Chronic Fungal Infection Research Articles

8270 A Rare Case Of PTHrP Induced Severe Hypercalcemia Secondary To Squamous Cell Carcinoma Of Tongue

Abstract Disclosure: N. Vennelaganti: None. S. Vennelaganti: None. K. McCowen: None. Background: PTHrP-mediated hypercalcemia is often associated with solid organ malignancies and indicates a poor prognosis. The occurrence of this condition due to SCC of the head and neck, particularly of the tongue, is uncommon. This case report aims to shed light on this rare clinical presentation. Clinical Case: A 70-year-old woman with a history of tobacco use disorder, alcoholic liver cirrhosis, and a chronic fungal prosthetic joint infection presented with altered mental status and acute kidney injury. Laboratory tests revealed a corrected calcium level of 15.4 mg/dL and suppressed PTH of 3 pg/mL, indicating non-PTH-dependent hypercalcemia. Differentials considered included malignancy, multiple myeloma, 1,25 OH Vit D mediated hypercalcemia via fungal granuloma formation, and immobilization. Diagnostic evaluation revealed normal levels of 25 hydroxy Vitamin D ie: 54 ng/mL, normal kappa to lambda ratio suggestive of negative myeloma screen, normal TSH of 2.81 uIU/mL, and a low 1,25 OH Vit D level ie: 11.4 pg/mL (Ref range: 19.9-79.3 pg/mL). An elevated PTHrP concentration of 9.7 pmol/L (ref range 0-3.4 pmol/L) was noted. CT angiography performed for stroke evaluation incidentally discovered a base of tongue mass, which was difficult to appreciate on exam due to obtundation. A biopsy confirmed SCC of the tongue, and she was determined to be Stage IVA. The patient's hypercalcemia was determined to be secondary to PTHrP production from the tongue SCC compounded by immobilization. She was treated with IV fluids and subcutaneous calcitonin, normalizing her calcium levels over 20 days. IV Bisphosphonates were held inpatient due to poor renal function. She was seen by oncology and determined to not be fit for surgical management or chemotherapy. Radiation therapy was advised for management and patient was discharged. While awaiting her outpatient radiation treatment, the patient had another episode of altered mental status and was found to have a serum calcium of 16.4 mg/dL. She was managed with IV fluids, calcitonin and IV Zoledronate which improved her serum calcium. She has since been receiving monthly IV Zometa with oncology for hypercalcemia of malignancy. She was recently readmitted with severe oropharyngeal and pharyngeal dysphagia and has received a PEG tube for feeding. She is still pending radiation therapy for SCC tongue. Conclusion: Initially, during the workup of this case, we believed her hypercalcemia was likely immobilization-induced, but thorough investigation and the elevated PTHrP levels steered us towards malignancy as a potential etiology. This case is an example of an occult malignancy which lead to severe hypercalcemia. It also contributes to the understanding of hypercalcemia in cancer patients and highlights the rare association of SCC of the tongue with PTHrP-mediated hypercalcemia . PTHrP secreting SCC of head and neck are typically associated with a poor prognosis. Presentation: 6/2/2024

Understanding chromoblastomycosis in Sri Lanka; insights into fungal aetiology and antifungal susceptibility patterns

Introduction: Chromoblastomycosis is a chronic disfiguring fungal infection of the subcutaneous tissue found mainly in the socio-economically marginalized population in the tropical and sub-tropical regions, characterized by the presence of sclerotic cells. This study was done with the aim of identifying the antifungal sensitivity patterns of the causative agents of chromoblastomycosis in Sri Lanka from 1992 to 2019.Methodology: Study was done on the stored isolates received from patients with chromoblastomycosis since 1992 to 2019, to the Mycology Reference Laboratory of Medical Research Institute, Colombo. Isolates were revived by subculture on Potato dextrose agar. Identification was done phenotypically. Antifungal sensitivity testing was performed by E test method. Available demographic and clinical data were analysed.Results: Of the 74 isolates, 71 (96%) were caused by Fonsecaea pedrosoi. Mean MIC for the antifungals tested were lowest for posaconazole 0.015 μg/ml followed by itraconazole 0.225 μg/ml, and voriconazole 0.768 μg/ml while amphotericin B demonstrated complete resistance with mean MIC of 30.591 μg/ml. No statistically significant differences were noted on the antifungal sensitivity of the isolates from 1992 to 2004 and 2005 to 2019.Conclusions: Fonsecaea pedrosoi was the commonest causative agent causing chromoblastomycosis in the studied population. Posaconazole demonstrated the lowest MIC values for the tested isolates followed by itraconazole and voriconazole. Amphotericin B demonstrated very high MIC values which were likely to result in clinical failure upon treatment. MIC values demonstrated minimal fluctuations throughout the tested time.

Drivers of diversification in fungal pathogen populations.

To manage and treat chronic fungal diseases effectively, we require an improved understanding of their complexity. There is an increasing appreciation that chronic infection populations are often heterogeneous due to diversification and drift, even within a single microbial species. Genetically diverse populations can contribute to persistence and resistance to treatment by maintaining cells with different phenotypes capable of thriving in these dynamic environments. In chronic infections, fungal pathogens undergo prolonged challenges that can drive trait selection to convergent adapted states through restricted access to critical nutrients, assault by immune effectors, competition with other species, and antifungal drugs. This review first highlights the various genetic and epigenetic mechanisms that promote diversity in pathogenic fungal populations and provide an additional barrier to assessing the actual heterogeneity of fungal infections. We then review existing studies of evolution and genetic heterogeneity in fungal populations from lung infections associated with the genetic disease cystic fibrosis. We conclude with a discussion of open research questions that, once answered, may aid in diagnosing and treating chronic fungal infections.

Simultaneous determination of three tyrosine kinase inhibitors and three triazoles in human plasma by LC-MS/MS: applications to therapeutic drug monitoring and drug-drug interaction studies

Tyrosine kinase inhibitors (TKIs) and triazole antifungals are the first-line drugs for treating chronic myeloid leukemia (CML) and fungal infections, respectively, but both suffer from large exposure differences and narrow therapeutic windows. Moreover, these two types of drugs are commonly used together in CML patients with fungal infections. Multiple studies and guidelines have suggested the importance of therapeutic drug monitoring (TDM) of TKIs and triazoles. Currently, methods for the simultaneous determination of both types of drugs are limited. We developed a simple, rapid, and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous quantification of three commonly used TKIs (imatinib, dasatinib, and nilotinib) and three commonly used triazoles (voriconazole, itraconazole, and posaconazole) in human plasma. The analytes were eluted on a Welch XB-C18 analytical column (50 × 2.1 mm, 5 µm) at 0.7 mL/min, using a gradient elution of 10 mM ammonium formate (A) and methanol–acetonitrile-isopropanol (80:10:10, v/v/v) containing 0.2 % formic acid (B) with a total analysis time of 3.5 min. The calibration curves were linear over the range from 20 to 4000 ng/mL for imatinib and nilotinib, from 2 to 400 ng/mL for dasatinib, and from 50 to 10,000 ng/mL for voriconazole, itraconazole, and posaconazole. Selectivity, accuracy, precision, recovery, matrix effect, and stability all met the validation requirements. The method was successfully used for TDM in CML patients who co-treated with both TKIs and triazoles. Drug-drug interaction analysis between TKIs and triazoles showed that a significant positive correlation was observed between imatinib and voriconazole, as well as dasatinib and voriconazole. Therefore, this method can be well applied in clinical TDM for patients receiving TKIs, triazoles, or both simultaneously.

Successful management of chromoblastomycosis utilizing conventional antifungal agents and imiquimod therapy

Chromoblastomycosis (CBM), a chronic fungal infection affecting the skin and subcutaneous tissues, is predominantly caused by dematiaceous fungi in tropical and subtropical areas. Characteristically, CBM presents as plaques and nodules, often leading to scarring post-healing. Besides traditional diagnostic methods such as fungal microscopy, culture, and histopathology, dermatoscopy and reflectance confocal microscopy can aid in diagnosis. The treatment of CBM is an extended and protracted process. Imiquimod, acting as an immune response modifier, boosts the host’s immune response against CBM, and controls scar hyperplasia, thereby reducing the treatment duration. We present a case of CBM in Guangdong with characteristic reflectance confocal microscopy manifestations, effectively managed through a combination of itraconazole, terbinafine, and imiquimod, shedding light on novel strategies for managing this challenging condition.

Potassium iodide enhances the killing effect of methylene blue mediated photodynamic therapy against F. monophora

BackgroundChromoblastomycosis (CMB) is a chronic granulomatous fungal infection that affect the skin and subcutaneous tissues. It is clinically problematic due to limited treatment options, low cure rates, and high rates of relapse. This underscores the necessity for innovative treatment approaches. In this study, potassium iodide (KI) combined with Methylene Blue (MB) mediated antimicrobial photodynamic therapy (PDT) were assessed in the treatment of Fonsecaea monophora (F. monophora) both in vitro and in vivo. And the underlying mechanism that contributes to the efficacy of this treatment approach was investigated. MethodsIn vitro experiments were conducted using different combinations and concentrations of MB, KI, and 660 nm light (60 mW/cm2) to inhibit F. monophora. The study was carried out using colony-forming unit (CFU) counts and scanning electron microscopy (SEM). The production of singlet oxygen (1O2), free iodine (I2), hydrogen peroxide (H2O2), and superoxide anion during the KI combined MB-mediated antimicrobial PDT process was also detected. In vivo experiments were developed using a Balb/c mouse paw infection model with F. monophora and treated with PBS, 10 mM KI, 2 mM MB +100 J/cm² and 10 mM KI+2 mM MB +100 J/cm² respectively. Inflammatory swelling, fungal load and histopathological analyses of the mouse footpads were assessed. ResultsKI enhanced the killing effect of MB-mediated antimicrobial PDT on the conidial spores of F. monophora at the cell and infected animal model level. During the process, the main antimicrobial agents in KI combined with MB- mediated antimicrobial PDT could produce stronger toxic active species including free I2 and H2O2. ConclusionKI combined with MB-mediated antimicrobial PDT could be an effective adjunct therapy for treating CBM.

The CARD9 Gene in Koalas (Phascolarctos cinereus): Does It Play a Role in the Cryptococcus-Koala Interaction?

Cryptococcus is a genus of fungal pathogens that can infect and cause disease in a range of host species and is particularly prominent in koalas (Phascolarctos cinerus). Like other host species, koalas display a range of outcomes upon exposure to environmental Cryptococcus, from external nasal colonization to asymptomatic invasive infection and, in rare cases, severe clinical disease resulting in death. Host factors contributing to these varied outcomes are poorly understood. Due to their close relationship with eucalypt trees (a key environmental niche for Cryptococcus gattii) and suspected continual exposure to the pathogen, koalas provide a unique opportunity to examine host susceptibility in natural infections. Caspase recruitment domain-containing protein 9 (CARD9) is a key intracellular signaling protein in the fungal innate immune response. Humans with mutations in CARD9 succumb to several different severe and chronic fungal infections. This study is the first to sequence and explore CARD9 variation in multiple koalas using Sanger sequencing. Four CARD9 exons were successfully sequenced in 22 koalas from a New South Wales, Australia population. We found minimal variation between koalas across all four exons, an observation that was also made when CARD9 sequences were compared between koalas and six other species, including humans and mice. Ten single-nucleotide polymorphisms (SNP) were identified in this study and explored in the context of cryptococcal exposure outcomes. While we did not find any significant association with variation in cryptococcal outcomes, we found a high degree of conservation between species at several SNP loci that requires further investigation. The findings from this study lay the groundwork for further investigations of CARD9 and Cryptococcus both in koalas and other species, and highlight several considerations for future studies.

Triazole antifungal drug interactions-practical considerations for excellent prescribing.

Systemic antifungal therapy is critical for reducing the mortality from many invasive and chronic fungal infections. Triazole antifungals are the most frequently prescribed antifungals but require attention to dosing and drug interactions. Nearly 600 severe drug-drug interactions and over 1100 moderate interactions requiring dose modifications are described or anticipated with systemic antifungal agents (see https://www.aspergillus.org.uk/antifungal-drug-interactions/). In this article, we address the common and less common, but serious, drug interactions observed in clinical practice with triazole antifungals, including a group of drugs that cannot be prescribed with all or most triazole antifungals (ivabradine, ranolazine, eplerenone, fentanyl, apomorphine, quetiapine, bedaquiline, rifampicin, rifabutin, sirolimus, phenytoin and carbamazepine). We highlight interactions with drugs used in children and new agents introduced for the treatment of haematological malignancies or graft versus host disease (midostaurin, ibrutinib, ruxolitinib and venetoclax). We also summarize the multiple interactions between oral and inhaled corticosteroids and triazole antifungals, and the strategies needed to optimize the therapeutic benefits of triazole antifungal therapy while minimizing potential harm to patients.

Chronic Rhinosinusitis with Extensive Recurrent Bilateral Nasal Polyposis-Third Times The Charm

The prevalence of recurrence in chronic rhinosinusitis with nasal polyposis (CRSwNP) is up to 40% after 18 months. Compliance to continuous medical therapy postoperatively is crucial to ensure disease resolution. CRSwNP endotype type 2 which is more common in Caucasian had shown higher recurrence. We report a case with third recurrence and the possible risk factors. A 37-year-old male smoker presented with rhinorrhea, bilateral facial pain, and anosmia for 3 years. He had two previous sinus surgeries and septoplasty. His nasal symptoms recurred a few months after both surgeries. Due to the recent pandemic, he defaulted on follow up. Rigid endoscopy at initial presentation revealed bilateral grade 2 nasal polyps which progressed to grade 4 despite medical polypectomy. Computed tomography of paranasal sinus showed pansinusitis with bilateral extensive polyposis, with presence of frontal intrasinus calcification possibly due to chronic sinusitis or fungal infection. He contracted Covid-19 category 2A infection two months before his planned surgery. The patient underwent bilateral endoscopic sinus surgery revealing extensive polyposis occupying all paranasal sinuses and the nasal cavity, completely obstructing the nasal. Intraoperative blood loss from the mucosa of the sinuses amounted to 2 liters without any arterial bleeding, causing an increase in operative time due to persistent need to secure hemostasis. Histopathological findings showed benign inflammatory polyps. There were reactionary polyps seen in bilateral maxillary sinuses and ethmoids at 2 weeks post operatively. A short course of steroid and chlarythromycin were given to prevent progression of polyps. At 5 weeks post operative, he reported on return of smell, and no more nasal blockage. We discuss the risk factors and endotypes of nasal polyps in recurrence cases with the operative challenges in revision endoscopic nasal surgery. In conclusion, recurrence nasal polyps after revision surgery is multifactorial with some possible prevention.International Journal of Human and Health Sciences Supplementary Issue 01: 2024 Page: S55

Chronic Severe Laryngeal Inflammation Caused by Basidiobolomycosis

Basidiobolomycosis is an uncommon fungal infection primarily found in plants. In humans, it typically affects the skin and gastrointestinal tract on manifestation of the infection. A 29-year-old female presented to our clinic with complaints of shortness of breath and voice changes. On examination, she exhibited severe laryngeal edema. She was initially diagnosed with type 3 hereditary angioedema with a normal C1 inhibitor and later as a case of laryngeal sarcoidosis, treatment for both conditions proved ineffective. Ultimately, after further microbiological assessment, she was diagnosed with chronic granulomatous laryngeal fungal infection caused by the Basidiobolus species. Subsequently, she displayed significant improvement with itraconazole treatment. Chronic laryngeal edema can have various underlying causes. This case underscores the importance of considering fungal pathogens, especially rare ones when assessing such conditions. In cases where the diagnosis is uncertain or standard treatments are ineffective, patient reassessment and repeated laryngeal biopsies are essential.

Natural products of plant origin: an emerging therapeutic for dermatomycosis.

Dermatomycosis or superficial mycosis is considered one of the chronic fungal infections and a global challenge for the public health system. The severity of dermatomycosis is proportionately increasing with the emerging population of immunocompromised individuals, and it is becoming more prevalent, even life-threatening, in several tropical countries. In this context, improper long-term treatment with synthetic antifungal drugs and their related side effects imposes additional challenges in treating dermatomycosis. Thus, the present scenario highlights the need for a novel and accurate treatment with minimal or no side effects. The multifaceted therapeutic properties of various natural products have garnered the interest of scientific communities in recent years. Generally, plant-based products have low toxicity levels and offer diverse formulations and unique biomolecules for clinical applicability against dermatomycosis. Thus, this study presents an overview of the pathogenesis and different treatment strategies for dermatomycosis. In addition, we highlight the implementation of natural products of plant origin for treating dermatomycosis infections and reducing adverse events. Further, their mode of action and role in the development of pharmaceutical drugs are discussed.

From diagnosis to treatment- Navigating Chromoblastomycosis

Chromoblastomycosis is a chronic fungal skin infection caused by dematiaceous fungi, characterized by nodular skin lesions and the presence of sclerotic bodies in affected tissues. Here, we report a case of chromoblastomycosis from Karnataka, India. A 22 years old female patient presented with a history of a vegetating ulcer with crusting. The diagnosis of chromoblastomycosis was made by demonstration of sclerotic bodies on histopathology of the biopsy specimen. Presence of pigment, multinucleate giant cells and eosinophils were the clues to search for the dematacious fungi on histopathology. High degree of suspicion by the clinician and the pathologist is important for definitive diagnosis.

Mechanisms of antifungal resistance and developments in alternative strategies to combat Candida albicans infection.

Candida albicans is a commensal fungus that infects the humans and becomes an opportunistic pathogen particularly in immuno-compromised patients. Among the Candida genus, yeast C. albicans is the most frequently incriminated species and is responsible for nearly 50-90% of human candidiasis, with vulvovaginal candidiasis alone, affecting about 75% of the women worldwide. One of the significant virulence traits in C. albicans is its tendency to alternate between the yeast and hyphae morphotypes, accounting for the development of multi-drug resistance in them. Thus, a thorough comprehension of the decision points and genes controlling this transition is necessary, to understand the pathogenicity of this, naturally occurring, pernicious fungus. Additionally, the formation of C. albicans biofilm is yet another pathogenesis trait and a paramount cause of invasive candidiasis. Since 1980 and in 90s, wide spread use of immune-suppressing therapies and over prescription of fluconazole, a drug used to treat chronic fungal infections, triggered the emergence of novel anti-fungal drug development. Thus, this review thoroughly elucidates the diseases associated with C. albicans infection as well as the anti-fungal resistance mechanism associated with them and identifies the emerging therapeutic agents, along with a rigorous discussion regarding the future strategies that can possibly be adopted for the cure of this deleterious pathogen.

Role of Ayurveda Drugs in Management of Fungal Skin Lesions of a Pediatric Age Group Patient – Case Study

Skin is the largest organ of the body. Because of the largest and maximum exposure to the environment, it is most likely to be infected, infested, and injured. Correspondingly, according to the World Health Organization (W.H.O.), Skin diseases have a high prevalence in the child age group (21-87%) in most developing countries and 10-20% of patients all over the world suffer from various fungal infections. An environment that is suitable and rich for fungal growth, the use of readily available and resistant drugs, and the low immunity of the child make the infection chronic and worrisome. Ayurveda simulates fungal infection with Dadru which is considered among Chudrakushtha (~minor skin diseases). In this case study, a six-year-old girl who was suffering from chronic fungal infections was treated through Ayurveda oral medications like Shatavari Churna, Jahar Mohra Pishti, Trikatu, Gandhak Rasayan, and Vidanga Lauh in Yoga(~mixture) form along with Lepa (~ paste for local application) having Triphala Churna, Dhatura, and Nimba leaves paste for sixty days. The effect of the treatment was seen from the evaluation scale obtained from previous research studies which yielded better results. Thus this study shows the effective use of Ayurveda medicines especially in fungal skin lesions in children.

A new method for improved topical drug delivery, Emulgel

Emulgel is used to treat injuries and diseases such as arthritis, headaches, muscle aches, backaches, and those brought on by colds. Patient compliance with topical formulations is crucial in the treatment of chronic dermatosis such psoriasis, acne, and fungal infections. Emulgel, a more recent NDDS technology used topically, combines the characteristics of an emulsion with a gel to provide a dual control release. Emulgels have emerged as one of the most exciting topical delivery methods because of their dual release control mechanism, which combines a gel with an emulsion. Gels have many benefits, but one significant drawback is that hydrophobic medication delivery is hampered. An emulsion-based approach is being developed to circumvent this limitation and enable even a hydrophobic medicinal component to take use of the unique properties of gels. Emulgel is the name given to the dosage form created by combining gel with emulsion. Emulgels can be added to analgesics and antifungal medications. In several aspects, these emulgels are superior to both cutting-edge vesicular systems and traditional systems.

Drug utilization pattern evaluation and cost variation analysis of anti-fungal agents in tinea infected patients in dermatology department of a tertiary care teaching hospital

Background: Tinea infections are chronic superficial fungal infections, highly prevalent in tropical countries like India. Therefore, long-term therapy is needed and this can inflict a financial burden on the patients. Aim of the study was to assess drug utilization patterns in patients diagnosed with tinea infection and to evaluate the cost variability of anti-fungal agents. Methods: A cross-sectional observational study was conducted in patients for 3 months after taking permission from IEC. All adult patients already diagnosed with tinea infection were enrolled. Evaluation of drug utilization pattern was carried out using WHO core drug prescribing indicators and percentage of cost variability was calculated between different brands of anti-fungal agents. Results: A total of 252 patients were enrolled. Tinea corporis and cruris were the most commonly diagnosed tinea infection. Pruritus was the most common presenting symptom. Past history of similar illness was seen in 74 (29.4%) patients mean of 3.83±0.87 drugs were prescribed per patient. Drugs prescribed from NLEM was only 42.1%. Most commonly prescribed drugs were oral itraconazole and topical miconazole. Percentage of cost variability was seen maximum with capsule itraconazole 200 mg (237.5%) by oral route and luliconazole 30 gm (175.6%) by topical route. Conclusions: Prescribing practices of drugs can be improved by promoting generic drug and prescribing drugs from NLEM. Wide range of cost variation can lead to high economic burden in tinea infected patients.

TRAF3 gene regulates macrophage migration and activation by lung epithelial cells infected with Aspergillus fumigatus.

Aspergillus fumigatus can infect immunocompromised individuals and cause chronic and fatal invasive fungal infections. A better understanding of the molecular mechanisms of A. fumigatus-host interactions may provide new references for disease treatment. In this study, we demonstrated that the TRAF3 gene plays an important role in the early infection of A. fumigatus by regulating the resistance of lung epithelial cells to A. fumigatus. Macrophages are the most abundant innate immune cells in the alveoli; however, few studies have reported on the interactions between lung epithelial cells and macrophages in response to A. fumigatus invasion. In our study, it was demonstrated that the TRAF3 gene reduces migration to macrophages and cytokine production by negatively regulating lung epithelial cell adhesion and internalization of A. fumigatus spores. Together, our results provide new insights into lung epithelial cell-macrophage interactions during A. fumigatus infection.

Regulation of lung inflammation by adiponectin.

Adiponectin is an insulin sensitizing hormone that also plays a role in the regulation of inflammation. Although adiponectin can exert pro-inflammatory effects, more studies have reported anti-inflammatory effects, even in non-adipose tissues such as the lung. Obesity is considered an inflammatory disease, is a risk factor for lung diseases, and is associated with decreased levels of plasma adiponectin. The results of recent studies have suggested that adiponectin exerts anti-inflammatory activity in chronic obstructive pulmonary disease, asthma and invasive fungal infection. The signaling receptors of adiponectin, AdipoR1 and AdipoR2, are expressed by epithelial cells, endothelial cells, and immune cells in the lung. In this mini-review, we discuss the anti-inflammatory mechanisms of adiponectin in lung cells and tissues.

Biosynthesis of copper oxide nanoparticles using Caesalpinia sappan extract: In vitro evaluation of antifungal and antibiofilm activities against Candida albicans.

Synthesis of nanoparticles using natural organic substances has attracted more attention due to avoiding inorganic toxicity. This work aimed to synthesize copper oxide nanoparticles (CuONPs) using Caesalpinia sappan heartwood extract as a reducing agent. The effects of pH of synthesis reaction were investigated. The obtained CuONPs were characterized using UV-visible spectroscopy, Fourier transform infrared spectroscopy, scanning electron microscopy, and energy dispersive X-ray spectroscopy. Their particle size, size distribution, and zeta potential were determined using photon correlation spectrophotometry. Candida albicans is a major cause of chronic fungal infections due to its biofilms leading to severe drug resistance problems. In this study, in vitro antifungal and antibiofilm activities as well as killing kinetics of the synthesized CuONPs against C. albicans were investigated. Additionally, fungal biofilm was observed by using confocal laser scanning microscopy. The results showed that the pH of the synthesis reaction played an important role in the physicochemical properties and antifungal activities of the obtained CuONPs. CuONPs synthesized at pH 10 and 12 showed the relatively small and narrow size distribution with high negative zeta potential and time-dependent killing kinetics. Confocal laser scanning microscopy confirms obvious fungal biofilm reduction and increased fungal cell death after exposure to CuONPs. These findings suggest the optimal pH of CuONPs synthesis using C. sappan extract as a reducing agent. The results on antifungal and antibiofilm activities indicate that the obtained CuONPs can be a promising agent for treating fungal infection.

Predictive factors for treatment response and mortality in chronic pulmonary aspergillosis.

Chronic pulmonary aspergillosis (CPA) is associated with significant mortality, and suboptimal antifungal treatment response. We describe predictive factors for treatment response and survival. We retrospectively analysed clinical, serological and radiological parameters at baseline and following antifungal treatment in patients with CPA and correlated with clinical and radiological response and survival. Fifty-nine patients were included with a mean age of 61 years. Thirty (51%) had a diagnosis of COPD. On clinical assessment at 6 months, 21 (36%) had clinically improved, 20 (34%) were clinically stable and 15 (25%) had deteriorated. Radiological improvement was observed in 30 (53%), stability in 11 (19%) and deterioration in 16 (28%). Only a lower C-reactive protein (CRP) at baseline was associated with a favourable clinical-radiological response. On univariate analysis, lower CRP, higher albumin, lower Aspergillus IgG and use of inhaled steroids were associated with lower mortality. An overall favourable response at 6 months was associated with lower mortality. Inflammatory markers and Aspergillus IgG were predictors of mortality in CPA. This suggests that mortality in CPA is driven mainly by the chronic fungal infection itself rather than the underlying disease, therefore early optimised treatment of CPA may lead to improved outcomes.