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Insmed Incorporated Message Board

  • fudfighter4 fudfighter4 Mar 20, 2013 11:38 AM Flag

    The need of a wide-spectrum label for Arikace

    Bearing in mind that NDM-1 keeps the FDA and EMEA awake at night, as carbapenems are viewed as a therapy of last resort -

    Objective: New Delhi metallo-beta-lactamase-1 (NDM-1) was reported in India and the United Kingdom in August 2010.

    The first case of NDM-1 in this hospital was detected in October 2010 ..... From October 2010 to October 2011, we detected 7 NDM-1 patients with no overseas travel in last 2 years.

    The objective of this study is to assess risk factors for and treatment outcome of NDM-1 Enterobacteriaceae.

    Method: We conducted a retrospective case-control (1:4 ratio) study from October 2010 to October 2011 for risk factors and treatment outcome .....

    Results: We detected 8 NDM-1 bacteria in 6 patients from clinical cultures (6 in urine, 1 in bile) and 1 from contact screening; 5 were Escherichia coli, 2 Klebsiella pneumoniae (KP) and 1 Enterobacter cloacae.

    All isolates were positive for at least 2 ESBL's (TEM-type, SHV-type and CTX-M-type) and plasmid AmpC (DHA-1 or CMY-type) and negative for VIM-type, IMP-type, KHM-1; OXA-48, KPC-1 and GES-type beta-lactamases or 16S rRNA methylases.

    Our NDM-1 isolates were distinct from the Indian NDM-1 by multilocus sequence typing. Cases and controls had similar demographic data, with no cases of Indian race. NDM-1 patients had more dementia (37.5% vs 6.3%, p=0.05). On univariate analysis, cases were more likely to be exposed to carbapenems within 30 days (OR 1.61, 95%CI 1.6–216.1, p=0.019) and fluoroquinolones within 90 days (OR 7.67, 95%CI 1.3–45.3, p=0.025), have other multi-drug resistant organisms (MDRO) (OR 5.95, 95%CI 1.1–31.2, p=0.035) and ESBL KP (OR 9.67, 95%CI 1.5–60.0, p=0.015) within 12 months.

    All isolates were resistant to all tested carbapenems, cephalosporins, penicillin-inhibitor combinations, and ciprofloxacin; 100% were susceptible to polymyxin B, 87.5% to amikacin, and 25% to gentamycin and ciprofloxacin. Three cases of urinary infections were cured with amikacin or polymyxin B.

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    • For the delusional bashers hoping to promote the fallacy that the FDA is under no pressure to leverage the full potential of Arikace, the Transatlantic Taskforce on Antimicrobial Resistance isn't the only forum likely to be monitoring the development of inhaled liposome antibacterials -

      The Interagency Task Force on Antimicrobial Resistance was initiated in 1999 following a congressional hearing on the topic "Antimicrobial Resistance: Solutions to a Growing Public Health Problem." The Task Force brings together multiple federal agencies to address the complex issue of antimicrobial resistance.


      Centers for Disease Control and Prevention (CDC)
      Food and Drug Administration (FDA)
      National Institutes of Health (NIH)

      Other Members:

      Agency for Healthcare Research and Quality (AHRQ)
      Centers for Medicare and Medicaid Services (CMS)
      Health Resources and Services Administration (HRSA)
      Department of Agriculture (USDA)
      Department of Defense (DoD)
      Department of Veterans Affairs (VA)
      Environmental Protection Agency (EPA)
      Health and Human Services/Office of the Assistant Secretary for Health
      Health and Human Services/Office of the Assistant Secretary for Preparedness and Response

      From the Research focus area of the 2012 Action Plan -

      "NIH currently supports clinical trials aimed at identifying ways to reduce the use of licensed antibacterials in both community and healthcare settings. These trials focus on areas of greatest antimicrobial drug exposure, such as pneumonia ... and employ strategies to reduce use, such as shorter courses of antimicrobial treatment ..."

      "Critical activities in this focus area include ... optimization of treatment for resistant pathogens, and translation of research findings into clinically useful products, such as novel approaches to ... treat antimicrobial-resistant infections."

      Bashers should try to grasp the concept that there is far more at stake here than just a therapy for two diseases.

    • Now that the safety of liposomal inhalation therapy has been confirmed, it seems to me that a liposomal inhalation combination therapy of Amikacin / Carbapenem / Polymyxin would be a powerful weapon against antimicrobial resistance. Dead pathogens don't develop resistant strains.

      But who am I to propose Insmed's next aniinfective? I'm completely unqualified compared with others who use this forum.

      However, it could be a mistake to assume that the decision will be left to the Insmed leadership team .....

      The Transatlantic Taskforce on Antimicrobial Resistance -

      "26 Feb 2013

      Since the endorsement of the report, the TATFAR Members have been working on the implementation of the recommendations and monitoring their progress through biannual audio conferences. Two audio conferences have taken place: the first one on 6 June 2012 and the second one on 11 December 2012.

      During these audio conferences, the TATFAR Members made updates on all the recommendations included in the report. Comprehensive information about the progress of this work can be found in their meeting report. After assessing the value of the transatlantic collaboration established through TATFAR, the group proposed to extend its working time for two more years and to hold a face-to-face meeting in 2013."

      "Recommendation 17: Exchange information on possible approaches to drug development for bacterial diseases where limited drugs are available (i.e. bacterial diseases where there is unmet need because there are insufficient antibacterial drug therapies available, often due to the development of antimicrobial resistance)

      Update: EMA and FDA had discussions at the Infectious Diseases Working Party workshop in London, October 2012 and the Brookings Institute meeting in Washington, DC in May 2012, where development of antibacterial drugs for bacterial diseases for which there are limited therapeutic options for treating patients were taken into consideration."

    • Here's some perspective on why NDM-1 is such a threat -

      The following info is from a study at Sultan Qaboos University Hospital from July 2005 to July 2007 of antibiotic resistance via extended spectrum beta-lactamases (ESBLs), during which they identified 301 ESBL-producing Escherichia coli and K. pneumoniae strains isolated from clinical samples -

      Overall Piperacillin-Tazobactam susceptibility was 57.9 (64.4% E. coli and 43.6% Klebsiella pneumoniae).

      Only 29.6 % of ESBLs (24.9% E. coli and 39.6% Klebsiella pneumoniae) were ciprofloxacin susceptible.

      98.1% E. coli and 93.1% of Klebsiella pneumoniae were susceptible to Piperacillin-Tazobactam plus Amikacin combination.

      73.7% E. coli and 61.4% of Klebsiella pneumoniae were susceptible to Piperacillin-Tazobactam plus Gentamicin combination.

      96.7% E. coli and 91.1% of Klebsiella pneumoniae were susceptible to Ciprofloxacin plus Amikacin combination.

      41.2% E. coli and 51.5% of Klebsiella pneumoniae were susceptible to Ciprofloxacin plus Gentamicin combination.

      "Conclusion: The ESBLs from Oman have similar resistance pattern as those reported from UK and USA. This resistance decreases when these drugs are combined with Amikacin.

      All ESBLs are susceptible to Carbapenems. However, carbepenam overuse can lead to emergence of carbapenems resistant gram negative bacilli and ESBLs.

      Combination of Amikacin plus Piperacillin/Tazobactam is a feasible empirical therapy for ESBLs."

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