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This study evaluated the epidemiological and clinical characteristics of human metapneumovirus (hMPV) infection among hospitalized patients with acute respiratory infections during 2015-2021 and assessed the impact of the coronavirus disease 2019 pandemic on hMPV infection. A single-center, retrospective cohort study was performed, including pediatric and adult patients with laboratory-confirmed hMPV. Of a total of 990 patients, 253 (25.6%), 105 (10.6%), 121 (12.2%), and 511 (51.6%) belonged to age groups 0-2, 3-17, 18-59, and ≥60 years, respectively. The highest percentage (23.0%) of patients were hospitalized during 2019 and the lowest (4.7%) during 2020. Patients < 18 years experienced high rates of comorbidities (immunodeficiencies: 14.4% and malignancies: 29.9%). Here, 37/39 (94.9%) of all bronchiolitis cases were diagnosed in patients < 2 years, whereas more patients in older age groups were diagnosed with pneumonia. A greater proportion of hMPV patients diagnosed with viral coinfection (mostly respiratory syncytial virus and adenovirus) were <18 years. The highest percentages of intensive care unit admissions were recorded among patients < 18 years. Our findings demonstrate that hMPV is an important cause of morbidity in young children and a possibly underestimated cause of morbidity among older adults.
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COVID-19 , Coinfección , Hospitalización , Metapneumovirus , Infecciones por Paramyxoviridae , Humanos , Estudios Retrospectivos , Metapneumovirus/aislamiento & purificación , Infecciones por Paramyxoviridae/epidemiología , Infecciones por Paramyxoviridae/virología , Israel/epidemiología , Persona de Mediana Edad , Niño , Masculino , Adulto , Femenino , Lactante , Adolescente , Preescolar , Hospitalización/estadística & datos numéricos , Adulto Joven , COVID-19/epidemiología , COVID-19/virología , Anciano , Coinfección/epidemiología , Coinfección/virología , Recién Nacido , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/virología , Comorbilidad , Anciano de 80 o más Años , SARS-CoV-2RESUMEN
BackgroundA new respiratory virus surveillance platform, based on nationwide hospital laboratory data, was established in Israel during the COVID-19 pandemic.AimWe aimed to evaluate the performance of this platform with respect to the detection of influenza and respiratory syncytial virus (RSV) from week 36 in 2020 to week 15 in 2023, and how it fits with the World Health Organization (WHO) mosaic surveillance framework.MethodsData of respiratory samples from hospitalised patients sent for laboratory confirmation of influenza virus or RSV from 25 general hospital laboratories nationwide were collected. We analysed the weekly number and percentage of samples positive for influenza virus or RSV vis-à-vis SARS-CoV-2 activity and compared data from the new surveillance platform with existing surveillance platforms. Using data in the new surveillance platform, we analysed early stages of a 2021 out-of-season RSV outbreak and evaluated the capabilities of the new surveillance system with respect to objectives and domains of the WHO mosaic framework.ResultsThe new hospital-laboratory surveillance platform captured the activity of influenza virus and RSV, provided crucial data when outpatient sentinel surveillance was not operational and supported an out-of-season RSV outbreak investigation. The new surveillance platform fulfilled important objectives in all three domains of the mosaic framework and could serve for gathering additional information to fulfil more domain objectives.ConclusionThe new hospital laboratory surveillance platform provided essential data during the COVID-19 pandemic and beyond, fulfilled important domain objectives of the mosaic framework and could be adapted for the surveillance of other viruses.
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COVID-19 , Gripe Humana , Pandemias , Infecciones por Virus Sincitial Respiratorio , SARS-CoV-2 , Organización Mundial de la Salud , Humanos , COVID-19/epidemiología , Israel/epidemiología , Infecciones por Virus Sincitial Respiratorio/epidemiología , Infecciones por Virus Sincitial Respiratorio/diagnóstico , Gripe Humana/epidemiología , Gripe Humana/diagnóstico , Vigilancia de Guardia , Laboratorios de Hospital/estadística & datos numéricos , Virus Sincitial Respiratorio Humano/aislamiento & purificación , Vigilancia de la Población/métodosRESUMEN
Community surveillance found the 2019-2020 A(H1N1)pdm09 predominant influenza season in Israel to be a high-intensity season with an early and steep morbidity peak. To further characterize disease severity in the 2019-2020 season, we analyzed a cohort of hospitalized patients with laboratory-confirmed influenza from this season (n = 636). Quantitative polymerase chain reaction was performed on clinical samples to detect the presence of influenza. Demographic, clinical, and laboratory data were retrieved via electronic health records and MDClone. Electronic health records were accessed to obtain data on intensive care unit patients, missing data and for data verification purposes. Univariate analysis was performed to compare demographic, comorbidity, and clinical characteristics across the three influenza strains. The A(H1N1)pdm09 predominant 2019-2020 influenza season in Israel was characterized by an early and steep morbidity peak, vaccine delays and shortages, and with the A(H3N2) and B/Victoria strains disproportionately targeting children and young adults, most probably due to reduced immunity to these strains. A greater proportion of children <5 years infected with A(H3N2) and B/Victoria developed severe influenza compared with those infected with A(H1N1)pdm09. Our study emphasizes the vulnerability of infants and young children in the face of rapidly evolving influenza strains and underscores the importance of influenza prevention measures in this population.
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Subtipo H1N1 del Virus de la Influenza A , Vacunas contra la Influenza , Gripe Humana , Niño , Lactante , Adulto Joven , Humanos , Preescolar , Gripe Humana/epidemiología , Subtipo H3N2 del Virus de la Influenza A , Estaciones del Año , Israel , Morbilidad , Virus de la Influenza BRESUMEN
BACKGROUND: To investigate the association of viral load (VL) with (i) tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon gamma-induced protein-10, C-reactive protein, and a combinatorial score (BV score), and (ii) clinical severity. STUDY DESIGN: In this prospective, multicentre cohort substudy, children with respiratory tract infection or fever without source were enrolled. VL for influenza virus, rhinovirus, respiratory syncytial virus, and adenovirus was measured from nasopharyngeal swabs. The reference standard diagnosis was established based on expert panel adjudication. RESULTS: Of 1140 recruited patients, 333 had a virus monodetection. VL for the aggregated data set correlated with TRAIL and IP-10 levels, with the length of oxygen therapy, and inversely with the BV score. At a single viral level, only the influenza VL yielded a correlation with TRAIL, IP-10 levels, and the BV score. Children with a viral reference standard diagnosis had significantly higher VL than those with bacterial infection (p = 0.0005). Low TRAIL (incidence rate ratio [IRR] 0.6, 95% confidence interval [CI] 0.39-0.91) and young age (IRR 0.62, 95% CI 0.49-0.79) were associated with a longer hospital stay, while young age (IRR 0.33, 95% CI 0.18-0.61), low TRAIL (IRR 0.25, 95% CI 0.08-0.76), and high VL (IRR 1.16, 95% CI 1.00-1.33) were predictive of longer oxygen therapy. CONCLUSION: These findings indicate that VL correlates with biomarkers and may serve as a complementary tool pertaining to disease severity.
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Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Infecciones del Sistema Respiratorio , Humanos , Niño , Lactante , Quimiocina CXCL10 , Estudios Prospectivos , Carga Viral , Ligandos , Infecciones del Sistema Respiratorio/diagnóstico , Biomarcadores , Gravedad del Paciente , Factor de Necrosis Tumoral alfa , OxígenoRESUMEN
COVID-19 patients are oftentimes over- or under-treated due to a deficit in predictive management tools. This study reports derivation of an algorithm that integrates the host levels of TRAIL, IP-10, and CRP into a single numeric score that is an early indicator of severe outcome for COVID-19 patients and can identify patients at-risk to deteriorate. 394 COVID-19 patients were eligible; 29% meeting a severe outcome (intensive care unit admission/non-invasive or invasive ventilation/death). The score's area under the receiver operating characteristic curve (AUC) was 0.86, superior to IL-6 (AUC 0.77; p = 0.033) and CRP (AUC 0.78; p < 0.001). Likelihood of severe outcome increased significantly (p < 0.001) with higher scores. The score differentiated severe patients who further deteriorated from those who improved (p = 0.004) and projected 14-day survival probabilities (p < 0.001). The score accurately predicted COVID-19 patients at-risk for severe outcome, and therefore has potential to facilitate timely care escalation and de-escalation and appropriate resource allocation.
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COVID-19 , Humanos , Quimiocina CXCL10 , Unidades de Cuidados Intensivos , Curva ROC , Estudios Retrospectivos , PronósticoRESUMEN
AIM: This paper describes the emergency, compassionate use of the COVID-19 vaccination for high-risk adolescents aged 12-15 years prior to approval by the American Food and Drugs Administration in May 2021. The target audience had underlying health conditions associated with severe disease and multisystem inflammatory syndrome in children (MIS-C) or severely immunosuppressed household members. METHODS: An orderly approval system was established in Israel for adolescents aged 12-15 years, based on a professional position paper and compassionate treatment regulations. From 12 February 2021, eligible adolescents were referred to the Israeli Ministry of Health for permission to vaccinate, via four health maintenance organisations. Data were collected about adverse events after vaccinations and the incidence of any cases of COVID-19. RESULTS: By 15 March 2021, the vaccine had been approved for 607 adolescents: 333 had received one dose, and 92 had received two doses. The median age was 14.6 years, and the major indication was obesity. Only one child tested positive for the virus, 4 days after vaccination, and no adverse effects were recorded. CONCLUSION: The emergency use of COVID-19 vaccination for 333 adolescents aged 12-15, 92 of them with 2 doses, based on a position paper and compassionate treatment regulations, did not result in any adverse effects. Since 27 July 2021, the same process was further applied in Israel among younger children, aged 5-11, preceding formal release of the clinical trial.
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Vacunas contra la COVID-19 , COVID-19 , Adolescente , COVID-19/complicaciones , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Niño , Preescolar , Ensayos de Uso Compasivo , Humanos , Israel , SARS-CoV-2 , Síndrome de Respuesta Inflamatoria Sistémica , Estados Unidos , VacunaciónRESUMEN
BACKGROUND: Antibiotic resistance is a worldwide problem associated with increased morbidity and mortality. OBJECTIVES: To evaluate multidrug resistant (MDR) bacteria carriage in selected populations. METHODS: Data were collected from all patients under 18 years who met our internal guidelines from 2015-2016. They were screened for carbapenem-resistant Enterobacteriaceae (CRE), extended spectrum beta-actamase (ESBL), methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (VRE). Indications for screening were non-resident non-Israeli patients (from the Palestinian Authority, Syria, and foreign patients), internal transfers from intensive care units, admission to high-risk departments, recent carriage of MDR bacteria, transfer from other hospitals, and recent hospitalization. Data were analyzed for MDR bacteria from at least one screening site (rectal, nasal, axillary, groin, throat). All data were analyzed per patient and per sample. RESULTS: During the study period 185/2632 positive screening sets (7%) were obtained from 725 patients. Of these, 165 patients (22.7%) were positive for at least one pathogen. Significantly fewer Israeli residents (120/615, 19.5%) tested positive compared to non-Israeli residents (45/110, 40.9%; P < 0.001). Past MDR bacteria carriage was the only significant screening indication (25/61, 41%; P < 0.001). CRE, VRE, MRSA, and ESBL prevalence rates were 0.6% (5/771), 0.5% (3/560) 0.5%, 4.2% (37/888), and 33.7% (139/413), respectively. Among non-ESBL carriers, MRSA was predominant with 38 positive cultures (n=34). CONCLUSIONS: Non-Israeli non-residents and patients with previous positive MDR screening are at higher risk for MDR bacteria. Indications used to identify high-risk patients for drug resistant pathogens were efficacious. More effort is needed to reduce excessive sampling.
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Staphylococcus aureus Resistente a Meticilina , Enterococos Resistentes a la Vancomicina , Humanos , Niño , Adolescente , Farmacorresistencia Bacteriana Múltiple , Hospitales , Hospitalización , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , PrevalenciaRESUMEN
OBJECTIVE: The popularity of social networks provide an incredible opportunity to enhance the impact of preventive medicine programs. We aimed to assess whether a targeted Facebook campaign among mothers may increase the uptake of human Papilloma virus (HPV) immunization among their 8th-grade daughters. METHODS: This field study was conducted among the members of a state-mandated health organization in Israel. Included were all 21,592 members who were mothers to 14 year-old daughters in the 2018-19 school-year. A total of 17,271 (80%) were randomly allocated to the campaign arm and the rest (n=4,321) were selected as a reference group. The Facebook ads addressed issues and concerns regarding HPV-related diseases and HPV vaccine. Main outcome measures were Facebook metrics on exposure to campaign and HPV immunization among eighth grade daughters of the study participants. RESULTS: Between 8/2018-10/2018, Facebook ads were shown 1.8-million times (a reach of 88%). The uptake of HPV vaccine among daughters of women allocated to the campaign arm (55.3%) was similar (p = 0.749) to 55.0% in the control group. The only significant differences between study groups were observed when stratifying by SES level. In the lowest SES quartile, Facebook campaign significantly (p = .02) reduced vaccine uptake (35% vs. 39.0%), with a relative risk of 0.90 (95%CI: 0.82-0.98), while in the second SES quartile, Facebook campaign increased vaccine uptake from 52.6% to 55.8%, with a RR of 1.06 (95%CI,1.00-1.12). Among mothers in higher SES levels, daughters of exposed and unexposed mothers had similar immunization rates. CONCLUSIONS: Facebook campaign may increase the uptake of HPV vaccine among daughters to mothers of medium-to-low SES level, but it may reduce vaccination among lower SES groups.
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Vacunas contra Papillomavirus/administración & dosificación , Medios de Comunicación Sociales/estadística & datos numéricos , Vacunación/estadística & datos numéricos , Adolescente , Adulto , Árabes/estadística & datos numéricos , Femenino , Promoción de la Salud/métodos , Humanos , Israel , Judíos/estadística & datos numéricos , Madres , Núcleo Familiar , Infecciones por Papillomavirus/prevención & control , Factores Socioeconómicos , Vacunación/psicologíaRESUMEN
AIM: Minimal data exist regarding the severity of COVID-19 in febrile infants under 60 days old. This multicentre prospective study explored the clinical course and outcomes of this hospitalised patient population, as, to date, the best approach has not been specifically addressed. METHODS: This study focused on the clinical features, laboratory parameters and outcomes of febrile infants up to 60 days old who tested positive for the virus and were hospitalised in Israel from March 2020 to January 2021. The data were extracted from a real-time prospective surveillance network for COVID-19 that includes 20 of the country's 26 hospitals. RESULTS: We identified 75 febrile young infants (60% female) with COVID-19 at a median age of 28 days (range 8-56 days). Of these, 84% had an unremarkable medical history, 29% had respiratory symptoms, and 96% had a mild illness. The Rochester criteria showed that 44% were considered at high-risk for serious bacterial infections, and we found that eight infants actually had concomitant bacterial infections. Outcomes were excellent, and no complications or fatalities were reported. CONCLUSION: The excellent outcomes of young febrile infants with COVID-19 closely resembled other respiratory viral aetiologies of fever in this age group, and there were no fatalities.
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Infecciones Bacterianas , COVID-19 , Femenino , Fiebre/epidemiología , Fiebre/etiología , Humanos , Lactante , Masculino , Estudios Prospectivos , SARS-CoV-2RESUMEN
Pseudomonas aeruginosa bacteremia is an infection associated with a high mortality rate. Piperacillin-tazobactam is a ß-lactam-ß-lactamase inhibitor combination that is frequently used for the management of Pseudomonas aeruginosa infections. The pharmacokinetic-pharmacodynamic index associated with in vitro maximal bacterial killing for piperacillin-tazobactam is the percentage of the time between doses at which the free fraction concentration remains above the MIC (%fT >MIC). However, the precise %fT >MIC target associated with improved clinical outcomes is unknown. The aim of this study was to investigate the correlation between the survival of patients with Pseudomonas aeruginosa bacteremia and the threshold of the piperacillin-tazobactam %fT >MIC This retrospective study included all adult patients hospitalized over an 82-month period with Pseudomonas aeruginosa bacteremia and treated with piperacillin-tazobactam. Patients with a polymicrobial infection or those who died within 72 h of the time of collection of a sample for culture were excluded. The %fT >MIC of piperacillin-tazobactam associated with in-hospital survival was derived using classification and regression tree analysis. After screening 270 patients, 78 were eligible for inclusion in the study; 18% died during hospitalization. Classification and regression tree analysis identified a %fT >MIC of >60.68% to be associated with improved survival, and this remained statistically significant after controlling for clinical covariates (odds ratio = 7.74, 95% confidence interval = 1.32 to 45.2). In conclusion, the findings recommend dosing of piperacillin-tazobactam with the aim of achieving a pharmacodynamic target %fT >MIC of at least 60% in these patients.
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Bacteriemia , Infecciones por Pseudomonas , Adulto , Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Humanos , Pruebas de Sensibilidad Microbiana , Ácido Penicilánico/uso terapéutico , Piperacilina , Combinación Piperacilina y Tazobactam/uso terapéutico , Infecciones por Pseudomonas/tratamiento farmacológico , Pseudomonas aeruginosa , Estudios RetrospectivosRESUMEN
Alpha1-antitrypsin (AAT) is a serum protease inhibitor that rises during inflammation and healthy pregnancies. Plasma-derived AAT, indicated for genetic AAT deficiency, is presently being explored for additional medical indications. Unlike corticosteroids, some anti-inflammatory activities of AAT involve NF-κB-dependent outcomes, e.g., induction of IL-1R antagonist. AAT activities were compared to dexamethasone (DEX), using various in-vitro cells assays, animal studies, and NF-κB-p65 localization and activity studies. Results demonstrate a cytokine shift towards resolution in AAT-treated cells, as opposed to pan-suppression in DEX-treated cells. AAT enhanced, while DEX suppressed LPS-induced IL-1Ra production and re-epithelialization. When drugs were combined, AAT allowed the immunosuppressive DEX activities, while DEX at medium to high levels antagonized beneficial AAT effects. Interestingly, lower levels of DEX maintained the immunosuppressive effect, while allowing upregulation of IL-1Ra. Therefore, AAT may represent a distinct endogenous anti-inflammatory, resolution-promoting agent that may improve tissue well-being while preventing undesired corticostroids side effects.
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Corticoesteroides/metabolismo , Inflamación/metabolismo , alfa 1-Antitripsina/metabolismo , Células A549 , Corticoesteroides/fisiología , Animales , Antiinflamatorios/farmacología , Citocinas/metabolismo , Dexametasona/metabolismo , Dexametasona/farmacología , Humanos , Proteína Antagonista del Receptor de Interleucina 1/metabolismo , Ratones , FN-kappa B/metabolismo , Células RAW 264.7 , Transducción de Señal/genética , Células THP-1 , Factor de Necrosis Tumoral alfa/metabolismo , alfa 1-Antitripsina/genética , alfa 1-Antitripsina/farmacología , alfa 1-Antitripsina/fisiologíaRESUMEN
To assess whether early administration of antimicrobials in open fractures of the limbs reduces infection risk. A historical cohort study included all adult patients admitted with an open fracture of the limbs, between January 1, 2012, and December 31, 2016. Epidemiological, clinical, and microbiological data was collected and analyzed. Microbiological infection was defined by positive wound cultures during the first 30 days, and clinical infection as defined by the treating physician. Of 167 patients, microbiological infection was identified in 12 (7%) patients, and clinical infection in 27 (16%) patients. All patients received the first dose of antimicrobials within 15 h of admission (median 1.29 h). Very early administration of the first dose did not reduce the risk of infection (median of 1.06 h and 1.31 h for patients that did vs. did not develop infection, respectively P = 0.58). In multivariate logistic regression, location of fracture in the lower limbs was associated with an increased risk of infection (OR 4.654, CI 1.407-15.398), and Gustilo-Anderson classification grade 1 or 2 was associated with a decreased risk of infection (OR 0.301, CI 0.104-0.872). Very early administration of antimicrobials did not reduce risk of infection in open limb fractures.
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Antibacterianos/administración & dosificación , Extremidades/lesiones , Fracturas Abiertas/tratamiento farmacológico , Infección de Heridas/prevención & control , Adulto , Femenino , Fracturas Abiertas/microbiología , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Infección de Heridas/epidemiología , Infección de Heridas/microbiología , Adulto JovenRESUMEN
Respiratory tract infections (RTI) are more commonly caused by viral pathogens in children than in adults. Surprisingly, little is known about antibiotic use in children as compared to adults with RTI. This prospective study aimed to determine antibiotic misuse in children and adults with RTI, using an expert panel reference standard, in order to prioritise the target age population for antibiotic stewardship interventions. We recruited children and adults who presented at the emergency department or were hospitalised with clinical presentation of RTI in The Netherlands and Israel. A panel of three experienced physicians adjudicated a reference standard diagnosis (i.e. bacterial or viral infection) for all the patients using all available clinical and laboratory information, including a 28-day follow-up assessment. The cohort included 284 children and 232 adults with RTI (median age, 1.3 years and 64.5 years, respectively). The proportion of viral infections was larger in children than in adults (209(74%) versus 89(38%), p < 0.001). In case of viral RTI, antibiotics were prescribed (i.e. overuse) less frequently in children than in adults (77/209 (37%) versus 74/89 (83%), p < 0.001). One (1%) child and three (2%) adults with bacterial infection were not treated with antibiotics (i.e. underuse); all were mild cases. This international, prospective study confirms major antibiotic overuse in patients with RTI. Viral infection is more common in children, but antibiotic overuse is more frequent in adults with viral RTI. Together, these findings support the need for effective interventions to decrease antibiotic overuse in RTI patients of all ages.
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Antibacterianos/uso terapéutico , Programas de Optimización del Uso de los Antimicrobianos/normas , Prescripción Inadecuada/estadística & datos numéricos , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Anciano , Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/epidemiología , Preescolar , Femenino , Humanos , Lactante , Israel/epidemiología , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Estudios Prospectivos , Estándares de Referencia , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/epidemiología , Virosis/diagnóstico , Virosis/tratamiento farmacológico , Virosis/epidemiologíaRESUMEN
AIM: Early-onset neonatal sepsis (EOS) may lead to significant morbidity and mortality, yet the recommended antimicrobials have not changed for many years. We aimed to optimise EOS treatment by examining EOS pathogens, resistance rates and resistance risk factors. METHODS: A retrospective, nationwide cohort study analysing 2010-2015 EOS data in Israel. RESULTS: The 21 participating centres constitute 92% of the total birth cohort (around 180 000 live births/year). Of 549 EOS neonates (0.57/1000 live births), 306 (56%) and 243 (44%) were full-term and preterm, respectively (0.35 vs. 2.94 per/1000 live births). Gram-negative pathogens predominated, especially in preterms. Escherichia coli and Streptococcus agalactiae were most common pathogens (0.2 and 0.19 per 1000 live births, respectively). In 277 Gram-negatives, 16%, 14%, 8% and 3% were gentamicin-resistant, extended-spectrum beta-lactamase (ESBL)-positive, gentamicin-resistant and ESBL-positive, and amikacin-resistant, respectively; preterms had higher resistance rates. No risk factors for antimicrobial resistance were identified. Mortality was reported in 21% of Gram-negative EOS versus 7% of Gram-positive EOS [OR 3.4 (95% CI 1.8-6.2), p < 0.01]. CONCLUSION: In this nationwide study, EOS was caused predominantly by Gram-negatives, with high gentamicin resistance and ESBL phenotype rates, without identifiable resistance risk factors. As EOS is life-threatening, modification of empiric therapy for amikacin-based regimens should be considered, mainly in preterms.
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Antibacterianos/uso terapéutico , Farmacorresistencia Microbiana , Sepsis Neonatal/epidemiología , Humanos , Recién Nacido , Recien Nacido Prematuro , Israel/epidemiología , Sepsis Neonatal/tratamiento farmacológico , Sepsis Neonatal/microbiologíaRESUMEN
Our aim was to assess the efficacy, safety, and tolerability of alpha-1 antitrypsin (AAT) as a therapeutic modality for ß-cell preservation in patients with recent-onset type 1 diabetes. Seventy type 1 diabetes patients (37 males; mean age 13.1 ± 4.1years) were randomized to treatment with 22 infusions of AAT (Glassia®) (60 or 120 mg/kg) or placebo. The primary outcome was the area under the curve (AUC) of C-peptide from a 2-h mixed-meal tolerance test after 52 weeks. At week 52, C-peptide was 0.9, 0.45, and 0.48 pmol/mL in the AAT-120, AAT-60, and placebo groups (p = 0.170 and p = 0.866 vs. placebo, respectively). The declines in C-peptide glycated hemoglobin (HbA1c) and the total insulin dose (U/kg) were similar across groups. Within the predefined 12-18-years subgroup, the C-peptide AUC decreased significantly in the placebo and AAT-60 groups (-0.34 and -0.54 pmol/mL, respectively, p < 0.01), with a borderline decrease in the AAT-120 group (-0.29 pmol/mL, p = 0.047). The mean HbA1c level was significantly lower in the AAT-120 group compared to the placebo (6.7% ± 0.9% vs. 8.2 ± 1.4%, p = 0.05), and a higher percentage of patients attained HbA1c ≤ 7% (75% vs. 25%, p = 0.05). AAT was tolerated well, with a similar safety profile between groups. The AAT intervention showed promise in the subgroup of adolescents with recent-onset type 1 diabetes. Further studies are warranted to determine the impact and proposed mechanism of action of AAT in ß-cell preservation.
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Diabetes Mellitus Tipo 1/tratamiento farmacológico , Factores Inmunológicos/uso terapéutico , alfa 1-Antitripsina/uso terapéutico , Adolescente , Adulto , Niño , Diabetes Mellitus Tipo 1/patología , Método Doble Ciego , Femenino , Humanos , Factores Inmunológicos/efectos adversos , Células Secretoras de Insulina/efectos de los fármacos , Células Secretoras de Insulina/patología , Masculino , Efecto Placebo , Resultado del Tratamiento , Adulto Joven , alfa 1-Antitripsina/efectos adversosRESUMEN
INTRODUCTION: Q fever is an acute zoonotic infection, which in some cases is complicated by a chronic disease. Diagnosis is based on serology, and in patients with a chronic disease, the source of infection must be investigated. AIMS: To describe patients with chronic Q fever, who were treated at the Hillel Yaffe Medical Center: risk factors, course of the disease, and serological findings. METHODS: This was an observational study; patients with chronic Q fever who were treated in the Infectious Diseases Clinic during the period 5/2015 - 1/2018 were included. The diagnosis was based on clinical findings and results of phase 1 IgG ≥ 800. Clinical, laboratory and imaging data from diagnosis to the end of treatment were collected. RESULTS: Sixteen patients were included in the study; all these patients were treated with antibiotics, and three also underwent operations. Risk factors for a chronic infection were a significant valvular disease in 11 patients (69%) and vascular diseases in five (31%). Trans-esophageal echocardiogram (TEE) was performed in 13 patients (81%), and a 18F-FDG/PET-CT was performed in eight patients (50%). The source of infection was found in seven patients, four with endocarditis and three with vascular infection. CONCLUSIONS: Endocarditis was more common than vascular infection. In 56% of the patients, the source of the infection was not found. DISCUSSION: We presented patients with chronic Q fever who were treated in a unique clinic in Israel. Diagnosing the source of the infection is challenging; the increasing use of 18F-FDG/PET-CT allowed accurate diagnosis in some patients in which TEE results were negative.
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Fiebre Q , Estudios de Seguimiento , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Fiebre Q/diagnóstico , Fiebre Q/terapiaRESUMEN
BACKGROUND: Little is known about Plasmodium malariae, a relatively rare cause of malaria in returned travelers. Recently, polymerase chain reaction (PCR) use for malaria diagnosis has enhanced specificity of P. malariae detection. The study objective was to describe the unique aspects of P. malariae diagnosis and clinical course in travelers. METHODS: Malaria is a reportable disease in Israel. All PCR-proven P. malariae monoinfections in Israeli travelers between January 2008 and January 2017 were retrieved from the Ministry of Health Reference Parasitology Laboratory. Data regarding method and timing of diagnosis, clinical characteristics, and laboratory testing were collected from patient charts. RESULTS: Eighteen patients with P. malariae were included. All cases were acquired in Africa. During the study period, the relative proportion of P. malariae increased (2%-10% of all malaria cases). Malaria was identified by blood smear in 10 of 18 patients (56%) on admission, and by rapid antigen test in 5 of 18 (29%) patients only, while P. malariae speciation was correctly identified by smear in 2 of 18 (11%) patients. Though all patients reported fever, only 4 of 18 (22%) described a quartan fever course. In 7 of 18 (39%) patients, malaria was contracted despite prophylactic treatment. Five patients had prolonged prepatent periods (median, 55 days), all of whom received prior prophylaxis. CONCLUSIONS: The relative proportion of P. malariae is on the rise. Diagnosis in routine clinical settings is inadequate due to the low sensitivity and specificity of blood smears. PCR should be considered when clinical suspicion is high. Prophylaxis failure, which caused delayed clinical presentation, was documented.
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Malaria , Plasmodium malariae , Viaje , Adulto , África , Anciano , Antimaláricos/uso terapéutico , Femenino , Humanos , Israel , Malaria/diagnóstico , Malaria/tratamiento farmacológico , Malaria/epidemiología , Masculino , Persona de Mediana Edad , Primaquina/uso terapéutico , Estudios Retrospectivos , Adulto JovenAsunto(s)
COVID-19 , SARS-CoV-2 , Adolescente , Niño , Pruebas Diagnósticas de Rutina , Humanos , Israel/epidemiología , VacunaciónRESUMEN
BACKGROUND: Nebulized hypertonic saline (HS) treatment is unavailable to large populations worldwide. OBJECTIVES: To determine the bacterial contamination and electrolyte concentrations in homemade (HM-HS) vs. pharmacy made (PM-HS). METHODS: We conducted three double-blind consecutive trials: 50 boiled-water homemade 3%-HS (B-HM-HS) bottles and 50 PM-HS. The bottles were cultured after 48 hours. Electrolyte concentrations were measured in 10 bottles (5 per group). Forty bottles (20 per group) were distributed to volunteers for simulation of realistic treatment by drawing 4 ml HS three times daily. From each bottle, 4 ml samples were cultured after 1, 5, and 7 days. Volunteers prepared 108 bottles containing 3%-HS, sterilizing them using a microwave oven (1100-1850W). These bottles were cultured 24 hours, 48 hours, and 1 month after preparation. RESULTS: Contamination rates of B-HM-HS and PM-HS after 48 hours were 56% and 14%, respectively (P = 0.008). Electrolyte concentrations were similar: 3.7% ± 0.4 and 3.5% ± 0.3, respectively (P = NS). Following a single day of simulation B-HM-HS bottles were significantly more contaminated than PM-HS bottles: 75% vs. 20%, respectively (P < 0.01). By day 7, 85% of PM-HS bottles and 100% of B-HM-HS bottles were contaminated (P = 0.23). All 108 microwave-oven prepared bottles (MICRO-HS) were sterile, which was significantly better than the contamination rate of B-HM-HS and PM-HS (P < 0.001). Calculated risk for a consecutive MICRO-HS to be infected was negligible. CONCLUSIONS: Microwave preparation provides sterile HS with adequate electrolyte concentrations, and is a cheap, fast, and widely available method to prepare HS.