RESUMO
OBJECTIVE: To compare the risk of mortality and other clinical outcomes in children with sepsis, severe sepsis, or septic shock who received antibiotics within the first hour of recognition (early antibiotics group) with those who received antibiotics after the first hour (delayed antibiotics group). STUDY DESIGN: In this prospective cohort study, we enrolled children <17 years of age presenting to the pediatric emergency and diagnosed with sepsis or septic shock without prior antibiotic therapy. Primary outcome was mortality and the secondary outcomes were day 1 Pediatric Logistic Organ Dysfunction score, ventilator-free days, and hospital-free days. These outcomes were compared between the early and the delayed antibiotic groups. The reference point for defining early and delayed antibiotic groups was time 0, which was measured from the time the patient was diagnosed to have sepsis, severe sepsis, or septic shock to the time of administration of the first dose of antibiotics. RESULTS: About three-fourths (77%) of the 441 children enrolled had septic shock. A total of 241 (55%) and 200 (45%) children were in the delayed and early antibiotic groups, respectively. Children in the delayed group had significantly higher odds of mortality than those in the early group (29% vs 20%; aOR 1.83; 95% CI, 1.14-2.92; P = .01). The time to shock reversal was significantly shorter, and the ventilator-free days and hospital-free days were significantly greater, in the early antibiotic group. There was no difference between the groups with regard to any of the other clinical outcomes. CONCLUSIONS: Delayed administration of antibiotics beyond 1 hour of recognition was associated with higher mortality rates in children with sepsis, severe sepsis, and septic shock. Antibiotics should be administered within the first hour, along with other resuscitative measures, in these children.
Assuntos
Antibacterianos/uso terapêutico , Sepse/tratamento farmacológico , Sepse/mortalidade , Choque Séptico/tratamento farmacológico , Choque Séptico/mortalidade , Criança , Pré-Escolar , Estudos de Coortes , Serviço Hospitalar de Emergência , Feminino , Mortalidade Hospitalar , Humanos , Lactente , Masculino , Tempo para o TratamentoRESUMO
BACKGROUND: Dengue virus (DENV) infections pose one of the largest global barriers to human health. The four serotypes (DENV 1-4) present different symptoms and influence immune response to subsequent DENV infections, rendering surveillance, risk assessments, and disease control particularly challenging. Early diagnosis and appropriate clinical management is critical and can be achieved by detecting DENV nonstructural protein 1 (NS1) in serum during the acute phase. However, few NS1-based tests have been developed that are capable of differentiating DENV serotypes and none are currently commercially available. METHODOLOGY/PRINCIPLE FINDINGS: We developed an enzyme-linked immunosorbent assay (ELISA) to distinguish DENV-1-4 NS1 using serotype-specific pairs of monoclonal antibodies. A total of 1,046 antibodies were harvested from DENV-immunized mice and screened for antigen binding affinity. ELISA clinical performance was evaluated using 408 polymerase chain reaction-confirmed dengue samples obtained from patients in Brazil, Honduras, and India. The overall sensitivity of the test for pan-DENV was 79.66% (325/408), and the sensitivities for DENV-1-4 serotyping were 79.1% (38/48), 80.41% (78/97), 100% (45/45), and 79.6% (98/123), respectively. Specificity reached 94.07-100%. SIGNIFICANCE: Our study demonstrates a robust antibody screening strategy that enabled the development of a serotype NS1-based ELISA with maximized specific and sensitive antigen binding. This sensitive and specific assay also utilized the most expansive cohort to date, and of which about half are from Latin America, a geographic region severely underrepresented in previous similar studies. This ELISA test offers potential enhanced diagnostics during the acute phase of infection to help guide patient care and disease control. These results indicate that this ELISA is a promising aid in early DENV-1-4 diagnosis and surveillance in regions of endemicity in addition to offer convenient monitoring for future vaccine interventions.
Assuntos
Vírus da Dengue/classificação , Vírus da Dengue/isolamento & purificação , Dengue/virologia , Ensaio de Imunoadsorção Enzimática/métodos , Sorogrupo , Proteínas não Estruturais Virais/análise , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/isolamento & purificação , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/isolamento & purificação , Brasil , Estudos de Coortes , Honduras , Humanos , Índia , América Latina , Camundongos Endogâmicos C57BL , Sensibilidade e EspecificidadeRESUMO
Swine origin influenza was first recognized in the border area of Mexico and United States in April 2009 and during a short span of two months became the first pandemic. The currently circulating strain of swine origin influenza virus of the H1N1 strain has undergone triple reassortment and contains genes from the avian, swine and human viruses. It is transmitted by droplets or fomites. Incubation period is 2 to 7 days. Common clinical symptoms are indistinguishable by any viral respiratory illness, and include fever, cough, sore throat and myalgia. A feature seen more frequently with swine origin influenza is GI upset. Less than 10% of patients require hospitalization. Patients at risk of developing severe disease are - younger than five years, elderly, pregnant women, with chronic systemic illnesses, adolescents on aspirin. Of the severe manifestations of swine origin influenza, pneumonia and respiratory failure are the most common. Unusual symptoms reported are conjunctivitis, parotitis, hemophagocytic syndrome. Infants may present with fever and lethargy with no respiratory symptoms. Diagnosis is based on RT PCR, Viral culture or increasing neutralizing antibodies. Principle of treatment consist of isolation, universal precautions, good infection control practices, supportive care and use of antiviral drugs. Antiviral drugs effective against H1N1 virus include: oseltamivir and zamanavir. With good supportive care case fatality is less than 1%. Preventive measures include: social distancing, practicing respiratory etiquette, hand hygiene and use of chemoprohylaxis with antiviral drugs. Vaccine against H1N1 is not available at present, but will be available in near future.