than meningitis and in the non-HIV population. A high index of clinical suspicion is paramount to promptly diagnose, treat, and improve cryptococcosis-related mortality in populations other than those with HIV infection or SOT.
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Affiliation(s)
- Shang-Ting Guan
- Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, 2F.-220, No. 33, Linsen S. Rd., Zhongzheng Dist., Taipei City 100025, Taiwan
- Health Data Research Center, National Taiwan University, Taipei City 10051, Taiwan
| | - Yu-Shan Huang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei City 100225, Taiwan
| | - Shih-Tsung Huang
- Department of Pharmacy, National Yang Ming Chiao Tung University, Taipei City 112304, Taiwan
- Center for Healthy Longevity and Aging Sciences, National Yang Ming Chiao Tung University, Taipei City 112304, Taiwan
| | - Fei-Yuan Hsiao
- Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, 2F.-220, No. 33, Linsen S. Rd., Zhongzheng Dist., Taipei City 100025, Taiwan
- School of Pharmacy, College of Medicine, National Taiwan University, Taipei City 100025, Taiwan
- Department of Pharmacy, National Taiwan University Hospital, Taipei City 100225, Taiwan
| | - Yee-Chun Chen
- Department of Internal Medicine, National Taiwan University Hospital, Taipei City 100225, Taiwan
- Department of Medicine, National Taiwan University College of Medicine, Taipei City 10051, Taiwan
- National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli County 35053, Taiwan
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Meena P, Bhargava V, Singh K, sethi J, Prabhakar A, panda S. Cryptococcosis in kidney transplant recipients: Current understanding and practices. World J Nephrol 2023; 12:120-131. [PMID: 38230297 PMCID: PMC10789088 DOI: 10.5527/wjn.v12.i5.120] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Revised: 10/15/2023] [Accepted: 11/02/2023] [Indexed: 12/22/2023] Open
Abstract
Cryptococcosis is the third most commonly occurring invasive fungal disease in solid organ transplant recipients (SOT). It is caused by encapsulated yeast, Cryptococcus species, predominantly Cryptococcus neoformans and Cryptococcus gattii. Though kidney transplant recipients are at the lowest risk of cryptococcosis when compared to other solid organ transplant recipients such as lung, liver or heart, still this opportunistic infection causes significant morbidity and mortality in this subset of patients. Mortality rates with cryptococcosis range from 10%-25%, while it can be as high as 50% in SOT recipients with central nervous system involvement. The main aim of diagnosis is to find out if there is any involvement of the central nervous system in disseminated disease or whether there is only localized pulmonary involvement as it has implications for both prognostication and treatment. Detection of cryptococcal antigen (CrAg) in cerebrospinal fluid or plasma is a highly recommended test as it is more sensitive and specific than India ink and fungal cultures. The CrAg lateral flow assay is the single point of care test that can rapidly detect cryptococcal polysaccharide capsule. Treatment of cryptococcosis is challenging in kidney transplant recipients. Apart from the reduction or optimization of immunosuppression, lipid formulations of amphotericin B are preferred as induction antifungal agents. Consolidation and maintenance are done with fluconazole; carefully monitoring its interactions with calcineurin inhibitors. This review further discusses in depth the evolving developments in the epidemiology, pathogenesis, diagnostic assays, and management approach of cryptococcosis in kidney transplant recipients.
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Affiliation(s)
- Priti Meena
- Department of Nephrology, All India Institute of Medical Sciences, Bhubaneswar 751019, Odhisha, India
| | - Vinant Bhargava
- Department of Nephrology, Sir Ganga Ram Hospital New Delhi, New Delhi 110001, New Delhi, India
| | - Kulwant Singh
- Department of Nephrology, Ivy Hospital, Mohali Punjab, Mohali 160071, Punjab, India
| | - Jasmine sethi
- Department of Nephrology, Post Graduate Institute of Medical Education & Research, Chandigarh 160012, Punjab, India
| | - Aniketh Prabhakar
- Department of Nephrology, Consultant Nephrologist, Sigma Hospital, Mysore 570009, Karnataka, India
| | - Sandip panda
- Department of Nephrology, All India Institute of Medical Sciences, Bhubaneswar 751019, Odhisha, India
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de Andrade IB, Alves V, Pereira L, Miranda B, Corrêa-Junior D, Galdino Figueiredo-Carvalho MH, Santos MV, Almeida-Paes R, Frases S. Effect of rapamycin on Cryptococcus neoformans: cellular organization, biophysics and virulence factors. Future Microbiol 2023; 18:1061-1075. [PMID: 37721517 DOI: 10.2217/fmb-2023-0097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/19/2023] Open
Abstract
Background: Cryptococcus neoformans is an opportunistic fungal pathogen that causes infections mainly in immunosuppressed individuals, such as transplant recipients. Aims: This study investigated the effects of rapamycin, an immunosuppressant drug, on the cellular organization, biophysical characteristics, and main virulence factors of C. neoformans. Methods: Morphological, structural, physicochemical and biophysical analyses of cells and secreted polysaccharides of the reference H99 C. neoformans strain were investigated under the effect of subinhibitory concentrations of rapamycin. Results: Rapamycin at a minimum inhibitory concentration of 2.5 μM reduced C. neoformans cell viability by 53%, decreased capsule, increased cell size, chitin and lipid body formation, and changed peptidase and urease activity. Conclusion: Further studies are needed to assess how rapamycin affects the virulence factors and pathogenicity of C. neoformans.
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Affiliation(s)
- Iara Bastos de Andrade
- Laboratório de Biofísica de Fungos, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Vinicius Alves
- Laboratório de Biofísica de Fungos, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Luiza Pereira
- Laboratório de Biofísica de Fungos, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Bruna Miranda
- Laboratório de Biofísica de Fungos, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Dario Corrêa-Junior
- Laboratório de Biofísica de Fungos, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | | | - Marcos Vinicius Santos
- Laboratório de Micologia, Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
| | - Rodrigo Almeida-Paes
- Laboratório de Micologia, Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
- Rede Micologia - FAPERJ, Rio de Janeiro, Brazil
| | - Susana Frases
- Laboratório de Biofísica de Fungos, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
- Rede Micologia - FAPERJ, Rio de Janeiro, Brazil
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12
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Lu YA, Lin CH, Chang CJ, Shu KH, Chung MC, Chou CC. Non-meningeal, non-pulmonary cryptococcosis with limited posterior uveitis in a kidney organ transplant recipient with antibody-mediated rejection: a case report. BMC Ophthalmol 2023; 23:409. [PMID: 37817150 PMCID: PMC10565975 DOI: 10.1186/s12886-023-03130-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Accepted: 09/11/2023] [Indexed: 10/12/2023] Open
Abstract
BACKGROUND Cryptococcosis is one of the most frequent fungal eye infections in patients with immunosuppression. Currently, treatment approaches for non-meningeal, non-pulmonary cryptococcosis are based on those used for cryptococcal meningitis or pneumonia. CASE PRESENTATION We present a rare case of non-meningeal, non-pulmonary cryptococcosis with clinical manifestations limited to one eye of a cadaveric kidney transplant recipient with chronic-active antibody-mediated rejection. Typical manifestations, diagnosis, and treatments, including antifungal therapies, adjunctive therapies, and immunosuppression reduction, are discussed. After timely diagnosis and treatment, her visual acuity recovered to baseline without recurrence or sequelae of cryptococcosis. CONCLUSIONS Clinicians should be aware of rare presentations of fungal infections, especially when a kidney transplant recipient with rejection has been treated with intensive immunosuppressants. Early diagnosis with individualized therapies may have a favorable prognosis.
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Affiliation(s)
- Yi-An Lu
- Department of Ophthalmology, Taichung Veterans General Hospital, 1650 Taiwan Boulevard Sect. 4, Taichung, 407219, Taiwan
| | - Chun-Hsien Lin
- Department of Ophthalmology, Taichung Veterans General Hospital, 1650 Taiwan Boulevard Sect. 4, Taichung, 407219, Taiwan
| | - Chia-Jen Chang
- Department of Ophthalmology, Taichung Veterans General Hospital, 1650 Taiwan Boulevard Sect. 4, Taichung, 407219, Taiwan
| | - Kuo-Hsiung Shu
- Division of Nephrology, Department of Internal Medicine, Lin Shin Hospital, No.36, Sec. 3, Huizhong Rd., Nantun District, Taichung City, 40867, Taiwan
| | - Mu-Chi Chung
- Division of Nephrology, Department of Medicine, Taichung Veterans General Hospital, 1650 Taiwan Boulevard Sect. 4, Taichung, 407219, Taiwan.
- PhD Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan.
- Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan.
- Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung, Taiwan.
| | - Chien-Chih Chou
- Department of Ophthalmology, Taichung Veterans General Hospital, 1650 Taiwan Boulevard Sect. 4, Taichung, 407219, Taiwan.
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
- College of Medicine, National Chung Hsing University, Taichung, Taiwan.
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13
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Hamed MF, Enriquez V, Munzen ME, Charles-Niño CL, Mihu MR, Khoshbouei H, Alviña K, Martinez LR. Clinical and pathological characterization of Central Nervous System cryptococcosis in an experimental mouse model of stereotaxic intracerebral infection. PLoS Negl Trop Dis 2023; 17:e0011068. [PMID: 36656900 PMCID: PMC9888703 DOI: 10.1371/journal.pntd.0011068] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Revised: 01/31/2023] [Accepted: 01/02/2023] [Indexed: 01/20/2023] Open
Abstract
Infection of the Central Nervous System (CNS) by the encapsulated fungus Cryptococcus neoformans can lead to high mortality meningitis, most commonly in immunocompromised patients. While the mechanisms by which the fungus crosses the blood-brain barrier to initiate infection in the CNS are well recognized, there are still substantial unanswered questions about the disease progression once the fungus is established in the brain. C. neoformans is characterized by a glucuronoxylomannan (GXM)-rich polysaccharide capsule which has been implicated in immune evasion, but its role during the host CNS infection needs further elucidation. Therefore, the present study aims to examine these key questions about the mechanisms underlying cryptococcal meningitis progression and the impact of fungal GXM release by using an intracerebral rodent infection model via stereotaxic surgery. After developing brain infection, we analyzed distinct brain regions and found that while fungal load and brain weight were comparable one-week post-infection, there were region-specific histopathological (with and without brain parenchyma involvement) and disease manifestations. Moreover, we also observed a region-specific correlation between GXM accumulation and glial cell recruitment. Furthermore, mortality was associated with the presence of subarachnoid hemorrhaging and GXM deposition in the meningeal blood vessels and meninges in all regions infected. Our results show that using the present infection model can facilitate clinical and neuropathological observations during the progression of neurocryptococcosis. Importantly, this mouse model can be used to further investigate disease progression as it develops in humans.
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Affiliation(s)
- Mohamed F. Hamed
- Department of Oral Biology, University of Florida College of Dentistry, Gainesville, Florida, United States of America
- Department of Pathology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt
| | - Vanessa Enriquez
- Department of Oral Biology, University of Florida College of Dentistry, Gainesville, Florida, United States of America
| | - Melissa E. Munzen
- Department of Oral Biology, University of Florida College of Dentistry, Gainesville, Florida, United States of America
| | - Claudia L. Charles-Niño
- Department of Oral Biology, University of Florida College of Dentistry, Gainesville, Florida, United States of America
- Department of Microbiology and Pathology, University Health Sciences Center, University of Guadalajara, Guadalajara, Mexico
| | - Mircea Radu Mihu
- Advanced Critical Care, Nazih Zuhdi Transplant Institute, Advanced Cardiac Care and 24/7 Shock Service, Integris Baptist Medical Center, Oklahoma City, Oklahoma, United States of America
- Department of Medicine/Cardiology, Oklahoma State University Health Science Center, Tulsa, Oklahoma, United States of America
| | - Habibeh Khoshbouei
- Department of Neuroscience, University of Florida, Gainesville, Florida, United States of America
- Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, United States of America
| | - Karina Alviña
- Department of Neuroscience, University of Florida, Gainesville, Florida, United States of America
- Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, United States of America
| | - Luis R. Martinez
- Department of Oral Biology, University of Florida College of Dentistry, Gainesville, Florida, United States of America
- Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, United States of America
- Center for Immunology and Transplantation, University of Florida, Gainesville, United States of America
- Emerging Pathogens Institute, University of Florida, Gainesville, Florida, United States of America
- * E-mail:
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14
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van der Torre MH, Andrews RA, Hooker EL, Rankin A, Dodd S. Systematic review on Cryptococcus neoformans/Cryptococcus gattii species complex infections with recommendations for practice in health and care settings. CLINICAL INFECTION IN PRACTICE 2022. [DOI: 10.1016/j.clinpr.2022.100154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022] Open
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15
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Yamamura D, Xu J. Update on Pulmonary Cryptococcosis. Mycopathologia 2021; 186:717-728. [PMID: 34181160 DOI: 10.1007/s11046-021-00575-9] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Accepted: 06/22/2021] [Indexed: 12/24/2022]
Abstract
Pulmonary cryptococcosis is a common but underdiagnosed opportunistic fungal infection in both immunocompromised and immunocompetent patients. The causal agents include at least eight evolutionary distinct haploid lineages as well as their hybrids of the human pathogenic Cryptococcus complex. In this update, we review recent advances in epidemiology, mode of transmission, risk factors, diagnostic methods, and therapy of pulmonary cryptococcosis. Our review suggests significant challenges and opportunities for research, from bedside to benchside and back to bedside.
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Affiliation(s)
- Deborah Yamamura
- Microbiology Department, Hamilton Regional Laboratory Medicine Program, Hamilton General Hospital, Hamilton, ON, L8L 2X2, Canada.,Department of Pathology and Molecular Medicine, McMaster University, Hamilton, L8S 4K1, Canada
| | - Jianping Xu
- Department of Biology, McMaster University, Hamilton, L8S 4K1, Canada.
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16
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How I perform hematopoietic stem cell transplantation on patients with a history of invasive fungal disease. Blood 2021; 136:2741-2753. [PMID: 33301030 DOI: 10.1182/blood.2020005884] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Accepted: 08/13/2020] [Indexed: 02/08/2023] Open
Abstract
Hematopoietic transplantation is the preferred treatment for many patients with hematologic malignancies. Some patients may develop invasive fungal diseases (IFDs) during initial chemotherapy, which need to be considered when assessing patients for transplantation and treatment posttransplantation. Given the associated high risk of relapse and mortality in the post-hematopoietic stem cell transplantation (HSCT) period, IFDs, especially invasive mold diseases, were historically considered a contraindication for HSCT. Over the last 3 decades, advances in antifungal drugs and early diagnosis have improved IFD outcomes, and HSCT in patients with a recent IFD has become increasingly common. However, an organized approach for performing transplantation in patients with a prior IFD is scarce, and decisions are highly individualized. Patient-, malignancy-, transplantation procedure-, antifungal treatment-, and fungus-specific issues affect the risk of IFD relapse. Effective surveillance to detect IFD relapse post-HSCT and careful drug selection for antifungal prophylaxis are of paramount importance. Antifungal drugs have their own toxicities and interact with immunosuppressive drugs such as calcineurin inhibitors. Immune adjunct cytokine or cellular therapy and surgery can be considered in selected cases. In this review, we critically evaluate these factors and provide guidance for the complex decision making involved in the peri-HSCT management of these patients.
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17
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Liu M, Sun LY, Zhu ZJ, Wei L, Qu W, Zeng ZG, Liu Y. Successful Treatment of Pulmonary Cryptococcosis in a Liver Transplant Recipient Before and After Liver Transplant: Case Report and Literature Review. EXP CLIN TRANSPLANT 2021; 19:264-268. [PMID: 33535937 DOI: 10.6002/ect.2020.0222] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Cryptococcosis is the third most common invasive fungal infection in solid-organ transplant recipients. Patients with cirrhosis are susceptible to pretransplant cryptococcosis infections. Outcomes and optimal treatment of patients with cirrhosis who develop pulmonary cryptococcosis before and after liver transplant are still not defined. Here, we describe a case of cholestatic cirrhosis in a 50-year-old woman with a pretransplant asymptomatic pulmonary nodule. She had taken steroids for more than 1 year before she was admitted to our hospital. This asymptomatic case with a lung nodule was detected via an abnormal chest computed tomography. Cryptococcal pneumonia was diagnosed according to lung biopsy results. Testing for cryptococcal antigens was negative in the serum. The patient received antifungal therapy with amphotericin B followed by oral fluconazole, which was then followed by liver transplant. After antifungal therapy with fluconazole posttransplant, a sustained clinical response was achieved. After literature review of patients with pulmonary cryptococcosis before and after liver transplant, we identified previously reported cases with pulmonary cryptococcosis that resembled lung nodule on imaging. In this report, we aimed to raise the awareness of unrecognized pretransplant cryptococ-cosis infections in patients with cirrhosis who are waiting for liver transplant and showed the successful management of a patient with pretransplant pulmonary cryptococcosis.
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Affiliation(s)
- Min Liu
- From the National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China
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18
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Nematollahi S, Dioverti-Prono V. Cryptococcal infection in haematologic malignancies and haematopoietic stem cell transplantation. Mycoses 2020; 63:1033-1046. [PMID: 32740974 DOI: 10.1111/myc.13153] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Revised: 07/22/2020] [Accepted: 07/23/2020] [Indexed: 12/18/2022]
Abstract
This review summarises both the recent and relevant studies about cryptococcal infections in haematologic malignancies and haematopoietic stem cell transplantation. Although uncommon in this patient population, this infection carries a high mortality, especially if left untreated. Given the limited data, we draw some conclusions with respect to management from the solid organ transplantation and HIV-infected literature. Herein, we discuss cryptococcosis with a particular attention to its background, epidemiology, risk factors, clinical presentation, diagnosis, treatment and prevention in this group.
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Affiliation(s)
- Saman Nematollahi
- Department of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Veronica Dioverti-Prono
- Department of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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19
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Cryptococcosis in Hematopoietic Stem Cell Transplant Recipients: A Rare Presentation Warranting Recognition. CANADIAN JOURNAL OF INFECTIOUS DISEASES & MEDICAL MICROBIOLOGY 2020; 2020:3713241. [PMID: 33144899 PMCID: PMC7599392 DOI: 10.1155/2020/3713241] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 07/06/2020] [Accepted: 07/15/2020] [Indexed: 12/18/2022]
Abstract
Cryptococcosis, a life-threatening mycosis caused mainly by Cryptococcus neoformans, appears to be distinctly rare in hematopoietic stem cell transplant (HSCT) recipients. When it occurs, this fungal infection is a major limitation for a successful transplant. This review comprehensively analyses 24 cases, reported in the literature, of patients with haematological malignancies including leukemias, multiple myeloma, and lymphomas, as indication for HSCT, who presented with cryptococcosis after transplantation. Of the 24 cases, 11 each occurred in patients receiving allogeneic and autologous stem cell transplants, from bone marrow, peripheral blood, and umbilical cord blood. HSCT recipients were slightly more often male, and the age of the patients ranged from 12 to 74 years. Antifungal prophylaxis was reported in most cases. Clinical manifestations of cryptococcal disease included more frequently central nervous system involvement followed by fungaemia, disseminated infection, pulmonary cryptococcosis, cerebellitis, and diarrhea. Diagnosis differed depending on the clinical presentation but habitually included cryptococcal antigen assay, India ink, and culture. Notably, not only C. neoformans but also C. albidus, C. terreus, C. laurentii, and C. adeliensis were identified as the causal species, the last two including strains resistant to fluconazole. Amphotericin B, alone or in combination, was the most common antifungal drug used for the treatment of cryptococcosis in HSCT recipients. Due to the small number of cases, it was not possible to establish if mortality rate, which was the same as survival rate, depends on the effect of the immunosuppressive regimen, the site of cryptococcal infection, and/or the antifungal therapy used to control the mycosis. Although uncommon, the recognition of cryptococcal disease in stem cell transplant is essential for a timely and adequate treatment, improved prognosis, reduced morbidity and mortality, and successful transplantation.
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20
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Singh N. Unique Rarity of Tuberculosis and Granulomatous Opportunistic Infections in Hematopoietic Cell Transplant Recipients. Clin Infect Dis 2020; 71:470-471. [PMID: 31584635 DOI: 10.1093/cid/ciz979] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Affiliation(s)
- Nina Singh
- Infectious Diseases Section, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
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21
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Pilmis B, Bougnoux M, Guery R, Senghor Y, Le Monnier A, Lanternier F, Bretagne S, Alanio A, Lortholary O. Failure of multiplex meningitis/encephalitis (ME) NAT during cryptococcal meningitis in solid organ recipients. Transpl Infect Dis 2020; 22:e13263. [DOI: 10.1111/tid.13263] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Revised: 01/23/2020] [Accepted: 02/02/2020] [Indexed: 01/29/2023]
Affiliation(s)
- Benoit Pilmis
- Service de Maladies Infectieuses et Tropicales Centre d'Infectiologie Necker‐Pasteur Hôpital Necker‐Enfants Malades Assistance Publique des Hôpitaux de Paris (AP‐HP) Université de Paris Paris France
- Equipe Mobile de Microbiologie Clinique Groupe Hospitalier Paris Saint‐Joseph Paris France
- EA4043 Unité Bactéries Pathogènes et Santé Université Paris‐Sud Saclay Chatenay‐Malabry France
| | - Marie‐Elizabeth Bougnoux
- Unité de Parasitologie Mycologie Hôpital Necker‐Enfants Malades Université de Paris Paris France
| | - Romain Guery
- Service de Maladies Infectieuses et Tropicales Centre d'Infectiologie Necker‐Pasteur Hôpital Necker‐Enfants Malades Assistance Publique des Hôpitaux de Paris (AP‐HP) Université de Paris Paris France
| | - Yaye Senghor
- Service de Microbiologie Clinique Groupe Hospitalier Paris Saint‐Joseph Paris France
| | - Alban Le Monnier
- Service de Microbiologie Clinique Groupe Hospitalier Paris Saint‐Joseph Paris France
| | - Fanny Lanternier
- Service de Maladies Infectieuses et Tropicales Centre d'Infectiologie Necker‐Pasteur Hôpital Necker‐Enfants Malades Assistance Publique des Hôpitaux de Paris (AP‐HP) Université de Paris Paris France
- Institut Pasteur Unité de Mycologie moléculaire Centre national de référence des mycoses invasives et antifongiques CNRS UMR2000 Paris France
| | - Stephane Bretagne
- Institut Pasteur Unité de Mycologie moléculaire Centre national de référence des mycoses invasives et antifongiques CNRS UMR2000 Paris France
- Laboratoire de Parasitologie‐Mycologie Hôpital Saint‐Louis Groupe Hospitalier Lariboisière, Saint‐Louis, Fernand Widal Assistance Publique des Hôpitaux de Paris (AP‐HP) Université Partis Diderot Sorbonne Paris Cité Paris France
- Université de Paris Paris France
| | - Alexandre Alanio
- Institut Pasteur Unité de Mycologie moléculaire Centre national de référence des mycoses invasives et antifongiques CNRS UMR2000 Paris France
- Laboratoire de Parasitologie‐Mycologie Hôpital Saint‐Louis Groupe Hospitalier Lariboisière, Saint‐Louis, Fernand Widal Assistance Publique des Hôpitaux de Paris (AP‐HP) Université Partis Diderot Sorbonne Paris Cité Paris France
| | - Olivier Lortholary
- Service de Maladies Infectieuses et Tropicales Centre d'Infectiologie Necker‐Pasteur Hôpital Necker‐Enfants Malades Assistance Publique des Hôpitaux de Paris (AP‐HP) Université de Paris Paris France
- Institut Pasteur Unité de Mycologie moléculaire Centre national de référence des mycoses invasives et antifongiques CNRS UMR2000 Paris France
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22
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Villalobos APC, Husain S. Infection prophylaxis and management of fungal infections in lung transplant. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:414. [PMID: 32355858 PMCID: PMC7186682 DOI: 10.21037/atm.2020.03.102] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Lung transplantation has emerged as a lifesaving treatment for a wide range of advanced lung diseases. While the survival of lung transplant recipients continues to improve, infectious complications contribute substantially to morbidity and mortality following lung transplantation. The incidence of invasive fungal infections is variable, with a mean occurrence of 8.6%. The majority of fungal infections in lung transplant recipients are caused Aspergillus and Candida species. This review provides an update in the current approaches for the diagnosis, management and prevention of fungal infections and the late complications that are associated.
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Affiliation(s)
| | - Shahid Husain
- Multi-Organ Transplant Unit, Division of Infectious Diseases, University Health Network, Toronto, ON, Canada
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23
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Azoulay E, Russell L, Van de Louw A, Metaxa V, Bauer P, Povoa P, Montero JG, Loeches IM, Mehta S, Puxty K, Schellongowski P, Rello J, Mokart D, Lemiale V, Mirouse A. Diagnosis of severe respiratory infections in immunocompromised patients. Intensive Care Med 2020; 46:298-314. [PMID: 32034433 PMCID: PMC7080052 DOI: 10.1007/s00134-019-05906-5] [Citation(s) in RCA: 139] [Impact Index Per Article: 27.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2019] [Accepted: 12/19/2019] [Indexed: 12/23/2022]
Abstract
An increasing number of critically ill patients are immunocompromised. Acute hypoxemic respiratory failure (ARF), chiefly due to pulmonary infection, is the leading reason for ICU admission. Identifying the cause of ARF increases the chances of survival, but may be extremely challenging, as the underlying disease, treatments, and infection combine to create complex clinical pictures. In addition, there may be more than one infectious agent, and the pulmonary manifestations may be related to both infectious and non-infectious insults. Clinically or microbiologically documented bacterial pneumonia accounts for one-third of cases of ARF in immunocompromised patients. Early antibiotic therapy is recommended but decreases the chances of identifying the causative organism(s) to about 50%. Viruses are the second most common cause of severe respiratory infections. Positive tests for a virus in respiratory samples do not necessarily indicate a role for the virus in the current acute illness. Invasive fungal infections (Aspergillus, Mucorales, and Pneumocystis jirovecii) account for about 15% of severe respiratory infections, whereas parasites rarely cause severe acute infections in immunocompromised patients. This review focuses on the diagnosis of severe respiratory infections in immunocompromised patients. Special attention is given to newly validated diagnostic tests designed to be used on non-invasive samples or bronchoalveolar lavage fluid and capable of increasing the likelihood of an early etiological diagnosis.
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Affiliation(s)
- Elie Azoulay
- Médecine Intensive et Réanimation, APHP, Saint-Louis Hospital and Paris University, Paris, France.
- Université de Paris, Paris, France.
| | - Lene Russell
- Department of Intensive Care, Rigshospitalet and Copenhagen Academy for Medical Simulation and Education, University of Copenhagen, Copenhagen, Denmark
| | - Andry Van de Louw
- Division of Pulmonary and Critical Care, Penn State University College of Medicine, Hershey, PA, USA
| | - Victoria Metaxa
- Department of Critical Care, King's College Hospital NHS Foundation Trust, London, UK
| | - Philippe Bauer
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA
| | - Pedro Povoa
- Polyvalent Intensive Care Unit, Hospital de São Francisco Xavier, NOVA Medical School, New University of Lisbon, Lisbon, Portugal
| | - José Garnacho Montero
- Intensive Care Clinical Unit, Hospital Universitario Virgen Macarena, Seville, Spain
| | - Ignacio Martin Loeches
- Department of Intensive Care Medicine, Multidisciplinary Intensive Care Research Organization (MICRO), St. James's Hospital, St James Street, Dublin 8, Ireland
| | - Sangeeta Mehta
- Department of Medicine and Interdepartmental Division of Critical Care Medicine, Sinai Health System, University of Toronto, Toronto, ON, Canada
| | - Kathryn Puxty
- Department of Intensive Care, Glasgow Royal Infirmary, Glasgow, UK
| | - Peter Schellongowski
- Department of Medicine I, Intensive Care Unit 13i2, Comprehensive Cancer Center, Center of Excellence in Medical Intensive Care (CEMIC), Medical University of Vienna, Vienna, Austria
| | - Jordi Rello
- Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto Salud Carlos III, Madrid, Spain
- CRIPS Department, Vall d'Hebron Institut of Research (VHIR), Barcelona, Spain
| | - Djamel Mokart
- Critical Care Department, Institut Paoli Calmettes, Marseille, France
| | - Virginie Lemiale
- Médecine Intensive et Réanimation, APHP, Saint-Louis Hospital and Paris University, Paris, France
| | - Adrien Mirouse
- Médecine Intensive et Réanimation, APHP, Saint-Louis Hospital and Paris University, Paris, France
- Université de Paris, Paris, France
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24
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Cryptococcal Immune Reconstitution Inflammatory Syndrome: a Paradoxical Response to a Complex Organism. CURRENT TREATMENT OPTIONS IN INFECTIOUS DISEASES 2020. [DOI: 10.1007/s40506-020-00210-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
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25
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Marinelli T, Anagnostou N, Daniel S, Wigg AJ, Teh J. Very early-onset of Cryptococcus neoformans disease following liver transplantation: Report of two cases and a review of the literature. Transpl Infect Dis 2019; 22:e13227. [PMID: 31785187 DOI: 10.1111/tid.13227] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2019] [Revised: 11/10/2019] [Accepted: 11/24/2019] [Indexed: 01/14/2023]
Abstract
Cryptococcosis is the third most common invasive fungal infection following solid organ transplantation, and mortality is high. Most cases occur late and are due to reactivation of latent infection; however, very early reactivation and donor-derived transmission can occur. Routine screening pre-transplant and antifungal prophylaxis for cryptococcosis post-transplant in solid organ transplantation are not standard practice. We present two cases of very early-onset Cryptococcus neoformans disease following liver transplantation to highlight the need to consider individualized pre-transplant screening and be aware that reactivation of Cryptococcosis neoformans can occur in the immediate post-transplant period.
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Affiliation(s)
- Tina Marinelli
- Department of Infectious Diseases, Flinders Medical Centre, Bedford Park, South Australia, Australia
| | - Nicholas Anagnostou
- Department of Infectious Diseases, Flinders Medical Centre, Bedford Park, South Australia, Australia
| | - Santhosh Daniel
- Department of Infectious Diseases, Flinders Medical Centre, Bedford Park, South Australia, Australia.,College of Medicine and Public Health, Flinders University, Bedford Park, South Australia, Australia
| | - Alan J Wigg
- College of Medicine and Public Health, Flinders University, Bedford Park, South Australia, Australia.,Hepatology and Transplantation Unit, Flinders Medical Centre, Bedford Park, South Australia, Australia
| | - Joanne Teh
- Department of Infectious Diseases, Flinders Medical Centre, Bedford Park, South Australia, Australia
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Cryptococcosis in Patients following Kidney Transplantation: A 9-Year Retrospective Clinical Analysis at a Chinese Tertiary Hospital. BIOMED RESEARCH INTERNATIONAL 2019; 2019:7165160. [PMID: 31828122 PMCID: PMC6885150 DOI: 10.1155/2019/7165160] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Revised: 09/14/2019] [Accepted: 10/24/2019] [Indexed: 12/27/2022]
Abstract
Background Cryptococcosis following kidney transplantation (KT) is rare but is associated with considerably increased risk of mortality. At present, data on the association between cryptococcosis and KT in mainland China remain relatively limited. Objectives This study aims to review our experience related to the management of cryptococcosis following KT at a Chinese tertiary hospital. Methods All patients with cryptococcosis following KT admitted to our hospital from January 2010 to December 2018 were reviewed. Results A total of 37 patients with cryptococcosis were enrolled (males: 62.2%). The mean age of the patients was 49.5 ± 9.38 (20-64) years. The average time to infection following KT was 7.0 ± 5.50 years (5 months to 21 years), and 30 patients (81.1%) had cryptococcosis onset >2 years following transplantation. The most common site of infection was the central nervous system, followed by the pulmonary system and skin. Most patients received fluconazole or voriconazole with or without flucytosine as their initial treatment regimen at our hospital. The 2-week mortality rate was 8.1% (3/37), and five patients (13.5%) died within 6 months of being diagnosed with cryptococcosis. Remarkably, all patients who received high-dose fluconazole (800 mg daily) or voriconazole ± flucytosine survived. Conclusions Cryptococcosis in kidney transplant recipients is typically a late-occurring infection, with most patients having cryptococcosis onset >2 years following KT at our hospital. The central nervous system, pulmonary system, and skin are the main sites of infection. Voriconazole or high-dose fluconazole can be used as an alternative therapy for post-KT cryptococcosis.
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Setianingrum F, Rautemaa-Richardson R, Denning DW. Pulmonary cryptococcosis: A review of pathobiology and clinical aspects. Med Mycol 2019; 57:133-150. [PMID: 30329097 DOI: 10.1093/mmy/myy086] [Citation(s) in RCA: 150] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2018] [Accepted: 09/05/2018] [Indexed: 01/13/2023] Open
Abstract
Pulmonary cryptococcosis is an important opportunistic invasive mycosis in immunocompromised patients, but it is also increasingly seen in immunocompetent patients. The main human pathogens are Cryptococcus neoformans and C. gattii, which have a worldwide distribution. In contrast to cryptococcal meningitis, pulmonary cryptococcosis is still underdiagnosed because of limitations in diagnostic tools. It can mimic lung cancer, pulmonary tuberculosis, bacterial pneumonia, and other pulmonary mycoses both clinically and radiologically. Pulmonary nodules are the most common radiological feature, but these are not specific to pulmonary cryptococcosis. The sensitivity of culture of respiratory samples for Cryptococcus is poor and a positive result may also reflect colonisation. Cryptococcal antigen (CrAg) with lateral flow device is a fast and sensitive test and widely used on serum and cerebrospinal fluid, but sera from patients with pulmonary cryptococcosis are rarely positive in the absence of disseminated disease. Detection of CrAg from respiratory specimens might assist the diagnosis of pulmonary cryptococcosis but there are very few data. Molecular detection techniques such as multiplex reverse transcription polymerase chain reaction (RT-PCR) could also provide better sensitivity but these still require validation for respiratory specimens. The first line of treatment for pulmonary cryptococcosis is fluconazole, or amphotericin B and flucytosine for those with central nervous system involvement. Pulmonary cryptococcosis worsens the prognosis of cryptococcal meningitis. In this review, we summarize the biological aspects of Cryptococcus and provide an update on the diagnosis and management of pulmonary cryptococcosis.
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Affiliation(s)
- Findra Setianingrum
- Division of Infection, Immunity and Respiratory Medicine, Faculty of Biology, Medicine and Health, University of Manchester, UK
- Parasitology Department, Universitas Indonesia, Jakarta, Indonesia
| | - Riina Rautemaa-Richardson
- Division of Infection, Immunity and Respiratory Medicine, Faculty of Biology, Medicine and Health, University of Manchester, UK
- Mycology Reference Centre Manchester, ECMM Centre of Excellence in Clinical and Laboratory Mycology and Clinical Studies, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK
- Department of Infectious Diseases, Wythenshawe Hospital Manchester University NHS Foundation Trust, Manchester, UK
| | - David W Denning
- Division of Infection, Immunity and Respiratory Medicine, Faculty of Biology, Medicine and Health, University of Manchester, UK
- Department of Infectious Diseases, Wythenshawe Hospital Manchester University NHS Foundation Trust, Manchester, UK
- National Aspergillosis Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK
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28
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Chen YT, Lee WS, Tsai CA, Fan WC, Wu PF, Wang FD. Incidence of and risk factors for cryptococcosis in kidney transplant recipients in Taiwan-A nationwide population-based study. Int J Infect Dis 2019; 88:154-158. [PMID: 31449926 DOI: 10.1016/j.ijid.2019.08.021] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2019] [Revised: 08/17/2019] [Accepted: 08/19/2019] [Indexed: 11/28/2022] Open
Abstract
OBJECTIVES The aim of this study was to determine the long-term incidence of cryptococcosis in kidney transplant recipients (KTRs) and to analyze its risk factors. METHODS This retrospective population-based cohort study analyzed data obtained from Taiwan's National Health Insurance Research Database for KTRs during 2000-2012 and matched cohorts. Both populations were followed until death, development of cryptococcosis, or December 2013. RESULTS A total of 4,933 KTRs and 49,930 matched patients were included. The cryptococcosis incidence rates for the KTR cohort and matched cohort were 10.59 and 0.4 per 10,000 person-years, respectively. The hazard ratio for cryptococcosis among KTRs was 26.65 (p<0.001); and 43.77 (p<0.001) for cryptococcosis affecting the central nervous system (CNS). The Kaplan-Meier method confirmed an elevated cumulative incidence of cryptococcosis among KTRs (1.00% vs. 0.04%). Predictors for cryptococcosis were advanced age (OR 1.39, 95% CI 1.02-1.89, P=0.038) and cancer (OR 2.63, 95% CI 1.22-5.67, P=0.013), but not the use of any particular class of immunosuppressants. CONCLUSIONS KTRs are at dramatically higher risk of developing cryptococcosis, especially with CNS involvement, relative to a non-KTR matched cohort. Older KTRs and those with cancer are at even higher risk of developing cryptococcosis.
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Affiliation(s)
- Yung-Tai Chen
- Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Nephrology, Taipei City Hospital, Heping Fuyou Branch, Taipei, Taiwan
| | - Wen-Sen Lee
- Division of Infectious Disease, Department of Internal Medicine, Wan Fang Medical Center, Taipei Medical University, Taipei, Taiwan; Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Che-An Tsai
- Division of Infectious Disease, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Wen-Chien Fan
- Divisionof Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Ping-Feng Wu
- Divisionof Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Fu-Der Wang
- Divisionof Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan.
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Beardsley J, Sorrell TC, Chen SCA. Central Nervous System Cryptococcal Infections in Non-HIV Infected Patients. J Fungi (Basel) 2019; 5:jof5030071. [PMID: 31382367 PMCID: PMC6787755 DOI: 10.3390/jof5030071] [Citation(s) in RCA: 67] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2019] [Revised: 07/22/2019] [Accepted: 07/29/2019] [Indexed: 12/27/2022] Open
Abstract
Central nervous system (CNS) cryptococcosis in non-HIV infected patients affects solid organ transplant (SOT) recipients, patients with malignancy, rheumatic disorders, other immunosuppressive conditions and immunocompetent hosts. More recently described risks include the use of newer biologicals and recreational intravenous drug use. Disease is caused by Cryptococcus neoformans and Cryptococcus gattii species complex; C. gattii is endemic in several geographic regions and has caused outbreaks in North America. Major virulence determinants are the polysaccharide capsule, melanin and several ‘invasins’. Cryptococcal plb1, laccase and urease are essential for dissemination from lung to CNS and crossing the blood–brain barrier. Meningo-encephalitis is common but intracerebral infection or hydrocephalus also occur, and are relatively frequent in C. gattii infection. Complications include neurologic deficits, raised intracranial pressure (ICP) and disseminated disease. Diagnosis relies on culture, phenotypic identification methods, and cryptococcal antigen detection. Molecular methods can assist. Preferred induction antifungal therapy is a lipid amphotericin B formulation (amphotericin B deoxycholate may be used in non-transplant patients) plus 5-flucytosine for 2–6 weeks depending on host type followed by consolidation/maintenance therapy with fluconazole for 12 months or longer. Control of raised ICP is essential. Clinicians should be vigilant for immune reconstitution inflammatory syndrome.
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Affiliation(s)
- Justin Beardsley
- Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Sydney 2145, Australia
| | - Tania C Sorrell
- Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Sydney 2145, Australia
- Westmead Institute for Medical Research, Westmead, Sydney 2145, Australia
| | - Sharon C-A Chen
- Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, NSW Health Pathology, Westmead Hospital and the Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Sydney 2145, Australia.
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30
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Ponzio V, Chen Y, Rodrigues AM, Tenor JL, Toffaletti DL, Medina-Pestana JO, Colombo AL, Perfect JR. Genotypic diversity and clinical outcome of cryptococcosis in renal transplant recipients in Brazil. Emerg Microbes Infect 2019; 8:119-129. [PMID: 30866766 PMCID: PMC6455115 DOI: 10.1080/22221751.2018.1562849] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Genotypic diversity and fluconazole susceptibility of 82 Cryptococcus neoformans and Cryptococcus gattii isolates from 60 renal transplant recipients in Brazil were characterized. Clinical characteristics of the patients and prognostic factors were analysed. Seventy-two (87.8%) isolates were C. neoformans and 10 (12.2%) were C. gattii. VNI was the most common molecular type (40 cases; 66.7%), followed by VNII (9 cases; 15%), VGII (6 cases; 10%), VNB (4 cases; 6.7%) and VNI/II (1 case; 1.7%). The isolates showed a high genetic diversity in the haplotype network and six new sequence types were described, most of them for VNB. There was a bias towards skin involvement in the non-VNI population (P = .012). VGII isolates exhibited higher fluconazole minimum inhibitory concentrations compared to C. neoformans isolates (P = 0.008). The 30-day mortality rate was 38.3%, and it was significantly associated with fungemia and absence of headache. Patients infected with VGII had a high mortality rate at 90 days (66.7%). A variety of molecular types produce disease in renal transplant recipients in Brazil and highlighted by VGII and VNB. We report the clinical appearance and impact of the molecular type, fluconazole susceptibility of the isolates, and clinical characteristics on patient outcome in this population.
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Affiliation(s)
- Vinicius Ponzio
- a Department of Medicine, Division of Infectious Diseases, Escola Paulista de Medicina , Universidade Federal de São Paulo (UNIFESP) , São Paulo , Brazil
| | - Yuan Chen
- b Division of Infectious Disease, Department of Medicine , Duke University School of Medicine , Durham , NC , USA
| | - Anderson Messias Rodrigues
- c Laboratory of Emerging Fungal Pathogens, Department of Microbiology, Immunology and Parasitology , Universidade Federal de São Paulo (UNIFESP) , São Paulo , Brazil
| | - Jennifer L Tenor
- b Division of Infectious Disease, Department of Medicine , Duke University School of Medicine , Durham , NC , USA
| | - Dena L Toffaletti
- b Division of Infectious Disease, Department of Medicine , Duke University School of Medicine , Durham , NC , USA
| | - José Osmar Medina-Pestana
- d Hospital do Rim Oswaldo Ramos Foundation, Discipline of Nephrology , Universidade Federal de São Paulo (UNIFESP) , São Paulo , Brazil
| | - Arnaldo Lopes Colombo
- a Department of Medicine, Division of Infectious Diseases, Escola Paulista de Medicina , Universidade Federal de São Paulo (UNIFESP) , São Paulo , Brazil
| | - John R Perfect
- b Division of Infectious Disease, Department of Medicine , Duke University School of Medicine , Durham , NC , USA
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31
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Baddley JW, Forrest GN. Cryptococcosis in solid organ transplantation-Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant 2019; 33:e13543. [PMID: 30900315 DOI: 10.1111/ctr.13543] [Citation(s) in RCA: 82] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2019] [Revised: 02/15/2019] [Accepted: 03/15/2019] [Indexed: 02/06/2023]
Abstract
These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of cryptococcosis in the pre- and post-transplant period. The current update now includes a discussion of cryptococcosis, which is the third most common invasive fungal infection in SOT recipients. Infection often occurs a year after transplantation; however, early infections occur and donor-derived infections have been described within 3 months after transplant. There are two main species that cause infection, Cryptococcus neoformans and C gattii. Clinical onset may be insidious, but headaches, fevers, and mental status changes should warrant diagnostic testing. The lateral flow cryptococcal antigen assay is now the preferred test from serum and cerebrospinal fluid due to its rapidity, accuracy, and cost. A lumbar puncture with measurement of opening pressure is recommended for patients with suspected or proven cryptococcosis. Lipid amphotericin B plus 5-flucytosine is used as initial treatment of meningitis, disseminated infection, and moderate-to-severe pulmonary infection, followed by fluconazole as consolidation therapy. Fluconazole is effective for mild-to-moderate pulmonary infection. Immunosuppression reduction as part of management may lead to immune reconstitution syndrome that may resemble active disease.
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Affiliation(s)
- John W Baddley
- University of Alabama at Birmingham and Birmingham VA Medical Center, Birmingham, Alabama
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32
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Isolated Pulmonary Cryptococcosis Confused with Lung Tumor 5 Years After Kidney Transplantation: A Case Report. Transplant Proc 2019; 51:561-564. [DOI: 10.1016/j.transproceed.2018.12.007] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2018] [Accepted: 12/09/2018] [Indexed: 12/12/2022]
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33
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Díaz-Ramírez GS, Martínez-Casas OY, Marín-Zuluaga JI, Muñoz-Maya O, Santos-Sánchez Ó, Ramírez IC, Restrepo-Gutiérrez JC. Disseminated Cryptococcosis After Liver Transplant: A Case Report. EXP CLIN TRANSPLANT 2019; 18:402-406. [PMID: 30696395 DOI: 10.6002/ect.2018.0051] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Cryptococcosis is an opportunistic infection caused by the Basidiomycota Cryptococcus neoformans (Cryptococcus gattii), which affects immunosuppressed patients and less frequently immunocompetent patients. Solid-organ transplant recipients are a particularly high-risk group, depending on the net state of immunosuppression. In these patients, the infection usually appears after the first year after transplant, although it may occur earlier in liver transplant recipients. In most cases, the infection is secondary to the reactivation of a latent infection, although it may be due to an unidentified pretransplant infection by primary infection. Less frequently, it may be transmitted by the graft. The lung and central nervous system are most frequently involved. Extrapulmonary involvement is seen in 75% of the cases, and disseminated disease occurs in 61%, with mortality ranging from 17% to 50% when the central nervous system is involved. Here, we report a case of disseminated cryptococcosis (lymphadenitis, meningitis, pulmonary nodules, and possibly sacroiliitis) in a patient after liver transplant, with good clinical and microbiological outcomes and without relapse.
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34
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White SL, Rawlinson W, Boan P, Sheppeard V, Wong G, Waller K, Opdam H, Kaldor J, Fink M, Verran D, Webster A, Wyburn K, Grayson L, Glanville A, Cross N, Irish A, Coates T, Griffin A, Snell G, Alexander SI, Campbell S, Chadban S, Macdonald P, Manley P, Mehakovic E, Ramachandran V, Mitchell A, Ison M. Infectious Disease Transmission in Solid Organ Transplantation: Donor Evaluation, Recipient Risk, and Outcomes of Transmission. Transplant Direct 2019; 5:e416. [PMID: 30656214 PMCID: PMC6324914 DOI: 10.1097/txd.0000000000000852] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2018] [Accepted: 08/15/2018] [Indexed: 12/11/2022] Open
Abstract
In 2016, the Transplantation Society of Australia and New Zealand, with the support of the Australian Government Organ and Tissue authority, commissioned a literature review on the topic of infectious disease transmission from deceased donors to recipients of solid organ transplants. The purpose of this review was to synthesize evidence on transmission risks, diagnostic test characteristics, and recipient management to inform best-practice clinical guidelines. The final review, presented as a special supplement in Transplantation Direct, collates case reports of transmission events and other peer-reviewed literature, and summarizes current (as of June 2017) international guidelines on donor screening and recipient management. Of particular interest at the time of writing was how to maximize utilization of donors at increased risk for transmission of human immunodeficiency virus, hepatitis C virus, and hepatitis B virus, given the recent developments, including the availability of direct-acting antivirals for hepatitis C virus and improvements in donor screening technologies. The review also covers emerging risks associated with recent epidemics (eg, Zika virus) and the risk of transmission of nonendemic pathogens related to donor travel history or country of origin. Lastly, the implications for recipient consent of expanded utilization of donors at increased risk of blood-borne viral disease transmission are considered.
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Affiliation(s)
- Sarah L White
- Central Clinical School, Sydney Medical School, The University of Sydney, Sydney, Australia
| | - William Rawlinson
- Serology and Virology Division, NSW Health Pathology Prince of Wales Hospital, Sydney, Australia
- Women's and Children's Health and Biotechnology and Biomolecular Sciences, University of New South Wales Schools of Medicine, Sydney, Australia
| | - Peter Boan
- Departments of Infectious Diseases and Microbiology, Fiona Stanley Hospital, Perth, Australia
- PathWest Laboratory Medicine, Perth, Australia
| | - Vicky Sheppeard
- Communicable Diseases Network Australia, New South Wales Health, Sydney, Australia
| | - Germaine Wong
- Centre for Transplant and Renal Research, Westmead Hospital, Sydney, Australia
- Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, Australia
- Sydney School of Public Health, The University of Sydney, Sydney, Australia
| | - Karen Waller
- Central Clinical School, Sydney Medical School, The University of Sydney, Sydney, Australia
| | - Helen Opdam
- Austin Health, Melbourne, Australia
- The Organ and Tissue Authority, Australian Government, Canberra, Australia
| | - John Kaldor
- Kirby Institute, University of New South Wales, Sydney, Australia
| | - Michael Fink
- Austin Health, Melbourne, Australia
- Department of Surgery, Melbourne Medical School, The University of Melbourne, Melbourne, Australia
| | - Deborah Verran
- Transplantation Services, Royal Prince Alfred Hospital, Sydney, Australia
| | - Angela Webster
- Centre for Transplant and Renal Research, Westmead Hospital, Sydney, Australia
- Sydney School of Public Health, The University of Sydney, Sydney, Australia
| | - Kate Wyburn
- Central Clinical School, Sydney Medical School, The University of Sydney, Sydney, Australia
- Renal Medicine, Royal Prince Alfred Hospital, Sydney, Australia
| | - Lindsay Grayson
- Austin Health, Melbourne, Australia
- Department of Surgery, Melbourne Medical School, The University of Melbourne, Melbourne, Australia
| | - Allan Glanville
- Department of Thoracic Medicine and Lung Transplantation, St Vincent's Hospital, Sydney, Australia
| | - Nick Cross
- Department of Nephrology, Canterbury District Health Board, Christchurch Hospital, Christchurch, New Zealand
| | - Ashley Irish
- Department of Nephrology, Fiona Stanley Hospital, Perth, Australia
- Faculty of Health and Medical Sciences, UWA Medical School, The University of Western Australia, Crawley, Australia
| | - Toby Coates
- Renal and Transplantation, Royal Adelaide Hospital, Adelaide, Australia
- Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, Australia
| | - Anthony Griffin
- Renal Transplantation, Princess Alexandra Hospital, Woolloongabba, Queensland, Australia
| | - Greg Snell
- Lung Transplant, Alfred Health, Melbourne, Victoria, Australia
| | - Stephen I Alexander
- Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, Australia
| | - Scott Campbell
- Department of Renal Medicine, University of Queensland at Princess Alexandra Hospital, Woolloongabba, Queensland, Australia
| | - Steven Chadban
- Central Clinical School, Sydney Medical School, The University of Sydney, Sydney, Australia
- Renal Medicine, Royal Prince Alfred Hospital, Sydney, Australia
| | - Peter Macdonald
- Department of Cardiology, St Vincent's Hospital, Sydney, Australia
- St Vincent's Hospital Victor Chang Cardiac Research Institute, University of New South Wales, Sydney, Australia
| | - Paul Manley
- Kidney Disorders, Auckland District Health Board, Auckland City Hospital, Auckland, New Zealand
| | - Eva Mehakovic
- The Organ and Tissue Authority, Australian Government, Canberra, Australia
| | - Vidya Ramachandran
- Serology and Virology Division, NSW Health Pathology Prince of Wales Hospital, Sydney, Australia
| | - Alicia Mitchell
- Department of Thoracic Medicine and Lung Transplantation, St Vincent's Hospital, Sydney, Australia
- Woolcock Institute of Medical Research, Sydney, Australia
- School of Medical and Molecular Biosciences, University of Technology, Sydney, Australia
| | - Michael Ison
- Divisions of Infectious Diseases and Organ Transplantation, Northwestern University Feinberg School of Medicine, Chicago, IL
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Mitsuki T, Kimura M, Araoka H, Kageyama K, Takagi S, Yamamoto G, Nakamura S, Miyazaki Y, Uchida N, Yoneyama A, Taniguchi S. Cryptococcal meningitis following umbilical cord blood transplantation, association between the occurrence of cryptococcal infection and tacrolimus discontinuation among allogeneic hematopoietic stem cell recipients. J Infect Chemother 2018; 25:289-292. [PMID: 30316744 DOI: 10.1016/j.jiac.2018.09.006] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2018] [Revised: 08/18/2018] [Accepted: 09/13/2018] [Indexed: 12/01/2022]
Abstract
Few cases of cryptococcal infection following umbilical cord blood transplantation (UCBT) have been reported. We report a case, where cryptococcal infection occurred soon after rapidly reducing the dose of tacrolimus in a UCBT recipient who received micafungin prophylaxis during the early phase of transplantation. The etiology of cryptococcal infection following allogeneic hematopoietic stem cell transplantation (allo-HSCT), including UCBT, might be associated with rapid dose-reduction of calcineurin inhibitors, such as tacrolimus during early phase of allo-HSCT. To our knowledge, this is the first English-language report to describe in detail a case of cryptococcal meningitis with fungemia during early phase of UCBT.
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Affiliation(s)
| | - Muneyoshi Kimura
- Department of Infectious Diseases, Toranomon Hospital, Tokyo, Japan.
| | - Hideki Araoka
- Department of Infectious Diseases, Toranomon Hospital, Tokyo, Japan; Okinaka Memorial Institute for Medical Research, Tokyo, Japan
| | - Kosei Kageyama
- Department of Hematology, Toranomon Hospital, Tokyo, Japan
| | | | - Go Yamamoto
- Department of Hematology, Toranomon Hospital, Tokyo, Japan
| | - Shigeki Nakamura
- Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Tokyo, Japan
| | - Yoshitsugu Miyazaki
- Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Tokyo, Japan
| | - Naoyuki Uchida
- Department of Hematology, Toranomon Hospital, Tokyo, Japan
| | - Akiko Yoneyama
- Department of Infectious Diseases, Toranomon Hospital, Tokyo, Japan; Okinaka Memorial Institute for Medical Research, Tokyo, Japan
| | - Shuichi Taniguchi
- Department of Hematology, Toranomon Hospital, Tokyo, Japan; Okinaka Memorial Institute for Medical Research, Tokyo, Japan
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Sohail A, Smibert OC, Snell G, Paraskeva M, Jenney A. Cryptococcal infection in lung transplant recipients: A 5-year retrospective review at an Australian transplant center. Transpl Infect Dis 2018; 20:e12976. [PMID: 30120885 DOI: 10.1111/tid.12976] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2018] [Revised: 07/26/2018] [Accepted: 08/06/2018] [Indexed: 11/30/2022]
Abstract
Cryptococcosis is a common invasive fungal infection (IFI) in solid organ transplant (SOT) recipients. Little is known about cryptococcosis in lung transplant (LTx) recipients despite having one of the highest risks of infection. The aim of this study was to describe demographic and clinical features of cryptococcal infection in LTx recipients. We performed a retrospective, observational study of cryptococcal infection in LTx recipients at The Alfred Hospital in Melbourne, Australia, from 2012 to 2017. A total of 11 cases were identified. Seven patients (64%) were male and the median age was 54.7 years (range 34-69 years). Diagnosis occurred at a median of 233 days (range 1-3650 days) post-transplant. Nine patients (82%) had isolated pulmonary infection of whom 7 (78%) were asymptomatic. All were treated with oral antifungal therapy and 1 required surgical resection of infected lung. Two patients (18%) had disseminated infection; 1 with pulmonary and central nervous system (CNS) infection and 1 with isolated CNS infection. Both patients presented with headache and brain imaging demonstrated cerebral edema, myelinosis, and leptomeningeal enhancement. One of these patients died. This study highlights the fact that cryptococcal infection should remain a consideration in asymptomatic LTx recipients, especially in the presence of non-specific nodules on chest imaging, and that the presence of headache in these patients requires urgent investigation for CNS infection.
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Affiliation(s)
- Asma Sohail
- Department of Infectious Diseases, The Alfred Hospital, Melbourne, Victoria, Australia
| | - Olivia C Smibert
- Department of Infectious Diseases, The Alfred Hospital, Melbourne, Victoria, Australia
| | - Greg Snell
- Lung Transplant Service, The Alfred Hospital, Melbourne, Victoria, Australia
| | - Miranda Paraskeva
- Lung Transplant Service, The Alfred Hospital, Melbourne, Victoria, Australia
| | - Adam Jenney
- Department of Infectious Diseases, The Alfred Hospital, Melbourne, Victoria, Australia.,Microbiology Unit, The Alfred Hospital, Melbourne, Victoria, Australia
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Abstract
PURPOSE OF REVIEW This article describes the diagnosis and management of neurologic problems during hematopoietic cell and solid organ transplantation using time elapsed since transplantation as a guide to expected complications, including drug toxicities, infections, strokes, autoimmune phenomena, disease recurrence, and secondary neoplasms. RECENT FINDINGS Growing clinical experience in the neurology of transplantation has led to appreciation of the diverse clinical and radiographic spectrum of calcineurin inhibitor-related posterior reversible encephalopathy syndrome (PRES) and progressive multifocal leukoencephalopathy. Novel autoimmune phenomena illustrate the delicate balance between adequate immunosuppression and necessary host inflammatory defenses that can lead to organ rejection. The spectrum of infectious complications has changed with the evolution of new conditioning regimens. SUMMARY Neurologic problems remain an important source of morbidity and mortality, both in the immediate transplantation period and for years after the procedure. As perioperative management has reduced the incidence of acute infections, graft versus host disease, and organ rejection, problems of long-term survivors require neurologic input into multidisciplinary management of chronic neurologic conditions impacting quality of life.
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Bini Viotti J, Loebe M, Brozzi N, Pinto A, Simkins J, Cloke CM, Camargo JF, Salama S, Abbo LM. Solving the mystery: Hyalinized cyst wall containing organism-like structures in a lung transplant donor. Transpl Infect Dis 2018; 20:e12940. [PMID: 29873170 DOI: 10.1111/tid.12940] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2018] [Revised: 05/11/2018] [Accepted: 05/28/2018] [Indexed: 11/30/2022]
Abstract
A 59-year-old man with non-ischemic cardiomyopathy underwent orthotopic heart transplantation. The donor, a 31-year-old male declared brain dead after a gunshot wound to the head, was considered high risk due to history of incarceration, illicit drug use, and sex with a HIV-positive partner. At organ procurement, the heart, kidneys, pancreas, and liver looked grossly normal. A small right lower lobe nodule was noticed, and lung biopsy was performed. Bronchoscopy showed purulent secretions in the right lower lobe. Images from pathology are presented. Lung biopsy confirmed the presence of hyalinized cyst wall containing organism-like structures. A combination of culture, microscopic morphology, and gene sequencing was used to identify the causative organism. The patient and all other organ recipients received appropriate antifungal prophylaxis and remain asymptomatic 6 months post-transplant.
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Affiliation(s)
- Julia Bini Viotti
- Department of Medicine, Division of Infectious Diseases, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Matthias Loebe
- Department of Cardiothoracic Surgery, University of Miller School of Medicine, Miami, FL, USA
| | - Nicolas Brozzi
- Department of Cardiothoracic Surgery, University of Miller School of Medicine, Miami, FL, USA
| | - Andre Pinto
- Department of Pathology and Laboratory Medicine, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Jacques Simkins
- Department of Medicine, Division of Infectious Diseases, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Christina M Cloke
- Department of Medicine, Division of Infectious Diseases, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Jose F Camargo
- Department of Medicine, Division of Infectious Diseases, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Sam Salama
- Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Lilian M Abbo
- Department of Medicine, Division of Infectious Diseases, University of Miami Miller School of Medicine, Miami, FL, USA
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Ponzio V, Camargo LF, Medina-Pestana J, Perfect JR, Colombo AL. Outcomes of cryptococcosis in renal transplant recipients in a less-resourced health care system. Transpl Infect Dis 2018; 20:e12910. [PMID: 29677399 DOI: 10.1111/tid.12910] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2017] [Revised: 03/11/2018] [Accepted: 03/20/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND Cryptococcosis is the second most common cause of invasive fungal infections in renal transplant recipients in many countries, and data on graft outcome after treatment for this infection is lacking in less-resourced health care settings. METHODS Data from 47 renal transplant recipients were retrospectively collected at a single institution during a period of 13 years. Graft dysfunction, graft loss, and mortality rates were evaluated. Predictors of mortality and graft loss were estimated. RESULTS A total of 38 (97.4%) patients treated with amphotericin B deoxycholate (AMBd) showed graft dysfunction after antifungal initiation and 8 (18.2%) had kidney graft loss. Graft loss within 30 days after cryptococcosis onset was significantly associated with disseminated infection, greater baseline creatinine levels, and graft dysfunction concomitant to AMBd therapy and an additional nephrotoxic condition. The 30-day mortality rate was 19.2% and it was significantly associated with disseminated and pulmonary infections, somnolence at admission, high CSF opening pressure, positive CSF India ink, creatinine levels greater than 2.0 mg/dL at admission, graft dysfunction in patients treated with AMBd and an additional nephrotoxic condition and graft loss within 30 days. CONCLUSION Graft dysfunction was common in renal transplant recipients with cryptococcosis treated with AMBd. The rate of graft loss rate was high, most frequently in patients with concomitant nephrotoxic conditions. Therefore, the clinical focus should be on the use of less nephrotoxic lipid formulations of amphotericin B in this specific population requiring a polyene induction regimen for treatment of severe cryptococcosis in all health care systems caring for transplantation recipients.
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Affiliation(s)
- Vinicius Ponzio
- Department of Medicine, Division of Infectious Diseases, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
| | - Luis Fernando Camargo
- Department of Medicine, Division of Infectious Diseases, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
| | - José Medina-Pestana
- Discipline of Nephrology, Hospital do Rim Oswaldo Ramos Foundation, Universidade Federal de São Paulo, São Paulo, Brazil
| | - John Robert Perfect
- Division of Infectious Diseases, Department of Medicine, Duke University School of Medicine, Durham, NC, USA
| | - Arnaldo Lopes Colombo
- Department of Medicine, Division of Infectious Diseases, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
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Elsegeiny W, Marr KA, Williamson PR. Immunology of Cryptococcal Infections: Developing a Rational Approach to Patient Therapy. Front Immunol 2018; 9:651. [PMID: 29670625 PMCID: PMC5893745 DOI: 10.3389/fimmu.2018.00651] [Citation(s) in RCA: 64] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2018] [Accepted: 03/16/2018] [Indexed: 12/13/2022] Open
Abstract
Cryptococcal meningoencephalitis is responsible for upwards of 15% of HIV-related deaths worldwide and is currently the most common cause of non-viral meningitis in the US, affecting both previously healthy and people with immune suppression caused by cancer chemotherapy, transplantation, and biologic therapies. Despite a continued 30-50% attributable mortality, recommended therapeutic strategies have remained largely unchanged since the 1950s. Recent murine models and human studies examining the role of the immune system in both susceptibility to the infection as well as host damage have begun to influence patient care decisions. The Damage Framework Response, originally proposed in 1999, was recently used to discuss dichotomous etiologies of host damage in cryptococcal disease. These include patients suffering microbiological damage with low host immunity (especially those immunosuppressed with HIV) and those having low (live) microbiological burden but high immune-mediated damage (HIV-related immune reconstitution syndrome and non-HIV-related postinfectious inflammatory response syndrome). Cryptococcal disease in previously healthy hosts, albeit rare, has been known for a long time. Immunophenotyping and dendritic cell-T cell signaling studies on cerebral spinal fluid of these rare patients reveal immune capacity for recognition and T-cell activation pathways including increased levels of HLA-DR and CD56. However, despite effective T-cell signals, brain biopsy and autopsy specimens demonstrated an M2 alternative macrophage polarization and poor phagocytosis of fungal cells. These studies expand the paradigm for cryptococcal disease susceptibility to include a prominent role for immune-mediated damage and suggest a need for careful individual consideration of immune activation during therapy of cryptococcal disease in diverse hosts.
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Affiliation(s)
- Waleed Elsegeiny
- Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, United States
| | | | - Peter R. Williamson
- Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, United States
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41
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Pedroso JL, Dutra LA, Braga-Neto P, Abrahao A, Andrade JBCD, Silva GLD, Viana LA, Pestana JOM, Barsottini OG. Neurological complications of solid organ transplantation. ARQUIVOS DE NEURO-PSIQUIATRIA 2017; 75:736-747. [DOI: 10.1590/0004-282x20170132] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/07/2017] [Accepted: 07/12/2017] [Indexed: 01/21/2023]
Abstract
ABSTRACT Solid organ transplantation is a significant development in the treatment of chronic kidney, liver, heart and lung diseases. This therapeutic approach has increased patient survival and improved quality of life. New surgical techniques and immunosuppressive drugs have been developed to achieve better outcomes. However, the variety of neurological complications following solid organ transplantation is broad and carries prognostic significance. Patients may have involvement of the central or peripheral nervous system due to multiple causes that can vary depending on time of onset after the surgical procedure, the transplanted organ, and the intensity and type of immunosuppressive therapy. Neurological manifestations following solid organ transplantation pose a diagnostic challenge to medical specialists despite extensive investigation. This review aimed to provide a practical approach to help neurologists and clinicians assess and manage solid organ transplant patients presenting with acute or chronic neurological manifestations.
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Affiliation(s)
| | | | - Pedro Braga-Neto
- Universidade Estadual do Ceará, Brasil; Universidade Federal do Ceará, Brasil
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2016 guidelines for the use of antifungal agents in patients with invasive fungal diseases in Taiwan. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2017; 51:1-17. [PMID: 28781150 DOI: 10.1016/j.jmii.2017.07.006] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/26/2017] [Accepted: 07/12/2017] [Indexed: 01/05/2023]
Abstract
The Infectious Diseases Society of Taiwan, Medical Foundation in Memory of Dr. Deh-Lin Cheng, Foundation of Professor Wei-Chuan Hsieh for Infectious Diseases Research and Education, and CY Lee's Research Foundation for Pediatric Infectious Diseases and Vaccines have updated the guidelines for the use of antifungal agents in adult patients with invasive fungal diseases in Taiwan. This guideline replaces the 2009 version. Recommendations are provided for Candida, Cryptococcus, Aspergillus and Mucormycetes. The focus is based on up-to-date evidence on indications for treatment or prophylaxis of the most common clinical problems. To support the recommendations in this guideline, the committee considered the rationale, purpose, local epidemiology, and key clinical features of invasive fungal diseases to select the primary and alternative antifungal agents. This is the first guideline that explicitly describes the quality and strength of the evidence to support these recommendations. The strengths of the recommendations are the quality of the evidence, the balance between benefits and harms, resource and cost. The guidelines are not intended nor recommended as a substitute for bedside judgment in the management of individual patients, the advice of qualified health care professionals, and more recent evidence concerning therapeutic efficacy and emergence of resistance. Practical considerations for individualized selection of antifungal agents include patient factors, pathogen, site of infection and drug-related factors, such as drug-drug interaction, drug-food intervention, cost and convenience. The guidelines are published in the Journal of Microbiology, Immunology and Infection and are also available on the Society website.
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Marques S, Carmo R, Ferreira I, Bustorff M, Sampaio S, Pestana M. Cryptococcosis in Renal Transplant Recipients: A Single-Center Experience. Transplant Proc 2017; 48:2289-2293. [PMID: 27742281 DOI: 10.1016/j.transproceed.2016.06.006] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND In solid organ transplant patients, 8% of invasive fungal infections are attributed to Cryptococcus. The aim of this study was to determine the frequency, risk factors, clinical characteristics, and outcome of kidney transplant recipients (TR) infected with Cryptococcus. CASE SERIES Between 2007 and 2014, a total of 500 kidney transplantations were performed at São João Hospital, in Porto, Portugal. Six infections by C. neoformans were reported, an incidence of 1.2% (3 disseminated, 2 meningeal, and 1 cutaneous). Patients were 65-72 years of age and 4 of 6 were male, compared with all kidney TR, among whom the mean age was 51.1 years and 60% were male. Three cases of crytococcosis occurred within the first 6 months after transplantation; 3 patients had cytomegalovirus infection and leukopenia, and 2 patients' immunosuppression had been increased in the last 6 months. Meningitis presented with headache, fever, and acute mental confusion; pulmonary involvement presented with respiratory insufficiency and infiltrative or nodular lung lesions; and cutaneous infections presented as cellulitis or skin abscess. Blood cultures for C. neoformans were positive in 3 cases; all of these patients had positive cryptococcal antigen of 1:128 to 1:8192. Five patients received liposomal amphotericin B for 9-21 days, followed by fluconazole. Four patients lost their grafts, and one patients died after a persistent vegetative state due to cryptococcal meningitis. CONCLUSIONS This small case series led to suspicion of an association between cryptococcosis and older age, renal dysfunction, cytomegalovirus infection, and intensification of immunosuppression after rejection episodes. In our series, cryptococcosis was associated with poor graft outcome.
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Affiliation(s)
- S Marques
- Department of Nephrology, Centro Hospitalar de São João, Alameda Prof. Hernâni Monteiro, Porto, Portugal.
| | - R Carmo
- Department of Nephrology, Centro Hospitalar de São João, Alameda Prof. Hernâni Monteiro, Porto, Portugal
| | - I Ferreira
- Department of Nephrology, Centro Hospitalar de São João, Alameda Prof. Hernâni Monteiro, Porto, Portugal
| | - M Bustorff
- Department of Nephrology, Centro Hospitalar de São João, Alameda Prof. Hernâni Monteiro, Porto, Portugal
| | - S Sampaio
- Department of Nephrology, Centro Hospitalar de São João, Alameda Prof. Hernâni Monteiro, Porto, Portugal
| | - M Pestana
- Department of Nephrology, Centro Hospitalar de São João, Alameda Prof. Hernâni Monteiro, Porto, Portugal
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Echenique IA, Angarone MP, Gordon RA, Rich J, Anderson AS, McGee EC, Abicht TO, Kang J, Stosor V. Invasive fungal infection after heart transplantation: A 7-year, single-center experience. Transpl Infect Dis 2017; 19. [DOI: 10.1111/tid.12650] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2015] [Revised: 07/19/2016] [Accepted: 09/12/2016] [Indexed: 01/05/2023]
Affiliation(s)
- Ignacio A. Echenique
- Division of Infectious Diseases; Department of Medicine; Northwestern University Feinberg School of Medicine; Chicago IL USA
| | - Michael P. Angarone
- Division of Infectious Diseases; Department of Medicine; Northwestern University Feinberg School of Medicine; Chicago IL USA
| | - Robert A. Gordon
- Division of Cardiology; Department of Medicine; Northwestern University Feinberg School of Medicine; Chicago IL USA
| | - Jonathan Rich
- Division of Cardiology; Department of Medicine; Northwestern University Feinberg School of Medicine; Chicago IL USA
| | - Allen S. Anderson
- Division of Cardiology; Department of Medicine; Northwestern University Feinberg School of Medicine; Chicago IL USA
| | - Edwin C. McGee
- Division of Cardiac Surgery; Department of Surgery; Northwestern University Feinberg School of Medicine; Chicago IL USA
| | - Travis O. Abicht
- Division of Cardiac Surgery; Department of Surgery; Northwestern University Feinberg School of Medicine; Chicago IL USA
| | - Joseph Kang
- Division of Biostatistics; Department of Preventative Medicine; Northwestern University Feinberg School of Medicine; Chicago IL USA
| | - Valentina Stosor
- Division of Infectious Diseases; Department of Medicine; Northwestern University Feinberg School of Medicine; Chicago IL USA
- Division of Organ Transplantation; Department of Surgery; Northwestern University Feinberg School of Medicine; Chicago IL USA
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45
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George IA, Santos CAQ, Olsen MA, Powderly WG. Epidemiology of Cryptococcosis and Cryptococcal Meningitis in a Large Retrospective Cohort of Patients After Solid Organ Transplantation. Open Forum Infect Dis 2017; 4:ofx004. [PMID: 28480277 PMCID: PMC5414000 DOI: 10.1093/ofid/ofx004] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2016] [Accepted: 01/09/2017] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Cryptococcosis is the third most common invasive fungal infection in solid organ transplant (SOT) recipients. There are no nationally representative data describing the incidence, risk factors, and outcomes of cryptococcosis after SOT. METHODS We assembled a large cohort of adult SOT recipients using Classification of Diseases, Ninth Revision, Clinical Modification billing data from Healthcare Cost and Utilization Project State Inpatient Databases of Florida (2006-2012), New York (2006-2011), and California (2004-2010). Demographics, comorbidities, death, and cryptococcal infections coded during hospitalization were identified. RESULTS A total of 42634 adults with SOT were identified during the study period. Cryptococcal disease was identified in 0.37% (n = 158), 44% of which had meningitis (n = 69). Median time to diagnosis of cryptococcosis was 464 days (range, 4-2393). The median time to onset of cryptococcosis was earlier for lung (191 days; range, 7.5-1816), heart (195 days; range, 4-1061), and liver (200 days; range, 4-1581) compared with kidney transplant recipients (616 days; range, 12-2393; P < .001, log rank test). Very early-onset disease (<30 days after transplantation) more frequently occurred in liver and lung transplant recipients. Lung transplant recipients had the highest risk of cryptococcosis (hazard ratio [HR], 2.10; 95% confidence interval [CI], 1.21-3.60). Cryptococcosis was associated with death (HR, 2.29; 95% CI, 1.68-3.11), after adjusting for age, type of SOT, and other comorbidities. CONCLUSIONS Cryptococcosis is rare after SOT, but it is associated with significantly increased risk of death. Lung transplant recipients are at highest risk for cryptococcosis among SOTs. Nonkidney transplants have earlier onset of cryptococcosis and higher risk of death compared with kidney transplant recipients.
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Affiliation(s)
| | | | - Margaret A Olsen
- Divisions of Infectious Diseases and
- Public Health Sciences, Washington University School of Medicine, St. Louis, Missouri
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46
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Disseminated cryptococcal infection in allogeneic stem cell transplant patients: a rare cause of acute kidney injury. Bone Marrow Transplant 2016; 51:1301-1304. [PMID: 27159179 DOI: 10.1038/bmt.2016.120] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2016] [Accepted: 03/18/2016] [Indexed: 11/08/2022]
Abstract
Hematopoietic stem cell transplantation (HSCT) can be lifesaving for some of the deadliest hematologic diseases. However, immunosuppression, polypharmacy and risk of infectious complications associated with HSCT can increase morbidity and mortality for recipients. Incidence of acute kidney injury (AKI) after HSCT can be as high as 70%, and concomitant infection can be a therapeutic challenge for oncologists, nephrologists and infectious disease specialists. We illustrate this challenge in the case of a 31-year-old man with acute lymphoblastic leukemia who underwent a double cord HSCT complicated by GvHD, systemic cryptococcal and BK virus infections and AKI. Kidney biopsy showed round to cup-shaped organisms with occasional budding, consistent with Cryptococcus and thrombotic microangiopathy. We discuss our findings and a literature review of disseminated cryptococcal infection with renal involvement after HSCT.
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47
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Schmidt-Hieber M, Silling G, Schalk E, Heinz W, Panse J, Penack O, Christopeit M, Buchheidt D, Meyding-Lamadé U, Hähnel S, Wolf HH, Ruhnke M, Schwartz S, Maschmeyer G. CNS infections in patients with hematological disorders (including allogeneic stem-cell transplantation)-Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO). Ann Oncol 2016; 27:1207-25. [PMID: 27052648 PMCID: PMC4922317 DOI: 10.1093/annonc/mdw155] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2015] [Accepted: 03/24/2016] [Indexed: 12/22/2022] Open
Abstract
Diagnosis of CNS infections remains a great challenge in patients with hematological disorders since symptoms might both be masked and be mimicked by other conditions such as metabolic disturbances or consequences from antineoplastic treatment. Thus, awareness of this complication is crucial and any suspicion of a CNS infection should lead to timely and adequate diagnostics and treatment to improve the outcome in this population. Infections of the central nervous system (CNS) are infrequently diagnosed in immunocompetent patients, but they do occur in a significant proportion of patients with hematological disorders. In particular, patients undergoing allogeneic hematopoietic stem-cell transplantation carry a high risk for CNS infections of up to 15%. Fungi and Toxoplasma gondii are the predominant causative agents. The diagnosis of CNS infections is based on neuroimaging, cerebrospinal fluid examination and biopsy of suspicious lesions in selected patients. However, identification of CNS infections in immunocompromised patients could represent a major challenge since metabolic disturbances, side-effects of antineoplastic or immunosuppressive drugs and CNS involvement of the underlying hematological disorder may mimic symptoms of a CNS infection. The prognosis of CNS infections is generally poor in these patients, albeit the introduction of novel substances (e.g. voriconazole) has improved the outcome in distinct patient subgroups. This guideline has been developed by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO) with the contribution of a panel of 14 experts certified in internal medicine, hematology/oncology, infectious diseases, intensive care, neurology and neuroradiology. Grades of recommendation and levels of evidence were categorized by using novel criteria, as recently published by the European Society of Clinical Microbiology and Infectious Diseases.
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Affiliation(s)
- M Schmidt-Hieber
- Department of Hematology, Oncology and Tumor Immunology, HELIOS Clinic Berlin-Buch, Berlin
| | - G Silling
- Department of Hematology, Oncology and Stem Cell Transplantation, University Hospital, Aachen, Medical Faculty, RWTH Aachen, Aachen
| | - E Schalk
- Department of Hematology and Oncology, Otto-von-Guericke University Hospital Magdeburg, Magdeburg
| | - W Heinz
- Department of Internal Medicine II, University Hospital Würzburg, Center of Internal Medicine, Würzburg
| | - J Panse
- Department of Hematology, Oncology and Stem Cell Transplantation, University Hospital, Aachen, Medical Faculty, RWTH Aachen, Aachen
| | - O Penack
- Department of Hematology, Oncology and Tumor Immunology, Charité University Medicine, Campus Virchow Clinic, Berlin
| | - M Christopeit
- Department of Stem Cell Transplantation, University Medical Center Hamburg Eppendorf, Hamburg
| | - D Buchheidt
- Department of Hematology and Oncology, Mannheim University Hospital, University of Heidelberg, Mannheim
| | - U Meyding-Lamadé
- Department of Neurology, Hospital Nordwest Frankfurt, Frankfurt/M., Germany Brunei Neuroscience Stroke and Rehabilitation Centre, Jerudong, Brunei Darussalam Department of Neuroinfectiology, Otto-Meyerhof-Centre, University of Heidelberg, Heidelberg
| | - S Hähnel
- Department of Neuroradiology, University Hospital Heidelberg, Heidelberg
| | - H H Wolf
- Department of Hematology and Oncology, University Hospital Halle, Halle
| | - M Ruhnke
- Paracelsus Clinic Osnabrück, Osnabrück
| | - S Schwartz
- Department of Hematology and Oncology, Charité University Medicine, Campus Benjamin Franklin, Berlin
| | - G Maschmeyer
- Department of Hematology, Oncology and Palliative Care, Ernst von Bergmann Clinic, Potsdam, Germany
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48
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Kennedy E, Vanichanan J, Rajapreyar I, Gonzalez B, Nathan S, Gregoric I, Kar B, Loyalka P, Weeks P, Chavez V, Wanger A, Ostrosky Zeichner L. A pseudo-outbreak of disseminated cryptococcal disease after orthotopic heart transplantation. Mycoses 2015; 59:75-9. [PMID: 26627342 DOI: 10.1111/myc.12433] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2015] [Revised: 10/13/2015] [Accepted: 10/18/2015] [Indexed: 12/23/2022]
Abstract
Cryptococcal infection is the third most common invasive fungal infection (IFI) among solid-organ transplant (SOT) recipients and is considered an important opportunistic infection due to its significant morbidity and mortality. To determine whether a cluster of cryptococcosis in heart transplant patients was of nosocomial nature, three cases of orthotopic heart transplant recipients with postoperative disseminated cryptococcal infection were investigated and paired with an environmental survey in a tertiary care hospital. The infection prevention department conducted a multidisciplinary investigation, which did not demonstrate any evidence of health care-associated environmental exposure. Moreover, multilocus sequence typing showed that one isolate was unique and the two others, although identical, were not temporally related and belong to the most common type seen in the Southern US. Additionally, all three patients had preexisting abnormalities of the CT chest scan and various degrees of acute and chronic rejection. Reactivation was suggested in all three patients. Screening methods may be useful to identify at risk patients and trigger a prophylactic or preemptive approach. However, more data is needed.
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Affiliation(s)
- E Kennedy
- Infection Prevention Department, Memorial Hermann Texas Medical Center, Houston, TX, USA
| | - J Vanichanan
- Division of Infectious Diseases, UT Health Medical School at Houston, Houston, TX, USA
| | - I Rajapreyar
- Program of Advanced Heart Failure, UT Health Medical School at Houston, Houston, TX, USA.,Program of Advanced Heart Failure, Memorial Hermann Texas Medical Center, Houston, TX, USA
| | - B Gonzalez
- Program of Advanced Heart Failure, Memorial Hermann Texas Medical Center, Houston, TX, USA
| | - S Nathan
- Program of Advanced Heart Failure, UT Health Medical School at Houston, Houston, TX, USA.,Program of Advanced Heart Failure, Memorial Hermann Texas Medical Center, Houston, TX, USA
| | - I Gregoric
- Program of Advanced Heart Failure, UT Health Medical School at Houston, Houston, TX, USA.,Program of Advanced Heart Failure, Memorial Hermann Texas Medical Center, Houston, TX, USA
| | - B Kar
- Program of Advanced Heart Failure, UT Health Medical School at Houston, Houston, TX, USA.,Program of Advanced Heart Failure, Memorial Hermann Texas Medical Center, Houston, TX, USA
| | - P Loyalka
- Program of Advanced Heart Failure, UT Health Medical School at Houston, Houston, TX, USA.,Program of Advanced Heart Failure, Memorial Hermann Texas Medical Center, Houston, TX, USA
| | - P Weeks
- Program of Advanced Heart Failure, Memorial Hermann Texas Medical Center, Houston, TX, USA
| | - V Chavez
- Department of Pathology, UT Health Medical School at Houston, Houston, TX, USA
| | - A Wanger
- Department of Pathology, UT Health Medical School at Houston, Houston, TX, USA
| | - L Ostrosky Zeichner
- Infection Prevention Department, Memorial Hermann Texas Medical Center, Houston, TX, USA.,Division of Infectious Diseases, UT Health Medical School at Houston, Houston, TX, USA
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49
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Cryptococcus: Shedding New Light on an Inveterate Yeast. J Fungi (Basel) 2015; 1:115-129. [PMID: 29376903 PMCID: PMC5753104 DOI: 10.3390/jof1020115] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2015] [Revised: 07/01/2015] [Accepted: 07/08/2015] [Indexed: 12/26/2022] Open
Abstract
Cryptococcus has emerged as a significant pathogen in immunocompromised patients. While the diagnostic testing and the antifungal treatment of cryptococcal infections have become firmly established in clinical practice, new developments and areas of ambiguity merit further consideration. These include the potential for donor transmission of Cryptococcus; cirrhosis-associated cryptococcosis, particularly during transplant candidacy; the utility of serum cryptococcal antigen testing of asymptomatic individuals in high-prevalence, poor-resource areas; pathogenesis and treatment of the immune reconstitution syndrome, specifically in relation to antiretroviral therapy and immunosuppressive medications; and new challenges posed by the emerging species of Cryptococcus gatti. In this article, we summarize the literature pertaining to these topics, focusing on recent progress.
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50
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Fungal infections in intestinal and multivisceral transplant recipients. Curr Opin Organ Transplant 2015; 20:295-302. [DOI: 10.1097/mot.0000000000000188] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
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