scholarly journals 1460. Imipenem/Cilastatin (IMI)/Relebactam (REL) in Hospital-Acquired/Ventilator-Associated Bacterial Pneumonia (HABP/VABP): Subgroup Analyses of Critically Ill Patients in the RESTORE-IMI 2 Trial

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S732-S732
Author(s):  
Luke F Chen ◽  
Maria C Losada ◽  
Kathryn A Mahoney ◽  
Jiejun Du ◽  
Michelle L Brown ◽  
...  
Keyword(s):  
Renal Impairment ◽  
Clinical Response ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Severe Renal Impairment ◽  
Study Drug ◽  
Apache Ii ◽  
Apache Ii Score ◽  
Double Blind ◽  
Mitt Population

Abstract Background HABP/VABP are serious infections associated with high mortality. Critically ill patients (pts) are at particularly high risk of adverse clinical outcomes. In the RESTORE-IMI 2 trial, IMI/REL was non-inferior to PIP/TAZ in primary and key secondary endpoints. We evaluated outcomes specifically in critically ill pts, according to several definitions, from that trial. Methods Randomized, controlled, double-blind, phase 3 trial in adult pts with HABP/VABP. Lower respiratory tract (LRT) specimens were obtained ≤48 hours prior to screening. Pts were randomized 1:1 to IMI/REL 500 mg/250 mg or PIP/TAZ 4 g/500 mg, given IV every 6 h for 7-14 d. The primary endpoint was Day 28 all-cause mortality (ACM) and the key secondary endpoint was clinical response at early follow-up (EFU; 7-14 d after completing therapy) in the modified intent-to-treat (MITT) population (randomized pts with ≥1 dose of study drug, excluding pts with only gram-positive cocci present on baseline Gram stain). This analysis assessed efficacy outcomes specifically in pts in the ICU and in pts with APACHE II score ≥15, both prespecified subgroups. In post-hoc analyses, outcomes were also specifically assessed in the subgroups of pts with moderate/severe renal impairment (creatinine clearance < 60 mL/min) and pts who received vasopressors. Results Of MITT pts (n=531) at baseline, 66.1% (175 IMI/REL, 176 PIP/TAZ) were in the ICU, 47.5% (125 IMI/REL, 127 PIP/TAZ) had APACHE-II score ≥15, and 24.7% (71 IMI/REL, 60 PIP/TAZ) had moderate/severe renal impairment. Further, 20.9% (54 IMI/REL, 57 PIP/TAZ) received vasopressors within 72 h of first dose of study drug and/or during the study. In each subgroup, baseline demographics, clinical characteristics, and causative LRT pathogens (mostly Enterobacterales, P. aeruginosa, and A. calcoaceticus-baumannii complex) were generally comparable between treatment arms. In pts with APACHE-II score ≥15, Day 28 ACM and clinical response rates with IMI/REL were favorable compared to PIP/TAZ (Table). Day 28 ACM was also favorable with IMI/REL in patients receiving vasopressors. Remaining outcomes were similar between treatment arms. Conclusion IMI/REL is an efficacious treatment option for critically ill pts with HABP/VABP. Table. Primary and key secondary efficacy outcomes by subgroup (MITT population) Disclosures Luke F. Chen, MBBS MPH MBA FRACP FSHEA FIDSA, Merck & Co., Inc. (Employee, Shareholder)Merck & Co., Inc. (Employee, Shareholder) Maria C. Losada, BA, Merck & Co., Inc. (Employee, Shareholder) Kathryn A. Mahoney, PharmD, Merck (Employee, Shareholder) Jiejun Du, PhD, Merck & Co., Inc. (Employee, Shareholder) Michelle L. Brown, BS, Merck & Co., Inc. (Employee, Shareholder) Robert Tipping, MS, Merck & Co., Inc. (Employee, Shareholder) Katherine Young, MS, Merck & Co., Inc. (Employee, Shareholder)Merck & Co., Inc. (Employee, Shareholder) C. Andrew DeRyke, PharmD, Merck & Co., Inc. (Employee, Shareholder) Joan R. Butterton, MD, Merck & Co., Inc. (Employee, Shareholder) Amanda Paschke, MD MSCE, Merck & Co., Inc. (Employee, Shareholder)

scholarly journals A Randomized, Double-blind, Multicenter Trial Comparing Efficacy and Safety of Imipenem/Cilastatin/Relebactam Versus Piperacillin/Tazobactam in Adults With Hospital-acquired or Ventilator-associated Bacterial Pneumonia (RESTORE-IMI 2 Study)

2020 ◽  
Author(s):  
Ivan Titov ◽  
Richard G Wunderink ◽  
Antoine Roquilly ◽  
Daniel Rodríguez Gonzalez ◽  
Aileen David-Wang ◽  
...  
Keyword(s):  
Clinical Response ◽  
Bacterial Pneumonia ◽  
Severe Renal Impairment ◽  
Apache Ii Score ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Gram Negative ◽  
Mitt Population ◽  
All Cause Mortality ◽  
Hospital Acquired

Abstract Background Imipenem combined with the β-lactamase inhibitor relebactam has broad antibacterial activity, including against carbapenem-resistant gram-negative pathogens. We evaluated efficacy and safety of imipenem/cilastatin/relebactam in treating hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP). Methods This was a randomized, controlled, double-blind phase 3 trial. Adults with HABP/VABP were randomized 1:1 to imipenem/cilastatin/relebactam 500 mg/500 mg/250 mg or piperacillin/tazobactam 4 g/500 mg, intravenously every 6 hours for 7–14 days. The primary endpoint was day 28 all-cause mortality in the modified intent-to-treat (MITT) population (patients who received study therapy, excluding those with only gram-positive cocci at baseline). The key secondary endpoint was clinical response 7–14 days after completing therapy in the MITT population. Results Of 537 randomized patients (from 113 hospitals in 27 countries), the MITT population comprised 264 imipenem/cilastatin/relebactam and 267 piperacillin/tazobactam patients; 48.6% had ventilated HABP/VABP, 47.5% APACHE II score ≥15, 24.7% moderate/severe renal impairment, 42.9% were ≥65 years old, and 66.1% were in the intensive care unit. The most common baseline pathogens were Klebsiella pneumoniae (25.6%) and Pseudomonas aeruginosa (18.9%). Imipenem/cilastatin/relebactam was noninferior (P < .001) to piperacillin/tazobactam for both endpoints: day 28 all-cause mortality was 15.9% with imipenem/cilastatin/relebactam and 21.3% with piperacillin/tazobactam (difference, −5.3% [95% confidence interval {CI}, −11.9% to 1.2%]), and favorable clinical response at early follow-up was 61.0% and 55.8%, respectively (difference, 5.0% [95% CI, −3.2% to 13.2%]). Serious adverse events (AEs) occurred in 26.7% of imipenem/cilastatin/relebactam and 32.0% of piperacillin/tazobactam patients; AEs leading to treatment discontinuation in 5.6% and 8.2%, respectively; and drug-related AEs (none fatal) in 11.7% and 9.7%, respectively. Conclusions Imipenem/cilastatin/relebactam is an appropriate treatment option for gram-negative HABP/VABP, including in critically ill, high-risk patients. Clinical Trials Registration NCT02493764.

scholarly journals 1574. Multivariate Regression Analysis to Determine Independent Predictors of Treatment Outcomes in the RESTORE-IMI 2 Trial

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S785-S786
Author(s):  
Robert Tipping ◽  
Jiejun Du ◽  
Maria C Losada ◽  
Michelle L Brown ◽  
Katherine Young ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Clinical Response ◽  
Treatment Outcomes ◽  
Multivariate Regression ◽  
Multivariate Regression Analysis ◽  
Apache Ii Score ◽  
Double Blind ◽  
Mitt Population ◽  
Study Results ◽  
All Cause Mortality

Abstract Background In the RESTORE-IMI 2 trial, imipenem/cilastatin/relebactam (IMI/REL) was non-inferior to PIP/TAZ for treating hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP) in the primary endpoint of Day 28 all-cause mortality (D28 ACM) and the key secondary endpoint of clinical response (CR) at early follow-up (EFU; 7-14 d after end of therapy). We performed a multivariate regression analysis to determine independent predictors of treatment outcomes in this trial. Methods Randomized, controlled, double-blind, phase 3, non-inferiority trial comparing IMI/REL 500 mg/250 mg vs PIP/TAZ 4 g/500 mg, every 6 h for 7-14 d, in adult patients (pts) with HABP/VABP. Stepwise-selection logistic regression modeling was used to determine independent predictors of D28 ACM and favorable CR at EFU, in the MITT population (randomized pts with ≥1 dose of study drug, except pts with only gram-positive cocci at baseline). Baseline variables (n=19) were pre-selected as candidates for inclusion (Table 1), based on clinical relevance. Variables were added to the model if significant (p < 0.05) and removed if their significance was reduced (p > 0.1) by addition of other variables. Results Baseline variables that met criteria for significant independent predictors of D28 ACM and CR at EFU in the final selected regression model are in Fig 1 and Fig 2, respectively. As expected, APACHE II score, renal impairment, elderly age, and mechanical ventilation were significant predictors for both outcomes. Bacteremia and P. aeruginosa as a causative pathogen were predictors of unfavorable CR, but not of D28 ACM. Geographic region and the hospital service unit a patient was admitted to were found to be significant predictors, likely explained by their collinearity with other variables. Treatment allocation (IMI/REL vs PIP/TAZ) was not a significant predictor for ACM or CR; this was not unexpected, since the trial showed non-inferiority of the two HABP/VABP therapies. No interactions between the significant predictors and treatment arm were observed. Conclusion This analysis validated known predictors for mortality and clinical outcomes in pts with HABP/VABP and supports the main study results by showing no interactions between predictors and treatment arm. Table 1. Candidate baseline variables pre-selected for inclusion Figure 1. Independent predictors of greater Day 28 all-cause mortality (MITT population; N=531) Figure 2. Independent predictors of favorable clinical response at EFU (MITT population; N=531) Disclosures Robert Tipping, MS, Merck & Co., Inc. (Employee, Shareholder) Jiejun Du, PhD, Merck & Co., Inc. (Employee, Shareholder) Maria C. Losada, BA, Merck & Co., Inc. (Employee, Shareholder) Michelle L. Brown, BS, Merck & Co., Inc. (Employee, Shareholder) Katherine Young, MS, Merck & Co., Inc. (Employee, Shareholder)Merck & Co., Inc. (Employee, Shareholder) Joan R. Butterton, MD, Merck & Co., Inc. (Employee, Shareholder) Amanda Paschke, MD MSCE, Merck & Co., Inc. (Employee, Shareholder) Luke F. Chen, MBBS MPH MBA FRACP FSHEA FIDSA, Merck & Co., Inc. (Employee, Shareholder)Merck & Co., Inc. (Employee, Shareholder)

scholarly journals Serum potassium levels and outcomes in critically ill patients in the medical intensive care unit

2018 ◽  
Vol 46 (3) ◽  
pp. 1254-1262 ◽  
Author(s):  
Surat Tongyoo ◽  
Tanuwong Viarasilpa ◽  
Chairat Permpikul
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Critically Ill ◽  
Serum Potassium ◽  
Critically Ill Patients ◽  
Medical Intensive Care Unit ◽  
Apache Ii ◽  
Apache Ii Score ◽  
Icu Mortality ◽  
Medical Intensive Care

Objective To compare the outcomes of patients with and without a mean serum potassium (K+) level within the recommended range (3.5–4.5 mEq/L). Methods This prospective cohort study involved patients admitted to the medical intensive care unit (ICU) of Siriraj Hospital from May 2012 to February 2013. The patients’ baseline characteristics, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, serum K+ level, and hospital outcomes were recorded. Patients with a mean K+ level of 3.5 to 4.5 mEq/L and with all individual K+ values of 3.0 to 5.0 mEq/L were allocated to the normal K+ group. The remaining patients were allocated to the abnormal K+ group. Results In total, 160 patients were included. Their mean age was 59.3±18.3 years, and their mean APACHE II score was 21.8±14.0. The normal K+ group comprised 74 (46.3%) patients. The abnormal K+ group had a significantly higher mean APACHE II score, proportion of coronary artery disease, and rate of vasopressor treatment. An abnormal serum K+ level was associated with significantly higher ICU mortality and incidence of ventricular fibrillation. Conclusion Critically ill patients with abnormal K+ levels had a higher incidence of ventricular arrhythmia and ICU mortality than patients with normal K+ levels.

APACHE II score for critically ill patients with a solid tumor: A reclassification study

2018 ◽  
Vol 65 (8) ◽  
pp. 447-455 ◽  
Author(s):  
F.D. Martos-Benítez ◽  
I. Cordero-Escobar ◽  
A. Soto-García ◽  
I. Betancourt-Plaza ◽  
I. González-Martínez
Keyword(s):  
Critically Ill ◽  
Solid Tumor ◽  
Critically Ill Patients ◽  
Apache Ii ◽  
Apache Ii Score

scholarly journals 439. Iclaprim Use for Acute Bacterial Skin and Skin Structure Infection (ABSSSI) is Not Associated with Hyperkalemia: Phase 3 REVIVE Studies

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S218-S218
Author(s):  
David B Huang ◽  
Stephanie S Noviello ◽  
Thomas Lodise ◽  
James McKinnell ◽  
Jamie P Dwyer
Keyword(s):  
Renal Impairment ◽  
Severe Renal Impairment ◽  
Angiotensin Receptor Blockers ◽  
Study Drug ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Distal Portion ◽  
Phase 3 ◽  
Two Phase ◽  
Double Blind ◽  
Converting Enzyme Inhibitors

Abstract Background Trimethoprim inhibits sodium channels in the distal portion of the renal tubule, thereby impairing renal potassium excretion. Trimethoprim has been associated with a greater risk of hyperkalemia compared with other antibiotics (amoxicillin, nitrofurantoin, cefalexin, ciprofloxacin). An analysis of Phase 3 studies was conducted to determine whether iclaprim, under development for ABSSSI and also a selective bacterial dihydrofolate reductase inhibitor like trimethoprim, is associated with hyperkalemia, relative to vancomycin, an antibiotic not associated with hyperkalemia. Methods A post-hoc safety analysis was conducted on pooled results of two Phase 3, double-blind, randomized (1:1), active-controlled trials (REVIVE-1/-2) in patients with ABSSSI. These trials compared iclaprim 80 mg fixed doses with vancomycin 15 mg/kg; both administered intravenously every 12 hours for 5–14 days. Hyperkalemia was defined as serum potassium (K) ≥5.5 mmol/L, if normal at baseline, while on study drug. Hyperkalemia was compared between treatment groups and stratified subgroup comparisons were performed. Results Demographics and baseline disease characteristics were similar between the pooled iclaprim and vancomycin groups (table). Hyperkalemia occurred during treatment in 1.5% (9/592) and 2.5% (15/599) of patients treated with iclaprim and vancomycin, respectively. Of the patients with hyperkalemia, one patient in each treatment group had moderate to severe renal impairment (creatinine clearance [CrCl] 15–59 mL/minute). Among patients with moderate to severe renal impairment on any RAS, KSD or K supplements, hyperkalemia occurred in 1/16 and 0/16 patients in the iclaprim and vancomycin groups, respectively, and in 2/83 and 0/46 patients with mild to no renal impairment. No patients with hyperkalemia experienced adverse events of palpitations, chest pain, myalgia, muscular weakness or fatigue. Conclusion No differences in hyperkalemia were seen between the iclaprim and vancomycin groups in the Phase 3 REVIVE studies. In general, few cases of hyperkalemia occurred among patients with renal impairment treated with concomitant angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers treated with iclaprim. Disclosures All authors: No reported disclosures.

Outcomes of Critically Ill Gynecological Cancer Patients Admitted to Intensive Care Unit

2012 ◽  
Vol 30 (1) ◽  
pp. 7-11 ◽  
Author(s):  
Silvio A. Ñamendys-Silva ◽  
María O. González-Herrera ◽  
Julia Texcocano-Becerra ◽  
Angel Herrera-Gómez
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Prognostic Factors ◽  
Mortality Rate ◽  
Hospital Mortality ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Gynecological Cancer ◽  
Apache Ii ◽  
Apache Ii Score

Purpose: To assess the characteristics of critically ill patients with gynecological cancer, and to evaluate their prognosis. Methods: Fifty-two critically ill patients with gynecological cancer admitted to intensive care unit (ICU) were included. Univariate and multivariate logistic regressions were used to identify factors associated with hospital mortality. Results: Thirty-five patients (67.3%) had carcinoma of the cervix uteri and 11 (21.2%) had ovarian cancer. The mortality rate in the ICU was 17.3% (9 of 52) and hospital mortality rate were 23%(12 of 52). In the multivariate analysis, independent prognostic factors for hospital mortality were vasopressor use (odds ratio [OR] = 8.60, 95% confidence interval [CI] 2.05-36; P = .03) and the Acute Physiology and Chronic Health Evaluation (APACHE) II score (OR = 1.43, 95% CI 1.01-2.09; P = .048). Conclusions: The independent prognostic factors for hospital mortality were the need for vasopressors and the APACHE II score.

Safety and Acid-Suppressant Properties of Histamine2-Receptor Antagonists for the Prevention of Stress-Related Mucosal Damage in Critical Care Patients

DICP ◽  
1989 ◽  
Vol 23 (10_suppl) ◽  
pp. S36-S39 ◽  
Author(s):  
Jerome J. Schentag ◽  
Charles A. Carter ◽  
Lynda S. Welage
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Severe Renal Impairment ◽  
Mucosal Damage ◽  
Clinical Experiences ◽  
Receptor Antagonists ◽  
Double Blind ◽  
Parallel Group ◽  
Number Of Patients ◽  
Comparative Safety

Therapeutic intervention for the prevention of stress-related mucosal damage (SRMD) is currently directed at decreasing mucosal exposure to endogenous hydrochloric acid. We conducted a double-blind, parallel-group study in critically ill patients to investigate the comparative safety and acid-suppressant properties of the intravenously administered H2-receptor antagonists cimetidine and famotidine. This is a preliminary analysis. Study patients received either famotidine 20 mg q12h or cimetidine 300 mg q6h or q12h. Cimetidine dosing intervals were based upon the degree of renal and hepatic dysfunction due to pharmacokinetic considerations. In critically ill patients with severe renal impairment, a pH of ≥4.0 was maintained more consistently with famotidine 20 mg q12h compared with treatment with cimetidine. In terms of safety, a greater number of patients receiving cimetidine reported adverse clinical experiences than those receiving famotidine and a greater number of cimetidine patients had to be withdrawn from the study when compared with famotidine patients. In conclusion, preliminary results of this study suggest that famotidine has superior acid-suppressant properties and a better safety profile when used intravenously for the prevention of SRMD in critically ill patients.

scholarly journals The Diagnostic Criteria of Refeeding Syndrome in Critically Ill Patients from four Chinese Hospitals: A Multicenter Prospective Study

2021 ◽  
Author(s):  
Kongmiao Lu ◽  
Xuping Shen ◽  
Xiangxin Zheng ◽  
Xin Xu ◽  
Zhijun Xu ◽  
...  
Keyword(s):  
Diagnostic Criteria ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Serum Phosphate ◽  
Apache Ii ◽  
Apache Ii Score ◽  
Serum Phosphate Level ◽  
Refeeding Syndrome ◽  
Group 3 ◽  
Group 2

Abstract Background: Refeeding syndrome (RFS) is a group of metabolic disorders associated with refeeding after starvation. However, the diagnostic criteria of RFS are highly heterogeneous. This study aimed to identify the best diagnostic criteria of RFS in critically ill patients.Methods: A multicenter, parallel, prospective trial enrolled patients (≥18 years) with mechanical ventilation for more than 3 days. RFS, defined as new-onset hypophosphatemia (<0.87mmol/L) within 72h after feeding and a decreased concentration of serum phosphate of more than 30%, from four hospital ICU of Zhejiang provinces in China. The primary endpoint was the 28-day mortality. Results: Between May 1, 2019 and April 30, 2020, 312 patients were enrolled. Of these, 302 patients were included and completed the trial. Except for APACHE II, there were no significant differences in age, gender, admission type, diagnosis, furosemide application, and hormone application. In the RFS2 and RFS3 groups, the APACHE II score was significantly higher than the non-RFS group (p=0.009 and p=0.01, respectively). In the nutritional baseline data, there were no significant differences between the groups in the PNI index, time to start of nutrition treatment, percentage of start nutrition within 48 hours, parenteral nutrition, feeding intolerance, and caloric intake and protein intake within first week. The NRS2002 score in group 2 and 3 was higher than the non-RFS group (p<0.001 and p=0.001, respectively). Moreover, the BMI index in group 3 was lower than the non-RFS group(p=0.001). Furthermore, the 28-day mortality increased in group 2 compared with the non-RFS group. The length of hospital stay in group 3 was significantly longer than that in the non-RFS group (p=0.008). More importantly, according to the preliminary RFS2 screening criteria, patients were further divided into patients with modified RFS and modified non-RFS. The nosocomial infection rate and 28- or 90-day mortality in the modified RFS group were higher than those of the modified non-RFS group (p=0.006 and p=0.02, respectively).Conclusions: The optimal criterion of RFS was a decrease in serum phosphate level of 0.65mmol/L and below, and a reduction of greater than 0.16 mmol/L within 72 h after starting nutritional support. Trial registration: ClinicalTrials.gov database, NCT04005300. Registered 1 July 2019, https://clinicaltrials.gov/ct2/show/ NCT04005300

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