US2023293488A1PendingUtilityA1

Compositions and methods of use of antibacterial drug combinations

72
Assignee: WASHINGTON UNIVERSITY ST LOUISPriority: Jul 9, 2015Filed: Dec 8, 2022Published: Sep 21, 2023
Est. expiryJul 9, 2035(~8.9 yrs left)· nominal 20-yr term from priority
Inventors:Gautam DantasPatrick GonzalesKevin ForsbergMitchell PeseskyMayland ChangShahriar Mobashery
A61K 45/06A61K 31/407A61K 31/496A61K 31/431A61K 31/43A61K 31/424A61P 31/04A61K 31/546
72
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Claims

Abstract

The present disclosure encompasses antibacterial compositions and methods of treating bacterial infections caused by resistant bacteria.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A method for treating an infection caused by an antibiotic resistant bacterium in a subject, wherein the resistance is due to a penicillin-binding protein 2a (PBP2a)-driven mechanism, the method comprising administering to the subject an effective amount of a composition comprising:
 i) at least one carbapenem or other suitable β-lactam capable of binding the allosteric site of PBP2a;   ii) at least one β-lactamase inhibitor; and   iii) at least one β-lactam that binds the open configuration of the active site of PBP2a.   
     
     
         2 . The method of  claim 1 , wherein the antibiotic resistant bacterium is from the genus  Staphylococcus.    
     
     
         3 . The method of  claim 1 , wherein the antibiotic resistant bacterium is selected from the group consisting of  S. aureus, S. epidermidis, S. hominis, S. lugdunensis, S. xylosus , and  S. felis.    
     
     
         4 . The method of  claim 1 , wherein the antibiotic resistant bacterium is methicillin-resistant  Staphylococcus aureus  (MRSA). 
     
     
         5 . The method of  claim 1 , wherein the at least one carbapenem or other suitable β-lactam capable of binding the allosteric site of PBP2a is selected from the group consisting of meropenem, imipenem, tomopenem, ceftaroline and ceftobiprole. 
     
     
         6 . The method of  claim 1 , wherein the at least one carbapenem or other suitable β-lactam capable of binding the allosteric site of PBP2a is selected from the group consisting of meropenem and imipenem. 
     
     
         7 . The method of  claim 1 , wherein the at least one β-lactamase inhibitor is selected from the group consisting of clavulanic acid (clavulanate), sulbactam, tazobactam and avibactam 
     
     
         8 . The method of  claim 1 , wherein the at least one β-lactamase inhibitor is selected from the group consisting of tazobactam and clavulanate. 
     
     
         9 . The method of  claim 1 , wherein the at least one β-lactam that binds the open configuration of the active site of PBP2a is selected from the group consisting of carbapenems, am inopenicillins, carboxypenicillins, ureidopenicillins, oxacillins, methicillins, and some cephalosporins. 
     
     
         10 . The method of  claim 9 , wherein the carbapenem is selected from the group consisting of meropenem, imipenem, doripenem, ertapenem, faropenem, and tebipenem. 
     
     
         11 . The method of  claim 9 , wherein the oxacillin or methicillin is selected from the group consisting of cloxacillin, dicloxacillin, flucloxacillin, oxacillin, methicillin and nafcillin. 
     
     
         12 . The method of  claim 9 , wherein the cephalosporin is selected from the group consisting of cefepime, cefozopran, cefpirome, cefquinome, ceftaroline, and ceftobiprole. 
     
     
         13 . The method of  claim 9 , wherein the aminopenicillin is selected from the group consisting of amoxicillin, ampicillin, pivampicillin, hetacillin, bacampicillin, metampicillin, talampicillin, and epicillin. 
     
     
         14 . The method of  claim 9 , wherein the carboxypenicillin is selected from the group consisting of carbenicillin, carindacillin, ticarcillin and temocillin. 
     
     
         15 . The method of  claim 9 , wherein the ureidopenicillin is selected from the group consisting of azlocillin, mezlocillin and piperacillin. 
     
     
         16 . The method of  claim 9 , wherein the at least one β-lactam that binds the open configuration of the active site of PBP2a is not mecillinam, cefradine and thienamycin. 
     
     
         17 . The method of  claim 1 , wherein the at least one β-lactam that binds the open configuration of the active site of PBP2a is selected from the group consisting of piperacillin and amoxicillin. 
     
     
         18 . The method of  claim 1 , wherein the carbapenem is meropenem, the β-lactamase inhibitor is tazobactam and the β-lactam that binds the open configuration of the active site of PBP2a is piperacillin. 
     
     
         19 . The method of  claim 1 , wherein the carbapenem is imipenem, the β-lactamase inhibitor is clavulanate and the β-lactam that binds the open configuration of the active site of PBP2a is piperacillin. 
     
     
         20 . The method of  claim 1 , wherein the carbapenem is meropenem, the β-lactamase inhibitor is tazobactam, the β-lactam that binds the open configuration of the active site of PBP2a is amoxicillin and wherein the ratio of (i), (ii) and (iii) is 1:1:1.

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