Methods for identifying novel dosing regimens
Methods of treating a Gram negative bacterial infection comprising a co-administration regimen of an effective amount of fosfomycin together with at least one antimicrobial agent selected from the group consisting of piperacillin-tazobactam, ceftazidime and meropenem to an infected subject. A further method of treating a subject with a bacterial infection that includes infection with a “resistant” mutant subpopulation selected from the group consisting of Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa, Acinetobacter baumannii and E. coli , the method comprising (a) obtaining a sample from a subject suffering from a bacterial infection; (b) identifying the presence of the “resistant” mutant subpopulation in said sample; and (c) co-administering fosfomycin and at least one antimicrobial agent to the subject, wherein after the co-administration, the bacterial density is effectively reduced and the “resistant” mutant subpopulation is inhibited.
1. A method of treating a Gram-negative bacterial infection, comprising a co-administration regimen of an effective amount of fosfomycin together with an effective amount of piperacillin-tazobactam, ceftolozane-tazobactam or ceftazidime-avibactam to an infected subject, wherein the bacterial infection is an infection with a carbapenem resistant mutant subpopulation of the Gram-negative bacteria.
2. The method of claim 1 , wherein the Gram-negative bacterial infection is an infection caused by Klebsiella pneumoniae.
3. The method of claim 1 , wherein the Gram-negative bacterial infection is an infection caused by Pseudomonas aeruginosa.
4. The method of claim 1 , wherein the Gram-negative bacterial infection is an infection caused by Acinetobacter baumannii.
5. The method of claim 1 , wherein the effective amount of fosfomycin is greater than the effective amount of the at least one antimicrobial agent when co-administered to the infected subject.
6. The method of claim 1 , wherein the effective amount of fosfomycin is less than the effective amount of the at least one antimicrobial agent when co-administered to the infected subject.
7. A method of treating a subject with a bacterial infection that includes infection with a carbapenem resistant mutant subpopulation selected from the group consisting of Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa, Acinetobacter baumannii and E. coli , the method comprising:
a. obtaining a sample from a subject suffering from a bacterial infection;
b. identifying the presence of the carbapenem resistant mutant subpopulation in said sample; and
c. co-administering fosfomycin and an effective amount of piperacillin-tazobactam, ceftolozane-tazobactam or ceftazidime-avibactam to the subject, wherein after the co-administration, the bacterial density is effectively reduced and the carbapenem resistant mutant subpopulation is inhibited.
8. The method of claim 7 , wherein the effective amount of fosfomycin is greater than the effective amount of the at least one antimicrobial agent when co-administered to the infected subject.
9. The method of claim 7 , wherein the effective amount of fosfomycin is less than the effective amount of the at least one antimicrobial agent when co-administered to the infected subject.