scholarly journals Safety, Tolerability, and Efficacy of GSK1322322 in the Treatment of Acute Bacterial Skin and Skin Structure Infections

2014 ◽  
Vol 58 (11) ◽  
pp. 6518-6527 ◽  
Author(s):  
Ralph Corey ◽  
Odin J. Naderer ◽  
William D. O'Riordan ◽  
Etienne Dumont ◽  
Lori S. Jones ◽  
...  
Keyword(s):  
Adverse Events ◽  
Group Treatment ◽  
Clinical Success ◽  
Treated Group ◽  
Success Rates ◽  
Lesion Area ◽  
Dose Selection ◽  
Skin Structure ◽  
Link Type ◽  
Intent To Treat

ABSTRACTGSK1322322 represents a new class of antibiotics that targets an essential bacterial enzyme required for protein maturation, peptide deformylase. This multicenter, randomized, phase IIa study compared the safety, tolerability, and efficacy of GSK1322322 at 1,500 mg twice daily (b.i.d.) with that of linezolid at 600 mg b.i.d. in patients suspected of having Gram-positive acute bacterial skin and skin structure infections (ABSSSIs). The primary endpoint was assessment of the safety of GSK1322322, and a key secondary endpoint was the number of subjects with a ≥20% decrease in lesion area from the baseline at 48 and 72 h after treatment initiation. GSK1322322 administration was associated with mild-to-moderate drug-related adverse events, most commonly, nausea, vomiting, diarrhea, and headache. Adverse events (86% versus 74%) and withdrawals (28% versus 11%) were more frequent in the GSK1322322-treated group. Treatment with GSK1322322 and linezolid was associated with ≥20% decreases from the baseline in the lesion area in 73% (36/49) and 92% (24/26) of the patients, respectively, at the 48-h assessment and in 96% (44/46) and 100% (25/25) of the patients, respectively, at the 72-h assessment. Reductions in exudate/pus, pain, and skin infection scores were comparable between the GSK1322322 and linezolid treatments. The clinical success rates within the intent-to-treat population and the per-protocol population that completed this study were 67 and 91%, respectively, in the GSK1322322-treated group and 89 and 100%, respectively, in the linezolid-treated group. These results will be used to guide dose selection in future studies with GSK1322322 to optimize its tolerability and efficacy in patients with ABSSSIs. (This study has been registered atClinicalTrials.govunder registration no. NCT01209078 and athttp://www.gsk-clinicalstudyregister.com[PDF113414].)

scholarly journals A Randomized, Evaluator-Blind, Phase 2 Study Comparing the Safety and Efficacy of Omadacycline to Those of Linezolid for Treatment of Complicated Skin and Skin Structure Infections

2012 ◽  
Vol 56 (11) ◽  
pp. 5650-5654 ◽  
Author(s):  
Gary J. Noel ◽  
Michael P. Draper ◽  
Howard Hait ◽  
S. Ken Tanaka ◽  
Robert D. Arbeit
Keyword(s):  
Adverse Events ◽  
Clinical Success ◽  
Phase 2 ◽  
Success Rates ◽  
Safety And Efficacy ◽  
Content Type ◽  
Skin Structure ◽  
Phase 2 Trial ◽  
Complicated Skin ◽  
Intent To Treat

ABSTRACTA randomized, investigator-blind, multicenter phase 2 trial involving patients with complicated skin and skin structure infections (cSSSI) compared the safety and efficacy of omadacycline, a broad-spectrum agent with activity against methicillin-resistantStaphylococcus aureus(MRSA), to those of linezolid (with or without aztreonam). Patients were randomized 1:1 to omadacycline (100 mg intravenously [i.v.] once a day [QD] with an option to transition to 200 mg orally QD) or linezolid (600 mg i.v. twice daily [BID] with an option to transition to 600 mg orally BID) at 11 U.S. sites. Patients suspected or documented to have infections caused by Gram-negative bacteria were given aztreonam (2 g i.v. every 12 h [q12h]) if randomized to linezolid or matching placebo infusions if randomized to omadacycline. Adverse events were reported in 46 (41.4%) omadacycline-treated and 55 (50.9%) linezolid-treated patients. Adverse events related to treatment were assessed by investigators in 24 (21.6%) omadacycline-treated and 33 (30.6%) linezolid-treated patients. The gastrointestinal tract was most commonly involved, with adverse events reported in 21 (18.9%) patients exposed to omadacycline and 20 (18.5%) exposed to linezolid. Rates of successful clinical response in the intent-to-treat (ITT) and clinical evaluable (CE) populations favored omadacycline (ITT, 88.3% versus 75.9%; 95% confidence interval [CI], 1.9 to 22.9; CE, 98.0% versus 93.2%; 95% CI, −1.7 to 11.3). For microbiologically evaluable (ME) patients withS. aureusinfections, the clinical success rates were 97.2% (70/72) in omadacycline-treated and 92.7% (51/55) in linezolid-treated patients. This phase 2 experience supports conclusions that omadacycline is well tolerated in cSSSI patients and that this aminomethylcycline has potential to be an effective treatment for serious skin infections.

scholarly journals Ceftobiprole Compared With Vancomycin Plus Aztreonam in the Treatment of Acute Bacterial Skin and Skin Structure Infections: Results of a Phase 3, Randomized, Double-blind Trial (TARGET)

2020 ◽  
Author(s):  
J Scott Overcash ◽  
Charles Kim ◽  
Richard Keech ◽  
Illia Gumenchuk ◽  
Borislav Ninov ◽  
...  
Keyword(s):  
Clinical Response ◽  
Clinical Success ◽  
Laboratory Data ◽  
European Medicines Agency ◽  
Success Rates ◽  
Phase 3 ◽  
Gram Positive ◽  
Double Blind ◽  
Gram Negative ◽  
Skin Structure

Abstract Background The development of novel broad-spectrum antibiotics, with efficacy against both gram-positive and gram-negative bacteria, has the potential to enhance treatment options for acute bacterial skin and skin structure infections (ABSSSIs). Ceftobiprole is an advanced-generation intravenous cephalosporin with broad in vitro activity against gram-positive (including methicillin-resistant Staphylococcus aureus) and gram-negative pathogens. Methods TARGET was a randomized, double-blind, active-controlled, parallel-group, multicenter, phase 3 noninferiority study that compared ceftobiprole with vancomycin plus aztreonam. The Food and Drug Administration-defined primary efficacy endpoint was early clinical response 48–72 hours after treatment initiation in the intent-to-treat (ITT) population and the European Medicines Agency-defined primary endpoint was investigator-assessed clinical success at the test-of-cure (TOC) visit. Noninferiority was defined as the lower limit of the 95% CI for the difference in success rates (ceftobiprole minus vancomycin/aztreonam) >−10%. Safety was assessed through adverse event and laboratory data collection. Results In total, 679 patients were randomized to ceftobiprole (n = 335) or vancomycin/aztreonam (n = 344). Early clinical success rates were 91.3% and 88.1% in the ceftobiprole and vancomycin/aztreonam groups, respectively, and noninferiority was demonstrated (adjusted difference: 3.3%; 95% CI: −1.2, 7.8). Investigator-assessed clinical success at the TOC visit was similar between the 2 groups, and noninferiority was demonstrated for both the ITT (90.1% vs 89.0%) and clinically evaluable (97.9% vs 95.2%) populations. Both treatment groups displayed similar microbiological success and safety profiles. Conclusions TARGET demonstrated that ceftobiprole is noninferior to vancomycin/aztreonam in the treatment of ABSSSIs, in terms of early clinical response and investigator-assessed clinical success at the TOC visit. Clinical Trials Registration NCT03137173.

scholarly journals Telavancin versus Standard Therapy for Treatment of Complicated Skin and Skin Structure Infections Caused by Gram-Positive Bacteria: FAST 2 Study

2006 ◽  
Vol 50 (3) ◽  
pp. 862-867 ◽  
Author(s):  
Martin E. Stryjewski ◽  
Vivian H. Chu ◽  
William D. O'Riordan ◽  
Brian L. Warren ◽  
Lala M. Dunbar ◽  
...  
Keyword(s):  
Standard Therapy ◽  
Clinical Success ◽  
Therapy Group ◽  
Success Rates ◽  
Standard Therapy Group ◽  
Gram Positive ◽  
Double Blind ◽  
Skin Structure ◽  
Complicated Skin ◽  
Cure Rates

ABSTRACT Telavancin is a bactericidal lipoglycopeptide with a multifunctional mechanism of action. We conducted a randomized, double blind, active-control phase II trial. Patients ≥18 years of age with complicated skin and skin structure infections caused by suspected or confirmed gram-positive organisms were randomized to receive either telavancin at 10 mg/kg intravenously every 24 h (q24h) or standard therapy (antistaphylococcal penicillin at 2 g q6h or vancomycin at 1 g q12h). A total of 195 patients were randomized and received at least one dose of study medication. Clinical success rates were similar in all analysis populations at test of cure. In microbiologically evaluable patients with Staphylococcus aureus at baseline (n = 91), 96% of the telavancin group and 90% of the standard-therapy group were cured. Among patients with methicillin-resistant S. aureus (MRSA) at baseline (n = 45), clinical cure rates were also 96% for telavancin and 90% for standard therapy. Microbiologic eradication in patients with S. aureus infection was better with telavancin compared to standard therapy (92% versus 78%, P = 0.07) and significantly better in patients with MRSA (92% versus 68%; P = 0.04). Therapy was discontinued for an adverse event (AE) in 6% and 3% of the patients receiving telavancin and standard therapy, respectively. Except for two cases of rash in the telavancin group, these AEs were similar in type and severity in the two groups. The overall incidences and severities of AEs and laboratory abnormalities were similar between the two groups. These data support the ongoing studies assessing the efficacy and safety of telavancin in the treatment of serious gram-positive infections, particularly involving MRSA.

Practice patterns, techniques, and outcomes of flexible endoscopic myotomy for Zenker’s diverticulum: a retrospective multicenter study

Endoscopy ◽  
2020 ◽  
Author(s):  
Chetan Mittal ◽  
David L. Diehl ◽  
Peter V. Draganov ◽  
Laith H. Jamil ◽  
Ammara Khalid ◽  
...  
Keyword(s):  
Adverse Events ◽  
Practice Patterns ◽  
Clinical Success ◽  
Zenker’S Diverticulum ◽  
Success Rates ◽  
Zenker's Diverticulum ◽  
Submucosal Dissection ◽  
Significant Difference ◽  
Endoscopic Myotomy ◽  
Needle Knife

Abstract Background Flexible endoscopic myotomy has been increasingly performed for Zenker’s diverticulum using various endoscopic techniques and devices. The main aims of this study were to assess practice patterns and compare outcomes of endoscopic myotomy for Zenker’s diverticulum. Methods Procedures performed at 12 tertiary endoscopy centers from 1/2012 to 12/2018 were reviewed. Patients (≥ 18 years) with Zenker’s diverticulum who had dysphagia and/or regurgitation and underwent endoscopic myotomy were included. Outcomes assessed included technical success, clinical success, and adverse events. Results 161 patients were included. Traditional endoscopic septotomy was performed most frequently (137/161, 85.1 %) followed by submucosal dissection of the septum and myotomy (24/161, 14.9 %). The hook knife (43/161, 26.7 %) and needle-knife (33/161, 20.5 %) were used most frequently. Overall, technical and clinical success rates were 98.1 % (158/161) and 78.1 % (96/123), respectively. Adverse events were noted in 13 patients (8.1 %). There was no significant difference in technical and clinical success between traditional septotomy and submucosal dissection groups (97.1 % vs. 95.8 %, P = 0.56 and 75.2 % vs. 90.9 %, P  = 0.16, respectively). Clinical success was higher with the hook knife (96.7 %) compared with the needle-knife (76.6 %) and insulated tip knife (47.1 %). Outcomes were similar between centers performing > 20, 11 – 20, and ≤ 10 procedures. Conclusions Flexible endoscopic myotomy is an effective therapy for Zenker’s diverticulum, with a low rate of adverse events. There was no significant difference in outcomes between traditional septotomy and a submucosal dissection approach, or with centers with higher volume, though clinical success was higher with the hook knife.

scholarly journals The EDGI new take on EDGE: EUS-directed transgastric intervention (EDGI), other than ERCP, for Roux-en-Y gastric bypass anatomy: a multicenter study

2019 ◽  
Vol 07 (10) ◽  
pp. E1231-E1240 ◽  
Author(s):  
Matthew R. Krafft ◽  
William Hsueh ◽  
Theodore W. James ◽  
Thomas M. Runge ◽  
Todd H. Baron ◽  
...  
Keyword(s):  
Gastric Bypass ◽  
Retrospective Study ◽  
Adverse Events ◽  
Multicenter Study ◽  
Clinical Success ◽  
Endoscopic Biopsy ◽  
Success Rates ◽  
Moderate Severity ◽  
Excluded Stomach ◽  
Heterogenous Group

Abstract Background and study aims Indications for accessing the duodenum, and/or excluded stomach in Roux-en-Y gastric bypass (RYGB) patients extend beyond diagnosis and treatment of pancreaticobiliary maladies. Given the high technical and clinical success of EUS-directed transgastric ERCP (EDGE) in RYGB anatomy, we adopted this transgastric (anterograde) approach to evaluate and treat luminal and extraluminal pathology in and around the excluded gut in RYGB patients. EUS-directed transgastric intervention (“EDGI”), other than ERCP, is the terminology we have chosen to describe this heterogenous group of transgastric diagnostic and/or interventional endoscopic procedures (transgastric interventions) performed via a lumen-apposing mental stent (LAMS) in select patients with RYGB. Patients and methods A multicenter (n = 4), retrospective study of RYGB patients with suspected luminal or extraluminal pathology, in or around the duodenum and/or excluded stomach, underwent EDGI using LAMS between December 2015 and January 2019. Results A total of 14 patients (78.6 % women; mean age, 55.7 + 12.4 years) underwent EDGI via LAMS. Technical and clinical success rates of EDGI were 100 %. The most common transgastric interventions were diagnostic EUS of extraluminal pathology (n = 6, 42.7 %) and endoscopic biopsy of gastroduodenal luminal abnormalities (n = 5, 35.7 %). Two moderate-severity adverse events due to LAMS maldeployment occurred during EUS-JG creation (14.3 %), and each instance was successfully rescued with a bridging stent. Conclusions A variety of gastroduodenal luminal and extraluminal disorders in RYGB patients can be effectively diagnosed and managed using EDGI via LAMS.

Safety of lumen-apposing stent with or without coaxial plastic stent for endoscopic ultrasound-guided drainage of pancreatic fluid collections: a retrospective study

Endoscopy ◽  
2018 ◽  
Vol 50 (10) ◽  
pp. 1022-1026 ◽  
Author(s):  
Manuel Puga ◽  
Claudia Consiglieri ◽  
Juli Busquets ◽  
Natàlia Pallarès ◽  
Lluis Secanella ◽  
...  
Keyword(s):  
Adverse Events ◽  
Endoscopic Ultrasound ◽  
Clinical Success ◽  
Success Rates ◽  
Plastic Stent ◽  
Frequent Adverse Event ◽  
Pancreatic Fluid Collections ◽  
Pancreatic Fluid ◽  
Transmural Drainage ◽  
Fluid Collections

Abstract Background The aim of this study was to evaluate whether the placement of a coaxial double-pigtail plastic stent (DPS) within a lumen-apposing metal stent (LAMS) may improve the safety of endoscopic ultrasound (EUS)-guided drainage of pancreatic fluid collections (PFCs). Methods This was a retrospective cohort study including patients with PFCs and an indication for transmural drainage. Two strategies (LAMS alone or LAMS plus DPS) were used at the endoscopist’s discretion. Results A total of 41 patients were treated (21 LAMS alone; 20 LAMS plus DPS). The characteristics of the PFCs, and the technical and clinical success rates did not differ between groups. The LAMS alone group had a significantly higher rate of adverse events than the LAMS plus DPS group (42.9 % vs. 10.0 %; P = 0.04). Bleeding was the most frequent adverse event observed. Conclusions The addition of a coaxial DPS to LAMS was associated with a lower rate of adverse events in EUS-guided drainage of PFCs.

scholarly journals Percutaneous cholecystostomy for biliary decompression in patients with cholangitis and pancreatitis

2018 ◽  
Vol 46 (10) ◽  
pp. 4120-4128 ◽  
Author(s):  
Jin Myung Park ◽  
Chang Don Kang ◽  
Minjong Lee ◽  
Sung Chul Park ◽  
Sung Joon Lee ◽  
...  
Keyword(s):  
Adverse Event ◽  
Adverse Events ◽  
Biliary Obstruction ◽  
Clinical Success ◽  
Adverse Event Rate ◽  
Serum Total Bilirubin ◽  
Percutaneous Cholecystostomy ◽  
Success Rates ◽  
Biliary Decompression ◽  
Significant Difference

Objective This study was performed to assess the effectiveness and safety of percutaneous cholecystostomy (PC) for biliary decompression. Methods We retrospectively analyzed our institution’s PC database from March 2015 to August 2017 and selected patients with biliary obstruction. The primary outcomes were the technical and clinical success rates. As secondary outcomes, adverse events and pain after PC were compared with those of patients who underwent PC for acute cholecystitis during the same period. Results Twenty patients underwent PC for biliary obstruction (cholangitis, 19; pancreatitis, 1). The technical and clinical success rates were 100%. The median serum total bilirubin level decreased considerably from 4.5 to 1.4 mg/dL after PC. An adverse event (catheter migration) occurred in 1 patient, and 17 patients developed pain after PC. During the same period, 104 patients underwent PC for cholecystitis. Adverse events occurred in 7 patients, and 62 developed pain. There was no significant difference in the adverse event rate between the cholangitis/pancreatitis and cholecystitis groups (5.0% vs. 6.7%, respectively), but pain occurred considerably more frequently in the cholangitis/pancreatitis group (94.4% vs. 63.9%, respectively). Conclusions PC is an effective and safe method for biliary decompression in selected patients. However, attention should be paid to postoperative pain.

scholarly journals High-Dose Azithromycin versus High-Dose Amoxicillin-Clavulanate for Treatment of Children with Recurrent or Persistent Acute Otitis Media

2003 ◽  
Vol 47 (10) ◽  
pp. 3179-3186 ◽  
Author(s):  
Antonio Arrieta ◽  
Adriano Arguedas ◽  
Pilar Fernandez ◽  
Stan L. Block ◽  
Paz Emperanza ◽  
...  
Keyword(s):  
Otitis Media ◽  
Clinical Success ◽  
Acute Otitis Media ◽  
High Dose ◽  
Success Rates ◽  
Double Blind ◽  
Amoxicillin Clavulanate ◽  
Risk Patients ◽  
History Of ◽  
Intent To Treat

ABSTRACT Infants and young children, especially those in day care, are at risk for recurrent or persistent acute otitis media (AOM). There are no data on oral alternatives to high-dose amoxicillin-clavulanate for treating AOM in these high-risk patients. In this double-blind, double-dummy multicenter clinical trial, we compared a novel, high-dose azithromycin regimen with high-dose amoxicillin-clavulanate for treatment of children with recurrent or persistent AOM. Three hundred four children were randomized; 300 received either high-dose azithromycin (20 mg/kg of body weight once a day for 3 days) or high-dose amoxicillin-clavulanate (90 mg/kg divided twice a day for 10 days). Tympanocentesis was performed at baseline; clinical response was assessed at day 12 to 16 and day 28 to 32. Two-thirds of patients were aged ≤2 years. A history of recurrent, persistent, or recurrent plus persistent AOM was noted in 67, 18, and 14% of patients, respectively. Pathogens were isolated from 163 of 296 intent-to-treat patients (55%). At day 12 to 16, clinical success rates for azithromycin and amoxicillin-clavulanate were comparable for all patients (86 versus 84%, respectively) and for children aged ≤2 years (85 versus 79%, respectively). At day 28 to 32, clinical success rates for azithromycin were superior to those for amoxicillin-clavulanate for all patients (72 versus 61%, respectively; P = 0.047) and for those aged ≤2 years (68 versus 51%, respectively; P = 0.017). Per-pathogen clinical efficacy against Streptococcus pneumoniae and Haemophilus influenzae was comparable between the two regimens. The rates of treatment-related adverse events for azithromycin and amoxicillin-clavulanate were 32 and 42%, respectively (P = 0.095). Corresponding compliance rates were 99 and 93%, respectively (P = 0.018). These data demonstrate the efficacy and safety of high-dose azithromycin for treating recurrent or persistent AOM.

scholarly journals Endoscopic ultrasound-directed transgastric ERCP (EDGE): a retrospective multicenter study

Endoscopy ◽  
2020 ◽  
Author(s):  
Thomas M. Runge ◽  
Austin L. Chiang ◽  
Thomas E. Kowalski ◽  
Theodore W. James ◽  
Todd H. Baron ◽  
...  
Keyword(s):  
Adverse Events ◽  
Endoscopic Ultrasound ◽  
Clinical Success ◽  
Success Rates ◽  
Long Term Outcomes ◽  
Gastrointestinal Series ◽  
Objective Testing ◽  
Endoscopic Closure ◽  
Retrospective Multicenter Study

Abstract Background Endoscopic ultrasound-directed transgastric endoscopic retrograde cholangiopancreatography (ERCP; EDGE) is an alternative to enteroscopy- and laparoscopy-assisted ERCP in patients with Roux-en-Y gastric bypass anatomy. Although short-term results are promising, the long-term outcomes are not known. The aims of this study were: (1) to determine the rates of long-term adverse events after EDGE, with a focus on rates of persistent gastrogastric or jejunogastric fistula; (2) to identify predictors of persistent fistula; (3) to assess the outcomes of endoscopic closure when persistent fistula is encountered. Methods This was a multicenter retrospective study involving 13 centers between February 2015 and March 2019. Adverse events were defined according to the ASGE lexicon. Persistent fistula was defined as an upper gastrointestinal series or esophagogastroduodenoscopy showing evidence of fistula. Results 178 patients (mean age 58 years, 79 % women) underwent EDGE. Technical success was achieved in 98 % of cases (175/178), with a mean procedure time of 92 minutes. Periprocedural adverse events occurred in 28 patients (15.7 %; mild 10.1 %, moderate 3.4 %, severe 2.2 %). The four severe adverse events were managed laparoscopically. Persistent fistula was diagnosed in 10 % of those sent for objective testing (9/90). Following identification of a fistula, 5 /9 patients underwent endoscopic closure procedures, which were successful in all cases. Conclusions The EDGE procedure is associated with high clinical success rates and an acceptable risk profile. Persistent fistulas after lumen-apposing stent removal are uncommon, but objective testing is recommended to identify their presence. When persistent fistulas are identified, endoscopic treatment is warranted, and should be successful in closing the fistula.

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