MRSA Infection

Durata Announces Antibiotic Surveillance Results for Dalbavancin Presented at ECCMID Meeting

Durata Announces Antibiotic Surveillance Results for Dalbavancin Presented at ECCMID Meeting | Business Wire.

Durata Therapeutics today announced surveillance data demonstrating potency of the Company’s lead antibiotic product, dalbavancin, a long-acting, intravenous (IV) lipoglycopeptide, against a broad spectrum of gram-positive bacteria prevalent in recent years. The surveillance data also confirmed that the susceptibility profile of dalbavancin has not changed since surveillance studies were first initiated over a decade ago. “The convenient, once-daily dalbavancin dosing regimen for projected acute bacterial skin and skin structure infection trials in future clinical practice will be a welcome addition to MRSA therapies in various clinical settings, including hospitals, emergency rooms and out-patient intravenous treatment programs.” The findings were presented in two posters titled, “Dalbavancin Surveillance Results for European Gram-positive Species in a Contemporary (2006-2009) Sample of 23,825 Strains” and “Dalbavancin Activity and Spectrum Evaluated Against a Contemporary (2007-2009) Worldwide Collection of Staphylococci (62,590 strains),” based on results from Dr. Ron Jones and his coauthors at the Jones Microbiology Institute (JMI) Laboratories in North Liberty, Iowa.

Durata Therapeutics Announces Worldwide Rights for the Development and Commercialization of Dalbavancin | Business Wire

Durata Therapeutics Announces Worldwide Rights for the Development and Commercialization of Advanced-Stage Antibiotic, Dalbavancin | Business Wire.

Durata Therapeutics today announced the Company has attained worldwide rights for the development and commercialization of Durata’s lead product, dalbavancin, a long-acting, intravenous (IV) lipoglycopeptide for the treatment of acute bacterial skin and skin structure infections (abSSSI). In December 2010, Durata acquired from RaQualia Pharma commercialization rights for dalbavancin in Japan. All other rights, including in North America and the European Union, were acquired from Pfizer upon the formation of Durata in late December 2009. Specific monetary terms of the acquisitions were not disclosed. “There is a growing, worldwide need for new, broad-spectrum agents to address antibiotic resistance, as seen with methicillin-resistant Staphylococcus aureus (MRSA)” “There is a growing, worldwide need for new, broad-spectrum agents to address antibiotic resistance, as seen with methicillin-resistant Staphylococcus aureus (MRSA),” commented Paul R. Edick, Chief Executive Officer of Durata. “Having initiated our pivotal clinical program for dalbavancin last month, we are continuing on track with the objective of submitting for regulatory approval in the United States, Europe and Asian regions. It is important for our program goals that we have attained unencumbered worldwide rights for this promising product.”

Dalbavancin effective agains MRSA in Turkey

HighWire Medline Abstract.

Dalbavancin is a new bactericidal second-generation lipoglycopeptide antibiotic to use in the treatment of multidrug-resistant staphylococcal infections. It is important to determine its activity against staphylococci isolated in Turkey. Dalbavancin has not yet been used in antimicrobial therapy in our country. Method: Dalbavancin was tested against a total of 453 staphylococcal strains by using the reference broth microdilution method. Organisms tested included: methicillin-resistant Staphylococcus aureus (MRSA; 237 strains), methicillin-susceptible S. aureus (MSSA; 144 strains) and methicillin- resistant coagulase-negative staphylococci (MR-CoNS; 72 strains). Results: MIC(50) and MIC(90) values of dalbavancin against MRSA, MSSA and MR-CoNS were found as ?0.008 and 0.25 mg/l; 0.016 and 0.125 mg/l; and 0.016 and 0.5 mg/l, respectively. The overall distribution of dalbavancin MIC values ranged from ?0.008 to 2 mg/l. If the interpretive breakpoint MIC value is ?1 mg/l, the susceptibility rates of MRSA, MSSA and MR-CoNS strains were determined as 99.6, 100 and 98.6%, respectively. Conclusion: The MIC results for dalbavancin have demonstrated a good activity against both methicillin-sensitive and -resistant staphylococci isolated from hospitalized patients. PMID: 21088395

Pfizer slow down on MRSA drug dalbavancin

» Pfizer to withdraw global marketing applications for Dalbavancin to conduct a new trial Outback senators.

Pfizer Inc today announced it commitment globally withdraw all dalbavancin marketing applications suited for the treatment of knotty skin and skin structure infections in adults, including the U.S. inexperienced drug application (NDA) and the European marketing authorization claim (MAA). Following feedback from regulatory authorities, the company plans to conduct an additional Phase 3 clinical trial with dalbavancin for the treatment of adults with complicated skin and skin structure infections caused by Gram-positive bacteria, including MRSA (methicillin resistant Staphylococcus aureus). The global multi-center study will generate additional clinical data to support planned future regulatory submissions. A pediatric program with dalbavancin is also planned.

Dalbavancin - good but maybe not good for VRSA

Link: HighWire Press -- Medline Abstract.

The best-studied dosing schedule for dalbavancin involves the i.v. administration of 1 g of dalbavancin followed by 500 mg one week later. Phase III clinical trials comprising more than 1,500 patients evaluated once-weekly dalbavancin in Gram-positive skin and soft tissue infections (SSTIs). When compared to linezolid, cefazolin or vancomycin, dalbavancin met the primary endpoint of noninferiority at two weeks following therapy. The side-effect profile of dalbavancin is mild, with headache and pyrexia being the most common adverse effects. Dalbavancin is eliminated renally and hepatically, and does not need dose adjustments in patients with renal insufficiency. Once-weekly dosing with dalbavancin gives it another advantage when compared with vancomycin, and may alleviate the need for the continued presence of indwelling catheters in some patients with SSTIs and other infections requiring prolonged doses of antibiotics. While some in vitro evidence supports dalbavancin's effectiveness against vancomycin-resistant S. aureus, the preponderance of in vivo evidence does not demonstrate its effectiveness against vancomycin-resistant S. aureus. (c) 2007 Prous Science. All rights reserved. Publication Type:

Dalbavancin: A New Option for the Treatment of Gram-Positive Infections

Link: The Annals of Pharmacotherapy.

     DATA SYNTHESIS: Dalbavancin, a novel lipoglycopeptide, has a mechanism of action similar to that of other glycopeptides. It has in vitro activity against a variety of gram-positive organisms, but no activity against gram-negative or vancomycin-resistant enterococci that possess VanA gene. Due to its prolonged half-life (6-10 days), dalbavancin can be administered intravenously once weekly. In Phase II and III clinical trials, dalbavancin was effective and well tolerated for the treatment of skin and soft-tissue infections, catheter-related bloodstream infections, and skin and skin-structure infections. To date, adverse events are mild and limited; the most common include pyrexia, headache, nausea, oral candidiasis, diarrhea, and constipation. CONCLUSIONS: Dalbavancin appears to be a promising antimicrobial agent for the treatment of gram-positive infections. A new drug application was filed with the Food and Drug Administration (FDA) in December 2004. The FDA issued an approvable letter in 2005 for dalbavancin. If approved, dalbavancin is expected to be launched in the first quarter of 2006.

Dalbavancin better than linezolid?

Link: Randomized

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.

Vicuron Pharmaceuticals Submits New Drug Application for Dalbavancin to U.S. Food and Drug Administration

Link: Vicuron Pharmaceuticals

KING OF PRUSSIA, Pa., Dec. 21 /PRNewswire-FirstCall/ -- Vicuron Pharmaceuticals Inc. (Nasdaq: MICU; Nuovo Mercato: MICU) today announced that it has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for dalbavancin, a novel antibiotic for the treatment of complicated skin and soft tissue infections (cSSTIs). Dalbavancin is a unique, once weekly IV lipoglycopeptide for the treatment of cSSTIs caused by Gram-positive bacteria, including the most difficult-to-treat strains of Staphylococcus-methicillin-resistant Staphylococcus aureus (MRSA). ADVERTISEMENT "This is a major milestone for us as we move closer to bringing this promising antibiotic to the market," said George F. Horner III, President and CEO of Vicuron.

Origin, structure, and activity in vitro and in vivo of dalbavancin

Link: Journal of Antimicrobial Chemotherapy.

Dalbavancin, prepared from a teicoplanin-like glycopeptide, has better activity, in vitro and in animal infection models, than vancomycin and teicoplanin. In particular, dalbavancin has excellent activity against staphylococci, including coagulase-negatives. A unique feature of dalbavancin is its pharmacokinetics, characterized by a long elimination t1/2 in humans which makes a once-weekly dosing regimen feasible. Dalbavancin recently completed Phase 3 clinical trials in skin and skin structure infection.

In vitro antistaphylococcal activity of dalbavancin

Link: Journal of Antimicrobial Chemotherapy.

Objectives: Dalbavancin is a novel, semi-synthetic glycopeptide antibiotic. The aim of this study was to further explore its activity against staphylococci. Methods: The bactericidal activity of dalbavancin was studied using MBC and time–kill methods. The potential for resistance to dalbavancin was examined using single-step and serial-passage experiments. Results: Dalbavancin was bactericidal against methicillin-susceptible and -resistant Staphylococcus aureus, in both the presence and absence of human serum. No resistance was seen with any isolate tested. After serial passage, bacterial populations were more homogeneous in their susceptibility to dalbavancin than to vancomycin or teicoplanin. Conclusion: Dalbavancin is bactericidal for staphylococci. Resistance to this semi-synthetic glycopeptide is not readily developed in vitro.

Vicuron antibiotic granted priority review

Link: Vicuron antibiotic granted priority review - Pharmaceutical Business Review.

Vicuron's investigational agent, dalbavancin, is a novel once-weekly antibiotic for the treatment of complicated skin and soft tissue infections (cSSTIs) including the most difficult to treat strain of staphylococcus, methicillin-resistant staphylococcus aureus (MRSA). The FDA grants priority designation to products which, if approved, would be a significant improvement in the treatment of a disease. "We are very pleased with this regulatory development which we believe further demonstrates the serious underserved medical need that dalbavancin has the potential to address," said George Horner III, president and CEO of Vicuron. "We expect to commercialize dalbavancin by the first quarter of 2006 pending FDA approval." The new drug application (NDA), which was submitted in December 2004, includes results from more than 1,850 subjects and three phase III trials that evaluated the safety and efficacy of dalbavancin in patients with SSTIs caused by gram-positive bacteria. The phase III clinical trials each met the primary and secondary endpoints of non-inferiority when compared to linezolid (Pfizer's Zyvox), cefazolin (Eli Lilly's Kefzol and GlaxoSmithKline's Ancef) or vancomycin (Pfizer's Vancocin), three currently used agents for SSTIs.

New Drug for Catheter Related MRSA

Link: HighWire Press -- Medline Abstract.

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.

FDA to test once a week MRSA drug

Link: Vicuron Pharmaceuticals

Vicuron Pharmaceuticals Inc. (Nasdaq: MICU; Nuovo Mercato: MICU) today announced that it has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for dalbavancin, a novel antibiotic for the treatment of complicated skin and soft tissue infections (cSSTIs). Dalbavancin is a unique, once weekly IV lipoglycopeptide for the treatment of cSSTIs caused by Gram-positive bacteria, including the most difficult-to-treat strains of Staphylococcus-methicillin-resistant Staphylococcus aureus (MRSA). ADVERTISEMENT click here "This is a major milestone for us as we move closer to bringing this promising antibiotic to the market," said George F. Horner III, President and CEO of Vicuron. "With the increase of infections caused by Gram-positive bacteria in the hospital, we believe dalbavancin will offer a potent alternative to older agents such as vancomycin

Positive results for Vicurons antibiotic and antifungal agents

Pharmaceutical Business Review
Highlights of data presented on anidulafungin and dalbavancin at the 44th annual interscience conference on antimicrobial agents and chemotherapy (ICAAC) included in vitro data demonstrating dalbavancin's potency against a broad range of gram-positive bacteria, including methicillin resistant staphylococcus aureus (MRSA) and in vitro data revealing anidulafungin to be more potent than fluconazole against candida albicans biofilms.