Fusariosis in Mexico: A 10-year retrospective series.

Fusarium species represent an opportunistic fungal pathogen. The data in Mexico about Fusarium infections in humans are scarce. Here, we present a retrospective series of patients with a confirmed diagnosis of fusariosis in eight different hospitals in Mexico from January 2010 to December 2019. The diagnosis of proven fusariosis was made according to the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium (EORT/MSG) criteria. A total of 49 cases were identified in our series. Most patients had burn injuries (49%), and 37% had hematological malignancies. Most patients had fire injuries (40%), followed by electric injuries (8%), febrile neutropenia (10%), and pancytopenia (6%). Patients had skin and soft tissue involvement in 49%, followed by blood culture isolation and biopsies from different sites of the body (lung, sinuses, bone tissue, and eyes). Febrile neutropenia (10%) and fungemia (8%) were the most common clinical syndromes in immunosuppressed patients. Most patients received monotherapy (67%), where voriconazole was used in 30% of the cases, followed by conventional amphotericin B (16%), and lipidic formulations of amphotericin B in 10% (either liposomal amphotericin B or amphotericin B lipid complex). Combination therapy was used in 20% of the cases, and the most common combination therapy was triazole plus any lipidic formulation of amphotericin B (10%). Mortality related to Fusarium infection occurred in 22% of patients. Fusariosis is a serious threat. Burn injuries and hematologic malignancies represent the most common causes of infection in this small series from Mexico.

This study describes the epidemiological characteristics of patients with fusariosis from a multicenter cohort in Mexico. These findings provide information from this invasive fungal disease that threatens different countries in Latin America.

Lipid-Like Biofilm from a Clinical Brain Isolate of Aspergillus terreus: Quantification, Structural Characterization and Stages of the Formation Cycle.

Invasive infections caused by filamentous fungi have increased considerably due to the alteration of the host's immune response. Aspergillus terreus is considered an emerging pathogen and has shown resistance to amphotericin B treatment, resulting in high mortality. The development of fungal biofilm is a virulence factor, and it has been described in some cases of invasive aspergillosis. In addition, although the general composition of fungal biofilms is known, findings related to biofilms of a lipid nature are rarely reported. In this study, we present the identification of a clinical strain of A. terreus by microbiological and molecular tools, also its in vitro biofilm development capacity: (i) Biofilm formation was quantified by Crystal Violet and reduction of tetrazolium salts assays, and simultaneously the stages of biofilm development were described by Scanning Electron Microscopy in High Resolution (SEM-HR). (ii) Characterization of the organizational structure of the biofilm was performed by SEM-HR. The hyphal networks developed on the surface, the abundant air channels created between the ECM (extracellular matrix) and the hyphae fused in anastomosis were described. Also, the presence of microhyphae is reported. (iii) The chemical composition of the ECM was analyzed by SEM-HR and CLSM (Confocal Laser Scanning Microscopy). Proteins, carbohydrates, nucleic acids and a relevant presence of lipid components were identified. Some structures of apparent waxy appearance were highlighted by SEM-HR and backscatter-electron diffraction, for which CLSM was previously performed. To our knowledge, this work is the first description of a lipid-type biofilm in filamentous fungi, specifically of the species A. terreus from a clinical isolate.

Invasive Fungal Infection Caused by Magnusiomyces capitatus in an Immunocompromised Pediatric Patient with Acute Lymphoblastic Leukemia in Mexico City: A Case Report.

Magnusiomyces capitatus (also denominated "Geotrichum capitatum" and "the teleomorph stage of Saprochaete capitata") mainly affects immunocompromised patients with hematological malignancies in rare cases of invasive fungal infections (IFIs). Few cases have been reported for pediatric patients with acute lymphoblastic leukemia (ALL), in part because conventional diagnostic methods do not consistently detect M. capitatus in infections. The current contribution describes a systemic infection in a 15-year-old female diagnosed with ALL. She arrived at the Children's Hospital of Mexico City with a fever and neutropenia and developed symptoms of septic shock 4 days later. M. capitatus ENCB-HI-834, the causal agent, was isolated from the patient's blood, urine, bile, and peritoneal fluid samples. It was identified with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and a phylogenetic reconstruction using internal transcribed spacer (ITS) and 28S ribosomal sequences. The phylogenetic sequence of M. capitatus ENCB-HI-834 clustered with other M. capitatus-type strains with a 100% identity. In vitro antifungal testing, conducted with the Sensititre YeastOne susceptibility system, found the following minimum inhibitory concentration (MIC) values (µg/mL): posaconazole 0.25, amphotericin B 1.0, fluconazole > 8.0, itraconazole 0.25, ketoconazole 0.5, 5-flucytosine ≤ 0.06, voriconazole 0.25, and caspofungin > 16.0. No clinical breakpoints have been defined for M. capitatus. This is the first clinical case reported in Mexico of an IFI caused by M. capitatus in a pediatric patient with ALL. It emphasizes the importance of close monitoring for a timely and accurate diagnosis of neutropenia-related IFIs to determine the proper treatment with antibiotics, antifungals, and chemotherapy for instance including children with ALL.

Identification of CSP Types and Genotypic Variability of Clinical and Environmental Isolates of Aspergillus fumigatus from Different Geographic Origins.

The CSP (cell surface protein) microsatellite marker is useful for typing Aspergillus fumigatus isolates and determining relationships at the subpopulation level because it has shown high discriminatory power. In the present study, 90 A. fumigatus isolates from Mexico (MX), Argentina (AR), France (FR), and Peru (PE) were identified through a phylogenetic analysis using the benA gene fragment and were typed with the CSP microsatellite, and the types were identified using the nomenclature recommended in the literature. Genetic variability was analyzed through haplotype diversity, nucleotide diversity, polymorphic sites, and nucleotide differences between pairs of sequences. The population structure was evaluated using the Tajima's D statistic. No new CSP types were recorded in the MX, FR, and PE isolates, while in the AR isolates, two new CSP types were identified (t25 and t26). The most common CSP types in the studied populations were t01, t02, t03, and t04A; these results are consistent with findings in other countries. In addition, the genetic diversity parameters we obtained revealed that the greatest genetic diversity was found in the MX population, followed by AR and FR. No population structure was identified among the isolates studied.

First report of a catheter-related bloodstream infection by Candida haemulonii in a children's hospital in Mexico City.

BACKGROUND: Candida haemulonii is an emergent, multi-resistant opportunistic pathogenic yeast that like Candida auris, can be misidentified when conventional diagnostic methods are used. Timely molecular identification using DNA sequence analysis variation in the internal transcriber spacer region, ITS1-ITS4 and the 28S ribosomal DNA gene (28S rDNA), and in vitro antifungal susceptibility assessment can lead to rapid therapeutic success. CASE REPORT: A case of Candida haemulonii candidiasis suffered by a male paediatric patient attended at Federico Gómez Children's Hospital of México City in September 2016 is reported. The isolate was yielded from peripheral blood and central catheter blood specimens. From in vitro antifungal susceptibility data, caspofungin was administered to the patient, who showed clear improvements at the end of antimicrobial administration, and the removal of the central venous catheter. Using a molecular phylogenetic approach, we identified the clinical isolate as C. haemulonii. The clinical isolate has been named as Candida haemulonii ENCB-87 from now on. C. haemulonii ENCB-87 grew well between the temperatures, 28 °C and 35 °C but not at 37 °C in YPD culture medium. The clinical isolate was susceptible to caspofungin, which resulted in therapeutic success for the patient. CONCLUSIONS: C. haemulonii is an emergent, opportunistic pathogen, closely related to C. auris, therefore, the timely and accurate identification and antifungal susceptibility assessments are paramount in generating a robust epidemiology of this emerging Candida species.

Successful posaconazole salvage therapy for rhinocerebral mucormycosis in a child with leukemia. Review of the literature.

BACKGROUND: Mucormycosis is a fungal infection caused by species of the Mucorales order. These microorganisms are angioinvasive, with rapid disease progression and potentially lethal in its rhinocerebral form. CASE REPORT: We present the case of a 12-year-old female with trisomy 21, acute lymphoblastic leukemia and diabetes, with fever and neutropenia who developed rhinocerebral mucormicosis. After treatment with amphotericin B lipid complex and extensive surgery, disease progressed and posaconazole was added as salvage treatment with full remission of the infection. Four years after diagnosis the patient continues without relapse of mucormycosis or leukemia. CONCLUSIONS: This case highlights the use of posaconazole as either monotherapy or combined therapy. Although it is still debated, it can be considered an option for salvage treatment in children with non-responding mucormycosis, despite lack of standard dosage in pediatric patients.

Successful posaconazole salvage therapy for rhinocerebral mucormycosis in a child with leukemia. Review of the literature / Tratamiento de rescate exitoso con posaconazol en una niña con leucemia y mucormicosis rinocerebral. Revisión de la literatura

Background: Mucormycosis is a fungal infection caused by species of the Mucorales order. These microorganisms are angioinvasive, with rapid disease progression and potentially lethal in its rhinocerebral form. Case report: We present the case of a 12-year-old female with trisomy 21, acute lymphoblastic leukemia and diabetes, with fever and neutropenia who developed rhinocerebral mucormicosis. After treatment with amphotericin B lipid complex and extensive surgery, disease progressed and posaconazole was added as salvage treatment with full remission of the infection. Four years after diagnosis the patient continues without relapse of mucormycosis or leukemia. Conclusions: This case highlights the use of posaconazole as either monotherapy or combined therapy. Although it is still debated, it can be considered an option for salvage treatment in children with non-responding mucormycosis, despite lack of standard dosage in pediatric patients

Antecedentes: La mucormicosis es una infección fúngica causada por especies del orden de los mucorales. Estos microorganismos se caracterizan por ser angioinvasivos, con progresión rápida de la enfermedad y potencialmente letales en la forma rinocerebral. Caso clínico: Presentamos el caso de una paciente de 12 años de edad con trisomía 21, leucemia linfoblástica aguda, diabetes, fiebre y neutropenia, que desarrolló una mucormicosis rinocerebral. La enfermedad progresó a pesar de recibir tratamiento con anfotericina B complejo lipídico y ser sometida a cirugía extensa. Se añadió posaconazol al tratamiento como terapia de salvamento, lo que llevó a la remisión total del proceso infeccioso. Cuatro años después la paciente continúa sin recaída de la mucormicosis o la leucemia. Conclusiones: Este caso destaca el uso del posaconazol, ya sea como monoterapia o terapia combinada en el tratamiento de la mucormicosis. Si bien aún es debatido su uso, se puede considerar como una opción en el tratamiento de niños con mucormicosis que no responden al tratamiento convencional a pesar de no contar con una dosis pediátrica establecida

Cost-effectiveness analysis of voriconazole, fluconazole, and amphotericin B for invasive fungal infections following allogeneic hematopoietic stem cell transplantation in Mexico.

BACKGROUND: Patients receiving allogeneic hematopoietic stem cell transplantation (alloHSCT) are at high risk of invasive fungal infections (IFIs), which are associated with high mortality and economic burden. The cost-effectiveness of prophylaxis for the prevention of IFIs in alloHSCT recipients in Mexico has not yet been assessed. METHODS: This analysis modeled a hypothetical cohort of 1,000 patients to estimate costs and outcomes for patients receiving prophylaxis for IFIs following alloHSCT, from the perspective of institutional payers in Mexico. The main prophylaxis agents currently used in Mexican clinical practice are voriconazole, fluconazole, and amphotericin B (AmB). The model accounted for event rates of IFIs during each treatment, assuming IFI causality due to invasive aspergillosis, invasive candidiasis, or other IFIs, and that the outcome for patients during follow-up was IFI-related death, death from other causes, or survival. Clinical efficacies were obtained from published literature; costs were based on local sources. Cost-effectiveness was assessed using incremental cost-effectiveness ratios (ICERs). Univariate (assessing the impact of varying each model parameter) and probabilistic sensitivity analyses were performed. RESULTS: Voriconazole was associated with the lowest number of breakthrough IFIs, IFI-related deaths, and total number of deaths. Total costs were lower for fluconazole (Mexican pesos [MXN] 72,944; US $4,079) than voriconazole (MXN 101,413; US $5,671) or AmB (MXN 110,529; US $6,180). Voriconazole had better clinical outcomes and lower costs than AmB and could be considered cost-effective compared with fluconazole in line with the local ICER threshold. Drug costs, monitoring costs, and duration of prophylaxis were most sensitive to variation from univariate sensitivity analysis. Findings from the probabilistic sensitivity analysis were consistent with the base-case results. CONCLUSION: Voriconazole had the most favorable clinical outcomes, but overall prophylaxis costs were higher than with fluconazole. Overall, based on local ICER thresholds (MXN 184,665; US $10,326), voriconazole was considered a cost-effective option for prophylaxis of IFI in Mexico.

Higher In vitro Proliferation Rate of Rhizopus oryzae in Blood of Diabetic Individuals in Chronic Glycaemic Control Compared with Non-diabetic Individuals.

Metabolic control improves outcomes associated with mucormycosis. The aim of this study was to compare the in vitro proliferation of Rhizopus oryzae in blood of individuals with and without diabetes at different glycaemic levels. Ninety-five individuals were included. Blood samples from each participant were incubated with sporangiospores of R. oryzae. The germination, filamentation and growth of R. oryzae were compared at different time points. Four groups were defined, one without (group A, n = 30) and three with diabetes: group B (HbA1c ≤7%, N = 24), group C (HbA1c 7.1-9%, N = 20) and group D (HbA1c > 9%, N = 21). The percentage of germinated sporangiospores was higher in the group A after 6 h (group A 56% ± 3, group B 35% ± 4, group C 48% ± 4, group D 46% ± 1.4, p = 0.01), 12 h (group A 54% ± 1.4, group B 19% ± 4, group C 16% ± 1, group D 9.5% ± 5, p < 0.001) and 24 h (group A 29% ± 1, group B 12% ± 4, group C 13.5% ± 3.5, group D 12% ± 1, p < 0.01). The filamentation was higher in groups with diabetes. Group B showed higher filamentation grade than group A at 6 h (0.4 ± 0.04 vs 1 ± 0.09, p < 0.001) and 24 h (1.6 ± 0.05 vs 2.1 ± 0.1, p = 0.05). In conclusion, R. oryzae proliferation was higher among diabetic individuals, including good glycaemic control, than among non-diabetic individuals.

Disseminated penicilliosis due to Penicillium chrysogenum in a pediatric patient with Henoch-Schönlein syndrome.

A case of disseminated infection caused by Penicillium chrysogenum in a 10-year-old boy with a history of Henoch-Schönlein purpura and proliferative glomerulonephritis, treated with immunosuppressors, is reported herein. The patient had a clinical picture of 2 weeks of fever that did not respond to treatment with broad-spectrum antibiotics and amphotericin B. Computed tomography imaging showed diffuse cotton-like infiltrates in the lungs, hepatomegaly, mesenteric lymphadenopathy, and multiple well-defined round hypodense lesions in the spleen. His treatment was changed to caspofungin, followed by voriconazole. One month later, a splenic biopsy revealed hyaline septate hyphae of >1µm in diameter. Fungal growth was negative. However, molecular analysis showed 99% identity with P. chrysogenum. A therapeutic splenectomy was performed, and treatment was changed to amphotericin B lipid complex and caspofungin. The patient completed 2 months of treatment with resolution of the infection. P. chrysogenum is a rare causative agent of invasive fungal infections in immunocompromised patients, and its diagnosis is necessary to initiate the appropriate antifungal treatment.

Isolation of Brucella melitensis from an abscess on the left foot of a 3-year-old infant.

An unusual case of a 3-year-old girl with a brucellar foot abscess is reported. Although direct microscopic examination of samples from the lesion did not reveal micro-organisms of any kind, a 7 day culture of caseous material yielded small colonies of Gram-negative cocobacilli in Löwenstein-Jensen medium. These were biochemically and molecularly identified as Brucella melitensis. The possibility of foot abscess being caused by Brucella should be considered in countries where brucellosis is endemic.

Factores asociados a mortalidad por fungemias causadas por Candida sp. en niños / Risk factors associated with mortality due to Candida sp. infections in children

Introducción. Durante los últimos años se ha reportado un incremento dramático en la incidencia de infecciones causadas por levaduras, siendo creciente el aislamiento de especies de Candida no albicans, en donde los principales factores asociados a mortalidad son: edad, procedimientos invasivos y uso previo de antibióticos. Material y métodos. Se trata de un estudio retrospectivo de serie de casos, que incluyó niños mayores de un mes hasta 18 años de edad, con diagnóstico de infección sistémica por hongos, con aislamiento de Candida albicans de sitios estériles, durante el período de mayo 1999 a diciembre de 2004. Se revisaron los registros microbiológicos de aislamientos en sitios estériles (hemocultivo, urocultivo, LCR, biopsia de tejidos, etc.) para microorganismos del tipo de levaduras. La información se obtuvo de los registros del Laboratorio de Micología del Hospital Infantil de México Federico Gómez. Una vez obtenidos dichos datos, se procedió a revisar los expedientes de cada paciente, analizando factores asociados al momento de identificar la infección y el antecedente de estos factores en los 30 días previos al evento. El objetivo fue analizar los factores asociados a muerte. Resultados. Se observó incremento en las tasas de infección por 1 000 egresos de 1999 a 2004. Se encontraron 45 eventos infecciosos causados por Candida sp., con una mortalidad de 35.5%. No se identificó la especie en 18 pacientes, siendo C. albicans en 16 eventos, y otras Candidas no albicans en 24%. El diagnóstico de base fue: neoplasias en 12 pacientes, malformaciones del tubo digestivo y sepsis en 6, cardiopatías congénitas e insuficiencia renal en 3, enfermedades hepáticas en 4, y otras en 10 pacientes. Siendo de tipo nosocomial en 88.8%. El grupo de edad con mayor mortalidad fue en neonatos. Los principales factores asociados a ésta fueron el antecedente de plaquetopenia y neutropenia, así como el estar intubados al momento de la infección. Conclusiones. Las infecciones por Candida sp. continúan siendo una causa importante de morbilidad y mortalidad. La intubación, el antecedente de neutropenia y plaquetopenia, además del uso de antibióticos son factores asociados a mayor mortalidad. Existe un incremento en el aislamiento de especies de Candida no albicans.

Introduction. A dramatic increase in the incidence of fungal infections has been reported in recent years. This is especially true with regards to infections due to Candida non albicans. The main risk factors associated with mortality include: age, invasive procedures and previous use of antibiotics. Material and methods. A retrospective study of series of cases, in the Hospital Infantil de Mexico Federico Gomez, including children less than 18 years of age, with a diagnosis of systemic fungal infection and the isolation of C. albicans from sterile sites, during the period from May 1999 to December 2004. The objective was to analyze the factors associated to death. We reviewed the microbiology archives to identify the isolation of yeast from sterile sites including: blood, urine, CSF, and biopsy specimens. The information was obtained from the Hospital mycology laboratory. The individual patient record was carefully reviewed in efforts to determine possible risk factors at the time of the positive cultures as well as the antecedent 30 days. Results. We observed an increase in the rates of infection per 1 000 discharges from 1999 to 2004. We observed 45 infectious events due to Candida sp., with a mortality of 35.5%. We did not identify the species in 18 patients, C. albicans in 16 events and other non albicans in 24%. In 12 patients the underlying diagnosis was cancer; gastrointestinal malformations in 6, congenital heart disease in 12 patients, malformations of digestive tube and sepsis in 6, congenital cardiopathy and renal failure in 3, hepatic diseases in 4 and others disease entities in 10 patients. In 88.8% the infections were of nosocomial origin. The age group with the highest mortality was newborns. The main factors associated with mortality were: the antecedent of thrombocytopenia and neutropenia, as well as being intubated at the moment of the infection. Conclusions. Fungal infections and particularly those due to Candida sp., represent an important cause of morbidity and mortality. The associated risk factors are those due to an immunocompromised state, protracted use of broad spectrum antibiotics and invasive procedures including endotracheal intubation. An increase in the isolation of non- albicans species was noted.

Successful treatment of a primary cutaneous zygomycosis caused by Absidia corymbifera in a premature newborn.

Mucormycosis (zygomycosis) normally occurs among individuals with predisposing factors such as prematurity, use of broad spectrum antibiotics, metabolic acidosis or advanced stages of immunosuppression. There have been reports of sporadic cases of cutaneous mucormycosis related to predisposing skin lesions and contact with contaminated material such as adhesive bandages and tongue depressors placed close to intravenous catheter insertion sites. We report successful treatment of a case of Absidia corymbifera infection with the combination of amphotericin B and surgical debridement of the affected area.