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Amphotericin B (AmB) use is limited by the occurrence of kidney toxicity. Here, we evaluated the incidence and impact of nephrotoxicity in a large series of patients receiving therapy with amphotericin B deoxycholate (d-AmB), liposomal AmB (L-AmB), or AmB lipid complex ( ABLC), in a clinical practice scenario. In a retrospective cohort study, patients treated with different AmB formulations between 2003 and 2012 were evaluated. Medical records and laboratory data were reviewed. Nephrotoxicity was determined according to modified RIFLE criteria. Predictors of nephrotoxicity and mortality were determined and treatment groups were compared. About 431 patients were studied (d-AmB, n = 236; L-AmB, n = 105; ABLC, n = 90). Frequency of severe nephrotoxicity ( RIFLE 'Failure') was 11.5%, 2.4% and 7.2% for d-AmB, L-AmB and ABLC, respectively ( P = 0.046). Use of L-AmB was found to be an independent protective factor ( OR: 0.18; 95% CI: 0.03-0.64; P = 0.006) for severe nephrotoxicity, considering d-AmB as a reference. L-AmB was also a protective factor for mortality ( OR: 0.56; 95% CI: 0.32-0.99; P = 0.046). In addition, in-hospital overall mortality was associated with cancer, previous dialysis, evolution to dialysis, and stay in the intensive care unit. Patients treated with ABLC showed similar frequency of severe kidney toxicity than those treated with d-AmB. L-AmB was associated with better outcomes than other formulations, including severe nephrotoxicity and overall mortality. [ABSTRACT FROM AUTHOR]

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Dear Editor, We report a particular case of skin rash in a patient with COVID-19. Could SARS-CoV-2 also interact with drugs, triggering a SDRIFE-like rash? SDRIFE-like rash in COVID-19 patient: drug reaction or another cutaneous manifestation of SARS-CoV-2?. [Extracted from the article]

Clostridium difficile is the major cause of nosocomial diarrhoea. Several detection methods are available for the laboratory diagnosis of C. difficile, but these vary in terms of sensitivity and specificity. In this study, we compared the performance of three following laboratory tests to detect C. difficile: in-house real-time PCR aiming for toxin B gene ( tcdB), EIA for detection of toxins A and B ( Premier Toxins A & B) and C. difficile culture in selective medium (bio Merieux). Our results were grouped into three categories as follows: (1) C. difficile-associated diarrhoea ( CDAD); (2) asymptomatic carriers; and (3) negative results. Among the 113 patients included in the study, 9 (8.0%) were classified as CDAD, 19 (16.8%) were asymptomatic carriers, 76 (67.2%) had negative results and 9 (8.0%) could not be categorized (positive test for C. difficile toxins only). PCR was found to be the most sensitive diagnostic test in our study, with the potential to be used as a screening method for C. difficile colonization/ CDAD. Diagnosis of CDAD would be better performed by a combination of PCR and EIA tests. [ABSTRACT FROM AUTHOR]

The triazole class of antifungal drugs comprises first-line agents for the treatment of several invasive fungal diseases. Isavuconazole is a novel broad-spectrum triazole agent. Here we summarize its characteristics and compare it with the currently available antifungal agents. Isavuconazole is administered as a prodrug, and it is water soluble. Oral and intravenous formulations are available. Its intravenous formulation does not contain cyclodextrin, which is an advantage over voriconazole, considering the potential for nephrotoxicity of cyclodextrin. As with other azoles, isavuconazole requires a loading dose. Due to its prolonged half-life, a once-a-day regimen is possible. Considering that isavuconazole shares the same mechanism of action with the other triazoles, cross-resistance is an important concern in the class. Tolerability and safety profiles are favorable, and no serious adverse events have been consistently reported. Significant interactions with drugs metabolized by cytochrome P450 are expected to occur, especially with substrates and inducers of the CYP3A4 enzyme. Isavuconazole has in vitro activity against most medically important fungi, including species of Candida, Aspergillus, and Cryptococcus. It has some activity against the agents of mucormycosis. Clinical data regarding isavuconazole remain limited because ongoing trials have not yet been completed or published. Isavuconazole has the potential to become first-line therapy for invasive aspergillosis. It also has the potential for use in the context of antifungal prophylaxis, salvage therapy, or in combination regimens. Results of clinical trials are ultimately expected in order to adequately position isavuconazole in the current antifungal armamentarium. [ABSTRACT FROM AUTHOR]

Invasive aspergillosis ( IA) seems to be an emerging condition in intensive care units ( ICUs). However, little attention has been given to the role of environmental factors that could increase the risk for IA in the ICU. The objective of this study was to determine the concentration of airborne fungi in three Brazilian ICUs, in an attempt to correlate fungal burden with the frequency of Aspergillus spp isolation from clinical samples of patients hospitalised in these units. During a 1-year period we quantitatively evaluated the presence of fungi in the air of three ICUs in Porto Alegre, Brazil. The quantity of fungi was correlated with environmental factors. Only one of the ICUs studied showed equal concentrations of Aspergillus conidia in the indoor air, in comparison with the outdoor environment. All cases of Aspergillus colonisation and IA cases observed during the study occurred in that particular ICU. Environmental factors have a direct influence on fungal spore concentration in the air in ICUs, as well as air filtration systems in air conditioners. Fungal contamination of the indoor air may influence the frequency of AI in ICU patients. [ABSTRACT FROM AUTHOR]

Aspergillomas develop from progressive layers of mycelial growth on the walls of pulmonary cavities over months. Aspergillomas are characteristic of chronic pulmonary aspergillosis and are a risk factor for azole resistance. We investigated genotypic and phenotypic alterations in Aspergillus fumigatus recovered from aspergillomas. Aspergillomas were removed from three patients (two at surgery, one at autopsy) and dissected. Overall 92 colonies of A. fumigatus were isolated. Microsatellite typing was conducted to determine genetic type. Itraconazole, voriconazole and posaconazole susceptibilities were performed. The cyp51A gene was sequenced in 22 isolates. Isolates from Patient 1 ( n = 25) were azole susceptible and resistant, although all cyp51A sequences were wild type, the isolates split into two distinct clades. In Patient 2, isolates were less variable ( n = 10), all were azole susceptible. In Patient 3 only azole-resistant strains ( n = 57) were isolated, with M220K or M220T Cyp51A alterations, and microevolution was indicated. Marked diversity was observed in isolates from these patients; revealing differences in azole susceptibility, mechanism of resistance and genetic type. Importantly, routine sampling from respiratory specimens proved suboptimal in all cases; azole resistance was missed (Patient 1), cultures were negative (Patient 2) and high-level posaconazole resistance was not detected (Patient 3). [ABSTRACT FROM AUTHOR]

Summary: Background: Whether nodular lesions have specific risk-factors or influence outcomes in lung transplant recipients with invasive aspergillosis, is not fully known. Methods: The study population consisted of 64 consecutive lung transplant recipients with proven or probable invasive aspergillosis. Nodules, with or without halo/air crescent-sign were considered nodular presentations. Outcomes assessed were response rate (successful versus unsuccessful outcome) and all-cause mortality at 12 weeks. Results: Overall, 34 patients had nodular and 30 had non-nodular lesions. Presence of nodular lesions was less likely to be associated with renal failure at baseline (adjusted OR 0.21, 95% CI, 0.04–0.97, p = 0.047), CMV infection (adjusted OR 0.18, 95% CI 0.04–0.75, p = 0.019) and receipt of antifungal prophylaxis (adjusted OR 0.22, 95% CI, 0.06–0.88, p = 0.032). Successful outcome and mortality rates in the study patients were 64.0% (41/64) and 25.0% (16/64), respectively. Nodular aspergillosis was associated with significantly higher successful outcome (adjusted OR 3.35, 95% CI, 1.06–10.54, p = 0.039) and lower mortality at 12 weeks (adjusted OR 0.20, 0.05–0.78, p = 0.021). Conclusions: Lung transplant recipients with nodular lesions due to invasive aspergillosis had better outcomes than those without such lesions. [Copyright &y& Elsevier]

Invasive fungal diseases have emerged as important causes of morbidity and mortality in haematological patients. In this study air samples were collected in two haematopoietic stem cell transplantation (HSCT) units, in which distinct air-control systems were in place. In hospital 1 no high-efficiency particulate air (HEPA) filter was available whereas in hospital 2 HSCT rooms were equipped with HEPA filters, with positive air pressure in relation to the corridor. A total of 117 samples from rooms, toilets and corridors were obtained during December 2009 to January 2011, using a six-stage Andersen sampler. In both hospitals, the concentration of potentially pathogenic fungi in the air was reduced in patients' rooms compared to corridors (P < 0·0001). Despite the presence of a HEPA filter in hospital 2, rooms in both hospitals showed similar concentrations of potentially pathogenic fungi (P = 0·714). These findings may be explained by the implementation of additional protective measures in hospital 1, emphasizing the importance of such measures in protected environments. [ABSTRACT FROM AUTHOR]

Histoplasmosis is caused by Histoplasma capsulatum and, although endemic in large parts of the world, is often underrecognized in many locations. In addition to underrecognition, inadequate availability of diagnostic tests is a major contributor to poor outcomes in disseminated disease in people with HIV. For those with advanced HIV and disseminated disease, antibody testing is less useful. Culture and histopathology can be useful in this situation, but each has limitations, including variable sensitivity by site and, in the case of culture, the need for a biosafety level three laboratory and a long period of growth. Antigen testing has proven useful for disseminated histoplasmosis due to the excellent sensitivity of urine. Yet, turnaround is slower than ideal due to use in a limited number of centers. The development of lateral flow assays has the potential to make for true rapid point-of-care assays for histoplasmosis, but in order to meet that promise, the tests must be widely available and affordable. [ABSTRACT FROM AUTHOR]

Invasive aspergillosis (IA) has emerged as an important medical problem in recent years. Despite advances in the diagnosis of this condition, as well as the availability of better-tolerated antifungal drugs, the mortality rates associated with IA have remained very high. Although several anfifungal drugs are known to have potent activity against Aspergillus spp., data from clinical trials remain limited. Here, the authors report the results of a systematic review of all randomized controlled trials published to date involving patients with IA. A critical review of each of these trials is presented. [ABSTRACT FROM AUTHOR]

Summary: Although systemic candidosis is common in hospitalised children, Candida involvement of lung parenchyma is rare and usually perceived only at autopsy. The purpose of this article was to review the evidence regarding lung involvement in Candida infections, with special attention to paediatric patients. Primary Candida pneumonia is rare and usually associated with aspiration of oropharyngeal contents. The majority of cases of Candida pneumonia are secondary to haematological dissemination of Candida organisms from a distant site, usually the gastrointestinal tract or the skin. The diagnosis of pulmonary candidosis is difficult because there is no specific clinical or radiological presentation. In addition, the presence of Candida in sputum or other respiratory specimens mostly represents contamination. A definitive diagnosis of Candida pneumonia requires histopathologic proof of lung invasion in association with inflammation. Children can also be affected by pulmonary allergic reactions caused by Candida species. Treatment of Candida pneumonia is essentially the same as for candidaemia. Preliminary evidence suggests that patients with severe asthma sensitised to Candida species may also benefit from antifungal drugs. [Copyright &y& Elsevier]

Azoles are the mainstay of oral therapy for aspergillosis. Azole resistance in Aspergillus has been reported infrequently. The first resistant isolate in Manchester, UK, was detected in 1999. In a clinical collection of 519 A. fumigatus isolates, the frequency of itraconazole resistance was 5%, a significant increase since 2004 (p<0.001). Of the 34 itraconazole-resistant isolates we studied, 65% (22) were cross-resistant to voriconazole and 74% (25) were cross-resistant to posaconazole. Thirteen of 14 evaluable patients in our study had prior azole exposure; 8 infections failed therapy (progressed), and 5 failed to improve (remained stable). Eighteen amino acid alterations were found in the target enzyme, Cyp51A, 4 of which were novel. A population genetic analysis of microsatellites showed the existence of resistant mutants that evolved from originally susceptible strains, different cyp51A mutations in the same strain, and microalterations in microsatellite repeat number. Azole resistance in A. fumigatus is an emerging problem and may develop during azole therapy. [ABSTRACT FROM AUTHOR]

Most of the information available about Aspergillus infections has originated from the study of A. fumigatus, the most frequent species in the genus. This review aims to compare the pathogenicity and clinical aspects of Aspergillosis caused by A. fumigatus an A. flavus. Experimental data suggests that A. flavus is more virulent than A. fumigatus. However, these were mostly models of disseminated Aspergillus infection which do not properly mimic the physiopathology of invasive aspergillosis, a condition that is usually acquired by inhalation. In addition, no conclusive virulence factor has been identified for Aspergillus species. A. flavus is a common cause of fungal sinusitis and cutaneous infections. Chronic conditions such as chronic cavitary pulmonary aspergillosis and sinuses fungal balls have rarely been associated with A. flavus. The bigger size of A. flavus spores, in comparison to those of A. fumigatus spores, may favour their deposit in the upper respiratory tract. Differences between these species justify the need for a better understanding of A. flavus infections. [ABSTRACT FROM AUTHOR]

Chronic pulmonary aspergillosis is broad term encompassing chronic cavitary, chronic fibrosing pulmonary aspergillosis and aspergilloma. All affect patients with structural lung diseases and many have subtle genetic immune defects. Almost all cases are caused by Aspergillus fumigatus. Here we report a patient with an aspergilloma which had Aspergillus flavus recovered from a surgical specimen and serum containing detectable precipitating antibody. [ABSTRACT FROM AUTHOR]

Toll-like receptors (TLRs) are important components of innate immunity. We investigated the association between polymorphisms in the TLR2, TLR4, and TLR9 genes and susceptibility to noninvasive forms of pulmonary aspergilosis. A significant association was observed between allele G on Asp299Gly (TLR4) and chronic cavitary pulmonary aspergillosis (odds ratio [OR], 3.46; P = .003). Susceptibility to allergic bronchopulmonary aspergillosis was associated with allele C on T-1237C (TLR9) (OR, 2.49; P = .043). No particular polymorphism was associated with severe asthma with fungal sensitization. These findings reinforce the importance of innate immunity in the pathogenesis of different forms of aspergillosis. [ABSTRACT FROM AUTHOR]

The rapid diagnosis of opportunistic infections (OIs) is critical for improving the health outcomes of people living with HIV/AIDS (PLWHA). This study aimed to describe the feasibility of implementing a package for the rapid diagnosis of tuberculosis, histoplasmosis, and cryptococcosis in patients with advanced HIV/AIDS disease in Porto Alegre, Brazil. The research involved two focus groups with health professionals, four in-depth interviews with healthcare managers, and twelve interviews with PLWHA. The corpus was analyzed using Descending Hierarchical Classification (DHC). The study found that the rapid test diagnosis intervention was generally well-received by patients and health professionals, improving diagnosis and treatment outcomes. However, it also identified several areas for improvement, including the need for expanded psychosocial support and enhanced coordination between health services. The findings have important implications for the development and implementation of policies and programs aimed at enhancing the diagnosis and treatment of OIs among PLWHA with advanced diseases. Further research should explore social determinants of HIV/AIDS mortality to offer valuable insights into improving prevention and treatment strategies. By prioritizing patient-centered care and improving coordination between health services, policymakers and health professionals can improve the health outcomes of PLWHA with advanced disease in Porto Alegre and other similar settings. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "1,3-β-Glucan Antigenemia for Early Diagnosis of Invasive Fungal Infections in Neutropenic Patients With Acute Leukemia," by Laurence Senn and colleagues.

Background Evidence for efficacy of single, high-dose liposomal amphotericin B (LAmB) in HIV-associated cryptococcal meningitis and histoplasmosis is growing. No systematic review has examined the safety of this regimen across multiple studies. Methods We systematically searched Medline, Scopus, and the Cochrane Library from inception to April 2023 for studies reporting grade 3 and 4 adverse events (AEs) with single high-dose LAmB vs traditional amphotericin regimens for HIV-associated fungal infections. Results Three trials (n = 946) were included. Compared with traditional regimens, single high-dose LAmB was associated with equivalent risk of grade 3 and 4 AEs (risk ratio [RR], 0.75; 95% CI, 0.53–1.06) and lower overall risk of grade 4 AEs (RR, 0.68; 95% CI, 0.55–0.86), grade 4 renal (RR, 0.43; 95% CI, 0.20–0.94) and grade 4 hematological AEs (RR, 0.46; 95% CI, 0.32–0.65). Conclusions Single, high-dose LAmB is associated with a lower risk of life-threatening AEs compared with other World Health Organization–endorsed amphotericin B–based regimens in invasive HIV–related fungal infection. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article that deals with the toxicity of Amphotericin B (AmB) to treat cryptococcal meningoencephalitis in patients with HIV infection.

Endemic fungal infections are responsible for high rates of morbidity and mortality in certain regions of the world. The diagnosis and management remain a challenge, and the reason could be explained by the lack of disease awareness, variability of symptoms, and insidious and often overlooked clinical presentation. Imaging findings are nonspecific and frequently misinterpreted as other more common infectious or malignant diseases. Patient demographics and clinical and travel history are important clues that may lead to a proper diagnosis. The purpose of this paper is to review the presentation and differential diagnosis of endemic mycoses based on the most common chest imaging findings. [ABSTRACT FROM AUTHOR]

We sought to determine the prevalence of probable disseminated histoplasmosis among advanced HIV disease (AHD) patients in Nigeria. We conducted a cross-sectional study in 10 sites across 5 of 6 geopolitical zones in Nigeria. We identified patients with urinary samples containing CD4 cell counts <200 cells/mm3 or World Health Organization stage 3 or 4 disease who also had >2 clinical features of disseminated histoplasmosis, and we tested them for Histoplasma antigen using a Histoplasma enzyme immune assay. Of 988 participants we recruited, 76 (7.7%) were antigen-positive. The 76 Histoplasma antigen-positive participants had significantly lower (p = 0.03) CD4 counts; 9 (11.8%) were also co-infected with tuberculosis. Most antigen-positive participants (50/76; 65.8%; p = 0.015) had previously received antiretroviral treatment; 26/76 (34.2%) had not. Because histoplasmosis is often a hidden disease among AHD patients in Nigeria, Histoplasma antigen testing should be required in the AHD package of care. [ABSTRACT FROM AUTHOR]

Histoplasmosis is a frequent fungal opportunistic infection in people living with HIV (PLHIV), associated every year to a total of 5% to 15% of AIDS-related deaths among this population. In 2020, the first global guidelines for diagnosing and managing disseminated histoplasmosis among PLHIV was published. This document recommends (1) detection of circulating Histoplasma antigens as the recommended laboratory assay to diagnose histoplasmosis among PLHIV; (2) the use of liposomal amphotericin for induction therapy in severe or moderately severe disease, followed by a maintenance therapy with itraconazole for 12 months; a shorter maintenance therapy could be considered if the patient is clinically stable and if immune status has improved; (3) antiretroviral therapy initiation as soon as possible among patients with histoplasmosis without involvement of central nervous system; and (4) that for the treatment of co-infection with histoplasmosis and tuberculosis (TB), treatment of TB should be initiated according to theWorld Health Organization treatment guidelines. Appropriate health education of providers, supportive supervision, and policy guidance for the care of PLHIV are required. [ABSTRACT FROM AUTHOR]