Exhibit
      10.4

     

    


     

    MIDDLEBROOK
      PHARMACEUTICALS, INC.

     

    


     

    SECOND
      AMENDMENT

    TO

    EXECUTIVE
      EMPLOYMENT AGREEMENT

    


     

    THIS
      SECOND AMENDMENT TO EXECUTIVE EMPLOYMENT AGREEMENT (this “Amendment”) is made as
      of November 19, 2007 (the “Effective Date”) by and between Beth A. Burnside,
      Ph.D. (the “Employee”), and MiddleBrook Pharmaceuticals, Inc., a corporation
      organized and existing under the laws of the State of Delaware and formerly
      known as Advancis Pharmaceutical Corporation (the “Company”).

     

    WHEREAS,
      the Employee and the Company are parties to an executive Employment Agreement,
      dated August 13, 2003 (the “Employment Agreement”); and

     

    WHEREAS,
      the Employee and the Company are also parties to a First Amendment to an
      Executive Employment Agreement, dated September 7, 2005.

     

    NOW,
      THEREFORE, in consideration of the mutual covenants and obligations contained
      herein, the sufficiency of which is hereby acknowledged, and intending to be
      legally bound, the parties, subject to the terms and conditions set forth
      herein, agree as follows, effective as of the Effective Date:

     

    1. All
      capitalized terms used herein and not otherwise defined have the meanings set
      forth in the Employment Agreement.

     

    2. The
      word
“termination” as used throughout the Employment Agreement with respect to the
      Employee’s employment hereby refers to a “separation from service” by the
      Employee from the Company, as defined by Treasury Regulation
§1.409A-1(h).

     

    3. Section
      [8.4(a)]
      of the
      Employment Agreement is hereby deleted in its entirety and replaced with one
      of
      the following sections as selected below by the Employee:

     

    
      	
            	x	
              “(a) In
                the event of the termination of the Employee’s employment under Section
                [8.3],
                the Employee shall be entitled to receive severance pay in the form
                of a
                lump sum payment within sixty (60) days of such termination, in an
                amount
                equal to the present value of the Salary that the Employee would
                have
                earned if the Employee had continued working for the Company during
                the
                [twelve
                (12)]
                month period immediately following the Employee’s date of termination,
                where such present value is to be determined using a discount rate
                equal
                to the applicable short-term federal rate prescribed under Section
                1274(d)
                of the Internal Revenue Code of 1986, as amended (the “Code”). Such
                payment shall be subject to all applicable withholding obligations
                for tax
                purposes.”

            


    

     

    
      
         

      

      
         

        
          

        

      

      
         

      

    

     

    
      	
            	o	
              “(a) In
                the event of the termination of the Employee’s employment under Section
                [8.3],
                the Employee shall be entitled to receive severance pay in an amount
                equal
                to [twelve
                (12)]
                months of Salary, calculated on the basis of the Salary in effect
                of the
                Employee’s date of termination, and paid in the same manner as Salary was
                then paid hereunder. Such payments shall be considered separate payments
                for purposes of Section 409A of the Code and shall be subject to
                all
                applicable withholding obligations for tax
                purposes.”

            


    

     

    4. Section
      8.4(b) of the Employment Agreement is hereby amended in its entirety to be
      and
      read as follows:

     

    “In
      the
      event of the termination of the Employee’s employment under Section
      [8.3],
      the
      Employee shall be entitled to receive all Benefits to which he was entitled
      on
      the date preceding his/her termination for a period of [twelve
      (12)]
      additional months following termination, made in accordance with any terms
      applicable to such Benefits. The provision of such Benefits is intended to
      be
      exempt from Section 409A of the Code. Accordingly, any reimbursement paid to
      the
      Employee for the cost of such Benefits shall be made no later than the December
      31st of the second calendar year following the calendar year in which such
      termination of employment occurs.””

     

    5. In
      all
      other respects, the Employment Agreement shall remain in full force and
      effect.


     

     

    IN
      WITNESS WHEREOF, the Employee and the Company have caused this Amendment to
      be
      executed on this 19th
      day of
      November 2007.

    


    
 

    
      	
              Employee

            	 	
              MiddleBrook
                Pharmaceuticals, Inc.

            
	 	 	 	 
	 	 	 	 
	 	 	 	 
	 	 	 	 
	
              /s/
                Beth A. Burnside

            	 	
              By:

            	
              /s/
                Edward M. Rudnic

            
	
              Beth
                A. Burnside, Ph.D.

            	 	 	
              Edward
                M. Rudnic, Ph.D.

            
	 	 	 	
              President
                & CEO