Multi-Drug Resistance Bacterial Infections in Critically Ill Patients Admitted with COVID-19

Introduction. It is known that bacterial infections represent a common complication during viral respiratory tract infections such as influenza, with a concomitant increase in morbidity and mortality. Nevertheless, the prevalence of bacterial co-infections and secondary infections in critically ill patients affected by coronavirus disease 2019 (COVID-19) is not well understood yet. We performed a review of the literature currently available to examine the incidence of bacterial secondary infections acquired during hospital stay and the risk factors associated with multidrug resistance. Most of the studies, mainly retrospective and single-centered, highlighted that the incidence of co-infections is low, affecting about 3.5% of hospitalized patients, while the majority are hospital acquired infections, developed later, generally 10–15 days after ICU admission. The prolonged ICU hospitalization and the extensive use of broad-spectrum antimicrobial drugs during the COVID-19 outbreak might have contributed to the selection of pathogens with different profiles of resistance. Consequently, the reported incidence of MDR bacterial infections in critically ill COVID-19 patients is high, ranging between 32% to 50%. MDR infections are linked to a higher length of stay in ICU but not to a higher risk of death. The only risk factor independently associated with MDR secondary infections reported was invasive mechanical ventilation (OR 1.062; 95% CI 1.012–1.114), but also steroid therapy and prolonged length of ICU stay may play a pivotal role. The empiric antimicrobial therapy for a ventilated patient with suspected or proven bacterial co-infection at ICU admission should be prescribed judiciously and managed according to a stewardship program in order to interrupt or adjust it on the basis of culture results.

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The Association between Nutritional Status and In-Hospital Mortality of COVID-19 in Critically-Ill Patients in the ICU

Nutrients ◽

10.3390/nu13103302 ◽

2021 ◽

Vol 13 (10) ◽

pp. 3302

Author(s):

Michał Czapla ◽

Raúl Juárez-Vela ◽

Vicente Gea-Caballero ◽

Stanisław Zieliński ◽

Marzena Zielińska

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Nutritional Status ◽

Hospital Mortality ◽

Critically Ill ◽

Critically Ill Patients ◽

Invasive Mechanical Ventilation ◽

Nutritional Risk ◽

Risk Of Death ◽

The Impact

Background: Coronavirus disease 2019 (COVID-19) has become one of the leading causes of death worldwide. The impact of poor nutritional status on increased mortality and prolonged ICU (intensive care unit) stay in critically ill patients is well-documented. This study aims to assess how nutritional status and BMI (body mass index) affected in-hospital mortality in critically ill COVID-19 patients Methods: We conducted a retrospective study and analysed medical records of 286 COVID-19 patients admitted to the intensive care unit of the University Clinical Hospital in Wroclaw (Poland). Results: A total of 286 patients were analysed. In the sample group, 8% of patients who died had a BMI within the normal range, 46% were overweight, and 46% were obese. There was a statistically significantly higher death rate in men (73%) and those with BMIs between 25.0–29.9 (p = 0.011). Nonsurvivors had a statistically significantly higher HF (Heart Failure) rate (p = 0.037) and HT (hypertension) rate (p < 0.001). Furthermore, nonsurvivors were statistically significantly older (p < 0.001). The risk of death was higher in overweight patients (HR = 2.13; p = 0.038). Mortality was influenced by higher scores in parameters such as age (HR = 1.03; p = 0.001), NRS2002 (nutritional risk score, HR = 1.18; p = 0.019), PCT (procalcitonin, HR = 1.10; p < 0.001) and potassium level (HR = 1.40; p = 0.023). Conclusions: Being overweight in critically ill COVID-19 patients requiring invasive mechanical ventilation increases their risk of death significantly. Additional factors indicating a higher risk of death include the patient’s age, high PCT, potassium levels, and NRS ≥ 3 measured at the time of admission to the ICU.

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Procalcitonin: Is This the Promised Biomarker for Critically Ill Patients?

Journal of Pediatric Intensive Care ◽

10.1055/s-0036-1583279 ◽

2016 ◽

Vol 05 (04) ◽

pp. 162-171 ◽

Cited By ~ 2

Author(s):

Jacques Lacroix ◽

Patricia Fontela

Keyword(s):

Antibiotic Therapy ◽

Critically Ill ◽

Critically Ill Patients ◽

Lower Respiratory Tract ◽

Bacterial Infections ◽

Clinical Utility ◽

Respiratory Tract Infections ◽

Care Setting ◽

Lower Respiratory Tract Infections ◽

Tract Infections

Objective Procalcitonin (PCT) has been increasingly used in the critical care setting to determine the presence of bacterial infection and also to guide antibiotic therapy. We reviewed PCT's physiologic role, as well as its clinical utility for the management of pediatric critically ill patients. Findings PCT is a precursor of the hormone calcitonin. Its production is induced by inflammatory conditions, especially bacterial infections. Literature shows that PCT is a moderately reliable diagnostic test for severe bacterial infection in children. Synthesis of available adult studies suggests that the use of PCT-based algorithms to support medical decision making reduces antibiotic exposure without compromising safety in critically ill patients. However, no study has addressed the usefulness and safety of PCT to guide antibiotic therapy in severely ill children. In pediatric patients with acute lower respiratory tract infections, the use of PCT-based algorithms also led to a safe decrease in antibiotic treatment duration. Conclusion PCT has demonstrated clinical utility in the pediatric critical care setting when used for the diagnosis of bacterial infections and to guide antibiotic use in children with acute lower respiratory tract infections. However, more research is needed in critically ill children to determine the utility of PCT-driven antibiotic therapy in this population.

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A Metabolomics approach for the diagnosis Of SecondAry InfeCtions in COVID-19 (MOSAIC): a study protocol

BMC Infectious Diseases ◽

10.1186/s12879-021-06832-y ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Gordan McCreath ◽

Phillip D. Whitfield ◽

Andrew J. Roe ◽

Malcolm J. Watson ◽

Malcolm A. B. Sim

Keyword(s):

Critically Ill ◽

Antimicrobial Therapy ◽

Critically Ill Patients ◽

Bacterial Infections ◽

Secondary Infection ◽

Data Sets ◽

Critical Care Units ◽

Secondary Infections ◽

Increased Risk ◽

Additional Sample

Abstract Background Critically ill patients with COVID-19 are at an increased risk of developing secondary bacterial infections. These are both difficult to diagnose and are associated with an increased mortality. Metabolomics may aid clinicians in diagnosing secondary bacterial infections in COVID-19 through identification and quantification of disease specific biomarkers, with the aim of identifying underlying causative microorganisms and directing antimicrobial therapy. Methods This is a multi-centre prospective diagnostic observational study. Patients with COVID-19 will be recruited from critical care units in three Scottish hospitals. Three serial blood samples will be taken from patients, and an additional sample taken if a patient shows clinical or microbiological evidence of secondary infection. Samples will be analysed using LC–MS and subjected to bioinformatic processing and statistical analysis to explore the metabolite changes associated with bacterial infections in COVID-19 patients. Comparisons of the data sets will be made with standard microbiological and biochemical methods of diagnosing infection. Discussion Metabolomics analyses may provide additional strategies for identifying secondary infections, which might permit faster initiation of specific tailored antimicrobial therapy to critically ill patients with COVID-19.

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High-Dose Methylprednisolone Pulses for 3 Days vs. Low-Dose Dexamethasone for 10 Days in Severe, Non-Critical COVID-19: A Retrospective Propensity Score Matched Analysis

Journal of Clinical Medicine ◽

10.3390/jcm10194465 ◽

2021 ◽

Vol 10 (19) ◽

pp. 4465

Author(s):

José María Mora-Luján ◽

Manel Tuells ◽

Abelardo Montero ◽

Francesc Formiga ◽

Narcís A. Homs ◽

...

Keyword(s):

Propensity Score ◽

Hospital Mortality ◽

Critically Ill ◽

Critically Ill Patients ◽

Low Dose ◽

Invasive Mechanical Ventilation ◽

Hospital Length Of Stay ◽

High Dose ◽

Icu Admission ◽

High Dose Methylprednisolone

Corticosteroids are largely recommended in patients with severe COVID-19. However, evidence to support high-dose methylprednisolone (MP) pulses is not as robust as that demonstrated for low-dose dexamethasone (DXM) in the RECOVERY trial. This is a retrospective cohort study on severe, non-critically ill patients with COVID-19, comparing 3-day MP pulses ≥ 100 mg/day vs. DXM 6 mg/day for 10 days. The primary outcome was in-hospital mortality, and the secondary outcomes were need of intensive care unit (ICU) admission or invasive mechanical ventilation (IMV). Propensity-score matching (PSM) analysis was applied. From March 2020 to April 2021, a total of 2,284 patients were admitted to our hospital due to severe, non-critically ill COVID-19, and of these, 189 (8.3%) were treated with MP, and 493 (21.6%) with DXM. The results showed that patients receiving MP showed higher in-hospital mortality (31.2% vs. 17.8%, p < 0.001), need of ICU admission (29.1% vs. 20.5%, p = 0.017), need of IMV (25.9% vs. 13.8, p < 0.001), and median hospital length of stay (14 days vs. 11 days, p < 0.001). Our results suggest that treatment with low-dose DXM for 10 days is superior to 3 days of high-dose MP pulses in preventing in-hospital mortality and need for ICU admission or IMV in severe, non-critically ill patients with COVID-19.

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Effect of timing of intubation on clinical outcomes of critically ill patients with COVID-19: a systematic review and meta-analysis of non-randomized cohort studies

Critical Care ◽

10.1186/s13054-021-03540-6 ◽

2021 ◽

Vol 25 (1) ◽

Author(s):

Eleni Papoutsi ◽

Vassilis G. Giannakoulis ◽

Eleni Xourgia ◽

Christina Routsi ◽

Anastasia Kotanidou ◽

...

Keyword(s):

Systematic Review ◽

Mechanical Ventilation ◽

Clinical Outcomes ◽

Critically Ill ◽

Critically Ill Patients ◽

Meta Analysis ◽

Mortality And Morbidity ◽

Icu Admission ◽

All Cause Mortality ◽

Detectable Difference

Abstract Background Although several international guidelines recommend early over late intubation of patients with severe coronavirus disease 2019 (COVID-19), this issue is still controversial. We aimed to investigate the effect (if any) of timing of intubation on clinical outcomes of critically ill patients with COVID-19 by carrying out a systematic review and meta-analysis. Methods PubMed and Scopus were systematically searched, while references and preprint servers were explored, for relevant articles up to December 26, 2020, to identify studies which reported on mortality and/or morbidity of patients with COVID-19 undergoing early versus late intubation. “Early” was defined as intubation within 24 h from intensive care unit (ICU) admission, while “late” as intubation at any time after 24 h of ICU admission. All-cause mortality and duration of mechanical ventilation (MV) were the primary outcomes of the meta-analysis. Pooled risk ratio (RR), pooled mean difference (MD) and 95% confidence intervals (CI) were calculated using a random effects model. The meta-analysis was registered with PROSPERO (CRD42020222147). Results A total of 12 studies, involving 8944 critically ill patients with COVID-19, were included. There was no statistically detectable difference on all-cause mortality between patients undergoing early versus late intubation (3981 deaths; 45.4% versus 39.1%; RR 1.07, 95% CI 0.99–1.15, p = 0.08). This was also the case for duration of MV (1892 patients; MD − 0.58 days, 95% CI − 3.06 to 1.89 days, p = 0.65). In a sensitivity analysis using an alternate definition of early/late intubation, intubation without versus with a prior trial of high-flow nasal cannula or noninvasive mechanical ventilation was still not associated with a statistically detectable difference on all-cause mortality (1128 deaths; 48.9% versus 42.5%; RR 1.11, 95% CI 0.99–1.25, p = 0.08). Conclusions The synthesized evidence suggests that timing of intubation may have no effect on mortality and morbidity of critically ill patients with COVID-19. These results might justify a wait-and-see approach, which may lead to fewer intubations. Relevant guidelines may therefore need to be updated.

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Prognostic impact of elevated lactate levels on mortality in critically ill patients with and without preadmission metformin treatment: a Danish registry-based cohort study

Annals of Intensive Care ◽

10.1186/s13613-020-00652-0 ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 3

Author(s):

Rene A. Posma ◽

Trine Frøslev ◽

Bente Jespersen ◽

Iwan C. C. van der Horst ◽

Daan J. Touw ◽

...

Keyword(s):

Cohort Study ◽

Mortality Rate ◽

Critically Ill ◽

Critically Ill Patients ◽

Cox Regression ◽

Lower Mortality ◽

Prognostic Impact ◽

Icu Admission ◽

Lactate Levels ◽

Restricted Cubic Splines

Abstract Background Lactate is a robust prognostic marker for the outcome of critically ill patients. Several small studies reported that metformin users have higher lactate levels at ICU admission without a concomitant increase in mortality. However, this has not been investigated in a larger cohort. We aimed to determine whether the association between lactate levels around ICU admission and mortality is different in metformin users compared to metformin nonusers. Methods This cohort study included patients admitted to ICUs in northern Denmark between January 2010 and August 2017 with any circulating lactate measured around ICU admission, which was defined as 12 h before until 6 h after admission. The association between the mean of the lactate levels measured during this period and 30-day mortality was determined for metformin users and nonusers by modelling restricted cubic splines obtained from a Cox regression model. Results Of 37,293 included patients, 3183 (9%) used metformin. The median (interquartile range) lactate level was 1.8 (1.2–3.2) in metformin users and 1.6 (1.0–2.7) mmol/L in metformin nonusers. Lactate levels were strongly associated with mortality for both metformin users and nonusers. However, the association of lactate with mortality was different for metformin users, with a lower mortality rate in metformin users than in nonusers when admitted with similar lactate levels. This was observed over the whole range of lactate levels, and consequently, the relation of lactate with mortality was shifted rightwards for metformin users. Conclusion In this large observational cohort of critically ill patients, early lactate levels were strongly associated with mortality. Irrespective of the degree of hyperlactataemia, similar lactate levels were associated with a lower mortality rate in metformin users compared with metformin nonusers. Therefore, lactate levels around ICU admission should be interpreted according to metformin use.

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Etiology, incidence, and outcomes of patient–ventilator asynchrony in critically-ill patients undergoing invasive mechanical ventilation

Scientific Reports ◽

10.1038/s41598-021-90013-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yongfang Zhou ◽

Steven R. Holets ◽

Man Li ◽

Gustavo A. Cortes-Puentes ◽

Todd J. Meyer ◽

...

Keyword(s):

Risk Factors ◽

Mechanical Ventilation ◽

Critically Ill ◽

Critically Ill Patients ◽

Invasive Mechanical Ventilation ◽

Surgical Intensive Care ◽

Mechanically Ventilated ◽

History Of ◽

Training Background ◽

The Relationship

AbstractPatient–ventilator asynchrony (PVA) is commonly encountered during mechanical ventilation of critically ill patients. Estimates of PVA incidence vary widely. Type, risk factors, and consequences of PVA remain unclear. We aimed to measure the incidence and identify types of PVA, characterize risk factors for development, and explore the relationship between PVA and outcome among critically ill, mechanically ventilated adult patients admitted to medical, surgical, and medical-surgical intensive care units in a large academic institution staffed with varying provider training background. A single center, retrospective cohort study of all adult critically ill patients undergoing invasive mechanical ventilation for ≥ 12 h. A total of 676 patients who underwent 696 episodes of mechanical ventilation were included. Overall PVA occurred in 170 (24%) episodes. Double triggering 92(13%) was most common, followed by flow starvation 73(10%). A history of smoking, and pneumonia, sepsis, or ARDS were risk factors for overall PVA and double triggering (all P < 0.05). Compared with volume targeted ventilation, pressure targeted ventilation decreased the occurrence of events (all P < 0.01). During volume controlled synchronized intermittent mandatory ventilation and pressure targeted ventilation, ventilator settings were associated with the incidence of overall PVA. The number of overall PVA, as well as double triggering and flow starvation specifically, were associated with worse outcomes and fewer hospital-free days (all P < 0.01). Double triggering and flow starvation are the most common PVA among critically ill, mechanically ventilated patients. Overall incidence as well as double triggering and flow starvation PVA specifically, portend worse outcome.

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Acute Respiratory Distress Syndrome and Time to Weaning Off the Invasive Mechanical Ventilator among Patients with COVID-19 Pneumonia

Journal of Clinical Medicine ◽

10.3390/jcm10132935 ◽

2021 ◽

Vol 10 (13) ◽

pp. 2935

Author(s):

Jose Bordon ◽

Ozan Akca ◽

Stephen Furmanek ◽

Rodrigo Silva Cavallazzi ◽

Sally Suliman ◽

...

Keyword(s):

Acute Respiratory Distress Syndrome ◽

Critical Illness ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Critically Ill ◽

Critically Ill Patients ◽

Distress Syndrome ◽

Invasive Mechanical Ventilation ◽

Overall Mortality

Acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) pneumonia is the main cause of the pandemic’s death toll. The assessment of ARDS and time on invasive mechanical ventilation (IMV) could enhance the characterization of outcomes and management of this condition. This is a city-wide retrospective study of hospitalized patients with COVID-19 pneumonia from 5 March 2020 to 30 June 2020. Patients with critical illness were compared with those with non-critical illness. We examined the severity of ARDS and other factors associated with (i) weaning patients off IMV and (ii) mortality in a city-wide study in Louisville, KY. Of 522 patients with COVID-19 pneumonia, 219 (41.9%) were critically ill. Among critically ill patients, the median age was 60 years; 53% were male, 55% were White and 32% were African American. Of all critically ill patients, 52% had ARDS, and 38% of these had severe ARDS. Of the 25% of patients who were weaned off IMV, those with severe ARDS were weaned within eleven days versus five days for those without severe ARDS, p = 0.023. The overall mortality for critically ill patients was 22% versus 1% for those not critically ill. Furthermore, the 14-day mortality was 31% for patients with severe ARDS and 12% for patients without severe ARDS, p = 0.019. Patients with severe ARDS versus non-severe ARDS needed twice as long to wean off IMV (eleven versus five days) and had double the 14-day mortality of patients without severe ARDS.

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Early Versus Late Use of Dexamethasone in Critically Ill Patients With COVID-19: A Multicenter, Prospective Cohort Study

10.21203/rs.3.rs-349677/v1 ◽

2021 ◽

Author(s):

Khalid Al Sulaiman ◽

Alaa Alhubaishi ◽

Ohoud Al Juhani ◽

Khalid Eljaaly ◽

Omar Al Harbi ◽

...

Keyword(s):

Critically Ill ◽

Critically Ill Patients ◽

Kidney Injury ◽

Early Initiation ◽

P Value ◽

Icu Mortality ◽

Icu Admission ◽

Icu Length Of Stay ◽

Beta Coefficient ◽

Multicenter Prospective Cohort Study

Abstract Background: Corticosteroids, especially dexamethasone, showed a survival benefit in critically ill COVID 19 patients. However, it is unclear whether the timing of dexamethasone initiation is associated with positive outcomes. The aim of this study is to evaluate the timing of dexamethasone initiation and 30-day ICU mortality in critically ill patients with COVID19. Methods: A multicenter, non-interventional, prospective study for all adult COVID19 admitted to intensive care units (ICUs) who received systemic dexamethasone between March 01 to December 31, 2020. Patients were divided into two groups based on the timing for dexamethasone initiation (early vs. late). Early use defined as the initiation of dexamethasone within three days of ICU admission. Multivariate logistic and generalized linear regression were used. We considered a P value of < 0.05 statistically significant. Results: A total of 475 patients were included in the study; dexamethasone was initiated early within three days of ICU admission in 433 patients. Early initiation of dexamethasone was associated with lower 30-day ICU mortality (OR [95%CI]: 0.43 [0.23, 0.81], p-value = 0.01), and acute kidney injury during ICU stay, (OR [95%CI]: 0.45 [0.21, 0.94], p-value = 0.03). Additionally, among survivors, early initiation was associated with shorter MV duration (beta coefficient [95% CI]: -0.94 [-1.477, -0.395], p-value = 0.0001), ICU length of stay (LOS) (beta coefficient [95%CI]: -0.73 [-0.9971, -0.469], p-value = 0.0001), and hospital LOS (beta coefficient [95%CI]: -0.68 [-0.913, -0.452], p-value = 0.0001). Conclusion: Early initiation of dexamethasone within three days of ICU admission in COVID-19 critically ill patients was associated with a mortality benefit. Additionally, it was associated with shorter MV duration, hospital, and ICU LOS.

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