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Purpose Low-grade intermediate-risk nonmuscle-invasive bladder cancer (LG IR NMIBC) is a recurrent disease, thus requiring repeated transurethral resection of bladder tumor under general anesthesia. We evaluated the efficacy and safety of UGN-102, a mitomycin-containing reverse thermal gel, as a primary chemoablative therapeutic alternative to transurethral resection of bladder tumor for patients with LG IR NMIBC. Materials and methods This prospective, phase 2b, open-label, single-arm trial recruited patients with biopsy-proven LG IR NMIBC to receive 6 once-weekly instillations of UGN-102. The primary end point was complete response (CR) rate, defined as the proportion of patients with negative endoscopic examination, negative cytology and negative for-cause biopsy 3 months after treatment initiation. Patients with CR were followed quarterly up to 12 months to assess durability of treatment effect. Safety and adverse events were monitored throughout the trial. Results A total of 63 patients (38 males and 25 females 33-96 years old) enrolled and received ≥1 instillation of UGN-102. Among the patients 41 (65%) achieved CR at 3 months, of whom 39 (95%), 30 (73%) and 25 (61%) remained disease-free at 6, 9 and 12 months after treatment initiation, respectively. A total of 13 patients had documented recurrences. The probability of durable response 9 months after CR (12 months after treatment initiation) was estimated to be 73% by Kaplan-Meier analysis. Common adverse events (incidence ≥10%) included dysuria, urinary frequency, hematuria, micturition urgency, urinary tract infection and fatigue. Conclusions Nonsurgical primary chemoablation of LG IR NMIBC using UGN-102 resulted in significant treatment response with sustained durability. UGN-102 may provide an alternative to repetitive surgery for patients with LG IR NMIBC.

Purpose To evaluate the pharmacokinetic properties of UGN-101, a mitomycin-containing reverse thermal gel used as primary chemoablative treatment for low-grade upper tract urothelial carcinoma (UTUC), in a subset of patients participating in a phase 3 clinical trial. Methods Pharmacokinetic parameters (Cmax, Tmax, AUC(0–6), λz, t½, and AUCinf) were evaluated in six participants (male or female, ≥ 18 years) with biopsy-proven, low-grade UTUC who received the first of 6 once-weekly instillations of UGN-101 to the renal pelvis and calyces via retrograde ureteral catheter. Plasma samples were collected prior to instillation and 30 min, 1, 2, 3, 4, 5, and 6 h post-instillation. Safety was assessed by laboratory evaluations, physical exam, and adverse event monitoring. Results The mean age of the six participants was 69 years; most were male (5/6) and Caucasian (5/6). Mean (SD) Cmax was 6.24 (4.11) ng/mL and mean Tmax was 1.79 (1.89) hours after instillation. Mean apparent t½ following instillation was 1.27 (0.63) hours. Mean total systemic exposure to mitomycin up to 6 h post-instillation was 20.30 (19.69) ng h/mL. At 6 h post-instillation, mitomycin plasma concentrations of 5/6 participants were Conclusion The reverse thermal gel formulation of UGN-101 is associated with higher concentration and extended dwell time of mitomycin in contact with the urothelium of the upper urinary tract while limiting systemic absorption of mitomycin. Registration NCT02793128; registered June 8, 2016.

Our goal was to evaluate long-term safety and durability of response to UGN-101, a mitomycin-containing reverse thermal gel, as primary chemoablative treatment for low-grade upper tract urothelial carcinoma.In this open-label, single-arm, multicenter, phase 3 trial (NCT02793128), patients ≥18 years of age with primary or recurrent biopsy-proven low-grade upper tract urothelial carcinoma received 6 once-weekly instillations of UGN-101 via retrograde catheter to the renal pelvis and calyces. Those with complete response (defined as negative ureteroscopic evaluation, negative cytology and negative for-cause biopsy) 4-6 weeks after the last instillation were eligible for up to 11 monthly maintenance instillations and were followed for ≥12 months with quarterly evaluation of response durability. Durability of complete response was determined by ureteroscopic evaluation; duration of response was estimated by the Kaplan-Meier method. Treatment-emergent adverse events (TEAEs) were monitored.Of 71 patients who initiated treatment, 41 (58%) had complete response to induction therapy and consented to long-term followup; 23/41 patients (56%) remained in complete response after 12 months (95% CI 40, 72), comprising 6/12 (50%) who did not receive any maintenance instillations and 17/29 (59%) who received ≥1 maintenance instillation. Kaplan-Meier analysis of durability was estimated as 82% (95% CI 66, 91) at 12 months. Ureteric stenosis was the most frequently reported TEAE (31/71, 44%); an increasing number of instillations appeared to be associated with increased incidence of urinary TEAEs.Durability of response to UGN-101 with or without maintenance treatment is clinically meaningful, offering a kidney-sparing therapeutic alternative for patients with low-grade disease.

INTRODUCTION AND OBJECTIVE:Standard treatment for low-grade upper tract urothelial carcinoma (LG UTUC) involving the renal pelvis and calyces is radical nephroureterectomy (RNU), or nephron-sparing...

INTRODUCTION AND OBJECTIVE:Urothelial cancer is less common, but may be associated with poorer outcomes in women than in men. The literature on gender-based differences in low-grade upper tract uro...

Objectives To compile and examine safety data from clinical studies of endoscopic management of patients with low-grade upper tract urothelial carcinoma (UTUC) to identify rates and factors associated with reported complications. Methods Ovid Medline and Ovid Medline Daily (with Embase as secondary search) including citations from 1946-2018 were queried using the following terms: ureteroscopy, ureter, catheter, endoscopy, complication, adverse events, morbidity, ablation, laser, upper tract urothelial carcinoma, ureteral stricture, ureteral stenosis, and ureteral injury. Abstracts were reviewed for relevance; diagnostic studies, case studies, and reviews were excluded. Results Thirty-eight publications (7 prospective, 31 retrospective) representing >1100 patients were identified. Ureteral stricture was the most frequently reported complication (studies; rates) (26/38; 0-27%), with incidence associated with number of procedures and treatment method. Bleeding, infection, and fever were most common with adjuvant treatment (BCG or mitomycin). Serious and fatal complications were rare. Conclusions Ureteral stricture is the most frequent complication of endoscopic UTUC management but can be managed successfully in most cases. Most complications were minor. Although additional prospective studies are needed, these results support the safety of ureteroscopic management of UTUC in appropriately selected patients.

INTRODUCTION AND OBJECTIVE:Low grade (LG) upper tract urothelial cancer (UTUC) accounts for 40% of all UTUC diagnosed in the US. Although LG UTUC has a low risk of progression, radical nephroureter...

Introduction:Low grade, intermediate risk non-muscle invasive bladder cancer (LG IR-NMIBC) is notable for a high rate of disease recurrence yet low risk of disease progression. Patients with LG IR-...

Most patients with low-grade upper tract urothelial cancer are treated by radical nephroureterectomy. We aimed to assess the safety and activity of a non-surgical treatment using instillation of UGN-101, a mitomycin-containing reverse thermal gel.In this open-label, single-arm, phase 3 trial, participants were recruited from 24 academic sites in the USA and Israel. Patients (aged ≥18 years) with primary or recurrent biopsy-proven, low-grade upper tract urothelial cancer (measuring 5-15 mm in maximum diameter) and an Eastern Cooperative Oncology Group performance status score of less than 3 (Karnofsky Performance Status score40) were registered to receive six instillations of once-weekly UGN-101 (mitomycin 4 mg per mL; dosed according to volume of patient's renal pelvis and calyces, maximum 60 mg per instillation) via retrograde catheter to the renal pelvis and calyces. All patients had a planned primary disease evaluation 4-6 weeks after the completion of initial therapy, in which the primary outcome of complete response was assessed, defined as negative 3-month ureteroscopic evaluation, negative cytology, and negative for-cause biopsy. Activity (complete response, expected to occur in15% of patients) and safety were assessed by the investigator in all patients who received at least one dose of UGN-101. Data presented are from the data cutoff on May 22, 2019. This study is registered with ClinicalTrials.gov, NCT02793128.Between April 6, 2017, and Nov 26, 2018, 71 (96%) of 74 enrolled patients received at least one dose of UGN-101. 42 (59%, 95% CI 47-71; p0·0001) patients had a complete response at the primary disease evaluation visit. The median follow-up for patients with a complete response was 11·0 months (IQR 5·1-12·4). The most frequently reported all-cause adverse events were ureteric stenosis in 31 (44%) of 71 patients, urinary tract infection in 23 (32%), haematuria in 22 (31%), flank pain in 21 (30%), and nausea in 17 (24%). 19 (27%) of 71 patients had study drug-related or procedure-related serious adverse events. No deaths were regarded as related to treatment.Primary chemoablation of low-grade upper tract urothelial cancer with intracavitary UGN-101 results in clinically significant disease eradication and might offer a kidney-sparing treatment alternative for these patients.UroGen Pharma.

Monotherapy with lefamulin, a novel, pleuromutilin antibiotic with intravenous and oral formulation options, was noninferior to moxifloxacin for efficacy and generally safe and well tolerated for community-acquired bacterial pneumonia (CABP). Lefamulin’s spectrum of activity targets bacteria that cause CABP., Background Lefamulin, a pleuromutilin antibiotic, is active against pathogens commonly causing community-acquired bacterial pneumonia (CABP). The Lefamulin Evaluation Against Pneumonia (LEAP 1) study was a global noninferiority trial to evaluate the efficacy and safety of lefamulin for the treatment of CABP. Methods In this double-blind study, adults with CABP of Pneumonia Outcomes Research Team risk class ≥III were randomized 1:1 to receive lefamulin at 150 mg intravenously (IV) every 12 hours or moxifloxacin at 400 mg IV every 24 hours. After 6 doses, patients could be switched to an oral study drug if prespecified improvement criteria were met. If methicillin-resistant Staphylococcus aureus was suspected, either linezolid or placebo was added to moxifloxacin or lefamulin, respectively. The US Food and Drug Administration primary endpoint was an early clinical response (ECR) 96 ± 24 hours after the first dose of the study drug in the intent-to-treat (ITT) population (noninferiority margin, 12.5%). The European Medicines Agency co-primary endpoints were an investigator assessment of clinical response (IACR) 5–10 days after the last dose of the study drug in the modified ITT (mITT) and clinically evaluable (CE) populations (noninferiority margin, 10%). Results There were 551 patients randomized (n = 276 lefamulin; n = 275 moxifloxacin). Lefamulin was noninferior to moxifloxacin for ECR (87.3% vs 90.2%, respectively; difference −2.9%, 95% confidence interval [CI] g −8.5 to 2.8) and IACR (mITT, 81.7% vs 84.2%, respectively; difference −2.6%, 95% CI −8.9 to 3.9; CE, 86.9% vs 89.4%, respectively; difference −2.5%, 95% CI −8.4 to 3.4). Rates of study drug discontinuation due to treatment-emergent adverse events were 2.9% for lefamulin and 4.4% for moxifloxacin. Conclusions Lefamulin was noninferior to moxifloxacin for the primary efficacy endpoints and was generally safe and well tolerated. Clinical Trials Registration NCT02559310.

INTRODUCTION AND OBJECTIVES:Only 30% of UTUC patients receive endoscopic, nephron-sparing treatments due to (1) high grade histology, (2) tumor burden, or (3) unfavorable tumor location. Endoscopic...

Lefamulin, a pleuromutilin antibiotic, is active against pathogens commonly causing community-acquired bacterial pneumonia (CABP). The Lefamulin Evaluation Against Pneumonia (LEAP 1) study was a global noninferiority trial to evaluate the efficacy and safety of lefamulin for the treatment of CABP.In this double-blind study, adults with CABP of Pneumonia Outcomes Research Team risk class ≥III were randomized 1:1 to receive lefamulin at 150 mg intravenously (IV) every 12 hours or moxifloxacin at 400 mg IV every 24 hours. After 6 doses, patients could be switched to an oral study drug if prespecified improvement criteria were met. If methicillin-resistant Staphylococcus aureus was suspected, either linezolid or placebo was added to moxifloxacin or lefamulin, respectively. The US Food and Drug Administration primary endpoint was an early clinical response (ECR) 96 ± 24 hours after the first dose of the study drug in the intent-to-treat (ITT) population (noninferiority margin, 12.5%). The European Medicines Agency co-primary endpoints were an investigator assessment of clinical response (IACR) 5-10 days after the last dose of the study drug in the modified ITT (mITT) and clinically evaluable (CE) populations (noninferiority margin, 10%).There were 551 patients randomized (n = 276 lefamulin; n = 275 moxifloxacin). Lefamulin was noninferior to moxifloxacin for ECR (87.3% vs 90.2%, respectively; difference -2.9%, 95% confidence interval [CI] g -8.5 to 2.8) and IACR (mITT, 81.7% vs 84.2%, respectively; difference -2.6%, 95% CI -8.9 to 3.9; CE, 86.9% vs 89.4%, respectively; difference -2.5%, 95% CI -8.4 to 3.4). Rates of study drug discontinuation due to treatment-emergent adverse events were 2.9% for lefamulin and 4.4% for moxifloxacin.Lefamulin was noninferior to moxifloxacin for the primary efficacy endpoints and was generally safe and well tolerated.NCT02559310.

Background New CABP treatments with targeted activity and improved tolerability are needed. LEF, a novel pleuromutilin antibiotic that binds to a conserved region of the bacterial ribosome, is in development for IV or oral CABP treatment. This Phase 3 clinical study evaluated the efficacy of LEF vs. MOX in adults with CABP. Methods In this multicenter, randomized, double-blind study, 551 adult patients with CABP (Patient Outcomes Research Team Risk Class ≥III) were randomized to LEF 150 mg IV Q12 hours (n = 276) or MOX 400 mg IV Q24 hours (n = 275). After 6 IV doses, qualifying patients could be switched to oral therapy. Adjunctive linezolid was given with MOX for suspected methicillin-resistant S. aureus. Primary outcomes were early clinical response (ECR) in the intent-to-treat (ITT) population (FDA endpoint), and investigator assessment of clinical response (IACR) at test of cure in the modified ITT (mITT) and clinically evaluable (CE-TOC) populations (co-primary EMA endpoints). The microITT population included all patients with a baseline CABP pathogen detected by respiratory tract or blood culture, urinary antigen test, serology, and real-time PCR from sputum, oropharyngeal and nasopharyngeal swabs. The microITT2 population included patients with a CABP pathogen detected by methods excluding PCR. Confirmatory identification and susceptibility testing of isolates, serology, and PCR were performed by a central laboratory. Results LEF was noninferior to MOX for ECR and IACR (LEF 87.3% [ITT], 81.7% [mITT], 86.9% [CE-TOC]; MOX 90.2% [ITT], 84.2% [mITT], 89.4% [CE-TOC]). The most common pathogen identified was S. pneumoniae. In the microITT population (n = 159 per arm), LEF and MOX demonstrated similar ECR and IACR rates (figure). LEF was efficacious against S. pneumoniae (including resistant phenotypes), H. influenzae, M. catarrhalis, S. aureus, and atypical pathogens. In the microITT2 population, response rates remained similar across baseline pathogens but showed more variation likely due to smaller sample sizes. Conclusion In this first Phase 3 clinical trial, LEF showed similar efficacy to MOX against the most commonly identified CABP pathogens. LEF demonstrates promise as a targeted monotherapy for the treatment of CABP in adults. Disclosures T. File, BioMerieux: Scientific Advisor, Consulting fee. Curetis: Scientific Advisor, Consulting fee. Melinta: Scientific Advisor, Consulting fee. Merck: Scientific Advisor, Consulting fee. MotifBio: Scientific Advisor, Consulting fee. Nabriva: Investigator and Scientific Advisor, Consulting fee and Research grant. Pfizer: Scientific Advisor, Consulting fee. Paratek: Scientific Advisor, Consulting fee. L. Goldberg, Nabriva: Employee, Employee Stock Options and Salary. S. Paukner, Nabriva: Employee and Shareholder, Salary. A. Das, Achaogen: Consultant, Consulting fee. Cempra: Consultant, Consulting fee. Contrafect: Consultant, Consulting fee. Paratek: Consultant, Consulting fee. Tetraphase: Consultant, Consulting fee. Wockhardt: Consultant, Consulting fee. Theravance: Consultant, Consulting fee. Zavante: Consultant, Consulting fee. UTILITY: Consultant, Consulting fee. S. P. Gelone, Nabriva Therapeutics: Employee, Equity, Shareholder and Salary. Achaogen: Shareholder, Equity, Shareholder. J. Saviski, Nabrica Therapeutics, plc: Employee, Salary. C. Sweeney, Nabriva: Employee, employee stock options and Salary. E. Seltzer, Nabriva (previous employee and salary): Employee and Shareholder, Salary. G. H. Talbot, Nabriva Therapeutics: Board Member, Consultant and Shareholder, Consulting fee and stock options, board fees. L. B. Gasink, Nabriva: Employee, Salary.

Three open-label studies assessed the safety, tolerability, and pharmacokinetics of intravenous dalbavancin in patients with hepatic or renal impairment, including patients with end-stage renal disease (ESRD) receiving dialysis. In each study, 4 to 10 patients with mild, moderate, or severe impairment and age-, sex-, and weight-matched controls were administered either a single dose (500 or 1000 mg) or 2 doses (1000 mg followed by 500 mg 1 week apart) of dalbavancin. Dalbavancin exposures were not increased due to mild renal impairment. The mean area under the concentration-time curve from time 0 to infinity (AUC0-infinity) values were approximately 50% higher in patients with moderate renal impairment or ESRD and 100% higher in patients with severe renal impairment. Dose adjustment is not considered necessary in patients with mild or moderate renal impairment or for patients with ESRD receiving hemodialysis; however, a lower dose of dalbavancin (750 mg followed 1 week later by 375 mg) may be considered for patients with severe renal impairment (creatinine clearance

Objectives Dalbavancin is a novel lipoglycopeptide antibiotic in development for the treatment of complicated skin and skin structure infections (cSSSIs) caused by Gram-positive bacteria. The aim of the present study was to assess the penetration of dalbavancin into skin blister fluid. Methods Nine healthy subjects (five males; ranging in age from 26 to 57 years) were administered a single 30 min intravenous infusion of dalbavancin at a dose of 1000 mg. Skin blisters were induced by application of cantharidin ointment. Plasma and blister fluid samples were collected over 7 days post-dose, and concentrations of dalbavancin were assessed by a validated LC/MS/MS assay. Pharmacokinetics were determined by non-compartmental methods, and drug penetration was assessed based on the ratio of area under the curve (AUC) in the blister fluid versus plasma for each subject. Results The mean (SD) peak concentration of dalbavancin in plasma and blister fluid was 285 (31.1) and 67.3 (18.2) mg/L, respectively; the corresponding AUC(Day 7) values were 10 806 (1926) and 6438 (1238) mg . h/L, respectively. The mean (SD) penetration of dalbavancin into blister fluid was 59.6% (6.3%). By Day 7, the mean concentration of dalbavancin in plasma and blister fluid was 46.5 and 30.3 mg/L, respectively. Conclusions Dalbavancin concentrations in blister fluid remained well above the MIC90 values for pathogens commonly implicated in cSSSIs such as Staphylococcus aureus, including methicillin-resistant S. aureus (MIC90 = 0.06 mg/L) and beta-haemolytic streptococci (MIC90 = 0.03 mg/L) through Day 7. These pharmacokinetic data support the use of dalbavancin in the treatment of cSSSIs caused by susceptible Gram-positive pathogens.

Background Dalbavancin, a novel lipoglycopeptide with a pharmacokinetic profile that allows weekly dosing, is active against gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). The efficacy of dalbavancin for treatment of skin and skin structure infections (SSSIs) was demonstrated in a phase 2 study. Methods In a phase 3 noninferiority study, patients with complicated SSSIs, including infections known or suspected to involve MRSA, were randomized (ratio, 2 : 1) in a double-blind manner to receive dalbavancin (1000 mg given intravenously on day 1 and 500 mg given intravenously on day 8) or linezolid (600 mg given intravenously or intravenously/orally every 12 h for 14 days). Efficacy was assessed by determining clinical and microbiological responses at the end of therapy and at the test-of-cure visit. Relapses were identified by additional follow-up approximately 1 month later. Results MRSA was identified in 51% of patients from whom a pathogen was isolated at baseline. Dalbavancin and linezolid demonstrated comparable clinical efficacy in the clinically evaluable population at the test-of-cure visit (88.9% and 91.2% success, respectively). The rate of clinical success at the end of therapy was >90% in both arms. Less than 1.0% of patients in either treatment arm experienced relapse after the test-of-cure visit. Both treatments yielded successful microbiological response in excess of 85% among microbiologically evaluable patients at end of therapy and at the test-of-cure visit for all pathogens combined, for all S. aureus strains, and for MRSA. Gastrointestinal symptoms were among the most common adverse events in both arms. A higher proportion of patients in the linezolid arm reported adverse events that were judged by the investigator to be probably/possibly related to treatment (dalbavancin arm, 25.4% of subjects; linezolid arm, 32.2% of subjects). Conclusions Two doses of dalbavancin (1000 mg given on day 1 followed by 500 mg given on day 8) were as well tolerated and as effective as linezolid given twice daily for 14 days for the treatment of patients with complicated SSSI, including those infected with MRSA.

Dalbavancin, a novel glycopeptide with a long elimination half-life ( approximately 9-12 days), was compared to standard antimicrobial therapy for skin and soft-tissue infections (SSTIs). In a randomized, controlled, open-label, phase 2 proof-of-concept trial, adults received 1100 mg of dalbavancin (as a single intravenous infusion), 1000 mg of dalbavancin intravenously and then 500 mg intravenously 1 week later, or a prospectively defined standard-of-care regimen. A gram-positive pathogen was isolated from samples obtained from 41 (66%) of 62 patients at baseline; Staphylococcus aureus was the most prevalent species (83% of pathogens). Clinical success rates at a follow-up visit (test of cure) were 94.1% among patients treated with 2 doses of dalbavancin, 61.5% among patients treated with 1 dose of dalbavancin, and 76.2% among patients treated with a standard-of-care regimen. All treatment regimens were well tolerated; drug-related adverse reaction rates were similar across the 3 groups. These findings suggest that a regimen of 2 doses of dalbavancin administered 1 week apart is effective in the treatment of complicated, gram-positive bacterial SSTIs and warrants further study.

Background. Catheter-related bloodstream infections (CR-BSIs) are associated with substantial mortality, prolongation of hospital stay, and increased cost of care. Dalbavancin, a new glycopeptide antibiotic with unique pharmacokinetic properties that have allowed clinical development of a weekly dosing regimen, possesses excellent activity against clinically important gram-positive bacteria, suggesting utility in the treatment of patients with CR-BSIs. Methods. A phase 2, open-label, randomized, controlled, multicenter study of 75 adult patients with CR-BSIs compared treatment with intravenous dalbavancin, administered as a single 1000-mg dose followed by a 500-mg dose 1 week later, with intravenous vancomycin, administered twice daily for 14 days. Gram-positive bacteria isolated in this study included coagulase-negative staphylococci (CoNS) and Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA). Results. Infected patients who received weekly dalbavancin (n = 33) had an overall success rate (87.0%; 95% confidence interval [CI], 73.2%-100.0%) that was significantly higher than that of those who received vancomycin (n = 34) (50.0%; 95% CI, 31.5%-68.5%). Adverse events and laboratory abnormalities were generally mild and were comparable for the 2 drugs. Conclusions. Dalbavancin thus appears to be an effective and well-tolerated treatment option for adult patients with CR-BSIs caused by CoNS and S. aureus, including MRSA.

Background Biomechanical stimulation promotes tissue regeneration and healing. Bladder regeneration is biomechanically stimulated by cycling (filling, storage and evacuation). Interruption of cycling in patients with neurogenic bladders leads to functional and structural alterations. Material and Methods Cycling impacts on bladder tissue regeneration in cystectomized animals implanted with cell-seeded PLGA-based scaffolds were evaluated and learnings applied to the Tengion Autologous Neo-Bladder Augment™ (NBA) Phase II clinical trial studying patients with neurogenic bladder due to spina bifida. Results Neo-bladder cycling was initiated in animals 2 weeks post-implantation for 3 days/week. Urodynamic assessments from three cycling cohorts were evaluated: HIGH (10 weeks, >3.75 hr/day, >60 hrs), LOW (10 weeks, Conclusions Early post-implantation cycling is essential for regenerative healing following implantation of autologous cell-seeded PLGA-based scaffolds in animals and humans. Insights from Preclinical studies are consistent with insights from a Phase II clinical trial of the Tengion Autologous Neo-Bladder Augment™ and confirm the importance of cycling in bladder regeneration.

Dalbavancin (DAL) is a semisynthetic lipoglycopeptide in phase 3 development with activity against Gram-positive bacteria. Weekly doses (1 g day 1/0.5 g day 8) are being investigated for the treatment of complicated skin and soft tissue infections. DAL has both renal and nonrenal routes of elimination. A study was performed to assess the need for dosage adjustments in patients with hepatic impairment.

Dalbavancin (DAL) is a novel, next-generation lipoglycopeptide with a pharmacokinetic profile that allows weekly dosing. The safety of DAL in the treatment of complicated skin and soft tissue infections was demonstrated versus comparators (COMP) in the phase 2/3 clinical development program.

Dalbavancin (DAL) is a novel semisynthetic glycopeptide in phase 3 clinical development that has activity against Gram(+) organisms, including resistant strains. Two doses given 1 week apart have been shown to be effective in complicated skin and soft tissue infections. A clinical study was performed to determine the need for dosage adjustments in subjects with mild to moderate renal impairment (RI).