The impact of multidrug resistance on the outcomes of critically ill patients with Gram-negative bacterial pneumonia

Summary Background Coronavirus disease 2019 (COVID-19) disrupts routine care and alters treatment pathways in every medical specialty, including intensive care medicine, which has been at the core of the pandemic response. The impact of the pandemic is inevitably not limited to patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and their outcomes; however, the impact of COVID-19 on intensive care has not yet been analyzed. Methods The objective of this propensity score-matched study was to compare the clinical outcomes of non-COVID-19 critically ill patients with the outcomes of prepandemic patients. Critically ill, non-COVID-19 patients admitted to the intensive care unit (ICU) during the first wave of the pandemic were matched with patients admitted in the previous year. Mortality, length of stay, and rate of readmission were compared between the two groups after matching. Results A total of 211 critically ill SARS-CoV‑2 negative patients admitted between 13 March 2020 and 16 May 2020 were matched to 211 controls, selected from a matching pool of 1421 eligible patients admitted to the ICU in 2019. After matching, the outcomes were not significantly different between the two groups: ICU mortality was 5.2% in 2019 and 8.5% in 2020, p = 0.248, while intrahospital mortality was 10.9% in 2019 and 14.2% in 2020, p = 0.378. The median ICU length of stay was similar in 2019: 4 days (IQR 2–6) compared to 2020: 4 days (IQR 2–7), p = 0.196. The rate of ICU readmission was 15.6% in 2019 and 10.9% in 2020, p = 0.344. Conclusion In this retrospective single center study, mortality, ICU length of stay, and rate of ICU readmission did not differ significantly between patients admitted to the ICU during the implementation of hospital-wide COVID-19 contingency planning and patients admitted to the ICU before the pandemic.

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Pharmacokinetic/Pharmacodynamic Target Attainment Based on Measured Versus Predicted Unbound Ceftriaxone Concentrations in Critically Ill Patients with Pneumonia: An Observational Cohort Study

Antibiotics ◽

10.3390/antibiotics10050557 ◽

2021 ◽

Vol 10 (5) ◽

pp. 557

Author(s):

Matthias Gijsen ◽

Erwin Dreesen ◽

Ruth Van Daele ◽

Pieter Annaert ◽

Yves Debaveye ◽

...

Keyword(s):

Renal Function ◽

Cohort Study ◽

Protein Binding ◽

Critically Ill ◽

Critically Ill Patients ◽

Observational Cohort Study ◽

Target Attainment ◽

Binding Model ◽

Observational Cohort ◽

The Impact

The impact of ceftriaxone pharmacokinetic alterations on protein binding and PK/PD target attainment still remains unclear. We evaluated pharmacokinetic/pharmacodynamic (PK/PD) target attainment of unbound ceftriaxone in critically ill patients with severe community-acquired pneumonia (CAP). Besides, we evaluated the accuracy of predicted vs. measured unbound ceftriaxone concentrations, and its impact on PK/PD target attainment. A prospective observational cohort study was carried out in adult patients admitted to the intensive care unit with severe CAP. Ceftriaxone 2 g q24h intermittent infusion was administered to all patients. Successful PK/PD target attainment was defined as unbound trough concentrations above 1 or 4 mg/L throughout the whole dosing interval. Acceptable overall PK/PD target attainment was defined as successful target attainment in ≥90% of all dosing intervals. Measured unbound ceftriaxone concentrations (CEFu) were compared to unbound concentrations predicted from various protein binding models. Thirty-one patients were included. The 1 mg/L and 4 mg/L targets were reached in 26/32 (81%) and 15/32 (47%) trough samples, respectively. Increased renal function was associated with the failure to attain both PK/PD targets. Unbound ceftriaxone concentrations predicted by the protein binding model developed in the present study showed acceptable bias and precision and had no major impact on PK/PD target attainment. We showed suboptimal (i.e., <90%) unbound ceftriaxone PK/PD target attainment when using a standard 2 g q24h dosing regimen in critically ill patients with severe CAP. Renal function was the major driver for the failure to attain the predefined targets, in accordance with results found in general and septic ICU patients. Interestingly, CEFu was reliably predicted from CEFt without major impact on clinical decisions regarding PK/PD target attainment. This suggests that, when carefully selecting a protein binding model, CEFu does not need to be measured. As a result, the turn-around time and cost for ceftriaxone quantification can be substantially reduced.

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A Systematic Review of Anticoagulation Strategies for Patients With Atrial Fibrillation in Critical Care.

Thrombosis and Haemostasis ◽

10.1055/a-1477-3760 ◽

2021 ◽

Author(s):

Alexandra Jayne Nelson ◽

Brian W Johnston ◽

Alicia Achiaa Charlotte Waite ◽

Gedeon Lemma ◽

Ingeborg Dorothea Welters

Keyword(s):

Atrial Fibrillation ◽

Critical Care ◽

Critically Ill ◽

Major Bleeding ◽

Critically Ill Patients ◽

Thromboembolic Events ◽

Bleeding Events ◽

Major Bleeding Events ◽

The Impact ◽

Anticoagulated Patients

Background. Atrial fibrillation (AF) is the most common cardiac arrhythmia in critically ill patients. There is a paucity of data assessing the impact of anticoagulation strategies on clinical outcomes for general critical care patients with AF. Our aim was to assess the existing literature to evaluate the effectiveness of anticoagulation strategies used in critical care for AF. Methodology. A systematic literature search was conducted using MEDLINE, EMBASE, CENTRAL and PubMed databases. Studies reporting anticoagulation strategies for AF in adults admitted to a general critical care setting were assessed for inclusion. Results. Four studies were selected for data extraction. A total of 44087 patients were identified with AF, of which 17.8-49.4% received anticoagulation. The reported incidence of thromboembolic events was 0-1.4% for anticoagulated patients, and 0-1.3% in non-anticoagulated patients. Major bleeding events were reported in three studies and occurred in 7.2-8.6% of the anticoagulated patients and up to 7.1% of the non-anticoagulated patients. Conclusions. There was an increased incidence of major bleeding events in anticoagulated patients with AF in critical care compared to non-anticoagulated patients. There was no significant difference in the incidence of reported thromboembolic events within studies, between patients who did and did not receive anticoagulation. However, the outcomes reported within studies were not standardised, therefore, the generalisability of our results to the general critical care population remains unclear. Further data is required to facilitate an evidence-based assessment of the risks and benefits of anticoagulation for critically ill patients with AF.

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The Impact of Obstructive Sleep Apnea on the Sleep of Critically Ill Patients

Critical Care Nursing Clinics of North America ◽

10.1016/j.cnc.2021.01.009 ◽

2021 ◽

Author(s):

Michaelynn Paul

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Critically Ill ◽

Critically Ill Patients ◽

Obstructive Sleep ◽

The Impact

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Vascular access: the impact of ultrasonography

Einstein (São Paulo) ◽

10.1590/s1679-45082016rw3129 ◽

2016 ◽

Vol 14 (4) ◽

pp. 561-566 ◽

Cited By ~ 3

Author(s):

Carlos Eduardo Saldanha de Almeida ◽

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Critically Ill ◽

Vascular Access ◽

Critically Ill Patients ◽

Albert Einstein ◽

Sao Paulo ◽

Future Studies ◽

The Impact ◽

Puncture Technique

ABSTRACT Vascular punctures are often necessary in critically ill patients. They are secure, but not free of complications. Ultrasonography enhances safety of the procedure by decreasing puncture attempts, complications and costs. This study reviews important publications and the puncture technique using ultrasound, bringing part of the experience of the intensive care unit of the Hospital Israelita Albert Einstein, São Paulo (SP), Brazil, and discussing issues that should be considered in future studies.

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Predictors of post-extubation stridor in patients on mechanical ventilation: a prospective observational study

Scientific Reports ◽

10.1038/s41598-021-99501-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Aiko Tanaka ◽

Akinori Uchiyama ◽

Yu Horiguchi ◽

Ryota Higeno ◽

Ryota Sakaguchi ◽

...

Keyword(s):

Mechanical Ventilation ◽

Observational Study ◽

Critically Ill ◽

Critically Ill Patients ◽

Prospective Observational Study ◽

Spontaneous Breathing Trial ◽

Leak Test ◽

Endotracheal Suctioning ◽

Cuff Leak ◽

The Impact

AbstractThe cuff leak test (CLT) has been widely accepted as a simple and noninvasive method for predicting post-extubation stridor (PES). However, its accuracy and clinical impact remain uncertain. We aimed to evaluate the reliability of CLT and to assess the impact of pre-extubation variables on the incidence of PES. A prospective observational study was performed on adult critically ill patients who required mechanical ventilation for more than 24 h. Patients were extubated after the successful spontaneous breathing trial, and CLT was conducted before extubation. Of the 191 patients studied, 26 (13.6%) were deemed positive through CLT. PES developed in 19 patients (9.9%) and resulted in a higher reintubation rate (8.1% vs. 52.6%, p < 0.001) and longer intensive care unit stay (8 [4.5–14] vs. 12 [8–30.5] days, p = 0.01) than patients without PES. The incidence of PES and post-extubation outcomes were similar in patients with both positive and negative CLT results. Compared with patients without PES, patients with PES had longer durations of endotracheal intubation and required endotracheal suctioning more frequently during the 24-h period prior to extubation. After adjusting for confounding factors, frequent endotracheal suctioning more than 15 times per day was associated with an adjusted odds ratio of 2.97 (95% confidence interval, 1.01–8.77) for PES. In conclusion, frequent endotracheal suctioning before extubation was a significant PES predictor in critically ill patients. Further investigations of its impact on the incidence of PES and patient outcomes are warranted.

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Population Pharmacokinetic Analysis of Colistin Methanesulfonate and Colistin after Intravenous Administration in Critically Ill Patients with Infections Caused by Gram-Negative Bacteria

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01361-08 ◽

2009 ◽

Vol 53 (8) ◽

pp. 3430-3436 ◽

Cited By ~ 333

Author(s):

D. Plachouras ◽

M. Karvanen ◽

L. E. Friberg ◽

E. Papadomichelakis ◽

A. Antoniadou ◽

...

Keyword(s):

Steady State ◽

Critically Ill ◽

Critically Ill Patients ◽

Compartment Model ◽

Population Pharmacokinetic Analysis ◽

Pharmacokinetic Analysis ◽

Population Pharmacokinetic ◽

Gram Negative Bacteria ◽

Gram Negative ◽

Colistin Methanesulfonate

ABSTRACT Colistin is used to treat infections caused by multidrug-resistant gram-negative bacteria (MDR-GNB). It is administered intravenously in the form of colistin methanesulfonate (CMS), which is hydrolyzed in vivo to the active drug. However, pharmacokinetic data are limited. The aim of the present study was to characterize the pharmacokinetics of CMS and colistin in a population of critically ill patients. Patients receiving colistin for the treatment of infections caused by MDR-GNB were enrolled in the study; however, patients receiving a renal replacement therapy were excluded. CMS was administered at a dose of 3 million units (240 mg) every 8 h. Venous blood was collected immediately before and at multiple occasions after the first and the fourth infusions. Plasma CMS and colistin concentrations were determined by a novel liquid chromatography-tandem mass spectrometry method after a rapid precipitation step that avoids the significant degradation of CMS and colistin. Population pharmacokinetic analysis was performed with the NONMEM program. Eighteen patients (6 females; mean age, 63.6 years; mean creatinine clearance, 82.3 ml/min) were included in the study. For CMS, a two-compartment model best described the pharmacokinetics, and the half-lives of the two phases were estimated to be 0.046 h and 2.3 h, respectively. The clearance of CMS was 13.7 liters/h. For colistin, a one-compartment model was sufficient to describe the data, and the estimated half-life was 14.4 h. The predicted maximum concentrations of drug in plasma were 0.60 mg/liter and 2.3 mg/liter for the first dose and at steady state, respectively. Colistin displayed a half-life that was significantly long in relation to the dosing interval. The implications of these findings are that the plasma colistin concentrations are insufficient before steady state and raise the question of whether the administration of a loading dose would benefit critically ill patients.

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