No abstract

Intra-abdominal infections (IAI) are an important cause of morbidity and are frequently associated with poor prognosis, particularly in high-risk patients.The cornerstones in the management of complicated IAIs are timely effective source control with appropriate antimicrobial therapy. Empiric antimicrobial therapy is important in the management of intra-abdominal infections and must be broad enough to cover all likely organisms because inappropriate initial antimicrobial therapy is associated with poor patient outcomes and the development of bacterial resistance.The overuse of antimicrobials is widely accepted as a major driver of some emerging infections (such as C. difficile), the selection of resistant pathogens in individual patients, and for the continued development of antimicrobial resistance globally. The growing emergence of multi-drug resistant organisms and the limited development of new agents available to counteract them have caused an impending crisis with alarming implications, especially with regards to Gram-negative bacteria.An international task force from 79 different countries has joined this project by sharing a document on the rational use of antimicrobials for patients with IAIs. The project has been termed AGORA (Antimicrobials: A Global Alliance for Optimizing their Rational Use in Intra-Abdominal Infections). The authors hope that AGORA, involving many of the world's leading experts, can actively raise awareness in health workers and can improve prescribing behavior in treating IAIs.

Antimicrobial de-escalation (ADE) is a strategy to reduce the spectrum of antimicrobials and aims to prevent the emergence of bacterial resistance. We present a systematic review describing the definitions, determinants and outcomes associated with ADE. We included 2 randomized controlled trials and 12 cohort studies. There was considerable variability in the definition of ADE. It was more frequently performed in patients with broad-spectrum and/or appropriate antimicrobial therapy (P= .05 to .002), when more agents were used (P= .002), and in the absence of multidrug-resistant pathogens (P< .05). Where investigated, lower or improving severity scores were consistently associated with ADE (P= .04 to <.001). The pooled effect of ADE on mortality is protective (relative risk, 0.68; 95% confidence interval, .52-.88). Because the determinants of ADE are markers of clinical improvement and/or of lower risk of treatment failure this effect on mortality cannot be retained as evidence. None of the studies were designed to investigate the effect of ADE on antimicrobial resistance.

Specific recommendations about prevention and management of A. baumannii infections in the ICU were elaborated by this multidisciplinary panel. The paucity of randomized controlled trials is noteworthy, so these recommendations are mainly based on observational studies and pharmacodynamics modeling.

We found wide variability in reported practices for antibiotic dosing and monitoring. Research is required to develop evidence-based guidelines to standardize practices.

Background The efficacy of high flow nasal canula oxygen therapy (HFNO) to prevent invasive mechanical ventilation (IMV) is not well established in severe coronavirus disease 2019 (COVID-19). The aim of this study was to compare the risk of IMV between two strategies of oxygenation (conventional oxygenation and HFNO) in critically ill COVID 19 patients. Methods This was a bicenter retrospective study which took place in two intensive care units (ICU) of tertiary hospitals in the Paris region from March 11, to May 3, 2020. We enrolled consecutive patients hospitalized for COVID-19 and acute respiratory failure (ARF) who did not receive IMV at ICU admission. The primary outcome was the rate of IMV after ICU admission. Secondary outcomes were death at day 28 and day 60, length of ICU stay and ventilator-free days at day 28. Data from the HFNO group were compared with those from the standard oxygen therapy (SOT) group using weighted propensity score. Results Among 138 patients who met the inclusion criteria, 62 (45%) were treated with SOT alone, and 76 (55%) with HFNO. In HFNO group, 39/76 (51%) patients received IMV and 46/62 (74%) in SOT group (OR 0.37 [95% CI, 0.18–0.76] p = 0.007). After weighted propensity score, HFNO was still associated with a lower rate of IMV (OR 0.31 [95% CI, 0.14–0.66] p = 0.002). Length of ICU stay and mortality at day 28 and day 60 did not significantly differ between HFNO and SOT groups after weighted propensity score. Ventilator-free days at days 28 was higher in HNFO group (21 days vs 10 days, p = 0.005). In the HFNO group, predictive factors associated with IMV were SAPS2 score (OR 1.13 [95%CI, 1.06–1.20] p = 0.0002) and ROX index > 4.88 (OR 0.23 [95%CI, 0.008–0.64] p = 0.006). Conclusions High flow nasal canula oxygen for ARF due to COVID-19 is associated with a lower rate of invasive mechanical ventilation.

Empirical broad spectrum antimicrobial therapy prescribed in life-threatening situations should be de-escalated to mitigate the risk of resistance emergence. Definitions of de-escalation (DE) vary among studies, thereby biasing their results. The aim of this study was to provide a consensus definition of DE and to establish a ranking of β-lactam according to both their spectra and their ecological consequences. Twenty-eight experts from intensive care, infectious disease and clinical microbiology were consulted using the Delphi method (four successive questionnaires) from July to November 2013. More than 70% of similar answers to a question were necessary to reach a consensus. According to our consensus definition, DE purpose was to reduce both the spectrum of antimicrobial therapy and the selective pressure on microbiota. DE included switching from combination to monotherapy. A six-rank consensual classification of β-lactams allowing gradation of DE was established. The group was unable to differentiate ecological consequences of molecules included in group 4, i.e. piperacillin/tazobactam, ticarcillin/clavulanic acid, fourth-generation cephalosporin and antipseudomonal third-generation cephalosporin. Furthermore, no consensus was reached on the delay within which DE should be performed and on whether or not the shortening of antibiotic therapy duration should be included in DE definition. This study provides a consensual ranking of β-lactams according to their global ecological consequences that may be helpful in future studies on DE. However, this work also underlines the difficulties of reaching a consensus on the relative ecological impact of each individual drug and on the timing of DE.

The antibiotic pipeline continues to diminish and the majority of the public remains unaware of this critical situation. The cause of the decline of antibiotic development is multifactorial and currently most ICUs are confronted with the challenge of multidrug-resistant organisms. Antimicrobial multidrug resistance is expanding all over the world, with extreme and pandrug resistance being increasingly encountered, especially in healthcare-associated infections in large highly specialized hospitals. Antibiotic stewardship for critically ill patients translated into the implementation of specific guidelines, largely promoted by the Surviving Sepsis Campaign, targeted at education to optimize choice, dosage, and duration of antibiotics in order to improve outcomes and reduce the development of resistance. Inappropriate antimicrobial therapy, meaning the selection of an antibiotic to which the causative pathogen is resistant, is a consistent predictor of poor outcomes in septic patients. Therefore, pharmacokinetically/pharmacodynamically optimized dosing regimens should be given to all patients empirically and, once the pathogen and susceptibility are known, local stewardship practices may be employed on the basis of clinical response to redefine an appropriate regimen for the patient. This review will focus on the most severely ill patients, for whom substantial progress in organ support along with diagnostic and therapeutic strategies markedly increased the risk of nosocomial infections.