scholarly journals 2233. Efficacy and Symptom Resolution by Visit in Adults With Community-Acquired Bacterial Pneumonia (CABP) Treated With Lefamulin (LEF) or Moxifloxacin (MOX): Pooled Analysis of Lefamulin Evaluation Against Pneumonia (LEAP) 1 and LEAP 2 Study Results

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S762-S763
Author(s):  
Jennifer Schranz ◽  
Anita F Das ◽  
Elizabeth Alexander ◽  
Gregory J Moran ◽  
Christian Sandrock ◽  
...  
Keyword(s):  
Clinical Response ◽  
Primary Endpoint ◽  
Study Drug ◽  
Antibiotic Use ◽  
Pooled Analysis ◽  
Success Rates ◽  
Symptom Resolution ◽  
Noninferiority Trials ◽  
Atypical Pathogens ◽  
Study Results

Abstract Background Efficacy and safety of LEF were shown in 2 noninferiority trials (LEAP 1/2) vs. MOX in adults with CABP. We assessed the efficacy of LEF by visit based on a pooled analyses of LEAP 1/2 data. Methods In LEAP 1, PORT III–V patients (patients) received LEF 150 mg IV q12h for 5–7 days or MOX 400 mg IV q24h for 7 days, with optional IV-to-oral switch (600 mg LEF q12h or 400 mg MOX q24h). In LEAP 2, PORT II–IV patients received oral LEF 600 mg q12h for 5 days or oral MOX 400 mg q24h for 7 days. Criteria for defining the FDA primary endpoint of early clinical response (ECR) at 96 ± 24 hours after first dose were applied to each visit through late follow-up (LFU; days 27–34) in the intent-to-treat (ITT; all randomized patients) population. Investigator assessment of clinical response (IACR) was examined at end of treatment (EOT; within 2 days after last dose), test-of-cure (TOC; 5–10 days after last dose; EMA primary endpoint), and LFU in the modified ITT (mITT; received ≥1 dose of study drug) and clinically evaluable (CE; met predefined evaluability criteria) populations. Results are presented by visit for pooled LEAP 1/2 data. Results 1289 ITT patients were randomized (LEF, n = 646; MOX, n = 643). Most patients in both groups achieved ECR at Day 3, with further increases through Day 7 and sustained efficacy through LFU (Fig 1). In mITT patients, IACR success rates at EOT/TOC/LFU were 87.1/85.0/83.2% with LEF and 88.1/87.1/86.1% with MOX; results were consistent in CE patients. The proportions of ITT patients with resolution of all baseline signs/symptoms of CABP increased similarly by visit in both treatment groups (Fig 2). Most patients did not achieve complete sign/symptom resolution until TOC, with fever generally being the first and cough the last to resolve. There was no apparent relationship between ECR and age, gender, renal status, SIRS, PORT, prior antibiotic use, baseline pathogens, typical/atypical pathogens, or mono/polymicrobial pathogens. The high percentage of patients at LFU with baseline symptom resolution suggests that symptom resolution was sustained. Conclusion In this pooled analysis, efficacy results were similar by visit in the LEF and MOX groups, with high ECR rates maintained through LFU. LEF will provide a potential new effective systemic monotherapy alternative to fluoroquinolones for the empiric treatment of CABP. Disclosures All authors: No reported disclosures.

scholarly journals A Phase-3 Study to Compare Delafloxacin to Moxifloxacin for the Treatment of Adults with Community-acquired Bacterial Pneumonia (DEFINE-CABP)

2019 ◽  
Author(s):  
Juan P Horcajada ◽  
Robert A Salata ◽  
Rodolfo Álvarez-Sala ◽  
Floarea Mimi Nitu ◽  
Laura Lawrence ◽  
...  
Keyword(s):  
Clinical Response ◽  
Bacterial Pneumonia ◽  
Study Drug ◽  
The United States ◽  
Efficacy And Safety ◽  
Success Rates ◽  
Phase 3 ◽  
Double Blind ◽  
Atypical Pathogens ◽  
Intent To Treat

Abstract Background The clinical and economic burden of community-acquired bacterial pneumonia (CABP) is significant and is anticipated to increase as the population ages and pathogens become more resistant. Delafloxacin is a fluoroquinolone antibiotic approved in the United States for the treatment of adults with acute bacterial skin and skin structure infections. Delafloxacin’s shape and charge profile uniquely impacts its spectrum of activity and side effect profile. This phase 3 study compared the efficacy and safety of delafloxacin to moxifloxacin for the treatment of CABP. Methods A randomized, double-blind, comparator-controlled, multicenter, global Phase 3 study compared the efficacy and safety of delafloxacin 300 mg BID or moxifloxacin 400 mg QD in adults with CABP. The primary endpoint was early clinical response (ECR) defined as improvement at 96 (± 24) hours after first dose of study drug. Clinical response at test of cure (TOC) and microbiologic response were also assessed. Results In the intent-to-treat analysis population (ITT), ECR rates were 88.9% in the delafloxacin group and 89.0% in the moxifloxacin group. Noninferiority of delafloxacin compared with moxifloxacin was demonstrated. At TOC in the ITT population, the success rates were similar between groups. Treatment-emergent adverse events considered at least possibly related to the study drug occurred in 65 subjects (15.2%) in the delafloxacin group and 54 (12.6%) in the moxifloxacin group. Conclusions IV/oral delafloxacin monotherapy is effective and well tolerated in the treatment of adults with CABP, providing coverage for grampositive, gramnegative, and atypical pathogens.

scholarly journals 2232. A Global Phase 3 Study of Delafloxacin (DLX) Compared with Moxifloxacin (MOX) in Patients with Community-acquired Bacterial Pneumonia (CABP)

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S762-S762 ◽  
Author(s):  
Robert Salata ◽  
Rodolfo Alvarez-Sala ◽  
Juan P Horcajada ◽  
Laura Lawrence ◽  
Megan Quintas ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Study Drug ◽  
Patient Characteristics ◽  
Antibiotic Use ◽  
Qt Prolongation ◽  
Phase 3 ◽  
Double Blind ◽  
Gram Negative ◽  
Atypical Pathogens ◽  
Evaluable Population

Abstract Background DLX is an IV/oral fluoroquinolone with no QT restrictions, and activity against Gram-positive, Gram-negative and atypical pathogens. DLX is approved for treatment of ABSSSI including those due to MRSA and Gram-negative pathogens. A Phase 3 trial of patients with CABP was recently completed. Methods Global active-comparator double-blind trial; adults with CABP with at least 2 clinical symptoms, physical signs, and radiographic evidence of pneumonia. Randomized 1:1 to DLX or MOX treatment for 5–10 days. Randomization stratified by PORT Class, history of COPD/asthma, and prior single-dose antibiotic use (limit 25%). Patients received a minimum of 3 days IV treatment, then were switched to oral at MD discretion. The primary endpoint for FDA was the Early Clinical Response (ECR): improvement at 96 hours after first dose of study drug in at least 2 of the baseline symptoms in the Intent to Treat (ITT) population. Results 859 patients were randomized; both groups were comparable. Patient characteristics: mean age 60 (range 18–93, 21% ≥ age 75); 58.7% male; 28.6% multi-lobar pneumonia; 26.8% PORT class IV/V. Bacterial pathogens were identified in 60.5% at baseline; most commonly S. pneumoniae, as well as S. aureus, atypicals and Gram-negatives. Patients received treatment ~ 8.5 days (6.3 days of IV, 2.2 days oral). DLX was non-inferior to MOX in ECR 88.9% DLX vs. 89.0% MOX [∆−0.2 (CI -4.4, 4.1)] in the ITT population; ECR in the evaluable population was 91.1% DLX vs. 91.8% MOX [∆−0.6 (CI -4.5, 3.2)]. Day 28 Mortality was 1.9% DLX vs. 1.4% MOX. In the micro evaluable population, DLX was comparable to MOX in eradication, 92.5% DLX vs. 93.5% MOX at Test of Cure 5–10 days after treatment, [∆ −1.0 (CI -5.8, 3.6)]. 30.5% DLX and 26.2% MOX patients had ≥1 treatment-emergent adverse events (AEs). The most common DLX AEs were diarrhea and transaminase elevations, which were mild-to-moderate and did not routinely lead to discontinuation (DC). Treatment DC due to treatment-related AEs was seen in 9 DLX and 4 MOX patients. There were no potential QT AEs with DLX. Conclusion IV/oral DLX was comparable to IV/oral MOX for treatment of CABP in patients. DLX has no preclinical signals for QT prolongation and has no QT prolongation in a validated challenge study. DLX appears effective and well tolerated in patients with CABP. Disclosures All authors: No reported disclosures.

scholarly journals 1338. A Pooled Analysis of Patients With Wound Infections in the Phase 3 REVIVE Trials: Randomized, Double-blind Studies to EValuate the Safety and Efficacy of Iclaprim Vs. Vancomycin for trEatment of Acute Bacterial Skin and Skin Structure Infections

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S409-S409
Author(s):  
David Huang ◽  
G Ralph Corey ◽  
Thomas L Holland ◽  
Thomas P Lodise ◽  
William O’Rirodan ◽  
...  
Keyword(s):  
Clinical Response ◽  
Board Member ◽  
Early Time ◽  
Study Drug ◽  
Surgical Site Infections ◽  
Pooled Analysis ◽  
Fixed Dose ◽  
Wound Infections ◽  
Phase 3 ◽  
Double Blind

Abstract Background The objective of this evaluation was to provide an analysis of pooled efficacy data from two parallel Phase 3 trials of iclaprim, a diaminopyrimidine dihydrofolate reducatase inhibitor, compared with vancomycin for the treatment of patients with wound infections including surgical site infections (SSI). Methods A pooled analysis of patients with wound infections was conducted from two parallel Phase 3, double-blind, randomized (1:1), active-controlled, multinational, multicenter trials (REVIVE-1 and REVIVE-2), which included a total of 602 patients with wound infections. The data were analyzed separately and then pooled to determine the efficacy of iclaprim 80 mg fixed dose compared with vancomycin 15 mg/kg. Both drugs were administered intravenously every 12 hours for 5 to 14 days according to the investigator assessment of clinical response. The primary endpoint of these studies was to determine whether iclaprim was noninferior (NI; 10% margin) to vancomycin in achieving a ≥20% reduction in lesion size (early clinical response [ECR] at 48 to 72 hours after initiation of the study drug (early time point [ETP]), compared with baseline in the intent-to-treat (ITT) population. Results Iclaprim had similar ECR rates at ETP compared with vancomycin among the subset of patients with wound infections (see table). The median treatment duration for both iclaprim and vancomycin was 7 days (range 5–14 days). Conclusion In this post-hoc analysis of the REVIVE studies, iclaprim achieved NI to vancomycin in both studies, based on ECR at ETP, in the subgroup of patients with wound infections. These results suggest that iclaprim may be a valuable treatment option for patients with wound infections, including SSI, suspected or confirmed to be due to Gram-positive pathogens. Disclosures D. Huang, Motif BioSciences: Employee, Salary. G. R. Corey, Motif BioSciences: Board Member, Consulting fee. T. L. Holland, Basilea: Consultant, Consulting fee. Motif Bio: Consultant and Scientific Advisor, Consulting fee. Theravance: Consultant, Speaker honorarium. Genentech: Consultant, Consulting fee. T. P. Lodise Jr., Motif BioSciences: Board Member, Consulting fee. W. O’Rirodan, Motif BioSciences: Board Member, Consulting fee. M. Wilcox, Motif BioSciences: Board Member, Consulting fee. T. M. File Jr., Motif BioSciences: Board Member, Consulting fee. M. Dryden, Motif BioSciences: Board Member, Consulting fee. B. Balser, Motif BioSciences: Consultant, Consulting fee. E. Desplats, Motif BioSciences: Consultant, Consulting fee.

scholarly journals 699. Hepatobiliary Safety in Adults With Community-Acquired Bacterial Pneumonia (CABP) Treated With Lefamulin (LEF) or Moxifloxacin (MOX): Pooled Analysis of Lefamulin Evaluation Against Pneumonia (LEAP) 1 and LEAP 2 Study Results

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S316-S316 ◽  
Author(s):  
James H Lewis ◽  
Anita F Das ◽  
Daniel Stein ◽  
Steven P Gelone ◽  
Jennifer Schranz
Keyword(s):  
Total Bilirubin ◽  
Severe Disease ◽  
Pooled Analysis ◽  
System Organ Class ◽  
Chronic Injury ◽  
Time To Peak ◽  
Noninferiority Trials ◽  
Study Results ◽  
Hy’S Law ◽  
End Stage

Abstract Background LEF efficacy and safety were shown in 2 noninferiority trials (LEAP 1/2) vs. MOX in adults with CABP. We assessed the hepatobiliary safety of LEF based on pooled analyses of LEAP 1/2 data. Methods In LEAP 1, PORT III–V patients received LEF 150 mg IV q12h for 5–7 days or MOX 400 mg IV q24h for 7 days, with optional IV-to-oral switch (600 mg LEF q12h or 400 mg MOX q24h). In LEAP 2, PORT II–IV patients received oral LEF 600 mg q12h for 5 days or oral MOX 400mg q24h for 7 days. Exclusion criteria included infection with HBV/HCV, acute hepatitis, cirrhosis, AST or ALT >5xULN, total bilirubin >3xULN (unless Gilbert’s disease), AST or ALT >3xULN and total bilirubin >2xULN, and manifestation of end-stage liver disease. Hepatic safety was assessed from baseline (BL) and multiple post-BL blood samples using a central laboratory, TEAEs, and expert consultant adjudication. Pooled analyses included all randomized/treated patients (safety population). Results Of 1282 randomized/treated patients, 1251 had BL and post-BL hepatobiliary data (table). Post-BL distribution of ALT/AST was generally similar for both groups, although ALT >AST in the absence of muscle injury or alcohol use. Overall, rates of patients experiencing an increase in ALT/AST >3xULN, ALP >2xULN, or total bilirubin >1.5xULN were low (table). Patients with elevated vs. normal BL transaminases (TAs) were more likely to have post-BL elevations >3xULN, but the vast majority remained <5xULN. Among patients with ALT >5xULN, peak increases were generally seen in the first week after the first LEF dose and declined to within/near normal levels by late follow-up (day 28); for MOX, time to peak ALT was less consistent (figure). No LEF pt and 1 MOX pt met laboratory criteria for Hy’s Law. Elevations in TAs were reversible, with no evidence of chronic injury. The LEF injury pattern was predominantly hepatocellular (50.0%)/mixed (40.0%), with no apparent gender, age, or ethnic predominance. TEAEs in the hepatobiliary disorders system organ class were reported in 6 (0.9%) LEF patients and 6 (0.9%) MOX patients, with similar levels seen in patients with elevated BL TAs. There were no symptomatic patients, severe disease, or evidence of hypersensitivity. Conclusion Low incidences of hepatobiliary parameter elevations and TEAEs were observed, with no apparent differences between LEF and MOX. Disclosures All authors: No reported disclosures.

scholarly journals Lefamulin efficacy and safety in a pooled phase 3 clinical trial population with community-acquired bacterial pneumonia and common clinical comorbidities

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Thomas M. File ◽  
Elizabeth Alexander ◽  
Lisa Goldberg ◽  
Anita F. Das ◽  
Christian Sandrock ◽  
...  
Keyword(s):  
Clinical Response ◽  
Bacterial Pneumonia ◽  
Study Drug ◽  
Chronic Obstructive ◽  
Success Rates ◽  
Chronic Lung Diseases ◽  
Elevated Liver Enzymes ◽  
Oral Switch ◽  
To Receive ◽  
Registration Date

Abstract Background Lefamulin, a first-in-class pleuromutilin antibiotic approved for intravenous and oral use in adults with community-acquired bacterial pneumonia (CABP), was noninferior to moxifloxacin in the Lefamulin Evaluation Against Pneumonia (LEAP) 1 intravenous-to-oral switch study and the LEAP 2 oral-only study. Using pooled LEAP 1/2 data, we examined lefamulin efficacy/safety overall and within subgroups of patients presenting with comorbidities typical in CABP management. Methods In LEAP 1, adults with CABP were randomized to receive intravenous lefamulin (150 mg every 12 h) for 5‒7 days or moxifloxacin (400 mg every 24 h) for 7 days, with optional intravenous-to-oral switch if predefined improvement criteria were met. In LEAP 2, adults with CABP were randomized to receive oral lefamulin (600 mg every 12 h) for 5 days or moxifloxacin (400 mg every 24 h) for 7 days. Both studies assessed early clinical response (ECR) at 96 ± 24 h after first study drug dose and investigator assessment of clinical response (IACR) at test-of-cure (5‒10 days after last dose). Pooled analyses of the overall population used a 10% noninferiority margin. Results Lefamulin (n = 646) was noninferior to moxifloxacin (n = 643) for ECR (89.3% vs 90.5%, respectively; difference  − 1.1%; 95% CI  − 4.4 to 2.2); IACR success rates at test-of-cure were similarly high (≥ 85.0%). High efficacy with both lefamulin and moxifloxacin was also demonstrated across all well-represented patient subgroups, including those with advanced age, diabetes mellitus, a history of cardiovascular diseases (e.g., hypertension, congestive heart failure, or arrhythmia) or chronic lung diseases (e.g., asthma or chronic obstructive pulmonary disease), elevated liver enzymes, or mild-to-moderate renal dysfunction. No new safety signals were identified. Conclusions Lefamulin may provide a valuable intravenous/oral monotherapy alternative to fluoroquinolones or macrolides for empiric treatment of patients with CABP, including cases of patients at risk for poor outcomes due to age or various comorbidities. Trial registration ClinicalTrials.gov LEAP 1 (NCT02559310; Registration Date: 24/09/2015) and LEAP 2 (NCT02813694; Registration Date: 27/06/2016).

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 &lt; 0.05) and removed if their significance was reduced (p &gt; 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 Monotherapy with meropenem versus combination therapy with ceftazidime plus amikacin as empiric therapy for fever in granulocytopenic patients with cancer. The International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer and the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto Infection Program.

1996 ◽  
Vol 40 (5) ◽  
pp. 1108-1115 ◽  
Author(s):  
A Cometta ◽  
T Calandra ◽  
H Gaya ◽  
S H Zinner ◽  
R de Bock ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Study Drug ◽  
Empiric Therapy ◽  
Successful Outcome ◽  
Combination Group ◽  
Monotherapy Group ◽  
Success Rates ◽  
Beta Lactams ◽  
European Organization ◽  
Gram Negative Bacteremia

Combinations of beta-lactams plus aminoglycosides have been standard therapy for suspected infections in granulocytopenic cancer patients, especially those with profound long-lasting granulocytopenia. With the advent of new broad-spectrum bactericidal antibiotics such as extended-spectrum cephalosporins or carbapenems, the need to combine beta-lactams with aminoglycosides became more controversial. The objective of this prospective randomized multicenter study was to compare the efficacy, safety, and tolerance of meropenem monotherapy with those of the combination of ceftazidime plus amikacin for the empirical treatment of fever in granulocytopenic cancer patients. Of 1,034 randomized patients, 958 were assessable in the intent-to-treat analysis for response to antibacterial therapy, including 483 in the meropenem group and 475 in the ceftazidime-plus-amikacin group. The median durations of neutropenia were 16 and 17 days, respectively. A successful outcome was reported in 270 of 483 (56%) patients treated with monotherapy compared with 245 of 475 (52%) patients treated with the combination group (P = 0.20). The success rates in the monotherapy group and the combination group were similar by type of infection (single gram-negative bacteremia, single gram-positive bacteremia, clinically documented infection, and possible infection). The occurrence of further infections assessed in patients for whom the allocated regimen was not modified did not differ between the two groups (12% in both groups). Mortality due to the presenting infection or further infection was relatively low (8 patients treated with the monotherapy compared with 13 patients treated with the combination). A total of 1,027 patients were evaluable for adverse events; the proportion of those who developed adverse effects was similar between the two groups (29% in both groups), and only 19 (4%) patients in the monotherapy group and 31 (6%) in the combination group experienced an adverse event related or probably related to the study drug. Allergic reactions were the only reason for stopping the protocol antibiotic(s) (3 and 5 patients, respectively). This study confirms that monotherapy with meropenem is as effective as the combination of ceftazidime plus amikacin for the empiric treatment of fever in persistently granulocytopenic cancer patients, and both regimens were well tolerated.

scholarly journals Correlation of Knowledge and Beliefs to Adherence with Antibiotic Use in Adult Patients at a Private Hospital in Sidoarjo

2020 ◽  
Vol 15 (2) ◽  
Author(s):  
Muhammad Hasan Wattiheluw ◽  
Fauna Herawati ◽  
Setiasih Setiasih ◽  
Rika Yulia
Keyword(s):  
Infectious Diseases ◽  
Antibiotic Therapy ◽  
Private Hospital ◽  
Antibiotic Use ◽  
Cross Sectional Study ◽  
P Value ◽  
Cross Sectional ◽  
Knowledge And Beliefs ◽  
Study Results ◽  
Hospitalization Period

Infectious diseases are one of the top ten causes of death in the world. Antibiotic therapy is administered for infectious diseases, but if bacteria are exposed to antibiotics continuously, then the bacteria are able to adapt to the medication, thereby resulting in antibiotic resistance. This condition results in an increase in mortality, long hospitalization period, and increased cost of antibiotic therapy and health services. Adherence to using antibiotics may be influenced by knowledge and beliefs about them. This study aimed to understand correlation between knowledge and belief with adherence to antibiotic use at a private hospital in Sidoarjo. This cross-sectional study, the data collected in three months period, was conducted with a questionnaire for assessment knowledge and belief. A pill count method was applied for assessment adherence to using antibiotics prescribed by doctors. The study results show that knowledge of the respondents was adequate for 76 people (69.7%), belief was adequate for 74 people (67.9%), and adherence to antibiotic use for 79 people (72%). Regression analysis showed that the variable that significantly influenced the adherence of patients in using antibiotics was perceived threat (p-value = 0,029). Sex, age, education, income, occupation, and marital status have no contribution to antibiotic knowledge, belief, and adherence.

Abstract 2600: Refinement of the MR Diffusion-perfusion Mismatch Concept for Thrombolytic Patient Selection: Insights from the Desmoteplase In Acute Stroke Trials

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Steven Warach ◽  
Yasir Al-Rawi ◽  
Anthony J Furlan ◽  
Jochen B Fiebach ◽  
Max Wintermark ◽  
...  
Keyword(s):  
Clinical Response ◽  
Patient Selection ◽  
Effect Size ◽  
Response Rate ◽  
Time Window ◽  
Placebo Response ◽  
Placebo Treatment ◽  
Pooled Analysis ◽  
Selection Strategy ◽  
Clinical Response Rate

The DIAS-2 study was the only large, randomized intravenous thrombolytic trial that selected patients based on the presence of ischemic penumbra. However, DIAS-2 did not confirm the positive findings of the smaller DEDAS and DIAS trials, which also used penumbral selection. Therefore a reevaluation of the penumbra selection strategy is warranted. In post-hoc analyses we assessed the relationships of MRI-measured lesion volumes to clinical measures in DIAS-2, and the relationships of the presence and size of the diffusion-perfusion mismatch to the clinical effect of desmoteplase in DIAS-2 (MRI-selected patients) and in pooled data from MRI-selected 90- and 125-μg/kg dose groups in DIAS, DEDAS, and DIAS-2. In DIAS-2, lesion volumes correlated with NIHSS at both baseline and final time points (P<0·0001), and lesion growth was inversely related to good clinical outcome (P=0.004). In the pooled analysis, treatment was associated with 47% clinical response rate in desmoteplase (n=143) versus 34% in placebo (n=73; P=0.08). For both the pooled sample and for DIAS-2, increasing the minimum baseline mismatch volume (MMV) for inclusion increased the desmoteplase effect size, preferentially decreasing the placebo-response rate. There was a trend of statistically significant differences in effect size in ≤60 mL versus >60 mL baseline mismatch subgroups (P=0.083). The odds ratio for good clinical response between desmoteplase and placebo treatment was 2.83 (95% CI, 1.16-6.94, P=0.023) for a MMV >60 mL. Increasing the minimum NIHSS for inclusion did not affect treatment effect size. Pooled across all desmoteplase trials, penumbral selection by MRI diffusion-perfusion mismatch favored desmoteplase clinical benefit, especially for larger MMV. Based on these results, a three-fold reduction in future trial sample size requirements would be achieved using a criterion of baseline MMV >60 mL over any visible mismatch. These results support a modified diffusion-perfusion mismatch hypothesis for patient selection in later-time-window thrombolytic trials.

scholarly journals 1374. Integrated Safety Summary of Omadacycline: A Novel Aminomethylcycline Antibiotic

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S421-S421 ◽  
Author(s):  
Steven Opal ◽  
Thomas M File ◽  
Tom Van Der Poll ◽  
Paul McGovern ◽  
Evan Tzanis ◽  
...  
Keyword(s):  
Adverse Events ◽  
Fungal Infections ◽  
Vital Signs ◽  
Study Drug ◽  
Drug Discontinuation ◽  
Once Daily ◽  
Atypical Pathogens ◽  
Safety Parameters ◽  
Study Drug Discontinuation ◽  
Electrocardiogram Ecg

Abstract Background Omadacycline (OMC) is a novel aminomethylcycline with activity against Gram-positive, many Gram-negative, anaerobic, and atypical pathogens. It is in clinical development as once-daily oral (PO) and intravenous (IV) monotherapy for acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP). Cumulative safety results from Phase 3 clinical trials are reported. Methods This pooled safety analysis is based on 2,150 subjects: OASIS-1 (N = 645), OASIS-2 (N = 735) in ABSSSI; OPTIC (N = 770) in CABP. Comparators were linezolid (LZD) 600 mg IV then PO in ABSSSI (n = 689); moxifloxacin (MOX) 400 mg IV then PO in CABP (n = 388). Safety parameters included treatment-emergent adverse events (TEAEs), laboratory evaluations, vital signs, and electrocardiogram (ECG) findings. Results A total of 1,073 subjects received OMC: 705 received OMC IV then PO (ABSSSI, n = 323; CABP, n = 382); 368 received OMC PO only for ABSSSI. Overall, 60.6% were male and 91.6% white; mean age ranges were 44.7–45.1 and 60.9–62.1 years in ABSSSI and CABP studies, respectively. TEAEs were observed in 47.5% (OMC), 41.2% (LZD), and 48.5% (MOX) of subjects, with gastrointestinal events the most common TEAEs. Serious TEAEs were low (3.6% OMC, 1.9% LZD, 6.7% MOX). Nausea (14.9% OMC, 8.7% LZD, 5.4% MOX) and vomiting (8.3% OMC, 3.9% LZD, 1.5% MOX) were the most frequently reported TEAEs. Diarrhea was observed in 2.4% OMC, 2.9% LZD, and 8.0% MOX subjects, with no cases of Clostridium difficile in OMC-treated subjects. Most TEAEs were mild to moderate and did not result in study drug discontinuation (3.1% OMC, 1.5% LZD, 7.0% MOX); 4 OMC, 1 LZD, and 0 MOX subjects discontinued for nausea and vomiting. Frequency of hepatic TEAEs was similar for OMC, LZD, and MOX: 4.3% OMC, 4.1% LZD, and 4.5% MOX subjects had post-baseline ALT &gt;3× upper limit of normal. Vital signs and ECGs had comparable clinically notable values post-baseline in each treatment group. Known tetracycline class adverse events such as fungal infections were similar in all groups. Conclusion Pooled analyses demonstrate a favorable OMC safety profile, consistent with its tetracycline heritage. OMC was generally well tolerated in subjects with ABSSSI and CABP, with infrequent treatment discontinuations. Disclosures T. M. File Jr., BioMerieux: Consultant, Consulting fee; Curetis: Consultant, Consulting fee; Melinta Therapeutics: Consultant, Consulting fee; Merck: Consultant, Consulting fee; Motif Bio: Consultant, Consulting fee; Nabriva Therapeutics: Consultant and Investigator, Consulting fee and Research grant; Paratek Pharmaceuticals: Consultant, Consulting fee; Pfizer: Consultant, Consulting fee. T. Van Der Poll, Paratek Pharmaceuticals: Consultant, Consulting fee. P. McGovern, Paratek Pharmaceuticals: Employee, Salary. E. Tzanis, Paratek Pharmaceuticals: Employee, Salary.

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