scholarly journals 127. Living on the Edge: The Impact of MIC Distributions on Empiric Antibiotic Selection

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S176-S177
Author(s):  
Karri A Bauer ◽  
Levita K Hidayat ◽  
Kenneth Klinker ◽  
Mary Motyl ◽  
C Andrew DeRyke
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Antibiotic Susceptibility ◽  
Empiric Therapy ◽  
First Line ◽  
Similar Frequency ◽  
Empiric Antibiotic ◽  
The Impact ◽  
Susceptibility Breakpoint

Abstract Background Due to variability in the precision of an MIC, concern may exist in optimizing PK/PD using standard doses when the MIC is at the susceptibility breakpoint (SBP). This is notable when treating infections in critically ill patients. Evaluating MIC distributions among commonly used antibiotics and accounting for isolates at the SBP represents an additional enhancement to inform empiric therapy. The aim of the study was to evaluate antibiotic susceptibility for commonly used β-lactams against Pseudomonas aeruginosa (PA) in a syndromic antibiogram, incorporating MIC distribution. Methods 20 US institutions submitted yearly up to 250 consecutive targeted Gram-negative pathogens from hospitalized patients as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART) in 2016-2019. MICs were determined by broth microdilution and interpreted using 2021 CLSI breakpoints. The syndromic antibiogram included PA from a blood or respiratory source based on patient location. Based on CLSI guidance, an empiric antibiotic susceptibility threshold of ≥ 90% was deemed optimal. Results 2,500 PA blood (n=680) and respiratory (n=1,820) isolates were evaluated; piperacillin/tazobactam (P/T), cefepime (FEP), meropenem (MEM), and ceftolozane/tazobactam (C/T) susceptibilities were 69.6%, 74.2%, 75.3%, and 95%, respectively (Figure 1). Isolates with MICs at the SBP were observed in 12.1%, 18.7%, 7.5%, and 6.5% for P/T, FEP, MEM, and C/T, respectively. Susceptibilities were lower when stratified by ICU, 64.8%, 71.2%, 70.7%, and 93.7% for P/T, FEP, MEM, and C/T, respectively with a similar frequency of SBP isolates (Figure 2). Figure 1. Syndromic antibiogram evaluating P. aeruginosa blood and respiratory isolates. Figure 2. Syndromic antibiogram evaluating Pseudomonas aeruginosa blood and respiratory isolates stratified by ICU. *MIC breakpoints used to determine susceptibility included: P/T MIC ≤ 16/4 µg/ml, FEP ≤ 8 µg/ml, MEM ≤ 2 µg/ml, C/T ≤ 4 µg/ml Conclusion Our analysis demonstrated that first line antipseudomonal agents, P/T and FEP, have susceptibility rates lower than the CLSI recommended threshold. A significant portion of the MICs within the susceptible range are at the SBP. Due to the frequency of baseline resistance and challenge in achieving adequate PK/PD in critically ill patients, clinicians may be concerned with relying on certain antibiotics when the MIC is at the SBP. Antimicrobial stewardship programs should consider incorporating MIC distributions into syndromic antibiograms to better inform empiric therapy recommendations. Disclosures Karri A. Bauer, PharmD, Merck & Co., Inc. (Employee, Shareholder) Levita K. Hidayat, PharmD BCIDP, Merck & Co., Inc. (Employee, Shareholder) Kenneth Klinker, PharmD, Merck & Co., Inc. (Employee, Shareholder) Mary Motyl, PhD, Merck & Co., Inc. (Employee, Shareholder) C. Andrew DeRyke, PharmD, Merck & Co., Inc. (Employee, Shareholder)

scholarly journals Use of a Precision Antibiotic Therapy (PAT) Prediction Model to Identify Multidrug-Resistant (MDR) Enterobacteriaceae

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S328-S328 ◽  
Author(s):  
Alexandra Varga ◽  
Leigh Cressman ◽  
Ebbing Lautenbach ◽  
Valerie Cluzet ◽  
Pam Tolomeo ◽  
...  
Keyword(s):  
Antibiotic Therapy ◽  
Antibiotic Susceptibility ◽  
Area Under The Curve ◽  
Empiric Therapy ◽  
Multidrug Resistant ◽  
Empiric Antibiotic Therapy ◽  
Brier Score ◽  
First Line ◽  
Roc Curve Analysis ◽  
Empiric Antibiotic

Abstract Background Emergence of multidrug-resistant (MDR) Enterobacteriaceae complicates the selection of empiric antibiotic therapy. Software called Precision Antibiotic Therapy (PAT) (Teqqa, LLC; Jackson, WY) operationalizes a predictive model using patient factors to make real-time, personalized predictions of antibiotic susceptibility for each antibiotic, allowing prescribers to choose empiric therapy for patients at risk for resistant infections. The purpose of this study was to determine the performance of PAT software in identifying MDR Enterobacteriaceaebloodstream infections (BSI) as well as to determine optimal thresholds of predicted antibiotic susceptibility to choose a broader-spectrum antibiotic. Methods We conducted a retrospective cohort study including 475 unique patients with BSIs caused by Enterobacteriaceaefrom January 1, 2016 through December 31, 2016. First-line antibiotic therapy for BSI was defined as cefepime, piperacillin-tazobactam, levofloxacin, or aztreonam. Susceptibilities predicted by PAT were compared with known susceptibilities determined by routine laboratory testing. PAT thresholds for broadening antibiotics were assessed when predicted susceptibilities were 80%, 85%, 90%, and 95% using receiver-operating characteristic (ROC) curves. Performance characteristics were calculated for each threshold. Brier score calculations were then used to compare the accuracy of PAT predictions using the optimized predicted susceptibility threshold, to that of aggregate institutional susceptibility data. Results ROC curve analysis demonstrated an area under the curve of 0.82 for the 95% threshold. The sensitivity for the PAT prediction utilizing the 95% threshold was 91.7% with a specificity of 74.3%. The Brier score for the 2016 antibiogram to determine antibiotic therapy was 0.085, whereas the Brier score using PAT software was 0.071, representing a 16% improvement in accuracy. Conclusion PAT software demonstrated excellent capability to discriminate between Enterobacteriaceae BSIs resistant and susceptible to first-line therapy. A predicted susceptibility threshold of 95% should be used to indicate a need for escalation of empiric antibiotic therapy using PAT. Disclosures All authors: No reported disclosures.

scholarly journals Outcomes of non-COVID-19 critically ill patients during the COVID-19 pandemic

2021 ◽  
Author(s):  
Răzvan Bologheanu ◽  
Mathias Maleczek ◽  
Daniel Laxar ◽  
Oliver Kimberger
Keyword(s):  
Intensive Care ◽  
Length Of Stay ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Medical Specialty ◽  
Routine Care ◽  
Treatment Pathways ◽  
Icu Length Of Stay ◽  
Matched Study ◽  
The Impact

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.

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

Antibiotics ◽  
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.

Multicenter study of ceftolozane/tazobactam for treatment of Pseudomonas aeruginosa infections in critically ill patients

2021 ◽  
pp. 106270
Author(s):  
Bárbara Balandin ◽  
Daniel Ballesteros ◽  
Rafael Ruiz de Luna ◽  
Loreto López-Vergara ◽  
Vicente Pintado ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Critically Ill ◽  
Multicenter Study ◽  
Critically Ill Patients

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

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.

scholarly journals Population Pharmacokinetics and Probability of Target Attainment of Different Dosing Regimens of Ceftazidime in Critically Ill Patients with a Proven or Suspected Pseudomonas aeruginosa Infection

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 612
Author(s):  
Annabel Werumeus Buning ◽  
Caspar J. Hodiamont ◽  
Natalia M. Lechner ◽  
Margriet Schokkin ◽  
Paul W. G. Elbers ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Hematologic Malignancy ◽  
Compartment Model ◽  
Target Attainment ◽  
Worst Case ◽  
Optimal Dosing ◽  
Population Pk ◽  
Pseudomonas Aeruginosa Infection

Altered pharmacokinetics (PK) of hydrophilic antibiotics in critically ill patients is common, with possible consequences for efficacy and resistance. We aimed to describe ceftazidime population PK in critically ill patients with a proven or suspected Pseudomonas aeruginosa infection and to establish optimal dosing. Blood samples were collected for ceftazidime concentration measurement. A population PK model was constructed, and probability of target attainment (PTA) was assessed for targets 100% T > MIC and 100% T > 4 × MIC in the first 24 h. Ninety-six patients yielded 368 ceftazidime concentrations. In a one-compartment model, variability in ceftazidime clearance (CL) showed association with CVVH. For patients not receiving CVVH, variability in ceftazidime CL was 103.4% and showed positive associations with creatinine clearance and with the comorbidities hematologic malignancy, trauma or head injury, explaining 65.2% of variability. For patients treated for at least 24 h and assuming a worst-case MIC of 8 mg/L, PTA was 77% for 100% T > MIC and 14% for 100% T > 4 × MIC. Patients receiving loading doses before continuous infusion demonstrated higher PTA than patients who did not (100% T > MIC: 95% (n = 65) vs. 13% (n = 15); p < 0.001 and 100% T > 4 × MIC: 20% vs. 0%; p = 0.058). The considerable IIV in ceftazidime PK in ICU patients could largely be explained by renal function, CVVH use and several comorbidities. Critically ill patients are at risk for underexposure to ceftazidime when empirically aiming for the breakpoint MIC for P. aeruginosa. A loading dose is recommended.

Pharmacological Management of Seizures and Status Epilepticus in Critically Ill Patients

2010 ◽  
Vol 23 (5) ◽  
pp. 441-454 ◽  
Author(s):  
Eljim P. Tesoro ◽  
Gretchen M. Brophy
Keyword(s):  
Status Epilepticus ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Neurological Disease ◽  
Medical Emergency ◽  
Significant Morbidity ◽  
First Line ◽  
Short Term ◽  
Pharmacological Management ◽  
First Line Treatment

Seizures are serious complications seen in critically ill patients and can lead to significant morbidity and mortality if the cause is not identified and treated quickly. Uncontrolled seizures can lead to status epilepticus (SE), which is considered a medical emergency. The first-line treatment of seizures is an intravenous (IV) benzodiazepine followed by anticonvulsant therapy. Refractory SE can evolve into a nonconvulsive state requiring IV anesthetics or induction of pharmacological coma. To prevent seizures and further complications in critically ill patients with acute neurological disease or injury, short-term seizure prophylaxis should be considered in certain patients.

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