Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 10 de 10
Filter
1.
Int J Mol Sci ; 23(10)2022 May 16.
Article in English | MEDLINE | ID: covidwho-1875643

ABSTRACT

Invasive aspergillosis (IA) is a life-threatening fungal disease that causes high morbidity and mortality in immunosuppressed patients. Early and accurate diagnosis and treatment of IA remain challenging. Given the broad range of non-specific clinical symptoms and the shortcomings of current diagnostic techniques, most patients are either diagnosed as "possible" or "probable" cases but not "proven". Moreover, because of the lack of sensitive and specific tests, many high-risk patients receive an empirical therapy or a prolonged treatment of high-priced antifungal agents, leading to unnecessary adverse effects and a high risk of drug resistance. More precise diagnostic techniques alongside a targeted antifungal treatment are fundamental requirements for reducing the morbidity and mortality of IA. Monoclonal antibodies (mAbs) with high specificity in targeting the corresponding antigen(s) may have the potential to improve diagnostic tests and form the basis for novel IA treatments. This review summarizes the up-to-date application of mAb-based approaches in assisting IA diagnosis and therapy.


Subject(s)
Antineoplastic Agents, Immunological , Aspergillosis , Invasive Fungal Infections , Mycoses , Antibodies, Monoclonal/therapeutic use , Antifungal Agents/therapeutic use , Antineoplastic Agents, Immunological/therapeutic use , Aspergillosis/diagnosis , Aspergillosis/drug therapy , Humans , Invasive Fungal Infections/drug therapy , Mycoses/drug therapy
2.
J Crit Care ; 69: 154004, 2022 06.
Article in English | MEDLINE | ID: covidwho-1739899

ABSTRACT

An increasing number of studies have tried to determine the incidence of invasive fungal infections (IFIs) in COVID-19 patients. Challenges in the diagnosis of pulmonary aspergillosis in these patients have led to new definitions of COVID-19-associated pulmonary aspergillosis (CAPA). The aim of this study was to determine the incidence and outcomes of and risk factors for IFIs in critically-ill COVID-19 patients, using the new definitions, in a tertiary center in Israel. METHODS: A case-controlled study (from 1 September 2020 to 31 March 2021) in which data from COVID-19 critically-ill patients with a diagnosis of IFI were collected and compared to a control group without IFI. RESULTS: The incidence of IFI amongst 311 COVID-19 critically-ill patients was 6.1%. 3.5% had CAPA and 3.5% had candidemia. In-hospital mortality was higher amongst patients with IFI compared to those without IFI (89.4% vs 60%, p < 0.03). The most significant predictors of IFI were cardiovascular co-morbidity and carbapenem use. CONCLUSIONS: The low incidence of CAPA in our group of COVID-19 critically-ill patients was consistent with recent reports, underscoring the importance of differentiating between true infection and colonization. Awareness and timely diagnosis of IFIs in COVID-19 critically-ill patients are imperative considering the associated high mortality.


Subject(s)
COVID-19 , Invasive Fungal Infections , Pulmonary Aspergillosis , Critical Illness , Humans , Invasive Fungal Infections/diagnosis , Invasive Fungal Infections/drug therapy , Invasive Fungal Infections/epidemiology , Israel/epidemiology , Tertiary Care Centers
3.
Drugs ; 81(15): 1703-1729, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1491481

ABSTRACT

The epidemiology of invasive fungal infections is changing, with new populations at risk and the emergence of resistance caused by the selective pressure from increased usage of antifungal agents in prophylaxis, empiric therapy, and agriculture. Limited antifungal therapeutic options are further challenged by drug-drug interactions, toxicity, and constraints in administration routes. Despite the need for more antifungal drug options, no new classes of antifungal drugs have become available over the last 2 decades, and only one single new agent from a known antifungal class has been approved in the last decade. Nevertheless, there is hope on the horizon, with a number of new antifungal classes in late-stage clinical development. In this review, we describe the mechanisms of drug resistance employed by fungi and extensively discuss the most promising drugs in development, including fosmanogepix (a novel Gwt1 enzyme inhibitor), ibrexafungerp (a first-in-class triterpenoid), olorofim (a novel dihyroorotate dehydrogenase enzyme inhibitor), opelconazole (a novel triazole optimized for inhalation), and rezafungin (an echinocandin designed to be dosed once weekly). We focus on the mechanism of action and pharmacokinetics, as well as the spectrum of activity and stages of clinical development. We also highlight the potential future role of these drugs and unmet needs.


Subject(s)
Antifungal Agents/pharmacology , Fungi/drug effects , Invasive Fungal Infections/drug therapy , Animals , Antifungal Agents/adverse effects , Antifungal Agents/classification , Drug Development , Drug Interactions , Drug Resistance, Fungal , Humans , Invasive Fungal Infections/microbiology
4.
BMC Infect Dis ; 21(1): 906, 2021 Sep 03.
Article in English | MEDLINE | ID: covidwho-1455941

ABSTRACT

BACKGROUND: COVID-19 disease may be associated with a wide range of bacterial and fungal infections. We report a patient with COVID-19 infection who developed rhino-facial mucormycosis during treatment with corticosteroids. CASE PRESENTATION: A 59-year-old non-diabetic male patient was admitted with a diagnosis of COVID-19 based on positive RT-PCR and CT of the lungs. Due to sever lung involvement, he was treated with methylprednisolone. The patient was re-admitted to hospital, due to nasal obstruction and left side facial and orbital swelling, several days after discharge. In sinus endoscopic surgery, debridement was performed and the specimens were sent to pathology and mycology laboratories. A nasal biopsy showed wide hyphae without septa. The sequenced PCR product revealed Rhizopus oryzae. Despite all medical and surgical treatment, the patient died. In addition, the characteristics of patients with COVID-19-associated mucormycosis were reviewed in 44 available literatures. In most studies, diabetes mellitus was the most common predisposing factor for mucormycosis. CONCLUSION: Our report highlights the need for assessing the presence of mucormycosis in patients with COVID-19 and also it shows that physicians should consider the potential for secondary invasive fungal infections in COVID-19 cases.


Subject(s)
COVID-19 , Diabetes Mellitus , Invasive Fungal Infections , Mucormycosis , Humans , Invasive Fungal Infections/diagnosis , Invasive Fungal Infections/drug therapy , Male , Middle Aged , Mucormycosis/diagnosis , Mucormycosis/drug therapy , SARS-CoV-2
6.
Infect Dis Clin North Am ; 35(2): 261-277, 2021 06.
Article in English | MEDLINE | ID: covidwho-1232974

ABSTRACT

Various uncommon fungal pathogens have been increasingly identified as causes of disseminated and invasive fungal disease (IFD) worldwide. Growing recognition and clinical knowledge of these emerging fungal pathogens has occurred through improved molecular diagnostics, nucleic sequence databases, and taxonomic reclassification of medically significant fungi. However, emerging fungal diseases carry significant morbidity and mortality and, due to a paucity of published literature, the collective clinical experience with these fungi is often limited. In this review, we focus on unusual emerging fungal pathogens not extensively covered elsewhere in this issue of Infectious Diseases Clinics of North America.


Subject(s)
Communicable Diseases, Emerging , Invasive Fungal Infections , Mycoses , Opportunistic Infections , Communicable Diseases, Emerging/diagnosis , Communicable Diseases, Emerging/drug therapy , Communicable Diseases, Emerging/epidemiology , Fungi , Humans , Invasive Fungal Infections/diagnosis , Invasive Fungal Infections/drug therapy , Invasive Fungal Infections/epidemiology , Mycoses/diagnosis , Mycoses/epidemiology , North America , Opportunistic Infections/diagnosis , Opportunistic Infections/drug therapy , Opportunistic Infections/epidemiology
8.
J Mycol Med ; 31(2): 101125, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1164245

ABSTRACT

Mucormycosis is an invasive fungal infection (IFI) due to several species of saprophytic fungi, occurring in patients with underlying co-morbidities (including organ transplantation). During the ongoing Coronavirus disease 2019 (COVID-19) pandemic, there have been increasing reports of bacterial and fungal co-infections occurring in COVID-19 patients, including COVID-19 associated pulmonary aspergillosis (CAPA). We describe a case of mucormycosis occurring after COVID-19, in an individual who received a recent heart transplant for severe heart failure. Two months after heart transplant, our patient developed upper respiratory and systemic symptoms and was diagnosed with COVID-19. He was managed with convalescent plasma therapy and supportive care. Approximately three months after COVID-19 diagnosis, he developed cutaneous mucormycosis at an old intravascular device site. He underwent extensive surgical interventions, combined with broad-spectrum antifungal therapy. Despite the aggressive therapeutic measures, he died after a prolonged hospital stay. In this case report, we also review the prior well-reported cases of mucormycosis occurring in COVID-19 patients and discuss potential mechanisms by which COVID-19 may predispose to IFIs. Similar to CAPA, mucormycosis with COVID-19 may need to be evaluated as an emerging disease association. Clinicians should be vigilant to evaluate for invasive fungal infections such as mucormycosis in patients with COVID-19 infection.


Subject(s)
COVID-19/complications , Heart Transplantation , Invasive Fungal Infections/complications , Mucormycosis/complications , Postoperative Complications/etiology , Rhizopus/isolation & purification , Aged , Anti-Infective Agents/therapeutic use , Bacteremia/complications , Bacteremia/drug therapy , Bacteremia/microbiology , COVID-19/therapy , Catheter-Related Infections/drug therapy , Catheter-Related Infections/etiology , Coinfection/drug therapy , Coinfection/microbiology , Combined Modality Therapy , Contraindications, Drug , Debridement , Dermatomycoses/drug therapy , Dermatomycoses/etiology , Disease Susceptibility , Fatal Outcome , Heart Failure/surgery , Humans , Hydroxychloroquine/therapeutic use , Immunization, Passive , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Intra-Aortic Balloon Pumping/instrumentation , Invasive Fungal Infections/drug therapy , Male , Mucormycosis/drug therapy , Mucormycosis/microbiology , Negative-Pressure Wound Therapy , Opportunistic Infections/complications , Opportunistic Infections/drug therapy , Opportunistic Infections/microbiology , Postoperative Complications/drug therapy , Postoperative Complications/microbiology , Postoperative Complications/virology , Surgical Wound Infection/complications , Surgical Wound Infection/drug therapy , Surgical Wound Infection/microbiology , Surgical Wound Infection/surgery
9.
J Mycol Med ; 31(2): 101124, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1096172

ABSTRACT

Aspergillus infection is a well-known complication of severe influenza and severe acute respiratory syndrome coronavirus (SARS-CoV), and these infections have been related with significant morbidity and mortality even when appropriately diagnosed and treated. Recent studies have indicated that SARS-CoV-2 might increase the risk of invasive pulmonary aspergillosis (IPA). Here, we report the first case of Aspergillus ochraceus in a SARS-CoV-2 positive immunocompetent patient, which is complicated by pulmonary and brain infections. Proven IPA is supported by the positive Galactomannan test, culture-positive, and histopathological evidence. The patient did not respond to voriconazole, and liposomal amphotericin B was added to his anti-fungal regimen. Further studies are needed to evaluate the prevalence of IPA in immunocompetent patients infected with SARS-CoV-2. Consequently, testing for the incidence of Aspergillus species in lower respiratory secretions and Galactomannan test of COVID-19 patients with appropriate therapy and targeted anti-fungal therapy based on the primary clinical suspicion of IPA are highly recommended.


Subject(s)
Aspergillosis/complications , Aspergillus ochraceus/isolation & purification , COVID-19/complications , Invasive Fungal Infections/complications , SARS-CoV-2/isolation & purification , Adult , Amphotericin B/therapeutic use , Antifungal Agents/therapeutic use , Aspergillosis/diagnostic imaging , Aspergillosis/drug therapy , Biomarkers , Brain Abscess/diagnostic imaging , Brain Abscess/etiology , Brain Abscess/microbiology , Bronchoalveolar Lavage Fluid/microbiology , COVID-19/diagnostic imaging , COVID-19 Nucleic Acid Testing , Fatal Outcome , Galactose/analogs & derivatives , Humans , Immunocompetence , Invasive Fungal Infections/diagnostic imaging , Invasive Fungal Infections/drug therapy , Invasive Fungal Infections/microbiology , Lung Diseases, Fungal/complications , Lung Diseases, Fungal/diagnostic imaging , Lung Diseases, Fungal/microbiology , Male , Mannans/blood , Voriconazole/therapeutic use
10.
BMJ Case Rep ; 13(5)2020 May 12.
Article in English | MEDLINE | ID: covidwho-822228

ABSTRACT

Critically ill patients are at risk of developing both acute kidney injury (AKI) and invasive fungal infections (IFIs). Prompt and efficient treatment of the IFI is essential for the survival of the patient. This article examines three distinct clinical situations where liposomal amphotericin B, a broad-spectrum antifungal agent, was successfully used in the setting of AKI. The first was Aspergillus infection in a 63-year-old man with bleeding oesophageal varices related to advanced liver disease. The second was gastrointestinal mucormycosis in a 74-year-old man who developed a small bowel obstruction following an autologous stem cell transplant for mantle cell lymphoma. The third was a Fusarium infection in a 32-year-old woman on immunosuppression for a bilateral lung transplant for cystic fibrosis. In all three cases, liposomal amphotericin B was required for urgent management of the patient's IFI. We discuss the rationale for treatment with a potentially nephrotoxic agent in this setting.


Subject(s)
Acute Kidney Injury/complications , Amphotericin B/therapeutic use , Antifungal Agents/therapeutic use , Critical Illness , Invasive Fungal Infections/drug therapy , Invasive Fungal Infections/microbiology , Adult , Aged , Female , Humans , Male , Middle Aged
SELECTION OF CITATIONS
SEARCH DETAIL