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BackgroundAntimicrobial de-escalation (ADE) is a strategy of antimicrobial stewardship, aiming at preventing the emergence of antimicrobial resistance (AMR) by decreasing the exposure to broad-spectrum antimicrobials. There is no high-quality research on ADE and its effects on AMR. Its definition varies and there is little evidence-based guidance for clinicians to use ADE in the intensive care unit (ICU).MethodsA task force of 16 international experts was formed in November 2016 to provide with guidelines for clinical practice to develop questions targeted at defining ADE, its effects on the ICU population and to provide clinical guidance. Groups of 2 experts were assigned 1–2 questions each within their field of expertise to provide draft statements and rationale. A Delphi method, with 3 rounds and an agreement threshold of 70% was required to reach consensus.ResultsWe present a comprehensive document with 13 statements, reviewing the evidence on the definition of ADE, its effects in the ICU population and providing guidance for clinicians in subsets of clinical scenarios where ADE may be considered.ConclusionADE remains a topic of controversy due to the complexity of clinical scenarios where it may be applied and the absence of evidence to the effects it may have on antimicrobial resistance.

Sepsis is a common consequence of infection, associated with a mortality rate > 25%. Although community-acquired sepsis is more common, hospital-acquired infection is more lethal. The most common site of infection is the lung, followed by abdominal infection, catheter-associated blood steam infection and urinary tract infection. Gram-negative sepsis is more common than gram-positive infection, but sepsis can also be due to fungal and viral pathogens. To reduce mortality, it is necessary to give immediate, empiric, broad-spectrum therapy to those with severe sepsis and/or shock, but this approach can drive antimicrobial overuse and resistance and should be accompanied by a commitment to de-escalation and antimicrobial stewardship. Biomarkers such a procalcitonin can provide decision support for antibiotic use, and may identify patients with a low likelihood of infection, and in some settings, can guide duration of antibiotic therapy. Sepsis can involve drug-resistant pathogens, and this often necessitates consideration of newer antimicrobial agents.

Severe or life threatening infections are common among patients in the intensive care unit (ICU). Most infections in the ICU are bacterial or fungal in origin and require antimicrobial therapy for clinical resolution. Antibiotics are the cornerstone of therapy for infected critically ill patients. However, antibiotics are often not optimally administered resulting in less favorable patient outcomes including greater mortality. The timing of antibiotics in patients with life threatening infections including sepsis and septic shock is now recognized as one of the most important determinants of survival for this population. Individuals who have a delay in the administration of antibiotic therapy for serious infections can have a doubling or more in their mortality. Additionally, the timing of an appropriate antibiotic regimen, one that is active against the offending pathogens based on in vitro susceptibility, also influences survival. Thus not only is early empiric antibiotic administration important but the selection of those agents is crucial as well. The duration of antibiotic infusions, especially for β-lactams, can also influence antibiotic efficacy by increasing antimicrobial drug exposure for the offending pathogen. However, due to mounting antibiotic resistance, aggressive antimicrobial de-escalation based on microbiology results is necessary to counterbalance the pressures of early broad-spectrum antibiotic therapy. In this review, we examine time related variables impacting antibiotic optimization as it relates to the treatment of life threatening infections in the ICU. In addition to highlighting the importance of antibiotic timing in the ICU we hope to provide an approach to antimicrobials that also minimizes the unnecessary use of these agents. Such approaches will increasingly be linked to advances in molecular microbiology testing and artificial intelligence/machine learning. Such advances should help identify patients needing empiric antibiotic therapy at an earlier time point as well as the specific antibiotics required in order to avoid unnecessary administration of broad-spectrum antibiotics.

The treatment of serious bacterial infections is complicated by the fact that time to initiation of effective antimicrobial therapy is a strong predictor of mortality. Therefore, therapy must be initiated before the causative pathogen is identified. However, inappropriate or inadequate initial empirical therapy is associated with increased mortality, morbidity, and length of hospital stay. Initial empirical therapy with broad-spectrum antimicrobials attempts to address this dilemma by “getting it right up front.” The goal is to provide treatment active against the most likely pathogens until culture/susceptibility test results are obtained. After the causative pathogen is identified, streamlining to more-precise therapy of the shortest acceptable duration is implemented. In this way, the risks of death, morbid complications, increased duration of hospital stay (as a result of ineffective initial treatment), and emergence of resistance (due to extended treatment with broad-spectrum agents) are lowered. Improved clinical and economic outcomes after such an approach have been demonstrated.

A recent increase in staphylococcal infections caused by methicillin-resistant Staphylococcus aureus (MRSA), combined with frequent, prolonged ventilatory support of an aging, often chronically ill population, has resulted in a large increase in cases of MRSA pneumonia in the health care setting. In addition, community-acquired MRSA pneumonia has become more prevalent. This type of pneumonia historically affects younger patients, follows infection with influenza virus, and is often severe, requiring hospitalization and causing the death of a significant proportion of those affected. Ultimately, hospital-acquired MRSA and community-acquired MRSA are important causes of pneumonia and present diagnostic and therapeutic challenges. Rapid institution of appropriate antibiotic therapy, including linezolid as an alternative to vancomycin, is crucial. Respiratory infection–control measures and de-escalation of initial broad-spectrum antibiotic regimens to avoid emergence of resistant organisms are also important. This article reviews the clinical features of, diagnosis of, and therapies for MRSA pneumonia.

Background Providing supplemental oxygen is fundamental in the management of mechanically ventilated patients. Increasing amounts of data show worse clinical outcomes associated with hyperoxia. However, these previous data in the critically ill have not focused on outcomes associated with brief hyperoxia exposure immediately after endotracheal intubation. Therefore, the objectives of this study were to evaluate the impact of isolated early hyperoxia exposure in the emergency department (ED) on clinical outcomes among mechanically ventilated patients with subsequent normoxia in the intensive care unit (ICU). Methods This was an observational cohort study conducted in the ED and ICUs of an academic center in the USA. Mechanically ventilated normoxic (partial pressure of arterial oxygen (P a O 2 ) 60–120 mm Hg) ICU patients with mechanical ventilation initiated in the ED were studied. The cohort was categorized into three oxygen exposure groups based on P a O 2 values obtained after ED intubation: hypoxia, normoxia, and hyperoxia (defined as P a O 2  < 60 mmHg, P a O 2 60–120 mm Hg, and P a O 2  > 120 mm Hg, respectively, based on previous literature). Results A total of 688 patients were included. ED normoxia occurred in 350 (50.9%) patients, and 300 (43.6%) had exposure to ED hyperoxia. The ED hyperoxia group had a median (IQR) ED P a O 2 of 189 mm Hg (146–249), compared to an ED P a O 2 of 88 mm Hg (76–101) in the normoxia group, P  < 0.001. Patients with ED hyperoxia had greater hospital mortality (29.7%), when compared to those with normoxia (19.4%) and hypoxia (13.2%). After multivariable logistic regression analysis, ED hyperoxia was an independent predictor of hospital mortality (adjusted OR 1.95 (1.34–2.85)). Conclusions ED exposure to hyperoxia is common and associated with increased mortality in mechanically ventilated patients achieving normoxia after admission. This suggests that hyperoxia in the immediate post-intubation period could be particularly injurious, and targeting normoxia from initiation of mechanical ventilation may improve outcome.

Introduction Pseudomonas aeruginosa nosocomial pneumonia ( Pa -NP) is associated with considerable morbidity, prolonged hospitalization, increased costs, and mortality. Methods We conducted a retrospective cohort study of adult patients with Pa -NP to determine 1) risk factors for multidrug-resistant (MDR) strains and 2) whether MDR increases the risk for hospital death. Twelve hospitals in 5 countries (United States, n = 3; France, n = 2; Germany, n = 2; Italy, n = 2; and Spain, n = 3) participated. We compared characteristics of patients who had MDR strains to those who did not and derived regression models to identify predictors of MDR and hospital mortality. Results Of 740 patients with Pa -NP, 226 patients (30.5%) were infected with MDR strains. In multivariable analyses, independent predictors of multidrug-resistance included decreasing age (adjusted odds ratio [AOR] 0.91, 95% confidence interval [CI] 0.96-0.98), diabetes mellitus (AOR 1.90, 95% CI 1.21-3.00) and ICU admission (AOR 1.73, 95% CI 1.06-2.81). Multidrug-resistance, heart failure, increasing age, mechanical ventilation, and bacteremia were independently associated with in-hospital mortality in the Cox Proportional Hazards Model analysis. Conclusions Among patients with Pa -NP the presence of infection with a MDR strain is associated with increased in-hospital mortality. Identification of patients at risk of MDR Pa -NP could facilitate appropriate empiric antibiotic decisions that in turn could lead to improved hospital survival.

Vancomycin is effective against methicillin-resistant Staphylococcus aureus and has been widely used in the past few years. However, several recent reports have highlighted the limitations of vancomycin, and its role in the management of serious infections is now being reconsidered. Vancomycin treatment failure rates are associated with an increase in the minimum inhibitory concentration as well as a decrease in the rate of bacterial killing. The intrinsic limitations of vancomycin also include poor tissue penetration, particularly in the lung; relatively slow bacterial killing; and the potential for toxicity. In addition, intermediate-level vancomycin resistance has emerged among staphylococci, as have rare cases of fully resistant strains. Because of these problems, when using vancomycin, it is probably prudent to carefully establish the diagnosis, test for antimicrobial susceptibility, and monitor serum trough concentrations to ensure adequate dosing.

Inadequate antimicrobial treatment, generally defined as microbiological documentation of an infection that is not being effectively treated, is an important factor in the emergence of infections due to antibiotic-resistant bacteria. Factors that contribute to inadequate antimicrobial treatment of hospitalized patients include prior antibiotic exposure, use of broad-spectrum antibiotics, prolonged length of stay, prolonged mechanical ventilation, and presence of invasive devices. Strategies to minimize inadequate treatment include consulting an infectious disease specialist, using antibiotic practice guidelines, and identifying quicker methods of microbiological identification. In addition, clinicians should determine the prevailing pathogens that account for the community-acquired and nosocomial infections identified in their hospitals. Clinicians can improve antimicrobial treatment by using empirical combination antibiotic therapy based on individual patient characteristics and the predominant bacterial flora and their antibiotic susceptibility profiles. This broad-spectrum therapy can then be narrowed when initial culture results are received. Further study evaluating the use of antibiotic practice guidelines and strategies to reduce inadequate treatment is necessary to determine their impact on patient outcomes.