A comparison of Australasian jurisdictional ambulance services’ paramedic clinical practice guidelines series: Adult sepsis

IntroductionThis article forms part of a series that seeks to identify interjurisdictional differences in the scope of paramedic practice and differences in patient treatment based upon which jurisdiction a patient is geographically located within at the time of their complaint. Methods The current CPGs of each JAS were accessed during June 2020, and updated in August 2021. Content was extracted and verified. ResultsNine services provide antibiotics for meningococcal septicaemia, with dosage ranging from 1 – 4 grams. Five services provide antibiotics for non-meningococcal sepsis (three under doctor approval), with choice of antibiotic including Ceftriaxone, Benzylpenicillin, Amoxicillin, and Gentamicin. Three services provide antipyretics, one provides corticosteroids under doctor approval, and all provide fluids (with dosage ranging from 20 – 60 ml/kg). ICPs are allowed to provide adrenaline infusions in nine services, noradrenaline in three services (one requiring doctor approval), and metaraminol in three services. Two additional services restrict metaraminol to specialist paramedics, with one of these requiring doctor approval. Two services perform phlebotomy and one takes lactate. Paramedics perform unassisted intubation in one service, with nine restricting this to ICPs. Facilitated or Ketamine-only intubation is performed by ICPs in one service. Rapid or delayed sequence induction is performed by ICPs in six services, and restricted to specialists in two services. ConclusionThe domestic jurisdictional ambulance services in Australasia have each created unique treatment clinical practice guidelines that are heterogeneous in their treatments and scopes of practice. A review of the evidence underlying each intervention is appropriate to determining best practice.

Type IV pilus retraction enables sustained bacteremia and plays a key role in the outcome of meningococcal sepsis in a humanized mouse model

Neisseria meningitidis (the meningococcus) remains a major cause of bacterial meningitis and fatal sepsis. This commensal bacterium of the human nasopharynx can cause invasive diseases when it leaves its niche and reaches the bloodstream. Blood-borne meningococci have the ability to adhere to human endothelial cells and rapidly colonize microvessels. This crucial step enables dissemination into tissues and promotes deregulated inflammation and coagulation, leading to extensive necrotic purpura in the most severe cases. Adhesion to blood vessels relies on type IV pili (TFP). These long filamentous structures are highly dynamic as they can rapidly elongate and retract by the antagonistic action of two ATPases, PilF and PilT. However, the consequences of TFP dynamics on the pathophysiology and the outcome of meningococcal sepsis in vivo have been poorly studied. Here, we show that human graft microvessels are replicative niches for meningococci, that seed the bloodstream and promote sustained bacteremia and lethality in a humanized mouse model. Intriguingly, although pilus-retraction deficient N. meningitidis strain (ΔpilT) efficiently colonizes human graft tissue, this mutant did not promote sustained bacteremia nor induce mouse lethality. This effect was not due to a decreased inflammatory response, nor defects in bacterial clearance by the innate immune system. Rather, TFP-retraction was necessary to promote the release of TFP-dependent contacts between bacteria and, in turn, the detachment from colonized microvessels. The resulting sustained bacteremia was directly correlated with lethality. Altogether, these results demonstrate that pilus retraction plays a key role in the occurrence and outcome of meningococcal sepsis by supporting sustained bacteremia. These findings open new perspectives on the role of circulating bacteria in the pathological alterations leading to lethal sepsis.

MODERN FEATURES OF MENINGOCOCCAL SEPSIS (MENINGOCOCCEMIA) IN CHILDREN

Meningococcal infection is a global health problem worldwide, which is caused by high mortality rates, difficulties in early diagnosis due to the nonspecific nature of the initial manifestations of the disease, and the unpredictability of the course. Invasive forms of infection are registered mainly in children of the first five years of life, which further actualizes this disease. In recent decades, the Republic of Belarus has seen a steady decline in morbidity rates, but given the epidemiological features of meningococcal infection (epidemiological ups and downs with a frequency of 10—20 years), experts are aware of the possible scale of the problem in the coming years. The article presents the results of the analysis (for the last 20 years) structures of invasive forms of meningococcal infection and clinical and laboratory features of meningococcal sepsis in children according to the data of the «City Children's Infectious Clinical Hospital» of Minsk.

Meningismus in IgA vasculitis (Henoch–Schönlein purpura)

IgA vasculitis is the most common acute systemic vasculitis in children. Typical symptoms include cutaneous purpura not associated with thrombocytopenia, acute-onset abdominal pain, arthritis, renal symptoms and, less commonly, neurological symptoms. The disease is usually mild and self-limiting. Although the aetiology of IgA vasculitis is unknown, autoimmune involvement is suspected. Symptomatic treatment is mainly used; therapeutic method that would reduce disease duration and prevent recurrence is unknown. Meningococcal sepsis should always be ruled out in a child with cutaneous purpura. We present a case of a 4-year-old boy with IgA vasculitis who developed symptoms of meningeal irritation.

Management of Meningococcal Disease Risk in Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) on Complement Inhibitors: 18 Years' Experience from the UK National PNH Service in Leeds

Eculizumab, the monoclonal antibody targeting C5, is the only licensed treatment for Paroxysmal Nocturnal Hemoglobinuria (PNH) in the UK. Inherent to the mechanism of action, C5 inhibitors increase patient susceptibility to encapsulated microorganisms, particularly Neisseria meningitidis. The PNH National service (UK), has 18 years of experience treating patients with PNH using complement inhibition. The risk of N. meningitidis is mitigated by vaccination, ciprofloxacin (500 mg bd) on days 1-13 since we moved to vaccination on day one of complement inhibitor therapy, followed by daily prophylaxis with penicillin (or erythromycin). Since a case of sepsis with penicillin-resistant meningococci was observed, patients also have a rescue course ciprofloxacin. Patient education, safety cards, prompt action in case of fever and a 24 hour on-call service for patients are equally important. Until 2010 patients were revaccinated with MenACWY every 3 years. Bexsero (MenB vaccine) vaccination (2 vaccines within first 6 months) with boosters every 5 years was added in 2015. In collaboration with the Public Health England Meningococcal Reference Unit in 2010 a program was developed to monitor antibody titers after vaccination and to revaccinate against MenACWY if titers declined to below protective levels. It is technically not possible to assay for meningoccal serogroup B antibody titers when on Eculizumab therapy. We present the outcome of this project. Methods: Antibody titers to serogroups ACWY were assayed following vaccination and then once per annum. Patients with unprotective antibody titers were revaccinated. We evaluate our practice and review the 9 meningococcal infections in 8 patients. We present disease characteristics, serogroup and outcome, vaccination history and antibody status. Results: Between May 2002 and July 2020, 324 patients commenced complement inhibitor treatment for PNH. 801 vaccinations with MenACWY were administered; median 2 vaccinations per patient (range 1 - 10). A total of 1,671 antibody titer assessments were conducted in 294 patients, median of 4 tests per patient (range 1 - 15). Every test assessed antibodies against all four serogroups. Titers were not assessed in 9% of patients (30), due to vaccination prior to change in practice or recent commencement on treatment. A protective antibody response to all serogroups after first vaccination was observed in 170 / 294 patients (57.8%) and a partial response (antibodies to 3 serotypes) in 51 /294 (17.3%). Revaccination of 51 partial responders resulted in an additional 21 patients with a full response. Revaccination of 73 non-responders (antibodies to 0-2 serotypes) resulted in 32 more partial or full responses. 287 of 324 patients received MenB vaccinations; median 2 vaccinations per patient (range 1 - 4). Eight of 324 (2%) patients with median age 22.5 years developed meningococcal sepsis (see table); patient 5 had 2 episodes. 3 of 5 cases with serogroup B infection were before serogroup B vaccination was introduced. The other 4 episodes in 3 patients were due to Y, C, W meningococci, in one the serogroup is unknown. All except patient 1 were compliant with antibiotic prophylaxis. Patient 7 died from meningococcemia, a delay in seeking medical attention may have contributed, however this was also a penicillin resistant strain. Discussion: We report the largest experience of managing meningococcal risk in patients on complement inhibitor therapy for PNH. Despite our proactive management we had 9 cases of meningococcal sepsis, with one fatal infection. Our most recently introduced practice of prompt treatment with ciprofloxacin if pyrexic on antibiotic prophylaxis will prevent cases like patient 7 with a penicillin resistant strain. Three patients had a meningococci sepsis with serogroups C, W and Y; whilst 1 patient had no check of titers due to recent commencement on treatment, the titres of the other 2 had suggested protective immunity. We demonstrated that a full antibody response can be obtained on a second vaccination in most patients if the first one failed. If no response is achieved upfront or revaccination then further MenACWY vaccination is not likely to be successful. Current practice significantly mitigates the risk of meningococcal disease, however it is essential patients remain vigilant for fever, seeking immediate medical attention stating their diagnosis of PNH on complement inhibitor therapy. Disclosures Arnold: Alexion Pharmaceuticals: Honoraria. Borrow:Pfizer: Research Funding; GlaxoSmithKline: Research Funding; Alexion pharmacueticals: Research Funding; Sanofi: Research Funding. Riley:Alexion: Honoraria. Munir:Alexion: Honoraria; F. Hoffmann-La Roche: Consultancy, Other: Medical writing support, furnished by Scott Battle, PhD, of Health Interactions, was funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland. Kelly:Alexion: Honoraria. Pike:Apellis: Research Funding. Hillmen:Acerta: Other: Financial or material support; Roche: Consultancy, Other: Financial or material support, Research Funding, Speakers Bureau; AbbVie: Consultancy, Other: Financial or material support, Research Funding, Speakers Bureau; Pharmacyclics: Other: Financial or material support, Research Funding; Janssen: Consultancy, Other: Financial or material support, Research Funding, Speakers Bureau; AstraZeneca: Consultancy, Speakers Bureau; Gilead: Other: Financial or material support, Research Funding; Alexion: Consultancy, Research Funding, Speakers Bureau; Apellis: Consultancy, Research Funding, Speakers Bureau. Griffin:Alexion Pharmaceuticals: Honoraria, Other: Conference Support; Biocryst: Membership on an entity's Board of Directors or advisory committees.