Currently, several antibiotics are active against methicillin-resistant
(MRSA) and can be used for the treatment of pneumonia. They show great variability in terms of antibiotic class, indication, ...pharmacodynamic/pharmacokinetic properties, type of available formulations, spectrum of activity against bacteria other than MRSA, and toxicity profile.
In this narrative review, the authors discuss the characteristics of currently available agents for the treatment of MRSA pneumonia.
The availability of different agents with anti-MRSA activity, and approved for the treatment of pneumonia can allow a personalized approach for any given patient based on the severity of the disease, the setting of occurrence, the patient's baseline risk of toxicity and drug interactions, and the possibility of oral therapy whenever early discharge or outpatient treatment are possible. Although some gray areas still remain, like the lack of high certainty evidence on the efficacy of some old agents and on the precise role of companion agents with toxin inhibitory activity in the case of necrotizing pneumonia, the frequent availability of different treatment choices, each with peculiar characteristics, is already allowing an important step toward a precision medicine approach for the treatment of MRSA pneumonia.
The latest guidelines for the hospital care of patients affected by coronavirus disease 2019 (COVID-19)-related acute respiratory failure have moved towards the widely accepted use of noninvasive ...respiratory support (NIRS) as opposed to early intubation at the pandemic onset. The establishment of severe COVID-19 pneumonia goes through different pathophysiological phases that partially resemble typical acute respiratory distress syndrome (ARDS) and have been categorized into different clinical-radiological phenotypes. These can variably benefit on the application of external positive end-expiratory pressure (PEEP) during noninvasive mechanical ventilation, mainly due to variable levels of lung recruitment ability and lung compliance during different phases of the disease. A growing body of evidence suggests that intense respiratory effort producing excessive negative pleural pressure swings (P
) plays a critical role in the onset and progression of lung and diaphragm damage in patients treated with noninvasive respiratory support. Routine respiratory monitoring is mandatory to avoid the nasty continuation of NIRS in patients who are at higher risk for respiratory deterioration and could benefit from early initiation of invasive mechanical ventilation instead. Here we propose different monitoring methods both in the clinical and experimental settings adapted for this purpose, although further research is required to allow their extensive application in clinical practice. We reviewed the needs and available tools for clinical-physiological monitoring that aims at optimizing the ventilatory management of patients affected by acute respiratory distress syndrome due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection.
Critically ill COVID-19 patients have pathophysiological lung features characterized by perfusion abnormalities. However, to date no study has evaluated whether the changes in the distribution of ...pulmonary gas and blood volume are associated with the severity of gas-exchange impairment and the type of respiratory support (non-invasive versus invasive) in patients with severe COVID-19 pneumonia.
This was a single-center, retrospective cohort study conducted in a tertiary care hospital in Northern Italy during the first pandemic wave. Pulmonary gas and blood distribution was assessed using a technique for quantitative analysis of dual-energy computed tomography. Lung aeration loss (reflected by percentage of normally aerated lung tissue) and the extent of gas:blood volume mismatch (percentage of non-aerated, perfused lung tissue-shunt; aerated, non-perfused dead space; and non-aerated/non-perfused regions) were evaluated in critically ill COVID-19 patients with different clinical severity as reflected by the need for non-invasive or invasive respiratory support.
Thirty-five patients admitted to the intensive care unit between February 29th and May 30th, 2020 were included. Patients requiring invasive versus non-invasive mechanical ventilation had both a lower percentage of normally aerated lung tissue (median interquartile range 33% 24-49% vs. 63% 44-68%, p < 0.001); and a larger extent of gas:blood volume mismatch (43% 30-49% vs. 25% 14-28%, p = 0.001), due to higher shunt (23% 15-32% vs. 5% 2-16%, p = 0.001) and non-aerated/non perfused regions (5% 3-10% vs. 1% 0-2%, p = 0.001). The PaO
/FiO
ratio correlated positively with normally aerated tissue (ρ = 0.730, p < 0.001) and negatively with the extent of gas-blood volume mismatch (ρ = - 0.633, p < 0.001).
In critically ill patients with severe COVID-19 pneumonia, the need for invasive mechanical ventilation and oxygenation impairment were associated with loss of aeration and the extent of gas:blood volume mismatch.
Stroke patients requiring mechanical ventilation often have a poor prognosis. The optimal timing of tracheostomy and its impact on mortality in stroke patients remains uncertain. We performed a ...systematic review and meta-analysis of tracheostomy timing and its association with reported all-cause overall mortality. Secondary outcomes were the effect of tracheostomy timing on neurological outcome (modified Rankin Scale, mRS), hospital length of stay (LOS), and intensive care unit (ICU) LOS.
We searched 5 databases for entries related to acute stroke and tracheostomy from inception to 25 November 2022. We adhered to PRISMA guidance for reporting systematic reviews and meta-analyses. Selected studies included (1) ICU-admitted patients who had stroke (either acute ischaemic stroke, AIS or intracerebral haemorrhage, ICH) and received a tracheostomy (with known timing) during their stay and (2) > 20 tracheotomised. Studies primarily reporting sub-arachnoid haemorrhage (SAH) were excluded. Where this was not possible, adjusted meta-analysis and meta-regression with study-level moderators were performed. Tracheostomy timing was analysed continuously and categorically, where early (< 5 days from initiation of mechanical ventilation to tracheostomy) and late (> 10 days) timing was defined per the protocol of SETPOINT2, the largest and most recent randomised controlled trial on tracheostomy timing in stroke patients.
Thirteen studies involving 17,346 patients (mean age = 59.8 years, female 44%) met the inclusion criteria. ICH, AIS, and SAH comprised 83%, 12%, and 5% of known strokes, respectively. The mean time to tracheostomy was 9.7 days. Overall reported all-cause mortality (adjusted for follow-up) was 15.7%. One in five patients had good neurological outcome (mRS 0-3; median follow-up duration was 180 days). Overall, patients were ventilated for approximately 12 days and had an ICU LOS of 16 days and a hospital LOS of 28 days. A meta-regression analysis using tracheostomy time as a continuous variable showed no statistically significant association between tracheostomy timing and mortality (β = - 0.3, 95% CI = - 2.3 to 1.74, p = 0.8). Early tracheostomy conferred no mortality benefit when compared to late tracheostomy (7.8% vs. 16.4%, p = 0.7). Tracheostomy timing was not associated with secondary outcomes (good neurological outcome, ICU LOS and hospital LOS).
In this meta-analysis of over 17,000 critically ill stroke patients, the timing of tracheostomy was not associated with mortality, neurological outcomes, or ICU/hospital LOS.
PROSPERO-CRD42022351732 registered on 17th of August 2022.
Recent studies have drawn increasing attention to brain-lung crosstalk in critically ill patients. However, further research is needed to investigate the pathophysiological interactions between the ...brain and lungs, establish neuroprotective ventilatory strategies for brain-injured patients, provide guidance on potentially conflicting treatment priorities in patients with concomitant brain and lung injury, and enhance prognostic models to inform extubation and tracheostomy decisions. To bring together such research, BMC Pulmonary Medicine welcomes submissions to its new Collection on 'Brain-lung crosstalk'.
The effects of tracheostomy on outcome as well as on intra or post-operative complications is yet to be defined. Admission of patients with tracheostomy to rehabilitation facility is at higher risk ...of suboptimal care and increased mortality. The aim of the study was to investigate ICU mortality, clinical outcome and quality of life up to 12 months after ICU discharge in tracheostomized critically ill patients. This is a prospective, multi-center, cohort study endorsed by Italian Society of Anesthesia, Analgesia, Reanimation, and Intensive Care (SIAARTI Prot. n° 643/13) registered in Clinicaltrial.gov (NCT01899352). Patients admitted to intensive care unit (ICU) and requiring elective tracheostomy according to physician in charge decision were included in the study. The primary outcome was ICU mortality. Secondary outcomes included risk factors for ICU mortality, prevalence of mortality at follow-up, rate of discharge from the hospital and rehabilitation, quality of life, performance status, and management of tracheostomy cannula at 3-, 6, 12-months from the day of tracheostomy. 694 critically ill patients who were tracheostomized in the ICU were included. ICU mortality was 15.8%. Age, SOFA score at the day of the tracheostomy, and days of endotracheal intubation before tracheostomy were risk factors for ICU mortality. The regression tree analysis showed that SOFA score at the day of tracheostomy and age had a preeminent role for the choice to perform the tracheostomy. Of the 694 ICU patients with tracheostomy, 469 completed the 12-months follow-up. Mortality was 33.51% at 3-months, 45.30% at 6-months, and 55.86% at 12-months. Patients with tracheostomy were less likely discharged at home but at hospital facilities or rehabilitative structures; and quality of life of patients with tracheostomy was severely compromised at 3-6 and 12 months when compared with patients without tracheostomy. In patients admitted to ICU, tracheostomy is associated with high mortality, difficult rehabilitation, and decreased quality of life. The choice to perform a tracheostomy should be carefully weighed on family burden and health-related quality of life.Clinical trial registration: Clinicaltrial.gov (NCT01899352).
An unexpected high prevalence of enterococcal bloodstream infection (BSI) has been observed in critically ill patients with COVID-19 in the intensive care unit (ICU).
The primary objective was to ...describe the characteristics of ICU-acquired enterococcal BSI in critically ill patients with COVID-19. A secondary objective was to exploratorily assess the predictors of 30-day mortality in critically ill COVID-19 patients with ICU-acquired enterococcal BSI.
During the study period, 223 patients with COVID-19 were admitted to COVID-19-dedicated ICUs in our centre. Overall, 51 episodes of enterococcal BSI, occurring in 43 patients, were registered. 29 (56.9%) and 22 (43.1%) BSI were caused by Enterococcus faecalis and Enterococcus faecium, respectively. The cumulative incidence of ICU-acquired enterococcal BSI was of 229 episodes per 1000 ICU admissions (95% mid-p confidence interval CI 172-298). Most patients received an empirical therapy with at least one agent showing in vitro activity against the blood isolate (38/43, 88%). The crude 30-day mortality was 42% (18/43) and 57% (4/7) in the entire series and in patients with vancomycin-resistant E. faecium BSI, respectively. The sequential organ failure assessment (SOFA) score showed an independent association with increased mortality (odds ratio 1.32 per one-point increase, with 95% confidence interval 1.04-1.66, p = .021).
The cumulative incidence of enterococcal BSI is high in critically ill patients with COVID-19. Our results suggest a crucial role of the severity of the acute clinical conditions, to which both the underlying viral pneumonia and the enterococcal BSI may contribute, in majorly influencing the outcome.
KEY MESSAGES
The cumulative incidence of enterococcal BSI is high in critically ill patients with COVID-19.
The crude 30-day mortality of enterococcal BSI in critically ill patients with COVID-19 may be higher than 40%.
There could be a crucial role of the severity of the acute clinical conditions, to which both the underlying viral pneumonia and the enterococcal BSI may contribute, in majorly influencing the outcome.
In December 2019, an outbreak of illness caused by a novel coronavirus (2019-nCoV, subsequently renamed SARS-CoV-2) was reported in Wuhan, China. Coronavirus disease 2019 (COVID-19) quickly spread ...worldwide to become a pandemic. Typical manifestations of COVID-19 include fever, dry cough, fatigue, and respiratory distress. In addition, both the central and peripheral nervous system can be affected by SARS-CoV-2 infection. These neurological changes may be caused by viral neurotropism, by a hyperinflammatory and hypercoagulative state, or even by mechanical ventilation-associated impairment. Hypoxia, endothelial cell damage, and the different impacts of different ventilatory strategies may all lead to increased stress and strain, potentially exacerbating the inflammatory response and leading to a complex interaction between the lungs and the brain. To date, no studies have taken into consideration the possible secondary effect of mechanical ventilation on brain recovery and outcomes. The aim of our review is to provide an updated overview of the potential pathogenic mechanisms of neurological manifestations in COVID-19, discuss the physiological issues related to brain-lung interactions, and propose strategies for optimization of respiratory support in critically ill patients with SARS-CoV-2 pneumonia.In December 2019, an outbreak of illness caused by a novel coronavirus (2019-nCoV, subsequently renamed SARS-CoV-2) was reported in Wuhan, China. Coronavirus disease 2019 (COVID-19) quickly spread worldwide to become a pandemic. Typical manifestations of COVID-19 include fever, dry cough, fatigue, and respiratory distress. In addition, both the central and peripheral nervous system can be affected by SARS-CoV-2 infection. These neurological changes may be caused by viral neurotropism, by a hyperinflammatory and hypercoagulative state, or even by mechanical ventilation-associated impairment. Hypoxia, endothelial cell damage, and the different impacts of different ventilatory strategies may all lead to increased stress and strain, potentially exacerbating the inflammatory response and leading to a complex interaction between the lungs and the brain. To date, no studies have taken into consideration the possible secondary effect of mechanical ventilation on brain recovery and outcomes. The aim of our review is to provide an updated overview of the potential pathogenic mechanisms of neurological manifestations in COVID-19, discuss the physiological issues related to brain-lung interactions, and propose strategies for optimization of respiratory support in critically ill patients with SARS-CoV-2 pneumonia.
Background:
The pathophysiological effects of positive end-expiratory pressure (PEEP) on respiratory mechanics, lung recruitment, and intracranial pressure (ICP) in acute brain-injured patients have ...not been completely elucidated. The primary aim of this study was to assess the effects of PEEP augmentation on respiratory mechanics, quantitative computed lung tomography (qCT) findings, and its relationship with ICP modifications. Secondary aims included the assessment of the correlations between different factors (respiratory mechanics and qCT features) with the changes of ICP and how these factors at baseline may predict ICP response after greater PEEP levels.
Methods:
A prospective, observational study included mechanically ventilated patients with acute brain injury requiring invasive ICP and who underwent two-PEEP levels lung CT scan. Respiratory system compliance (Crs), arterial partial pressure of carbon dioxide (PaCO
2
), mean arterial pressure (MAP), data from qCT and ICP were obtained at PEEP 5 and 15 cmH
2
O.
Results:
Sixteen examinations (double PEEP lung CT and neuromonitoring) in 15 patients were analyzed. The median age of the patients was 54 years (interquartile range, IQR = 39–65) and 53% were men. The median Glasgow Coma Scale (GCS) at intensive care unit (ICU) admission was 8 (IQR = 3–12). Median alveolar recruitment was 2.5% of total lung weight (−1.5 to 4.7). PEEP from 5 to 15 cmH
2
O increased ICP median values from 14.0 (11.2–17.5) to 23.5 (19.5–26.8) mmHg,
p
< 0.001, respectively. The amount of recruited lung tissue on CT was inversely correlated with the change (Δ) in ICP (rho = −0.78;
p
= 0.0006). Additionally, ΔCrs (rho = −0.77,
p
= 0.008), ΔPaCO
2
(rho = 0.81,
p
= 0.0003), and ΔMAP (rho = −0.64,
p
= 0.009) were correlated with ΔICP. Baseline Crs was not predictive of ICP response to PEEP.
Conclusions:
The main factors associated with increased ICP after PEEP augmentation included reduced Crs, lower MAP and lung recruitment, and increased PaCO
2
, but none of these factors was able to predict, at baseline, ICP response to PEEP. To assess the potential benefits of increased PEEP in patients with acute brain injury, hemodynamic status, respiratory mechanics, and lung morphology should be taken into account.
Acute brain injured (ABI) patients are at high risk of developing ventilator-associated pneumonia (VAP). However, incidence, risk factors and effects on outcome of VAP are not completely elucidated ...in this population. The primary aim of this study was to determine the incidence of VAP in a cohort of ABI patients. The secondary objectives included the identification of risk factors for development of VAP, and the impact of VAP on clinical outcomes. Clinical outcomes were defined as intensive care unit length of stay (ICU-LOS), duration of invasive mechanical ventilation (IMV), and ICU mortality.
Pre-planned sub-analysis of the Extubation strategies in Neuro-Intensive care unit (ICU) patients and associations with Outcomes (ENIO) international multi-center prospective observational study. Patients with available data on VAP, who received at least 48 h of IMV and ICU-LOS ≥ 72 h were included.
Out of 1512 patients included in the ENIO study, 1285 were eligible for this analysis. The prevalence of VAP was 39.5% (33.7 cases /1000 ventilator-days), with a high heterogeneity across countries and according to the type of brain injury. VAP was significantly more frequent in male patients, in those with smoke habits and when intraparenchymal probe (IP), external ventricular drain (EVD) or hypothermia (p < 0.001) were used. Independent risk factors for VAP occurrence were male gender, the use of IP, hypothermia, and the occurrence of tracheobronchitis during ICU stay. VAP was not an independent risk factor for ICU mortality (Hazard Ratio, HR = 0.71 95%CI 0.43-1.16, p = 0.168), but was independently associated with longer ICU stay (OR = 2.55 95%CI 2.01-3.23, p < 0.001).
VAP is common in ABI patients. Male gender, IP and EVD insertion, tracheobronchitis, and the use of therapeutic hypothermia were significantly associated with VAP occurrence. VAP did not affect mortality but increased ICU-LOS.
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