Showing papers in "Current Fungal Infection Reports in 2019"

Mucormycosis: Pathogenesis and Pathology

Abstract: Mucormycosis is an opportunistic fungal infection associated with high mortality. Understanding the pathogenesis and the resultant pathology in various organs enables to improve early diagnosis and treatment options. An immunocompetent host with intact skin/mucosal barrier and innate immunity is usually resistant to the infection; however, natural disasters and trauma account for the disease in healthy hosts. Neutropenia, immunosuppression, hyperglycemia, ketoacidosis, and other factors impair host defenses and make increased serum iron available to the pathogen for its growth. The fungus has special iron assimilation mechanisms. The cell wall composition and genetic alterations allow rapid growth in host environment and evade host defenses. Expression of CotH proteins on the spores and hyphae facilitates adhesion to the receptors on endothelial cells, angioinvasion, and dissemination. Elaboration of lytic enzymes and proteases along with mycotoxins augment fungal invasion. Rhinocerebral mucormycosis is the most common clinical form. The pathology hall mark in various organs is angioinvasion resulting in hemorrhage, infarction, and suppurative inflammation. The host defenses and how the risk factors alter and impair the host’s ability to prevent the invasion of the fungus are reviewed. The virulence factors of the fungus to rapidly grow and disseminate in the host by evading recognition, suppressing immune response, manipulate the environment to derive nutrition, and cause disease are discussed.

Fungal Infections with Ibrutinib and Other Small-Molecule Kinase Inhibitors

Abstract: Small-molecule kinase inhibitors (SMKIs) have revolutionized the management of malignant and autoimmune disorders. Emerging clinical reports point towards an increased risk for invasive fungal infections (IFIs) in patients treated with certain SMKIs. In this mini-review, we highlight representative examples of SMKIs that have been associated with or are expected to give rise to IFIs. The clinical use of the Bruton’s tyrosine kinase inhibitor ibrutinib as well as other FDA-approved SMKIs has been associated with IFIs. The fungal infection susceptibility associated with the clinical use of certain SMKIs underscores their detrimental effects on innate and adaptive antifungal immune responses. The unprecedented development and clinical use of SMKIs is expected to give rise to an expansion of iatrogenic immunosuppressive factors predisposing to IFIs (and other opportunistic infections). Beyond increased clinical surveillance, better understanding of the pathogenesis of SMKI-associated immune dysregulation should help in devising improved risk stratification and prophylaxis strategies in vulnerable patients.

The Human Lung Mycobiome in Chronic Respiratory Disease: Limitations of Methods and Our Current Understanding

Abstract: This review summarises the characteristics of the lung mycobiome in patients with chronic respiratory diseases and fungal lung diseases. We have also reviewed the limitations of the current methods in mycobiome studies. Available studies in the impacts of the mycobiome in chronic and fungal lung diseases are scarce and comparison of the available studies is hindered by heterogeneity in the sample sizes, methods and patient selection. The impact of the diversity and composition of the lung mycobiome in chronic and fungal lung diseases is poorly understood. Most studies involve detection of fungi in respiratory samples by culture. However, such methods lack sensitivity and the emergence of next-generation sequencing technologies is an important advance. However, differences in the sequencing methodologies limit study comparisons. Well-designed methodological approaches and large cohort studies are needed to evaluate the impact of the lung mycobiome in respiratory diseases.

New) Methods for Detection of Aspergillus fumigatus Resistance in Clinical Samples.

Abstract: The incidence of invasive aspergillosis has increased substantially over the past few decades, accompanied by a change in susceptibility patterns of Aspergillus fumigatus with increasing resistance observed against triazole antifungals, including voriconazole and isavuconazole, the most commonly used antifungal agents for the disease. Culture-based methods for determining triazole resistance are still the gold standard but are time consuming and lack sensitivity. We sought to provide an update on non-culture-based methods for detecting resistance patterns to Aspergillus. New molecular-based approaches for detecting triazole resistance to Aspergillus, real-time polymerase chain reaction (PCR) to detect mutations to the Cyp51A protein, have been developed which are able to detect most triazole-resistant A. fumigatus strains in patients with invasive aspergillosis. Over the last few years, a number of non-culture-based methods for molecular detection of Aspergillus triazole resistance have been developed that may overcome some of the limitations of culture. These molecular methods are therefore of high epidemiological and clinical relevance, mainly in immunocompromised patients with hematological malignancies, where culture has particularly limited sensitivity. These assays are now able to detect most triazole-resistant Aspergillus fumigatus strains. Given that resistance rates vary, clinical utility for these assays still depends on regional resistance patterns.

Histoplasmosis: Epidemiology, Diagnosis, and Clinical Manifestations

Abstract: This review highlights the epidemiology, diagnosis, and clinical manifestations of histoplasmosis. There is an increasing awareness of histoplasmosis in Central and South America in patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), and deaths from histoplasmosis in this region may outnumber deaths from tuberculosis. Diagnosis in this region is hampered by lack of rapid diagnostic tests. Growth of H. capsulatum in culture is definitive, but takes weeks. In areas in which antigen testing is available, this has become an important rapid diagnostic tool, and methods combining antigen and antibody testing appear to improve diagnostic accuracy for acute pulmonary and central nervous system histoplasmosis. Pulmonary histoplasmosis, although usually self-limited, rarely can lead to life-threatening complications. Uncommon, but serious and sometimes fatal complications of disseminated histoplasmosis include Addison’s disease, meningitis, culture-negative endocarditis, and hemophagocytic lymphohistiocytosis. The use of antigen testing has improved our ability to diagnose histoplasmosis, but these tests are not universally available. Complications of both pulmonary and disseminated histoplasmosis remain challenging.

Clinical Aspects of Immune Damage in Cryptococcosis

Abstract: To perform an extensive review of recent literature and provide an update on the current epidemiology, clinical features, and management of cryptococcal disease with a focus on the differences between patients depending on their immune status. Emerging literature has highlighted the inflammatory pathophysiology and varied manifestations of cryptococcal infections in patients who are apparently healthy but paradoxically have a more critical clinical course compared with their immunosuppressed counterparts. Non-HIV cryptococcal meningitis has greater mortality compared with that seen in HIV patients. Basic science experiments closely analyzing the underlying pathophysiological response to this infection have demonstrated the predominant role of T cell–mediated inflammatory injury in causing worse clinical outcomes. Further studies are needed to define the need for immunosuppressive agents in the treatment of this illness.

Non-Aspergillus Fungal Infections in Chronic Granulomatous Disease

Abstract: Management of Aspergillus infection in chronic granulomatous disease (CGD) patients remains a challenge even in new azoles era. However, epidemiology, diagnosis, and management of non-Aspergillus fungal infection (NAFI) in CGD setting are poorly described. NAFI appears to be rare in CGD patients and receiving antifungal prophylaxis. Clinical presentation is not specific of fungal species and patients often suffer from mild disease with prolonged course. While candidiasis and mucormycosis are also common in other immunocompromised population, infections caused by Phellinus tropicalis, Trichosporon inkin, and Rasamsonia argillacea have a unique predilection for CGD patients. Improved fungal identification with molecular methods allows description of new fungal species. The available data for NAFI during CGD are limited and based on case reports and small series. Invasive tissue biopsies and advanced molecular methods are often required for diagnosis and guiding antifungal strategy in addition to a close collaboration between clinician, pathologist, and mycologist.

Small-Molecule Protein Kinases Inhibitors and the Risk of Fungal Infections

Abstract: This review discusses fungal infections associated with licenced small-molecule protein kinase inhibitors. For each major drug class, the mechanism of action and targeted pathways and the impact on host defence against fungi are described. Protein kinase inhibitors are successfully used in the treatment of malignancies and immune-mediated diseases, targeting signalling pathways for a broad spectrum of cytokines and growth-stimuli. These agents predispose to fungal infections by the suppression of integral components of the adaptive and innate immune response. The greatest risk of fungal infections is seen with bruton tyrosine kinase inhibitors, e.g. ibrutinib. Infections are also reported with agents that target mTOR, Janus kinase and break point cluster (Bcr) gene–Abelson (Abl) tyrosine kinase (BCR-ABL). The type of fungal infection fits mechanistically with the specific pathway targeted. Infections are often disseminated and present soon after the initiation of therapy. The pharmacokinetic profile, possibility of off-target kinase inhibition, and underlying disease pathology contribute to infection risk.

The Manaus Declaration: Current Situation of Histoplasmosis in the Americas, Report of the II Regional Meeting of the International Histoplasmosis Advocacy Group

Abstract: The aim of this report is to summarize the conclusions of the II Regional Meeting on Histoplasmosis in the Americas held in Manaus, Brazil, on March 22–24, 2019. Persons living with advanced HIV are at high risk for developing histoplasmosis. Clinical signs and symptoms of this disease are often non-specific, making it difficult to establish a diagnosis. Although with the recent technological advances, in vitro diagnostics and medicines for histoplasmosis are often not available in many regions around the world. In addition, histoplasmosis is often not included in HIV care and treatment programs, resulting in inadequate health system planning and missed opportunities to save lives. The II Regional Meeting on Histoplasmosis in the Americas gathered a multidisciplinary audience. Developed recommendations to be included in the WHO guidelines for diagnosis and treatment of histoplasmosis in advanced HIV were the product of this meeting, and guidelines are aimed to be published in early 2020.

Pneumocystis jirovecii Pneumonia: Epidemiology, Clinical Manifestation and Diagnosis

Abstract: The purpose of this study is to provide an understanding of the increased range of patient cohorts at risk of Pneumocystis jirovecii pneumonia (PCP) and describe typical clinical presentations together with advances in diagnostic assays and strategies. The range of immuno-compromised patients at risk of PCP continues to expand. Apart from human immunodeficiency virus (HIV)-positive patients, those with solid tumours or suffering from haematological malignancy, solid organ transplant recipients or with autoimmune and inflammatory conditions receiving immuno-modulating therapies and patients diagnosed with primary immune deficiencies are all at increased risk of PCP. The clinical presentation of respiratory distress may be mild/moderate in the HIV-positive patient, but fulminant in HIV-negative. While typical clinical signs of PCP, along with underlying risk factors and the absence of alternative diagnoses, may be sufficient to commence therapy, every effort should be made to achieve a mycological diagnosis. With the advent of modern diagnostics techniques (real-time polymerase chain reaction (PCR) and (1-3)-β-D-Glucan), a laboratory-based diagnosis should always be attempted, although microscopic identification of Pneumocystis within respiratory samples remains the reference method. By combining different assays, it may be possible to both exclude and confirm PCP, without the need for invasive samples. This review will summarize the epidemiology, clinical manifestations and diagnostic options for PCP, and also briefly cover therapeutic management, the emerging issue of resistance and PCP in paediatric age group.

Updates in Ocular Antifungal Pharmacotherapy: Formulation and Clinical Perspectives

Abstract: In this review, a compilation on the current antifungal pharmacotherapy is discussed, with emphases on the updates in the formulation and clinical approaches of the routinely used antifungal drugs in ocular therapy. Natamycin (Natacyn® eye drops) remains the only approved medication in the management of ocular fungal infections. This monotherapy shows therapeutic outcomes in superficial ocular fungal infections, but in case of deep-seated mycoses or endophthalmitis, successful therapeutic outcomes are infrequent, as a result of which alternative therapies are sought. In such cases, amphotericin B, azoles, and echinocandins are used off-label, either in combination with natamycin or with each other (frequently) or as standalone monotherapies, and have provided effective therapeutic outcomes. In recent times, amphotericin B, azoles, and echinocandins have come to occupy an important niche in ocular antifungal pharmacotherapy, along with natamycin (still the preferred choice in most clinical cases), in the management of ocular fungal infections.

Antifungal Resistance Testing and Implications for Management

Abstract: Antifungal agents are the mainstay in the management of patients with invasive fungal disease. However, resistance to current antifungal agents can develop with clinical use, which may negatively impact clinical outcomes. We review the strengths and weaknesses of antifungal susceptibility testing and how the detection of resistance, either phenotypically or molecularly, correlates with clinical outcomes. Phenotypic resistance is associated with worse outcomes, although this must be taken in context with other patient factors. Newer molecular assays have been developed that have shown promising results for the detection of resistance mechanisms, including azole resistance in Aspergillus fumigatus and echinocandin resistance in different Candida species. Further work is needed to improve the clinical utility of these assays for faster turn-around-time and direct use on specimens. Detection of antifungal resistance may provide useful information for the treatment of invasive fungal disease.

Diagnostic Aspects of Chronic Pulmonary Aspergillosis: Present and New Directions

Abstract: Diagnosis of chronic pulmonary aspergillosis (CPA) is important since many diseases have a similar appearance, but require different treatment. This review presents the well-established diagnostic criteria and new laboratory diagnostic approaches that have been evaluated for the diagnosis of this condition. Respiratory fungal culture is insensitive for CPA diagnosis. There are many new tests available, especially new platforms to detect Aspergillus IgG. The most recent innovation is a lateral flow device, a point-of-care test that can be used in resource-constrained settings. Chest radiographs without cavitation or pleural thickening have a 100% negative predictive value for chronic cavitary pulmonary aspergillosis in the African setting. Early diagnosis of CPA is important to avoid inappropriate treatment. It is our contention that these new diagnostics will transform the diagnosis of CPA and reduce the number of undiagnosed cases or cases with a late diagnosis.

Genetic variation and fungal infection risk: State of the art

Abstract: Fungal infections cause significant mortality in patients with acquired immunodeficiencies including AIDS, hematological malignancies, transplantation, and receipt of corticosteroids, biologics or small-molecule kinase inhibitors that impair key immune pathways. The contribution of several such pathways in antifungal immunity has been uncovered by inherited immunodeficiencies featuring profound fungal susceptibility. Furthermore, the risk of fungal infection in patients with acquired immunodeficiencies may be modulated by single nucleotide polymorphisms (SNPs) in immune-related genes. This review outlines key features underlying human genetic fungal infection predisposition. The discovery of monogenic disorders that cause fungal disease and the characterization of immune-related gene SNPs that may regulate fungal susceptibility have provided important insights into how genetic variation affects development and outcome of fungal infections in humans. Recognition of individualized genetic fungal susceptibility traits in humans should help devise precision-medicine strategies for risk assessment, prognostication, and treatment of patients with opportunistic fungal infections.

Fungal Necrotizing Skin and Soft Tissue Infections

Abstract: This review summarizes the medical literature regarding fungal necrotizing skin and soft tissue infections (NSTI). The available epidemiologic, microbiologic, treatment, and outcome data are presented by the most common causal organisms of this disease process. With the exception of cutaneous mucormycosis, which often progresses to necrotizing infection, clinical data for other fungal NSTI are largely limited to case reports and small case series. Fungal NSTI are rare but some data suggests that incidence may be increasing. These infections occur in both immunocompromised and immunocompetent hosts, especially following trauma. Mortality varies by host factors, organism, and extent of disease. Foundations of treatment include targeted antifungal therapy and aggressive surgical debridement. Fungal NSTI is a rarely described clinical entity associated with a high mortality. More study is needed to better understand the epidemiology and optimal management of these infections.

Tinea Gladiatorum: an Update

Abstract: This article summarizes the main epidemiological characteristics of tinea gladiatorum, new outbreaks that have been presented over the years, and theories about their transmission, diagnosis, treatment, and prophylactic measures. Despite the controversy, recent studies defined that the transmission of tinea gladiatorum is by skin-to-skin contact and through fomites. Once the infection is acquired, it is difficult to control due to its rapid dissemination to other wrestlers, so great importance has been taken to prevention. Despite dermatophytosis still being considered as one of the major public health problems in wrestlers, very little attention has been paid by the medical community. In the literature, the majority are reports of outbreaks, so the challenge would be to conduct a more conclusive study that allows us to have a broader picture of this condition.

Chromoblastomycosis in Solid Organ Transplant Recipients

Abstract: There is growing recognition of melanized fungi as uncommon but important causes of infection among solid organ transplant recipients. Chromoblastomycosis and phaeohyphomycosis exist at opposing ends of the spectrum of disease caused by these fungi. We aim to systematically review the reports of chromoblastomycosis among transplant recipients to assess for trends in epidemiology and clinical outcomes. We identified 19 reported cases of histologically confirmed chromoblastomycosis among solid organ transplant recipients published between 1985 and 2018. Despite these patients’ impaired immunity, chromoblastomycosis remained localized to the skin and subcutaneous tissue in the majority of patients. Clinical outcomes were generally good with medical, surgical, or combined management. Although chromoblastomycosis has a low incidence in this population, it is important to consider as a cause of chronic, non-healing skin infections. Further research is needed to better elucidate the impact of transplantation on the natural course of this condition.

Dosing Antifungals in Obesity: a Literature Review

Abstract: To summarize the available evidence regarding antifungal dosing in obese adults as well as to provide meaningful guidance on the dosing of each antifungal agent in obese patients. The pharmacokinetic evidence regarding dosing antifungal agents in obesity is limited. Fluconazole’s volume of distribution (VD) is influenced by BMI. Therapeutic drug monitoring (TDM) studies provide some insights into dosing voriconazole in obesity, but not with posaconazole. Isavuconazole seems to be unaffected by weight. The available data for echinocandins suggests that increased doses are likely necessary in obese patients. TDM may be beneficial, particularly for azoles when available in a timely manner. Fluconazole and voriconazole dosing should be based on total body weight and adjusted body weight, respectively. Posaconazole may have reduced exposures in obese patients, but data on its new dosage forms is lacking. Isavuconazole appears unaffected by weight. Echinocandin doses likely need to be increased in obese patients, but the exact weight and dosages remain elusive.

Adult Tinea Capitis: a Clinical Entity in Increasing Frequency

Abstract: This review summarizes the fungal literature currently available for adult tinea capitis (ATC), as well as providing data for clinical practice. Available studies in ATC are scarce; however, they provide essential information for treating ATC. Treatment of TC is effective; however, it needs a minimum of 1 month to watch clinical efficacy. Systemic treatment is often needed to favor drug penetration to the deepest part of the hair follicle. The newest oral antifungal has higher efficacy rates than conventional therapy, as well as much shorter duration of treatment but at higher costs. We review the literature concerning ATC, including treatment schemes.

Pityriasis Versicolor in Children and Adolescents: an Update

Abstract: Pityriasis versicolor (PV) is a superficial mycosis that it can occur at any age, even in newborns. In this review, we will describe epidemiological data, mycological characteristics of yeast, pathogenesis and clinical characteristics of the disease, different diagnostic resources, and the current recommendations for treatment. The typical morphology and topography of PV allow us to make a quick diagnosis, but atypical presentations have been described. Diagnostic tools, such as dermoscopy, can also reveal patterns that allow the evaluation of characteristics of scales and pigment in lesions. The discovery of new species and new mechanisms of interaction with the host has broadened the panorama of aetiological possibilities. Although PV is a common disorder, extensive research is necessary to better understand the pathophysiology of the disease, immunological characteristics of the pathogen-host relationship and resources needed to precisely diagnose the disease, treat the disease, and avoid its chronic and recurrent course.

The use of whole genome and next-generation sequencing in the diagnosis of invasive fungal disease

Abstract: This review examines how next-generation nucleic acid sequencing (NGS) is being used in the diagnosis of invasive fungal disease (IFD) and how well its implementation compares to PCR-based diagnosis. The comparison allows for the assessment of the advantages and potential limitations of NGS in the diagnosis of IFD. NGS is established as a method for sequencing of microbial genomes. It is increasingly being tested as a direct diagnostic method from various sample types including samples such as plasma, formalin fixed and paraffin embedded specimens, and bronchoalveolar lavage. In these cases, the methodology was generally able to identify the causative agents of IFD. NGS-based methods will play an increasingly important role in diagnosis of IFD. The major limitation is currently cost, the need to standardise methods of nucleic acid isolation, and sequence analysis to enable broad uptake and application of the method.

Cryptococcal Pathogenicity and Morphogenesis

Abstract: The aim of this review is to give an overall idea of Cryptococcus biology paying special attention to its capacity to adapt through its morphogenetic program to the hostile host environment. This morphogenetic program consists of a significant increase in capsule size and the formation of Titan cells. Research on Titan cells had been hampered by the need of obtaining these cells from the lungs of infected mice. The production of Titan cells in vitro has supposed a major step in understanding the role of this morphotype in the virulence of Cryptococcus. In this regard, Cryptococcus has acquired the capacity of inducing a heterogeneous population during infection that allows it to evade the host immune system attack, proliferate, and disseminate to the CNS where it produces meningoencephalitis which is fatal if not treated properly.

Update on the Diagnosis of Candidemia and Invasive Candidiasis

Abstract: This review summarizes the fungal diagnostic tests and clinical prediction rules available for use in patients at risk for developing invasive candidiasis (IC). The advantages and limitations of each method is described based on available literature. Available studies show elevated sensitivity and specificity of novel diagnostic tests such as T2Candida and fungal sequencing. They still remain to be incorporated into routine clinical practice. The use B-D glucan, a major fungal wall component, is a sensitive tool to diagnose IC when consecutive positive results are found. Consecutively negative results allow discontinuation of empirical antifungal therapy, contributing to stewardship programs. T2Candida combines PCR and magnetic resonance to identify IC that is culture negative and monitor post-treatment candidemia clearance. Prediction rules using clinical risk factors for IC allows identification of patients likely to benefit from prophylaxis or early treatment.

Epidemiology of Emerging Fungal Infections in ICU

Abstract: Globally, a change has been noticed in the epidemiology of fungal infections in the intensive care units (ICUs). The current review provides an insight into the current epidemiology of emerging fungal infections with special reference to their prevalence, spectrum of pathogen, outbreaks, and emergence of antifungal resistance reported from different ICUs of the world. The ICUs across the world are witnessing multiple changes in the epidemiology of fungal infections including change in prevalence and spectrum of etiological agents, new susceptible risk groups, geographical variations, emergence of novel multi-drug resistant Candida auris, outbreak due to rare fungal species, emergence of antifungal resistance, etc. An understanding of the contemporary local epidemiology of fungal agents in ICU is essential for optimal patient management. Invasive candidiasis and invasive aspergillosis continue to haunt as major pathogens in the ICU, and several new risk factors associated with these infections have surfaced up. There is a contrasting picture for the species distribution of Candida among the different countries of the world. C. auris, the yeast behaving like bacteria, has emerged as a potential threat to ICUs across the five continents. Other mycelial agents like Mucorales, Paecilomyces spp., Fusarium spp., and Cladosporium spp., although encountered infrequently, continue to be reported as serious infections in ICU. The ICUs are also vulnerable sites for fungal infection outbreaks due to several fungi including rare ones like Cryptococcus spp., Pichia anomala, and Kodamaea ohmeri.

From Culture to Fungal Biomarkers: the Diagnostic Route of Fungal Infections in Children with Primary Immunodeficiencies

Abstract: To provide an overview of the diagnostic tests available to identify invasive fungal disease (IFD) in children with a primary immunodeficiency and to evaluate the relative strengths and weaknesses of those tests. Novel tools to aid the diagnosis of IFD, such as fungal PCRs and lateral flow devices (for Aspergillus spp.), are emerging. However, the paucity of high-quality, multicentre clinical trials evaluating the performance of these diagnostic tools, particularly in the paediatric cohort of interest, remains a challenge. Children with primary immunodeficiencies are seldom referenced in existing studies. It is difficult to provide recommendations for the majority of fungal diagnostic tests, with the exception of histopathology, microscopy, culture, and imaging modalities, due to their poorly studied and largely unvalidated nature. Moving forward, multicentre trials considering the role of these tools in the investigation of children with probable IFD and a primary immunodeficiency are strongly encouraged.

Update of Vulvovaginal Candidiasis in Pregnant and Non-pregnant Patients

Abstract: Candida albicans vulvovaginitis is one of the most frequent symptomatic infections in women and its incidence increases in reproductive age and pregnancy. Currently there are more specific and sensitive tests to identify Candida species that are resistant to antifungal agents, such as PCR and MALDI TOF MS, in order to improve prognosis. The genus Candida is part of the microbiota in humans; however, many species can become pathogenic. Vulvovaginitis caused by non-albicans Candida are becoming very important due to their high levels of antifungal resistance, which makes treatment difficult. Therefore, in addition to using phenotypic, biochemical tests, molecular analyses should be used to improve diagnosis and give appropriate treatment. Both in childhood and in reproductive age, women are exposed to several episodes of vulvovaginitis, mainly due to bacteria and fungi, due to various risk factors. Among the fungi, the most common agent is Candida albicans and within the non-albicans is Candida glabrata, but there are other species related to greater resistance and recurrence.

Epidemiology of Endemic Mycosis in Children

Abstract: This review is aimed to overview clinical and epidemiological aspects, as well as the diagnosis and management of four endemic mycosis in children. The studies available in the specialized literature concerning endemic mycosis in children are scarce and have great variation due to the characteristic heterogeneity of diseases. The clinical image of these diseases shows clear differences as well as their expression in immunocompromised patients. An understanding of the geographic range, typical manifestations, diagnostic methods, and treatment of the endemic mycoses is key in assessing patients presenting with atypical infections who may have traveled to endemic areas.

Onychomycosis in Patients Living with HIV/AIDS

Abstract: As both onychomycosis and HIV/AIDS are frequently encountered, we aimed to make a review of the existent information to this moment, including classification, evaluation and treatment. The new description of dermatophytes will surely originate changes in the classification and probably in the therapeutic approach. Also, we must be watchful for the modifications that may develop in this pathology with the newer antirretrovirals which are in constant evolution and could modify the patients’ response to dermatophytosis. At this moment, we know that onychomycosis is very common in patients living with HIV. Although they present similar clinical patterns and aetiological agents to the general population, we must focus in the many differences they present to further understand the physiopathology in the HIV setting. We are still searching for the ideal antimycotic and the full understanding of the pathogenesis of the infection in this particular group of patients.

AIDS-Related Mycoses in the Paediatric Population

Abstract: Fungal infections account for significant morbidity and mortality in HIV-infected children particularly in developing countries where there is lack of skilled personnel and infrastructure to make the appropriate diagnosis. This is further compounded by poor availability and accessibility of the antifungals needed to treat these infections. The purpose of this review is to highlight the paucity of data on AIDS-related mycoses in the paediatric age group and make appropriate recommendations to address challenges associated with mycoses in this population. These infections are categorised in two broad groups in this population: mucocutaneous, which commonly affects nutrition and adherence to therapy and invasive fungal infections which are life-threatening. A literature search revealed a total of 29 published literatures across all AIDS-related mycoses in the paediatric population. Research to determine the true burden of the problem and greater funding with implementation of a package of care that will result in substantial reductions in morbidity and mortality in relation to AIDS-related mycoses in children are needed. It is imperative that the programmatic optimal package of care for children with advanced HIV disease is designed and implemented.

Usefulness of Antifungal Reference In Vitro Susceptibility Tests as a Guide in Therapeutic Management

Abstract: This review provides information on the utility of reference antifungal susceptibility testing methods in the clinical setting. Clinical and Laboratory Standards Institute (CLSI)/European Committee for Antimicrobial Susceptibility Testing breakpoints (BPs) as predictors of therapy response (reported as either “cured” or “failure”) and epidemiological cutoff endpoints (ECVs/ECOFFS) of mutants (harboring specific resistance mechanisms) have been established. Although ECVs are available for other species and agents and for commercial methods, only reference triazole and echinocandin BPs have been established. Therefore, correlations of in vitro/in vivo results in this review were based on BPs or ECVs for Candida spp. and/or Aspergillus fumigatus. We also included CLSI ECVs for the Cryptococcus neoformans complex and tentative values for Candida auris. Overall, BPs/ECVs appear to be useful, but most available data are for correlations between BPs and minimal inhibitory concentrations (MICs) for susceptible isolates. Although ECVs can discriminate between MICs for WT (wild type) and mutants (non-WT), an MIC overlap could be present.