Liposomal amphotericin B-the future.

Advances in medicine have led to a growing number of people with compromised or suppressed immune systems who are susceptible to invasive fungal infections. In particular, severe fungal infections are becoming increasingly common in ICUs, affecting people within and outside of traditional risk groups alike. This is exemplified by the emergence of severe viral pneumonia as a significant risk factor for invasive pulmonary aspergillosis, and the recognition of influenza-associated pulmonary aspergillosis and, more recently, COVID-19-associated pulmonary aspergillosis. The treatment landscape for haematological malignancies has changed considerably in recent years, and some recently introduced targeted agents, such as ibrutinib, are increasing the risk of invasive fungal infections. Consideration must also be given to the risk of drug-drug interactions between mould-active azoles and small-molecule kinase inhibitors. At the same time, infections caused by rare moulds and yeasts are increasing, and diagnosis continues to be challenging. There is growing concern about azole resistance among both moulds and yeasts, mandating continuous surveillance and personalized treatment strategies. It is anticipated that the epidemiology of fungal infections will continue to change and that new populations will be at risk. Early diagnosis and appropriate treatment remain the most important predictors of survival, and broad-spectrum antifungal agents will become increasingly important. Liposomal amphotericin B will remain an essential therapeutic agent in the armamentarium needed to manage future challenges, given its broad antifungal spectrum, low level of acquired resistance and limited potential for drug-drug interactions.

Is low dose of liposomal amphotericin B effective in management of acute invasive fungal rhinosinusitis? Our conclusions from Al-Mowassat University Hospital, Syria: a prospective observational study.

BACKGROUND: Acute invasive fungal rhinosinusitis (AIFRS) is a fatal infection associated with high morbidity and mortality. Although it is a rare disease, upsurge of AIFRS was noticed during the second wave of COVID-19 disease. Early diagnosis and management is the cornerstone for good outcomes. However, management of AIFRS is challengeable especially in developing countries due to limited resources and high prices of antifungal agents. No previous studies have been conducted to evaluate the outcomes of management of AIFRS in Syria. The purpose of this study is to report the results of management of AIFRS with low doses of liposomal amphotericin B in our tertiary hospital in Syria. METHODS: The outcomes of management of AIFRS cases were followed through a prospective observational study between January 2021 and July 2022. The required medical data were collected for each individual. Three-month mortality rate was studied. SPSS v.26 was used to perform the statistical analysis. Pearson Chi-square test was used to study the associations between different variables and mortality. Survival curves were plotted by the Kaplan-Meier to compare the survival probability. Log Rank (Mantel-Cox) test and Cox regression were conducted to evaluate the factors affecting survival within the follow up period. RESULTS: Of 70 cases, 36 (51.4%) were males and 34 (48.6%) were females. The mean age of patients was 52.5 years old. The most common underlying risk factor was diabetes mellitus (84.3%). The used dose of liposomal amphotericin B ranged between 2-3 mg/kg per day. The overall 3-month mortality rate was 35.7%. Significant association was found between survival and the following variables: Age, orbital involvement, stage, and comorbidity. CONCLUSION: The overall mortality rate was close to other studies. However, survival rate was worse than comparable studies in selected cases of AIFRS (older ages, involved orbits, advanced stages, and chronic immunodeficiency). Therefore, low doses of liposomal amphotericin B could be less effective in such cases and high doses are recommended.

Recommendations and guidelines for the diagnosis and management of Coronavirus Disease-19 (COVID-19) associated bacterial and fungal infections in Taiwan.

Coronavirus disease-19 (COVID-19) is an emerging infectious disease caused by SARS-CoV-2 that has rapidly evolved into a pandemic to cause over 600 million infections and more than 6.6 million deaths up to Nov 25, 2022. COVID-19 carries a high mortality rate in severe cases. Co-infections and secondary infections with other micro-organisms, such as bacterial and fungus, further increases the mortality and complicates the diagnosis and management of COVID-19. The current guideline provides guidance to physicians for the management and treatment of patients with COVID-19 associated bacterial and fungal infections, including COVID-19 associated bacterial infections (CABI), pulmonary aspergillosis (CAPA), candidiasis (CAC) and mucormycosis (CAM). Recommendations were drafted by the 7th Guidelines Recommendations for Evidence-based Antimicrobial agents use Taiwan (GREAT) working group after review of the current evidence, using the grading of recommendations assessment, development, and evaluation (GRADE) methodology. A nationwide expert panel reviewed the recommendations in March 2022, and the guideline was endorsed by the Infectious Diseases Society of Taiwan (IDST). This guideline includes the epidemiology, diagnostic methods and treatment recommendations for COVID-19 associated infections. The aim of this guideline is to provide guidance to physicians who are involved in the medical care for patients with COVID-19 during the ongoing COVID-19 pandemic.

Disease-specific gaps within fungal respiratory tract infections: clinical features, diagnosis, and management in critically ill patients.

PURPOSE OF REVIEW: We aim to examine the most recent findings in the area of invasive pulmonary fungal infections to determine the appropriate/and or lack of prevention measures and treatment of upper fungal respiratory tract infections in the critically ill. RECENT FINDINGS: This will be addressed by focusing on the pathogens and prognosis over different bedridden periods in ICU patients, the occurrence of invasive fungal respiratory superinfections in patients with severe coronavirus disease 2019 which has been recently noted following the SARS-CoV-2 pandemic. Relevant reports referenced within include randomized controlled trials, meta-analyses, observational studies, systematic reviews, and international guidelines, where applicable. Of note, it is clear there is a significant gap in our knowledge regarding whether bacterial and fungal infections in coronavirus disease 2019 are directly attributable to SARS-CoV-2 or a consequence of factors such as managing high numbers of critically unwell patients, and the prolonged duration of mechanical ventilation/ICU admission duration of stay. SUMMARY: An optimal diagnostic algorithm incorporating fungal biomarkers and molecular tools for early and accurate diagnosis of Pneumocystis pneumonia, invasive aspergillosis, candidemia, and endemic mycoses continues to be limited clinically. There is a lack of standardized molecular approach to identify fungal pathogens directly in formalin-fixed paraffin-embedded tissues and suboptimal diagnostic approaches for mould blood cultures, tissue culture processing for Mucorales, and fungal respiratory cultures (i.e., the routine use of bronchoscopic examination in ICU patients with influenza-associated pulmonary aspergillosis) for fungal point-of-care testing to detect and identify new, emerging or underrecognized, rare, or uncommon fungal pathogens.

RHINOSINUSITIS IN PATIENTS IN POST-COVID-19 PERIOD: ETIOLOGY, CLINICAL AND MORPHOLOGICAL CHARACTERISTICS.

OBJECTIVE: The aim is to identify the etiology, clinical and morphological features of rhinosinusitis in patients in post-COVID-19 period. PATIENTS AND METHODS: Materials and methods: In the present study, it was carried out the analysis of 11 cases of rhinosinusitis, which developed after COVID-19 infection. The diagnosis of rhi¬nosinusitis was established on the basis of anamnesis, clinical and laboratory examination, specialized instrumental examination (rhinoendoscopy, X-ray, magnetic resonance imaging, spiral and 3D computed tomography). All patients underwent endoscopic sanitation of the nasal cavity, expansion of the maxillary anastomosis, maxillary sinusotomy, sanitation of the maxillary sinuses and removal of pathologically altered tissues. Microbiological examination of the swab from the nasal cavity was carried out in all patients. Histological and morphometric research methods were used during the morphological study of surgical material. The nonparametric Mann-Whitney U test was used to compare the means in the groups. RESULTS: Results: The conducted comprehensive study made it possible to identify chronic atrophic rhinosinusitis at the stage of exacerbation caused by associations of bacteria and fungi in patients in post-COVID-19 period. Among bacteria, the authors most often noted Staphylococcus aureus, Staphylococcus epidermidis, Klebsiella pneumonia, Streptococcus pneumonia and Enterococcus faecalis. Among fungi, there were Aspergillus, Candida, Mucor and Coccidioides. Fungal infection was characterized by invasion into the mucous membrane of the nose and paranasal sinuses. In patients in post-COVID-19 period the invasive bacterial-fungal chronic atrophic rhinosinusitis at the stage of exacerbation was predominantly bilateral, characterized by the involvement of several or all paranasal sinuses in the process. Patients with such pathology complained of periodic fever, headaches and malaise; nasal congestion and constant difficulty in nasal breathing; yellowish-greenish-reddish discharge from the nasal cavity, sometimes with a fetid odor; discomfort and pain in the area of paranasal sinuses; immobility of the eyeball, hyposmia or anosmia; reduction or complete loss of vision. Frequent risk factors for the development of invasive bacterial-fungal chronic atrophic rhinosinusitis at the stage of exacerbation in patients in post-COVID-19 period were the information about moderate or severe course of this infection in anamnesis; comorbidities (predominantly diabetes mellitus, hypertensive disease and ischemic heart disease). CONCLUSION: Conclusions: The study conducted by the authors made it possible to identify the etiological, clinical and morphological features, as well as risk factors of rhinosinusitis in patients in post-COVID-19 period. This information will contribute to a better understanding of such pathology by the doctors and improve the diagnostic and treatment process.

Post-COVID fungal infections of maxillofacial region: a systematic review.

With the advent of coronavirus disease (COVID-19) pandemic, a wide range of life-threatening maxillofacial fungal coinfections have also been observed in patients. We conducted this systematic review to collate and evaluate the data to enable clinicians to understand the disease pattern and types of mycosis and provide meticulous management of these infections in COVID-19 patients. The review was carried out in accordance with Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. A systematic electronic literature search was conducted on major databases using keywords in combination with Boolean Operators. Manuscripts discussing cases of maxillofacial fungal infections in COVID-19 patients were included. A total of 11 studies were systematically reviewed to assess the fungal coinfections in COVID-19 patients. Twenty-one cases of mucormycosis, 58 of candidiasis, and 1 each of aspergillosis and mixed infection were observed in the region of head and neck. Significant increase in invasive fungal infection is evident in patients suffering from COVID-19 which could be due to immunosuppression and other pre-existing comorbidities. Early diagnosis and intervention like systemic antifungals or surgical debridement is mandatory to reduce morbidity and mortality.

Fungal Bloodstream Co-infection by Trichosporon asahii in a COVID-19 Critical Patient: Case Report and Literature Review.

Opportunistic infections are serious complications in critically ill COVID-19 patients, especially co-infections with bacterial and fungal agents. Here we report a rare case of bloodstream co-infection by Trichosporon asahii, an emerging yeast, and Acinetobacterbaumannii, an opportunistic nosocomial pathogen, both multidrug resistant, in a tertiary hospital from southern Brazil. A review of the literature regarding similar cases is also included. Treatment with multiple antimicrobials failed, and the patient progressed to death four days after the diagnosis of bacteremia and fungemia.

Orofacial Mycoses in Coronavirus Disease-2019 (COVID-19): A Systematic Review.

OBJECTIVES: Studies reviewing orofacial mycoses in coronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome 2 (SARS-CoV-2) infection are sparse. Here we review the major oral and maxillofacial mycoses of COVID-19, the associated comorbidities, and the probable precipitating factors. METHODS: English-language manuscripts published between March 2020 and October 2021 were searched using PubMed, OVID, SCOPUS, and Web of Science databases, using appropriate keywords. RESULTS: We identified 30 articles across 14 countries, which met the inclusion criteria of PRISMA guidelines. These yielded a total of 292 patients with laboratory-confirmed COVID-19, 51.4% (n = 150) of whom presented with oral and maxillofacial fungal infections, mainly comprising candidosis, mucormycosis, and aspergillosis. Candida infections were the most prevalent, present in 64% (n = 96), followed by mucormycosis, and only a single case of aspergillosis was noted. Oral and maxillofacial mycoses were predominantly seen in those with comorbidities, especially in those with diabetes (52.4%). Oral mucormycosis was noted in 8.6% (n = 13) and mainly manifested on the hard palate. An overall event rate of oral/maxillofacial mucormycosis manifestation in patients with COVID-19 with diabetes mellitus type 1/2 was about 94% (49/52; 95% confidence interval, 0.73%-0.89%), implying a very high association between diabetes mellitus and the latter condition. All fungal infections appeared either concurrently with COVID-19 symptoms or during the immediate recovery period. CONCLUSIONS: SARS-CoV-2 infection-related immunosuppression, steroid therapy, as well as comorbidities such as diabetic hyperglycemia appear to be the major predisposing factors for the onset of oral and maxillofacial mycoses in patients with COVID-19 across all age groups.

Utility of MGG and Papanicolaou stained smears in the detection of Mucormycosis in nasal swab/scraping/biopsy samples of COVID 19 patients.

BACKGROUND: COVID 19 has been rapidly spreading across the globe. As a result of alteration of the immune milieu by COVID 19 and its treatment, there has been a rise in opportunistic fungal infections particularly Mucormycosis in these patients. Delay in diagnosis of these fungal infections can be fatal. The usual diagnostic modalities used to detect Mucor include potassium hydroxide (KOH) mount, fungal culture, and histopathology. Since histopathology and fungal culture have a long turnaround time we are dependent on KOH mount for rapid results. Here we investigate the role of stained cytology smears in the rapid diagnosis of Mucormycosis. METHODS: A prospective observational study was conducted in a tertiary health care hospital on samples of patients clinically suspected to have Mucormycosis. We performed May Grunwald Giemsa (MGG) and Papanicolaou (PAP) stains on the remnant samples of nasal swabs/scrapings/biopsies after KOH test and fungal culture. We took 16 KOH positive and 16 KOH negative samples. We also examined 16 fresh samples from patients whose earlier samples were reported to be negative on KOH test. RESULTS: The 6/16 KOH positive samples were found to be positive on stained cytology smears and 2 were mixed infections wherein both Mucor and Aspergillus were seen. The 4/16 KOH negative samples were positive for Mucor with one sample having both Mucor and Aspergillus. The 3/16 repeat samples which were earlier negative on KOH test were positive for Mucor. CONCLUSION: Stained cytology smears if used in conjunction with KOH test can increase the overall sensitivity of detection of Mucormycosis and mixed infections.

Fungal infections diagnosis - Past, present and future.

Despite the scientific advances observed in the recent decades and the emergence of new methodologies, the diagnosis of systemic fungal infections persists as a problematic issue. Fungal cultivation, the standard method that allows a proven diagnosis, has numerous disadvantages, as low sensitivity (only 50% of the patients present positive fungal cultures), and long growth time. These are factors that delay the patient's treatment and, consequently, lead to higher hospital costs. To improve the accuracy and quickness of fungal infections diagnosis, several new methodologies attempt to be implemented in clinical microbiology laboratories. Most of these innovative methods are independent of pathogen isolation, which means that the diagnosis goes from being considered proven to probable. In spite of the advantage of being culture-independent, the majority of the methods lack standardization. PCR-based methods are becoming more and more commonly used, which has earned them an important place in hospital laboratories. This can be perceived now, as PCR-based methodologies have proved to be an essential tool fighting against the COVID-19 pandemic. This review aims to go through the main steps of the diagnosis for systemic fungal infection, from diagnostic classifications, through methodologies considered as "gold standard", to the molecular methods currently used, and finally mentioning some of the more futuristic approaches.

A National Strategy to Diagnose Coronavirus Disease 2019-Associated Invasive Fungal Disease in the Intensive Care Unit.

BACKGROUND: Fungal coinfection is a recognized complication of respiratory virus infections, increasing morbidity and mortality, but can be readily treated if diagnosed early. An increasing number of small studies describing aspergillosis in coronavirus disease 2019 (COVID-19) patients with severe respiratory distress are being reported, but comprehensive data are lacking. The aim of this study was to determine the incidence, risk factors, and impact of invasive fungal disease in adult COVID-19 patients with severe respiratory distress. METHODS: An evaluation of a national, multicenter, prospective cohort evaluation of an enhanced testing strategy to diagnose invasive fungal disease in COVID-19 intensive care patients. Results were used to generate a mechanism to define aspergillosis in future COVID-19 patients. RESULTS: One-hundred and thirty-five adults (median age: 57, M/F: 2.2/1) were screened. The incidence was 26.7% (14.1% aspergillosis, 12.6% yeast infections). The overall mortality rate was 38%; 53% and 31% in patients with and without fungal disease, respectively (P = .0387). The mortality rate was reduced by the use of antifungal therapy (mortality: 38.5% in patients receiving therapy vs 90% in patients not receiving therapy (P = .008). The use of corticosteroids (P = .007) and history of chronic respiratory disease (P = .05) increased the likelihood of aspergillosis. CONCLUSIONS: Fungal disease occurs frequently in critically ill, mechanically ventilated COVID-19 patients. The survival benefit observed in patients receiving antifungal therapy implies that the proposed diagnostic and defining criteria are appropriate. Screening using a strategic diagnostic approach and antifungal prophylaxis of patients with risk factors will likely enhance the management of COVID-19 patients.

Paving the Way to Overcome Antifungal Drug Resistance: Current Practices and Novel Developments for Rapid and Reliable Antifungal Susceptibility Testing.

The past year has established the link between the COVID-19 pandemic and the global spread of severe fungal infections; thus, underscoring the critical need for rapid and realizable fungal disease diagnostics. While in recent years, health authorities, such as the Centers for Disease Control and Prevention, have reported the alarming emergence and spread of drug-resistant pathogenic fungi and warned against the devastating consequences, progress in the diagnosis and treatment of fungal infections is limited. Early diagnosis and patient-tailored therapy are established to be key in reducing morbidity and mortality associated with fungal (and cofungal) infections. As such, antifungal susceptibility testing (AFST) is crucial in revealing susceptibility or resistance of these pathogens and initiating correct antifungal therapy. Today, gold standard AFST methods require several days for completion, and thus this much delayed time for answer limits their clinical application. This review focuses on the advancements made in developing novel AFST techniques and discusses their implications in the context of the practiced clinical workflow. The aim of this work is to highlight the advantages and drawbacks of currently available methods and identify the main gaps hindering their progress toward clinical application.

Mycotic infection prevalence among patients undergoing bronchoalveolar lavage with search of SARS-CoV-2 after two negative nasopharyngeal swabs.

The evidence that severe coronavirus disease 2019 (COVID-19) is a risk factor for development of mycotic respiratory infection with an increased mortality is rising. Immunosuppressed are among the most susceptible patients andAspergillusspecies is the most feared superinfection. In this study we evaluated mycotic isolation prevalence on bronchoalveolar lavage (BAL) of patients who underwent bronchoscopy in search of severe acute respiratory coronavirus 2 (SARS-CoV-2) RNA. Moreover, we described the clinical characteristics and main outcomes of these patients. We included 118 patients, 35.9% of them were immunosuppressed for different reasons: in 23.7% we isolated SARS-CoV-2 RNA, in 33.1% we identified at least one mycotic agent and both in 15.4%. On BAL we observed in three casesAspergillusspp, in six casesPneumocystisand in 32Candidaspp. The prevalence of significant mold infection was 29.3% and 70.7% of cases were false positive or clinically irrelevant infections. In-hospital mortality of patients with fungal infection was 15.3%. The most frequent computed tomography (CT) pattern, evaluated with the Radiological Society of North America consensus statement, among patients with a mycotic pulmonary infection was the atypical one (p< 0.0001). Mycotic isolation on BAL may be interpreted as an innocent bystander, but its identification could influence the prognosis of patients, especially in those who need invasive investigations during the COVID-19 pandemic; BAL plays a fundamental role in resolving clinical complex cases, especially in immunosuppressed patients independently from radiological features, without limiting its role in ruling out SARS-CoV-2 infection.

Pediatric Allergic Fungal Sinusitis: A Clinical Review.

Allergic fungal sinusitis (AFS) is the most common type of fungal sinus infection. AFS is a robust allergic reaction to inhaled soil fungi that causes sinus inflammation, and the fungal debris then accumulates in the sinus cavities. This accumulation can cause nasal polyps, facial pain and pressure, bone remodeling of the face, and even bone erosion, which can cause damage to the eyes and brain. AFS can also cause thick, sticky nasal mucus and postnasal drip, and it can affect the sense of smell. Most patients with AFS are adolescents who also have chronic symptoms of allergic rhinitis and asthma. Endoscopic sinus surgery to remove the disease and open the sinus cavities is the main treatment approach. Adjuvant immunotherapy is helpful in reducing the inflammatory response and preventing future recurrence of this allergy-mediated condition. [Pediatr Ann. 2021;50(7):e297-e303.].

Emerging Fungal Infections.

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.

Geospatial Spread of Antimicrobial Resistance, Bacterial and Fungal Threats to Coronavirus Infectious Disease 2019 (COVID-19) Survival, and Point-of-Care Solutions.

CONTEXT.­: Point-of-care testing (POCT) is inherently spatial, that is, performed where needed, and intrinsically temporal, because it accelerates decision-making. POCT efficiency and effectiveness have the potential to facilitate antimicrobial resistance (AMR) detection, decrease risks of coinfections for critically ill patients with coronavirus infectious disease 2019 (COVID-19), and improve the cost-effectiveness of health care. OBJECTIVES.­: To assess AMR identification by using POCT, describe the United States AMR Diagnostic Challenge, and improve global standards of care for infectious diseases. DATA SOURCES.­: PubMed, World Wide Web, and other sources were searched for papers focusing on AMR and POCT. EndNote X9.1 (Clarivate Analytics) consolidated abstracts, URLs, and PDFs representing approximately 500 articles were assessed for relevance. Panelist insights at Tri•Con 2020 in San Francisco and finalist POC technologies competing for a US $20,000,000 AMR prize are summarized. CONCLUSIONS.­: Coinfections represent high risks for COVID-19 patients. POCT potentially will help target specific pathogens, refine choices for antimicrobial drugs, and prevent excess morbidity and mortality. POC assays that identify patterns of pathogen resistance can help tell us how infected individuals spread AMR, where geospatial hotspots are located, when delays cause death, and how to deploy preventative resources. Shared AMR data "clouds" could help reduce critical care burden during pandemics and optimize therapeutic options, similar to use of antibiograms in individual hospitals. Multidisciplinary health care personnel should learn the principles and practice of POCT, so they can meet needs with rapid diagnostic testing. The stakes are high. Antimicrobial resistance is projected to cause millions of deaths annually and cumulative financial loses in the trillions by 2050.

Bacterial and fungal coinfections in COVID-19 patients hospitalized during the New York City pandemic surge.

We observed bacterial or fungal coinfections in COVID-19 patients admitted between March 1 and April 18, 2020 (152 of 4,267, 3.6%). Among these patients, mortality was 57%; 74% were intubated; 51% with bacteremia had central venous catheters. Time to culture positivity was 6-7 days, and 79% had received prior antibiotics. Metallo-ß-lactamase-producing E. cloacae coinfections occurred in 5 patients.

Acute Invasive Rhino-Orbital Mucormycosis in a Patient With COVID-19-Associated Acute Respiratory Distress Syndrome.

Acute invasive fungal rhinosinusitis is a rare, although highly morbid, infection primarily affecting immunosuppressed individuals. The same population is at particularly high risk of complications and mortality in the setting of SARS-CoV-2 infection and coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome. The authors present a case of acute invasive fungal rhino-orbital mucormycosis in a patient with COVID-19 and discuss the prevalence, diagnosis, and treatment of fungal coinfections in COVID-19. Prompt recognition, initiation of therapy, and consideration of the challenges of rapidly evolving COVID-19 therapy guidelines are important for improving patient survival.

Systemic mycoses: a potential alert for complications in COVID-19 patients.

As the global COVID-19 pandemic spreads worldwide, new challenges arise in the clinical landscape. The need for reliable diagnostic methods, treatments and vaccines for COVID-19 is the major worldwide urgency. While these goals are especially important, the growing risk of co-infections is a major threat not only to the health systems but also to patients' lives. Although there is still not enough published statistical data, co-infections in COVID-19 patients found that a significant number of patients hospitalized with COVID-19 developed secondary systemic mycoses that led to serious complications and even death. This review will discuss some of these important findings with the major aim to warn the population about the high risk of concomitant systemic mycoses in individuals weakened by COVID-19.