What’s New in ID April-June 2020. – Travanj-Lipanj 2020.

What’s new in ID April 2020 – June 2020.

Authors: Marija Kusulja, Vladimir Krajinović

1. Association of a Care Bundle for Early Sepsis Management With Mortality Among Patients With Hospital-Onset or Community-Onset Sepsis

This retrospective cohort study aimed to asses the difference that the Early Management Bundle for Severe Sepsis/Septic Shock (SEP-1) has on mortality and organ dysfunction in 2296 patients with hospital-onset sepsis and 4108 patients with community-onset sepsis. Patients with community-onset sepsis benefited several components of SEP-1 budle: early lactate level testing (within 3 hours of admission), blood culures and broad-spectrum intravenous antibiotic treatment, requiring fewer vasopressor days. Patients with hospital-onset sepsis benefited only from broad-spectrum intravenous antibiotic treament, which lowered mortality. Care completely adherent to SEP-1 budle did not reduce mortality significantly in either group. The auhors suggest that current sepsis quality metrics need to be refined.

Baghdadi JD, Brook R,  Uslan DZ, Needleman J, Bell DS, Cunningham WE et al. Association of a Care Bundle for Early Sepsis Management With Mortality Among Patients With Hospital-Onset or Community-Onset Sepsis. JAMA Intern Med. Published online April 6, 2020. doi:10.1001/jamainternmed.2020.0183

2. New Kaposi’s sarcoma-associated herpesvirus variant in men who have sex with men associated with severe pathologies

This study evaluated MSM population in France for Kaposi’s sarcoma-associated herpesvirus diversity. It involved 57 HIV-infected MSM patients with Kaposi’s sarcoma, multicentric Castleman disease and primary effusion lymphoma; as well as a group of 199 patients to screen for a new variant of herpesvirus. The resulsts showed that the most common Kaposi’s sarcoma-associated herpesvirus strain was subtype C (51%) and second most common was subtype A (33%). The study found that four patients with severe disease (Kaposi’s sarcoma, multicentric Castleman disease and primary effusion lymphoma) had a new virus variant similar to Ugandan subtype F, whose prevalence in Caucasian MSM is 4.5% and which doesn’t appear in other epidemiological groups. The study suggests that screening for a new variant of Kaposi’s sarcoma-associated herpesvirus (subtype F2) might be needed in MSM population, given its connection to severe clinical presentation.

Jary A, Leducq V, Desire N, Petit H, Palich R, Joly V et al. New Kaposi’s sarcoma-associated herpesvirus variant in men who have sex with men associated with severe pathologies. J Infect Dis. 2020 Apr 13. pii: jiaa180. doi: 10.1093/infdis/jiaa180. [Epub ahead of print]

3. Specificity and diagnostic utility of CSF CXCL13 in Lyme neuroborreliosis.

This study assessed utility of nonspecific inflammation marker CXCL13 in CSF in patients with neuroinflammatory disorders. CSF CSCL13 was compared to other markers of inflammation and Borrelia-specific antibody levels in 132 patients. The results revealed that CSF CXCL13 elevation was correlated with CSF IgG synthesis and cell count. However, in neuroborreliosis, CXCL13 levels were much higher than what would be expected with simultaneously measured overall CSF IgG and Borrelia-specific antibody. The difference between CXCL13 concentration in patients with Borrelia-specific antibodies and those with other neuroinflammatory disorders (including „probable“ neuroborreliosis without Borrelia-specific antibodies) was more than 500 greater. The disproportionate increase in CXCL13 might serve as an additional tool for definite neuroborreliosis diagnosis, helping with very early dianognosis of neuroborreliosis, as well as differentiation of active and treated neuroborreliosis.

Eckman EA, Clausen DM, Herdt AR, Pacheco-Quinto J, Halperin JJ. Specificity and diagnostic utility of CSF CXCL13 in Lyme neuroborreliosis. Clin Infect Dis. 2020 Mar 28. pii: ciaa335. doi: 10.1093/cid/ciaa335.

4. Epidemiology and Risk Factors for Community Associated Clostridioides difficile in Children.

This case-control study’s aim was to retrospectively asses the risk factors for community-associated Clostridioides difficile infection in children of ages 1-17. The study group tested children’s stool specimens from Northern California health centres from 2012 to 2016 and age-matched those with community-associated C. difficile with those with negative results. They found a noticeable increase in incidence of C. difficile diarrhea in 2012 (9.6 per 100 000 children per year) and in  2015 (16.9 per 100 000 children per year). The risk factors were non-Hispanic ethnicity; use of amoxicillin-clavulanate, cephalosporin and clindamycin within previous 12 weeks, previous positive C. difficile test within 6 months and increased health-case visits in the previous year. The authors warn that the increased incidence of C. difficile diarrhea in children warrants stricted antibiotic stewardship measures.

Miranda-Katz M, Parmar D, Dang R, Alabaster A, Greenhow TL. Epidemiology and Risk Factors for Community Associated Clostridioides difficile in Children. J Pediatr 2020. https://doi.org/10.1016/j.jpeds.2020.02.005

5. Evaluation of a Paradigm Shift From Intravenous Antibiotics to Oral Step-Down Therapy for the Treatment of Infective Endocarditis: A Narrative Review

This review article warns that longer administrassion of intravenous antibiotics is associated with many adverse events and since many orally administered antibiotics now achieve adequate blood levels, various studies have recently considered them in step-down treatment of infective endocarditis involving right-sided, left-sided and prosthetic valves. Out of 21 reviewed studies, non found the oral antibiotic step-down regime inferior to full course of intravenous antibiotic treatment, and multiple studies described improved clinical cure rate and mortality among the oral step-down group. In conclusion, there is plenty evidence that oral step-down antibiotic treatment should be practiced in treatment of infective endocarditis after clearing bacteremia and achieving clinical stability with intravenous treatment.

Spellberg B, Chambers HF, Musher DM, Walsh TL; Bayer AS. Evaluation of a Paradigm Shift From Intravenous Antibiotics to Oral Step-Down Therapy for the Treatment of Infective Endocarditis: A Narrative Review. JAMA Intern Med ; 2020 Mar 30.

6. Efficacy of a tetravalent dengue vaccine in healthy children aged 4-16 years: a randomised, placebo-controlled, phase 3 trial.

There is still need for effective dengue virus vaccine, especially to denue-naive persons and those younger than 9. This randomised, placebo-controlled trial involved 20 099 participants and assessed a two-dose live attenuated tetravalent dengue vaccine (TAK-003) in healthy children 4-16 years old in endemic regions in Asia and Latin America, who were followed-up for 18 months. In the first 11 months after vaccination, overall vaccine efficacy was 80.2% (61 cases of virologically confirmed dengue in the vaccine group and 149 cases in placebo group). After 17 months, the overal vaccine efficace was 73.3% overall; 76.1% in those who were seropositive at baseline and 66.2% in those seronegative at baseline. Efficacy was highest for DENV2 seroype (95.1%) and lowest for DENV3 serotype (48.9%). Serious adverse events were similar in vaccine and placebo groups. This study indicates good efficacy and safety profile of TAK-003 vaccine aainst symptomatic dengue in children regardles of previous serostatus.

Biswal S, Borja-Tabora C, Martinez Vargas L, Velásquez H, Theresa Alera M, Sierra V et al.  Efficacy of a tetravalent dengue vaccine in healthy children aged 4-16 years: a randomised, placebo-controlled, phase 3 trial. Lancet. 2020 May 2;395(10234):1423-1433. doi: 10.1016/S0140-6736(20)30414-1. Epub 2020 Mar 17.

7. International guidelines for the management of septic shock in children (May 2020)

The new 2020 Surviving Sepsis Campaign international guidelines for the management of septic shock in children are available. The guidelines include an initial resuscitation algorithm for children for both intensive care capable and resource-limited settings that emphasizes early recognition of septic shock and timely administration of balanced crystalloid fluid resuscitation, empiric broad-spectrum antibiotics, and, for patients not adequately responding to fluid resuscitation, vasoactive agents (eg, epinephrine or norepinephrine). Important changes from prior guidance include preference for balanced crystalloid solutions (eg, Ringer’s lactate) during fluid resuscitation, use of ideal body weight for calculation of fluid volume, and use of direct measures of hemodynamic variables (eg, cardiac output or systemic vascular resistance) in addition to bedside clinical signs for ongoing management of fluid-refractory and catecholamine-resistant shock.

Weiss SL, Peters MJ, Alhazzani W, et al. Executive Summary: Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-Associated Organ Dysfunction in Children. Pediatr Crit Care Med. 2020;21(2):186‐195. doi:10.1097/PCC.0000000000002197

Weiss SL, Peters MJ, Alhazzani W, et al. Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-Associated Organ Dysfunction in Children. Pediatr Crit Care Med. 2020;21(2):e52‐e106. doi:10.1097/PCC.0000000000002198

Uptodate, June 2020.