Risk Factors for Serious Bacterial Infection in Febrile Young Infants in a Community Referral Hospital

Differentiation of serious bacterial infection (SBI) from self-limiting viral illness in febrile infants younger than three months is a significant challenge for clinicians. We aimed to assess the risk factors for SBI in febrile infants. Data were obtained from 221 infants younger than three months who visited a single community referral hospital for fever and underwent a complete sepsis workup between August 2003 and July 2006. The causes of fever were febrile illness without a documented cause (FISDC, 65%), urinary tract infection (UTI, 12%), aseptic meningitis (12%), bacteremia (4%), bacterial meningitis (2%). Cerebrospinal fluid enterovirus polymerase chain reaction was positive in 28% of FISDC and 48% of aseptic meningitis cases. When UTI was excluded, the risk factors for SBI were 1) C-reactive protein (CRP) level of ≥1.87 mg/dL and 2) fevers of ≥38.9℃. The specificity and negative predictive values of risk factors 1) and 2) for the diagnosis of SBI were 94% and 95%, respectively. We concluded that enteroviral infection may be a major cause of febrile episodes in infants younger than three months. If UTI could be excluded, the presence of CRP levels ≥1.87 mg/dL and fevers of ≥38.9℃ can be used as criteria to rule out SBI in these infants

Neonatal sepsis: within and beyond China.

Sepsis remains a significant cause of neonatal morbidity and mortality in China. A better understanding of neonatal sepsis in China as compared with other industrialized and non-industrialized countries may help optimize neonatal health care both regionally and globally. Literature cited in this review was retrieved from PubMed using the keywords "neonatal sepsis," "early-onset (EOS)" and "late-onset (LOS)" in English, with the focus set on population-based studies. This review provides an updated summary regarding the epidemiology, pathogen profile, infectious work-up, and empirical treatment of neonatal sepsis within and beyond China. The incidence of neonatal EOS and the proportion of Group B Streptococcus (GBS) within pathogens causing EOS in China seem to differ from those in developed countries, possibly due to different population characteristics and intrapartum/postnatal health care strategies. Whether to adopt GBS screening and intrapartum antibiotic prophylaxis in China remains highly debatable. The pathogen profile of LOS in China was shown to be similar to other countries. However, viruses as potential pathogens of neonatal LOS have been underappreciated. Growing antimicrobial resistance in China reflects limitations in adapting antibiotic regimen to local microbial profile and timely cessation of treatment in non-proven bacterial infections. This review stresses that the local epidemiology of neonatal sepsis should be closely monitored in each institution. A prompt and adequate infectious work-up is critically important in diagnosing neonatal sepsis. Adequate and appropriate antibiotic strategies must be overemphasized to prevent the emergence of multi-resistant bacteria in China

Characterization of a pneumococcal meningitis mouse model

<p>Abstract</p> <p>Background</p> <p><it>S. pneumoniae </it>is the most common causative agent of meningitis, and is associated with high morbidity and mortality. We aimed to develop an integrated and representative pneumococcal meningitis mouse model resembling the human situation.</p> <p>Methods</p> <p>Adult mice (C57BL/6) were inoculated in the cisterna magna with increasing doses of <it>S. pneumoniae </it>serotype 3 colony forming units (CFU; n = 24, 10⁴, 10⁵, 10⁶and 10⁷CFU) and survival studies were performed. Cerebrospinal fluid (CSF), brain, blood, spleen, and lungs were collected. Subsequently, mice were inoculated with 10⁴CFU <it>S. pneumoniae </it>serotype 3 and sacrificed at 6 (n = 6) and 30 hours (n = 6). Outcome parameters were bacterial outgrowth, clinical score, and cytokine and chemokine levels (using Luminex^®) in CSF, blood and brain. Meningeal inflammation, neutrophil infiltration, parenchymal and subarachnoidal hemorrhages, microglial activation and hippocampal apoptosis were assessed in histopathological studies.</p> <p>Results</p> <p>Lower doses of bacteria delayed onset of illness and time of death (median survival CFU 10⁴, 56 hrs; 10⁵, 38 hrs, 10⁶, 28 hrs. 10⁷, 24 hrs). Bacterial titers in brain and CSF were similar in all mice at the end-stage of disease independent of inoculation dose, though bacterial outgrowth in the systemic compartment was less at lower inoculation doses. At 30 hours after inoculation with 10⁴CFU of <it>S. pneumoniae</it>, blood levels of KC, IL6, MIP-2 and IFN- γ were elevated, as were brain homogenate levels of KC, MIP-2, IL-6, IL-1β and RANTES. Brain histology uniformly showed meningeal inflammation at 6 hours, and, neutrophil infiltration, microglial activation, and hippocampal apoptosis at 30 hours. Parenchymal and subarachnoidal and cortical hemorrhages were seen in 5 of 6 and 3 of 6 mice at 6 and 30 hours, respectively.</p> <p>Conclusion</p> <p>We have developed and validated a murine model of pneumococcal meningitis.</p

Cannabidiol reduces host immune response and prevents cognitive impairments in Wistar rats submitted to pneumococcal meningitis

Pneumococcal meningitis is a life-threatening disease characterized by an acute infection affecting the pia matter, arachnoid and subarachnoid space. The intense inflammatory response is associated with a significant mortality rate and neurologic sequelae, such as, seizures, sensory-motor deficits and impairment of learning and memory. The aim of this study was to evaluate the effects of acute and extended administration of cannabidiol on pro-inflammatory cytokines and behavioral parameters in adult Wistar rats submitted to pneumococcal meningitis. Male Wistar rats underwent a cisterna magna tap and received either 10 mu l of sterile saline as a placebo or an equivalent volume of S. pneumoniae suspension. Rats subjected to meningitis were treated by intraperitoneal injection with cannabidiol (2.5, 5, or 10 mg/kg once or daily for 9 days after meningitis induction) or a placebo. Six hours after meningitis induction, the rats that received one dose were killed and the hippocampus and frontal cortex were obtained to assess cytokines/chemokine and brain-derived neurotrophic factor levels. On the 10th day, the rats were submitted to the inhibitory avoidance task. After the task, the animals were killed and samples from the hippocampus and frontal cortex were obtained. The extended administration of cannabidiol at different doses reduced the TNF-alpha level in frontal cortex. Prolonged treatment with canabidiol, 10 mg/kg, prevented memory impairment in rats with pneumococcal meningitis. Although descriptive, our results demonstrate that cannabidiol has anti-inflammatory effects in pneumococcal meningitis and prevents cognitive sequel. (C) 2012 Elsevier B.V. All rights reserved.CNPqFAPEMIGFAPESCUNESCNENASC project (PRONEX program CNPq/FAPESC)INCT-TMResearch Support Center on Applied Neuroscience (NAPNA-USP) [2011.1.9333.1.3]L'Oreal-UNESCO Brazil Fellowship for Women in Scienc

TRIM5α and TRIM22 are differentially regulated according to HIV-1 infection phase and compartment.

CAPRISA, 2014.The antiviral role of TRIM E3 ligases in vivo is not fully understood. To test the hypothesis that TRIM5α and TRIM22 have differential transcriptional regulation and distinct anti-HIV roles according to infection phase and compartment, we measured TRIM5α, TRIM22, and type I interferon (IFN-I)-inducible myxovirus resistance protein A (MxA) levels in peripheral blood mononuclear cells (PBMCs) during primary and chronic HIV-1 infection, with chronic infection samples being matched PBMCs and central nervous system (CNS)-derived cells. Associations with biomarkers of disease progression were explored. The impact of IFN-I, select proinflammatory cytokines, and HIV on TRIM E3 ligase-specific expression was investigated. PBMCs from individuals with primary and chronic HIV-1 infection had significantly higher levels of MxA and TRIM22 than did PBMCs from HIV-1-negative individuals (P < 0.05 for all comparisons). PBMCs from chronic infection had lower levels of TRIM5α than did PBMCs from primary infection or HIV-1-uninfected PBMCs (P = 0.0001 for both). In matched CNS-derived samples and PBMCs, higher levels of MxA (P = 0.001) and TRIM5α (P = 0.0001) in the CNS were noted. There was a negative correlation between TRIM22 levels in PBMCs and plasma viral load (r = -0.40; P = 0.04). In vitro, IFN-I and, rarely, proinflammatory cytokines induced TRIM5α and TRIM22 in a cell type-dependent manner, and the knockdown of either protein in CD4(+) lymphocytes resulted in increased HIV-1 infection. These data suggest that there are infection-phase-specific and anatomically compartmentalized differences in TRIM5α and TRIM22 regulation involving primarily IFN-I and specific cell types and indicate subtle differences in the antiviral roles and transcriptional regulation of TRIM E3 ligases in vivo

Early lumbar puncture in adult bacterial meningitis-rationale for revised guidelines

Current international guidelines recommend cerebral computerized tomography (CT) before lumbar puncture (LP) in many adults with suspected acute bacterial meningitis (ABM), due to concern about LP-induced cerebral herniation. Despite guideline emphasis on early treatment based on symptoms, performing CT prior to LP implies a risk of delayed ABM treatment, which may be associated with a fatal outcome. Firm evidence for LP-induced herniation in adult ABM is absent and brain CT cannot discard herniation. Thus, the recommendation to perform CT before LP may contribute to an avoidable delay of LP and ABM treatment. The inappropriate use of the diagnostic treatment sequence of brain CT scan, followed by LP, followed by antibiotics and corticosteroids should be avoided in adults with suspected ABM by omitting needless contraindications for LP, thus eliminating an unnecessary fear of immediate LP. Revised Swedish guidelines regarding early LP are presented, and the background documentation and reasons for omitting impaired consciousness, new onset seizures, and immunocompromised state as contraindications to LP are discussed