#Severe Manifestations of #Chikungunya Fever in #Children, #India, 2016 (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 24, Number 9—September 2018 / Dispatch

Severe Manifestations of Chikungunya Fever in Children, India, 2016

Pradeep Kumar Sharma  , Maneesh Kumar, Girraj K. Aggarwal, Virender Kumar, R.D. Srivastava, Ashish Sahani, and Rohit Goyal

Author affiliations: Sri Balaji Action Medical Institute, New Delhi, India

 

Abstract

Chikungunya is a relatively benign disease with a paucity of literature on severe manifestations in children. We describe a cohort of pediatric chikungunya fever patients in New Delhi, India, who had severe sepsis and septic shock, which can develop during the acute phase of illness.

Keywords: Chikungunya Fever; India; Sepsis; Septic Shock.

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#Azithromycin in combination with #ceftriaxone reduces systemic inflammation and provides survival benefit in murine model of polymicrobial #sepsis (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Azithromycin in combination with ceftriaxone reduces systemic inflammation and provides survival benefit in murine model of polymicrobial sepsis

Anasuya Patel a,b, Jiji Joseph b, Hariharan Periasamy b and Santosh Mokale a#

Author Affiliations: a Y. B. Chavan College of Pharmacy, Aurangabad, Maharashtra, India; b Wockhardt Research Centre, Aurangabad, Maharashtra, India

 

ABSTRACT

Sepsis is a life threatening systemic inflammatory condition triggered as a result of excessive host immune response to infection. In the past, immunomodulators have demonstrated protective effect in sepsis. Azithromycin (macrolide antibiotic) having immunomodulatory activity was therefore evaluated in combination with ceftriaxone in a clinically relevant murine model of sepsis induced by caecal ligation and puncture (CLP). First, mice underwent CLP and 3 h later were administered with vehicle or sub-protective dose of ceftriaxone (100 mg/kg, subcutaneous) alone or in combination with immunomodulatory dose of azithromycin (100 mg/kg, intraperitoneal). Survival was monitored for 5 days. In order to assess the immunomodulatory activity, parameters such as plasma and lung cytokines concentrations (interleukin IL-6, IL-1β, tumor necrosis factor-α), plasma glutathione (GSH), plasma and lung myeloperoxidase (MPO), body temperature, blood glucose, total white blood cell count, along with bacterial load in blood, peritoneal fluid and lung homogenate were measured 18 h after CLP challenge. Azithromycin in presence of ceftriaxone significantly improved the survival of CLP challenged mice. Further, the combination attenuated the elevated levels of inflammatory cytokines and MPO in plasma and lung tissue and increased the body temperature, blood glucose and GSH which were otherwise markedly decreased in CLP mice. Ceftriaxone exhibited significant reduction in bacterial load, while co-administration of azithromycin did not show further reduction. Therefore, the survival benefit by azithromycin was due to immunomodulation and not by its antibacterial action. Findings of this study indicate that azithromycin could provide clinical benefits in sepsis in conjunction with appropriate antibacterial agents.

 

FOOTNOTES

#Address correspondence to Santosh Mokale, santoshmokale@rediffmail.com

Copyright © 2018 American Society for Microbiology. All Rights Reserved.

Keywords: Antibiotics; Sepsis; Immunomodulators; Azithromycin; Ceftriaxone.

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#Risk of #Infection and #Sepsis in #Pediatric Patients with Traumatic #Brain #Injury Admitted to Hospital Following Major Trauma (Sci Rep., abstract)

[Source: Scientific Reports, fu ll page: (LINK). Abstract, edited.]

Risk of Infection and Sepsis in Pediatric Patients with Traumatic Brain Injury Admitted to Hospital Following Major Trauma

Anjli Pandya, Kathleen Helen Chaput, Andrea Schertzer, Diane Moser, Jonathan Guilfoyle, Sherry MacGillivray, Jaime Blackwood, Ari R. Joffe & Graham C. Thompson

Scientific Reports, volume 8, Article number: 9798 (2018)

 

Abstract

Head injury accounts for 29% of all traumatic deaths in children. Sepsis is significantly associated with an increased risk of mortality in adult traumatic brain injury patients. In the pediatric population, this relationship is not well understood. The objective of this study was to compare the proportion of pediatric traumatic brain injury (TBI) patients and trauma patients without brain injury (NTBI) who developed sepsis or any infection during their index hospital admission. We performed a retrospective study of all trauma patients <18 years of age, admitted to trauma centres in Alberta, Canada from January 1, 2003 to December 31, 2012. Patients who died within 24 hrs of trauma (n = 147) and those with burns as the primary mechanism of injury (n = 53) were excluded. Hospital admission data for the remaining 2556 patients was analyzed. 1727 TBI patients and 829 NTBI patients were included. TBI was associated with lower odds of developing sepsis (OR 0.32 95% CI 0.14–0.77 p = 0.011). TBI was not found to be independently associated with developing any infectious complication after adjusting for confounding by Injury Severity Score (OR 1.25 95% CI 0.90–1.74 p = 0.180). These relationships warrant further study.

Keywords: Sepsis; Neurology.

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#HPeV-3 predominated among #Parechovirus A positive #infants during an #outbreak in 2013-2014 in #Queensland, #Australia (J Clin Virol., abstract)

[Source: Journal of Clinical Virology, full page: (LINK). Abstract, edited.]

HPeV-3 predominated among Parechovirus A positive infants during an outbreak in 2013-2014 in Queensland, Australia

Donna McNeale, Claire Y.T. Wang, Katherine E. Arden, Ian M. Mackay

DOI: http://dx.doi.org/10.1016/j.jcv.2017.12.003

Published online: December 05, 2017 – Accepted: December 4, 2017 – Received in revised form: November 22, 2017 – Received: September 1, 2017

 

Highlights

  • HPeV-3 was the only Parechovirus A genotype found in CNS of ill Queensland infants.
  • HPeV testing requests peaked between spring 2013 to autumn 2014.
  • HPeV testing should be routine for CSF from infants with acute CNS-related symptoms.
  • VP3/VP1 HPeV sequence analysis is rapid and can robustly identify most genotypes.

 

Abstract

Background

Parechoviruses (HPeV) are endemic seasonal pathogens detected from the respiratory tract, gut, blood and central nervous system (CNS) of children and adults, sometimes in conjunction with a range of acute illnesses. HPeV CNS infection may lead to neurodevelopmental sequelae, especially following infection by HPeV-3, hence screening and genotyping are important to inform epidemiology, aetiology and prognosis.

Objectives

To identify and characterise HPeVs circulating during an outbreak between November 2013 and April 2014 in Queensland, Australia.

Study design

To perform PCR-based screening and comparative nucleotide sequence analysis on samples from children with clinically suspected infections submitted to a research laboratory for HPeV investigations.

Results

HPeVs were detected among 25/62 samples, identified as HPeV-3 from 23 that could be genotyped. These variants closely matched those which have occurred worldwide and in other States of Australia.

Conclusions

The inclusion of PCR-based HPeV testing is not systematically applied but should be considered essential for children under 3 months of age with CNS symptoms as should long-term follow-up of severe sepsis-like cases.

Keywords: Human parechovirus, genotyping, central nervous system, infants, sepsis, Australia

© 2017 Elsevier B.V. All rights reserved.

Keywords: Parechovirus; Sepsis; Australia; Queensland.

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Prehospital #antibiotics in the #ambulance for #sepsis: a multicentre, open label, randomised trial (Lancet Resp Med., abstract)

[Source: The Lancet Respiratory Medicine, full page: (LINK). Abstract, edited.]

Prehospital antibiotics in the ambulance for sepsis: a multicentre, open label, randomised trial

Nadia Alam, MD, Erick Oskam, MD, Patricia M Stassen, PhD, Pieternel van Exter, MD, Peter M van de Ven, PhD, Prof Harm R Haak, PhD, Frits Holleman, PhD, Arthur van Zanten, PhD, Hien van Leeuwen-Nguyen, MD, Victor Bon, MSc, Bart A M Duineveld, MD, Rishi S Nannan Panday, MD, Prof Mark H H Kramer, FRCP, Prabath W B Nanayakkara, FRCP on behalf of the PHANTASi Trial Investigators and the ORCA (Onderzoeks Consortium Acute Geneeskunde) Research Consortium the Netherlands†

†Investigators are listed in the appendix

Published: 28 November 2017 /  DOI: http://dx.doi.org/10.1016/S2213-2600(17)30469-1

© 2017 Elsevier Ltd. All rights reserved.

 

Summary

Background

Emergency medical services (EMS) personnel have already made substantial contributions to improving care for patients with time-dependent illnesses, such as trauma and myocardial infarction. Patients with sepsis could also benefit from timely prehospital care.

Methods

After training EMS personnel in recognising sepsis, we did a randomised controlled open-label trial in ten large regional ambulance services serving 34 secondary and tertiary care hospitals in the Netherlands. We compared the effects of early administration of antibiotics in the ambulance with usual care. Eligible patients were randomly assigned (1:1) using block-randomisation with blocks of size 4 to the intervention (open-label intravenous ceftriaxone 2000 mg in addition to usual care) or usual care (fluid resuscitation and supplementary oxygen). Randomisation was stratified per region. The primary outcome was all-cause mortality at 28 days and analysis was by intention to treat. To assess the effect of training, we determined the average time to antibiotics (TTA) in the emergency department and recognition of sepsis by EMS personnel before and after training. The trial is registered at ClinicalTrials.gov, number NCT01988428.

Findings

2698 patients were enrolled between June 30, 2014, and June 26, 2016. 2672 patients were included in the intention-to-treat analysis: 1535 in the intervention group and 1137 in the usual care group. The intervention group received antibiotics a median of 26 min (IQR 19–34) before arriving at the emergency department. In the usual care group, median TTA after arriving at the emergency department was 70 min (IQR 36–128), compared with 93 min (IQR 39–140) before EMS personnel training (p=0·142). At day 28, 120 (8%) patients had died in the intervention group and 93 (8%) had died in the usual care group (relative risk 0·95, 95% CI 0·74–1·24). 102 (7%) patients in the intervention group and 119 (10%) in the usual care group were re-admitted to hospital within 28 days (p=0·0004). Seven mild allergic reactions occurred, none of which could be attributed to ceftriaxone.

Interpretation

In patients with varying severity of sepsis, EMS personnel training improved early recognition and care in the whole acute care chain. However, giving antibiotics in the ambulance did not lead to improved survival, regardless of illness severity.

Funding

The NutsOhra Foundation, Netherlands Society of Internal Medicine (NIV).

Keywords: Sepsis; Antibiotics.

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Prolonged versus short-term intravenous #infusion of #antipseudomonal β-lactams for patients with #sepsis: a systematic review and meta-analysis of randomised trials (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Prolonged versus short-term intravenous infusion of antipseudomonal β-lactams for patients with sepsis: a systematic review and meta-analysis of randomised trials

Dr Konstantinos Z Vardakas, MD, Georgios L Voulgaris, PharmD, Athanasios Maliaros, BSc, Prof George Samonis, MD, Prof Matthew E Falagas, MD

Published: 25 October 2017 / DOI: http://dx.doi.org/10.1016/S1473-3099(17)30615-1

© 2017 Elsevier Ltd. All rights reserved.

 

Summary

Background

The findings of randomised controlled trials (RCT), observational studies, and meta-analyses vary regarding the effectiveness of prolonged β-lactam infusion. We aimed to identify the effectiveness of prolonged versus short-term infusion of antipseudomonal β-lactams in patients with sepsis.

Methods

We did a systematic review and meta-analysis to compare prolonged versus short-term intravenous infusion of antipseudomonal β-lactams in patients with sepsis. Two authors independently searched PubMed, Scopus, and the Cochrane Library of clinical trials until November, 2016, without date or language restrictions. Any RCT comparing mortality or clinical efficacy of prolonged (continuous or ≥3 h) versus short-term (≤60 min) infusion of antipseudomonal β-lactams for the treatment of patients with sepsis was eligible. Studies were excluded if they were not RCTs, the antibiotics in the two arms were not the same, neither mortality nor clinical efficacy was reported, only pharmacokinetic or pharmacodynamic outcomes were reported, or if ten or fewer patients were enrolled or randomised. Data were extracted in prespecified forms and we then did a meta-analysis using a Mantel-Haenszel random-effects model. The primary outcome was all-cause mortality at any timepoint. This meta-analysis is registered with the PROSPERO database, number CRD42016051678, and is reported according to PRISMA guidelines.

Findings

2196 articles were identified and screened, and 22 studies (1876 patients) were included in the meta-analysis. According to the Grading of Recommendations Assessment, Development, and Evaluation tool, the quality of evidence for mortality was high. Carbapenems, penicillins, and cephalosporins were studied. Patients with variable age, Acute Physiology and Chronic Health Evaluation (APACHE) II score, severity of sepsis and renal function were enrolled. Prolonged infusion was associated with lower all-cause mortality than short-term infusion (risk ratio [RR] 0·70, 95% CI 0·56–0·87). Heterogeneity was not observed (p=0·93, I2=0%). The funnel plot and the Egger’s test (p=0·44) showed no evidence of publication bias.

Interpretation

Prolonged infusion of antipseudomonal β-lactams for the treatment of patients with sepsis was associated with significantly lower mortality than short-term infusion. Further studies in specific subgroups of patients according to age, sepsis severity, degree of renal dysfunction, and immunocompetence are warranted.

Funding

None.

Keywords: Pseudomonas spp.; Antibiotics; Sepsis.

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Beneficial effects of Red #LED #treatment in experimental #model of acute #lung injury induced by #sepsis (Sci Rep., abstract)

[Source: Scientific Reports, full page: (LINK). Abstract, edited.]

Beneficial effects of Red Light-Emitting Diode treatment in experimental model of acute lung injury induced by sepsis

Silvia Goes Costa,  Éric Diego Barioni,  Aline Ignácio,  Juliana Albuquerque,  Niels Olsen Saraiva Câmara,  Christiane Pavani,  Luana Beatriz Vitoretti,  Amílcar Sabino Damazo,  Sandra Helena Poliselli Farsky &  Adriana Lino-dos-Santos-Franco

Scientific Reports 7, Article number: 12670(2017) / doi:10.1038/s41598-017-13117-5

Respiration – Respiratory distress syndrome

Received: 14 February 2017 – Accepted: 19 September 2017 – Published online: 04 October 2017

 

Abstract

Sepsis is a severe disease with a high mortality index and it is responsible for the development of acute lung injury (ALI). We evaluated the effects of light-emitting diode (LED) on ALI induced by sepsis. Balb-c mice were injected with lipopolysaccharide or saline and then irradiated or not with red LED on their tracheas and lungs for 150 s, 2 and 6 h after LPS injections. The parameters were investigated 24 h after the LPS injections. Red LED treatment reduced neutrophil influx and the levels of interleukins 1β, 17 A and, tumor necrosis factor-α; in addition to enhanced levels of interferon γ in the bronchoalveolar fluid. Moreover, red LED treatment enhanced the RNAm levels of IL-10 and IFN-γ. It also partially reduced the elevated oxidative burst and enhanced apoptosis, but it did not alter the translocation of nuclear factor κB, the expression of toll-like receptor 4 (TLR4), as well as, oedema or mucus production in their lung tissues. Together, our data has shown the beneficial effects of short treatment with LED on ALI that are caused by gram negative bacterial infections. It is suggested that LED applications are an inexpensive and non-invasive additional treatment for sepsis.

Keywords: Sepsis; Acute Lung Injury; Animal Models.

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