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1
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Nakamura K, Kanazawa M, Koike Y, Konno T, Onodera O. Early diagnosis of cryptococcal meningoencephalitis in HIV-negative patients: Integration of brain MRI and clinical findings. eNeurologicalSci 2025; 38:100552. [PMID: 39876874 PMCID: PMC11772152 DOI: 10.1016/j.ensci.2025.100552] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Revised: 12/05/2024] [Accepted: 01/05/2025] [Indexed: 01/31/2025] Open
Abstract
Purpose Cryptococcal meningoencephalitis (CM) in human immunodeficiency virus (HIV)-negative patients are often diagnosed later than in HIV-infected patients, which increases mortality rates concerning the former. Consequently, early diagnosis and treatment are crucial for improving clinical prognosis in HIV-negative patients. This study investigated the utility of magnetic resonance imaging (MRI) in combination with clinical and laboratory findings for early diagnosis of CM in HIV-negative patients. Methods This retrospective cohort analysis included consecutive patients diagnosed with central nervous system (CNS) infections. Demographic profiles, laboratory findings, admission symptoms, and MRI findings were assessed. A comparative analysis between CM and other CNS infections was performed. Results Twelve HIV-negative patients were diagnosed with CM, while 38 exhibited other CNS infections (two fungal, 23 bacterial, 12 viral, one parasitic). Pseudocysts on MRI (p = 0.002), absence of fever (p = 0.001), headache (p = 0.005), and normal C-reactive protein (CRP) levels (p = 0.020) were specific findings in CM. By applying a cut-off value of one point in combination of pseudocysts, absence of fever, headache, and normal CRP levels in differentiating CM from other CNS infections, the sensitivity and specificity were calculated as 76.3 % and 91.7 %, respectively. Conclusion Integrating pseudocysts, absence of fever, headache, and normal CRP levels predicts early CM diagnosis, potentially improving outcomes.
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Affiliation(s)
- Kosei Nakamura
- Department of Neurology, Brain Research Institute, Niigata University, Japan
| | - Masato Kanazawa
- Department of Neurology, Brain Research Institute, Niigata University, Japan
| | - Yuka Koike
- Department of Neurology, Brain Research Institute, Niigata University, Japan
| | - Takuya Konno
- Department of Neurology, Brain Research Institute, Niigata University, Japan
| | - Osamu Onodera
- Department of Neurology, Brain Research Institute, Niigata University, Japan
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Chen WY, Zhong C, Zhou JY, Zhou H. False positive detection of serum cryptococcal antigens due to insufficient sample dilution: A case series. World J Clin Cases 2023; 11:1837-1846. [PMID: 36970012 PMCID: PMC10037290 DOI: 10.12998/wjcc.v11.i8.1837] [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: 12/06/2022] [Revised: 02/02/2023] [Accepted: 02/17/2023] [Indexed: 03/07/2023] Open
Abstract
At present, with the development of technology, the detection of cryptococcal antigen (CRAG) plays an increasingly important role in the diagnosis of cryptococcosis. However, the three major CRAG detection technologies, latex agglutination test (LA), lateral flow assay (LFA) and Enzyme-linked Immunosorbent Assay, have certain limitations. Although these techniques do not often lead to false-positive results, once this result occurs in a particular group of patients (such as human immunodeficiency virus patients), it might lead to severe consequences.
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Affiliation(s)
- Wen-Yu Chen
- Department of Respiratory, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 314000, Zhejiang Province, China
- Department of Respiratory, The Affiliated Hospital of Jiaxing University, Jiaxing 314000, Zhejiang Province, China
| | - Cheng Zhong
- Department of Respiratory, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 314000, Zhejiang Province, China
| | - Jian-Ying Zhou
- Department of Respiratory, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 314000, Zhejiang Province, China
| | - Hua Zhou
- Department of Respiratory, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 314000, Zhejiang Province, China
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Malhotra S, Ranjan V, Suman C, Patil S, Malhotra A, Bhatia NK. Advanced Microbiological Diagnostic Techniques in Fungal Infections of the Central Nervous System. VIRAL AND FUNGAL INFECTIONS OF THE CENTRAL NERVOUS SYSTEM: A MICROBIOLOGICAL PERSPECTIVE 2023:419-463. [DOI: 10.1007/978-981-99-6445-1_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Fatahi-Bafghi M. Characterization of the Rothia spp. and their role in human clinical infections. INFECTION GENETICS AND EVOLUTION 2021; 93:104877. [PMID: 33905886 DOI: 10.1016/j.meegid.2021.104877] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Revised: 01/01/2021] [Accepted: 04/19/2021] [Indexed: 11/25/2022]
Abstract
The genus Rothia are emerging as opportunistic pathogens associated with various infections in immunocompromised and immunocompetent individuals. This review describes the taxonomy, cell wall structure, pathogenesis, phenotypic and molecular characteristics, clinical diseases, treatment and, as well as, the related genera that may be misidentified by Rothia species.
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Affiliation(s)
- Mehdi Fatahi-Bafghi
- Department of Microbiology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
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5
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McHugh KE, Gersey M, Rhoads DD, Procop GW, Zhang Y, Booth CN, Sturgis CD. Sensitivity of Cerebrospinal Fluid Cytology for the Diagnosis of Cryptococcal Infections: A 21-Year Single-Institution Retrospective Review. Am J Clin Pathol 2019; 151:198-204. [PMID: 30321269 DOI: 10.1093/ajcp/aqy133] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Objectives Cryptococcal meningoencephalitis is the most common fungal infection of the central nervous system diagnosed by cerebrospinal fluid cytology (CSF) studies. Existing literature suggests that routine CSF cytomorphologic evaluations are exquisitely specific; however, less is known about their sensitivity. Methods An electronic record review of the cytopathology and microbiology files was conducted for the 21-year interval from January 1, 1995, through December 31, 2015. Results In 21 years, 12,584 CSF samples were processed in the laboratory. Of these, 24 (0.2%) were reported positive for cryptococcal organisms by light microscopy, and 129 CSF fungal cultures were positive for Cryptococcus species. All cotested specimens with positive cytology results were positive on culture (15 specimens, 100% specificity). Twenty-four samples with positive culture results were negative by CSF cytology (sensitivity 39%). Conclusions When culture is used as a gold standard, CSF cytology is 100% specific and 39% sensitive, with a positive predictive value of 100% and a negative predictive value of 99.8%.
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Affiliation(s)
- Kelsey E McHugh
- Department of Laboratory Medicine, Cleveland Clinic, Cleveland, OH
| | - Melanie Gersey
- Department of Laboratory Medicine, Cleveland Clinic, Cleveland, OH
| | - Daniel D Rhoads
- Department of Pathology, Case Western Reserve University, Cleveland, OH
- Department of Pathology, University Hospitals Cleveland Medical Center, Cleveland, OH
| | - Gary W Procop
- Department of Laboratory Medicine, Cleveland Clinic, Cleveland, OH
| | - Yaxia Zhang
- Department of Pathology, Hospital for Special Surgery, New York, NY
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Ramanan P, Wengenack NL, Theel ES. Laboratory Diagnostics for Fungal Infections: A Review of Current and Future Diagnostic Assays. Clin Chest Med 2017; 38:535-554. [PMID: 28797494 DOI: 10.1016/j.ccm.2017.04.013] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
This article reviews the current diagnostic approaches, both serologic and molecular, for the detection of fungi associated with pulmonary disease. Classic serologic techniques, including immunodiffusion and complement fixation, both of which remain a cornerstone for fungal diagnostic testing, are reviewed and their performance characteristics presented. More recent advances in this field, including novel lateral-flow assays for fungal antigen detection, are also described. Molecular techniques for fungal identification both from culture and directly from patient specimens, including nucleic acid probes, mass spectrometry-based methods, nucleic acid amplification testing, and traditional and broad-range sequencing, are discussed and their performance evaluated.
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Affiliation(s)
- Poornima Ramanan
- Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street, Rochester, MN 55905, USA
| | - Nancy L Wengenack
- Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street, Rochester, MN 55905, USA
| | - Elitza S Theel
- Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street, Rochester, MN 55905, USA.
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Low Cryptococcus Antigen Titers as Determined by Lateral Flow Assay Should Be Interpreted Cautiously in Patients without Prior Diagnosis of Cryptococcal Infection. J Clin Microbiol 2017; 55:2472-2479. [PMID: 28566315 DOI: 10.1128/jcm.00751-17] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2017] [Accepted: 05/24/2017] [Indexed: 12/16/2022] Open
Abstract
Detection of Cryptococcus antigen (CrAg) is invaluable for establishing cryptococcal disease. Multiple different methods for CrAg detection are available, including a lateral flow assay (LFA). Despite excellent performance of the CrAg LFA, we have observed multiple cases of low-titer (≤1:5) positive CrAg LFA results in patients for whom cryptococcosis was ultimately excluded. To investigate the accuracy of low-titer positive CrAg LFA results, we performed chart reviews for all patients with positive CrAg LFA results between June 2014 and December 2016. During this period, serum and/or cerebrospinal fluid (CSF) samples from 3,969 patients were tested with the CrAg LFA, and 55 patients (1.5%) tested positive. Thirty-eight of those patients lacked a history of cryptococcal disease and were the focus of this study. Fungal culture or histopathology confirmed Cryptococcus infection for 20 patients (52.6%), and CrAg LFA titers in serum and CSF samples ranged from 1:5 to ≥1:2,560. For the 18 patients (47.4%) without culture or histopathological confirmation, the CrAg LFA results were considered true-positive results for 5 patients (titer range, 1:10 to ≥1:2,560), due to clinical improvement with targeted therapy and decreasing CrAg LFA titers. The remaining 13 patients had CrAg LFA titers of 1:2 (n = 11) or 1:5 (n = 2) and were ultimately diagnosed with an alternative condition (n = 11) or began therapy for possible cryptococcosis without improvement (n = 2), leading to an overall CrAg LFA false-positive rate of 34%. We recommend careful clinical correlation prior to establishing a diagnosis of cryptococcal infection for patients with first-time positive CrAg LFA titers of 1:2.
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Srichatrapimuk S, Sungkanuparph S. Integrated therapy for HIV and cryptococcosis. AIDS Res Ther 2016; 13:42. [PMID: 27906037 PMCID: PMC5127046 DOI: 10.1186/s12981-016-0126-7] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2016] [Accepted: 11/16/2016] [Indexed: 12/27/2022] Open
Abstract
Cryptococcosis has been one of the most common opportunistic infections and causes of mortality among HIV-infected patients, especially in resource-limited countries. Cryptococcal meningitis is the most common form of cryptococcosis. Laboratory diagnosis of cryptococcosis includes direct microscopic examination, isolation of Cryptococcus from a clinical specimen, and detection of cryptococcal antigen. Without appropriate treatment, cryptococcosis is fatal. Early diagnosis and treatment is the key to treatment success. Treatment of cryptococcosis consists of three main aspects: antifungal therapy, intracranial pressure management for cryptococcal meningitis, and restoration of immune function with antiretroviral therapy (ART). Optimal integration of these three aspects is crucial to achieving successful treatment and reducing the mortality. Antifungal therapy consists of three phases: induction, consolidation, and maintenance. A combination of two drugs, i.e. amphotericin B plus flucytosine or fluconazole, is preferred in the induction phase. Fluconazole monotherapy is recommended during consolidation and maintenance phases. In cryptococcal meningitis, intracranial pressure rises along with CSF fungal burden and is associated with morbidity and mortality. Aggressive control of intracranial pressure should be done. Management options include therapeutic lumbar puncture, lumbar drain insertion, ventriculostomy, or ventriculoperitoneal shunt. Medical treatment such as corticosteroids, mannitol, and acetazolamide are ineffective and should not be used. ART has proven to have a great impact on survival rates among HIV-infected patients with cryptococcosis. The time to start ART in HIV-infected patients with cryptococcosis has to be deferred until 5 weeks after the start of antifungal therapy. In general, any effective ART regimen is acceptable. Potential drug interactions between antiretroviral agents and amphotericin B, flucytosine, and fluconazole are minimal. Of most potential clinical relevance is the concomitant use of fluconazole and nevirapine. Concomitant use of these two drugs should be cautious, and patients should be monitored closely for nevirapine-associated adverse events, including hepatotoxicity. Overlapping toxicities of antifungal and antiretroviral drugs and immune reconstitution inflammatory syndrome are not uncommon. Early recognition and appropriate management of these consequences can reinforce the successful integrated therapy in HIV-infected patients with cryptococcosis.
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Cryptococcosis. DIAGNOSIS AND TREATMENT OF FUNGAL INFECTIONS 2015. [PMCID: PMC7122569 DOI: 10.1007/978-3-319-13090-3_15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Cryptococcosis is an infectious disease caused by the encapsulated fungi Cryptococcus neoformans and Cryptococcus gattii. Once a relatively uncommon cause of human disease, cryptococcal infection can develop in apparently immunocompetent hosts and has emerged as an important opportunistic infection in humans over the past several decades as immunocompromised populations expand in the setting of HIV/AIDS, organ transplantation, malignancies, and treatment for other conditions. Clinical manifestations are myriad but pulmonary and central nervous system (CNS) infections are the most common. Improvements in diagnostic testing and standardized approaches to antifungal therapy, when available, have made considerable impact in the management of this infection. While the widespread use of highly active antiretroviral therapy (HAART) has improved the outcome of cryptococcosis in many HIV-infected patients, cryptococcosis remains an entity of considerable morbidity and mortality in many parts of the world, and restoration of host immunity can present management challenges that require individualized management. As immunocompromised populations continue to expand, it is likely that cryptococcosis will remain an important opportunistic fungal infection of humans requiring ongoing investigation.
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Arendrup M, Boekhout T, Akova M, Meis J, Cornely O, Lortholary O. ESCMID† and ECMM‡ joint clinical guidelines for the diagnosis and management of rare invasive yeast infections. Clin Microbiol Infect 2014; 20 Suppl 3:76-98. [DOI: 10.1111/1469-0691.12360] [Citation(s) in RCA: 363] [Impact Index Per Article: 33.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2013] [Revised: 08/16/2013] [Accepted: 08/16/2013] [Indexed: 12/27/2022]
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Spivey JR, Drew RH, Perfect JR. Future strategies for the treatment of cryptococcal meningoencephalitis in pediatric patients. Expert Opin Orphan Drugs 2014. [DOI: 10.1517/21678707.2014.880649] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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12
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Chavan RS, Pannaraj PS, Luna RA, Szabo S, Adesina A, Versalovic J, Krance RA, Kennedy-Nasser AA. Significant morbidity and mortality attributable to rothia mucilaginosa infections in children with hematological malignancies or following hematopoietic stem cell transplantation. Pediatr Hematol Oncol 2013; 30:445-54. [PMID: 23659597 DOI: 10.3109/08880018.2013.783893] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Rothia mucilaginosa is a gram-positive coccus that poses a diagnostic challenge and often requires DNA pyrosequencing for diagnosis as it can be easily mistaken for coagulase-negative staphylococci on initial culture results. While it is often times normal human oral and upper respiratory tract microbiota, it can be a virulent pathogen in immunocompromised patients. Most commonly, it causes bacteremia (catheter and non-catheter related) and meningitis in these patients. Our objective was to report the incidence of R. mucilaginosa infections in neutropenic children with hematological malignancies or following hematopoietic stem cell transplantation at a major children's hospital. We report 11 patients in this cohort who developed clinically significant R. mucilaginosa infections, including three deaths directly attributable to this microorganism. Three patients developed significant neurological involvement, accounting for two of the deaths, and one patient died of disseminated infection. Except for one, all patients had severe neutropenia, central line catheters, and mucosal breakdown at the time of infection. Patients who succumbed never achieved neutrophil recovery. In conclusion, R. mucilaginosa can lead to life-threatening infections in immunocompromised hosts, especially in profoundly neutropenic patients.
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Affiliation(s)
- Rishikesh S Chavan
- Department of Pediatric Hematology Oncology, Tulane University School of Medicine, New Orleans, LA 70112–2699, USA.
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13
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Bhatt VR, Viola GM, Ferrajoli A. Invasive fungal infections in acute leukemia. Ther Adv Hematol 2013; 2:231-47. [PMID: 23556092 DOI: 10.1177/2040620711410098] [Citation(s) in RCA: 55] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Invasive fungal infection (IFI) is among the leading causes for morbidity, mortality, and economic burden for patients with acute leukemia. In the past few decades, the incidence of IFI has increased dramatically. The certainty of diagnosis of IFI is based on host factors, clinical evidence, and microbiological examination. Advancement in molecular diagnostic modalities (e.g. non-culture-based serum biomarkers such as β-glucan or galactomannan assays) and high-resolution radiological imaging has improved our diagnostic approach. The early use of these diagnostic tests assists in the early initiation of preemptive therapy. Nonetheless, the complexity of IFI in patients with leukemia and the limitations of these diagnostic tools still mandate astute clinical acumen. Its management has been further complicated by the increasing frequency of infection by non-Aspergillus molds (e.g. zygomycosis) and the emergence of drug-resistant fungal pathogens. In addition, even though the antifungal armamentarium has expanded rapidly in the past few decades, the associated mortality remains high. The decision to initiate antifungal treatment and the choice of anti-fungal therapy requires careful consideration of several factors (e.g. risk stratification, local fungal epidemiologic patterns, concomitant comorbidities, drug-drug interactions, prior history of antifungal use, overall cost, and the pharmacologic profile of the antifungal agents). In order to optimize our diagnostic and therapeutic management of IFI in patients with acute leukemia, further basic research and clinical trials are desperately needed.
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Affiliation(s)
- Vijaya R Bhatt
- Department of Internal Medicine, Staten Island University Hospital, New York, USA
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Ribeiro HB, Paiva TFD, Mamprin GPR, Gorzoni ML, Rocha AJD, Lancellotti CLP. Carcinomatous encephalitis as clinical presentation of occult lung adenocarcinoma: case report. ARQUIVOS DE NEURO-PSIQUIATRIA 2008; 65:841-4. [PMID: 17952293 DOI: 10.1590/s0004-282x2007000500022] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/16/2007] [Accepted: 06/02/2007] [Indexed: 11/22/2022]
Abstract
Carcinomatous encephalitis is a rare entity, originally described by Madow and Alpers in 1951, which is characterized by tumoral spreading perivascular, without mass effect. Clinical manifestations such as hemiparesis, seizures, ataxia, speech difficulties, cerebrospinal fluid findings as well as computed tomography are nonspecific. This leads the physician to pursue more frequent diseases that could explain those manifestations--toxic, metabolic, and/or infectious encephalopathy. A magnetic resonance imaging (MRI) with gadolinium, the method of choice, presumes the diagnosis. Previous reports of this unusual form of metastatic disease have described patients with prior diagnosis of pulmonary adenocarcinoma. We present the case of carcinomatous encephalitis in a 76-year-old woman as the primary manifestation of occult pulmonary adenocarcinoma with its clinical, imaging, and anatomopathological findings.
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Affiliation(s)
- Henrique Barbosa Ribeiro
- Department of Medicine, Faculty of Medical Sciences, Santa Casa de São Paulo, Rua de Cesário Mota Jr. 112, 01221-900 São Paulo, SP, Brazil
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15
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Lee AB, Harker-Murray P, Ferrieri P, Schleiss MR, Tolar J. Bacterial meningitis from Rothia mucilaginosa in patients with malignancy or undergoing hematopoietic stem cell transplantation. Pediatr Blood Cancer 2008; 50:673-6. [PMID: 17588235 DOI: 10.1002/pbc.21286] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Opportunistic infections contribute to morbidity and mortality of patients undergoing hematopoietic stem cell transplantation and treatment for malignancies. Rothia mucilaginosa, a gram-positive bacterium, is responsible for rare, but often fatal meningitis in severely immunocompromised patients. We describe two cases of meningitis from discrete strains of R. mucilaginosa on our pediatric bone marrow transplant unit, summarize the published cases of R. mucilaginosa meningitis in oncology and stem cell transplant patients, and provide updated recommendations regarding the use of antibiotic therapy in this patient population.
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Affiliation(s)
- Alisa B Lee
- University of Minnesota Medical School, Minneapolis, Minnesota, USA
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Thakur K, Singh G, Agarwal S, Rani L. MENINGITIS CAUSED BY RHODOTORULA RUBRA IN AN HUMAN IMMUNODEFICIENCY VIRUS INFECTED PATIENT. Indian J Med Microbiol 2007. [DOI: 10.1016/s0255-0857(21)02182-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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Abstract
In the past 2 decades, Cryptococcus has emerged in its clinical significance and as a model yeast for understanding molecular pathogenesis. C neoformans and C gattii are currently considered major primary and secondary pathogens in a wide array of hosts that are known to be immunocompromised or apparently immunocompetent. A recent outbreak of C gattii infections further underscores the clinical importance of the yeast through its epidemiology and pathogenicity features. With an enlarging immunosuppressed population caused by HIV infection, solid organ transplantation, and clinical use of potent immunosuppressives, such as cancer chemotherapy, monoclonal antibodies, and corticosteroids, this fungus has become a well-established infectious complication of modern medicine. This article examines current issues in cryptococcal infections, including new classification, epidemiology, pathogenesis, and specific clinical aspects.
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Affiliation(s)
- Methee Chayakulkeeree
- Department of Medicine, Division of Infectious Diseases and International Health, Duke University Medical Center, P.O. Box 3353, Durham, NC 27710, USA
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18
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Abstract
Cryptococcus neoformans has risen to a worldwide highly recognizable major opportunistic pathogen with deadly consequences. It has become a model fungus to study a variety of paradigms in the host-fungus relationships. Genomic studies are advancing knowledge on its evolution and dissecting its virulence composite. Studies designed to understand host immunology to this fungus are leading to development of active and passive prevention and therapeutic strategies. This article collates and analyzes both new and old knowledge about the pathogen to help frame the meaning of human cryptococcosis as it starts to evolve in the new millennium.
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Affiliation(s)
- John R Perfect
- Department of Medicine, Division of Infectious Diseases, Duke University Medical Center, PO Box 3353, Durham, NC 27710, USA.
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Ascioglu S, Rex JH, de Pauw B, Bennett JE, Bille J, Crokaert F, Denning DW, Donnelly JP, Edwards JE, Erjavec Z, Fiere D, Lortholary O, Maertens J, Meis JF, Patterson TF, Ritter J, Selleslag D, Shah PM, Stevens DA, Walsh TJ. Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus. Clin Infect Dis 2002; 34:7-14. [PMID: 11731939 DOI: 10.1086/323335] [Citation(s) in RCA: 1792] [Impact Index Per Article: 77.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2000] [Revised: 05/14/2001] [Indexed: 12/12/2022] Open
Abstract
During the past several decades, there has been a steady increase in the frequency of opportunistic invasive fungal infections (IFIs) in immunocompromised patients. However, there is substantial controversy concerning optimal diagnostic criteria for these IFIs. Therefore, members of the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group formed a consensus committee to develop standard definitions for IFIs for clinical research. On the basis of a review of literature and an international consensus, a set of research-oriented definitions for the IFIs most often seen and studied in immunocompromised patients with cancer is proposed. Three levels of probability are proposed: "proven," "probable," and "possible." The definitions are intended for use in the context of clinical and/or epidemiological research, not for clinical decision making.
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Denning DW, Evans EG, Kibbler CC, Richardson MD, Roberts MM, Rogers TR, Warnock DW, Warren RE. Guidelines for the investigation of invasive fungal infections in haematological malignancy and solid organ transplantation. British Society for Medical Mycology. Eur J Clin Microbiol Infect Dis 1997; 16:424-36. [PMID: 9248745 DOI: 10.1007/bf02471906] [Citation(s) in RCA: 92] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Invasive fungal infections are increasing in incidence and now affect as many as 50% of neutropenic/bone marrow transplant patients and 5 to 20% of solid organ transplant recipients. Unfortunately, many of the diagnostic tests available have a low sensitivity. The guidelines presented here have been produced by a working party of the British Society for Medical Mycology in an attempt to optimise the use of these tests. The yield of fungi from blood cultures can be increased by ensuring that at least 20 ml of blood are taken for aerobic culture, by using more than one method of blood culture, and by employing terminal subculture if continuous monitoring systems are used with a five-day incubation protocol. Skin lesions in febrile neutropenic patients should be biopsied and cultured for fungi. The detection of galactomannan in blood or urine is of value in diagnosing invasive aspergillosis only if tests are performed at least twice weekly in high-risk patients. Antigen detection tests for invasive candidiasis are less valuable. Computed tomography scanning is particularly valuable in diagnosing invasive pulmonary fungal infection when the chest radiograph is negative or shows only minimal changes. Bronchoalveolar lavage is most useful in patients with diffuse changes on computed tomography scan. The major advances in the diagnosis of invasive fungal infection in patients with haematological malignancy or solid organ transplantation have been in the use of imaging techniques, rather than in the development of new mycological methods in the routine laboratory.
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Affiliation(s)
- D W Denning
- Department of Infectious Diseases and Tropical Medicine (Monsall Unit), North manchester General Hospital, UK
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21
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Mitchell TG, Perfect JR. Cryptococcosis in the era of AIDS--100 years after the discovery of Cryptococcus neoformans. Clin Microbiol Rev 1995; 8:515-48. [PMID: 8665468 PMCID: PMC172874 DOI: 10.1128/cmr.8.4.515] [Citation(s) in RCA: 813] [Impact Index Per Article: 27.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
Abstract
Although Cryptococcus neoformans and cryptococcosis have existed for several millennia, a century has passed since the discovery of this encapsulated yeast and its devastating disease. With the advent of the AIDS pandemic, cryptococcal meningitis has emerged as a leading cause of infectious morbidity and mortality and a frequently life-threatening opportunistic mycosis among patients with AIDS. Both basic and clinical research have accelerated in the 1990s, and this review attempts to highlight some of these advances. The discussion covers recent findings, current concepts, controversies, and unresolved issues related to the ecology and genetics of C. neoformans; the surface structure of the yeast; and the mechanisms of host defense. Regarding cell-mediated immunity, CD4+ T cells are crucial for successful resistance, but CD8+ T cells may also participate significantly in the cytokine-mediated activation of anticryptococcal effector cells. In addition to cell-mediated immunity, monoclonal antibodies to the major capsular polysaccharide, the glucuronoxylomannan, offer some protection in murine models of cryptococcosis. Clinical concepts are presented that relate to the distinctive features of cryptococcosis in patients with AIDS and the diagnosis, treatment, and prevention of cryptococcosis in AIDS patients.
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Affiliation(s)
- T G Mitchell
- Department of Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA
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Sutcliffe IC, Old LA. Stomatococcus mucilaginosus produces a mannose-containing lipoglycan rather than lipoteichoic acid. Arch Microbiol 1995; 163:70-5. [PMID: 7710324 DOI: 10.1007/bf00262206] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
Five strains of Stomatococcus mucilaginosus were investigated to determine whether the organism produces a lipoteichoic acid or a lipoglycan. Crude phenol extracts were purified by hydrophobic interaction chromatography and shown to contain lipoglycan. The major carbohydrate component present was mannose, indicating that the macroamphiphile is a lipomannan. The fatty acid composition of the lipoglycan was similar to that of stomatococcal whole cells. These data provide additional chemotaxonomic evidence supporting the suprageneric classification of the genus Stomatococcus within a group of actinomycete genera that also includes the genus Micrococcus.
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Affiliation(s)
- I C Sutcliffe
- Department of Oral Biology, University of Newcastle upon Tyne, The Dental School, UK
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Cunniffe JG, Mallia C, Alcock PA. Stomatococcus mucilaginosus lower respiratory tract infection in a patient with AIDS. J Infect 1994; 29:327-30. [PMID: 7884227 DOI: 10.1016/s0163-4453(94)91312-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
We describe a case of recurrent Stomatococcus mucilaginosus lower respiratory tract infection in a patient with AIDS. Apart from S. mucilaginosus no other pathogens were found to account for infection. There was a rapid response to rifampicin, the organism being resistant to penicillin, co-trimoxazole and ciprofloxacin. Infections caused by this organism are increasingly described, but there are few reports of lower respiratory tract infection.
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Affiliation(s)
- J G Cunniffe
- Public Health Laboratory, Central Pathology Laboratory, Hartshill, Stoke-on-Trent, U.K
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