Incidence Of Fungal Infections Research Articles

In vitro characterization and molecular epidemiology of Cryptococcus spp. isolates from non-HIV patients in Guangdong, China.

The burden of cryptococcosis in mainland China is enormous. However, the in vitro characterization and molecular epidemiology in Guangdong, a key region with a high incidence of fungal infection in China, are not clear. From January 1, 2010, to March 31, 2019, clinical strains of Cryptococcus were collected from six medical centres in Guangdong. The clinical information and characteristics of the strains were analysed. Furthermore, molecular types were determined. A total of 84 strains were collected, mostly from male and young or middle-aged adult patients. Pulmonary and cerebral infections (82.1%) were most common. All strains were Cryptococcus neoformans, grew well at 37°C and had capsules around their cells. One melanin- and urea- and one melanin+ and urea- variants were found. Although most strains exhibited a low minimum inhibitory concentration (MIC) value for voriconazole (mean: 0.04 μg/mL) and posaconazole (mean: 0.12 μg/mL), the results for these isolates showed a high degree of variation in the MIC values of fluconazole and 5-fluorocytosine, and resistance was observed for 4 out of 6 drugs. A significant proportion of these strains had MIC values near the ECV values, particularly in the case of amphotericin B. The proportion of strains near the clinical breakpoints was as follows: fluconazole: 3.66%; voriconazole: 3.66%; itraconazole: 6.10%; posaconazole: 13.41%; amphotericin B: 84.15%; 5-fluorocytosine: 2.44%. These strains were highly homogeneous and were dominated by the Grubii variant (95.2%), VNI (94.0%), α mating (100%), and ST5 (89.3%) genotypes. Other rare types, including ST4, 31, 278, 7, 57 and 106, were also found. Phenotypically variant and non-wild-type strains were found in Guangdong, and a significant proportion of these strains had MIC values near the ECV values towards the 6 antifungal drugs, and resistance was observed for 4 out of 6 drugs. The molecular type was highly homogeneous but compositionally diverse, with rare types found. Enhanced surveillance of the aetiology and evolution and continuous monitoring of antifungal susceptibility are needed to provide references for decision-making in the health sector and optimization of disease prevention and control.

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

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. The present study aims to explore the risk factors of invasive fungal infections (IFI) in preterm infants and to identify some prevention strategies. 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. There were statistically significant differences between the two groups in the gestational age, length of hospital stay, and duration of antibiotic therapy. 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.

Межмикробные взаимодействия в бактериально-грибковых ассоциациях

One of the factors contributing to the increase in the incidence of mycoses is the formation of intermicrobial associations with opportunistic microbiota. Changing the balance in such communities may cause the emergence of other associated diseases. The influence of microorganisms on each other occurs through signaling molecules and exometabolites. Complex bacterial and fungal associations of pathogens of purulent-inflammatory infections are more difficult to respond to antimicrobial therapy and lead to a more severe clinical course or death. This review examines the features of bacterial-fungal interactions of Candida sрp., Aspergillus spp., Cryptococcus spр. According to literature, the decisive role in the virulent activity of fungi in bacterial-fungal associations is played by the species composition of associates involved in the development of the pathological process. In addition, it is necessary to take into account the quantitative ratio of microorganisms, as well as the degree of virulence of fungi, which increases significantly under the influence of metabolites of associated bacteria. Therefore, further study of fungal-bacterial associations is necessary to understand fundamental issues related to the evolution of microbial virulence and antimicrobial resistance. The interactions in the studied bacterial-fungal associations are very dynamic and diverse. The nature of the relationships between microorganisms affects not only survival, but also the virulence of each other.

New azole derivatives linked to indole/indoline moieties combined with FLC against drug-resistant Candida albicans.

Candida albicans is the most common fungal pathogen associated with human opportunistic infections. Invasive infections caused by C. albicans are becoming increasingly serious. However, with the rising incidence of fungal infection, many fungi are resistant to commonly used drugs. Therefore, there is an urgent need for exploring new anti-fungal drugs that fungi are not resistant to. A series of novel azole derivatives linked to indole/indoline moieties were prepared, and in vitro antifungal activity evaluated. All compounds combined with FLC showed excellent activity against drug-resistant C. albicans with low toxicity. A preliminary mechanistic study indicated that S1 combined with FLC could inhibit the formation of C. albicans biofilms as well as destroy the integrity of cell-membrane structure and mitochondrial function. S1 could be considered a new fungal agent for further study.

Species Distribution and Antifungal Susceptibility of Candida spp among Superficial Candidiasis in Outpatients at RMCH

Background: The increase in the incidence of fungal infections, especially those caused by Candida albicans and non albicans Candida species, necessitates the understanding and treatment of Candida-associated infection. Due to frequent use of antifungal drugs, a shift is observed towards non-albicans Candida species and change in the pattern of susceptibility of antifungal drugs. The aim of this study was to isolate and identify the Candida species from different superficial candidial infections in adult patients and to observe their antifungal susceptibility patterns. Materials and Methods: A cross sectional study was performed over a period of one year in at tertiary care hospital that involved 180 patients. The candidial species were isolated, their antifungal susceptibility patterns were determined from vaginal swab, oral swab and skin appendages. Results: Commonest age group involved was of 30-39 years age (30%, 54/180). Among 67 culture positive samples,C. albicans was the most common isolates and found in 39/67(58.21%) cases. Non-candidal species likeC. tropicalis and C. kruseiwere isolated in16/67(23.88%), 09/67 (13.43%)cases respectively. Caspofungin was found to be the most sensitive and fluconazole was found to be the least sensitive antifungal drugs. Non-albicansCandida species showed more antifungal resistance than C. albicans. Conclusions: Candida albicans were predominant isolated from the superficial candidial infection but C. tropicalis was the most frequently isolated among non albicans species. They showed a wide range of susceptibility towards different antifungal agents and fluconazole was found to be less sensitive drugs. TAJ 2023; 36: No-2: 93-100

Features of development and prevalence of diseases on soybean in the forest-steppe of Western Siberia

In recent years, there has been a significant deterioration of phytosanitary situation in plantings of many agricultural crops, including fodder crops. One of the valuable forage crops is soybean, which is becoming increasingly widespread outside its natural climatic zone. Under the conditions of Western Siberia, soybean crops are almost annually affected by a complex of diseases that significantly reduce the yield and quality of the seed material, which requires a comprehensive approach to ensure a minimum infectious background in crops. The development of epiphytotics on crops follows a certain dependence. The peak incidence of fungal infections is associated with increased temperature and humidity. Bacterial infections have a greater tolerance to low temperatures and may develop during the final phase of soybean vegetation. We investigated the correlation between the incidence rates of fungal and bacterial diseases of soybean and weather and climatic conditions of all the years of research. The research was conducted in 2016–2022 in the Novosibirsk region. The choice of the years of research is due to the formation of established populations of soybean phytopathogens that cause annual epiphytotics. SibNIIK 315 soybean variety was used as a sample for the study of the disease incidence in soybean crops. Based on long-term studies, this variety is the most affected of all the varieties. The leaf-stalk infections such as false mildew and pustular bacteriosis were considered as countable diseases. The use of correlation analysis to establish the degree of interrelation between the main indicators of soybean crop infestation and weather and climatic conditions of the growing season allowed to reveal a certain relationship – mainly due to the fact that fungal infections in all the years of research were manifested by the type of the epiphytotics. However, this method is not well suited for low prevalence diseases and diseases with short-term outbreaks.

2446. Effect of the Implementation of a Fluconazole Prophylaxis Protocol on the Incidence of Invasive Fungal Infection in High-Risk Neonates

Abstract Background Invasive fungal infection (IFI) is one of the most important causes of morbidity and mortality in the neonatal intensive care unit. International societies have supported the use of fluconazole prophylaxis for neonates weighing < 1000 grams, but administration to other high-risk patients remains controversial. An institutional fluconazole prophylaxis guideline was implemented in December 2020 to include two other groups of neonates. Methods One hundred thirty infants who were admitted at the NICU from January 2020 to January 2022 and fulfilled one of the following criteria: weight of < 1000 grams (Group A), weight of ≤1500 grams and on broad-spectrum antibiotics (Group B), or weight of >1500 grams and on prolonged nil per os (NPO) (Group C) were included in the study. They were divided into two groups: those who were born prior to the implementation of the protocol (January to December 2020) and not given fluconazole prophylaxis, and those born after (January 2021 to January 2022) and given prophylaxis. The primary outcome was the development of IFI. Results A total of 130 infants were included in this study with 21 (5 control, 16 prophylaxis), 69 (28 control, 41 prophylaxis), and 40 (16 control, 24 prophylaxis) patients in Groups A, B, and C, respectively. There were no significant differences in the development of IFI among the groups (Group A: control - 40%, prophylaxis - 62%; Group B: control - 21.4%, prophylaxis - 22%; Group C: control - 29.2%, prophylaxis 31.5%) with a p-value of > 0.05. The presence of a central vascular access line, endotracheal tube, placement on NPO, histamine H2-blockers, and necrotizing enterocolitis were associated with the development of IFI. Candida parapsilosis comprised 60% of isolates. All isolates had 100% susceptibility to fluconazole. Jaundice developed in 3.7% of patients given fluconazole, with elevations in AST, ALT, and TB. Incidence of fungal infection in high-risk neonates There were no significant differences in the development of IFI among the three high-risk groups, with p-value of > 0.05. Conclusion Invasive fungal infection remains a heavy burden to high-risk neonates. The protocol at present does not significantly prevent the occurrence of IFI. There is a need to revise the protocol to include the presence of a combination of multiple risk factors (central line, endotracheal tube, prolonged NPO, H2-blockers, and necrotizing enterocolitis) before initiating fluconazole prophylaxis. Disclosures All Authors: No reported disclosures

A successfully rehabilitated post-mucormycosis maxillary defect with guided quad-zygomatic implants: A case report

Introduction: Mucormycosis infection has received occasional attention because of the low number of cases in comparison with other frequent infections. With the emergence of the SARS-CoV-2 disease, the incidence of fungal infections like mucormycosis has increased. In mucormycosis, after surgical debridement, the defects that result are different from other maxillary defects. In terms of functional and aesthetic rehabilitation there are several treatment options for patients with maxillectomy defects. Amidst all, zygomatic implants are more favorable and viable solution for the above-mentioned defects. Since there is a scarcity in literature on the use of zygomatic implants in such cases, we presented a case report using the utmost advantage of these implants in rehabilitation of maxillary defects. Case Report: In the present case report, a 38-year-old male patient presented with an absence of the maxillary alveolar bone and anterior nasal spine and minimal presence of hard palate. Such type of maxillary defect following mucormycosis was managed with quad zygomatic implants with computer-guided approach. Conclusion: Thus, the author concluded through this case report that a severe maxillectomy defects can be managed well with the zygomatic implants. In the present article, the author preferred to perform under guide in order to avoid errors while placement of implants. Hence, proper diagnosis with definitive surgical approach can help in achieving precise treatment outcome and establishing patient’s self-esteem.

Invasive fungal infection incidence and risk factors in patients receiving ibrutinib in real-life settings: A nationwide population-based cohort study.

Data on the risk of invasive fungal infections (IFI) with ibrutinib treatment are scarce. This study aimed to determine IFI incidence and risk factors in ibrutinib-treated patients in real-life settings. We constituted a cohort of ibrutinib incident users in the French National Healthcare Database. All patients ≥18 years with a first dispensing of ibrutinib between 21 November 2014 and 31 December 2019 were included. Patients were followed from the cohort entry date until IFI, ibrutinib discontinuation, death, or 31 December 2020, whichever came first. The cumulative incidence function method was used to estimate the probability of IFI accounting for competing risk of death. A multivariate cause-specific Cox proportional hazards model was used to assess independent IFI risk factors. Among 6937 ibrutinib-treated patients, 1-year IFI cumulative incidence was 1.3%, with invasive aspergillosis being the most frequent. Allogenic or autologous stem cell transplantation (ASCT) (hazard ratio [HR] 3.59, 95% confidence interval [1.74; 7.41]), previous anticancer treatment (HR 2.12, CI 95% [1.34; 3.35]) and chronic respiratory disease (HR 1.66, [1.03; 2.67]) were associated with higher risk of IFI. Besides neutropenia and corticosteroids, use of anti-CD20 agents was significantly more frequent in patients having experienced IFI (HR 3.68, [1.82; 7.45]). In addition to patients with ASCT history, severe neutropenia or treated with corticosteroids, our findings support active surveillance of IFIs in those with chronic respiratory disease, previously treated, or treated with anti-CD20 agents in combination with ibrutinib. Further studies are needed to optimise IFI prophylaxis in these patient subgroups.

Assessment of fungal contamination and biosecurity risk factors in duck-breeding farms in South Korea

Fungi are pathogens that infect all types of poultry and farmers, leading to economic losses in poultry production. Fungi can be isolated from environmental samples and are ubiquitous in the air. This study aimed to evaluate fungal contamination in domestic duck farm environments and analyze biosecurity risk factors associated with fungal infection incidence to assess the vulnerability of the farms to fungal infection. The average fungal concentration was 203 colony-forming units (CFU)/m3 in the air and 365×103 CFU/m2 in the wall surface samples. Sixteen fungal genera were recovered from air and wall surface samples from 19 duck-breeding farms, Aspergillus being the most frequently isolated (air: 43.2%; wall surface: 40%). Eleven additional fungal genera (Acrophialophora, Byssochlamys, Fusarium, Lichtheimia, Paecilomyces, Penicillium, Polycephalomyces, Rhizomucor, Scopulariopsis, Talaromyces, and Thermoascus) were isolated from air samples. Also, 8 additional fungal genera (Chaetomium, Lichtheimia, Penicillium, Petriella, Rhizomucor, Rhizopus, Talaromyces, and Trichosporon) were isolated from wall surface samples. The characteristics of the poultry farms (geographic region, stocking density, breeding house type, affiliate, duck age, and season) and fungal concentrations in the air and wall surface samples were analyzed to evaluate the biosecurity risk of the farms. Fungal infections were significantly affected by high stocking density (>2 ducks/m2), duck age (18-25 wk and >60 wk), and high fungal concentration in the wall surface samples (>300×103 CFU/m2).

Corticosteroids and invasive fungal infections in hospitalized COVID-19 patients – A single-center cross-sectional study

Background: During the coronavirus disease 2019 (COVID-19) epidemic, an increase in the incidence of fungal infections was observed. However, the real magnitude of these fungal infections and their risk factors among COVID-19 patients in the Indian population is unknown. Aim: To study the frequency, and spectrum of invasive fungal infections (IFI) among hospitalized COVID-19 patients, and the risk factors associated with invasive fungal infections. Methods: We performed a retrospective, cross-sectional study; including all adult patients, admitted to Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), a tertiary care hospital in Southern India between April 2020 and August 2021, with COVID-19. Based on clinical-radiological features, patients with fungal infections were grouped into three diagnostic categories. Demographics, clinical, and laboratory features of patients with fungal infections were analyzed to identify the risk factors. Results: About 10% (449 out of 4650) of the admitted patients with recent COVID-19, had some form of IFI. Among the patients with IFI, 80% (366 out of 449) were hospitalized for active COVID-19, whereas almost all the patients admitted with post-COVID complications had IFI. Of the 449 patients with IFI, 377 had mold infections and 88 had invasive candidiasis. Mucormycosis was the most common mold infection. Diabetes and diabetic ketoacidosis were strong independent predictors of IFI. We also found an association between end-stage renal disease, central venous catheterization, antibiotic usage, prior stroke, and corticosteroid therapy with IFI. Conclusions: The frequency of fungal infections among hospitalized COVID-19 patients was high. Special precautions in COVID-19 patients with diabetes mellitus, corticosteroid therapy, and prior antibiotic usage may help to reduce invasive fungal infections.

Influence of storage conditions on viability and vigour of Sunflower (Helianthus annuus L.) seeds

The storage experiment examined the effects of storage temperatures, seed moisture contents (SMC), and storage durations (SD) on the viability and vigour of sunflower seeds. Certified sunflower seeds were evaluated for seed germination, seedling vigour, and fungal infection. A 3x3x6 factorial experiment in Completely Randomized Design was set out in four replicates. The three factors were temperature (5, 20, 35 ºC), SMC (6,8,10%), and SD (15, 30, 45, 60, 75, 90Days After Storage, DAS). Before storage (0 DAS), the initial germination percentage (GP=94%), Germination index (GI=322), Seedling vigour index (SVI=2118), and fungal infection incidence (FII=52%) were determined and used as control. The lowest GP of 67%, GI (269.2), SVI (1295), and FII (78.0%), was found in seeds stored at a temperature of 35 ºC and SMC of 10% at 90DAS. Upon the interaction effect at the end of 90DAS, the temperature of 5 ºC with SMC of 6% followed by the temperature of 20 ºC with SMC of 6% recorded the greatest GP of 87.5 and 87.0%, GI of 304.3 and 296.8 SVI of 1910 and 1877 and fewer fungi incidence (%) of 61.5 and 63 respectively. The germination percentage was above the minimum certification standards of 85%, as per the Tanzania Official Seed Certification Institute. Conclusively, our results discovered that the optimum storage conditions-Temperature of 5 and 20 ºC with SMC of 6 and 8% could be suitable for maintaining the viability and vigour of sunflower seeds throughout the storage duration (90 DAS).

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

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. 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. 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.

Improving Outcomes with Haploidentical Stem Cell Transplantation [HaploSCT] in Children Using Post-transplant Cyclophosphamide: a Single Center Experience.

Haplo-identical stem cell transplant using post-transplant cyclophosphamide is increasingly being used in children without a matched sibling donor. Between 2010 and June 2021, 127 children underwent 138 transplants with a median age of 7.1years for malignant and non-malignant disorders. Conditioning regimens included both myeloablative and reduced intensity regimens with peripheral blood stem cells as the main graft source. Engraftment occurred in 113 [81.9%] at a median of 16days [range: 10-32] with primary graft failure in 10.2%. Cumulative incidence of grade II-IV acute graft versus host disease (GVHD) was 49.5% and chronic GVHD in 40.7%. Majority [92.7%] had at least one infection with 31% incidence of bacterial infection, 76% incidence of viral and 16% incidence of fungal infection. The 2-year overall survival (OS) is 54.9 ± 4.6% with a lower survival among young children aged 0-5years [28.2 ± 6.4%] compared to 5-10years [71.3 ± 6.8%] and 11-15years [55.7 ± 8.8%] [p = 0.032]. 2-year OS has gradually improved from 25.0 ± 2.1% for 2010-2013 to 47.5 ± 6.2% for 2014-2017 and 67.1 ± 6.6% for 2018-2021 [p = 0.049]. On multivariate analysis, bacterial infection [p = 0.017], invasive fungal disease [p = 0.002] and graft failure [p = 0.029] negatively impacted overall survival. Haplo-identical SCT with post-transplant cyclophosphamide is a reasonable option for children who do not have a matched sibling donor. Strategies to reduce graft failure, infection related mortality and GVHD needs to be explored.

ANTIFUNGAL RESISTANCE: A GROWING CONCERN

Globally, the increasing number of drug-resistant human pathogens represents a major threat to public health. Among these pathogens, fungi that have acquired resistance to the already scarce arsenal of antifungals are of particular significance, as they present therapeutic challenges that increase morbidity and mortality rates. Particularly, most mycoses are opportunistic since they mainly affect hosts with a weakened immune system, including patients with cancer, hematological malignancies, prolonged neutropenia, solid organ transplants, HIV/AIDS, patients in intensive care units, using central venous catheters or on dialysis, using corticosteroids, among others. In most cases, fungal infections have a significant medical and economic burden that outweighs the burden of the underlying disease alone and changes the outcome. In addition, the treatment for mycoses, which consists of four classes of antifungals described several decades ago, polyenes, flucytosine, azoles, and echinocandins, continues to be a major challenge. With the increase in patients at risk, the incidence of mycoses is therefore a growing concern. Considering as well, the scarcity of drugs, together with toxicity, the high price of some formulations, the low availability in low-resource countries, and the development of resistance, there is an urgent need to discover new antifungals or therapeutic strategies or to modify the existing molecules with antifungal activity. This reflection article reveals that various of the most common human fungal pathogens have had the ability to acquire antifungal resistance as antifungal drugs are developed.

Antifungal activity of novel azetidine tethered chitosan synthesized via multicomponent reaction approach.

The increasing incidences of fungal infections among Covid-19 infected patients is a global public concern and urgently demands novel antifungals. Biopolymers like chitosan hold unique structural properties and thus can be utilized in the synthesis of biologically important scaffolds. To address the current scenario, the author's synthesized novel chitosan-azetidine derivative by adopting one-pot multicomponent reaction approach. The influence of chemical modification on the structural characteristics was investigated by means of spectroscopic techniques viz. FT-IR and 1HNMR and elemental analysis. Additionally, the authors investigated the antifungal potential of chitosan-azetidine derivative against Aspergillus fumigatus 3007 and the results indicated higher antifungal effect with an antifungal inhibitory index of 26.19%. The SEM and confocal microscopy images also reflected a significant inhibitory effect on the morphology of fungal mycelia, thus reflecting the potential of synthesized chitosan-azetidine derivativeas a potential antifungal agent.

Multicenter Observational Retrospective Study on Febrile Events in Patients with Acute Myeloid Leukemia Treated with Cpx-351 in "Real-Life": The SEIFEM Experience.

In the present study, we aimed to evaluate the absolute risk of infection in the real-life setting of AML patients treated with CPX-351. The study included all patients with AML from 30 Italian hematology centers of the SEIFEM group who received CPX-351 from July 2018 to June 2021. There were 200 patients included. Overall, 336 CPX-351 courses were counted: all 200 patients received the first induction cycle, 18 patients (5%) received a second CPX-351 induction, while 86 patients (26%) proceeded with the first CPX-351 consolidation cycle, and 32 patients (10%) received a second CPX-351 consolidation. A total of 249 febrile events were recorded: 193 during the first or second induction, and 56 after the first or second consolidation. After the diagnostic work-up, 92 events (37%) were classified as febrile neutropenia of unknown origin (FUO), 118 (47%) were classifiable as microbiologically documented infections, and 39 (17%) were classifiable as clinically documented infections. The overall 30-day mortality rate was 14% (28/200). The attributable mortality-infection rate was 6% (15/249). A lack of response to the CPX-351 treatment was the only factor significantly associated with mortality in the multivariate analysis [p-value: 0.004, OR 0.05, 95% CI 0.01-0.39]. Our study confirms the good safety profile of CPX-351 in a real-life setting, with an incidence of infectious complications comparable to that of the pivotal studies; despite prolonged neutropenia, the incidence of fungal infections was low, as was infection-related mortality.

Imaging Findings in Aspergillosis: From Head to Toe.

Aspergillosis is a mycotic infection induced by airborne fungi that are ubiquitous. Inhalation of Aspergillus conidia results in transmission through the respiratory tract. The clinical presentation is dependent on organism and host specifics, with immunodeficiency, allergies, and preexisting pulmonary disease constituting the most important risk factors. In recent decades, the incidence of fungal infections has increased dramatically, due in part to the increased number of transplants and the pervasive use of chemotherapy and immunosuppressive drugs. The spectrum of clinical manifestations can range from an asymptomatic or mild infection to a swiftly progressive, life-threatening illness. Additionally, invasive infections can migrate to extrapulmonary sites, causing infections in distant organs. Recognition and familiarity with the various radiological findings in the appropriate clinical context are essential for patient management and the prompt initiation of life-saving treatment. We discuss the radiological characteristics of chronic and invasive pulmonary aspergillosis, as well as some of the typically unexpected extrapulmonary manifestations of disseminated disease.

Small molecules restore azole activity against drug-tolerant and drug-resistant Candida isolates.

Each year, fungi cause more than 1.5 billion infections worldwide and have a devastating impact on human health, particularly in immunocompromised individuals or patients in intensive care units. The limited antifungal arsenal and emerging multidrug-resistant species necessitate the development of new therapies. One strategy for combating drug-resistant pathogens is the administration of molecules that restore fungal susceptibility to approved drugs. Accordingly, we carried out a screen to identify small molecules that could restore the susceptibility of pathogenic Candida species to azole antifungals. This screening effort led to the discovery of novel 1,4-benzodiazepines that restore fluconazole susceptibility in resistant isolates of Candida albicans, as evidenced by 100-1,000-fold potentiation of fluconazole activity. This potentiation effect was also observed in azole-tolerant strains of C. albicans and in other pathogenic Candida species. The 1,4-benzodiazepines selectively potentiated different azoles, but not other approved antifungals. A remarkable feature of the potentiation was that the combination of the compounds with fluconazole was fungicidal, whereas fluconazole alone is fungistatic. Interestingly, the potentiators were not toxic to C. albicans in the absence of fluconazole, but inhibited virulence-associated filamentation of the fungus. We found that the combination of the potentiators and fluconazole significantly enhanced host survival in a Galleria mellonella model of systemic fungal infection. Taken together, these observations validate a strategy wherein small molecules can restore the activity of highly used anti-infectives that have lost potency. IMPORTANCE In the last decade, we have been witnessing a higher incidence of fungal infections, due to an expansion of the fungal species capable of causing disease (e.g., Candida auris), as well as increased antifungal drug resistance. Among human fungal pathogens, Candida species are a leading cause of invasive infections and are associated with high mortality rates. Infections by these pathogens are commonly treated with azole antifungals, yet the expansion of drug-resistant isolates has reduced their clinical utility. In this work, we describe the discovery and characterization of small molecules that potentiate fluconazole and restore the susceptibility of azole-resistant and azole-tolerant Candida isolates. Interestingly, the potentiating 1,4-benzodiazepines were not toxic to fungal cells but inhibited their virulence-associated filamentous growth. Furthermore, combinations of the potentiators and fluconazole decreased fungal burdens and enhanced host survival in a Galleria mellonella model of systemic fungal infections. Accordingly, we propose the use of novel antifungal potentiators as a powerful strategy for addressing the growing resistance of fungi to clinically approved drugs.

Cross-sectional investigation of mycological diagnosis challenges in Saudi Arabia.

The global incidence of fungal infection has increased dramatically over the last two decades. Fungal diseases threaten both immunocompetent, and immunocompromised patients. The current fungal diagnostics status in Saudi Arabia needs to be evaluated, especially with the increase of the immunosuppressed population. This cross-sectional study investigated the gaps in mycological diagnosis on a national level. The call interview questionnaire responses were collected to evaluate the demand for fungal assays, diagnostic methods' quality, and mycological expertise of laboratory technologists in both public and private medical intuitions. The data were analyzed using (IBM SPSS ® software version 22.0). A total of 57 hospitals from all Saudi regions participated in the questionnaire; however, only 32% received or processed mycological samples. Most participants were from the Mecca region (25%), Riyadh region (19%), and Eastern region (14%). The top fungal isolates identified were Candida spp., Aspergillus spp., and dermatophyte. Fungal investigation is highly requested by intensive care, dermatology, and obstetrics and gynecology units. Most laboratories rely on fungal culture and microscopic examination, which mostly identify Candida to the genus level, and use 37°C incubators for culture (67%). Antifungal susceptibility testing (AST) and serological and molecular methods are rarely performed and mostly outsourced. Using accurate identification and AST are the primary factors to improve fungal diagnosis in respect to turnaround time and cost. The three major obstacles identified were availability of facility (47%), reagents and kits (32%), and good training (21%). The results indicated that fungal diagnosis demand was relatively higher in high-population regions. This study highlighted the gaps in fungal diagnostics reference laboratories to encourage their improvement in Saudi hospitals.