RESUMEN
BACKGROUND: Conidiobolus spp. (mainly C. coronatus) are the causal agents of rhino-facial conidiobolomycosis, a limited soft tissue infection, which is essentially observed in immunocompetent individuals from tropical areas. Rare cases of invasive conidiobolomycosis due to C. coronatus or other species (C.incongruus, C.lamprauges) have been reported in immunocompromised patients. We report here the first case of invasive pulmonary fungal infection due to Conidiobolus pachyzygosporus in a Swiss patient with onco-haematologic malignancy. CASE PRESENTATION: A 71 year-old female was admitted in a Swiss hospital for induction chemotherapy of acute myeloid leukemia. A chest CT performed during the neutropenic phase identified three well-circumscribed lung lesions consistent with invasive fungal infection, along with a positive 1,3-beta-d-glucan assay in serum. A transbronchial biopsy of the lung lesions revealed large occasionally septate hyphae. A Conidiobolus spp. was detected by direct 18S rDNA in the tissue biopsy and subsequently identified at species level as C. pachyzygosporus by 28S rDNA sequencing. The infection was cured after isavuconazole therapy, recovery of the immune system and surgical resection of lung lesions. CONCLUSIONS: This is the first description of C. pachyzygosporus as human pathogen and second case report of invasive conidiobolomycosis from a European country.
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Conidiobolus/genética , Leucemia Mieloide Aguda/complicaciones , Enfermedades Pulmonares Fúngicas/complicaciones , Enfermedades Pulmonares Fúngicas/diagnóstico , Cigomicosis/complicaciones , Cigomicosis/diagnóstico , Anciano , Antifúngicos/uso terapéutico , Biopsia , Conidiobolus/aislamiento & purificación , ADN de Hongos/genética , ADN Ribosómico/genética , Femenino , Humanos , Hifa/aislamiento & purificación , Huésped Inmunocomprometido , Enfermedades Pulmonares Fúngicas/tratamiento farmacológico , Enfermedades Pulmonares Fúngicas/patología , Nitrilos/uso terapéutico , Piridinas/uso terapéutico , Suiza , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Triazoles/uso terapéutico , Cigomicosis/tratamiento farmacológico , Cigomicosis/patologíaRESUMEN
Metabolic syndrome after transplantation is a major concern following solid organ transplantation (SOT). The CREB-regulated transcription co-activator 2 (CRTC2) regulates glucose metabolism. The effect of CRTC2 polymorphisms on new-onset diabetes after transplantation (NODAT) was investigated in a discovery sample of SOT recipients (n1=197). Positive results were tested for replication in two samples from the Swiss Transplant Cohort Study (STCS, n2=1294 and n3=759). Obesity and other metabolic traits were also tested. Associations with metabolic traits in population-based samples (n4=46'186, n5=123'865, n6>100,000) were finally analyzed. In the discovery sample, CRTC2 rs8450-AA genotype was associated with NODAT, fasting blood glucose and body mass index (Pcorrected<0.05). CRTC2 rs8450-AA genotype was associated with NODAT in the second STCS replication sample (odd ratio (OR)=2.01, P=0.04). In the combined STCS replication samples, the effect of rs8450-AA genotype on NODAT was observed in patients having received SOT from a deceased donor and treated with tacrolimus (n=395, OR=2.08, P=0.02) and in non-kidney transplant recipients (OR=2.09, P=0.02). Moreover, rs8450-AA genotype was associated with overweight or obesity (n=1215, OR=1.56, P=0.02), new-onset hyperlipidemia (n=1007, OR=1.76, P=0.007), and lower high-density lipoprotein-cholesterol (n=1214, ß=-0.08, P=0.001). In the population-based samples, a proxy of rs8450G>A was significantly associated with several metabolic abnormalities. CRTC2 rs8450G>A appears to have an important role in the high prevalence of metabolic traits observed in patients with SOT. A weak association with metabolic traits was also observed in the population-based samples.
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Síndrome Metabólico/epidemiología , Síndrome Metabólico/genética , Trasplante de Órganos/efectos adversos , Polimorfismo de Nucleótido Simple , Factores de Transcripción/genética , Diabetes Mellitus/epidemiología , Diabetes Mellitus/genética , Dislipidemias/epidemiología , Dislipidemias/genética , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Heterocigoto , Homocigoto , Humanos , Incidencia , Modelos Lineales , Modelos Logísticos , Síndrome Metabólico/diagnóstico , Análisis Multivariante , Obesidad/epidemiología , Obesidad/genética , Oportunidad Relativa , Fenotipo , Prevalencia , Medición de Riesgo , Factores de Riesgo , Suiza/epidemiología , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVE: The natural course of chronic hepatitis C varies widely. To improve the profiling of patients at risk of developing advanced liver disease, we assessed the relative contribution of factors for liver fibrosis progression in hepatitis C. DESIGN: We analysed 1461 patients with chronic hepatitis C with an estimated date of infection and at least one liver biopsy. Risk factors for accelerated fibrosis progression rate (FPR), defined as ≥ 0.13 Metavir fibrosis units per year, were identified by logistic regression. Examined factors included age at infection, sex, route of infection, HCV genotype, body mass index (BMI), significant alcohol drinking (≥ 20 g/day for ≥ 5 years), HIV coinfection and diabetes. In a subgroup of 575 patients, we assessed the impact of single nucleotide polymorphisms previously associated with fibrosis progression in genome-wide association studies. Results were expressed as attributable fraction (AF) of risk for accelerated FPR. RESULTS: Age at infection (AF 28.7%), sex (AF 8.2%), route of infection (AF 16.5%) and HCV genotype (AF 7.9%) contributed to accelerated FPR in the Swiss Hepatitis C Cohort Study, whereas significant alcohol drinking, anti-HIV, diabetes and BMI did not. In genotyped patients, variants at rs9380516 (TULP1), rs738409 (PNPLA3), rs4374383 (MERTK) (AF 19.2%) and rs910049 (major histocompatibility complex region) significantly added to the risk of accelerated FPR. Results were replicated in three additional independent cohorts, and a meta-analysis confirmed the role of age at infection, sex, route of infection, HCV genotype, rs738409, rs4374383 and rs910049 in accelerating FPR. CONCLUSIONS: Most factors accelerating liver fibrosis progression in chronic hepatitis C are unmodifiable.
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Hepacivirus/genética , Hepatitis C Crónica/complicaciones , Cirrosis Hepática/etiología , Polimorfismo de Nucleótido Simple , ARN Viral/análisis , Medición de Riesgo/métodos , Biopsia , Progresión de la Enfermedad , Femenino , Estudio de Asociación del Genoma Completo , Hepatitis C Crónica/virología , Humanos , Incidencia , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/epidemiología , Masculino , Estudios Retrospectivos , Factores de Riesgo , Suiza/epidemiología , Factores de TiempoRESUMEN
Acute schistosomiasis is a regularly encountered disease in travelers. Because of the temporal delay, its unspecific presentation and the spontaneous resolution, acute schistosomiasis can easily remain unrecognized by physicians who are not familiar with tropical pathologies. In December 2011, a female traveler was admitted to the hospital with undetermined fever after having returned from Madagascar where she bathed in fresh water. Acute schistosomiasis was diagnosed and infection was suspected among other travelers of her group. Seroconversion was confirmed among 78% of participants. This article intends to clarify the preventive and diagnostic strategies based on the lessons learned from this cluster of 42 travelers exposed to schistosomiasis.
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Fiebre/parasitología , Esquistosomiasis/diagnóstico , Viaje , Enfermedad Aguda , Adolescente , Adulto , Anciano , Femenino , Humanos , Madagascar/epidemiología , Masculino , Persona de Mediana Edad , Esquistosomiasis/epidemiologíaRESUMEN
Genetic polymorphisms near IL28B are associated with spontaneous and treatment-induced clearance of hepatitis C virus (HCV). Our objective was to assess the predictive value of IL28B polymorphisms in the treatment of chronic hepatitis C of patients with HCV genotypes 4, for which data are currently limited. We analysed the association of IL28B polymorphisms with the virological response to treatment among 182 naïve chronic hepatitis C patients with HCV genotype 4, all from Syria. Associations of alleles with the response patterns were evaluated by univariate analysis and multivariate logistic regression, accounting for all relevant covariates. Sustained virological response (SVR) was achieved in 26% of rs8099917 TG/GG carriers compared with 60% of TT carriers (P < 0.0001) and 35% of rs12979860 CT/TT carriers compared with 62% of CC carriers (P = 0.0011). By multivariate analysis, the association between rs8099917 and SVR remained significant (OR = 0.19, 95% CI 0.07-0.50, for TG/GG vs TT, P = 0.0007), with the only significant covariate being advanced fibrosis (OR = 0.13, 95% CI 0.04-0.37, P = 0.0002). In conclusion, IL28B polymorphisms are the strongest predictors of response to therapy among chronic hepatitis C patients with HCV genotype 4.
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Antivirales/administración & dosificación , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Interleucinas/genética , Polimorfismo de Nucleótido Simple , Adulto , Quimioterapia Combinada , Femenino , Frecuencia de los Genes , Genotipo , Hepacivirus/efectos de los fármacos , Hepatitis C Crónica/virología , Humanos , Interferón-alfa/administración & dosificación , Interferones , Modelos Logísticos , Masculino , Persona de Mediana Edad , Polietilenglicoles/administración & dosificación , ARN Viral/genética , Proteínas Recombinantes/administración & dosificación , Ribavirina/administración & dosificación , Siria , Resultado del Tratamiento , Carga ViralRESUMEN
Hepatitis C viral (HCV) kinetics after initiation of interferon-based therapy provide valuable insights for understanding virus pathogenesis, evaluating treatment antiviral effectiveness and predicting treatment outcome. Adverse effects of liver fibrosis and steatosis on sustained virological response have been frequently reported, yet their impacts on the early viral kinetics remain unclear. In this study, associations between histology status and early viral kinetics were assessed in 149 HCV genotype 1-infected patients treated with pegylated interferon alfa-2a and ribavirin (DITTO trial). In multivariate analyses adjusted for critical factors such as IL28B genotype and baseline viral load, presence of significant fibrosis (Ishak stage > 2) was found to independently reduce the odds of achieving an initial reduction (calculated from day 0 to day 4) in HCV RNA of ≥2 logIU/mL (adjusted OR 0.03, P = 0.004) but was not associated with the second-phase slope of viral decline (calculated from day 8 to day 29). On the contrary, presence of liver steatosis was an independent risk factor for not having a rapid second-phase slope, that is, ≥0.3 logIU/mL/week (adjusted OR 0.22, P = 0.012) but was not associated with the first-phase decline. Viral kinetic modelling theory suggests that significant fibrosis primarily impairs the treatment antiviral effectiveness in blocking viral production by infected cells, whereas the presence of steatosis is associated with a lower net loss of infected cells. Further studies will be necessary to identify the biological mechanisms underlain by these findings.
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Hígado Graso/virología , Hepacivirus/aislamiento & purificación , Hepatitis C Crónica/virología , Interferón-alfa/administración & dosificación , Cirrosis Hepática/virología , Polietilenglicoles/administración & dosificación , Ribavirina/administración & dosificación , Carga Viral , Adulto , Antivirales/administración & dosificación , Hígado Graso/patología , Femenino , Genotipo , Hepacivirus/clasificación , Hepacivirus/genética , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/patología , Humanos , Hígado/patología , Cirrosis Hepática/patología , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/administración & dosificación , Resultado del TratamientoRESUMEN
BACKGROUND & AIMS: Single nucleotide polymorphisms (SNPs) associated with IL28B influence the outcome of peginterferon-α/ribavirin therapy of chronic hepatitis C virus (HCV) infection. We analyzed the kinetics of HCV RNA during therapy as a function of IL28B SNPs. METHODS: IL28B SNPs rs8099917, rs12979860, and rs12980275 were genotyped in 242 HCV treatment-naïve Caucasian patients (67% genotype 1, 28% genotype 2 or 3) receiving peginterferon-α2a (180 µg weekly) and ribavirin (1000-1200 mg daily) with serial HCV-RNA quantifications. Associations between IL28B polymorphisms and early viral kinetics were assessed, accounting for relevant covariates. RESULTS: In the multivariate analyses for genotype 1 patients, the T allele of rs12979860 (T(rs12979860)) was an independent risk factor for a less pronounced first phase HCV RNA decline (log(10) 0.89IU/ml among T carriers vs. 2.06 among others, adjusted p < 0.001) and lower rapid (15% vs. 38%, adjusted p = 0.007) and sustained viral response rates (48% vs. 66%, adjusted p < 0.001). In univariate analyses, T(rs12979860) was also associated with a reduced second phase decline (p = 0.002), but this association was no longer significant after adjustment for the first phase decline (adjusted p = 0.8). In genotype 2/3 patients, T(rs12979860) was associated with a reduced first phase decline (adjusted p = 0.04), but not with a second phase decline. CONCLUSIONS: Polymorphisms in IL28B are strongly associated with the first phase viral decline during peginterferon-α/ribavirin therapy of chronic HCV infection, irrespective of HCV genotype.
Asunto(s)
Hepacivirus/fisiología , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/genética , Interleucinas/genética , Polimorfismo de Nucleótido Simple/genética , ARN Viral/sangre , Adulto , Alelos , Antivirales/uso terapéutico , Femenino , Frecuencia de los Genes , Genotipo , Hepacivirus/genética , Humanos , Interferón-alfa/uso terapéutico , Interferones , Masculino , Persona de Mediana Edad , Análisis Multivariante , Polietilenglicoles/uso terapéutico , Proteínas Recombinantes/uso terapéutico , Ribavirina/uso terapéutico , Factores de TiempoRESUMEN
The progression of liver fibrosis in chronic hepatitis C has long been considered to be independent from viral genotypes. However, recent studies suggest an association between Hepatitis C virus (HCV) genotype 3 and accelerated liver disease progression. We completed a systematic review and meta-analysis of studies evaluating the association between HCV genotypes and fibrosis progression. PubMed, Embase and ISI Web of Knowledge databases were searched for cohort, cross-sectional and case-control studies on treatment-naïve HCV-infected adults in which liver fibrosis progression rate (FPR) was assessed by the ratio of fibrosis stage in one single biopsy to the duration of infection (single-biopsy studies) or from the change in fibrosis stage between two biopsies (paired biopsies studies). A random effect model was used to derive FPR among different HCV genotypes. Eight single-biopsy studies (3182 patients, mean/median duration of infection ranging from 9 to 21 years) and eight paired biopsies studies (mean interval between biopsies 2-12 years) met the selection criteria. The odds ratio for the association of genotype 3 with accelerated fibrosis progression was 1.52 (95% CI 1.12-2.07, P = 0.007) in single-biopsy studies and 1.37 (95% CI 0.87-2.17, P = 0.17) in paired biopsy studies. In conclusion, viral genotype 3 was associated with faster fibrosis progression in single-biopsy studies. This observation may have important consequences on the clinical management of genotype 3-infected patients. The association was not significant in paired biopsies studies, although the latter may be limited by important indication bias, short observation time and small sample size.
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Hepacivirus/genética , Hepacivirus/patogenicidad , Hepatitis C Crónica/patología , Cirrosis Hepática/patología , Biopsia , Estudios de Casos y Controles , Estudios de Cohortes , Progresión de la Enfermedad , Genotipo , Hepatitis C Crónica/genética , Humanos , Hígado/virología , Cirrosis Hepática/virología , Oportunidad Relativa , Factores de RiesgoRESUMEN
The outcome of hepatitis C virus (HCV) infection and the likelihood of a sustained virological response (SVR) to antiviral therapy depends on both viral and host characteristics. In vitro studies demonstrated that bile acids (BA) interfere with antiviral interferon effects. We investigate the influence of plasma BA concentrations and an ABCB11 polymorphism associated with lower transporter expression on viral load and SVR. Four hundred and fifty-one Caucasian HCV-patients treated with PEG-interferon and ribavirin were included in the study. ABCB11 1331T>C was genotyped, and plasma BA levels were determined. The 1331C allele was slightly overrepresented in HCV-patients compared to controls. In HCV-patients, a significant difference between patients achieving SVR vs non-SVR was observed for HCV-2/3 (5 vs 9 µm; P=0.0001), while median BA levels in HCV-1 were marginally elevated. Normal BA levels <8 µm were significantly associated with SVR (58.3%vs 36.3%; OR 2.48; P=0.0001). This difference was significant for HCV-2/3 (90.7%vs 67.6%; P=0.002) but marginal in HCV-1 (38.7%vs 27.8%; P=0.058). SVR rates were equivalent between ABCB11 genotypes for HCV-1, but increased for HCV-2/3 (TT 100%vs CC 78%; OR 2.01; P=0.043). IL28B genotype had no influence on these associations. No correlation between BA levels and HCV RNA was detected for any HCV genotype. The higher allelic frequency of ABCB11 1331C in HCV-patients compared to controls may indirectly link increased BA to HCV chronicity. Our data support a role for BA as host factor affecting therapy response in HCV-2/3 patients, whereas a weaker association was found for HCV-1.
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Transportadoras de Casetes de Unión a ATP/genética , Antivirales/uso terapéutico , Ácidos y Sales Biliares/sangre , Hepacivirus/efectos de los fármacos , Hepatitis C Crónica/tratamiento farmacológico , Polimorfismo de Nucleótido Simple , Miembro 11 de la Subfamilia B de Transportador de Casetes de Unión al ATP , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Quimioterapia Combinada , Femenino , Genotipo , Hepatitis C Crónica/genética , Hepatitis C Crónica/virología , Humanos , Interferón-alfa/antagonistas & inhibidores , Interferón-alfa/uso terapéutico , Masculino , Persona de Mediana Edad , Polietilenglicoles/uso terapéutico , Proteínas Recombinantes/antagonistas & inhibidores , Proteínas Recombinantes/uso terapéutico , Ribavirina/administración & dosificación , Ribavirina/uso terapéutico , Resultado del TratamientoRESUMEN
Accumulating evidence suggests that polymorphisms in Toll-like receptors (TLRs) influence the pathogenesis of mycobacterial infections, including leprosy, a disease whose manifestations depend on host immune responses. Polymorphisms in TLR2 are associated with an increased risk of reversal reaction, but not susceptibility to leprosy itself. We examined whether polymorphisms in TLR4 are associated with susceptibility to leprosy in a cohort of 441 Ethiopian leprosy patients and 197 healthy controls. We found that two single nucleotide polymorphisms (SNPs) in TLR4 (896G>A [D299G] and 1196C>T [T399I]) were associated with a protective effect against the disease. The 896GG, GA and AA genotypes were found in 91.7, 7.8 and 0.5% of leprosy cases versus 79.9, 19.1 and 1.0% of controls, respectively (odds ratio [OR] = 0.34, 95% confidence interval [CI] 0.20-0.57, P < 0.001, additive model). Similarly, the 1196CC, CT and TT genotypes were found in 98.1, 1.9 and 0% of leprosy cases versus 91.8, 7.7 and 0.5% of controls, respectively (OR = 0.16, 95% CI 0.06--.40, P < 0.001, dominant model). We found that Mycobacterium leprae stimulation of monocytes partially inhibited their subsequent response to lipopolysaccharide (LPS) stimulation. Our data suggest that TLR4 polymorphisms are associated with susceptibility to leprosy and that this effect may be mediated at the cellular level by the modulation of TLR4 signalling by M. leprae.
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Lepra/genética , Lepra/inmunología , Polimorfismo de Nucleótido Simple , Receptor Toll-Like 4/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Haplotipos , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Mycobacterium leprae/inmunología , Adulto JovenRESUMEN
Bacillus cereus bacteraemia can be severe, especially among patients with haematologic malignancy. We retrospectively reviewed first episodes of true B. cereus bacteraemia (more than one positive bottle plus signs of infection) at our institution between 1997 and 2013 with the aim to compare haematologic versus nonhaematologic patients and analyse episodes with complicated outcome. Among 56 episodes of positive-blood cultures for B. cereus, 21 were considered significant. Median age was 54 years (range 23-82 years). Ten patients (48%) had a haematologic malignancy; all were neutropenic at the time of B. cereus bacteraemia. Nonhaematologic patients were either intravenous drug users (n = 3, 14%), polytraumatized (n = 3, 14%) or had multiple chronic comorbidities (n = 5, 24%). Most episodes were hospital acquired (15, 71%). Sources of bacteraemia were intravascular catheter (n = 11, 52%), digestive tract (n = 6, 29%), drug injection (n = 3, 14%) and wound (n = 1, 5%). Adequate antibiotic therapy was provided to 18 patients (86%) during a median of 17 days (range 2-253 days). The intravascular catheter was removed in eight cases (42%). Three haematologic patients had a complicated course with neurologic complications (meningoencephalitis and cerebral abscesses). Complications appeared to be associated with catheter infection (100% of complicated cases vs. 29% of noncomplicated cases). In conclusion, B. cereus bacteraemia can have a complicated course in a subset of patients, mainly those with haematologic malignancy. Catheter infection may be associated with a worse outcome with frequent neurologic complications.
RESUMEN
We initiated a prospective study with a group of practitioners to assess the etiology, clinical presentation, and outcome of community-acquired pneumonia in patients diagnosed in the outpatient setting. All patients with signs and symptoms suggestive of pneumonia and an infiltrate on chest X-ray underwent an extensive standard workup and were followed over 4 weeks. Over a 4-year period, 184 patients were eligible, of whom 170 (age range, 15-96 yr; median, 43 yr) were included and analyzed. In 78 (46%), no etiologic agent could be demonstrated. In the remaining 92 patients, 107 etiologic agents were implicated: 43 were due to "pyogenic" bacteria (39 Streptococcus pneumoniae, 3 Haemophilus spp., 1 Streptococcus spp.), 39 were due to "atypical" bacteria (24 Mycoplasma pneumoniae, 9 Chlamydia pneumoniae, 4 Coxiella burnetii, 2 Legionella spp.), and 25 were due to viruses (20 influenza viruses and 5 other respiratory viruses). There were only a few statistically significant clinical differences between the different etiologic categories (higher age and comorbidities in viral or in episodes of undetermined etiology, higher neutrophil counts in "pyogenic" episodes, more frequent bilateral and interstitial infiltrates in viral episodes). There were 2 deaths, both in patients with advanced age (83 and 86 years old), and several comorbidities. Only 14 patients (8.2%) required hospitalization. In 6 patients (3.4%), the pneumonia episode uncovered a local neoplasia. This study shows that most cases of community-acquired pneumonia have a favorable outcome and can be successfully managed in an outpatient setting. Moreover, in the absence of rapid and reliable clinical or laboratory tests to establish a definite etiologic diagnosis at presentation, the spectrum of the etiologic agents suggest that initial antibiotic therapy should cover both S. pneumoniae and atypical bacteria, as well as possible influenza viruses during the epidemic season.
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Neumonía/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Infecciones Comunitarias Adquiridas , Comorbilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neumonía/diagnóstico , Neumonía/etiología , Neumonía/fisiopatología , Neumonía/terapia , Estudios Prospectivos , Estaciones del Año , Sensibilidad y Especificidad , Suiza/epidemiología , Resultado del TratamientoRESUMEN
Viridans streptococci have long been considered, with the exception of the ability to cause endocarditis, as minor pathogenic agents. More recently, however, these bacteria have become a major concern in neutropenic patients undergoing a chemotherapeutic treatment. In this high-risk population, they can be responsible for up to 39% of bacteremia cases and are the most frequent cause of this type of infection. The most frequently isolated species in blood cultures are Streptococcus mitis and Streptococcus sanguis II. Viridans streptococcus bacteremia can be accompanied by serious complications, like adult respiratory distress syndrome (ARDS) (3% to 33%), shock (7% to 18%) or endocarditis (7% to 8%). Mortality rates range from 6% to 30%. Case-control studies have identified the following risk factors: severe neutropenia (< 100 neutrophils/mm3), prophylactic antibiotic treatments with quinolone or co-trimoxazole, absence of intravenous antibiotics at the time of bacteremia, high doses of cytosine arabinoside, oropharyngeal mucositis, and heavy colonization by viridans streptococci. The introduction of penicillin in prophylactic antibiotic treatments has reduced the incidence of these infections, but the long-term use of penicillin could be compromised by the emergence of resistant strains.
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Bacteriemia/microbiología , Neutropenia/complicaciones , Infecciones Estreptocócicas/microbiología , Bacteriemia/epidemiología , Bacteriemia/prevención & control , Bacteriemia/terapia , Humanos , Factores de Riesgo , Infecciones Estreptocócicas/epidemiología , Infecciones Estreptocócicas/prevención & control , Infecciones Estreptocócicas/terapiaRESUMEN
While genetic polymorphisms play a paramount role in tuberculosis (TB), less is known about their contribution to the severity of diseases caused by other intracellular bacteria and fastidious microorganisms. We searched electronic databases for observational studies reporting on host factors and genetic predisposition to infections caused by intracellular fastidious bacteria published up to 30 May 2014. The contribution of genetic polymorphisms was documented for TB. This includes genetic defects in the mononuclear phagocyte/T helper cell type 1 (Th1) pathway contributing to disseminated TB disease in children and genome-wide linkage analysis (GWAS) in reactivated pulmonary TB in adults. Similarly, experimental studies supported the role of host genetic factors in the clinical presentation of illnesses resulting from other fastidious intracellular bacteria. These include IL-6 -174G/C or low mannose-binding (MBL) polymorphisms, which are incriminated in chronic pulmonary conditions triggered by C. pneumoniae, type 2-like cytokine secretion polymorphisms, which are correlated with various clinical patterns of M. pneumoniae infections, and genetic variation in the NOD2 gene, which is an indicator of tubal pathology resulting from Chamydia trachomatis infections. Monocyte/macrophage migration and T lymphocyte recruitment defects are corroborated to ineffective granuloma formation observed among patients with chronic Q fever. Similar genetic polymorphisms have also been suggested for infections caused by T. whipplei although not confirmed yet. In conclusion, this review supports the paramount role of genetic factors in clinical presentations and severity of infections caused by intracellular fastidious bacteria. Genetic predisposition should be further explored through such as exome sequencing.
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Bacterias/inmunología , Infecciones Bacterianas/genética , Infecciones Bacterianas/inmunología , Predisposición Genética a la Enfermedad , Adulto , Bacterias/patogenicidad , Niño , HumanosRESUMEN
BACKGROUND: A novel dinucleotide variant TT/∆G (ss469415590) has been associated with hepatitis C virus clearance. AIM: To assess the role of the ss469415590 variant, compared with the known IL28B polymorphisms (rs8099917, rs12979860 and rs12980275) for predicting virological response to therapy in chronic hepatitis C, and its association with the CXCL10 chemokine serum levels - a surrogate marker of interferon-stimulated genes activation. METHODS: Multivariate analysis of factors predicting rapid and sustained virological response in 280 consecutive, treatment-naïve, nondiabetic, Caucasian patients with chronic hepatitis C treated with peginterferon alpha and ribavirin. RESULTS: In hepatitis C virus genotype 1, the OR (95% CI) for rapid and sustained virological response for the wild-type ss469415590 TT was 9.88 (1.99-48.99) and 7.25 (1.91-27.51), respectively, similar to those found for rs12979860 CC [9.55 (1.93-47.37) and 6.30 (1.71-23.13)] and for rs12980275 AA [9.62 (1.94-47.77] and 7.83 (2.02-30.34)], but higher than for rs8099917 TT [4.8 (1.73-13.33) and 4.75 (2.05-10.98)]. In hepatitis C virus genotype 1, mean (SD) CXCL10 levels in patients with the TT/TT, TT/∆G and ∆G/∆G variants were, respectively, 355.1 (240.6), 434.4 (247.4) and 569.9 (333.3) (P = 0.04). In patients with genotypes 2 and 3 no significant association was found for TT/∆G with viral response. The predictive value of ss469415590 was stronger in patients with advanced fibrosis. CONCLUSIONS: The novel IL28B variants at marker ss469415590 predict response to IFN alpha in chronic hepatitis C patients, especially in those with advanced fibrosis. Their determination may be superior to that of known IL28B variants for patient management using IFN-based regimens.
Asunto(s)
Antivirales/uso terapéutico , Quimiocina CXCL10/sangre , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Adulto , Antivirales/administración & dosificación , Estudios de Cohortes , Quimioterapia Combinada , Femenino , Genotipo , Hepacivirus/aislamiento & purificación , Hepatitis C Crónica/virología , Humanos , Interferón alfa-2 , Interferón-alfa/administración & dosificación , Interferón-alfa/uso terapéutico , Masculino , Persona de Mediana Edad , Análisis Multivariante , Polietilenglicoles/administración & dosificación , Polietilenglicoles/uso terapéutico , Polimorfismo de Nucleótido Simple , Estudios Prospectivos , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/uso terapéutico , Ribavirina/administración & dosificación , Ribavirina/uso terapéutico , Resultado del Tratamiento , Población BlancaRESUMEN
BACKGROUND: Hepatitis C virus (HCV) is a major cause of chronic liver disease, cirrhosis and hepatocellular carcinoma and the identification of the predictors of response to antiviral therapy is an important clinical issue. AIM: To determine the independent contribution of factors including IL28B polymorphisms, IFN-gamma inducible protein-10 (IP-10) levels and the homeostasis model assessment of insulin resistance (HOMA-IR) score in predicting response to therapy in chronic hepatitis C (CHC). METHODS: Multivariate analysis of factors predicting rapid (RVR) and sustained (SVR) virological response in 280 consecutive, treatment-naive CHC patients treated with peginterferon alpha and ribavirin in a prospective multicentre study. RESULTS: Independent predictors of RVR were HCV RNA <400 000 IU/mL (OR 11.37; 95% CI 3.03-42.6), rs12980275 AA (OR 7.09; 1.97-25.56) and IP-10 (OR 0.04; 0.003-0.56) in HCV genotype 1 patients and lower baseline γ-glutamyl-transferase levels (OR=0.02; 0.0009-0.31) in HCV genotype 3 patients. Independent predictors of SVR were rs12980275 AA (OR 9.68; 3.44-27.18), age <40 years (OR=4.79; 1.50-15.34) and HCV RNA <400 000 IU/mL (OR 2.74; 1.03-7.27) in HCV genotype 1 patients and rs12980275 AA (OR=6.26; 1.98-19.74) and age <40 years (OR 5.37; 1.54-18.75) in the 88 HCV genotype 1 patients without a RVR. RVR was by itself predictive of SVR in HCV genotype 1 patients (OR 33.0; 4.06-268.32) and the only independent predictor of SVR in HCV genotype 2 (OR 9.0, 1.72-46.99) or genotype 3 patients (OR 7.8, 1.43-42.67). CONCLUSIONS: In HCV genotype 1 patients, IL28B polymorphisms, HCV RNA load and IP-10 independently predict RVR. The combination of IL28B polymorphisms, HCV RNA level and age may yield more accurate pre-treatment prediction of SVR. HOMA-IR score is not associated with viral response.
Asunto(s)
Antivirales/uso terapéutico , Quimiocina CXCL10/sangre , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Interleucinas/genética , Polimorfismo Genético , Carga Viral , Adulto , Estudios de Cohortes , Quimioterapia Combinada , Ensayo de Inmunoadsorción Enzimática , Femenino , Genotipo , Hepatitis C Crónica/sangre , Hepatitis C Crónica/genética , Humanos , Interferón-alfa/uso terapéutico , Interferones , Masculino , Persona de Mediana Edad , Polietilenglicoles/uso terapéutico , Estudios Prospectivos , ARN Viral/sangre , Proteínas Recombinantes/uso terapéutico , Ribavirina/uso terapéuticoAsunto(s)
Antibacterianos/uso terapéutico , Sepsis/tratamiento farmacológico , Choque Séptico/tratamiento farmacológico , Quimioterapia Combinada/uso terapéutico , Humanos , Sepsis/epidemiología , Sepsis/microbiología , Choque Séptico/epidemiología , Choque Séptico/microbiología , Resultado del TratamientoRESUMEN
Between 1988 and 1991, 26 episodes of bacteremia due to viridans streptococci occurred in 25 neutropenic patients undergoing intensive chemotherapy for hematologic malignancies. Complications related to the bacteremia were observed in 10 episodes: unilateral pulmonary infiltrates (4), acute respiratory distress syndrome (ARDS) (4), hypotension (3), and endocarditis (2). All patients with ARDS had received high doses of cytosine arabinoside and had bacteremia due to Streptococcus mitis. Death occurred in three patients (12%) but was possibly related to bacteremia in only one case. Case patients who had received prophylaxis with quinolones were compared with matched control patients who received similar prophylaxis but who did not have bacteremia due to viridans streptococci. Multivariate analysis of predisposing factors showed that high doses of cytosine arabinoside (P = .01), the presence of mucositis (P = .02), and the absence of previous therapy with parenteral antibiotics (P = .01) were independent risk factors for the development of viridans streptococcal bacteremia. Of 259 patients who had received quinolone prophylaxis during the study period, 22 (8.5%) developed an episode of viridans streptococcal bacteremia as compared with three episodes (3.7%) in 82 patients who had received a quinolone and penicillin (P = .07). However, the latter three episodes were caused by strains with decreased susceptibility to penicillin, thus suggesting that resistance to penicillin might limit the use of this antibiotic as a prophylactic agent in the future.
Asunto(s)
Bacteriemia/epidemiología , Enfermedad de Hodgkin/complicaciones , Leucemia Mieloide Aguda/complicaciones , Linfoma no Hodgkin/complicaciones , Mieloma Múltiple/complicaciones , Neutropenia/complicaciones , Penicilinas/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Infecciones Estreptocócicas/epidemiología , 4-Quinolonas , Adolescente , Adulto , Anciano , Antiinfecciosos/uso terapéutico , Bacteriemia/complicaciones , Bacteriemia/tratamiento farmacológico , Estudios de Casos y Controles , Femenino , Enfermedad de Hodgkin/tratamiento farmacológico , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Linfoma no Hodgkin/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Mieloma Múltiple/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Factores de Riesgo , Infecciones Estreptocócicas/complicaciones , Infecciones Estreptocócicas/tratamiento farmacológico , Resultado del TratamientoRESUMEN
Endocarditis is a common disease in hospital practice. Identification of the microorganism responsible for the valvular damage is essential to establish the prognosis and to determine the optimal antibiotic treatment. In some cases of endocarditis the diagnosis is laborious, especially when the responsible microorganism is difficult to detect using standard culture techniques. Here we report a case of native aortic valve endocarditis due to Kingella kingae, a Gram negative organism of the HACEK group. In addition we review 6 other cases of endocarditis caused by organism belonging to this group, treated in our hospital between 1983 and 1999. Epidemiological studies show that less than 5% of all cases of endocarditis are caused by organisms of the HACEK group. The diagnosis is often delayed because their slow growth on a standard culture medium. We describe clinical and microbiological characteristics of this group of endocarditis.
Asunto(s)
Endocarditis Bacteriana/diagnóstico , Endocarditis Bacteriana/microbiología , Kingella kingae , Infecciones por Neisseriaceae/diagnóstico , Infecciones por Neisseriaceae/microbiología , Adulto , Anciano , Antibacterianos/uso terapéutico , Biopsia , Ecocardiografía , Endocarditis Bacteriana/tratamiento farmacológico , Endocarditis Bacteriana/epidemiología , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Infecciones por Neisseriaceae/tratamiento farmacológico , Infecciones por Neisseriaceae/epidemiología , PronósticoRESUMEN
Most guidelines for the management of hospitalized patients with community-acquired pneumonia (CAP) recommend commencing therapy with intravenous antibiotics, primarily because of concern about absorption of oral antibiotics in acutely ill patients. However, patients who respond are rapidly switched to oral therapy, which has been shown to reduce costs and to shorten the length of stay. The aim of the present study was to determine whether a full course of oral antibiotics is as efficacious and as safe as intravenous-to-oral sequential antibiotic therapy for the treatment of hospitalized, non-ICU patients with CAP. In an open-labelled, controlled study, 129 hospitalized patients with CAP were randomly assigned in a 2:1 ratio to receive either a full course of oral levofloxacin (500 mg q12 h) or an intravenous-to-oral sequential therapy consisting of intravenous ceftriaxone (2 g q24 h) with or without clarithromycin (500 mg q12 h) followed by an oral antibiotic (a beta-lactam agent in the majority of patients). The primary study endpoint was the resolution of CAP; secondary endpoints included length of stay and overall mortality. CAP resolved in 72 of 79 (91.1%) patients in the levofloxacin group and in 34 of 37 (91.9%) patients in the intravenous-to-oral sequential therapy group (difference, -0.8%, 95%CI, -11.6-10.0). Median length of stay was 8 days (range, 2-74 days) in the levofloxacin group and 10 days (range, 3-29 days) in the intravenous-to-oral sequential therapy group ( P=0.28). Day 30 mortality rates were 1.3% (1 of 79) and 8.1% (3 of 37), respectively (difference, -6.8%, 95%CI, -16.0-2.3). Full-course oral levofloxacin is as efficacious and as safe as standard intravenous-to-oral sequential antibiotic therapy for the treatment of hospitalized patients with CAP.