Bacterial and fungal secondary infections occurring in COVID-19 patients followed in intensive care: a retrospective study.

INTRODUCTION: We aimed to investigate the effects of secondary bacterial and fungal infections on patient outcomes in patients followed up in the intensive care unit (ICU) due to coronavirus disease 2019 (COVID-19). METHODOLOGY: We retrospectively analyzed reverse transcriptase polymerase chain reaction (RT-PCR) positive COVID-19 patients followed in the ICU of our hospital between March 2020 and June 2021, using the hospital information system. Demographic data, pathogens causing a secondary infection, onset time of secondary infection, and patient outcomes were recorded. RESULTS: A total of 251 RT-PCR positive patients who met the inclusion criteria were evaluated. The mean length of stay (LOS) in the ICU was 13.3 ± 9.6 days. During this period, 165 (65.7%) patients died. When blood, urine, respiratory tract, and catheter cultures were examined, the number of patients with growth in at least one culture was 129 (51.4%). There was growth in a total of 227 cultures. The highest culture positivity rate was observed in respiratory tract samples (n = 94, 41.4%). Gram-negative bacterial pathogens (n = 130, 58.4%) predominated. Candida spp. was more frequent in urine cultures. The median day of the occurrence of secondary infection was 10 (range: 6-15). Patients who developed secondary infection had a longer LOS and higher mortality rate than patients who did not (p < 0.001). CONCLUSIONS: Gram-negative secondary infections, predominantly in respiratory tract cultures, occurred in COVID-19 patients followed in the ICU. As a result, the LOS was prolonged and mortality rates increased.

Development and validation of machine learning-based models for predicting healthcare-associated bacterial/fungal infections among COVID-19 inpatients: a retrospective cohort study.

BACKGROUND: COVID-19 and bacterial/fungal coinfections have posed significant challenges to human health. However, there is a lack of good tools for predicting coinfection risk to aid clinical work. OBJECTIVE: We aimed to investigate the risk factors for bacterial/fungal coinfection among COVID-19 patients and to develop machine learning models to estimate the risk of coinfection. METHODS: In this retrospective cohort study, we enrolled adult inpatients confirmed with COVID-19 in a tertiary hospital between January 1 and July 31, 2023, in China and collected baseline information at admission. All the data were randomly divided into a training set and a testing set at a ratio of 7:3. We developed the generalized linear and random forest models for coinfections in the training set and assessed the performance of the models in the testing set. Decision curve analysis was performed to evaluate the clinical applicability. RESULTS: A total of 1244 patients were included in the training cohort with 62 healthcare-associated bacterial/fungal infections, while 534 were included in the testing cohort with 22 infections. We found that patients with comorbidities (diabetes, neurological disease) were at greater risk for coinfections than were those without comorbidities (OR = 2.78, 95%CI = 1.61-4.86; OR = 1.93, 95%CI = 1.11-3.35). An indwelling central venous catheter or urinary catheter was also associated with an increased risk (OR = 2.53, 95%CI = 1.39-4.64; OR = 2.28, 95%CI = 1.24-4.27) of coinfections. Patients with PCT > 0.5 ng/ml were 2.03 times (95%CI = 1.41-3.82) more likely to be infected. Interestingly, the risk of coinfection was also greater in patients with an IL-6 concentration < 10 pg/ml (OR = 1.69, 95%CI = 0.97-2.94). Patients with low baseline creatinine levels had a decreased risk of bacterial/fungal coinfections(OR = 0.40, 95%CI = 0.22-0.71). The generalized linear and random forest models demonstrated favorable receiver operating characteristic curves (ROC = 0.87, 95%CI = 0.80-0.94; ROC = 0.88, 95%CI = 0.82-0.93) with high accuracy, sensitivity and specificity of 0.86vs0.75, 0.82vs0.86, 0.87vs0.74, respectively. The corresponding calibration evaluation P statistics were 0.883 and 0.769. CONCLUSIONS: Our machine learning models achieved strong predictive ability and may be effective clinical decision-support tools for identifying COVID-19 patients at risk for bacterial/fungal coinfection and guiding antibiotic administration. The levels of cytokines, such as IL-6, may affect the status of bacterial/fungal coinfection.

Infectious Diseases in a Changing Climate.

This JAMA Insights in the Climate Change and Health series discusses the importance of clinicians having awareness of changes in the geographic range, seasonality, and intensity of transmission of infectious diseases to help them diagnose, treat, and prevent these diseases.

Epidemiology of fungal infection in COVID 19 in Spain during 2020 and 2021: a nationwide study.

We realize a nationwide population-based retrospective study to analyze the characteristics and risk factors of fungal co-infections in COVID-19 hospitalized patients as well as describe their causative agents in the Spanish population in 2020 and 2021. Data were obtained from records in the Minimum Basic Data Set of the National Surveillance System for Hospital Data in Spain, provided by the Ministry of Health, and annually published with two years lag. The assessment of the risk associated with the development of healthcare-associated fungal co-infections was assessed using an adjusted logistic regression model. The incidence of fungal co-infection in COVID-19 hospitalized patients was 1.41%. The main risk factors associated were surgery, sepsis, age, male gender, obesity, and COPD. Co-infection was associated with worse outcomes including higher in-hospital and in ICU mortality, and higher length of stay. Candida spp. and Aspergillus spp. were the microorganisms more frequent. This is the first study analyzing fungal coinfection at a national level in hospitalized patients with COVID-19 in Spanish population and one of the few studies available that demonstrate that surgery was an independent risk factor of Aspergillosis coinfection in COVID-19 patients.

Impact of ontogenic changes on the dynamics of a fungal crop disease model motivated by coffee leaf rust.

Ontogenic resistance has been described for many plant-pathogen systems. Conversely, coffee leaf rust, a major fungal disease that drastically reduces coffee production, exhibits a form of ontogenic susceptibility, with a higher infection risk for mature leaves. To take into account stage-dependent crop response to phytopathogenic fungi, we developed an SEIR-U epidemiological model, where U stands for spores, which differentiates between young and mature leaves. Based on this model, we also explored the impact of ontogenic resistance on the sporulation rate. We computed the basic reproduction number [Formula: see text], which classically determines the stability of the disease-free equilibrium. We identified forward and backward bifurcation cases. The backward bifurcation is generated by the high sporulation of young leaves compared to mature ones. In this case, when the basic reproduction number is less than one, the disease can persist. These results provide useful insights on the disease dynamics and its control. In particular, ontogenic resistance may require higher control efforts to eradicate the disease.

Lung infections due to emerging fungal pathogens.

PURPOSE OF REVIEW: This review highlights the epidemiology, pathogenesis and clinical management of pulmonary infections caused by emerging fungal organisms. RECENT FINDINGS: Emerging fungal infections have arisen as a result of population and environmental changes. An enlarging pool of immunocompromised hosts on triazole antifungal prophylaxis has led to an increased incidence of non- Aspergillus molds, such as Fusarium , Scedosporium and Lomentospora spp. Advances in diagnostic capabilities led to the identification of the Emergomyces genus and non- dermatitidis Blastomyces species, which have a significant disease burden in Africa and the Middle East. Climate change has contributed to changing the distribution of previously confined endemic mycoses, like coccidioidomycosis and talaromycosis. These emerging organisms pose important diagnostic and therapeutic challenges. SUMMARY: Newly recognized pathogenic fungi and established endemic mycoses with expanding geographic boundaries have become important agents of pulmonary disease. There is a dearth of clinical evidence on the appropriate management of these infections.

Invasive fungal pathogens from the tropical and temperate areas - a challenge in pathology and diagnosis.

Fungi play a vital role in ensuring a physiological balance in the surrounding environments, interacting closely with humans, plants, and animals. While most of the time their contribution is beneficial, occasionally, they can become harmful, especially in patients with weakened immune systems. The work at hand aims to present the most common fungal pathogens involved in invasive infections, focusing on fungi that are present in the tropical and temperate areas of the world. While in the former, due to the humid climate, most fungal infections are caused by dimorphic fungi such as Coccidioides spp., Blastomyces spp., Histoplasma spp., Emergomyces spp. and Paracoccidioides spp., in the latter, after Candida spp., the most frequent fungi that are involved in disseminated mycosis are Aspergillus spp., Fusarium spp. and species from the order Mucorales. Nowadays, the etiology, severity, and number of cases of fungal diseases are starting to rise significantly. There are no exact reasons reported for this increase, but several factors are thought to be incriminated: the expansion of the range of medical conditions that constitute risk factors for developing the disease, an improvement in the available diagnostic methods, the commodity offered by modern traveling services associated with the lack of an available vaccine against fungal infections, as well as climatic influences. All the above-mentioned aspects consequently caused infections that used to be endemic to be spread worldwide. Therefore, it is of critical importance to understand the epidemiology, clinical manifestations of fungi induced diseases, virulence factors, and diagnosis for each of those pathogens.

FIRST RECORD OF BATRACHOCHYTRIUM DENDROBATIDIS IN THE NORTHERN NETHERLANDS.

Batrachochytrium dendrobatidis (Bd) infects amphibians and has been linked to the decline of hundreds of anuran amphibians all over the world. In the province of Groningen in the Netherlands, this fungal pathogen was not detected before this study. To determine whether Groningen was Bd-free, we surveyed 12 locations in this province in 2020 and 2021. Samples were then used to quantify the presence of Bd with a qPCR assay. In total, 2 out of 110 (∼0.02%) collected in 2020 and 11 out of 249 samples collected in 2021 tested positive for Bd. Infected amphibians were found in 4 out of the 12 sites, and the prevalence of Bd was estimated at 4% for both years combined. Our study provides the first record of Bd in Groningen, and we hypothesize that Bd is present throughout the Netherlands in regions currently considered "Bd-free." Furthermore, we warn scientists and policymakers to be apprehensive when calling a site free from Bd when sampling is limited or not recent.

Establishing associated risk factors, including fungal and parasitic infections among Malaysians living with schizophrenia.

The aetiology of schizophrenia is multifactorial, and the identification of its risk factors are scarce and highly variable. A cross-sectional study was conducted to investigate the risk factors associated with schizophrenia among Malaysian sub-population. A total of 120 individuals diagnosed with schizophrenia (SZ) and 180 non-schizophrenic (NS) individuals participated in a questionnaire-based survey. Data of complete questionnaire responses obtained from 91 SZ and 120 NS participants were used in statistical analyses. Stool samples were obtained from the participants and screened for gut parasites and fungi using conventional polymerase chain reaction (PCR). The median age were 46 years (interquartile range (IQR) 37 to 60 years) and 35 years (IQR 24 to 47.75 years) for SZ and NS respectively. Multivariable binary logistic regression showed that the factors associated with increased risk of SZ were age, sex, unemployment, presence of other chronic ailment, smoking, and high dairy consumption per week. These factors, except sex, were positively associated with the severity of SZ. Breastfed at infancy as well as vitamin and supplement consumption showed a protective effect against SZ. After data clean-up, fungal or parasitic infections were found in 98% (39/42). of SZ participants and 6.1% (3/49) of NS participants. Our findings identified non-modifiable risk factors (age and sex) and modifiable lifestyle-related risk factors (unemployment, presence of other chronic ailment, smoking, and high dairy consumption per week) associated with SZ and implicate the need for medical attention in preventing fungal and parasitic infections in SZ.

Incidence and Impact of Fungal Infections in Post-Transplantation Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis and Haploidentical Hematopoietic Cell Transplantation: A Center for International Blood and Marrow Transplant Research Analysis.

Fungal infection (FI) after allogeneic hematopoietic cell transplantation (HCT) is associated with increased morbidity and mortality. Neutropenia, HLA mismatch, graft-versus-host disease (GVHD), and viral infections are risk factors for FI. The objectives of this Center for International Blood and Marrow Transplant Research registry study were to compare the incidence and density of FI occurring within 180 days after HCT in matched sibling (Sib) transplants with either calcineurin inhibitor (CNI)-based or post-transplantation cyclophosphamide (PTCy)-based GVHD prophylaxis and related haploidentical transplants receiving PTCy, and to examine the impact of FI by day 180 on transplantation outcomes. METHODS: Patients who underwent their first HCT between 2012 and 2017 for acute myeloid leukemia, acute lymphoblastic leukemia, and myelodysplastic syndrome and received a related haploidentical transplant with PTCy (HaploCy; n = 757) or a Sib transplant with PTCy (SibCy; n = 403) or CNI (SibCNI; n = 1605) were analyzed. The incidence of FI by day 180 post-HCT was calculated as cumulative incidence with death as the competing risk. The associations of FI with overall survival, transplant-related mortality, chronic GVHD, and relapse at 2 years post-HCT were examined in Cox proportional hazards regression models. Factors significantly associated with the outcome variable at a 1% level were kept in the final model. RESULTS: By day 180 post-HCT, 56 (7%) HaploCy, 24 (6%), SibCy, and 59 (4%) SibCNI recipients developed ≥1 FI (P < .001). The cumulative incidence of yeast FI was 5.2% (99% confidence interval [CI], 3.3% to 7.3%) for HaploCy, 2.2% (99% CI, .7% to 4.5%) for SibCy, and 1.9% (99% CI, 1.1% to 2.9%) for SibCNI (P = .001), and that of mold FI was 2.9% (99% CI, 1.5% to 4.7%), 3.7% (99% CI, 91.7% to 6.6%), and 1.7% (99% CI, 1.0% to 2.6%), respectively (P = .040). FI was associated with an increased risk of death, with an adjusted hazard ratio (HR) of 4.06 (99% CI, 2.2 to 7.6) for HaploCy, 4.7 (99% CI, 2.0 to 11.0) for SibCy, and 3.4 (99% CI, 1.8 to 6.4) for SibCNI compared with SibCNI without FI (P < .0001 for all). Similar associations were noted for transplantation-related mortality. FI did not impact rates of relapse or chronic GVHD. CONCLUSIONS: Rates of FI by day 180 ranged between 1.9% and 5.2% for yeast FI and from 1.7% to 3.7% for mold FI across the 3 cohorts. The use of PTCy was associated with higher rates of yeast FI only in HaploHCT and with mold FI in both HaploHCT and SibHCT. The presence of FI by day 180 was associated with increased risk for overall mortality and transplant-related mortality at 2 years regardless of donor type or PTCy use. Although rates of FI were low with PTCy, FI is associated with an increased risk of death, underscoring the need for improved management strategies.

Plain language summary: Did the COVID-19 pandemic change the resistance to current antifungal medicines?

WHAT IS THIS SUMMARY ABOUT?: Previous research shows that patients with COVID-19 have a high chance of getting fungal infections. Medicines called antifungals are used to treat fungal infections. However, some fungi are resistant, which means the fungi are not killed by the antifungals and they keep growing, which can make the patients sicker and even die. This is a summary of a study that looked at whether different types of fungi and their resistance to antifungals changed from before COVID-19 to during the pandemic. WHAT WERE THE RESULTS?: We found that some fungi were more common before while others were more common during the pandemic. We also observed that resistance to antifungals did not change much either between fungi collected before and during the COVID-19 pandemic. WHAT DO THE RESULTS OF THE STUDY MEAN?: Knowing which fungal species are resistant to each antifungal can help doctors choose the best treatment. The results from this study may help scientists understand the effect of the COVID-19 pandemic on antifungal resistance.

An analysis of the risk factors for invasive fungal infections in preterm infants and a discussion of prevention strategies.

BACKGROUND: Although the success rate of resuscitation in preterm infants is increasing, the long length of hospital stay in preterm infants and the need for more invasive operations, coupled with the widespread use of empirical antibiotics, have increased the prevalence of fungal infections in preterm infants in neonatal intensive care units (NICUs) year on year. OBJECTIVE: The present study aims to explore the risk factors of invasive fungal infections (IFI) in preterm infants and to identify some prevention strategies. METHODS: A total of 202 preterm infants with a gestational age of 26 weeks to 36+6 weeks and a birth weight of less than 2,000 g, admitted to our neonatal unit during the 5-year period from January 2014 to December 2018, were selected for the study. Among these preterm infants, six cases that developed fungal infections during hospitalization were enrolled as the study group, and the remaining 196 infants who did not develop fungal infections during hospitalization were the control group. The gestational age, length of hospital stay, duration of antibiotic therapy, duration of invasive mechanical ventilation, indwelling duration of the central venous catheter, and duration of intravenous nutrition of the two groups were compared and analyzed. RESULTS: There were statistically significant differences between the two groups in the gestational age, length of hospital stay, and duration of antibiotic therapy. CONCLUSION: A small gestational age, a lengthy hospital stay, and long-term use of broad-spectrum antibiotics are the high-risk factors for fungal infections in preterm infants. Medical and nursing measures to address the high-risk factors might reduce the incidence of fungal infections and improve the prognosis in preterm infants.

Donor-derived endemic mycoses after solid organ transplantation: A review of reported cases.

BACKGROUND: Donor-derived endemic mycoses are infrequently reported. We summarized the clinical characteristics and outcomes of these infections to provide guidance to transplant clinicians. METHODS: Multiple databases were reviewed from inception through May 31, 2023 using endemic fungi as key words (e.g., Coccidioides, histoplasma, blastomyces, talaromyces, paracoccidioides). Only donor-derived infections (DDI) were included. RESULTS: Twenty-four cases of DDI were identified from 18 published reports; these included 16 coccidioidomycosis, seven histoplasmosis, and one talaromycosis. No cases of blastomycosis and paracoccidiodomycosis were published. The majority were male (17/24,70.8%). Half of the cases were probable (12/24, 50%), seven were possible (29.2%), and only five were proven DDI (20.8%). Donor-derived coccidioidomycosis were observed in kidney (n = 11), lung (n = 6), liver (n = 3), heart (n = 2) and combined SOT recipients (1 KP, 1 KL) at a median time of .9 (range .2-35) months after transplantation. For histoplasmosis, the majority were kidney recipients (6 of 7 cases) at a median onset of 8 (range .4-48) months after transplantation. The single reported possible donor-derived talaromycosis occurred in a man whose organ donor had at-risk travel to Southeast Asia. Collectively, the majority of donors had high-risk exposure to Coccidioides (9/11) or Histoplasma sp. (6/6). Most donor-derived endemic mycoses were disseminated (18/24, 75%), and mortality was reported in almost half of recipients (11/24, 45.8%). CONCLUSION: Donor-derived endemic mycoses are often disseminated and are associated with high mortality. A detailed evaluation of donors for the potential of an undiagnosed fungal infection prior to organ donation is essential to mitigate the risk of these devastating infections.

Frequency of fungal pathogens in autopsy studies of people who died with HIV in Africa: a scoping review.

BACKGROUND: Fungal infections are common in HIV-infected individuals and significantly contribute to mortality. However, a substantial number of cases are undiagnosed before death. OBJECTIVE: To determine the frequency of fungal pathogens in autopsy studies of people who died with HIV in Africa. METHODS: We conducted a scoping review of autopsy studies conducted in Africa. DATA SOURCES: PubMed, Scopus, Web of Science, Embase, Google Scholar, and African Journal Online. STUDY ELIGIBILITY CRITERIA: The review encompasses studies published from inception to September 2023, and no language restrictions were imposed during the search process. We included studies that reported histopathological or microbiological evidence for the diagnosis of fungal infections and other pathogens. DATA SYNTHESIS: Data were summarized using descriptive statistics and no meta-analysis was performed. RESULTS: We examined 30 articles reporting studies conducted between 1991 and 2019, encompassing a total of 13 066 HIV-infected decedents across ten African countries. In five studies, the autopsy type was not specified. Among those studies with specified autopsy types, 20 involved complete diagnostic autopsies, whereas 5 were categorized as partial or minimally invasive autopsies. There were 2333 pathogens identified, with 946 (40.5%) being mycobacteria, 856 (36.7%) fungal, 231 (3.8%) viral, 208 (8.9%) parasitic, and 92 (3.9%) bacterial. Of the 856 fungal pathogens identified, 654 (28.0%) were Cryptococcus species, 167 (7.2%) Pneumocystis jirovecii, 16 (0.69%) Histoplasma species, 15 (0.64%) Aspergillus species, and 4 (0.17%) Candida species. Other major non-fungal pathogens identified were cytomegalovirus 172 (7.37%) and Toxoplasma gondii 173 (7.42%). CONCLUSIONS: Invasive fungal infections occur in over one-third of people who succumb to HIV in Africa. In addition to cryptococcosis and Pneumocystis jirovecii pneumonia, integrating other priority fungal pathogen detection and management strategies into the broader framework of HIV care in Africa is recommended. This involves increasing awareness regarding the impact of fungal infections in advanced HIV disease and strengthening diagnostic and treatment capacity.

The Nairobi Declaration 2023: A commitment to address deadly yet neglected fungal diseases in Africa.

On May 30th and 31st, 2023, delegates representing various African subregions, together with global representatives from the International Society of Human and Animal Mycology (ISHAM), the European Confederation of Medical Mycology (ECMM), the United States Centre for Disease Control and Prevention (CDC), and Global Action for Fungal Infections (GAFFI), convened in Nairobi, Kenya under the aegis of the Pan African Mycology Working Group, a working group of ISHAM. The meeting objectives were, amongst others, to deliberate on a continental response to the World Health Organisation Fungal Priority Pathogen List and facilitate interaction between global and regional leaders. Country delegates and international speakers addressed Africa's fungal disease burden; capacity for diagnosis and management; ongoing surveillance; knowledge gaps and trends in invasive fungal diseases such as Candida auris, mucormycosis, aspergillosis, and Acquired Immune Deficiency Syndrome (AIDS)-related mycoses; and current laboratory practice. During the technical sessions, expert panels deliberated on establishing and financing of national/regional surveillance networks for mycoses; establishing and sustaining African-led collaborations; expanding on existing laboratory and point-of-care diagnostic capacity as well as planning a mycology reference laboratory service and network in Africa. The meeting also highlighted successful African-led collaborations, capacity building, and clinical trial initiatives. The meeting conclusions informed the resolutions of the Nairobi Declaration calling for improved awareness; strong collaborations between clinical and laboratory teams across Africa; improved fungal disease surveillance within the continent; access to antifungals and diagnostics; and leveraging qualified human resources for mycology present within and outside Africa to facilitate trainings, collaborations, and exchanges.

This review presents the current state of the art in medical mycology in Africa discussed at the first scientific meeting of the Pan African Mycology Working Group, an affiliate of the International Society for Human and Animal Mycology (ISHAM) held in Nairobi, Kenya on May 30th and 31st, 2023.

A study on prevalence, profile, and risk factors of developing fungal infection in patients with diabetic foot ulcer.

BACKGROUND: Many chronic nonhealing diabetic foot ulcers (DFUs) with increased rates of amputation are frequently associated with fungal infections. PURPOSE: To evaluate the prevalence, profile, and risk factors of developing a fungal infection in patients with DFU. METHODS: This prospective observational study was carried out from October 2018 to July 2020. All adult patients with DFUs admitted to the surgery ward were recruited. Patients on antifungal therapy or who received such therapy within 6 weeks prior to admission were excluded. Three deep tissue samples were sent for bacterial culture, fungal culture, and histopathological examination of fungal elements. RESULTS: A total of 251 patients were enrolled in the study. Of the 23.3% of patients with positive fungal growth (n = 47/202), 2% (n = 4/202) had pure fungal growth and 21.3% (n = 43/202) had mixed growth with bacteria in their ulcers (ie, non-contaminated samples). A significant association was found between wound grade (P = .027), ulcer duration (P = .028), and positive fungal growth in DFUs. CONCLUSIONS: In this study, the prevalence of fungal infection in DFUs was 23.3%; Candida tropicalis (27.08%) was the most common isolate, followed by C. albicans (20.83%). The rate of fungal infections was high in patients with mild diabetic foot infection or DFU of 7 to 14 days' duration.

Higher antibody titres against Pseudogymnoascus destructans are associated with less white-nose syndrome skin lesions in Palearctic bats.

Introduction: Serological tests can be used to test whether an animal has been exposed to an infectious agent, and whether its immune system has recognized and produced antibodies against it. Paired samples taken several weeks apart then document an ongoing infection and/or seroconversion. Methods: In the absence of a commercial kit, we developed an indirect enzyme-linked immunosorbent assay (ELISA) to detect the fungus-specific antibodies for Pseudogymnoascus destructans, the agent of white-nose syndrome in bats. Results and Discussion: Samples collected from European Myotis myotis (n=35) and Asian Myotis dasycneme (n=11) in their hibernacula at the end of the hibernation period displayed 100% seroprevalence of antibodies against P. destructans, demonstrating a high rate of exposure. Our results showed that the higher the titre of antibodies against P. destructans, the lower the infection intensity, suggesting that a degree of protection is provided by this arm of adaptive immunity in Palearctic bats. Moreover, P. destructans infection appears to be a seasonally self-limiting disease of Palearctic bats showing seroconversion as the WNS skin lesions heal in the early post-hibernation period.

Fungal Diseases Caused by Serious Contamination of Pharmaceuticals and Medical Devices, and Rapid Fungal Detection Using Nano-Diagnostic Tools: A Critical Review.

Fungal-contaminated compounded pharmaceuticals and medical devices pose a public health problem. This review aimed to provide an organized overview of the literature on that critical issue. Firstly, it was found that compounding pharmacies can produce drugs that are contaminated with fungi, leading to outbreaks of severe fungal diseases. Secondly, inadequate sterile compounding techniques or storage conditions, or exceeding the limit of a fungal count, can result in fungal contamination. Lastly, nanotools can be used to rapidly detect fungi, thus improving fungal diagnostic procedures. To achieve this goal, we have reviewed the published data on PubMed, the CDC, and FDA Web sites, and a literature search was undertaken to identify severe fungal infections associated with compounding pharmacies outside of hospitals, limited by the dates 2003 to 2021. The "Preferred Reporting Items for Critical Reviews" were followed in searching, including, and excluding papers. Fungal outbreaks have been documented due to contaminated pharmaceuticals and medical devices. In 2013, 55 people died from fungal meningitis caused by contaminated steroid injections containing methylprednisolone acetate. Additionally, in 2021, Aspergillus penicillioides contamination was reported in ChloraPrep drugs, which was attributed to the storage conditions that were conducive to the growth of this fungus. These incidents have resulted in severe infectious diseases, such as invasive mycoses, cornea infections, Endophthalmitis, and intestinal and gastric mycosis. By implementing preventive measures and policies, it is possible to avoid these outbreaks. Creating Nano-diagnostics presents a major challenge, where promptly diagnosing fungal infections is required to determine the proper corrective and preventive measures.

The impact of immunosuppressive therapy on secondary infections and antimicrobial use in COVID-19 inpatients: a retrospective cohort study.

BACKGROUND: Immunosuppressive therapies have become a cornerstone of the management of severe COVID-19. The impact of these therapies on secondary infections and antimicrobial prescribing remains unclear. We sought to assess antimicrobial use and the incidence of bacterial and fungal infections in patients with severe COVID-19, and to explore their associations with receipt of immunosuppressive therapies. METHODS: Our retrospective cohort study included 715 hospitalised, adult patients with severe COVID-19 admitted to St George's Hospital, London, UK, during the first UK pandemic wave (1st March-10th June 2020). Co-infections (occurring within 48 h of admission) and secondary infections (≥ 48 h) were defined as a positive microbiological culture with supporting clinical, radiological or laboratory data to suggest true infection. Cox regression models with time-dependent covariates were used to explore the association between immunosuppressant use and secondary infection. RESULTS: Microbiologically confirmed co-infection occurred in 4.2% (n = 30) and secondary infection in 9.3% (n = 66) of the cohort (n = 715) and were associated with in-hospital mortality (48% vs 35%, OR 1.8, 95%CI 1.1-2.7, p = 0.01). Respiratory (n = 41, 39%) and bloodstream infections (n = 38, 36%) predominated, with primarily Gram-negative pathogens. 606 (84.7%) patients received an antimicrobial, amounting to 742 days of therapy per 1000 patient-days (DOTs). In multivariable models, receipt of high-dose steroids (≥ 30 mg prednisolone or equivalent) or tocilizumab was significantly associated with increased antimicrobial consumption (+ 5.5 DOTs, 95%CI 3.4-7.7 days) but not secondary infection (HR 0.56, 95%CI 0.26-1.18). CONCLUSIONS: Bacterial and fungal infections in severe COVID-19 were uncommon. Receipt of steroids or tocilizumab was independently associated with antimicrobial consumption despite its lack of association with secondary infection. These findings should galvanise efforts to promote antimicrobial stewardship in patients with COVID-19.

Vaccine development for pathogenic fungi: current status and future directions.

INTRODUCTION: Fungal infections are caused by a broad range of pathogenic fungi that are found worldwide with different geographic distributions, incidences, and mortality rates. Considering that there are relatively few approved medications available for combating fungal diseases and no vaccine formulation commercially available, multiple groups are searching for new antifungal drugs, examining drugs for repurposing and developing antifungal vaccines, in order to control deaths, sequels, and the spread of these complex infections. AREAS COVERED: This review provides a summary of advances in fungal vaccine studies and the different approaches under development, such as subunit vaccines, whole organism vaccines, and DNA vaccines, as well as studies that optimize the use of adjuvants. We conducted a literature search of the PubMed with terms: fungal vaccines and genus of fungal pathogens (Cryptococcus spp. Candida spp. Coccidioides spp. Aspergillus spp. Sporothrix spp. Histoplasma spp. Paracoccidioides spp. Pneumocystis spp. and the Mucorales order), a total of 177 articles were collected from database. EXPERT OPINION: Problems regarding the immune response development in an immunocompromised organism, the similarity between fungal and mammalian cells, and the lack of attention by health organizations to fungal infections are closely related to the fact that, at present, there are no fungal vaccines available for clinical use.