Methods, Devices And Formulations For Targeted Endobronchial Therapy

Abstract

The present invention provides an improved means of treating tracheobronchitis, bronchiectasis and pneumonia in the nosocomial patient, preferably with aerosolized anti gram-positive and anti-gram negative antibiotics administered in combination or in seriatim in reliably sufficient amounts for therapeutic effect. In one aspect, the invention assures this result when aerosol is delivered into the ventilator circuit. In one embodiment the result is achieved mechanically. In another embodiment, the result is achieved by aerosol formulation. In another aspect, the invention assures the result when aerosol is delivered directly to the airways distal of the ventilator circuit. The treatment means eliminates the dosage variability that ventilator systems engender when aerosols are introduced via the ventilator circuit. The treatment means also concentrates the therapeutic agent specifically at affected sites in the lung such that therapeutic levels of administrated drug are achieved without significant systemic exposure of the patient to the drug. The invention further provides a dose control device to govern this specialized regimen.

We claim: 
     
         1 . A method of treating an antibiotic-resistant infection, comprising: a) identifying an intubated subject with an antibiotic-resistant infection; and b) administering an aerosolized antibiotic to said subject under conditions such that said antibiotic-resistant infection is eliminated. 
     
     
         2 . The method of  claim 1 , wherein said conditions comprise delivering said aerosolized antibiotic with a device, said device comprising a vibrational element and a dome-shaped aperture plate. 
     
     
         3 . The method of  claim 1 , wherein said conditions comprise delivering the aerosolized antibiotic so that said aerosol first contacts said subject at said subject's trachea. 
     
     
         4 . The method of  claim 3 , wherein aerosolized antibiotic is delivered to the trachea and deep lung. 
     
     
         5 . The method of  claim 1 , wherein a reduction of antibiotic-resistant organisms are detected in culture obtained from said subject post administering. 
     
     
         6 . The method of  claim 1 , wherein a reduction of antibiotic-resistant organisms are detected in culture obtained from said subject two weeks post administering. 
     
     
         7 . The method of  claim 1 , wherein no antibiotic-resistant organisms are detected in culture obtained from said subject two weeks post administering. 
     
     
         8 . The method of  claim 1 , wherein the antibiotic-resistant infection is an infection of antibiotic resistant gram positive bacteria. 
     
     
         9 . The method of  claim 1 , wherein the antibiotic-resistant infection is an infection of methicillin-resistant  S. aureus.    
     
     
         10 . The method of  claim 1 , wherein the antibiotic-resistant infection is an infection of antibiotic resistant gram negative bacteria. 
     
     
         11 . The method of  claim 1 , wherein said subject was treated systemically with antibiotic prior to said administering of step b). 
     
     
         12 . The method of  claim 1 , wherein said subject is treated systemically with antibiotic at the same time as or during administering of step b). 
     
     
         13 . A method of treating an antibiotic-resistant infection, comprising: a) identifying an subject on a ventilator circuit with an antibiotic-resistant infection, said circuit comprising a Y-piece; and b) administering an aerosolized antibiotic to said subject under conditions such that said antibiotic-resistant infection is eliminated. 
     
     
         14 . The method of  claim 13 , wherein said conditions comprise delivering said aerosolized antibiotic with a device, said device attached to said Y-piece, said device comprising a vibrational element and a dome-shaped aperture plate. 
     
     
         15 . The method of  claim 13 , wherein said conditions comprise delivering the aerosolized antibiotic so that said aerosol first contacts said patient at said patient's trachea. 
     
     
         16 . The method of  claim 15 , wherein aerosolized antibiotic is delivered to the trachea and deep lung. 
     
     
         17 . The method of  claim 13 , wherein no antibiotic-resistant organisms are detected in said patient two weeks post administering. 
     
     
         18 . The method of  claim 13 , wherein the antibiotic-resistant infection is an infection of methicillin-resistant  S. aureus.    
     
     
         19 . The method of  claim 13 , wherein said subject was treated systemically with antibiotic prior to said administering of step b). 
     
     
         20 . The method of  claim 13 , wherein said subject is treated systemically with antibiotic at the same time as or during administering of step b). 
     
     
         21 . A method of treating an antibiotic-resistant infection, comprising: a) identifying a subject with an antibiotic-resistant infection of the lung; and b) administering an aerosolized antibiotic to said subject under conditions such that said antibiotic-resistant infection is eliminated. 
     
     
         22 . The method of  claim 21 , wherein said conditions comprise delivering said aerosolized antibiotic with a device, said device comprising a vibrational element and a dome-shaped aperture plate. 
     
     
         23 . The method of  claim 21 , wherein said conditions comprise delivering the aerosolized antibiotic so that said aerosol first contacts said subject at said subject's trachea. 
     
     
         24 . The method of  claim 23 , wherein aerosolized antibiotic is delivered to the trachea and deep lung. 
     
     
         25 . The method of  claim 21 , wherein a reduction of antibiotic-resistant organisms are detected in culture obtained from said subject post administering. 
     
     
         26 . The method of  claim 21 , wherein a reduction of antibiotic-resistant organisms are detected in culture obtained from said subject two weeks post administering. 
     
     
         27 . The method of  claim 21 , wherein no antibiotic-resistant organisms are detected in culture obtained from said subject two weeks post administering. 
     
     
         28 . The method of  claim 21 , wherein the antibiotic-resistant infection is an infection of antibiotic resistant gram positive bacteria. 
     
     
         29 . The method of  claim 21 , wherein the antibiotic-resistant infection is an infection of methicillin-resistant  S. aureus.    
     
     
         30 . The method of  claim 21 , wherein the antibiotic-resistant infection is an infection of antibiotic resistant gram negative bacteria.