European society of clinical microbiology and infectious diseases guidelines for antimicrobial stewardship in emergency departments (endorsed by European association of hospital pharmacists).

Scope: This European Society of Clinical Microbiology and Infectious Diseases guideline provides evidence-based recommendations to support a selection of appropriate antibiotic use practices for patients seen in the emergency department (ED) and guidance for their implementation. The topics addressed in this guideline are (a) Do biomarkers or rapid pathogen tests improve antibiotic prescribing and/or clinical outcomes? (b) Does taking blood cultures in common infectious syndromes improve antibiotic prescribing and/or clinical outcomes? (c) Does watchful waiting without antibacterial therapy or with delayed antibiotic prescribing reduce antibiotic prescribing without worsening clinical outcomes in patients with specific infectious syndromes? (d) Do structured culture follow-up programs in patients discharged from the ED with cultures pending improve antibiotic prescribing?

Methods: An expert panel was convened by European Society of Clinical Microbiology and Infectious Diseases and the guideline chair. The panel selected in consensus the four most relevant antimicrobial stewardship topics according to pre-defined relevance criteria.

Follow-up of patients with urinary tract infections discharged from the emergency department: a mixed methods study.

Objectives: To evaluate the quality of culture follow-up after emergency department (ED) discharge in patients with urinary tract infections (UTIs).

Methods: This convergent mixed methods study included an observational cohort study and a qualitative interview study in UTI patients discharged from the ED of a Dutch university hospital. The primary outcomes of the observational study were the proportion of patients requiring adjustment of antibiotic therapy after culture review, and the proportion of patients in whom these adjustments were made.

Differences in local immune cell landscape between Q fever and atherosclerotic abdominal aortic aneurysms identified by multiplex immunohistochemistry.

Background: Chronic Q fever is a zoonosis caused by the bacterium which can manifest as infection of an abdominal aortic aneurysm (AAA). Antibiotic therapy often fails, resulting in severe morbidity and high mortality. Whereas previous studies have focused on inflammatory processes in blood, the aim of this study was to investigate local inflammation in aortic tissue.

Quality indicators for appropriate antimicrobial therapy in the emergency department: a pragmatic Delphi procedure.

Objectives: Antimicrobial stewardship (AMS) has established its importance for inpatient care. AMS is, however, also urgently needed in emergency departments (ED), where many antimicrobial prescriptions are initiated. It is currently unclear what metrics stewardship teams can use to measure and improve the appropriateness of antimicrobial prescription in the ED.

Antimicrobial stewardship in the emergency department: characteristics and evidence for effectiveness of interventions.

Background: Emergency departments (EDs) are the entrance gates for patients presenting with infectious diseases into the hospital, yet most antimicrobial stewardship programmes are primarily focused on inpatient management. With equally high rates of inappropriate antibiotic use, the ED is a frequently overlooked yet important unit for targeted antimicrobial stewardship (AMS) interventions.

Objectives: We aimed to (a) describe the specific aspects of antimicrobial stewardship in the ED and (b) summarize the findings from improvement studies that have investigated the effectiveness of antimicrobial stewardship interventions in the ED setting.

Single nucleotide polymorphism (SNP) rs3751143 in P2RX7 is associated with therapy failure in chronic Q fever while rs7125062 in MMP1 is associated with fewer complications.

Objectives: Chronic Q fever is a persistent infection with the intracellular bacterium Coxiella burnetii. Development of chronic Q fever is associated with single nucleotide polymorphisms (SNPs) in genes encoding for pattern recognition receptors, for phagolysosomal pathway components and for matrix metalloproteinases (MMPs). We evaluated the association of SNPs in these innate-immunity and MMP genes with clinical outcomes.

Genetic variations in innate immunity genes affect response to Coxiella burnetii and are associated with susceptibility to chronic Q fever.

Objectives: Chronic Q fever is a persistent infection, mostly of aortic aneurysms, vascular prostheses or damaged heart valves, caused by the intracellular bacterium Coxiella burnetii. Only a fraction of C. burnetii-infected individuals at risk develop chronic Q fever.

Viable Coxiella burnetii Induces Differential Cytokine Responses in Chronic Q Fever Patients Compared to Heat-Killed Coxiella burnetii.

Cytokine responses of chronic Q fever patients to the intracellular bacterium have mostly been studied using stimulation of immune cells with heat-killed due to the extensive measures needed to work with viable biosafety level 3 agents. Whether research with heat-killed can be translated to immune responses to viable is imperative for the interpretation of previous and future studies with heat-killed Peripheral blood mononuclear cells (PBMCs) of chronic Q fever patients ( = 10) and healthy controls ( = 10) were stimulated with heat-killed or viable of two strains, Nine Mile and the Dutch outbreak strain 3262, for 24 h, 48 h, and 7 days in the absence or presence of serum containing anti- antibodies. When stimulated with viable , PBMCs of chronic Q fever patients and controls produced fewer proinflammatory cytokines (interleukin-6 [IL-6], tumor necrosis factor alpha, and IL-1β) after 24 h than after stimulation with heat-killed In the presence of Q fever seronegative serum, IL-10 production was higher after stimulation with viable rather than heat-killed ; however, when incubating with anti- antibody serum, the effect on IL-10 production was reduced.

Interferon-γ and CXCL10 responses related to complaints in patients with Q fever fatigue syndrome.

Approximately 20% of patients with acute Q fever develop Q fever fatigue syndrome (QFS), a debilitating fatigue syndrome. This study further investigates the role of C. burnetii-specific IFNγ, but also IL-2, CXCL9, CXCL10, and CXLC11 production in QFS patients.

CXCL9, a promising biomarker in the diagnosis of chronic Q fever.

Background: In the aftermath of the largest Q fever outbreak in the world, diagnosing the potentially lethal complication chronic Q fever remains challenging. PCR, Coxiella burnetii IgG phase I antibodies, CRP and F-FDG-PET/CT scan are used for diagnosis and monitoring in clinical practice. We aimed to identify and test biomarkers in order to improve discriminative power of the diagnostic tests and monitoring of chronic Q fever.

Involvement of matrix metalloproteinases in chronic Q fever.

Objectives: Chronic Q fever is a persistent infection with the intracellular Gram-negative bacterium Coxiella burnetii, which can lead to complications of infected aneurysms. Matrix metalloproteinases (MMPs) cleave extracellular matrix and are involved in infections as well as aneurysms. We aimed to study the role of MMPs in the pathogenesis of chronic Q fever.

Intact interferon-γ response against Coxiella burnetii by peripheral blood mononuclear cells in chronic Q fever.

Objectives: Q fever is caused by Coxiella burnetii, an intracellular bacterium that infects phagocytes. The aim of the present study was to investigate whether the C. burnetii-induced IFN-γ response is defective in chronic Q fever patients.

A Functional Genomics Approach to Understand Variation in Cytokine Production in Humans.

As part of the Human Functional Genomics Project, which aims to understand the factors that determine the variability of immune responses, we investigated genetic variants affecting cytokine production in response to ex vivo stimulation in two independent cohorts of 500 and 200 healthy individuals. We demonstrate a strong impact of genetic heritability on cytokine production capacity after challenge with bacterial, fungal, viral, and non-microbial stimuli. In addition to 17 novel genome-wide significant cytokine QTLs (cQTLs), our study provides a comprehensive picture of the genetic variants that influence six different cytokines in whole blood, blood mononuclear cells, and macrophages.

A fatal case of disseminated chronic Q fever: a case report and brief review of the literature.

Background: Chronic Q fever is a rare infection, which mainly manifests as endocarditis, infection of vascular prostheses or aortic aneurysms. We present the case of a 74-year-old immunocompromised man with a haematologically disseminated Coxiella burnetii infection, which has never been reported before.

Case Report: He was diagnosed with a chronic Q fever infection of an aneurysm with an endovascular prosthesis in 2015, but he died despite optimal treatment.

Altered interferon-γ response in patients with Q-fever fatigue syndrome.

Objectives: Whether immunological mechanisms underlie Q-fever fatigue syndrome (QFS) remains unclear. For acute Q-fever, the antigen-specific interferon-γ (IFNγ) response may be a useful tool for diagnosis, and the IFNγ/interleukin(IL)-2 production ratio may be a marker for chronic Q-fever and treatment monitoring. Here we explored the specific IFNγ production and IFNγ/IL-2 ratio in QFS patients.

Coverage of the 2011 Q fever vaccination campaign in the Netherlands, using retrospective population-based prevalence estimation of cardiovascular risk-conditions for chronic Q fever.

Background: In 2011, a unique Q fever vaccination campaign targeted people at risk for chronic Q fever in the southeast of the Netherlands. General practitioners referred patients with defined cardiovascular risk-conditions (age >15 years). Prevalence rates of those risk-conditions were lacking, standing in the way of adequate planning and coverage estimation.

Specific in vitro interferon-gamma and IL-2 production as biomarkers during treatment of chronic Q fever.

Background: Antibiotic treatment of chronic Q fever is cumbersome and of long duration. To monitor treatment, there is a need for alternative biomarkers. Coxiella burnetii-specific interferon (IFN)-γ and interleukin (IL)-2 production reflect the type of effector and memory T-cell response.

Genetic Variation in Pattern Recognition Receptors and Adaptor Proteins Associated With Development of Chronic Q Fever.

Background: Q fever is an infection caused by Coxiella burnetii. Persistent infection (chronic Q fever) develops in 1%-5% of patients. We hypothesize that inefficient recognition of C.

Early cytokine and antibody responses against Coxiella burnetii in aerosol infection of BALB/c mice.

Coxiella burnetii, a Gram-negative intracellular bacterium, can give rise to Q fever in humans and is transmitted mainly by inhalation of infected aerosols from animal reservoirs. Serology is commonly used to diagnose Q fever, but the early cellular immune response-i.e.

Adverse events and association with age, sex and immunological parameters of Q fever vaccination in patients at risk for chronic Q fever in the Netherlands 2011.

Background: Following a large Q fever outbreak in the Netherlands, patients at risk for chronic Q fever received a whole-cell Q fever vaccine. Sensitized people were excluded based on pre-vaccination screening with skin test (ST) and serology. An investigational IFN-γ-production assay was added.

The effect of C. burnetii infection on the cytokine response of PBMCs from pregnant goats.

In humans, infection with Coxiella burnetii, the causative agent of Q fever, leads to acute or chronic infection, both associated with specific clinical symptoms. In contrast, no symptoms are observed in goats during C. burnetii infection, although infection of the placenta eventually leads to premature delivery, stillbirth and abortion.

Recognition of Coxiella burnetii by toll-like receptors and nucleotide-binding oligomerization domain-like receptors.

Background: Infection with Coxiella burnetii can lead to acute and chronic Q fever. Toll-like receptor 1 (TLR1), TLR2, TLR4, TLR6, nucleotide-binding oligomerization domain receptor 1 (NOD1), NOD2, and the mitogen-activated protein kinases are central in the innate immune response against microorganisms, but little is known about their role in the recognition of C. burnetii in humans.

Diagnosis of Coxiella burnetii infection: comparison of a whole blood interferon-gamma production assay and a Coxiella ELISPOT.

Diagnosis of ongoing or past infection with Coxiella burnetii, the causative agent of Q fever, relies heavily on serology: the measurement of C. burnetii-specific antibodies, reflecting the host's humoral immune response. However, cell-mediated immune responses play an important, probably even more relevant, role in infections caused by the intracellular C.

Acute and probable chronic Q fever during anti-TNFα and anti B-cell immunotherapy: a case report.

Background: Q fever is caused by the intracellular bacterium Coxiella burnetii. Initial infection can present as acute Q fever, while a minority of infected individuals develops chronic Q fever endocarditis or vascular infection months to years after initial infection. Serology is an important diagnostic tool for both acute and chronic Q fever.