RESUMO
A multinational outbreak of nosocomial fusarium meningitis occurred among immunocompetent patients who had undergone surgery with epidural anesthesia in Mexico. The pathogen involved had a high predilection for the brain stem and vertebrobasilar arterial system and was associated with high mortality from vessel injury. Effective treatment options remain limited; in vitro susceptibility testing of the organism suggested that it is resistant to all currently approved antifungal medications in the United States. To highlight the severe complications associated with fusarium infection acquired in this manner, we report data, clinical courses, and outcomes from 13 patients in the outbreak who presented with symptoms after a median delay of 39 days.
Assuntos
Surtos de Doenças , Fusariose , Fusarium , Doença Iatrogênica , Meningite Fúngica , Humanos , Antifúngicos/uso terapêutico , Fusariose/epidemiologia , Fusariose/etiologia , Fusarium/isolamento & purificação , Doença Iatrogênica/epidemiologia , Meningite Fúngica/epidemiologia , Meningite Fúngica/etiologia , México/epidemiologia , Surtos de Doenças/estatística & dados numéricos , Internacionalidade , Imunocompetência , Farmacorresistência Fúngica , Analgesia Epidural/efeitos adversosRESUMO
BACKGROUND: Public health officials are responding to an outbreak of fungal meningitis among patients who received procedures under epidural anesthesia at two clinics (River Side Surgical Center and Clinica K-3) in Matamoros, Mexico, during January 1-May 13, 2023. This report describes outbreak epidemiology and outlines interim diagnostic and treatment recommendations. METHODS: Interim recommendations for diagnosis and management were developed by the Mycoses Study Group Research Education and Consortium (MSGERC) based on the clinical experience of clinicians caring for patients during the current outbreak or during previous outbreaks of healthcare-associated fungal meningitis in Durango, Mexico, and the United States. RESULTS: As of July 7, 2023, the situation has evolved into a multistate and multinational fungal meningitis outbreak. A total of 185 residents in 22 U.S. states and jurisdictions have been identified who might be at risk of fungal meningitis because they received epidural anesthesia at the clinics of interest in 2023. Among these patients, 11 suspected, 10 probable, and 10 confirmed U.S. cases have been diagnosed, with severe vascular complications and eight deaths occurring. Fusarium solani species complex has been identified as the causative agent, with antifungal susceptibility testing of a single isolate demonstrating poor in vitro activity for most available antifungals. Currently, triple therapy with intravenous voriconazole, liposomal amphotericin B, and fosmanogepix is recommended. CONCLUSIONS: Efforts to understand the source of this outbreak and optimal treatment approaches are ongoing, but infectious diseases physicians should be aware of available treatment recommendations. New information will be available on CDC's website.
RESUMO
Invasive candidiasis (IC) is the most frequent health care associated invasive fungal infection. It is also associated with high morbidity, mortality, and cost. The most frequent etiologic agent is Candida albicans, but non-albicans species are increasing and associated with reduced antifungal susceptibility and outbreaks. Candida auris is an emerging multidrug-resistant species recently described. IC presents as a spectrum of disease, going from fungemia to deep-seated candidiasis, and to septic shock with multiorgan failure. Diagnosis of IC is challenging. Several biomarkers and molecular methods are available for improving diagnosis. Early initial treatment with echinocandins is the treatment of choice. Step-down therapy when antifungal susceptibility is available is possible. Several new antifungal agents for the treatment of IC are in clinical development.
Assuntos
Antifúngicos/uso terapêutico , Candidíase Invasiva/tratamento farmacológico , Candidíase Invasiva/epidemiologia , Candida/efeitos dos fármacos , Candidíase Invasiva/microbiologia , Farmacorresistência Fúngica Múltipla , Equinocandinas/uso terapêutico , Humanos , Testes de Sensibilidade MicrobianaRESUMO
BACKGROUND: Treatment of serious infections due to multidrug-resistant (MDR) Pseudomonas aeruginosa remains a challenge, despite the introduction of novel therapeutics. In this study, we report 2 extensively drug-resistant clinical isolates of sequence type (ST) 309 P aeruginosa resistant to all ß-lactams, including the novel combinations ceftolozane/tazobactam, ceftazidime/avibactam, and meropenem/vaborbactam. METHODS: Isolates were sequenced using both short-read (Illumina) and long-read technology to identify resistance determinants, polymorphisms (compared with P aeruginosa PAO1), and reconstruct a phylogenetic tree. A pair of ß-lactamases, Guiana extended spectrum ß-lactamase (GES)-19 and GES-26, were cloned and expressed in a laboratory strain of Escherichia coli to examine their relative impact on resistance. Using cell lysates from E coli expressing the GES genes individually and in tandem, we determined relative rates of hydrolysis for nitrocefin and ceftazidime. RESULTS: Two ST309 P aeruginosa clinical isolates were found to harbor the extended spectrum ß-lactamases GES-19 and GES-26 clustered in tandem on a chromosomal class 1 integron. The presence of both enzymes in E coli was associated with significantly elevated minimum inhibitory concentrations to aztreonam, cefepime, meropenem, ceftazidime/avibactam, and ceftolozane/tazobactam, compared with those expressed individually. The combination of ceftazidime/avibactam plus aztreonam was active in vitro and used to achieve cure in one patient. Phylogenetic analysis revealed ST309 P aeruginosa are closely related to MDR strains from Mexico also carrying tandem GES. CONCLUSIONS: The presence of tandem GES-19 and GES-26 is associated with resistance to all ß-lactams, including ceftolozane/tazobactam. Phylogenetic analysis suggests that ST309 P aeruginosa may be an emerging threat in the United States.
RESUMO
BACKGROUND: Fungicide exposure in the environment has driven the emergence of azole-resistant Aspergillus fumigatus worldwide. A screening test allows identification of resistant isolates. OBJECTIVES: We screened clinical samples for azole-resistant Aspergillus through azole-containing agar plates and identified mutations in the cyp51A gene of A. fumigatus. METHODS: Aspergillus isolates from clinical samples collected in a tertiary care centre from 2014 to 2017 were screened for azole resistance. Samples were subcultured in azole-containing agar plates. Isolates with a positive screening test were subject to DNA extraction, DNA amplification and sequencing of the cyp51A gene (coding and promoter regions). Clinical data were obtained from medical records. RESULTS: We screened 43 Aspergillus isolates from 39 patients for azole resistance. Three isolates from three patients grew on azole-containing agar plates: two A. fumigatus and one Aspergillus flavus. PCR analysis and cyp51A sequencing identified the TR34/L98H mutation in both A. fumigatus isolates. The prevalence of cyp51A mutations among A. fumigatus was 8.3% (2/24). Both patients with TR34/L98H mutants were azole naive and presented with invasive aspergillosis; one had multiple myeloma and the other was a liver retransplant recipient. They suffered progressive disease and failed voriconazole therapy. CONCLUSIONS: To the best of our knowledge, this is the first report of azole-resistant A. fumigatus with the TR34/L98H mutation in two azole-naive patients with refractory invasive aspergillosis in Mexico.
Assuntos
Antifúngicos/farmacologia , Aspergilose/epidemiologia , Aspergilose/virologia , Aspergillus fumigatus/efeitos dos fármacos , Aspergillus fumigatus/genética , Azóis/farmacologia , Sistema Enzimático do Citocromo P-450/genética , Farmacorresistência Fúngica , Proteínas Fúngicas/genética , Antifúngicos/uso terapêutico , Aspergilose/tratamento farmacológico , Azóis/uso terapêutico , Humanos , México/epidemiologia , Mutação , Vigilância em Saúde PúblicaRESUMO
BACKGROUND: The mortality of Candida Bloodstream Infection (CBSI) remains high. Antifungal susceptibility breakpoints were recently updated for Candida species, the impact remains unknown. In this study we evaluated the impact of inappropriate antifungal treatment according to recent breakpoints on 30-day mortality of CBSI. METHODS: From June 2008 to July 2014, data on CBSI episodes from two tertiary-care centers, treated > 72 h were analyzed. Antifungal therapy and 30-day mortality were registered. Inappropriate antifungal treatment according to current Clinical & Laboratory Standards Institute (CLSI) breakpoints was adjusted with 30-day mortality-related co-variates. RESULTS: One hundred forty-nine episodes of CBSI were analyzed. The most frequent species were: C. albicans (40%), C. tropicalis (23%) and C. glabrata complex (20%). According to the 2012 CLSI, 10.7% received inappropriate treatment. The 30-day mortality was 38%; severe sepsis [Odds ratio (OR) 3.4; 95% CI 1.3-8.4], cirrhosis (OR 36; 95% CI 12.2-605), early central venous catheter removal (OR 0.23; 95% CI 0.08-0.66) and previous antifungal therapy (OR 0.15; 95%CI 0.03-0.62), were associated with 30-day mortality by multivariate analysis. Inappropriate antifungal treatment was not (OR 0.19; 95% CI 0.03-1.2). CONCLUSIONS: Appropriate antifungal therapy according to CLSI 2012 did not have an impact on mortality. Mortality of CBSI remains high due to disease severity and comorbidities; early antifungal therapy and catheter removal may reduce it.
Assuntos
Candidemia/mortalidade , Sepse/mortalidade , Adulto , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida albicans/efeitos dos fármacos , Candida albicans/isolamento & purificação , Candida glabrata/efeitos dos fármacos , Candida glabrata/isolamento & purificação , Candidemia/tratamento farmacológico , Candidemia/microbiologia , Candidemia/patologia , Farmacorresistência Fúngica , Feminino , Fluconazol/farmacologia , Fluconazol/uso terapêutico , Humanos , Unidades de Terapia Intensiva , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Estudos Retrospectivos , Sepse/tratamento farmacológico , Sepse/microbiologia , Sepse/patologia , Índice de Gravidade de Doença , Centros de Atenção TerciáriaRESUMO
Despite increasing rates of invasive fungal infections being reported globally, only a single antifungal drug has been approved during the last decade. Resistance, toxicity, drug interactions and restricted routes of administration remain unresolved issues. This review focuses on new antifungal compounds which are currently in various clinical phases of development. We discuss two azoles with a tetrazole moiety that allows selective activity against the fungal CYP: VT-1161 for Candida infections and VT-1129 for cryptococcal meningoencephalitis. We also discuss two glucan synthesis inhibitors: CD101, an echinocandin with an increased half-life, and SCY-078 with oral bioavailability and increased activity against echinocandin-resistant isolates. Among the polyenes, we discuss MAT023, an encochleated amphotericin B formulation that allows oral administration. Two novel classes of antifungal drugs are also described: glycosylphosphatidylinositol inhibitors, and the leading drug APX001, which disrupt the integrity of the fungal wall; and the orotomides, inhibitors of pyrimidine synthesis with the leading drug F901318. Finally, a chitin synthesis inhibitor and progress on human monoclonal antifungal antibodies are discussed.
Assuntos
Antifúngicos/química , Micoses/tratamento farmacológico , Acetamidas/farmacologia , Acetamidas/uso terapêutico , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Azóis/química , Azóis/farmacologia , Azóis/uso terapêutico , Química Farmacêutica , Desenvolvimento de Medicamentos , Equinocandinas/farmacologia , Equinocandinas/uso terapêutico , Humanos , Piperazinas/farmacologia , Piperazinas/uso terapêutico , Polienos/química , Polienos/farmacologia , Polienos/uso terapêutico , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Pirróis/farmacologia , Pirróis/uso terapêuticoRESUMO
INTRODUCTION: Larger populations at risk, broader use of antibiotics and longer hospital stays have impacted on the incidence of Candida sp. bloodstream infections (CBSI). OBJECTIVE: To determine clinical and epidemiologic characteristics of patients with CBSI in two tertiary care reference medical institutions in Mexico City. DESIGN: Prospective and observational laboratory-based surveillance study conducted from 07/2008 to 06/2010. METHODS: All patients with CBSI were included. Identification and antifungal susceptibility were performed using CLSI M27-A3 standard procedures. Frequencies, Mann-Whitney U test or T test were used as needed. Risk factors were determined with multivariable analysis and binary logistic regression analysis. RESULTS: CBSI represented 3.8% of nosocomial bloodstream infections. Cumulative incidence was 2.8 per 1000 discharges (incidence rate: 0.38 per 1000 patient-days). C. albicans was the predominant species (46%), followed by C. tropicalis (26%). C. glabrata was isolated from patients with diabetes (50%), and elderly patients. Sixty-four patients (86%) received antifungals. Amphotericin-B deoxycholate (AmBD) was the most commonly used agent (66%). Overall mortality rate reached 46%, and risk factors for death were APACHE II score ≥ 16 (OR = 6.94, CI95%â= 2.34-20.58, p<0.0001), and liver disease (OR = 186.11, CI95%â= 7.61-4550.20, p = 0.001). Full susceptibility to fluconazole, AmBD and echinocandins among C. albicans, C. tropicalis, and C. parapsilosis was observed. CONCLUSIONS: The cumulative incidence rate in these centers was higher than other reports from tertiary care hospitals from Latin America. Knowledge of local epidemiologic patterns permits the design of more specific strategies for prevention and preemptive therapy of CBSI.
Assuntos
Candida , Candidíase/mortalidade , Adulto , Idoso , Anfotericina B/química , Candida albicans , Candida glabrata , Candida tropicalis , Candidíase/epidemiologia , Ácido Desoxicólico/química , Combinação de Medicamentos , Feminino , Fluconazol/uso terapêutico , Humanos , Incidência , Masculino , México , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Análise de Regressão , Fatores de Risco , Centros de Atenção Terciária , Resultado do TratamentoRESUMO
Objetivo. Describir los resultados de la vigilancia de tuberculosis en trabajadores de la salud en un centro hospitalario de tercer nivel. Material y métodos. Se revisaron los re-gistros de vigilancia de trabajadores durante 1992-1998, analizando variables demográficas, laborales, antecedentes clínicos, así como pruebas previas, prueba de la tuberculina (PPD), refuerzos y seguimiento. Como medida de asociación se utilizó la razón de momios (RM) con su respectiva signi-ficancia y los intervalos de confianza; la comparación entre diferentes subgrupos se realizó con la prueba c2, y se determinó tiempo de conversión con análisis de Kaplan Meier. Resultados. Se vigilaron 1 617 trabajadores, 68 por ciento, mujeres y 32 por ciento, hombres. La edad promedio fue 26.9ñ7.6 (15-68) años. Del total, 30.5 por ciento eran enfermeras; 14.6 por ciento, médicos residentes, y 14.1 por ciento, internos. Un 65.8 por ciento provenía del Distrito Federal. El 71.6 por ciento tenía BCG, y 15.1 por ciento, PPD previo. El PPD al ingreso fue positivo en 39.6 por ciento de los casos; negativo, en el 48.3 por ciento, y sin lectura, en el 12.1 por ciento restante. Se aplicaron 483 refuerzos (booster) en aquellos inicialmente negativos, y se encontraron 49 positivos. Se vigiló la conversión a PPD+ por aplicaciones periódicas en 231 trabajadores, y se encontró dicha conversión en 100 de ellos (43.3 por ciento). El tiempo promedio para detectar la conversión fue de 22.8ñ12.4 meses. La tasa de conversión a los 12 meses fue de 20 por ciento. Únicamente 50 trabajadores (50 por ciento) recibieron y aceptaron profilaxis con isoniazida. Conclusiones. Un alto porcentaje de trabajadores son PPD+ al ingreso. Los refuerzos detectan 10 por ciento más de casos. La tasa de conversión enfatiza la necesidad de organizar estos programas en México.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Recursos Humanos em Hospital , Tuberculose Pulmonar/epidemiologia , Monitoramento Epidemiológico , Tuberculina , Teste TuberculínicoRESUMO
Aunque prevenible por vacunación, el tétanos aún tiene una alta mortalidad, sobre todo en países en desarrollo en donde la población no está protegida y la atención médica oportuna no está disponible. Presentamos un caso de tétanos en un paciente anciano con neumonía por broncoaspiración después de un ahogamiento. No se sospechó de ningún otro sitio de entrada con tanta relación temporal como la del incidente de broncoaspiración. La broncoaspiración de materia orgánica y heces fecales suministran tanto la fuente del agente causal como un ambiente polimicrobiano para el desarrollo de la enfermedad. Es bajo esas condiciones que proponemos este sitio de entrada inusual como la causa de tétanos en nuestro paciente. Se hace especial énfasis en la importancia de los programas de inmunización en adultos y sobre la manera en que incidentes como éste deben de ser tomados en cuenta para el cuidado de la población anciana
Assuntos
Humanos , Masculino , Idoso , Acidentes , Pneumonia Aspirativa/complicações , Tétano/transmissão , Poluição da ÁguaRESUMO
To study the immune response within the subarachnoid space in patients with neurocysticercosis, we measured the cerebrospinal fluid contents of immunoglobulins A, E, G, and M in 38 patients and the contents of the proinflammatory cytokines TNF-alpha, IL-1b, IL-6 and IFN-gamma in 17 patients. The same measurements were made in 30 neurological patients without inflammatory or immune-mediated disorders. Each immunoglobulin and cytokine, including the gender and age of the patient, was compared by multiple regression analysis with the CSF contents of cells, protein and ELISA for cysticercal antigens. A direct correlation was found of IgM with cell content (p<0.058) and with ELISA values (p<0.027); of age with protein content (p<0.006); of IL-6 with protein content (p<0.018) and of IL-1b with ELISA values (p<0.004). An inverse correlation was found of glucose with ELISA values (p<0.008). A complex function of the immune response within the subarachonid space was observed: mean values of IgG, IgM, IgE and interleukins 1b and 6 were increased, whereas values of IgA, TNF-alpha and IFN-gamma were similar to those of controls