Background: Tracheostomy can be performed safely in patients with coronavirus disease 2019 (COVID-19). However, little is known about the optimal timing, effects on outcome, and complications. Methods: A multicenter, retrospective, observational study. This study included 153 tracheostomized COVID-19 patients from 11 intensive care units (ICUs). The primary endpoint was the median time to tracheostomy in critically ill COVID-19 patients. Secondary endpoints were survival rate, length of ICU stay, and post-tracheostomy complications, stratified by tracheostomy timing (early versus late) and technique (surgical versus percutaneous). Results: The median time to tracheostomy was 15 (1–64) days. There was no significant difference in survival between critically ill COVID-19 patients who received tracheostomy before versus after day 15, nor between surgical and percutaneous techniques. ICU length of stay was shorter with early compared to late tracheostomy (p < 0.001) and percutaneous compared to surgical tracheostomy (p = 0.050). The rate of lower respiratory tract infections was higher with surgical versus percutaneous technique (p = 0.007). Conclusions: Among critically ill patients with COVID-19, neither early nor percutaneous tracheostomy improved outcomes, but did shorten ICU stay. Infectious complications were less frequent with percutaneous than surgical tracheostomy.

Candida auris is an emerging healthcare-associated infection that can easily cause dissemination in hospitals through colonizing the skin and contaminating environmental surfaces, especially in Intensive Care Units (ICU). Difficulties with identification of this organism, uncertainty about routes of transmission and antifungals resistance have impacted significantly outbreak detection and management. Here, we describe our experience with colonization/infection of C. auris among critically ill patients, admitted to a referral ICU of a University Hospital, in a transitional period (July 2021–March 2022) between management of non-COVID-19 and COVID-19 patients due to the reconversion of the ICU between two waves. A total of 8 patients presented colonization from C. auris, and two of them developed invasive infection from C. auris. The fungal pathogen was cultured from different sites: the skin (7 isolates), urine (2), respiratory tract (1), blood (1). The median time from admission to first detection is 24 days with 100% of patients requiring mechanical ventilation. All 8 patients received broad-spectrum antibiotic therapy for bacterial infections before identification of C. auris; 62.5% of the patients had prior antifungal exposure; 87.5% received steroids; 37.5% patients used immunomodulatory; and 75% had severe COVID-19 illness prior to C. auris identification. Only two cases (25%) were treated with antifungals as C. auris infections (1 patient for suspected UTI; 1 patient with candidemia). Infection control measures, including rapid microbiological identification, contact isolation, screening of contacts, antisepsis of colonized patients, dedicated equipment, cleaning and disinfection of the environment and subsequent follow-up sampling, remain essential in critically ill patients. Our experience highlights the importance of establishing a multidisciplinary model and bundling of practices for preventing C. auris’ spread.

Considering the growing prevalence of carbapenem-resistant Gram-negative bacteria (CR-GNB) bloodstream infection (BSI) in intensive care units (ICUs), the identification of specific risk factors and the development of a predictive model allowing for the early identification of patients at risk for CR-Klebsiella pneumoniae, Acinetobacter baumannii or Pseudomonas aeruginosa are essential. In this retrospective case–control study including all consecutive patients showing an episode of BSI in the ICUs of a university hospital in Italy in the period January–December 2016, patients with blood culture positive for CR-GNB pathogens and for any other bacteria were compared. A total of 106 patients and 158 episodes of BSI were identified. CR-GNBs induced BSI in 49 patients (46%) and 58 episodes (37%). Prognosis score and disease severity at admission, parenteral nutrition, cardiovascular surgery prior to admission to ICU, the presence of sepsis and septic shock, ventilation-associated pneumonia and colonization of the urinary or intestinal tract were statistically significant in the univariate analysis. The duration of ventilation and mortality at 28 days were significantly higher among CR-GNB cases. The prognostic model based on age, presence of sepsis, previous cardiovascular surgery, SAPS II, rectal colonization and invasive respiratory infection from the same pathogen showed a C-index of 89.6%. The identified risk factors are in line with the international literature. The proposal prognostic model seems easy to use and shows excellent performance but requires further studies to be validated.

Normal levels of plasma antithrombin (AT) activity might decrease heparin requirements to achieve an adequate level of anticoagulation during treatment with extracorporeal membrane oxygenation (ECMO). Acquired AT deficiency during ECMO is common, but formal recommendations on target, timing, and rate of AT supplementation are lacking. Thus, we conceived a pilot trial to evaluate the feasibility and safety of prolonged AT supplementation in patients requiring veno-venous ECMO for respiratory failure. Grifols Antithrombin Research Awards (GATRA) is a prospective, randomized, single blinded, multicenter, controlled two-arm trial. Patients undergoing veno-venous ECMO will be randomized to either receive AT supplementation to maintain a functional AT level between 80 and 120% (AT supplementation group) or not (control group) for the entire ECMO course. In both study groups, anticoagulation will be provided with unfractionated heparin following a standardized protocol. The primary endpoint will be the dose of heparin required to maintain the ratio of activated partial thromboplastin time between 1.5 and 2. Secondary endpoints will be the adequacy of anticoagulation and the incidence of hemorrhagic and thrombotic complications. GATRA is a pilot trial that will test the efficacy of a protocol of AT supplementation in decreasing the heparin dose and improving anticoagulation adequacy during ECMO. If positive, it might provide the basis for a future larger trial aimed at verifying the impact of AT supplementation on a composite outcome endpoint including hemorrhagic events, transfusion requirements, and mortality. ClinicalTrials.gov, NCT03208270 . Registered on 5 July 2017.

More than two-thirds of critically ill patients receive an antimicrobial therapy with a percentage between 30% and 50% of all prescribed antibiotics reported to be unnecessary, inappropriate or misused. Since inappropriate prescription of antibiotic drugs concurs to dissemination of the multidrug resistant organisms, a reasoned antibiotics use is crucial especially in Intensive Care Unit (ICU), where up to 60% of the admitted patients develops an infection during their ICU stay. Even if the concept of antimicrobial stewardship (AS) has been clearly described as a series of coordinated interventions designed to improve antimicrobial agents use, few studies are reporting about its effectiveness to improve outcomes, reduce adverse events and costs and decrease resistance rate spread. Moreover, although it is recognized that AS programs are particularly indicated in the critical setting due to the huge number of antimicrobial drugs used, the optimal characteristics of these interventions and the best system to evaluate their effectiveness are still unclear. Specific interventions, designed tacking into account the peculiarities of the ICU setting, are hence necessary to set-up an "in-ICU-stewardship," including prompt identification of infected patients, selection of appropriate empiric treatments, optimization of dosing and route of administration, improvement of diagnostic techniques, early de-escalation to achieve shorter duration and avoid unnecessary therapies. The present narrative review summarizes the "state of art" about AS programmes and discusses the effects of the interventions possibly applied in ICU setting to optimize the patient's treatment, reduce the micro-organisms resistance and contain the hospital resources utilization.

Background: Bacterial superinfections are common complications during viral infections, but the impact of multidrug-resistant (MDR) pathogens in critically ill patients affected by coronavirus disease 2019 (COVID-19) is still debated. Methods: This is an observational, monocentric, and prospective study designed to investigate the incidence, risk factors, and outcomes of MDR bacterial superinfections in COVID-19 patients admitted to the intensive care unit (ICU). Results: A high incidence of superinfections (66%, 159/241) was observed: ventilator-associated pneumonia (VAP) (65%, 104/159) and bloodstream infection (BSI, 32%, 51/159) were the most common. Superinfections, Extra-Corporeal Membrane Oxygenation (ECMO) support, and prone positioning increased the risk of death five, four, and more-than-two times, respectively (OR = 5.431, IC 95%: 1.637–18.014; 4.462, IC 95%: 1.616–12.324 and 2.346, IC 95%: 1.127–4.883). MDR bacteria were identified in 61% of patients with superinfection, with a cumulative incidence of 37.2% at day 14. Carbapenem-resistant Acinetobacter baumannii (CR-AB) and CR-Klebsiella pneumoniae (CR-KP) were the most common causative agents (24.3% and 13.7%). CR-AB was found to significantly increase both ICU and in-hospital mortality (76.4% and 78.2%), whereas CR-KP had no direct impact on mortality. Prior rectal colonization (p < 0.0001), mechanical ventilation (p = 0.0017), a prolonged ICU stay (p < 0.0001), the use of iNO (p = 0.0082), vasopressors (p = 0.0025), curarization (p = 0.0004), and prone positioning (p = 0.0084) were found to be risk factors for CR-AB. Conclusions: Critically ill COVID-19 patients are at high risk of developing MDR superinfection. While CR-KP had no direct impact on mortality, CR-AB appeared to increase ICU and in-hospital mortality.