Population genomic analyses reveal high diversity, recombination and nosocomial transmission among Candida glabrata (Nakaseomyces glabrata) isolates causing invasive infections.

Candida glabrata is a commensal yeast of the gastrointestinal tract and skin of humans. However, it causes opportunistic infections in immunocompromised patients, and is the second most common Candida pathogen causing bloodstream infections. Although there are many studies on the epidemiology of C. glabrata infections, the fine- and large-scale geographical nature of C. glabrata remain incompletely understood. Here we investigated both the fine- and large-scale population structure of C. glabrata through genome sequencing of 80 clinical isolates obtained from six tertiary hospitals in Qatar and by comparing with global collections. Our fine-scale analyses revealed high genetic diversity within the Qatari population of C. glabrata and identified signatures of recombination, inbreeding and clonal expansion within and between hospitals, including evidence for nosocomial transmission among coronavirus disease 2019 (COVID-19) patients. In addition to signatures of recombination at the population level, both MATa and MATα alleles were detected in most hospitals, indicating the potential for sexual reproduction in clinical environments. Comparisons with global samples showed that the Qatari C. glabrata population was very similar to those from other parts of the world, consistent with the significant role of recent anthropogenic activities in shaping its population structure. Genome-wide association studies identified both known and novel genomic variants associated with reduced susceptibilities to fluconazole, 5-flucytosine and echinocandins. Together, our genomic analyses revealed the diversity, transmission patterns and antifungal drug resistance mechanisms of C. glabrata in Qatar as well as the relationships between Qatari isolates and those from other parts of the world.

The current state of laboratory mycology in Asia/Pacific: A survey from the European Confederation of Medical Mycology (ECMM) and International Society for Human and Animal Mycology (ISHAM).

INTRODUCTION: Invasive fungal infections (IFIs) in Asia/Pacific are a particular threat to patients with malignancies, uncontrolled diabetes mellitus or undiagnosed/untreated human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS). Adequate and early access to diagnostic tools and antifungals is essential for IFI clinical management and patient survival. METHODS: Details on institution profile, self-perception on IFI, and access to microscopy, culture, serology, antigen detection, molecular testing, and therapeutic drug monitoring for IFI were collected in a survey. RESULTS: As of June 2022, 235 centres from 40 countries/territories in Asia/Pacific answered the questionnaire. More than half the centres were from six countries: India (25%), China (17%), Thailand (5%), Indonesia, Iran, and Japan (4% each). Candida spp. (93%) and Aspergillus spp. (75%) were considered the most relevant pathogens. Most institutions had access to microscopy (98%) or culture-based approaches (97%). Furthermore, 79% of centres had access to antigen detection, 66% to molecular assays, and 63% to antibody tests. Access to antifungals varied between countries/territories. At least one triazole was available in 93% of the reporting sites (voriconazole [89%] was the most common mould-active azole), whereas 80% had at least one amphotericin B formulation, and 72% had at least one echinocandin. CONCLUSION: According to the replies provided, the resources available for IFI diagnosis and management vary among Asia/Pacific countries/territories. Economical or geographical factors may play a key role in the incidence and clinical handling of this disease burden. Regional cooperation may be a good strategy to overcome shortcomings.

Osteoarticular Mycoses.

Osteoarticular mycoses are chronic debilitating infections that require extended courses of antifungal therapy and may warrant expert surgical intervention. As there has been no comprehensive review of these diseases, the International Consortium for Osteoarticular Mycoses prepared a definitive treatise for this important class of infections. Among the etiologies of osteoarticular mycoses are Candida spp., Aspergillus spp., Mucorales, dematiaceous fungi, non-Aspergillus hyaline molds, and endemic mycoses, including those caused by Histoplasma capsulatum, Blastomyces dermatitidis, and Coccidioides species. This review analyzes the history, epidemiology, pathogenesis, clinical manifestations, diagnostic approaches, inflammatory biomarkers, diagnostic imaging modalities, treatments, and outcomes of osteomyelitis and septic arthritis caused by these organisms. Candida osteomyelitis and Candida arthritis are associated with greater events of hematogenous dissemination than those of most other osteoarticular mycoses. Traumatic inoculation is more commonly associated with osteoarticular mycoses caused by Aspergillus and non-Aspergillus molds. Synovial fluid cultures are highly sensitive in the detection of Candida and Aspergillus arthritis. Relapsed infection, particularly in Candida arthritis, may develop in relation to an inadequate duration of therapy. Overall mortality reflects survival from disseminated infection and underlying host factors.

A New Filter Based Cultivation Approach for Improving Aspergillus Identification using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS).

Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) is widely used in clinical laboratories for routine identification of bacteria and yeasts. However, methodological difficulties are still apparent when applied to filamentous fungi. The liquid cultivation method recommended by Bruker Daltonics GmbH for identification of filamentous fungi by MALDI-TOF MS is labour intensive and time-consuming. In this study, growth of Aspergillus species on different (porous) surfaces was investigated with the aim to develop a more reliable, quicker and less laborious identification method using MALDI-TOF MS. Mycelial growth without sporulation mimicking liquid cultivation and reliable MALDI-TOF MS spectra were obtained when A. fumigatus strains were grown on and in between a polycarbonate membrane filter on Sabouraud dextrose agar. A database of in-house reference spectra was created by growing Aspergillus reference strains (mainly focusing on sections Fumigati and Flavi) under these selected conditions. A test set of 50 molecularly identified strains grown under different conditions was used to select the best growth condition for identification and to perform an initial validation of the in-house database. Based on these results, the cultivation method on top of a polycarbonate filter proved to be most successful for species identification. This method was therefore selected for the identification of two sets of clinical isolates that mainly consisted of Aspergilli (100 strains originating from Indonesia, 70 isolates from Qatar). The results showed that this cultivation method is reliable for identification of clinically relevant Aspergillus species, with 67% and 76% correct identification of strains from Indonesia and Qatar, respectively. In conclusion, cultivation of Aspergilli on top of a polycarbonate filter showed improved results compared to the liquid cultivation protocol recommended by Bruker in terms of percentage of correct identification, ease of MSP creation, time consumption, cost and labour intensity. This method can be reliably applied for identification of clinically important Aspergilli and has potential for identification of other filamentous fungi.

Molecular epidemiology of clinical filamentous fungi in Qatar beyond Aspergillus and Fusarium with notes on the rare species.

Due to an increasing number of patients at risk (i.e., those with a highly compromised immune system and/or receiving aggressive chemotherapy treatment), invasive fungal infections (IFI) are increasingly being reported and associated with high mortality rates. Aspergillus spp., particularly A. fumigatus, is the major cause of IFI caused by filamentous fungi around the world followed by Fusarium spp., however, other fungi are emerging as human pathogens. The aim of this study was to explore the epidemiology and prevalence of the non-Aspergillus and non-Fusarium filamentous fungi in human clinical samples over an 11-year period in Qatar using molecular techniques. We recovered 53 filamentous fungal isolates from patients with various clinical conditions. Most patients were males (75.5%), 9.4% were immunocompromised, 20.7% had IFI, and 11.3% died within 30 days of diagnosis. The fungal isolates were recovered from a variety of clinical samples, including the nasal cavity, wounds, respiratory samples, body fluids, eye, ear, tissue, abscess, and blood specimens. Among the fungi isolated, 49% were dematiaceous fungi, followed by Mucorales (30%), with the latter group Mucorales being the major cause of IFI (5/11, 45.5%). The current study highlights the epidemiology and spectrum of filamentous fungal genera, other than Aspergillus and Fusarium, recovered from human clinical samples in Qatar, excluding superficial infections, which can aid in the surveillance of uncommon and emerging mycoses.

We recovered 53 non-Aspergillus and non-Fusarium filamentous fungal isolates from 53 patients in Qatar. Dematiaceous (black) fungi were the most isolated fungi followed by Mucorales, with the latter group Mucorales being the major cause of invasive infections in this study.

Serum Cytokine Profile in Patients with Candidemia versus Bacteremia.

Bloodstream Candida infections constitute a major threat for hospitalized patients in intensive care units and immunocompromised hosts. Certain serum cytokines play a decisive role in anti-microbial host defense. Cytokines may act as discriminatory biomarkers that can significantly increase in candidemia compared to bacteremia patients. The concentration of secreted cytokine/chemokines was determined using a multiplexed cytometric bead array run on a cell analyzer. The cytokines tested during the study were interleukin (IL)-1ß, IL-6, IL-17A, IL-10, IFN-γ, IL-4, IL-2, IL-8, IL-12p70 and the tumor necrosis factor (TNF)-α. The cytokines of 51 candidemia patients were characterized and compared to the cytokine levels of 20 bacteremia patients. Levels were significantly elevated in patients with bloodstream infections compared to healthy controls. Cytokines comprising IL-2, IL-17A, IL-6 and IL-10 were significantly elevated in the patients with bloodstream Candida infection as compared to the patients having bloodstream bacterial infections. The levels were found to be promising as a potential diagnostic marker for bloodstream Candida infections.

Where the infection is isolated rather than the specific species correlates with adherence strength, whereas biofilm density remains static in clinically isolated Candida and arthroconidial yeasts.

To colonize and infect the host, arthroconidial yeasts must avoid being killed by the host's defenses. The formation of biofilms on implanted devices allows fungi to avoid host responses and to disseminate into the host. To better study the mechanisms of infection by arthroconidial yeasts, adherence and biofilm formation were assayed using patient samples collected over 10 years. In clinical samples, adherence varies within species, but the relative adherence is constant for those samples isolated from the same infection site. Herein we document, for the first time, in-vitro biofilm formation by Trichosporon dohaense, T. ovoides, T. japonicum, T. coremiiforme, Cutaneotrichosporon mucoides, Cutaneotrichosporon cutaneum, Galactomyces candidus, and Magnusiomyces capitatus on clinically relevant catheter material. Analysis of biofilm biomass assays indicated that biofilm mass changes less than 2-fold, regardless of the species. Our results support the hypothesis that most pathogenic fungi can form biofilms, and that biofilm formation is a source of systemic infections.

Global guideline for the diagnosis and management of rare mould infections: an initiative of the European Confederation of Medical Mycology in cooperation with the International Society for Human and Animal Mycology and the American Society for Microbiology.

With increasing numbers of patients needing intensive care or who are immunosuppressed, infections caused by moulds other than Aspergillus spp or Mucorales are increasing. Although antifungal prophylaxis has shown effectiveness in preventing many invasive fungal infections, selective pressure has caused an increase of breakthrough infections caused by Fusarium, Lomentospora, and Scedosporium species, as well as by dematiaceous moulds, Rasamsonia, Schizophyllum, Scopulariopsis, Paecilomyces, Penicillium, Talaromyces and Purpureocillium species. Guidance on the complex multidisciplinary management of infections caused by these pathogens has the potential to improve prognosis. Management routes depend on the availability of diagnostic and therapeutic options. The present recommendations are part of the One World-One Guideline initiative to incorporate regional differences in the epidemiology and management of rare mould infections. Experts from 24 countries contributed their knowledge and analysed published evidence on the diagnosis and treatment of rare mould infections. This consensus document intends to provide practical guidance in clinical decision making by engaging physicians and scientists involved in various aspects of clinical management. Moreover, we identify areas of uncertainty and constraints in optimising this management.

A case of mycetoma-like chromoblastomycosis in Qatar.

Chromoblastomycosis is one of the neglected tropical mycoses associated with chronic infection of the skin and subcutaneous tissues. We report a case of 49-year-old patient originally from India presented with a mycetoma-like lesion in his right foot which was slowly progressing over three-year period. The diagnosis of chromoblastomycosis was confirmed following surgical excision and identification of the unique histological pathology of muriform bodies. The patient was subsequently treated with a prolonged course of oral itraconazole with a favorable outcome. The clinical presentations, assessment and management of the disease are outlined.

Incidence and clinical outcome of Cryptococcosis in a nation with advanced HIV surveillance program.

BACKGROUND: Cryptococcosis is a major opportunistic invasive mycosis that mostly affects immunocompromised patients. METHODS: This was an observational study of all culture-confirmed cases of cryptococcosis conducted in the State of Qatar from January 2005 to December 2016. Cryptococcus fungi were identified using Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS). RESULTS: Fourteen culture-confirmed cases of cryptococcosis were identified during the study period. Four patients had a Human Immunodeficiency Virus (HIV) infection with low CD4 count and five were receiving immunosuppressant medications. The rest of the patients were apparently immuno-competent. The central nervous system was the most common site of infection (57%) followed by bloodstream infection (36%) and pneumonia (14%). One patient had a cryptococcal scrotal infection. Twelve isolates were Cryptococcus neoformans and 2 were Cryptococcus laurentii. All isolates were within the wild type ECV values to amphotericin B and fluconazole. Only 2 patients with bloodstream infection (HIV negative) died. The rest were cured of the infection. CONCLUSION: Cryptococcosis is a rare fungal disease in the State of Qatar, mostly diagnosed in Asian immigrants. The central nervous system is the most common site of infection. The presence of the fungus in the blood carries a high mortality.

The Emergence of Rare Clinical Aspergillus Species in Qatar: Molecular Characterization and Antifungal Susceptibility Profiles.

Aspergillus are ubiquitous mold species that infect immunocompetent and immunocompromised patients. The symptoms are diverse and range from allergic reactions, bronchopulmonary infection, and bronchitis, to invasive aspergillosis. The aim of this study was to characterize 70 Aspergillus isolates recovered from clinical specimens of patients with various clinical conditions presented at Hamad general hospital in Doha, Qatar, by using molecular methods and to determine their in vitro antifungal susceptibility patterns using the Clinical and Laboratory Standards Institute (CLSI) M38-A2 reference method. Fourteen Aspergillus species were identified by sequencing ß-tubulin and calmodulin genes, including 10 rare and cryptic species not commonly recovered from human clinical specimens. Aspergillus welwitschiae is reported in this study for the first time in patients with fungal rhinosinusitis (n = 6) and one patient with a lower respiratory infection. Moreover, Aspergillus pseudonomius is reported in a patient with fungal rhinosinusitis which is considered as the first report ever from clinical specimens. In addition, Aspergillus sublatus is reported for the first time in a patient with cystic fibrosis. In general, our Aspergillus strains exhibited low MIC values for most of the antifungal drugs tested. One strain of Aspergillus fumigatus showed high MECs for echinocandins and low MICs for the rest of the drugs tested. Another strain of A. fumigatus exhibited high MIC for itraconazole and categorized as non-wild type. These findings require further analysis of their molecular basis of resistance. In conclusion, reliable identification of Aspergillus species is achieved by using molecular sequencing, especially for the emerging rare and cryptic species. They are mostly indistinguishable by conventional methods and might exhibit variable antifungal susceptibility profiles. Moreover, investigation of the antifungal susceptibility patterns is necessary for improved antifungal therapy against aspergillosis.

Molecular Analysis of Resistance and Detection of Non-Wild-Type Strains Using Etest Epidemiological Cutoff Values for Amphotericin B and Echinocandins for Bloodstream Candida Infections from a Tertiary Hospital in Qatar.

A total of 301 Candida bloodstream isolates collected from 289 patients over 5 years at a tertiary hospital in Qatar were evaluated. Out of all Candida infections, 53% were diagnosed in patients admitted to the intensive care units. Steady increases in non-albicans Candida species were reported from 2009 to 2014 (30.2% for Candida albicans versus 69.8% for the other Candida species). Etest antifungal susceptibility testing was performed on all recovered clinical isolates to determine echinocandin (micafungin and anidulafungin) and amphotericin B susceptibilities and assess non-wild-type (non-WT) strains (strains for which MICs were above the epidemiological cutoff values). DNA sequence analysis was performed on all isolates to assess the presence of FKS mutations, which confer echinocandin resistance in Candida species. A total of 3.9% of isolates (12/301) among strains of C. albicans and C. orthopsilosis contained FKS hot spot mutations, including heterozygous mutations in FKS1 For C. tropicalis, the Etest appeared to overestimate strains non-WT for micafungin, anidulafungin, and amphotericin B, as 14%, 11%, and 35% of strains, respectively, had values above the epidemiological cutoff value. However, no FKS mutations were identified in this species. For all other species, micafungin best reported the echinocandin non-WT strains relative to the FKS genotype, as anidulafungin tended to overestimate non-wild-type strains. Besides C. tropicalis, few strains were classified as non-WT for amphotericin B.

Azole-Resistance in Aspergillus terreus and Related Species: An Emerging Problem or a Rare Phenomenon?

Objectives: Invasive mold infections associated with Aspergillus species are a significant cause of mortality in immunocompromised patients. The most frequently occurring aetiological pathogens are members of the Aspergillus section Fumigati followed by members of the section Terrei. The frequency of Aspergillus terreus and related (cryptic) species in clinical specimens, as well as the percentage of azole-resistant strains remains to be studied. Methods: A global set (n = 498) of A. terreus and phenotypically related isolates was molecularly identified (beta-tubulin), tested for antifungal susceptibility against posaconazole, voriconazole, and itraconazole, and resistant phenotypes were correlated with point mutations in the cyp51A gene. Results: The majority of isolates was identified as A. terreus (86.8%), followed by A. citrinoterreus (8.4%), A. hortai (2.6%), A. alabamensis (1.6%), A. neoafricanus (0.2%), and A. floccosus (0.2%). One isolate failed to match a known Aspergillus sp., but was found most closely related to A. alabamensis. According to EUCAST clinical breakpoints azole resistance was detected in 5.4% of all tested isolates, 6.2% of A. terreus sensu stricto (s.s.) were posaconazole-resistant. Posaconazole resistance differed geographically and ranged from 0% in the Czech Republic, Greece, and Turkey to 13.7% in Germany. In contrast, azole resistance among cryptic species was rare 2 out of 66 isolates and was observed only in one A. citrinoterreus and one A. alabamensis isolate. The most affected amino acid position of the Cyp51A gene correlating with the posaconazole resistant phenotype was M217, which was found in the variation M217T and M217V. Conclusions:Aspergillus terreus was most prevalent, followed by A. citrinoterreus. Posaconazole was the most potent drug against A. terreus, but 5.4% of A. terreus sensu stricto showed resistance against this azole. In Austria, Germany, and the United Kingdom posaconazole-resistance in all A. terreus isolates was higher than 10%, resistance against voriconazole was rare and absent for itraconazole.

Genomic Understanding of an Infectious Brain Disease from the Desert.

Rhinocladiella mackenziei accounts for the majority of fungal brain infections in the Middle East, and is restricted to the arid climate zone between Saudi Arabia and Pakistan. Neurotropic dissemination caused by this fungus has been reported in immunocompromised, but also immunocompetent individuals. If untreated, the infection is fatal. Outside of humans, the environmental niche of R. mackenziei is unknown, and the fungus has been only cultured from brain biopsies. In this paper, we describe the whole-genome resequencing of two R. mackenziei strains from patients in Saudi Arabia and Qatar. We assessed intraspecies variation and genetic signatures to uncover the genomic basis of the pathogenesis, and potential niche adaptations. We found that the duplicated genes (paralogs) are more susceptible to accumulating significant mutations. Comparative genomics with other filamentous ascomycetes revealed a diverse arsenal of genes likely engaged in pathogenicity, such as the degradation of aromatic compounds and iron acquisition. In addition, intracellular accumulation of trehalose and choline suggests possible adaptations to the conditions of an arid climate region. Specifically, protein family contractions were found, including short-chain dehydrogenase/reductase SDR, the cytochrome P450 (CYP) (E-class), and the G-protein ß WD-40 repeat. Gene composition and metabolic potential indicate extremotolerance and hydrocarbon assimilation, suggesting a possible environmental habitat of oil-polluted desert soil.

Corrigendum: Azole-Resistance in Aspergillus terreus and Related Species: An Emerging Problem or a Rare Phenomenon?

[This corrects the article DOI: 10.3389/fmicb.2018.00516.].

Persistence of Candida dubliniensis and lung function in patients with cystic fibrosis.

OBJECTIVES: Candida dubliniensis is an emerging yeast and demonstrated a high adherence property to cystic fibrosis respiratory tract. Therefore, it is important to determine the persistence of C. dubliniensis and to assess the possible relationship to the body mass index (BMI) and forced expiratory volume in 1st second (FEV1). RESULTS: Candida isolates were identified by MALDI-TOF MS to species level from 40/52 (76.9%) cystic fibrosis patients. C. dubliniensis was the most common organism isolated from 50/77 (65%) lower respiratory specimens of 29 patients. Patients with persistent C. dubliniensis isolates have higher mean BMI in comparison to intermittent C. dubliniensis group. However, this difference did not reach statistical significance (P = 0.539). In contrast, patients with persistent C. dubliniensis isolates have significantly lower FEV1% mean in comparison to intermittent C. dubliniensis group particularly at initial two visits (P < 0.05); however, at subsequent visit the difference observed was not statistically significant (P = 0.456). The persistence of C. dubliniensis is more frequent in adults having more advanced disease, co-infections with chronic P. aeruginosa, cystic fibrosis related diabetes, long-term nebulized tobramycin and oral Zithromax therapy than patients with intermittent C. dubliniensis. Patients with persistent C. dubliniensis have lower FEV1 percentage and higher BMI than the intermittent C. dubliniensis.

Phylogenetic analysis reveals two genotypes of the emerging fungus Mucor indicus, an opportunistic human pathogen in immunocompromised patients.

Mucormycosis is a rare fungal infection caused by Mucor indicus. Phylogenetic analysis of many M. indicus isolates, mainly sampled from different clinical and environmental specimens collected worldwide, revealed two genotypes, I and II, based on ITS and D1/D2 LSU rDNA sequences. A retrospective review of the literature revealed 13 cases. Eight (76.9%) patients had disseminated infections, and the overall mortality rate was 30.7%. A pulmonary infection caused by M. indicus genotype I in a liver transplant recipient was disseminated to include the skin and was successfully treated with liposomal amphotericin B and aggressive surgery. M. indicus can infect a wide variety of patients with no real preference for the site of infection. We concluded that M. indicus has emerged as a significant cause of invasive mycosis in severely immunocompromised patients worldwide. Early diagnosis and initiation of appropriate therapy could enhance survival in these immunocompromised patient populations.

Bone and joint infections caused by mucormycetes: A challenging osteoarticular mycosis of the twenty-first century.

Osteomyelitis and arthritis caused by mucormycetes are rare diseases that rank among the most challenging complications in orthopedic and trauma surgery. The aim of this work is to review the epidemiological, clinical, diagnostic, and therapeutic aspects of the osteoarticular mucormycosis with particular emphasis on high-risk patients. A systematic review of osteoarticular mucormycosis was performed using PUBMED and EMBASE databases from 1978 to 2014. Among 34 patients with median age 41 (0.5-73 years), 24 (71%) were males. While 12 (35%) were immunocompromised patients, 14 (41%) had prior surgery, and seven (21%) suffered trauma. Other underlying conditions included diabetes mellitus, hematological malignancies, transplantation, and corticosteroid therapy. The median diagnostic delay from onset of symptoms and signs was 60 (10-180) days. The principal mechanism of the infection was direct inoculation (n = 19; 56%), and in immunocompromised patients was usually hematogenous disseminated. The long bones were infected by trauma or surgery, while a wide variety of bones were involved by hematogenous dissemination. Combined surgery and amphotericin B treatment were implemented in 28 (82%) and eight (23%) had an unfavorable outcome. Osteoarticular mucormycosis occurs most frequently after trauma or surgical procedures. These infections are progressively destructive and more virulent in individuals with impaired immune systems. Early diagnosis, timely administration of amphotericin B, control of underlying conditions, and surgical debridement of infected tissue are critical for successful management of osteoarticular mucormycosis.

Reduced Multidrug Susceptibility Profile Is a Common Feature of Opportunistic Fusarium Species: Fusarium Multi-Drug Resistant Pattern.

The resistance among various opportunistic Fusarium species to different antifungal agents has emerged as a cause of public health problems worldwide. Considering the significance of multi-drug resistant (MDR), this paper emphasizes the problems associated with MDR and the need to understand its clinical significance to combat microbial infections. The search platform PubMed/MEDLINE and a review of 32 cases revealed a common multidrug-resistant profile exists, and clinically relevant members of Fusarium are intrinsically resistant to most currently used antifungals. Dissemination occurs in patients with prolonged neutropenia, immune deficiency, and especially hematological malignancies. Amphotericin B displayed the lowest minimum inhibitory concentrarions (MICs) followed by voriconazole, and posaconazole. Itraconazole and fluconazole showed high MIC values, displaying in vitro resistance. Echinocandins showed the highest MIC values. Seven out of ten (70%) patients with neutropenia died, including those with fungemia that progressed to skin lesions. Clinical Fusarium isolates displayed a common MDR profile and high MIC values for the most available antifungal agents with species- and strain-specific differences in antifungal susceptibility. Species identification of Fusarium infections is important. While the use of natamycin resulted in a favorable outcome in keratitis, AmB and VRC are the most used agents for the treatment of fusariosis in clinical settings.

Aspergillus arthritis: analysis of clinical manifestations, diagnosis, and treatment of 31 reported cases.

Aspergillus arthritis is a debilitating form of invasive aspergillosis. Little is known about its epidemiology, clinical manifestations, laboratory features, treatment, and prognosis. Cases of Aspergillus arthritis were reviewed in the English literature from 1967 through 2015 for variables of arthritis with Aspergillus spp. recovered from joint and/or adjacent bone, underlying conditions, symptoms, signs, inflammatory biomarkers, diagnostic imaging, management, and outcome. Among 31 evaluable cases, 87% were males and 13% pediatric. Median age was 50 y (range 1-83 y). Seventeen (55%) patients were immunosuppressed with such conditions as hematological malignancies (26%), corticosteroids (39%), and/or transplantation (26%). Approximately one-half (52%) of patients had hematogenous seeding of the joint, and more than 80% had de novo infection with no prior antifungal therapy. Oligoarticular infection (2-3 joints) occurred in 45% and contiguous osteomyelitis was present in 61%. Clinical manifestations included pain (87%), edema (26%), and limited function (23%), with knees (35%), intervertebral discs (26%), and hips (16%) being most commonly infected. Aspergillus fumigatus constituted 77% of cases followed by Aspergillus flavus in 13%, Aspergillus niger in 3%, and not specified in 7%. Median ESR was 90 mm/hr and median CRP was 3.6 mg/dl. Median synovial fluid WBC was 17,200/µL (7,300-128,000) with 72% PMNs (range 61-92). Osteolysis occurred in 35%, and soft-tissue extension 47%. Nineteen patients (61%) were managed with combined medical and surgical therapy, 10 (32%) with medical therapy only, and 2 (6%) surgery only. Amphotericin B and itraconazole were the most frequently used agents with median duration of therapy of 219 days (range 30-545). Surgical interventions included debridement in 61%, drainage 19%, and amputation 6%. Complete or partial response was achieved in 71% and relapse occurred in 16%. Medical therapy was reinstituted with successful outcome in these patients. Overall survival was 65%. Aspergillus arthritis mainly develops as a de novo infection involving knees and intervertebral disks in immunocompromised patients with localizing symptoms. Contiguous osteomyelitis is frequently observed. Diagnosis is established by synovial fluid culture. Aspergillus arthritis is therapeutically challenging with most patients undergoing surgery and protracted antifungal therapy.