Antifungal Combination Research Articles

Isavuconazole and Amphotericin B Synergic Antifungal Activity: In Vitro Evaluation on Pulmonary Aspergillosis Molds Isolates.

Background/Objectives. Pulmonary aspergillosis is a severe respiratory infection caused by Aspergillus spp., whose resistance profiles and invasive attitude complicate therapeutical strategies. Several aspergillosis cases emerged as superinfections during the SARS-CoV-2 pandemic when isavuconazole and amphotericin B became essential antifungal alternatives. The main purpose of the present study was to investigate a possible synergic activity between these molecules against Aspergillus spp. isolated from respiratory samples. Methods. The gradient test method detected isavuconazole and amphotericin B MIC values, prompting an arrangement of their combination into an R.P.M.I. agar medium. According to Liofilchem s.r.l. instructions, the FIC index was used to establish synergy, additivity, indifference, or antagonism. Results. Among 36 Aspergillus spp. isolates, only A. fumigatus strains showed both synergy and additivity episodes. A. niger reported the highest antagonism percentage, while A. terreus revealed several indifference episodes. Conclusions. Isavuconazole and amphotericin B remain fundamental therapeutical alternatives, including a possible synergic effect against A. fumigatus. On the basis of this species-related difference, further studies will be essential to investigate different antifungal drug combinations against filamentous fungi isolates.

Antifungal combinations in paediatric invasive fungal infections: a protocol for systematic review and meta-analysis.

Invasive fungal infections (IFIs) significantly impact immunocompromised paediatric patients, contributing to high rates of morbidity and mortality. Despite the evolution of antifungal therapy, the efficacy and safety of combination antifungal therapies in paediatric patients, especially those with haematological malignancies, remain controversial. This systematic review and meta-analysis seeks to critically evaluate the efficacy and safety of antifungal combinations in paediatric IFIs. We will conduct a search in PubMed, ScienceDirect, Cochrane Library, BMJ and Springer databases to include randomised controlled trials and observational studies focused on combination antifungal therapies in paediatric patients under 18 years with IFIs, using COVIDENCE for data management and analysis, ensuring rigorous quality assessment and statistical integrity in synthesising data. The time frame for the search will encompass publications from the inception of each database to the present, ensuring a comprehensive coverage of the literature. The database search will not be restricted by date. The review will assess combined antifungal treatment against placebo or single-antifungal therapy, examining outcomes like response rates, survival, mortality, adverse effects, cost-effectiveness and quality of life. The review will be disseminated to healthcare professionals, community groups and policy-makers via journal publication and conference presentations to help them tailor antifungal prophylaxis treatment and outcomes for paediatric patients with IFIs. The analysis will not include any individual patient data, so ethical approval is not required. CRD42024503620.

Action enhancement of antimicrobial peptides by their combination with enzymes hydrolyzing fungal quorum molecules

Recently, the lactonase activity of several enzymes (lactonase AiiA, organophosphate hydrolase (His6-OPH) and New Delhi metallo-β-lactamase (NDM-1)) was revealed in the hydrolysis of lactone-containing fungal Quorum Sensing molecules (FQSM). This study was aimed at the investigation of possible use of these enzymes as components of antifungal combinations with antimicrobial peptides (AMPs) to increase their action efficiency against various fungi. For this, the interaction of various AMPs with AiiA, NDM-1 or His6-OPH, as well as the effect of AMPs on the catalytic characteristics of these enzymes in the hydrolysis of FQSM in enzyme/AMP combinations, were studied using in silico computer modeling methods. Enzymes combinations with 3 AMPs Bacitracin, Colistin and Polymyxin B were selected as the most rational in terms of maintaining the effectiveness of AMP and the catalytic activity of enzymes. The antifungal action of the selected combinations against cells of mycelial fungi and yeast was studied in vitro. It was found that combinations of the enzymes AiiA, His6-OPH and NDM-1 with Bacitracin, Colistin and Polymyxin B provide a significant increase in the action efficiency (up to 5000 times) of both AMPs and enzymes against fungi. The most effective variants were obtained for Polymyxin B in multicomponent combinations with enzymes.

Reassessment of the role of combination antifungal therapy in the current era.

Given the high mortality and morbidity associated with invasive fungal diseases (IFDs), the use of combination antifungal therapies is often considered despite the dearth of data. This review aims to summarize the current state of literature of combination antifungal therapies, discussing the potential roles of newer antifungal combinations and key considerations for their clinical use. In infections other than cryptococcal meningitis or in the setting of empirical treatment for suspected azole-resistant Aspergillus infections, the utility of the combination antifungal approaches remains controversial given the paucity of well designed randomized controlled trials. Data on potential combined antifungal treatments have been primarily limited to in-vitro studies, animal models, case reports and/or observational studies. With availability of novel antifungal agents (e.g. ibrexafungerp, fosmanogepix), combination therapy to treat mould infections should be re-visited. A phase 2 clinical trial of ibrexafungerp combined with voriconazole to treat invasive pulmonary aspergillosis is on-going. There is a need to investigate the use of combination antifungal agents. This includes delineating the indication of these combined antifungal therapies and determining how to use them most appropriately in the clinical setting.

Favorable outcome of Lasiodiplodia theobromae keratomycosis : a clinical case and systematic review

BackroudKeratitis caused by Lasiodiplodia theobromae is rare and typically associated with a poor prognosis. Current literature lacks sufficient evidence on effective management of patients with this condition.Case presentationA 74-year-old former agricultural worker presented with a red right eye, discomfort, and decreased visual acuity, progressing over three days without treatment. Examination revealed type 2 diabetes and a non-perforating, spiculated corneal abscess with a hypopyon in the right eye. Initial treatment included a triple antibiotic therapy and supportive care. Direct mycological examination identified numerous septate mycelial filaments. Antifungal treatment with natamycin and voriconazole, both topically and orally, was initiated. Cultures confirmed Lasiodiplodia theobromae. The patient showed significant improvement. Treatment continued for eight weeks, with a final visual acuity of 20/50 due to a stromal scar.ConclusionAn extensive literature review conducted in November 2023, using databases such as PubMed and Google Scholar with the keywords “lasiodiplodia” and “keratitis” yielded no previous cases of this specific condition being managed solely with the combined use of natamycin and voriconazole. This antifungal combination is commonly included in most management protocols for fungal keratitis. Factors such as the use of corticosteroids and delayed diagnosis were noted to adversely affect the prognosis. This case and this systematic review underscores the potential for non-surgical management options in severe fungal keratitis.

Vancomycin-Conjugated Polyethyleneimine-Stabilized Gold Nanoparticles Attenuate Germination and Show Potent Antifungal Activity against Aspergillus spp.

Antifungal drug resistance in filamentous fungi, particularly Aspergillus species, is increasing worldwide. Therefore, new antifungal drugs or combinations of drugs are urgently required to overcome this public health situation. In the present study, we examined the antifungal activity of vancomycin-functionalized AuNPs. These functionalized AuNPs were characterized, and their antifungal activity and associated killing mechanism were investigated using conventional methodologies against the conidia of A. fumigatus and A. flavus. The differential antifungal activity of vancomycin-functionalized Au-NPs against the conidia of Aspergillus species is dependent on structural differences in the conidial cell wall. The results demonstrated potent fungicidal activity against A. fumigatus, with a MIC value of 4.68 µg/mL, 93% germination inhibition, and 38.4% killing rate within 8 h of exposure. However, the activity against A. flavus was fungistatic; a MIC value of 18.7 µg/mL and 35% conidial germination inhibition, followed by 28.4% killing rate, were noted under similar conditions. Furthermore, endogenous reactive oxygen species (ROS) accumulation was 37.4 and 23.1% in conidial populations of A. fumigatus and A. flavus, respectively. Raman spectroscopy analysis confirmed the possible (but not confirmed) binding of functionalized AuNPs with the chitin and galactomannan components of the cell wall. A potential strategy that involves the exploration of antibacterial drugs using AuNPs as efficient drug carriers may also be appropriate for countering emerging drug resistance in filamentous fungi.

Genetic diversity and antifungal susceptibilities of environmental Cryptococcus neoformans and Cryptococcus gattii species complexes

Cryptococcosis is an opportunistic systemic mycosis caused by Cryptococcus neoformans and C. gattii species complexes and is of increasing global importance. Maintaining continued surveillance of the antifungal susceptibility of environmental C. neoformans and C. gattii isolates is desirable for better managing cryptococcosis by identifying resistant isolates and revealing the emergence of intrinsically resistant species. Relevant research data from Egypt are scarce. Thus, this study aimed to report the genetic diversity of C. neoformans and C. gattii species complexes originating from different environmental sources in Egypt, antifungal susceptibility profiles, antifungal combinations, and correlations of susceptibility with genotypes. A total of 400 environmental samples were collected, 220 from birds and 180 from trees. Cryptococcus spp. were found in 58 (14.5%) of the samples, 44 (75.9%) of the isolates were recovered from birds and 14 (24.1%) from trees. These isolates were genotyped using M13 polymerase chain reaction-fingerprinting and URA5 gene restriction fragment length polymorphism analysis. Of the 31 C. neoformans isolates, 24 (77.4%), 6 (19.4%) and one (4.4%) belonged to VNI, VNII, and VNIII genotypes, respectively. The 27 C. gattii isolates belonged to VGI (70.4%), VGII (18.5%), and VGIII (11.1%) genotypes. Non-wild type C. neoformans and C. gattii isolates that may have acquired resistance to azoles, amphotericin B (AMB), and terbinafine (TRB) were observed. C. gattii VGIII was less susceptible to fluconazole (FCZ) and itraconazole (ITZ) than VGI and VGII. C. neoformans isolates showed higher minimum inhibitory concentrations (MICs) to FCZ, ITZ, and voriconazole (VRZ) than those of C. gattii VGI and VGII. Significant (P < 0.001) correlations were found between the MICs of VRZ and ITZ (r = 0.64) in both C. neoformans and C. gattii isolates, FCZ and TRB in C. neoformans isolates, and FCZ and TRB (r = 0.52) in C. gattii isolates.There is no significant differences in the MICs of TRB in combination with FCZ (P = 0.064) or in combination with AMB (P = 0.543) and that of TRB alone against C. gattii genotypes. By calculating the fractional inhibitory concentration (FIC) index, the combination of FCZ + AMB was synergistic against all tested genotypes. These findings expand our knowledge of ecological niches, genetic diversity, and resistance traits of C. neoformans and C. gattii genotypes in Egypt. Further investigations into how they are related to clinical isolates in the region are warranted.

An international survey of recalcitrant and recurrent tinea of the glabrous skin-A potential indicator of antifungal resistance.

There has been a global rise in cases of dermatophytosis and, in particular, recalcitrant and recurrent cases on tinea of the glabrous skin. This phenomenon, particularly prevalent in India, has been linked to the concerning rise of antifungal resistance. The challenge is amplified by a dearth of comprehensive, international data to understand the global scope and characteristics of such cases. This study aims to collate international insights, focusing on areas outside Europe (as this was previously published), to map the extent and characteristics of clinical and, where possible, laboratory confirmed tinea of the glabrous skin through an online survey administered to dermatologists globally. An online survey was distributed from February 2022 to July 2023 and captured data on respondents' experience of recalcitrant and recurrent tinea of the glabrous skin over the preceding 3 years. A total of 260 responses were received spreads across 36 countries, excluding Europe. In total, 91.7% reported seeing cases of recalcitrant or recurrent tinea of the glabrous skin over the preceding 3 years. Common anatomical sites affected were the trunk and groin. T. mentagrophytes and T. rubrum were the predominant species implicated, and there were low rates of laboratory confirmed dermatophyte resistance. The high rates of reported recalcitrant and recurrent tinea of the glabrous skin underscore an urgent need for global collaborative efforts and enhanced diagnostic measures. The findings advocate for the establishment of a standardized global disease registry, regulation of over-the-counter antifungal and steroid combinations, correlation of clinical suspicion with laboratory confirmed drug resistance and exploration of alternative therapeutic strategies to mitigate the burgeoning challenge of dermatophyte resistance.

Success of Combination Therapy with Isavuconazole in a Pediatric Patient with Breakthrough Invasive Aspergillosis

AbstractThe increasing incidence of invasive fungal infections, coupled with the growing population of immunocompromised patients, has led to an increased need for antifungal agents. The newest azole, isavuconazole, plays an important role in the treatment of invasive aspergillosis in adults due to its broad spectrum, tolerability, and no need for therapeutic drug monitoring. This agent, which has not yet been approved for use in children, has significant problems with drug supply in Türkiye. We present the treatment response to isavuconazole combination therapy used in salvage treatment in a patient with breakthrough invasive aspergillosis, who had treatment failure with different antifungal combination treatment options and surgical resection.

An open-labeled randomized non-comparative clinical trial on the efficacy of fairfoot ointment in Vipadika

In Ayurveda, cracked or fissured feet are often associated with an imbalance in the Vata dosha. An excess of Vata in the body can lead to various skin issues, including dry and cracked skin, not only on the feet but on other parts of the body. Fairfoot ointment, a proprietary product, is an antifungal and antiseptic combination of Jathyadi Grutham, Jeevanthyadi Yamakam and Karanja Thailam, intended for external application of cracked feet and other skin conditions like chapped lips, anal fissures etc. An open-labeled randomized non-comparative clinical trial study was conducted on 30 patients presenting with cracked feet, fissures, dry scaly skin, pain, and itching to prove the efficacy in Vipadika. The associated symptoms of pigmentation and skin elasticity were also evaluated as part of this trial. A visual analog scale (VAS) was used to quantify pain. On a Likert scale of 1 to 5, dryness, wrinkles, scaling, itching, and skin laxity were scored. At each point of examination, the amount of cracking and pigmentation were counted. The study involved four evaluations of the participants. Following pairwise analysis using the SPSS 16.0 program, data were examined using Repeated Measure ANOVA. The results of the study showed a considerable reduction in the symptoms of dryness, cracking, pain, and itching. Additionally, there was a statistically significant decline in the symptoms of skin laxity, wrinkles, sealing, and pigmentation. No adverse events were observed during the course of the experiment, suggesting that the medication is safe. Clinical findings indicate that Fairfoot ointment could be used for the improvement and treatment of patients with Vipadika.

In vitro evaluation of antifungal combinations against neurotropic dematiaceous fungi associated with primary cerebral phaeohyphomycosis.

Primary cerebral phaeohyphomycosis is a life-threatening disease caused by neurotropic dematiaceous fungi. At present, there are no consensus guidelines regarding optimal antifungal therapy in such cases. Generally, a combination of antifungal agents is recommended for treatment. However, the activities of antifungal combinations against these fungi have not been investigated. In this study, we evaluated the in vitro activities of 13 double and five triple antifungal combinations against clinical isolates of Cladophialophora bantiana (n = 7), Fonsecaea monophora (n = 2), and Cladosporium cladosporioides (n = 1), using a simplified checkerboard procedure. The minimum inhibitory concentrations (MICs) of nine antifungal drugs were determined by the broth microdilution method, and the interaction between antifungal agents in each combination was assessed by the fractional inhibitory concentration index. Excellent activity was observed for posaconazole and itraconazole. Flucytosine had potent activity against C. bantiana but was ineffective against F. monophora, and C. cladosporioides. The echinocandins demonstrated high MICs for all the isolates. Synergistic interactions were observed for all the double combinations, except when itraconazole was combined with either amphotericin B or flucytosine. The combination of amphotericin B with caspofungin showed synergistic interactions against 40% of the isolates. Antagonism was observed with isavuconazole-flucytosine combination against two C. bantiana isolates. The triple combinations of caspofungin and flucytosine with amphotericin B or posaconazole were synergistic against one isolate of F. monophora. For C. cladosporioides, synergy was observed for the triple combination of amphotericin B with caspofungin and flucytosine. Our results indicate that combination of caspofungin with amphotericin B or a triazole, with or without 5-flucytosine has great potential against neurotropic dematiaceous fungi.IMPORTANCEThis research uses a modified version of the checkerboard assay to standardize the in vitro testing of double and triple combinations of antifungal agents against neurotropic dematiaceous fungi. Antifungal combination therapy is associated with improved outcomes in cerebral phaeohyphomycosis. In this study, we demonstrate that posaconazole is the single most active antifungal drug against this group of fungi. The double combination of amphotericin B with caspofungin or a trizole, and the triple combinations of caspofungin and flucytosine with amphotericin B or posaconazole might hold promise in the treatment of cerebral phaeohyphomycosis. Our findings will guide in developing optimal therapeutic strategies for these refractory infections.

Malassezia restricta as an unexpected cause of infectious osteomyelitis diagnosed by metagenomic sequencing: a case report and literature review

BackgroundMalassezia restricta, a lipophilic and lipodependent yeast belonging to the basidiomycetes group, is an opportunistic fungal pathogen associated with various skin diseases, including seborrheic dermatitis and dandruff. Typically, Malassezia infection in neonates manifests as fungemia or hematogenous dissemination to the bone or lungs. However, vertebral osteomyelitis caused by these fungi is rarely reported owing to non-specific clinical presentations and laboratory/imaging findings. The Pathogen Metagenomics Sequencing (PMseq) technique enables direct high-throughput sequencing of infected specimens, facilitating the rapid and accurate detection of all microorganisms in clinical samples through comprehensive reports.Case presentationA 52-year-old male was admitted to our hospital on July 20, 2022 with a 3-month history of ambulatory difficulties and localized low back pain. Magnetic Resonance Imaging (MRI) examination of the spinal column revealed irregular bone destruction affecting the L2, L3, and L5 vertebral bodies. Additionally, low T1 and high T2 intensity lesions were observed at the intervertebral discs between L3 and L5. The presumptive diagnosis of tuberculous spondylitis was made based on the imaging findings, despite negative results in all mycobacterium tests. However, the patient exhibited no improvement after receiving regular anti-tuberculosis treatment for 3 months. Subsequent MRI revealed an expansive abnormal signal within the vertebral body, leading to progressive bone destruction. The absence of spinal tuberculosis or other infective microorganisms was confirmed through culture from blood and pathological tissue from the L4 vertebral body. Subsequently, PMseq was performed on the specimens, revealing M. restricta as the predominant pathogen with the highest relative abundance value. The pathological examination revealed the presence of fungal mycelium in the L4 vertebral body, with positive findings on periodic Schiff-methenamine and periodic acid-Schiff staining. The anti-tuberculosis treatment was discontinued, and an antifungal combination of fluconazole and voriconazole was administered. All symptoms were resolved after 7 consecutive months of treatment, and the patient was able to ambulate autonomously. Vertebral lesions were reduced on MRI during the 13-month follow-up.ConclusionsM. restricta is not a commonly recognized pathogen associated with infectious vertebral osteomyelitis. However, PMseq can aid in diagnosis, timely treatment, and decision making for some non-specific infectious diseases.

Invasive Fungal Infections of the Head and Neck: A Tertiary Hospital Experience.

From the existing millions of fungal species, only a few cause disease. In this study, we investigated invasive fungal infections in the head and neck (H&N) over a 19-year period (2005 to 2024) at a large academic healthcare system. Among the 413 documented fungal H&N infections, 336 were noninvasive, and 77 were invasive. The highest incidence of invasive infections occurred in the sinonasal cavities, with a 15-fold difference compared to other sites. Most infections affected adults over 40 years old. The most common organisms were Mucorales (51%), hyaline molds (29%), and Candida (11%). Risk factors included malignancy, transplant, diabetes, and illicit drug use. Mortality was high in patients with malignancy and/or transplant. Infections affecting the mandible were usually a complication of osteoradionecrosis and were associated with the coinfection of Candida and Actinomyces. At other sites, infections were rare and were usually the result of penetrating injuries or immunosuppression. Treatment typically involved a combination of antifungals and surgical procedures.

The Addition of Systemic Terbinafine to Antifungal Combination Therapy in the Treatment of Disseminated Drug-Resistant Mold Infections in a National Cancer Institute Comprehensive Cancer Center: A Six-Year Study.

Introduction Combination antifungal regimens are frequently employed in the treatment of invasive fungal infections in patients who are immunocompromised, particularly for cancer and transplant patients. Terbinafine is a potential agent of interest for combination regimens. Methods We reviewed data over a six-year period examining patient outcomes in terms of bothmortality and distribution of pathogens. The total number of patients in our study was 64. The use of terbinafine versus no terbinafine in combination therapy was assessed. Of the 64 patients analyzed, only 14 received terbinafine. Mortality was calculated for both groups, and demographics were analyzed by descriptive statistics. Results There was no statistical difference in mortality outcomes in either group. The addition of terbinafine was well tolerated and did not appear to result in any undue toxicity concerns. Discussion We wish to draw greater attention to this potential agent within our armamentarium for invasive fungal infections. To our knowledge, the total number of patients in our study, while small, representsthe largestreported cohort in the literature to date. Sensitivities are crucial to be obtained for fungal pathogens as this likely undermined the utility of terbinafine in our study with larger than expected numbers of multidrug-resistant Fusarium. With limited patient numbers, a multicenter trial would be beneficial to further examine terbinafine in combination regimens.

Efficacy and Safety of Combination Treatment of Oral Terbinafine and Itraconazole in Patients with Extensive Superficial Dermatophytes

Background: Dermatophytosis, a prevalent fungal infection, is instigated by species like Trichophyton, Epidermophytonand Microsporum. The current approach for treating dermatophytosis involves a blend of systemic and topical antifungal therapies, applicable to all patients except those with localized, untreated Tinea. Notably, there is a growing incidence of inadequate response to the standard treatment regimen in recent times. Objective: To evaluate the efficacy andsafety of combination treatment of oralterbinafine anditraconazole in patients with extensive superficial dermatophytes. Materials and Methods: This research comprised a randomized clinical trial involving 50 individuals diagnosed with extensive superficial dermatophytosis. Study conducted at the Department of Dermatology and Venereology, Combined Military HospitalCumilla, the study spanned from July 2022 to June 2023. During the six-week duration, patients underwent treatment with terbinafine and itraconazole, with follow-up examinations every two weeks, including relevant investigations. Evaluation of treatment outcomes occurred at both four and six weeks. Statistical analysis was performed using version 25 of the Statistical Package for the Social Sciences (SPSS). Results: This study shows the majority of the participants within the age range of 16-30 years (56.0%) and the average age of the participants is 31.74±11.77 years. In terms of gender, the majority are male (78.0%). The most prevalent diagnosis is Tinea corporis (68.0%), followed by Tinea cruris (36.0%), Tinea faciei (28.0%), and Tinea incognito (12.0%). The majority of participants (85.0%) have had the disease for 12 months or less. The most common sites are the trunk (35.0%), whole body (26.0%), and crural area (24.0%). The majority of participants experience severe itching (56.0%), followed by moderate itching (34.0%), and a smaller percentage report mild itching (10.0%). The majority of participants showed improvement, with percentages increasing from 66.0% after 2 weeks to 84.0% after 4 weeks.The percentage of cured individuals also increased over time, reaching a substantial 90.0% after 6 weeks. Conclusion: The amalgamation of terbinafine and itraconazole demonstrates a superior clinical cure rate compared to use of single systemic antifungals. However, the observed clinical cure rate percentage is lower when juxtaposed with findings from previous studies. Notably, neither combination of systemic antifungals has exhibited efficacy against tinea infections previously treated with formulations containing topical steroids

Optimizing the Treatment of Invasive Candidiasis-A Case for Combination Therapy.

Invasive candidiasis is a rising global health threat with increasing incidence, persistently high mortality, and diminishing treatment options. Antifungal resistance has rapidly emerged and spread, with multidrug-resistant species deemed an urgent and serious threat. While acknowledging the key role of antifungal stewardship and infection control in curbing spread, we examine the role of antifungal monotherapy in driving resistance and the potential for combination therapy to prevent stress adaptation and emergence of drug resistance. In addition to its role in mitigating resistance, combination treatment may improve drug penetration, expedite fungal clearance, and allow lower, less toxic doses of individual drugs to be used. A growing body of laboratory-based evidence suggests that antifungal combinations can yield synergistic activity against Candida spp., including against frequently multidrug-resistant Candida auris. It is imperative to test these combinations in clinical trials, incorporating resistance end points as a marker of success.

Comparison of Different Betadine and Saline Combinations on Microorganisms: An Original Research.

Pathogenic bacteria in the oral cavity or a physiological microbiome imbalance can cause or maintain disease. Thus, this work examined a novel betadine-saline combination for antibacterial and antifungal activities. This study was in vitro. Betadine, saline, and their mixtures were tested for Bacillus subtilis, Staphylococcus aureus (gram-positive), Pseudomonas aeruginosa, Escherichia coli, and Aspergillus niger (gram-negative). Pour plate and disc diffusion methods were used to test CFUs, DZI, and RZI for various agent combinations. For Lactobacillus acidophilus, Betadine 90% + saline 10% had the greatest DZI and RZI at 24 and 12 mm, respectively. For E. coli, Betadine 50% + saline 50% had the highest at 16 and 8 mm. Betadine 60% + saline 40% had 14 mm RZI and the highest antifungal activity. The novel betadine-saline antibacterial and antifungal combination performed well. In vivo research should confirm the existing findings.

Clinical characteristics and outcomes of Fusarium infections in adult patients after hematopoietic stem cell transplantation: A meta-summary of case reports.

Fusarium infections have increased, particularly among patients with hematological malignancies and in those receiving hematopoietic stem cell transplantation (HSCT). This meta-summary summarizes the clinical characteristics, treatment, and outcomes of Fusarium infections in HSCT recipients. The PubMed, ScienceDirect, and Ovid SP databases were searched from inception to January 2024 to identify relevant case reports. A total of 31 patients diagnosed with Fusarium infections after HSCT were included. The most common infection sites were the skin and soft tissues (74.2%), blood (54.8%), and lungs (41.9%). Fusarium species complex was identified in 67.7% of the patients, and the most common species was Fusarium solani (51.6%). Of the included patients, 58.1% received antifungal monotherapy, whereas 41.9% received antifungal combination therapy. The overall mortality rate was 74.2%. Cutaneous infection was associated with a low mortality rate. The median time to mortality was 28 days. Fusarium infections commonly present as disseminated infections in HSCT recipients.

Pediatric Cryptococcosis.

Seroprevalence studies have shown that 70% of children are exposed to Cryptococcus , the most common cause of meningitis in people living with human immunodeficiency virus (HIV), but reported pediatric disease prevalence is much lower than in adults. PubMed and Ovid Global Health databases were searched with the terms "cryptococcosis," "cryptococcal meningitis," " Cryptococcus neoformans " or " Cryptococcus gattii ." All studies reporting pediatric specific data in the English language from 1980 up until December 2022 were included. One hundred sixty-eight publications were reviewed totaling 1469 children, with the majority reported from Africa (54.2%). Sixty-five percent (961) were HIV positive, 10% (147) were non-HIV immunocompromised and 19% (281) were immunocompetent. Clinical signs and symptoms were only reported for 458 children, with fever (64%), headache (55%) and vomiting (39%) being the most common. Most children (80%) suffered from meningoencephalitis. Lung involvement was rarely described in HIV-positive children (1%), but significantly more common in the non-HIV immunocompromised (36%) and immunocompetent (40%) groups ( P < 0.0001). Only 22% received the recommended antifungal combination therapy, which was significantly higher in immunocompetent children than those with HIV (39% vs. 6.8%; P < 0.0001). Overall mortality was 23%. A significant higher mortality was observed in children with HIV compared with immunocompetent children (32% vs. 16%; P < 0.001), but not compared with children with non-HIV immunosuppression (25). This is the largest review of pediatric cryptococcosis with new observations on differences in clinical presentation and outcome depending on the underlying condition. The lack of granular clinical data urges prospective clinical epidemiological studies for improved insight in the epidemiology, management and outcome of cryptococcosis in children.

Chronic Pulmonary Aspergillosis: Clinical Presentation and Management.

Chronic pulmonary aspergillosis (CPA) refers to a number of clinical syndromes resulting from the presence and local proliferation of Aspergillus organisms in the lungs of patients with chronic lung disease. CPA is more common than was realized two decades ago. Recognition remains poor, despite recent studies from many countries highlighting the high prevalence in at-risk populations. In low- and middle-income countries, CPA may be misdiagnosed and treated as tuberculosis (TB). In addition, CPA may develop following successful TB treatment. The coronavirus disease pandemic has resulted in significant disruption to provision of TB care, likely leading to more extensive lung damage, which could increase the risk for CPA.Although CPA refers to various syndromes, the classic presentation is that of chronic cavitary pulmonary aspergillosis, which manifests as one or more progressive cavities with or without a fungal ball, accompanied by systemic and respiratory symptoms for at least 3 months. Diagnosis relies on Aspergillus immunoglobulin G in serum, as sputum culture lacks sensitivity. Differential diagnosis includes mycobacterial infection, bacterial lung abscess or necrotizing pneumonia, lung cancer, and endemic fungi.The aim of antifungal treatment in CPA is to improve symptoms and quality of life, and to halt progression, and possibly reverse radiological changes. Current recommendations suggest treatment for 6 months, although in practice many patients remain on long-term treatment. Improvement may manifest as weight gain and improvement of symptoms such as productive cough, hemoptysis, and fatigue. Surgical management should be considered in cases of diagnostic uncertainty, in significant hemoptysis, and when there is concern for lack of response to therapy. Itraconazole and voriconazole are the first-line azoles, with more experience now accumulating with posaconazole and isavuconazole. Side effects are frequent and careful monitoring including therapeutic drug monitoring is essential. Intravenous antifungals such as echinocandins and amphotericin B are used in cases of azole intolerance or resistance, which often develop on treatment. Relapse is seen after completion of antifungal therapy in around 20% of cases, mostly in bilateral, high-burden disease.Several research priorities have been identified, including characterization of immune defects and genetic variants linked to CPA, pathogenetic mechanisms of Aspergillus adaptation in the lung environment, the contribution of non-fumigatus Aspergillus species, and the role of new antifungal agents, immunotherapy, and combination therapy.