Background Age has been traditionally considered a risk factor for mortality in elderly patients admitted to intensive care units. The aim of this prospective, observational, multicenter cohort study is to determine the risk factors for mortality in elderly and very elderly critically ill patients with sepsis. Results A total of 1490 patients with ≥ 65 years of age were included in the study; most of them 1231 (82.6%) had a cardiovascular failure. The mean age (± SD) was 74.5 (± 5.6) years, and 876 (58.8%) were male. The patients were divided into two cohorts: (1) elderly: 65–79 years and (2) very elderly: ≥ 80 years. The overall hospital mortality was 48.8% ( n = 727) and was significantly higher in very elderly compared to elderly patients (54.2% vs. 47.4%; p = 0.02). Factors independently associated with mortality were APACHE II score of the disease, patient location at sepsis diagnosis, development of acute kidney injury, and thrombocytopenia in the group of elderly patients. On the other hand, in the group of very elderly patients, predictors of hospital mortality were age, APACHE II score, and prompt adherence of the resuscitation bundle. Conclusion This prospective multicenter study found that patients aged 80 or over had higher hospital mortality compared to patients between 65 and 79 years. Age was found to be an independent risk factor only in the very elderly group, and prompt therapy provided within the first 6 h of resuscitation was associated with a reduction in hospital mortality in the very elderly patients.

BackgroundRecent reports have suggested the efficacy of a double carbapenem (DC) combination, including ertapenem, for the treatment of carbapenem-resistant Klebsiella pneumoniae (CR-Kp) infections. We aimed to evaluate the clinical impact of such a regimen in critically ill patients.MethodsThis case–control (1:2), observational, two-center study involved critically ill adults with a microbiologically documented CR-Kp invasive infection treated with the DC regimen matched with those receiving a standard treatment (ST) (i.e., colistin, tigecycline, or gentamicin).ResultsThe primary end point was 28-day mortality. Secondary outcomes were clinical cure, microbiological eradication, duration of mechanical ventilation and of vasopressors, and 90-day mortality. Forty-eight patients treated with DC were matched with 96 controls. Occurrence of septic shock at infection and high procalcitonin levels were significantly more frequent in patients receiving DC treatment (p < 0.01). The 28-day mortality was significantly higher in patients receiving ST compared with the DC group (47.9% vs 29.2%, p = 0.04). Similarly, clinical cure and microbiological eradication were significantly higher when DC was used in patients infected with CR-Kp strains resistant to colistin (13/20 (65%) vs 10/32 (31.3%), p = 0.03 and 11/19 (57.9%) vs 7/27 (25.9%), p = 0.04, respectively). In the logistic regression and multivariate Cox-regression models, the DC regimen was associated with a reduction in 28-day mortality (OR 0.33, 95% CI 0.13–0.87 and OR 0.43, 95% CI 0.23–0.79, respectively).ConclusionsImproved 28-day mortality was associated with the DC regimen compared with ST for severe CR-Kp infections. A randomized trial is needed to confirm these observational results.Trial registrationClinicalTrials.gov NCT03094494. Registered 28 March 2017.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-017-1769-z) contains supplementary material, which is available to authorized users.

This study supports the use of serum BDG results in the management of systemic antifungal drug prescription in septic patients. These findings need to be confirmed in additional studies.

Background and purpose: The objective of this study was to assess the neurological manifestations in a series of consecutive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients, comparing their frequency with a population hospitalized in the same period for flu/respiratory symptoms, finally not related to SARS-CoV-2. Methods: Patients with flu/respiratory symptoms admitted to Fondazione Policlinico Gemelli hospital from 14 March 2020 to 20 April 2020 were retrospectively enrolled. The frequency of neurological manifestations of patients with SARS-CoV-2 infection was compared with a control group. Results: In all, 213 patients were found to be positive for SARS-CoV-2, after reverse transcriptase polymerase chain reaction on nasal or throat swabs, whilst 218 patients were found to be negative and were used as a control group. Regarding central nervous system manifestations, in SARS-CoV-2-positive patients a higher frequency of headache, hyposmia and encephalopathy always related to systemic conditions (fever or hypoxia) was observed. Furthermore, muscular involvement was more frequent in SARS-CoV-2 infection. Conclusions: Patients with COVID-19 commonly have neurological manifestations but only hyposmia and muscle involvement seem more frequent compared with other flu diseases.

IntroductionNosocomial pneumonia develops after ≥48 h of hospitalisation and is classified as ventilator-associated pneumonia (VAP) and hospital-acquired pneumonia (HAP); the latter may require mechanical ventilation (V-HAP) or not (NV-HAP).Main findingsVAP and HAP affect a significant proportion of hospitalised patients and are characterised by poor clinical outcomes. Among them, V-HAP has the greatest 28-day mortality rate followed by VAP and NV-HAP (27.8% versus 18% versus 14.5%, respectively). However, no differences in terms of pathophysiology, underlying microbiological pathways and subsequent therapy have been identified. International guidelines suggest specific flow charts to help clinicians in the therapeutic management of such diseases; however, there are no specific recommendations beyond VAP and HAP classification. HAP subtypes are scarcely considered as different entities and the lack of data from the clinical scenario limits any final conclusion. Hopefully, recent understanding of the pathophysiology of such diseases, as well as the discovery of new therapies, will improve the outcome associated with such pulmonary infections.ConclusionNosocomial pneumonia is a multifaced disease with features of pivotal interest in critical care medicine. Due to the worrisome data on mortality of patients with nosocomial pneumonia, further prospective studies focused on this topic are urgently needed.

Background In critically ill patients, the use of high tigecycline dosages (HD TGC) (200 mg/day) has been recently increasing but few pharmacokinetic/pharmacodynamic (PK/PD) data are available. We designed a prospective observational study to describe the pharmacokinetic/pharmacodynamic (PK/PD) profile of HD TGC in a cohort of critically ill patients with severe infections. Results This was a single centre, prospective, observational study that was conducted in the 20-bed mixed ICU of a 1500-bed teaching hospital in Rome, Italy. In all patients admitted to the ICU between 2015 and 2018, who received TGC (200 mg loading dose, then 100 mg q12) for the treatment of documented infections, serial blood samples were collected to measure steady-state TGC concentrations. Moreover, epithelial lining fluid (ELF) concentrations were determined in patients with nosocomial pneumonia. Amongst the 32 non-obese patients included, 11 had a treatment failure, whilst the other 21 subjects successfully eradicated the infection. There were no between-group differences in terms of demographic aspects and main comorbidities. In nosocomial pneumonia, for a target AUC0-24/MIC of 4.5, 75% of the patients would be successfully treated in presence of 0.5 mcg/mL MIC value and all the patients obtained the PK target with MIC ≤ 0.12 mcg/mL. In intra-abdominal infections (IAI), for a target AUC0-24/MIC of 6.96, at least 50% of the patients would be adequately treated against bacteria with MIC ≤ 0.5 mcg/mL. Finally, in skin and soft-tissue infections (SSTI), for a target AUC0-24/MIC of 17.9 only 25% of the patients obtained the PK target at MIC values of 0.5 mcg/mL and less than 10% were adequately treated against germs with MIC value ≥ 1 mcg/mL. HD TGC showed a relevant pulmonary penetration with a median and IQR ELF/plasma ratio (%) of 152.9 [73.5–386.8]. Conclusions The use of HD TGC is associated with satisfactory plasmatic and pulmonary concentrations for the treatment of severe infections due to fully susceptible bacteria (MIC < 0.5 mcg/mL). Even higher dosages and combination strategies may be suggested in presence of difficult to treat pathogens, especially in case of SSTI and IAI.

BackgroundTo determine the safety and clinical efficacy of an innovative integrated airway system (AnapnoGuard™ 100 system) that continuously monitors and controls the cuff pressure (Pcuff), while facilitating the aspiration of subglottic secretions (SS).MethodsThis was a prospective, single centre, open-label, randomized, controlled feasibility and safety trial. The primary endpoint of the study was the rate of device related adverse events (AE) and serious AE (SAE) as a result of using AnapnoGuard (AG) 100 during mechanical ventilation. Secondary endpoints were: (1) mechanical complications rate (2) ICU staff satisfaction; (3) VAP occurrence; (4) length of mechanical ventilation; (5) length of Intensive Care Unit stay and mortality; (6) volume of evacuated subglottic secretions.Sixty patients were randomized to be intubated with the AG endotracheal-tube (ETT) and connected to the AG 100 system allowing Pcuff adjustment and SS aspiration; or with an ETT combined with SS drainage and Pcuff controlled manually.ResultsNo difference in adverse events rate was identified between the groups. The use of AG system was associated with a significantly higher incidence of Pcuff determinations in the safety range (97.3% vs. 71%; p<0.01) and a trend to a greater volume of aspirated SS secretions: (192.0[64–413] ml vs. 150[50–200], p = 0.19 (total)); (57.8[20–88.7] ml vs. 50[18.7–62] ml, p = 0.11 (daily)). No inter-group difference was detected using AG system vs. controls in terms of post-extubation throat pain level (0 [0–2] vs. 0 [0–3]; p = 0.7), hoarseness (42.9% vs. 75%; p = 0.55) and tracheal mucosa oedema (16.7% vs. 10%; p = 0.65).Patients enrolled in the AG group had a trend to reduced VAP risk of ventilator-associated pneumonia(VAP) (14.8% vs. 40%; p = 0.06), which were more frequently monomicrobial (25% vs. 70%; p = 0.03).No statistically significant difference was observed in duration of mechanical ventilation, ICU stay, and mortality.ConclusionsThe use AG 100 system and AG tube in critically ill intubated patients is safe and effective in Pcuff control and SS drainage. Its protective role against VAP needs to be confirmed in a larger randomized trial.Trial registrationClinicalTrials.gov NCT01550978. Date of registration: February 21, 2012.

A relationship between vitamin D status and mortality in patients in intensive care units (ICU) has been documented. The present study aims to describe the clinical profile and sepsis-related outcome of critically ill septic patients with extremely low (<7 ng/mL) vitamin D levels at ICU admission. We conducted an observational study in the ICU of a teaching hospital including all patients admitted with severe sepsis/septic shock and undergoing 25-hydroxyvitamin D (25(OH)D) testing within the first 24 hours from admission. We studied 107 patients over 12 months. At ICU admission vitamin D deficiency (≤20 ng/mL) was observed in 93.5% of the patients: 57 (53.3%) showed levels <7 ng/mL. As primary outcome, sepsis-related mortality rate was higher in patients with vitamin D levels <7 ng/mL (50.9% versus 26%). Multivariate regression analysis showed that vitamin D concentration <7 ng/mL on ICU admission (p 0.01) and higher mean SAPS II (p <0.01) score were independent predictors of sepsis-related mortality. Patients with very low vitamin D levels suffered higher rate of microbiologically confirmed infections but a lower percentage of microbiological eradication with respect to patients whose values were >7 ng/mL (80.7% versus 58%, p 0.02; 35.3% versus 68%; p 0.03, respectively). Post hoc analysis showed that, in the extremely low vitamin D group, the 52 patients with pneumonia showed a longer duration of mechanical ventilation (9 days (3.75-12.5 days) versus 4 days (2-9 days), p 0.04) and the 66 with septic shock needed vasopressor support for a longer period of time (7 days (4-10 days) versus 4 days (2-7.25 days), p 0.02). Our results suggest that in critical septic patients extremely low vitamin D levels on admission may be a major determinant of clinical outcome. Benefits of vitamin D replacement therapy in this population should be elucidated.