Vincenzo De Santis

Introduction: Not enough data exist to inform the optimal duration and type of antimicrobial therapy against GN infections in critically ill patients. Methods: Narrative review based on a literature search through PubMed and Cochrane using the following keywords: “multi-drug resistant (MDR)”, “extensively drug resistant (XDR)”, “pan-drug-resistant (PDR)”, “difficult-to-treat (DTR) Gram-negative infection,” “antibiotic duration therapy”, “antibiotic combination therapy” “antibiotic monotherapy” “Gram-negative bacteremia”, “Gram-negative pneumonia”, and “Gram-negative intra-abdominal infection”. Results: Current literature data suggest adopting longer (≥10–14 days) courses of synergistic combination therapy due to the high global prevalence of ESBL-producing (45–50%), MDR (35%), XDR (15–20%), PDR (5.9–6.2%), and carbapenemases (CP)/metallo-β-lactamases (MBL)-producing (12.5–20%) Gram-negative (GN) microorganisms (i.e., Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumanii). On the other hand, shorter courses (≤5–7 days) of monotherapy should be limited to treating infections caused by GN with higher (≥3 antibiotic classes) antibiotic susceptibility. A general approach should be based on (i) third or further generation cephalosporins ± quinolones/aminoglycosides in the case of MDR-GN; (ii) carbapenems ± fosfomycin/aminoglycosides for extended-spectrum β-lactamases (ESBLs); and (iii) the association of old drugs with new expanded-spectrum β-lactamase inhibitors for XDR, PDR, and CP microorganisms. Therapeutic drug monitoring (TDM) in combination with minimum inhibitory concentration (MIC), bactericidal vs. bacteriostatic antibiotics, and the presence of resistance risk predictors (linked to patient, antibiotic, and microorganism) should represent variables affecting the antimicrobial strategies for treating GN infections. Conclusions: Despite the strategies of therapy described in the results, clinicians must remember that all treatment decisions are dynamic, requiring frequent reassessments depending on both the clinical and microbiological responses of the patient.

We report the characteristics, timing, and factors related to the decision to perform a tracheostomy in patients with confirmed COVID-19 infection admitted to eight Italian intensive care units (ICUs). Prospective observational cohort study of patients with COVID-19 disease on mechanical ventilation. Long-term functional impairment (up to 180 days’ post-hospital discharge) was assessed using the Karnofsky scale. Kaplan–Meier analysis assessed differences in survival and freedom from tracheostomy in relation to ICU stay. Cox regression model was used to assess which variables impacted on tracheostomy as a categorical outcome. A total of 248 patients were recruited in the eight participating ICUs. Patients undergoing tracheostomy (n = 128) had longer ICU (25 (18–36) vs. 10 (7–16), P = 0.001) and hospital (37 (26.5–50) vs. 19 (8.5–34.5) P = 0.02) stays. ICU and hospital mortality of patients tracheostomized was 34% and 37%, respectively. Cumulative survival Kaplan–Meier analysis documented improved survival rates in patients undergoing tracheostomy (Log-Rank, Mantel–Cox = 4.8, P = 0.028). Median Karnofsky scale values improved over time but were similar between survivors receiving or not receiving tracheostomy. No healthcare worker involved in the tracheostomy procedure developed COVID-19 infection during the study period. Patients with COVID-19 infection who underwent tracheostomy had a better cumulative survival but similar long-term functional outcomes at 30, 60, and 180 days after hospital discharge.

Purpose To investigate the prevalence, incidence and characteristics of bacterial infections and their impact on outcome in critically ill patients infected with COVID-19. Methods We conducted a prospective observational study in eight Italian ICUs from February to May 2020; data were collected through an interactive electronic database. Kaplan–Meier analysis (limit product method) was used to identify the occurrence of infections and risk of acquisition. Results During the study period 248 patients were recruited in the eight participating ICUs. Ninety (36.3%) patients developed at least one episode of secondary infection. An ICU length of stay between 7 and 14 days was characterized by a higher occurrence of infectious complications, with ventilator-associated pneumonia being the most frequent. At least one course of antibiotic therapy was given to 161 (64.9%) patients. Overall ICU and hospital mortality were 33.9% and 42.9%, respectively. Patients developing bacteremia had a higher risk of ICU mortality [45.9% vs. 31.6%, odds ratio 1.8 (95% CI 0.9–3.7), p = 0.069] and hospital mortality [56.8% vs. 40.3%, odds ratio 1.9 (95% CI 1.1–3.9), p = 0.04]. Conclusion In critically ill patients infected with COVID-19 the incidence of bacterial infections is high and associated with worse outcomes. Regular microbiological surveillance and strict infection control measures are mandated.