Search

Early, accurate diagnosis of invasive fungal disease (IFD) improves clinical outcomes. 1,3-beta-d-glucan (BDG) (Fungitell, Associates of Cape Cod, Inc., Falmouth, MA, USA) detection can improve IFD diagnosis but has been unavailable in Australia.To assess performance of serum BDG for IFD diagnosis in a high-risk Australian haematology population.We compared the diagnostic value of weekly screening of serum BDG with screening by Aspergillus polymerase chain reaction and Aspergillus galactomannan in 57 at-risk episodes for the diagnosis of IFD (proven, probable, possible IFD).IFD episodes were: proven (n = 4); probable (n = 4); possible (n = 18); and no IFD (n = 31). Using two consecutive BDG results of ≥80 pg/mL to call a result 'positive', the sensitivity, specificity, positive predictive value and negative predictive value was 37.5%, 64.5%, 23.1% and 80.7% respectively. For invasive aspergillosis, test performance increased to 50%, 90.3%, 57.1% and 87.5% respectively if any two of serum BDG/Aspergillus polymerase chain reaction/galactomannan yielded a 'positive' result. In proven/probable IFD, five of eight episodes returned a positive BDG result earlier (mean 6.6 days) than other diagnostic tests. False-negative BDG results occurred in three of eight episodes of proven/probable IFD, and false positive in 10 of 31 patients with no IFD. Erratic patterns of BDG values predicted false positive results (P = 0.03). Using serum BDG results, possible IFD were reassigned to either 'no' or 'probable' IFD in 44% cases. Empiric anti-fungal therapy use may have been optimised by BDG monitoring in 38.5% of courses.The BDG assay can add diagnostic speed and value but was hampered by low sensitivity and positive predictive value in Australian haematology patients.

Chaetomium sp. is a mold, member of the phylum Ascomycota. Clinical disease in humans is rare, particularly in children, for which only five cases have been reported. We report a 7-months-old female patient with a diagnosis of visceral heterotaxy syndrome who was admitted to a private center in Mexico. After two episodes of focal myoclonic seizure, a brain magnetic resonance imaging (MRI) revealed a right porencephalic cyst and a right frontal abscess with ventriculitis. Seventy-two hours after temporal abscesses drainage procedure, the culture showed a rapidly growing pale white fungal colony. Sequencing of internal transcribed spacer (ITS) and D1/D2 led to the identification of Chaetomium strumarium. Although Chaetomium sp. is a rare fungal infection in humans, clinicians should consider it as a plausible etiologic agent that can form brain abscess.

The opioid overdose epidemic is one of the leading causes of death in adults. Its devastating effects have included not only a burgeoning overdose crisis but also multiple converging infectious diseases epidemics. The use of both opioids and other substances through intravenous (IV) administration places individuals at increased risks of infectious diseases ranging from invasive bacterial and fungal infections to human immunodeficiency virus (HIV) and viral hepatitis. In 2012, there were 530,000 opioid use disorder (OUD)-related hospitalizations in the United States (US), with $700 million in costs associated with OUD-related infections. The scale of the crisis has continued to increase since that time, with hospitalizations for injection drug use-related infective endocarditis (IDU-IE) increasing by as much as 12-fold from 2010 to 2015. Deaths from IDU-IE alone are estimated to result in over 7,260,000 years of potential life lost over the next 10 years. There have been high-profile injection-related HIV outbreaks, and injection drug use (IDU) is now the most common risk factor for hepatitis C virus (HCV). As this epidemic continues to grow, clinicians in all aspects of medical care are increasingly confronted with infectious complications of IDU. This review will describe the pathogenesis, clinical syndromes, epidemiology, and models of treatment for common infectious complications among persons who inject drugs (PWIDs).

BACKGROUND Germline autosomal dominant and autosomal recessive mutations in PERP encoding p53 effector related to PMP-22 (PERP), a component of epidermal desmosomes, have been associated with a spectrum of keratodermas. Monoallelic nonsense mutations cause Olmsted syndrome with severe periorificial and palmoplantar keratoderma (PPK). Biallelic recessive frameshift and missense mutations are associated with milder forms of the disease, including generalized erythrokeratoderma and PPK. OBJECTIVES To add new insights into the genotype-phenotype correlations as a consequence of PERP mutations and to provide a comprehensive review of the literature. METHODS Among 26 previously unresolved families within a cohort of 180 extended Iranian families with syndromic or nonsyndromic ichthyosis, two families with shared clinical features were examined by whole-exome sequencing (WES) and genome-wide homozygosity mapping (HM). Mycological and dermatopathological studies were performed to further characterize their atypical phenotypic presentations. RESULTS In two unrelated multiplex consanguineous families affected by ichthyosis, two novel biallelic PERP variants, NM_022121.5, c.89T>C, p.Leu30Pro and c.466G>C, p.Gly156Arg, located inside of genomic homozygosity regions of the probands were detected. Interestingly, some patients had areas of scaly psoriasiform plaques on a background of generalized ichthyosis that appeared during active cutaneous fungal infections. Mycological examinations of these lesions revealed infections caused by Candida albicans, Epidermophyton floccosum, or Trichophyton rubrum. Histopathology of the psoriasiform lesions shared some features with psoriasis, which when combined with clinical presentation, led to incorrect diagnoses of guttate psoriasis or pustular psoriasis. CONCLUSIONS PERP variants in ichthyosis patients can confer susceptibility to recalcitrant cutaneous fungal infections. Additionally, patients with episodic psoriasiform dermatitis in the setting of keratoderma should be considered for PERP genotyping and cutaneous fungal examinations.

Fungi are recognized as key pathogens in immunocompromised patients. The invasive infection always remains a problem for clinicians due to high morbidity and mortality. The treatments of fungal infections are hampered by conventional drugs, which are associated with resistance. Drug resistance has become an important problem in a variety of infectious diseases. The rise in the incidence of fungal infections and drug resistance has intensified the need for alternative therapies that affect a new target. This new target must be a growth essential gene product like the stress pathway. It has been found that stress pathways can be a potential target in opportunistic fungal infection, which played an important role in the virulence of pathogens. It was helpful in protection from host defense, normal fungal growth, and antifungal drug resistance. The disruption of the pathway using alternative strategies (chemosensitization and photo-dynamics therapy) can be a novel approach in fighting fungal infections and for drug design.

Mucormycosis is becoming more common in patients infected with or recovering from COVID-19 under the current situation. However, there is a scarcity of research on a specific group of COVID-19 individuals who are predisposed to mucormycosis. As a result, a retrospective observational study was undertaken to assess the possible connection of mucormycosis with COVID-19. The goal was also to investigate the link between diabetes mellitus, mucormycosis and COVID-19. The occurrence and severity of the disease among the case records were assessed using signs and symptoms, investigations conducted during COVID-19, and serological test results. Patients were classified as previously known diabetics, recently diagnosed diabetics, or non-diabetics based on their history of pre-existing DM and HBA1c levels at the time of reporting for mucormycosis. The findings show that mild COVID-19-infected patients and non-diabetic patients have a high incidence of COVID-19-associated mucormycosis (CAM). As a result, all clinicians participating in the care of COVID-infected patients must be aware of the significant risk of secondary mucormycosis in the post-recovery phase, even in those with mild or moderate symptoms.

The current pandemic of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a global, unanticipated public health crisis. Another emerging challenge is the prevalence of "black fungus", or mucormycosis, among patients who recovered from COVID-19 infection. A retrospective study was conducted on 12 patients in a post-COVID recovery phase who developed mucormycosis. The study parameters evaluated lymphocyte count, CD4+ T cell status, and associated systemic co-morbidities for the patient, namely diabetes. The interventions during the treatment for COVID were also recorded to include administration of oxygen, ventilator assistance (invasive and non-invasive)/oxygen support, and steroid use. The possible relationship between low lymphocyte and CD4+ counts with diabetes and fungal growth was evaluated. It was observed that the majority of the patients who had a positive history for diabetes with low lymphocyte and CD4+ counts were more susceptible to opportunistic fungal infections. Most of the patients, but not all, had a history of receiving oxygen or assisted ventilation, as well as steroids, during the treatment for COVID infection. These interventions may be considered as accessory contributing factors for fungal infection. Post-exposure to SARS-CoV-2, therapies should be targeted at prevention of functional exhaustion of lymphocytes and maintaining optimal lymphocyte and subset counts in susceptible hosts for the prevention of opportunistic fungal infections. The relationship between functional exhaustion of the lymphocyte, diabetes, and COVID mandates further research.

Graphical abstract, Being considered minor vexations, fungal infections hinder the life of about 15% of the world population superficially, with rare threats to life in case of invasive sepsis. A significant rise in the intrusive mycoses due to machiavellian fungal species is observed over the years due to increased pathology and fatality in people battling life-threatening diseases. Individuals undergoing therapy with immune suppressive drugs plus recovering from viral infections have shown to develop fungal sepsis as secondary infections while recovering or after. Currently, the whole world is fighting against the fright of Coronavirus disease (COVID-19), and corticosteroids being the primitive therapeutic to combat the COVID-19 inflammation, leads to an immune-compromised state, thereby allowing the not so harmful fungi to violate the immune barrier and flourish in the host. A wide range of fungal co-infection is observed in the survivors and patients of COVID-19. Fungal species of Candida, Aspergillus and Mucorales, are burdening the lives of COVID-19 patients/survivors in the form of Yellow/Green, White and Black fungus. This is the first article of its kind to assemble note on fungal infections seen in the current human health scenario till date and provides a strong message to the clinicians, researchers and physicians around the world “non-pathological fungus should not be dismissed as contaminants, they can quell immunocompromised hosts”.

Background Over the years, the focus of infectious diseases in many African countries has been mainly on viral, bacterial and parasitic infections. Serious fungal infections (SFI) with comparable morbidity rate in these countries, remain neglected. Objectives To estimate the burden of SFI in Togo and to stimulate efforts for improved attention. Methods Literature was thoroughly searched for epidemiological data on SFI in Togo. Incidence and/or prevalence of SFI was estimated using socio-demographics, health system's information, risk-groups data and SFI rates obtained from national and international studies. Results About 5.29% of the 7,265,286 Togolese population is estimated to suffer from SFI annually. Among HIV patients, 1,342, 1,650 and 330 may develop cryptococcal meningitis, Pneumocystis pneumonia and disseminated histoplasmosis respectively per year. Oral and oesophageal candidiasis may annually affect 19,800 and 7,535 persons living with HIV respectively. Estimated incidence of invasive aspergillosis (IA) was 283 cases. Prevalence of chronic pulmonary aspergillosis (CPA) was estimated at 191 cases. The annual incidence of allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitization (SAFS) was respectively 4,577 and 6,042 cases. Tinea capitis and recurrent Candida vaginitis presumably affects 232,271 children and 108,979 women respectively. Candidaemia incidence is estimated at 5 cases per 100, 000 inhabitants and fungal keratitis may affect 981 persons annually. Conclusions Serious fungal infections in Togo are probably more significant than expected. These findings underscore the need to increase awareness among healthcare professionals, enhance diagnostic and therapeutic capacities and intensify epidemiological studies for effective management of fungal infections in Togo.

With the advent of coronavirus disease (COVID-19) pandemic, a wide range of life-threatening maxillofacial fungal coinfections have also been observed in patients. We conducted this systematic review to collate and evaluate the data to enable clinicians to understand the disease pattern and types of mycosis and provide meticulous management of these infections in COVID-19 patients. The review was carried out in accordance with Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. A systematic electronic literature search was conducted on major databases using keywords in combination with Boolean Operators. Manuscripts discussing cases of maxillofacial fungal infections in COVID-19 patients were included. A total of 11 studies were systematically reviewed to assess the fungal coinfections in COVID-19 patients. Twenty-one cases of mucormycosis, 58 of candidiasis, and 1 each of aspergillosis and mixed infection were observed in the region of head and neck. Significant increase in invasive fungal infection is evident in patients suffering from COVID-19 which could be due to immunosuppression and other pre-existing comorbidities. Early diagnosis and intervention like systemic antifungals or surgical debridement is mandatory to reduce morbidity and mortality.

Background In COVID-19 patients, information regarding superinfection, antimicrobial assessment, and the value of metagenomic sequencing (MS) could help develop antimicrobial stewardship. Method This retrospective study analyzed 323 laboratory-confirmed COVID-19 patients for co-infection rate and antimicrobial usage in the Shanghai Public Health Clinical Center (SPHCC) from January 23rd to March 14th 2020. The microbiota composition was also investigated in patients with critically severe COVID-19. Results The total population co-infection rate was 17/323 (5.3%) and 0/229 (0), 4/78 (5.1%), and 13/16 (81.3%) for the mild, severe, and critically severe subgroups, respectively. Proven fungal infection was significantly associated with a higher mortality rate (p = 0.029). In critically severe patients, the rate of antimicrobials and carbapenem usage were 16/16 (100%) and 13/16 (81.3%), respectively, in which the preemptive and empiric antimicrobial days accounted for 51.6% and 30.1%, respectively. Targeted therapy only accounted for 18.3%. MS was implemented to detect non-COVID-19 virus co-existence and the semi-quantitative surveillance of bacteremia, with clear clinical benefit seen in cases with MS-based precision antimicrobial management. Airway microbiome analysis suggested that the microbiota compositions in critically severe COVID-19 patients were likely due to intubation and mechanical ventilation. Conclusions In the SPHCC cohort, we observed a non-negligible rate of super-infection, especially for the critically ill COVID-19 patients. Fungal co-infection requires intensive attention due to the high risk of mortality, and the clinical benefit of MS in guiding antimicrobial management warrants further investigation.

There has been a growing appreciation of the importance of respiratory fungal diseases in recent years, with better understanding of their prevalence as well as their global distribution. In step with the greater awareness of these complex infections, we are currently poised to make major advances in the characterization and treatment of these fungal diseases, which in itself is largely a consequence of post-genomic technologies which have enabled rational drug development and a path towards personalized medicines. These advances are set against a backdrop of globalization and anthropogenic change, which have impacted the world-wide distribution of fungi and antifungal resistance, as well as our built environment. The current revolution in immunomodulatory therapies has led to a rapidly evolving population at-risk for respiratory fungal disease. Whilst challenges are considerable, perhaps the tools we now have to manage these infections are up to this challenge. There has been a welcome acceleration of the antifungal pipeline in recent years, with a number of new drug classes in clinical or pre-clinical development, as well as new focus on inhaled antifungal drug delivery. The “post-genomic” revolution has opened up metagenomic diagnostic approaches spanning host immunogenetics to the fungal mycobiome that have allowed better characterization of respiratory fungal disease endotypes. When these advances are considered together the key challenge is clear: to develop a personalized medicine framework to enable a rational therapeutic approach.

We report the first case of peritoneal dialysis (PD)-associated peritonitis due to Sporothrix schenckii, a thermally dimorphic black fungus transmitted from epiphytotic disease. The patient presented with PD-associated peritonitis and fungal colonisation inside the PD catheter’s lumen after an exposing ‘wet contamination’ event with a phytopathogen 11 days prior to the onset of infection. The human pathogen and phytopathogen were confirmed the same species by nucleotide sequences of the internal transcribed spacer and large subunit regions of the ribosomal RNA gene. A ‘wet contamination’ should be closely monitored for an extended period, and a broader spectrum of organisms might lead to peritonitis, particularly in centres with a high prevalence of fungal infection. PD patients and their caregivers should have periodic retraining of aseptic technique and personnel hygiene. We also recommend a long course of antifungal medication in eradicating peritoneal sporotrichosis to prevent unfavourable outcomes and relapsing peritonitis from this organism.

Objective. We sought to analyze the distribution and antibiotic sensitivity of pathogens in hospitalized patients and to provide a scientific reference for the rational application of antibiotics. Methods. From January 2014 to December 2018, urine cultures from patients in our hospital were collected and analyzed retrospectively for the presence, distribution, and drug sensitivity of pathogens. Results. A total of 42,854 midstream urine cultures were collected from which 11,891 (27.75%) pathogens were isolated, including 8101 (68.13%) strains of gram-negative bacteria, 2580 (21.69%) strains of gram-positive bacteria, and 1210 (10.18%) strains of fungi. Escherichia coli and Enterococci were the most common species of gram-negative and gram-positive bacteria, respectively. Drug sensitivity varied among different pathogens. Clear drug resistance was observed in bacteria, while fungus exhibited relatively lower resistance. Conclusion. Pathogens responsible for urinary tract infections in hospitalized patients are diversiform and display resistance to some antibiotics. Drug resistance monitoring should be enhanced to optimize antimicrobial therapy.

Respiratory infections caused by fungal pathogens present a growing global health concern and are a major cause of death in immunocompromised patients. Worryingly, coronavirus disease-19 (COVID-19) resulting in acute respiratory distress syndrome has been shown to predispose some patients to airborne fungal co-infections. These include secondary pulmonary aspergillosis and mucormycosis. Aspergillosis is most commonly caused by the fungal pathogen Aspergillus fumigatus and primarily treated using the triazole drug group, however in recent years, this fungus has been rapidly gaining resistance against these antifungals. This is of serious clinical concern as multi-azole resistant forms of aspergillosis have a higher risk of mortality when compared against azole-susceptible infections. With the increasing numbers of COVID-19 and other classes of immunocompromised patients, early diagnosis of fungal infections is critical to ensuring patient survival. However, time-limited diagnosis is difficult to achieve with current culture-based methods. Advances within fungal genomics have enabled molecular diagnostic methods to become a fast, reproducible, and cost-effective alternative for diagnosis of respiratory fungal pathogens and detection of antifungal resistance. Here, we describe what techniques are currently available within molecular diagnostics, how they work and when they have been used.

Purpose of review This review will comment on the current knowledge for the diagnosis of the main causes of COVID-19-associated invasive fungal disease (IFD); it will discuss the optimal strategies and limitations and wherever available, will describe international recommendations. Recent findings A range of secondary IFDs complicating COVID-19 infection have been described and while COVID-19-associated pulmonary aspergillosis was predicted, the presentation of significant numbers of COVID-19-associated candidosis and COVID-19-associated mucormycosis was somewhat unexpected. Given the range of IFDs and prolonged duration of risk, diagnostic strategies need to involve multiple tests for detecting and differentiating various causes of IFD. Although performance data for a range of tests to diagnose COVID-19-associated pulmonary aspergillosis is emerging, the performance of tests to diagnose other IFD is unknown or based on pre-COVID performance data. Summary Because of the vast numbers of COVID-19 infections, IFD in COVID-19 critical-care patients represents a significant burden of disease, even if incidences are less than 5%. Optimal diagnosis of COVID-19-associated IFD requires a strategic approach. The pandemic has highlighted the potential impact of IFD outside of the typical high-risk clinical cohorts, given the ever-increasing population at risk of IFD and enhanced surveillance of fungal infections is required.

Invasive fungal infection often complicates patients with severe viral infection, especially those admitted to critical care units. Severe SARS-CoV-2 infection has been no exception and a significant association with Aspergillus spp. has been documented, resulting in high patient mortality. In this summary we describe the clinical presentation, the underlying diseases most commonly linked with this association, radiological manifestations and therapeutic management of CAPA.

Background Pneumocystis jirovecii pneumonia (PCP)-related risk factors among patients with solid tumors are not completely defined. Thus, we aimed to characterize PCP cases with underlying solid tumors, to highlight the factors contributing to its development besides the prolonged use of moderate-to-high dose corticosteroids. Methods We retrospectively reviewed the medical records of patients with solid tumors diagnosed with PCP between 2006 and 2018 at a cancer center in Tokyo, Japan. Demographic and clinical data were collected, which included malignancy types, total lymphocyte count, coexisting pulmonary disease, chemotherapy, radiation therapy, corticosteroid use, and PCP-attributable mortality. Results Twenty cases of PCP with solid tumors were documented in 151,718 patients and 788,914 patient-years. Lung cancer (n = 6, 30%) was the most common underlying tumor, followed by breast cancer (n = 3, 15%). Only six (30%) patients were taking a dosage of ≥20 mg prednisone equivalents daily for ≥4 weeks from the onset of PCP. Among the remaining 14 patients, seven (50%) had coexisting pulmonary diseases, 10 (71%) had received chemotherapy within 90 days prior to PCP diagnosis, seven (50%) had undergone chest radiation therapy before PCP diagnosis, seven (50%) had received only intermittent corticosteroids, and one (7%) received no corticosteroids. Mortality attributable to PCP was 40%. Conclusions More than half of the patients were not taking a dosage of ≥20 mg prednisone equivalents daily for ≥4 weeks. Multiple other factors (e.g., lymphocytopenia, radiation to chest) may have potentially contributed to PCP in patients with solid tumors in a composite manner. We need to establish a method for estimating the likelihood of PCP taking multiple factors into account in this patient population.

The recovery of other pathogens in patients with SARS-CoV-2 infection has been reported, either at the time of a SARS-CoV-2 infection diagnosis (co-infection) or subsequently (superinfection). However, data on the prevalence, microbiology, and outcomes of co-infection and superinfection are limited. The purpose of this study was to examine the occurrence of co-infections and superinfections and their outcomes among patients with SARS-CoV-2 infection.We searched literature databases for studies published from October 1, 2019, through February 8, 2021. We included studies that reported clinical features and outcomes of co-infection or superinfection of SARS-CoV-2 and other pathogens in hospitalized and non-hospitalized patients. We followed PRISMA guidelines, and we registered the protocol with PROSPERO as: CRD42020189763.Of 6639 articles screened, 118 were included in the random effects meta-analysis. The pooled prevalence of co-infection was 19% (95% confidence interval [CI]: 14%-25%, I2 = 98%) and that of superinfection was 24% (95% CI: 19%-30%). Pooled prevalence of pathogen type stratified by co- or superinfection were: viral co-infections, 10% (95% CI: 6%-14%); viral superinfections, 4% (95% CI: 0%-10%); bacterial co-infections, 8% (95% CI: 5%-11%); bacterial superinfections, 20% (95% CI: 13%-28%); fungal co-infections, 4% (95% CI: 2%-7%); and fungal superinfections, 8% (95% CI: 4%-13%). Patients with a co-infection or superinfection had higher odds of dying than those who only had SARS-CoV-2 infection (odds ratio = 3.31, 95% CI: 1.82-5.99). Compared to those with co-infections, patients with superinfections had a higher prevalence of mechanical ventilation (45% [95% CI: 33%-58%] vs. 10% [95% CI: 5%-16%]), but patients with co-infections had a greater average length of hospital stay than those with superinfections (mean = 29.0 days, standard deviation [SD] = 6.7 vs. mean = 16 days, SD = 6.2, respectively).Our study showed that as many as 19% of patients with COVID-19 have co-infections and 24% have superinfections. The presence of either co-infection or superinfection was associated with poor outcomes, including increased mortality. Our findings support the need for diagnostic testing to identify and treat co-occurring respiratory infections among patients with SARS-CoV-2 infection.

Aim Bacterial and fungal infections are serious, life-threatening conditions after kidney transplantation. The development of oral/oesophageal candidiasis after kidney transplantation is not a reported risk factor for subsequent severe infection. This study was performed to investigate the relationship between oral/oesophageal candidiasis after kidney transplantation and the development of subsequent infection requiring hospitalization. Methods This retrospective study included 522 consecutive patients who underwent kidney transplantation at Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital from 1 January 2010 to 1 February 2019. Ninety-five percentage of patients were living donor transplant recipients. Visual examination was performed to detect oral candidiasis, beginning immediately after kidney transplantation; upper gastrointestinal endoscopy was performed 8-10 months after kidney transplantation. Twenty-five patients developed candidiasis (Candida-onset group) and 497 did not (non-Candida-onset group). The follow-up periods were 67 (37-86) months in the Candida-onset group and 55 (34-89) months in the non-Candida-onset group. Severe infection was defined as bacterial or fungal infection requiring hospitalization; viral infections were excluded. Results Severe infection developed in 9/25 (36%) patients in the Candida-onset group and in 77/497 (15%) patients in the non-Candida-onset group (p = .006). Binomial logistic analysis revealed that Candida infection (odds ratio [OR] 2.53, 95% confidence interval [CI] 1.06-6.06; p = .037) and use of rituximab (OR 1.81, 95% CI 1.12-2.93; p = .016) were significant predictors of subsequent severe infection. Conclusion Oral/oesophageal candidiasis is a risk factor for severe infection after kidney transplantation and suggests an over-immunosuppressive state, which should prompt evaluation of immunosuppression.

Fungal respiratory tract colonisation is a common finding in patients with hematologic neoplasms due to immunosuppression inherent in the diseases and exacerbated by therapy. This greatly increases the risk of fungal infections of the lungs, which is associated with significant mortality. Therefore, reliable diagnostic methods with rapidly available results are needed to administer adequate antifungal therapy.We have established an improved method for fungal DNA extraction and amplification that allows simultaneous detection of fungal families based on a set of multiplexed real time PCR reactions (fuPCR). We analysed respiratory rinses and blood of 94 patients with haematological systemic diseases by fuPCR and compared it with the results of culture and serological diagnostic methods. 40 healthy subjects served as controls.Regarding Candida species, the highest prevalence resulted from microbiological culture of respiratory rinses and from detection of antibodies in blood serum in patients (61% and 47%, respectively) and in the control group (29% and 51%, respectively). Detection of other pathogenic yeasts, such as Cryptococcus and Trichosporon, and moulds, such as Fusarium, was only possible in patients by fuPCR from both respiratory rinses and whole blood and serum. These fungal species were found statistically significantly more frequent in respiratory rinses collected from patients after myeloablative therapy for stem cell transplantation compared to samples collected before treatment (p ).The results show that fuPCR is a valuable complement to culturing and its inclusion in routine mycological diagnostics might be helpful for early detection of pathophysiologically relevant respiratory colonisation for patients with hematologic neoplasms. Lay abstract We validated a set of PCR reactions (fuPCR) for use in routine diagnostic. In contrast to culture and serological methods, only by fuPCR pathogenic yeasts (Cryptococcus and Trichosporon) and moulds (Aspergillus and Fusarium) were detected in respiratory rinses and blood of haematological patients.

Purpose Central nervous system (CNS) bacterial and fungal infections can cause secondary vasculitis which worsens the prognosis due to development of complications like infarctions or hemorrhages. In this prospective study, we aim to study intracranial vessel wall imaging findings in bacterial and fungal infections. Methods We included 12 cases of nontubercular bacterial and fungal CNS infections each, in whom definitive microbiological diagnosis could be made. High-resolution vessel wall imaging (VWI) and time of flight MR angiography (TOF MRA) were incorporated in the routine imaging protocol. All cases were evaluated for the presence of vascular enhancement, pattern of enhancement, and stenosis on VWI. Statistical analysis was done to evaluate association between findings of vessel wall imaging and infarctions. Results We found infarctions in 5 out of 12 cases (41.7%) of the bacterial group and 7 out of 12 cases (58.3%) of the fungal group. Vessel wall enhancement was seen in 5 cases (41.7%) of the bacterial group and 9 cases (75%) of the fungal group. There was a significant association between infarctions and vessel wall enhancement in the fungal group. However, pattern of enhancement or stenosis on VWI was not significantly associated with presence of infarction. VWI detected more cases of vascular involvement than TOF MRA. Conclusion Secondary infectious vasculitis in bacterial and fungal infections can be detected by VWI, which can play an important role in better patient management as detection of vascular involvement can prompt early treatment to prevent complications like infarctions or hemorrhages.

Chodun Wiktoria, Ruszel Kinga, Dubel Robert, Nieradko-Iwanicka Barbara. Selected skin diseases of the feet. Journal of Education, Health and Sport. 2021;11(8):422-426. eISSN 2391-8306. DOI http://dx.doi.org/10.12775/JEHS.2021.11.08.047 https://apcz.umk.pl/czasopisma/index.php/JEHS/article/view/JEHS.2021.11.08.047 https://zenodo.org/record/5379138 The journal has had 5 points in Ministry of Science and Higher Education parametric evaluation. § 8. 2) and § 12. 1. 2) 22.02.2019. © The Authors 2021; This article is published with open access at Licensee Open Journal Systems of Nicolaus Copernicus University in Torun, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author (s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non commercial license Share alike. (http://creativecommons.org/licenses/by-nc-sa/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. The authors declare that there is no conflict of interests regarding the publication of this paper. Received: 15.08.2021. Revised: 15.08.2021. Accepted: 28.08.2021. Selected skin diseases of the feet Wiktoria Chodun1, Kinga Ruszel1, Robert Dubel1, Barbara Nieradko-Iwanicka2 1Students Scientific Association at the Chair and Department of Hygiene Medical University of Lublin 2Chair and Department of Hygiene, Medical University of Lublin Radziwiłowska 11 Street, 20-080 Lublin Correspondence: Wiktoria Chodun e-mail wiktoria.chodun19@wp.pl Abstract Foot skin diseases are common problems encountered by dermatologists. They involve the skin and nails. In addition to the health aspect, there is also an aesthetic aspect, especially troublesome in the summer. It is recommended to visit a dermatologist with any disturbing skin lesion. The article presents an overview of the most common diseases in dermatology and podiatry offices. Key words: athlete's foot, calluses, warts, mycoses

s Background Pneumocystis pneumonia (PCP) is a common opportunistic infection with high mortality in individuals with decreased immunity. Pulmonary coinfections with PCP are associated with poor prognosis. The study aims to identify radiological predictors for pulmonary coinfections in patients with PCP and risk factors for mortality. Methods This is a retrospective, five-year study was conducted in a medical center, enrolling patients diagnosed with PCP, who received a chest computed tomography (CT) scan. The radiological findings and medical records of all participants were reviewed carefully by 2 independent doctors. Univariable and multivariable analysis was performed to identify radiological predictors for pulmonary coinfection and clinical risk factors for poor prognosis. Results A total of 101 participants were included, of which 39 were HIV-infected and 62 were non-HIV-infected. In multivariable analysis, radiologic predictors on chest CT for coinfection with bacteria pneumonia included lack of ground glass opacity (adjusted odds ratio [aOR], 6.33; 95% confidence interval [CI], 2.03-19.77; p = 0.001) and presence of pleural effusion (aOR, 3.74; 95% CI, 1.27-10.99; p = 0.017). Predictors for fungal pneumonia included diffuse consolidation (adjusted OR, 6.27; 95% CI, 1.72-22.86; p = 0.005) and presence of pleural effusion (adjusted OR, 5.26; 95% CI, 1.44-19.17; p = 0.012). A significantly higher in-hospital mortality was associated with older age, recent corticosteroid exposure, cytomegalovirus coinfection, and acute respiratory failure. Conclusion Early identification of pulmonary coinfections in PCP using radiological features on the CT scans, will enable appropriate treatment which is crucial to improve the prognosis.

Background In recent years, talaromycosis is reportedly on the rise in human immunodeficiency virus (HIV)-uninfected patients. However, the misdiagnosis and mistreatment of talaromycosis is more likely in HIV-uninfected patients than in HIV-infected patients because talaromycosis can be easily mistaken for tuberculosis or any other opportunistic infection. Therefore, we used metagenomic next-generation sequencing (mNGS), a novel gene detection method, for the diagnosis of talaromycosis in HIV-uninfected patients. Case presentation We report five cases diagnosed as talaromycosis by mNGS in HIV-uninfected patients, which were further confirmed by tissue culture. There were 3 male and 2 female patients. Two patients had a history of rat contact. The misdiagnosis duration ranged from 88 to 245 days. While the results of tissue culture changed from repeated negative to positive, the mNGS result for Talaromyces marneffei was positive earlier in 4 patients. The reads of Talaromyces marneffei in mNGS ranged from 5 to 414. After antifungal therapy, one of the outcomes was death due to the longest duration of misdiagnosis, and the other outcomes were clinical improvement. Conclusions mNGS is perhaps a rapid and effective diagnosis approach for the early confirmation of talaromycosis. Antifungal therapy is recommended once Talaromyces marneffei was revealed by mNGS. mNGS might reduce misdiagnosis duration and improve prognosis. Through these findings, we hope to provide some reference for talaromycosis in HIV-uninfected patients diagnosed early with the help of mNGS.

Oral cavity is habitat for plethora of micro-organism causing various diseases. The most common includes dental caries, periodontal diseases, etc. Dental practice may rarely encounter unusual and subtle symptoms with nonpathognomonic clinical signs of several fatal diseases which may pretend like a common oral disease. Hence, the knowledge and clinical acumen of diagnostician are necessary for the early diagnosis of such fatal infections to prevent untoward consequences. Mucormycosis is an angioinvasive necrotic fungal infection with a high morbidity and mortality rate. It commonly occurs in patients with debilitating diseases and immunocompromised individuals. Clinically, it manifests as rhino-orbito-cerebral, pulmonary, cutaneous, gastrointestinal, renal, and disseminated form. Disease affecting the facial region is a challenge as it often disseminates with orbital and cranial involvement at the time of diagnosis. This article presents a case of mucormycosis which mimicked as severe periodontitis in a patient leading to delay in the diagnosis and challenges during the treatment.

Background Talaromyces marneffei (T. marneffei) is a thermally dimorphic fungus causing systemic mycosis. Due to the atypical symptoms and diverse imaging findings, T. marneffei-infected patients may be misdiagnosed thus preventing timely antifungal therapy. Moreover, HIV-negative patients with T. marneffei infection may be congenitally immunocompromised because of the mutation of immune-related genes. Case presentation We describe a case of an HIV-negative child who developed disseminated T. marneffei infection in a nonendemic area. Chest CT showed similar imaging changes of miliary pulmonary tuberculosis, while there was no other evidence of tuberculosis infection, and empirical antituberculosis treatment was not effective. Lymphocyte subset analysis showed reduced natural killer cells, and the immunoglobulin profile showed low levels of IgM, C3 and C4. A bone marrow smear revealed T. marneffei infection, and ascites culture also proved T. marneffei infection. Despite antifungal treatment, the child died of multiple organ failure. Two gene mutations in caspase recruitment domain-containing protein 9 (CARD9) were detected, which had not been reported previously in T. marneffei-infected patients. Conclusions HIV-negative patients with CARD9 mutations may be potential hosts of T. marneffei. Abnormalities in the immunoglobin profile and lymphocyte subset may provide clues for immunocompromised patients, and further genetic testing is advised to identify gene mutations in HIV-negative patients with T. marneffei infection.

Background Pulmonary mycoses resemble clinically and radiologically chronic pulmonary tuberculosis. Studies describing the prevalence, etiology and clinical features of pulmonary mycosis are of crucial importance in the Brazilian Amazon. Aims To estimate the frequency of pulmonary mycoses in smear-negative tuberculosis patients; to describe their demographic, epidemiological, and clinical characteristics; and to evaluate diagnostic methods. Methods A cross-sectional study was conducted at two tuberculosis reference institutions in Amazonas, Brazil. We included 213 patients and collected clinical data, blood and induced sputum to perform serological, direct microscopy, microbiologic culture and PCR-based assays to identify infections caused by Aspergillus fumigatus, Paracoccidioides brasiliensis, Histoplasma capsulatum, Cryptococcus, and HIV. Chest computed tomography was also performed. Results Pulmonary mycoses were diagnosed in 7% (15/213) of the cases, comprising ten aspergillosis cases, three cases of paracoccidioidomycosis and one case each of histoplasmosis and cryptococcosis. Among the patients with pulmonary mycoses, 86.7% were former tuberculosis patients. The most significant clinical characteristics associated with pulmonary mycoses were cavity-shaped lung injuries, prolonged chronic cough and hemoptysis. Conclusions Our study confirmed the high prevalence of pulmonary mycoses in smear-negative tuberculosis patients in the Brazilian Amazon.

Summary Background SARS-CoV-2 predisposes patients to secondary infections; however, a better understanding of the impact of coinfections on the outcome of hospitalized COVID-19 patients is still necessary. Aim To analyse death risk due to coinfections in COVID-19 patients. Methods The odds of death of 212 severely ill COVID-19 patients were evaluated, with detailed focus on the risks for each pathogen, site of infection, comorbidities and length of hospitalization. Findings The mortality rate was 50.47%. Fungal and/or bacterial isolation occurred in 89 patients, of whom 83.14% died. Coinfected patients stayed hospitalized longer and had an increased odds of dying (odds ratio (OR): 13.45; R2 = 0.31). The risk of death was increased by bacterial (OR: 11.28) and fungal (OR: 5.97) coinfections, with increased levels of creatinine, leucocytes, urea and C-reactive protein. Coinfections increased the risk of death if patients suffered from cardiovascular disease (OR: 11.53), diabetes (OR: 6.00) or obesity (OR: 5.60) in comparison with patients with these comorbidities but without pathogen isolation. The increased risk of death was detected for coagulase-negative Staphylococcus (OR: 25.39), Candida non-albicans (OR: 11.12), S. aureus (OR: 10.72), Acinetobacter spp. (OR: 6.88), Pseudomonas spp. (OR: 4.77), and C. albicans (OR: 3.97). The high-risk sites of infection were blood, tracheal aspirate, and urine. Patients with coinfection undergoing invasive mechanical ventilation were 3.8 times more likely to die than those without positive cultures. Conclusion Severe COVID-19 patients with secondary coinfections required longer hospitalization and had higher risk of death. The early diagnosis of coinfections is essential to identify high-risk patients and to determine the right interventions to reduce mortality.

Background and objective With the widespread use of antifungals to treat superficial mycoses, reports of antifungal resistance are increasing. Antifungal resistance is becoming a public health challenge and needs to be addressed in parallel with antibacterial and antiviral resistance. Methods We review the growing resistance of fungal pathogens such as Trichophyton species and the emergence of novel pathogens, including multidrug-resistant strains in superficial mycoses. We also discuss the importance of laboratory diagnosis and antifungal susceptibility testing (AFST) in the management of recalcitrant infections. Results and conclusion Antifungal resistance can occur naturally or develop over time when fungi are exposed to antifungals. The frequency of terbinafine-resistant Trichophyton isolates is increasing. Opportunistic pathogens such as Aspergillus and Candida species have developed resistance to classic azoles such as itraconazole and fluconazole, and the newer azoles such as posaconazole and voriconazole. Although uncommon, topical antifungals such as efinaconazole and tavaborole have shown to induce resistance in Trichophyton rubrum. The emergence of multidrug-resistant Trichophyton mentagrophytes/interdigitale, Candida auris, and Aspergillus species causing severe infections is highly concerning. Routine AFST should be considered to determine the most effective treatment, especially if there is failure to therapy. Combination treatment of oral and topical antifungals may be a consideration for managing recalcitrant infections.

Background Indonesia is a tropical country, warm and humid, with numerous environmental fungi. Data on fungal disease burden helps policy makers and clinicians. Objectives We have estimated the incidence and prevalence of serious fungal diseases. Methods We found all published and unpublished data and estimated the incidence and prevalence of fungal diseases based on populations at risk. HIV data were derived from UNAIDS (2017), pulmonary tuberculosis (PTB) data from 2013-2019, data on chronic pulmonary aspergillosis (CPA) was used to estimate CPA prevalence and likely deaths, COPD data from Hammond (2020), lung cancer incidence was from Globocan 2018, and fungal rhinosinusitis was estimated using community data from India. Results Overall ~7.7 million Indonesians (2.89%) have a serious fungal infection each year. The annual incidence of cryptococcosis in AIDS was 7,540. Pneumocystis pneumonia incidence was estimated at 15,400 in HIV and an equal number in non-HIV patients. An estimated 1% and 0.2% of new AIDS patients have disseminated histoplasmosis or Talaromyces marneffei infection. The incidence of candidemia is 26,710. The annual incidence of invasive aspergillosis was estimated at 49,500 and the prevalence of CPA is at 378,700 cases. Allergic bronchopulmonary aspergillosis prevalence in adults is estimated at 336,200, severe asthma with fungal sensitization at 443,800, and fungal rhino sinusitis at 294,000. Recurrent vulvovaginal candidiasis is estimated at 5 million/ year (15 - 50 years old). The incidence of fungal keratitis around 40,050. Tinea capitis prevalence in schoolchildren about 729,000. Conclusions Indonesia has a high burden of fungal infections.

Purpose: This literature review summarizes the main immunological characteristics of type III interferons (IFN) and highlights the clinically relevant aspects and future therapeutic perspectives for these inflammatory molecules. Source: Relevant articles in PubMed MEDLINE from the first publication (2003) until 2020. N=101 articles were included in this review. Principal findings: Type III IFNs represent a relatively newly described inflammatory cytokine family. Although they induce substantially similar signalling to the well-known type I IFNs, significant functional differences make these molecules remarkable. Type III IFNs have extensive biological effects, contributing to the pathogenesis of several diseases and also offering new diagnostic and therapeutic approaches: 1) their potent anti-viral properties make them promising therapeutics against viral hepatitis and even against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is causing the current coronavirus disease 2019 (COVID-19) pandemic; 2) imbalances in the IFN-λs contribute to several forms of chronic inflammation (e.g., systemic and organ-specific autoimmune diseases) and potentially predict disease progression and therapeutic response to biologic therapies; and 3) the antitumor properties of the type III IFNs open up new therapeutic perspectives against malignant diseases. Conclusion: Over the last 18 years, researchers have gathered extensive information about the presence and role of these versatile inflammatory cytokines in human diseases, but further research is needed to clarify the mechanistic background of those observations. Better understanding of their biological activities will permit us to use type III IFNs more efficiently in new diagnostic approaches and individualized therapies, consequently improving patient care.

Osteomyelitis of the phalanx caused by Candida species are rare. A 49-year-old female patient was admitted to an external center with a splinter injury of the third phalanx of the middle finger of her left hand about 45 days ago. She was referred to our clinic with persistent pain and discharge, despite four-week antibiotherapy. Debridement and curettage were performed and partial excision of the distal phalanx at an appropriate level was done. Her complaints gradually resolved postoperatively with prescribed antibiotics for the pathogen identified as Candida lusitaniae based on the intraoperative cultures. At her three-month follow-up visit, treatment yielded near-excellent results. To the best of our knowledge, this is the first case of osteomyelitis of the distal phalanx caused by Candida lusitaniae in the literature, highlighting the importance of definitive diagnosis and pathogen-specific treatment, rather than empirical treatment, to achieve favorable results with cure.

The endemic mycoses are a diverse group of environmental fungi that share several characteristics. Pitfalls in the recognition and management of endemic fungal infections are common. A general understanding of common presenting manifestations and their lingering effects is of paramount importance to the treating physician. We review the unmet needs of recently published guidelines and outline future areas of research.

Quinoline derivatives are considered broad-spectrum pharmacological compounds that exhibit a wide range of biological activities. Integration of quinoline moiety can improve its physical and chemical properties and also pharmacological behavior. Due to its wide range of pharmaceutical applications, it is a very popular compound to design new drugs for the treatment of multiple diseases like cancer, dengue fever, malaria, tuberculosis, fungal infections, AIDS, Alzheimer’s disease and diabetes. In this review, our major focus is to pay attention to the biological activities of quinoline compounds in the treatment of these diseases such as anti-viral, anti-cancer, anti-malarial, antibacterial, anti-fungal, anti-tubercular and anti-diabetic.

Objectives The aims of this study were to review recent fungal infection case reports published, evaluate the treatment regimens and clinical outcomes, and provide recommendations for future management. Methods A review of case reports published over the last decade was conducted. PubMed was searched to collect the relevant citations using a combination of the key words ("burn," "burned," "burns," "fungal," "fungi," and "fungus") in title or abstract. Case series, reviews, guidelines, and experimental and non-English studies were excluded. Statistical analyses were performed using Microsoft Excel 2019. Results A total of 36 case reports encompassing a total of 44 burn patients with fungal infection were included in the final analysis. Ablative surgeries, including surgical excision, debridement, skin graft, vitrectomy, teeth extraction, valve replacement, or amputation, were performed in 38 cases after the suspicion or identification of fungal infection. Twenty-nine of them were eventually discharged, yielding a survival rate of 76.3%. In the remaining 6 cases, ablative surgery was not mentioned and 3 of them eventually died, yielding a survival rate of 50%. The total mortality was 27.27%. Among the 12 death cases, 1 was infected with Candida albicans, 1 with non-albicans Candida, 2 with Aspergillus spp, 2 with Fusarium spp, 4 with Zygomycetes, and 2 with other fungal species. Conclusions The overall mortality of fungal wound infection is still high in burn patients around the world, especially those infected with non-Candida species. Early diagnosis of fungal infection, early initiation of appropriate antifungal therapy, and effective surgical intervention are key measures to improve the treatment effect and reduce the mortality of fungal infection in burn patients.

The thinking about fungi has evolved from unusual agents considered contaminants and colonizers to actual pathogens. Fungi are ubiquitous in nature and are found throughout in association with food, soil, mammals, and insects. Fungi have become important pathogens in animals and humans causing infections extending from superficial disease to disseminated infection. Because the gastrointestinal tract is continually exposed to fungi, it is frequently colonized and infected by numerous yeast and other fungi. It is also the origin of many disseminated fungal infections. The increased incidence of fungal infections has led to the approval and use of novel antifungals.

Various uncommon fungal pathogens have been increasingly identified as causes of disseminated and invasive fungal disease (IFD) worldwide. Growing recognition and clinical knowledge of these emerging fungal pathogens has occurred through improved molecular diagnostics, nucleic sequence databases, and taxonomic reclassification of medically significant fungi. However, emerging fungal diseases carry significant morbidity and mortality and, due to a paucity of published literature, the collective clinical experience with these fungi is often limited. In this review, we focus on unusual emerging fungal pathogens not extensively covered elsewhere in this issue of Infectious Diseases Clinics of North America.

Many studies have shown successful performance of MALDI-TOF MS for rapid yeast and mold identification, yet very few laboratories have chosen to apply this technology into their routine clinical mycology workflow. Some of this hesitation may be attributable to the lack of standardization regarding culture methods, extraction methods, databases, and acquisition methods. This review will provide an overview of the current status of MALDI-TOF MS for fungal identification, including key findings in the literature, processing and database considerations, updates in technology, and exciting future prospects. Significant advances towards standardization have taken place over recent years; thus, accurate species level identification of yeasts and molds, particularly within species complexes and cryptic organisms, should be highly attainable, achievable, and practical in most clinical laboratories.

Over the past 15 years, there has been an increase in the development and utilization of newer antifungal agents. The ideal antifungal, however, in regard to spectrum of activity, pharmacokinetic/pharmacodynamic properties, development of resistance, safety, and drug interaction profile remains elusive. This article reviews pharmacologic aspects of Food and Drug Administration-approved polyenes, flucytosine, azoles, and echinocandins as well as promising pipeline antifungal agents. Unique properties of these newer agents are highlighted. The clinical role of established and investigational antifungal agents as treatment and/or prevention of invasive fungal infections is discussed.

Paediatric patients with cancer and those undergoing haematopoietic cell transplantation are at high risk of bacterial infections. The 8th European Conference on Infections in Leukaemia (ECIL-8) convened a Paediatric Group to review the literature and to formulate recommendations for the use of antibiotics according to the European Society of Clinical Microbiology and Infectious Diseases grading system. The evaluation of antibacterial prophylaxis included mortality, bloodstream infection, febrile neutropenia, emergence of resistance, and adverse effects as endpoints. Initial antibacterial therapy and antibiotic de-escalation or discontinuation focused on patients with a clinically stable condition and without previous infection or colonisation by resistant bacteria, and on patients with a clinically unstable condition or with previous infection or colonisation by resistant bacteria. The final considerations and recommendations of the ECIL-8 Paediatric Group on antibacterial prophylaxis, initial therapy, and de-escalation strategies are summarised in this Policy Review.

Invasive candidiasis (IC) is a collective term that refers to a group of infectious syndromes caused by a variety of species of Candida, 6 of which cause most cases globally. Candidemia is probably the most commonly recognized syndrome associated with IC; however, Candida can cause invasive infection of any organ, especially visceral organs, vasculature, bones and joints, the eyes and central nervous system. Targeted prevention and empirical therapy are important interventions for patients at high risk for IC, and the current approach should be based on a combination of clinical risk factors and non-culture-based diagnostics, when available.

Objective To assess the association between commonly obtained endoscopic and serologic data and bronchoalveolar lavage pepsin assay (BAL) results in children with chronic cough. Study design We performed a retrospective chart review of seventy-two children with a BAL pepsin obtained through our Aerodigestive Center over an 18-month period. BAL outcomes include evidence of viral, bacterial, or fungal infection, presence of lipid laden macrophages, and cytology (eosinophils, neutrophils, and lymphocytes). Gastrointestinal outcomes include esophagogastroduodenoscopy (EGD) and pH impedance probe findings. Other characteristics include serum eosinophil, neutrophils, and lymphocytes; spirometry; FeNO; and IgE. Results Seventy-two patients underwent BAL pepsin testing. Median age was 4.9 years, 30.6% had severe persistent asthma, and 59.2% were on reflux medication. There was an association between positive BAL pepsin assay and positive viral panel (p=0.002) or fungal culture (p=0.027). No significant association found between positive BAL bacterial culture; BAL cytology; presence of BAL lipid laden macrophages; IgE; spirometry; FeNO; CBC neutrophil, eosinophil, or lymphocytes; pH impedance testing parameters; or EGD pathology. Conclusions BAL pepsin is associated with a positive BAL viral PCR or fungal culture. Lack of correlation between pepsin-positivity and pH-impedance parameters or EGD pathology suggests microaspiration may be due to an acute event (such as a respiratory infection) rather than chronic GERD. This may be especially true in the presence of a positive viral panel or fungal culture when a BAL pepsin is obtained. This article is protected by copyright. All rights reserved.

Pneumonia is among the most common causes of death worldwide. The epidemiologic and clinical heterogeneity of pneumonia results in challenges in diagnosis and treatment. There is inconsistency in the definition of the group of microorganisms that cause "atypical pneumonia." Nevertheless, the use of this term in the medical and radiologic literature is common. Among the causes of communityacquired pneumonia, atypical bacteria are responsible for approximately 15% of cases. Zoonotic and nonzoonotic bacteria, as well as viruses, have been considered among the causes of atypical pneumonia in a patient who is immunocompetent and have been associated with major community outbreaks of respiratory infection, with relevant implications in public health policies. Considering the difficulty of isolating atypical microorganisms and the significant overlap in clinical manifestations, a targeted empirical therapy is not possible. Imaging plays an important role in the diagnosis and management of atypical pneumonia, as in many cases its findings may first suggest the possibility of an atypical infection. Clarifying and unifying the definition of atypical pneumonia among the medical community, including radiologists, are of extreme importance. The prompt diagnosis and prevention of community spread of some atypical microorganisms can have a relevant impact on local, regional, and global health policies. (C) RSNA, 2021

Fungal infections of the central nervous system (CNS) are rare. However, because of the increase in the number of immunocompromised individuals, they have been gaining prominence in the differential diagnosis of CNS infections. Imaging techniques are sensitive for detecting and localizing an abnormality, in many cases allowing the origin of a lesion to be categorized as infectious, inflammatory, neoplastic, or vascular. This essay illustrates the magnetic resonance imaging and computed tomography findings of the most common fungal infections of the CNS, based on the experience of the Radiology Department of the Hospital de Clínicas de Porto Alegre, in the city of Porto Alegre, RS, Brazil. Resumo As infecções fúngicas do sistema nervoso central (SNC) são raras, entretanto, com o aumento no número de indivíduos imunocomprometidos elas têm ganhado destaque no diagnóstico diferencial de infecções no SNC. As atuais técnicas de imagem são sensíveis para detectar uma anormalidade, localizá-la, e em muitos casos categorizar a lesão como de origem infecciosa e/ou inflamatória, neoplásica ou vascular. Este ensaio ilustra os achados de ressonância magnética e tomografia computadorizada mais comuns nas infecções fúngicas do SNC baseadas na experiência do Serviço de Radiologia do Hospital de Clínicas de Porto Alegre.

Background There is a paucity of studies describing the incidence and risk factors for late‐occurring (≥1 year) infectious complications in contemporary survivors of hematopoietic cell transplantation (HCT). Methods This was a retrospective cohort study of 641 1‐year survivors of HCT, transplanted between 2010 and 2013 as adults, and in remission from their primary disease. Standardized definitions were used to characterize viral, fungal, and bacterial infections. Cumulative incidence of infections was calculated, with relapse/progression considered as a competing risk event. Fine‐Gray subdistribution hazard ratio estimates and 95% confidence intervals (CI) were obtained, adjusted for relevant covariates. Results Median age at HCT was 55.2 years (range 18.1–78.1 years); 54.0% were survivors of allogeneic HCT. The 5‐year cumulative incidence of a late‐occurring infection for the entire cohort was 31.6%; the incidence of polymicrobial (≥2) infections was 10.1%. In survivors who developed at least one infection, the 5‐year incidence of a subsequent infection was 45.3%. Among allogeneic HCT survivors, patients with acute lymphoblastic (HR = 1.82 95% CI [1.12–2.96]) or myeloid (HR = 1.50 95% CI [1.02–2.20]) leukemia, and those with an elevated HCT‐Comorbidity index score (HR = 1.09 95% CI [1.01–1.17]) were more likely to develop late‐occurring infections; there was an incremental risk associated with severity of graft versus host disease (GVHD) at 1‐year post‐HCT (mild: HR = 2.17, 95% CI [1.09–4.33]; moderate/severe: HR = 3.78, 95% CI [1.90–7.53]; reference: no GVHD). Conclusions The burden of late‐occurring infections in HCT survivors is substantial, and there are important patient‐ and HCT‐related modifiers of risk over time. These findings may help guide personalized screening and prevention strategies to improve outcomes after HCT., Highlights the high burden of late‐occurring infections by GVHD status at 1 year post‐HCT—a time point that typically corresponds to survivors transitioning away from the specialized HCT center to the community setting.

Background Invasive fungal infections in the United States are chronically underdiagnosed and a lack of coordinated surveillance makes the true burden of disease difficult to determine. The purpose of this analysis was to capture mortality-associated burden of risk conditions and fungal infections. Methods We analyzed data from the National Vital Statistics System from 1999 through 2018 to estimate the mortality attributed to risk conditions and related fungal disease. Results The number of risk conditions associated with fungal disease is steadily rising in the United States, with 1 047 422 diagnoses at time of death in 2018. While fungal disease decreased substantially from 1999 to 2010, primarily due to the control of human immunodeficiency virus (HIV) infection, the number of deaths with fungal diagnosis has increased in the non-HIV cohort, with significant increases in patients with diabetes, cancer, immunosuppressive disorders, or sepsis. Conclusions The landscape of individuals at risk for serious fungal diseases is changing, with a continued decline in HIV-associated incidence but increased diagnoses in patients with cancer, sepsis, immunosuppressive disorders, and influenza. Additionally, there is an overall increase in the number of fungal infections in recent years, indicating a failure to control fungal disease mortality in these new immunocompromised cohorts. Improvement in the prevention and management of fungal diseases is needed to control morbidity and mortality in the rising number of immunocompromised and at-risk patients in the United States.

Ocular infection induced by bacteria and fungi is a major cause of visual impairment and blindness. Topical administration of antibiotics remains the first-line treatment, as effective eradication of pathogens is the core of the anti-infection strategy. Whereas, eye drops lack efficiency and have relatively low bioavailability. Intraocular injection may cause concurrent ocular damage and secondary infection. In addition, antibiotic-based management can be limited by the low sensitivity to multidrug-resistant bacteria. Nanomedicine is proposed as a prospective, effective, and noninvasive platform to mediate ocular delivery and combat pathogen or even resistant strains. Nanomedicine can not only carry antimicrobial agents to fight against pathogens but also directly active microbicidal capability, killing pathogens. More importantly, by modification, nanomedicine can achieve enhanced residence time and release time on the cornea, and easy penetration through corneal tissues into anterior and posterior segments of the eye, thus improving the therapeutic effect for ocular infection. In this review, several categories of antimicrobial nanomedicine are systematically discussed, where the efficiency and possibility of further embellishment and improvement to adapt to clinical use are also investigated. All in all, novel antimicrobial nanomedicine provides potent and prospective ways to manage severe and refractory ocular infections.