Epidemiology, Mechanisms of Resistance and Treatment Algorithm for Infections Due to Carbapenem-Resistant Gram-Negative Bacteria: An Expert Panel Opinion.

Antimicrobial resistance represents a serious threat for global health, causing an unacceptable burden in terms of morbidity, mortality and healthcare costs. In particular, in 2017, carbapenem-resistant organisms were listed by the WHO among the group of pathogens for which novel treatment strategies are urgently needed. Fortunately, several drugs and combinations have been introduced in recent years to treat multi-drug-resistant (MDR) bacteria. However, a correct use of these molecules is needed to preserve their efficacy. In the present paper, we will provide an overview on the epidemiology and mechanisms of resistance of the most common MDR Gram-negative bacteria, proposing a treatment algorithm for the management of infections due to carbapenem-resistant bacteria based on the most recent clinical evidence.

Computed tomography imaging of septic shock. Beyond the cause: the "CT hypoperfusion complex". A pictorial essay.

Septic shock is a medical emergency that represents one of the most important underlying causes for presentation to the Emergency Department. Sepsis is defined as organ dysfunction, life-threatening event caused by a deregulated inflammatory host response to infection, with a mortality risk ranging from 10 to 40%. Early sepsis identification is the cornerstone of management and diagnostic imaging can play a pivotal role in this clinical context. The choice of imaging modality depends on several factors, associated with the clinical condition and the presence or absence of localising signs and symptoms. The diagnostic accuracy of contrast-enhanced total-body CT has been well established during septic shock, allowing for a rapid, panoramic, and detailed study of multiple body areas, simultaneously. The aim of this article is to illustrate the controversial CT hypoperfusion complex in patients with septic shock, characterised by the following imaging features: decreased enhancement of the viscera; increased mucosal enhancement; luminal dilation of the small bowel; mural thickening and fluid-filled loops of the small bowel; the halo sign and flattening of the inferior vena cava; reduced aortic diameter; peripancreatic oedema; abnormal parenchymal perfusion; and other controversial findings that are variably associated with each other and reversible during the early stages. Increasing physicians' awareness of the significance of these findings could prompt alternative approaches to the early assessment and management of septic shock. In this perspective, CT imaging represents a useful tool for a complete, rapid and detailed diagnosis of clinically suspected septic shock, which can be used to improve patient outcomes.

Adjunctive IgM-enriched immunoglobulin therapy with a personalised dose based on serum IgM-titres versus standard dose in the treatment of septic shock: a randomised controlled trial (IgM-fat trial).

INTRODUCTION: In patients with septic shock, low levels of circulating immunoglobulins are common and their kinetics appear to be related to clinical outcome. The pivotal role of immunoglobulins in the host immune response to infection suggests that additional therapy with polyclonal intravenous immunoglobulins may be a promising option in patients with septic shock. Immunoglobulin preparations enriched with the IgM component have largely been used in sepsis, mostly at standard dosages (250 mg/kg per day), regardless of clinical severity and without any dose adjustment based on immunoglobulin serum titres or other biomarkers. We hypothesised that a personalised dose of IgM enriched preparation based on patient IgM titres and aimed to achieve a specific threshold of IgM titre is more effective in decreasing mortality than a standard dose. METHODS AND ANALYSIS: The study is designed as a multicentre, interventional, randomised, single-blinded, prospective, investigator sponsored, two-armed study. Patients with septic shock and IgM titres <60 mg/dL will be randomly assigned to an IgM titre-based treatment or a standard treatment group in a ratio of 1:1. The study will involve 12 Italian intensive care units and 356 patients will be enrolled. Patients assigned to the IgM titre-based treatment will receive a personalised daily dose based on an IgM serum titre aimed at achieving serum titres above 100 mg/dL up to discontinuation of vasoactive drugs or day 7 after enrolment. Patients assigned to the IgM standard treatment group will receive IgM enriched preparation daily for three consecutive days at the standard dose of 250 mg/kg. The primary endpoint will be all-cause mortality at 28 days. ETHICS AND DISSEMINATION: The study protocol was approved by the ethics committees of the coordinating centre (Comitato Etico dell'Area Vasta Emilia Nord) and collaborating centres. The results of the trial will be published within 12 months from the end of the study and the steering committee has the right to present them at public symposia and conferences. TRIAL REGISTRATION DETAILS: The trial protocol and information documents have received a favourable opinion from the Area Vasta Emilia Nord Ethical Committee on 12 September 2019. The trial protocol has been registered on EudraCT (2018-001613-33) on 18 April 2018 and on ClinicalTrials.gov (NCT04182737) on 2 December 2019.

Experienced Use of Dexmedetomidine in the Intensive Care Unit: A Report of a Structured Consensus.

OBJECTIVE: Management of pain, agitation and delirium (PAD) remains to be a true challenge in critically ill patients. The pharmacological proprieties of dexmedetomidine (DEX) make it an ideal candidate drug for light and cooperative sedation, but many practical questions remain unanswered. This structured consensus from 17 intensivists well experienced on PAD management and DEX use provides indications for the appropriate use of DEX in clinical practice. METHODS: A modified RAND/UCLA appropriateness method was used. In four predefined patient populations, the clinical scenarios do not properly cope by the current recommended pharmacological strategies (except DEX), and the possible advantages of DEX use were identified and voted for agreement, after reviewing literature data. RESULTS: Three scenarios in medical patients, five scenarios in patients with acute respiratory failure undergoing non-invasive ventilation, three scenarios in patients with cardiac surgery in the early postoperative period and three scenarios in patients with overt delirium were identified as challenging with the current PAD strategies. In these scenarios, the use of DEX was voted as potentially useful by most of the panellists owing to its specific pharmacological characteristics, such as conservation of cognitive function, lack of effects on the respiratory drive, low induction of delirium and analgesia effects. CONCLUSION: DEX might be considered as a first-line sedative in different scenarios even though conclusive data on its benefits are still lacking.