RESUMEN
The aetiology of schizophrenia is multifactorial, and the identification of its risk factors are scarce and highly variable. A cross-sectional study was conducted to investigate the risk factors associated with schizophrenia among Malaysian sub-population. A total of 120 individuals diagnosed with schizophrenia (SZ) and 180 non-schizophrenic (NS) individuals participated in a questionnaire-based survey. Data of complete questionnaire responses obtained from 91 SZ and 120 NS participants were used in statistical analyses. Stool samples were obtained from the participants and screened for gut parasites and fungi using conventional polymerase chain reaction (PCR). The median age were 46 years (interquartile range (IQR) 37 to 60 years) and 35 years (IQR 24 to 47.75 years) for SZ and NS respectively. Multivariable binary logistic regression showed that the factors associated with increased risk of SZ were age, sex, unemployment, presence of other chronic ailment, smoking, and high dairy consumption per week. These factors, except sex, were positively associated with the severity of SZ. Breastfed at infancy as well as vitamin and supplement consumption showed a protective effect against SZ. After data clean-up, fungal or parasitic infections were found in 98% (39/42). of SZ participants and 6.1% (3/49) of NS participants. Our findings identified non-modifiable risk factors (age and sex) and modifiable lifestyle-related risk factors (unemployment, presence of other chronic ailment, smoking, and high dairy consumption per week) associated with SZ and implicate the need for medical attention in preventing fungal and parasitic infections in SZ.
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Micosis , Enfermedades Parasitarias , Esquizofrenia , Adulto , Humanos , Persona de Mediana Edad , Estudios Transversales , Enfermedades Parasitarias/complicaciones , Enfermedades Parasitarias/epidemiología , Factores de Riesgo , Esquizofrenia/diagnóstico , Esquizofrenia/epidemiología , Micosis/complicaciones , Micosis/epidemiologíaRESUMEN
BACKGROUND: Invasive fungal infections (IFIs) are a common infectious complication during the treatment of acute myeloid leukemia (AML), high-risk myelodysplastic syndrome (MDS) or post hematopoietic cell transplantation (HCT). For these patients, the National Comprehensive Cancer Network recommends posaconazole or voriconazole for IFI prophylaxis. In clinical practice, however, there has been increased use of isavuconazole due to favorable pharmacokinetic and pharmacodynamic parameters despite limited data for this indication. The comparative prophylactic efficacy of antifungals in this patient population has not been reported, and an analysis is warranted. METHODS: This retrospective, matched cohort, single-center study, included AML, MDS, or HCT patients who began treatment or underwent transplant between January 1, 2015 and July 31, 2021. Isavuconazole patients were matched 1:2 with patients receiving posaconazole or voriconazole prophylaxis. RESULTS: A total of 126 patients were included, 42 received isavuconazole, 81 received posaconazole, and three received voriconazole. The majority of patients were male receiving secondary IFI prophylaxis while receiving steroids for treatment of GVHD. The incidence of possible, probable or proven IFI was 16.7% in the isavuconazole group compared to 10.7% in the posaconazole and voriconazole group (OR 1.28, 95% CI -0.9-1.4; p = .67). Hepatotoxicity occurred in 16 total patients, 14 receiving posaconazole and two receiving isavuconazole. CONCLUSION: Patients who received isavuconazole prophylaxis during AML induction therapy or post-HCT experienced a similar incidence of breakthrough fungal infections compared to those who received posaconazole or voriconazole. These results suggest no difference in antifungal prophylactic efficacy; however larger prospective comparative studies are needed.
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Infecciones Fúngicas Invasoras , Leucemia Mieloide Aguda , Micosis , Humanos , Masculino , Femenino , Voriconazol/efectos adversos , Estudios Retrospectivos , Incidencia , Estudios Prospectivos , Micosis/epidemiología , Micosis/prevención & control , Micosis/tratamiento farmacológico , Antifúngicos/efectos adversos , Infecciones Fúngicas Invasoras/epidemiología , Infecciones Fúngicas Invasoras/prevención & control , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/tratamiento farmacológicoRESUMEN
Background: Diagnosis of co-infections with multiple pathogens among hospitalized coronavirus disease 2019 (COVID-19) patients can be jointly challenging and essential for appropriate treatment, shortening hospital stays and preventing antimicrobial resistance. This study proposes to investigate the burden of bacterial and fungal co-infections outcomes on COVID-19 patients. It is a single center cross-sectional study of hospitalized COVID-19 patients at Beit-Jala hospital in Palestine. Methods: The study included 321 hospitalized patients admitted to the ICU between June 2020 and March 2021 aged ≥20 years, with a confirmed diagnosis of COVID-19 via reverse transcriptase-polymerase chain reaction assay conducted on a nasopharyngeal swab. The patient's information was gathered using graded data forms from electronic medical reports. Results: The diagnosis of bacterial and fungal infection was proved through the patient's clinical presentation and positive blood or sputum culture results. All cases had received empirical antimicrobial therapy before the intensive care unit (ICU) admission, and different regimens during the ICU stay. The rate of bacterial co-infection was 51.1%, mainly from gram-negative isolates ( Enterobacter species and K.pneumoniae). The rate of fungal co-infection caused by A.fumigatus was 48.9%, and the mortality rate was 8.1%. However, it is unclear if it had been attributed to SARS-CoV-2 or coincidental. Conclusions: Bacterial and fungal co-infection is common among COVID-19 patients at the ICU in Palestine, but it is not obvious if these cases are attributed to SARS-CoV-2 or coincidental, because little data is available to compare it with the rates of secondary infection in local ICU departments before the pandemic. Comprehensively, those conclusions present data supporting a conservative antibiotic administration for severely unwell COVID-19 infected patients. Our examination regarding the impacts of employing antifungals to manage COVID-19 patients can work as a successful reference for future COVID-19 therapy.
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Infecciones Bacterianas , COVID-19 , Coinfección , Micosis , Árabes , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/epidemiología , COVID-19/epidemiología , Coinfección/epidemiología , Estudios Transversales , Hospitales , Humanos , Unidades de Cuidados Intensivos , Micosis/tratamiento farmacológico , Micosis/epidemiología , Micosis/microbiología , Estudios Retrospectivos , SARS-CoV-2RESUMEN
The past year has established the link between the COVID-19 pandemic and the global spread of severe fungal infections; thus, underscoring the critical need for rapid and realizable fungal disease diagnostics. While in recent years, health authorities, such as the Centers for Disease Control and Prevention, have reported the alarming emergence and spread of drug-resistant pathogenic fungi and warned against the devastating consequences, progress in the diagnosis and treatment of fungal infections is limited. Early diagnosis and patient-tailored therapy are established to be key in reducing morbidity and mortality associated with fungal (and cofungal) infections. As such, antifungal susceptibility testing (AFST) is crucial in revealing susceptibility or resistance of these pathogens and initiating correct antifungal therapy. Today, gold standard AFST methods require several days for completion, and thus this much delayed time for answer limits their clinical application. This review focuses on the advancements made in developing novel AFST techniques and discusses their implications in the context of the practiced clinical workflow. The aim of this work is to highlight the advantages and drawbacks of currently available methods and identify the main gaps hindering their progress toward clinical application.
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Antifúngicos/uso terapéutico , COVID-19/epidemiología , Micosis/diagnóstico , Micosis/tratamiento farmacológico , COVID-19/virología , Pruebas Diagnósticas de Rutina , Farmacorresistencia Fúngica , Humanos , Pruebas de Sensibilidad Microbiana , Micosis/epidemiología , Micosis/microbiología , Pandemias , SARS-CoV-2/aislamiento & purificaciónRESUMEN
Background: Pulmonary mycosis (PM) poses a great diagnostic challenge due to the lack of pathognomonic and radiological features, especially in the absence of mycology laboratory tests. This study was aimed to isolate, phenotypically identify, determine the prevalence of pulmonary fungal pathogens and antifungal susceptibility pattern of isolates of presumptive tuberculosis (PTB) patients attending Federal Teaching Hospital (FTH) Gombe, Nigeria. Methods: After ethical approval, three consecutive early morning sputa were collected from 216 participants with presumptive of PTB attending FTH Gombe, between May 2, 2017 and May 30, 2018. Samples were processed using standard mycological staining, microscopy, sugar biochemistry, and antifungal susceptibility test protocols. Sociodemographic variables and risk factors of pulmonary fungal infection were assessed through structured questionnaires. Pulmonary fungal infection was defined by the positive culture in at least two sputa. PTB was defined by Genexpert® nested polymerase chain reaction. Results: Of the 216 participants, 19.9% had PTB and 73.6% had pulmonary fungal pathogens. Among the isolated pulmonary fungal pathogens, Aspergillus fumigatus made the highest occurrence, while 6.5% had PTB-fungal co-infection. No significant association existed between the prevalence of PM with age and sex of participants (P < 0.05). Cigarette smoking (adjusted odds ratio [aOR] = 15.9 [95% confidence interval (CI): 0.9-268.8]), prolong antibiotic use (aOR = 77.9 [95% CI: 4.7-1283]) and possession of domestic pet (aOR = 77.9 [95% CI: 4.7-1283]) were significant risk factors of PM (P < 0.05). Penicillium citrinum, Mucor spp. and Aspergillus flavus are more susceptible to voriconazole, and Candida albicans was found to be more susceptible to Nystatin. Of the 159 fungal isolates, 92.5% were resistant to fluconazole. Conclusion: Findings from this study revealed high level pulmonary fungal pathogens, especially among PTB patients. A majority of fungal isolates were resistant to fluconazole. It's recommended that persons should do away with or minimize risk factors for pulmonary fungal pathogens identified in this study.
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Antifúngicos/uso terapéutico , Hongos/clasificación , Hongos/efectos de los fármacos , Enfermedades Pulmonares/microbiología , Micosis/epidemiología , Tuberculosis/epidemiología , Adolescente , Adulto , Coinfección/epidemiología , Coinfección/microbiología , Estudios Transversales , Femenino , Hongos/patogenicidad , Humanos , Enfermedades Pulmonares/tratamiento farmacológico , Enfermedades Pulmonares/epidemiología , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Micosis/tratamiento farmacológico , Micosis/microbiología , Nigeria/epidemiología , Prevalencia , Factores de Riesgo , Esputo/microbiología , Tuberculosis/diagnóstico , Tuberculosis/microbiología , Adulto JovenRESUMEN
BACKGROUND: To explore and describe the current literature surrounding bacterial/fungal coinfection in patients with coronavirus infection. METHODS: MEDLINE, EMBASE, and Web of Science were searched using broad-based search criteria relating to coronavirus and bacterial coinfection. Articles presenting clinical data for patients with coronavirus infection (defined as SARS-1, MERS, SARS-CoV-2, and other coronavirus) and bacterial/fungal coinfection reported in English, Mandarin, or Italian were included. Data describing bacterial/fungal coinfections, treatments, and outcomes were extracted. Secondary analysis of studies reporting antimicrobial prescribing in SARS-CoV-2 even in absence of coinfection was performed. RESULTS: 1007 abstracts were identified. Eighteen full texts reporting bacterial/fungal coinfection were included. Most studies did not identify or report bacterial/fungal coinfection (85/140; 61%). Nine of 18 (50%) studies reported on COVID-19, 5/18 (28%) on SARS-1, 1/18 (6%) on MERS, and 3/18 (17%) on other coronaviruses. For COVID-19, 62/806 (8%) patients were reported as experiencing bacterial/fungal coinfection during hospital admission. Secondary analysis demonstrated wide use of broad-spectrum antibacterials, despite a paucity of evidence for bacterial coinfection. On secondary analysis, 1450/2010 (72%) of patients reported received antimicrobial therapy. No antimicrobial stewardship interventions were described. For non-COVID-19 cases, bacterial/fungal coinfection was reported in 89/815 (11%) of patients. Broad-spectrum antibiotic use was reported. CONCLUSIONS: Despite frequent prescription of broad-spectrum empirical antimicrobials in patients with coronavirus-associated respiratory infections, there is a paucity of data to support the association with respiratory bacterial/fungal coinfection. Generation of prospective evidence to support development of antimicrobial policy and appropriate stewardship interventions specific for the COVID-19 pandemic is urgently required.
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Antiinfecciosos/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Coinfección/tratamiento farmacológico , SARS-CoV-2/efectos de los fármacos , Programas de Optimización del Uso de los Antimicrobianos , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/epidemiología , Infecciones Bacterianas/microbiología , COVID-19/epidemiología , COVID-19/microbiología , Coinfección/epidemiología , Coinfección/microbiología , Farmacorresistencia Microbiana , Humanos , Micosis/tratamiento farmacológico , Micosis/epidemiología , Micosis/microbiologíaRESUMEN
BACKGROUND: The new Rasamsonia spp. complex can develop invasive infection in immunosuppression or chronic pulmonary disease. It has potential to be misidentified as other genera due to morphological similarities. Nowadays, there is a gap of knowledge on this fungi. OBJECTIVES: To provide knowledge base of risk factors and therapeutic decisions in invasive Rasamsonia spp. complex infection. PATIENTS/METHODS: Cases of invasive infection due to Rasamsonia spp. (formerly Geosmithia/Penicillium spp.) from FungiScope® registry and all reported cases from a literature were included. RESULTS: We identified 23 invasive infections due to Rasamsonia spp., six (26.1%) in the FungiScope® registry. Main risk factors were chronic granulomatous disease (n = 12, 52.2%), immunosuppressive treatment (n = 10, 43.5%), haematopoietic stem cell transplantation (n = 7, 30.4%), graft-versus-host disease and major surgery (n = 4, 17.4%, each). Predominantly affected organs were the lungs (n = 21, 91.3%), disease disseminated in seven cases (30.4%). Fungal misidentification occurred in 47.8% (n = 11), and sequencing was used in 69.6% of the patients (n = 16) to diagnose. Breakthrough infection occurred in 13 patients (56.5%). All patients received antifungal treatment, mostly posaconazole (n = 11), caspofungin (n = 10) or voriconazole (n = 9). Combination therapy was administered in 13 patients (56.5%). Susceptibility testing showed high minimum inhibitory concentrations for azoles and amphotericin B, but not for echinocandins. No preferable treatment influencing favourable outcome was identified. Overall mortality was 39% (n = 9). CONCLUSION: Rasamsonia spp. are emerging fungi causing life-threatening infections, especially in immunocompromised and critically ill patients. Mortality is high. Treatment is challenging and clinicians dealing with this patient population should become aware of this infection constituting a medical emergency.
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Antifúngicos/uso terapéutico , Enfermedades Transmisibles Emergentes/epidemiología , Eurotiales/patogenicidad , Infecciones Fúngicas Invasoras/epidemiología , Micosis/epidemiología , Adolescente , Adulto , Antifúngicos/farmacología , Canadá/epidemiología , Enfermedades Transmisibles Emergentes/tratamiento farmacológico , Enfermedades Transmisibles Emergentes/microbiología , Enfermedades Transmisibles Emergentes/mortalidad , Tos , Disnea , Europa (Continente)/epidemiología , Eurotiales/efectos de los fármacos , Femenino , Enfermedades Hematológicas/complicaciones , Humanos , Huésped Inmunocomprometido , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Infecciones Fúngicas Invasoras/microbiología , Infecciones Fúngicas Invasoras/mortalidad , Japón/epidemiología , Enfermedades Pulmonares Fúngicas/tratamiento farmacológico , Enfermedades Pulmonares Fúngicas/epidemiología , Enfermedades Pulmonares Fúngicas/microbiología , Enfermedades Pulmonares Fúngicas/mortalidad , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Micosis/tratamiento farmacológico , Micosis/microbiología , Micosis/mortalidad , Sistema de Registros , Factores de Riesgo , Estados Unidos/epidemiología , Adulto JovenRESUMEN
BACKGROUND: In recent years, there has been a significant increase in the incidence of fungal infections attributed to Candida species worldwide, with a major shift toward non-albicans Candida (NAC). In this study, we have described the distribution of Candida species among different hospital departments and calculated the antifungal consumption in our facility. We also correlated the consumption of certain antifungals and the prevalence of specific Candida species. METHODS: This was a retrospective review of all the Candida isolates recovered from the computerised microbiology laboratory database of Makassed General Hospital, a tertiary care centre in Beirut, Lebanon, between January 2010 and December 2015. Data on antifungal consumption between January 2008 and December 2015 were extracted from the hospital pharmacy electronic database. We used Spearman's coefficient to find a correlation between Candida species distribution and antifungal consumption. RESULTS: Between 2008 and 2015, we observed that the highest antifungal consumption was in the haematology/oncology department (days of therapy/1000 patient days = 348.12 ± 85.41), and the lowest was in the obstetrics/gynaecology department (1.36 ± 0.47). In general, the difference in antifungal consumption among various departments was statistically significant (P < 0.0001). Overall, azoles were the most common first-line antifungals in our hospital. Echinocandins and amphotericin B were mostly prescribed in the haematology/oncology department. As for Candida species distribution, a total of 1377 non-duplicate isolates were identified between 2010 and 2015. A non-homologous distribution of albicans vs. non-albicans was noted among the different departments (P = 0.02). The most commonly isolated NAC was Candida glabrata, representing 14% of total Candida species and 59% of NAC. Candida famata (9% of NAC), Candida parapsilosis (3.6% of NAC) and Candida krusei (3% of NAC) were recovered unequally from the different departments. The total antifungal consumption correlated positively with the emergence of NAC. The use of azoles correlated positively with Candida glabrata, while amphotericin B formulations correlated negatively with it. None of these correlations reached statistical significance. CONCLUSION: Different Candida species were unequally distributed among different hospital departments, and this correlated with consumption of antifungals in respective departments, highlighting the need for antifungal stewardship.
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Antifúngicos/uso terapéutico , Candida/clasificación , Candidiasis , Departamentos de Hospitales/estadística & datos numéricos , Micosis , Centros Médicos Académicos , Adulto , Anfotericina B/uso terapéutico , Candida/aislamiento & purificación , Candida albicans/aislamiento & purificación , Candida glabrata/aislamiento & purificación , Candidiasis/tratamiento farmacológico , Candidiasis/epidemiología , Candidiasis/microbiología , Niño , Farmacorresistencia Fúngica , Equinocandinas/uso terapéutico , Femenino , Humanos , Incidencia , Líbano/epidemiología , Masculino , Pruebas de Sensibilidad Microbiana , Micosis/tratamiento farmacológico , Micosis/epidemiología , Micosis/microbiología , Estudios RetrospectivosRESUMEN
Daikenchuto (DKT), a Japanese Kampo medicine, had been reported to increase small intestinal blood flow after liver resection. The aim of this study was to evaluate the effects of early enteral feeding of DKT on portal venous flow and early bowel movement after living donor liver transplantation (LDLT) in an attempt to clarify whether these effects on bowel motility can prevent bacterial and/or fungal translocation. MATERIALS AND METHODS: Our prospective study included the consecutive 16 LDLT recipients at Mie University Hospital between June 2006 and September 2009. Sixteen patients were divided into the 2 groups according to enteral feeding starting postoperative day (POD) 1: 8 patients in DKT (15 g/d) administration (DKT group, for 1 week) and 8 patients in tepid water administration (non-DKT group, for 1 week). Portal venous flow, portal venous pressure, presence of fungal infection (serum level of ß-D-glucan and fungal polymerase chain reaction assay), time to first food intake, and time to first defecation were serially examined. RESULTS: Portal venous flow (mean [SD] velocity) was significantly increased in DKT group compared with non-DKT group: 47.5 (12.9) vs 31.8 (15.4) (P = .04) on POD 1, 46.8 (11.5) vs 28.8 (12.5) (P = .03) on POD 3, and 42.3 (17.2) vs 25.2 (9.0) (P = .05) on POD 5. However, mean (SD) portal venous pressures did not significantly change between the 2 groups. Between the 2 groups (DKT vs non-DKT), the day of first oral intake was not significantly different: 6.9 (2.5) vs 11.3 (8.7) (P = .061), but the mean (SD) day of first defecation was significantly shorter in the DKT group: 3.9 (1.1) vs 5.5 (2.6) (P = .02). Although fungal polymerase chain reaction assay was not significantly different between the 2 groups (4 vs 4 positive cases), the mean (SD) serum levels of ß-D-glucan were significantly lower in the DKT group than in the non-DKT group: 9.0 (7.4) vs 18.4 (15.9) pg/mL (P = .04). CONCLUSION: Early enteral feeding of DKT after LDLT increased portal vein blood flow without increasing portal vein pressure and stimulated early bowel movement, which in turn might prevent fungal translocation.
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Defecación/efectos de los fármacos , Motilidad Gastrointestinal/efectos de los fármacos , Trasplante de Hígado , Extractos Vegetales/administración & dosificación , Adulto , Anciano , Nutrición Enteral/métodos , Femenino , Humanos , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/métodos , Donadores Vivos , Masculino , Persona de Mediana Edad , Micosis/epidemiología , Micosis/etiología , Panax , Presión Portal/efectos de los fármacos , Vena Porta/fisiología , Periodo Posoperatorio , Estudios Prospectivos , Adulto Joven , Zanthoxylum , ZingiberaceaeRESUMEN
Fungal infections are a major cause of morbidity and mortality despite the latest developments of diagnostic tools and therapeutic options. Early initiation of the appropriate antifungal therapy has been demonstrated to have a direct impact on the patient's outcome. Antifungal susceptibility testing methods are available to detect antifungal resistance and to determine the best treatment for a specific fungus. American and European standards have been developed, as well as equivalent commercial systems, which are more appropriate for clinical laboratories. These studies have allowed the development of interpretative breakpoints against the most frequent agents of fungal infections in the world. Surveillance of antifungal susceptibility patterns can provide the local drug resistance data to the clinicians, which can further aid better management of patients. Antifungal susceptibility tests have become essential tools to identify resistance to antifungals, to know the local and global disease epidemiology and to guide the treatment of fungal diseases. The distribution of species and the prevalence of antifungal resistance in fungi isolates varied among different areas. Here we summarize the epidemiology of antifungal susceptibility pattern of different fungal species.
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Antifúngicos/uso terapéutico , Farmacorresistencia Fúngica , Micosis/tratamiento farmacológico , Micosis/epidemiología , Antifúngicos/farmacología , Humanos , Pruebas de Sensibilidad MicrobianaRESUMEN
Airborne microorganisms occur ubiquitously in the ambient air. Besides allergic and irritative-toxic effects, they can cause infections after inhalation. Occupational studies have shown that an increased incidence of respiratory diseases is found in adequately exposed workers. In addition to respiratory diseases, severe systemic infections can also occur in particular cases, such as in the case of a hantavirus infection that is recognized as an occupational disease. In studies from environmental medicine, respiratory diseases have also been observed in residents living in the vicinity of livestock facilities and evaporative cooling towers. In the latter case, an infection risk may be caused by inhalation of legionella-contaminated aerosol from the exhaust air of such systems.Currently, there are no health-related exposure limits for airborne microorganisms released from such facilities. Environmental risk assessment can be carried out on the basis of the guideline VDI 4250 part 1, which relies on an excess of natural background concentration by facility-specific emissions. For the approval practice, the LAI-Leitfaden Bioaerosole is a uniform, standardized method for the determination and assessment of bioaerosol exposure.In indoor spaces, only a few mold types, such as Aspergillus fumigatus are able to trigger infections by local or systemic infection of the human organism. In particular, persons with an immune deficiency or allergies must be informed about the risks of mold exposure in indoor air. In general, mold growth in indoor spaces is a hygienic problem and must not be accepted as a matter of principle.
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Microbiología del Aire , Contaminación del Aire/estadística & datos numéricos , Infecciones Bacterianas/epidemiología , Infecciones Bacterianas/microbiología , Exposición por Inhalación/estadística & datos numéricos , Micosis/epidemiología , Micosis/microbiología , Causalidad , Monitoreo del Ambiente/métodos , Medicina Basada en la Evidencia , Humanos , Prevalencia , Factores de RiesgoRESUMEN
The emergence and spread of antimicrobial-resistant bacterial, viral, and fungal pathogens for which diminishing treatment options are available is of major global concern. New viral respiratory tract infections with epidemic potential, such as severe acute respiratory syndrome, swine-origin influenza A H1N1, and Middle East respiratory syndrome coronavirus infection, require development of new antiviral agents. The substantial rise in the global numbers of patients with respiratory tract infections caused by pan-antibiotic-resistant Gram-positive and Gram-negative bacteria, multidrug-resistant Mycobacterium tuberculosis, and multiazole-resistant fungi has focused attention on investments into development of new drugs and treatment regimens. Successful treatment outcomes for patients with respiratory tract infections across all health-care settings will necessitate rapid, precise diagnosis and more effective and pathogen-specific therapies. This Series paper describes the development and use of new antimicrobial agents and immune-based and host-directed therapies for a range of conventional and emerging viral, bacterial, and fungal causes of respiratory tract infections.
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Infecciones Bacterianas/epidemiología , Farmacorresistencia Bacteriana , Farmacorresistencia Fúngica , Farmacorresistencia Viral , Micosis/epidemiología , Infecciones del Sistema Respiratorio/epidemiología , Virosis/epidemiología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Antivirales/farmacología , Antivirales/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/microbiología , Terapia Biológica/métodos , Terapia Biológica/tendencias , Descubrimiento de Drogas/tendencias , Quimioterapia/métodos , Quimioterapia/tendencias , Humanos , Micosis/tratamiento farmacológico , Micosis/microbiología , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/microbiología , Infecciones del Sistema Respiratorio/virología , Resultado del Tratamiento , Virosis/tratamiento farmacológico , Virosis/virologíaRESUMEN
With a growing understanding of the pathogenesis and immunological basis of psoriasis, the medical community has seen the development of more focused biological treatment options for patients suffering from the disease, which are beginning to revolutionize the treatment of psoriasis. It is already well known that certain biologics are associated with an increased risk of reactivating tuberculosis in patients with latent disease, however, with increasing use of biologic agents across indications, there has also been a rise in reports of associated deep fungal infections. The mechanism of action of these biologic anti-psoriatic therapies allows physicians to address the underlying cause of patients' symptoms. The question though, is whether this same therapeutic mechanism may predispose patients to serious infections, including deep fungal infections.
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Terapia Biológica , Factores Inmunológicos/uso terapéutico , Micosis/epidemiología , Psoriasis/terapia , Humanos , Factores Inmunológicos/efectos adversos , Incidencia , Micosis/etiología , Pronóstico , Factores de RiesgoRESUMEN
Mortality linked to invasive fungal diseases remains very high despite the availability of novel antifungals and new therapeutic strategies. Candida albicans and Aspergillus fumigatus account for most invasive mycosis produced by yeast or moulds, respectively. Other Candida non-albicans are increasingly being reported and newly emerging, as well as cryptic, filamentous fungi often cause disseminated infections in immunocompromised hosts. Management of invasive fungal infections is becoming a challenge as emerging fungal pathogens generally show poor response to many antifungals. The ability of reference antifungal susceptibility testing methods to detect emerging resistance patterns, together with the molecular characterization of antifungal resistance mechanisms, are providing useful information to optimize the effectiveness of antifungal therapy. The current status of antifungal resistance epidemiology with special emphasis on the molecular resistant mechanisms that have been described in the main pathogenic fungal species are reviewed.
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Antifúngicos/uso terapéutico , Farmacorresistencia Fúngica , Micosis/tratamiento farmacológico , Humanos , Pruebas de Sensibilidad Microbiana , Micosis/epidemiologíaRESUMEN
OBJECTIVE: Biologic agents are increasingly used to treat patients with rheumatoid arthritis (RA). We aimed to review their association with opportunistic infections (OIs), including fungal, viral (with a focus on herpesvirus-related infections), tuberculosis and other mycobacterial infections. METHODS: We searched PubMed and EMBASE through June 24, 2013, and complemented the search with the reference lists of eligible articles. The analysis included randomized trials on RA that compared any approved biologic agent with controls and reported the risk of OIs. RESULTS: A total of 70 trials that included 32 504 patients (21 916 patients receiving biologic agents and 10 588 receiving placebo) were deemed eligible. Biologic agents increased the risk of OIs (pooled Peto odds ratio [OR], 1.79; 95% confidence interval [CI], 1.17-2.74; I(2) = 3%), resulting in 1.7 excess infections per 1000 patients treated (number needed to harm, 582). A significant risk was noted for mycobacterial (OR, 3.73; 95% CI, 1.72-8.13; I(2) = 0), and viral (OR, 1.91; 95% CI, 1.02-3.58; I(2) = 0) infections. Interestingly, no significant differences were found for invasive and superficial fungal infections (1.31; 95% CI, .46-3.72), invasive fungal infections (2.85; .68-11.91), P. jirovecii pneumonia (1.77; .42-7.47), varicella-zoster virus (1.51; .71-3.22), as well as overall mortality attributed to OIs (1.91; .29-12.64). CONCLUSIONS: Among patients with RA, biologic agents are associated with a small but significant risk of specific OIs. This increase is associated with mycobacterial diseases and does not seem to affect overall mortality. Because OIs are a relatively rare complication of biologic agents, large registries are needed to identify the exact effect in different OIs and to compare the different biologic agents.
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Antirreumáticos/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Terapia Biológica/efectos adversos , Infecciones por Mycobacterium/epidemiología , Micosis/epidemiología , Infecciones Oportunistas/epidemiología , Virosis/epidemiología , Anticuerpos Monoclonales/efectos adversos , Humanos , Infecciones Oportunistas/mortalidad , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de RiesgoRESUMEN
BACKGROUND: Intestinal transplantation is a potential option for patients with short gut syndrome (SGS), and infection is common in the postoperative period. The aim of our study was to identify the incidence and characteristics of bacterial and fungal infections of adult small bowel or multivisceral (SB/MV) transplantation recipients in the 30-day postoperative period. METHODS: This retrospective chart review assessed the incidence and characteristics of bacterial and fungal infections in patients who underwent SB/MV transplant at our center between April 2004 and November 2008. Patient data were retrieved from computerized databases, flow-charts, and medical records. RESULTS: A total of 40 adult patients with a mean age of 38.7 ± 13.4 years received transplants during this period: 27 patients received isolated SB, 12 received MV, and 1 received SB and kidney. Our immunosuppressive regimen included basiliximab for induction, and tacrolimus, sirolimus, and methylprednisolone for maintenance therapy. The most common indications for transplant were SGS, intestinal ischemia, Crohn's disease, trauma, motility disorders, and Gardner's syndrome. We report a 30-day postoperative infection rate of 57.5% and mean time to first infection of 10.78 ± 8.99 days. A total of 36 infections were documented in 23 patients. Of patients who developed infections, 56.5% developed 1 infection, 30.4% developed 2 infections, and 13% developed 3 infections. The most common site of infection was the abdomen, followed by blood, urine, lung, and wound infection. The isolates were gram-negative bacteria in 49.3%, gram-positive bacteria in 39.4%, and 11.3% were fungi. The most common organisms were Pseudomonas (19%), Enterococcus (15%), and Escherichia coli (13%). Overall, 47% of infections were due to drug-resistant pathogens; 31% of E. coli and Klebsiella species were extended-spectrum beta-lactamase-producing organisms, 36% of Pseudomonas was multidrug resistant (MDR), 75% of Enterococcus was vancomycin resistant, and 100% of Staphylococcus aureus was methicillin resistant. CONCLUSION: These findings demonstrate that bacterial and fungal infections remain an important complication in SB/MV transplant recipients within the early postoperative period. Infections due to MDR organisms have emerged as an important clinical problem in this patient population.
Asunto(s)
Antiinfecciosos/uso terapéutico , Infecciones Bacterianas/epidemiología , Micosis/epidemiología , Trasplante de Órganos/efectos adversos , Complicaciones Posoperatorias/epidemiología , Adolescente , Adulto , Bacterias/efectos de los fármacos , Bacterias/aislamiento & purificación , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/microbiología , Femenino , Hongos/efectos de los fármacos , Hongos/aislamiento & purificación , Humanos , Huésped Inmunocomprometido , Incidencia , Intestino Delgado/trasplante , Estimación de Kaplan-Meier , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Micosis/tratamiento farmacológico , Micosis/microbiología , Complicaciones Posoperatorias/tratamiento farmacológico , Complicaciones Posoperatorias/microbiología , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Invasive fungal infections (IFIs) present a major issue in clinical practice, due to their high morbidity and mortality rates. In a pivotal multi-centre, randomized clinical trial, posaconazole prophylaxis prevented IFIs more effectively than did either fluconazole or itraconazole, and improved overall survival. OBJECTIVE: The aim of this study was to perform an economic evaluation of the aforementioned therapeutic strategies for IFI prophylaxis in neutropenic patients, in the Greek healthcare setting. METHOD: A decision analytic model was developed, which described the course of neutropenic patients under posaconazole or standard azole (fluconazole or itraconazole) treatment. Effectiveness data for each treatment regimen were derived from published results of a pivotal, multi-centre, randomized clinical trial. Cost and healthcare resources utilization data depict Greek clinical practice and are derived from official Greek sources, from a third party payer perspective. RESULTS: Prophylaxis with posaconazole resulted in fewer IFIs (0.05 vs 0.11 per patient) compared to treatment with fluconazole or itraconazole, during the first 100 days from initiation of prophylaxis treatment. The cost per avoided IFI with posaconazole was 6455, while the incremental cost per life year gained (LYG) was estimated at 24,196. Extensive sensitivity analyses corroborated the base-case results. Possible limitations of the study are the exclusion of indirect and outpatient costs from the analysis and the inherent uncertainty with regards to the transferability of the clinical efficacy results of the clinical trial to the Greek healthcare setting. CONCLUSIONS: The utilization of posaconazole for prophylaxis of IFIs neutropenic patients is a therapeutic strategy that provides superior clinical efficacy, while being cost-effective compared to alternative therapies.
Asunto(s)
Antifúngicos/economía , Fluconazol/economía , Huésped Inmunocomprometido , Itraconazol/economía , Micosis/prevención & control , Triazoles/economía , Antifúngicos/uso terapéutico , Análisis Costo-Beneficio , Técnicas de Apoyo para la Decisión , Fluconazol/uso terapéutico , Grecia/epidemiología , Gastos en Salud , Humanos , Itraconazol/uso terapéutico , Modelos Económicos , Micosis/epidemiología , Neutropenia/epidemiología , Triazoles/uso terapéuticoRESUMEN
Invasive fungal infections (IFIs) are associated with a high mortality rate for liver transplantation (LT) recipients. To study the incidence of and risk factors for IFIs in LT recipients and the associated mortality rates, we retrospectively reviewed the records of first-time deceased donor LT recipients (January 2003 to December 2007). The incidence of IFIs was 12%. Non-albicans Candida species accounted for 55% of IFIs; 50% of these IFIs were Candida parapsilosis. Only 43% of Candida isolates were fluconazole-susceptible (minimum inhibitory concentration ≤ 8 µ/mL). All C. parapsilosis isolates were fluconazole-resistant, and this coincided with a surge of these isolates during a peak period of LT. Factors associated with IFIs included a creatinine level > 2 mg/mL [hazard ratio (OR) = 2.4, 95% confidence interval (CI) = 1.2-5.0, P = 0.01], a Model for End-Stage Liver Disease score > 25 (OR = 2.4, 95% CI = 1.2-4.9, P = 0.02), pretransplant fungal colonization (OR = 7.0, 95% CI = 3.2-15.3, P < 0.001), and a daily prophylactic fluconazole dosage < 200 mg (OR = 2.8, 95% CI = 1.1-7.4, P = 0.03). According to a multivariate analysis, only pretransplant fungal colonization was associated with IFIs (OR = 7.8, 95% CI = 3.9-16.2, P < 0.001). The 1-year patient survival rates with and without IFIs were 41% and 80%, respectively, and the survival rates with C. parapsilosis, other non-albicans Candida, and Candida albicans IFIs were 28%, 50%, and 75%, respectively. In conclusion, IFIs after LT (especially non-albicans Candida species and fluconazole-resistant C. parapsilosis) were associated with reduced survival. The risk factors highlight the importance of pretransplant risk assessments. The identification of pretransplant fungal colonization may allow for risk modifications before or at the time of LT. Additionally, the number of LT procedures and prophylactic strategies may affect institutional outbreaks of resistant Candida strains.
Asunto(s)
Antifúngicos/uso terapéutico , Candida , Farmacorresistencia Fúngica , Fluconazol/uso terapéutico , Trasplante de Hígado/efectos adversos , Micosis/epidemiología , Micosis/microbiología , Adolescente , Adulto , Anciano , Candida/clasificación , Candida/efectos de los fármacos , Candida/aislamiento & purificación , Distribución de Chi-Cuadrado , Femenino , Humanos , Incidencia , Estimación de Kaplan-Meier , Trasplante de Hígado/mortalidad , Modelos Logísticos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Minnesota/epidemiología , Análisis Multivariante , Micosis/tratamiento farmacológico , Micosis/mortalidad , Oportunidad Relativa , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Adulto JovenRESUMEN
The invasive fungal infections (IFIs) have increased in critically ill patients in recent years and are a serious complication that determine the evolution and prognosis of critically ill patients, especially invasive candidiasis (IC)and candidemia. Fortunately, treatment options for these infections have increased and there is a large arsenal of antifungal agents. This review of the literature, using PubMed and Cochrane databases, assesses the situation of the IFIs in critically ill patients and discusses the role of micafungin in this context. The broader spectrum of this candin, which gets the antifungal effect with lower MICs and that translates into greater clinical efficacy with a lower rate of adverse effects and easier to use, with proven cost-effectiveness compared with other antifungal, position micafungin as a useful therapeutic option for the management of invasive candidiasis / candidemia in critically ill patients.
Asunto(s)
Antifúngicos/uso terapéutico , Enfermedad Crítica , Equinocandinas/uso terapéutico , Lipopéptidos/uso terapéutico , Micosis/tratamiento farmacológico , Candidiasis/tratamiento farmacológico , Candidiasis/microbiología , Hongos/efectos de los fármacos , Humanos , Micafungina , Pruebas de Sensibilidad Microbiana , Micosis/epidemiología , PronósticoRESUMEN
UNLABELLED: Yeasts occur as part of the normal human microbiota. Nevertheless, some species are opportunistic, affecting immunocompromised patients such as those undergoing oncologic treatment. OBJECTIVE: To detect the presence of yeasts in patients suffering from head and neck cancer who are receiving radiation therapy and display lesions in the oral cavity, compatible with candidiasis; and to evaluate the antifungal susceptibility of the isolates recovered. METHODS: Sixty samples from patients were obtained by swabbing the oral mucosa. Identification of isolates were performed by classical taxonomic, morphological and biochemical methods as well as by using commercial identification kits. Susceptibility to antifungal drugs was determined by the agar diffusion method with Neosensitabs(®) disks. RESULTS: Forty-six samples (77%) yielded positive findings, and species recovered were: Candida albicans (22 isolates), Candida tropicalis (13 isolates), Candida parapsilosis (six strains), Candida krusei (three strains), Candida dubliniensis and Saccharomyces cerevisiae (one each). All strains were susceptible to itraconazole, clotrimazole, voriconazole, nystatin and amphotericin B. On the other hand, 65% of strains were miconazole-susceptible while 35%, showed intermediate susceptibility. With regard to ketoconazole, only three strains (7%) corresponding to C. albicans (one isolate) and C. krusei (two isolates) displayed intermediate susceptibility. Only C. krusei strains were resistant to fluconazole while all the other species were susceptible. Eventually, only six isolates (13%) were susceptible to terbinafine while the remaining strains were resistant in vitro. CONCLUSION: Early detection of etiological agents causing lesions, as well as the evaluation of their susceptibility to commonly used drugs, are crucial in order to choose the appropriate treatment that will minimize complications while improving the quality of patients' lives.