Potentiation of antibiotic effect
View Patent ↗The present invention relates to compositions, kits and methods using combinations of surfactants or cell wall-hydrolyzing enzymes with antibiotics to potentiate the antibiotic effect against bacterial infections. In some embodiments, the surfactant is a pore-forming biosurfactant such as rhamnolipids and the antibiotic is an aminoglycoside antibiotic such as tobramycin.
1 . A method of treating a bacterial infection comprising a biofilm in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a surfactant and at least one of an aminoglycoside antibiotic or vancomycin, wherein:
(a) the surfactant consists of palmitoleic acid;
(b) the aminoglycoside antibiotic comprises streptomycin, kanamycin A, amikacin, dibekacin, sisomicin, netilmicin, neomycin B, neomycin C, neomycin E, or any combination thereof;
(c) the surfactant synergizes with the aminoglycoside antibiotic or vancomycin to decrease the minimum inhibitory concentration (MIC) of the aminoglycoside antibiotic or vancomycin;
wherein the bacterial infection comprising a biofilm is caused by gram-positive bacteria; and
wherein the bacterial infection comprising a biofilm is treated.
2 . A method of reducing the risk of recurrence of a bacterial infection in a subject in need thereof, comprising administering to the subject having a bacterial infection comprising a biofilm a therapeutically effective amount of a surfactant and at least one of an aminoglycoside antibiotic or vancomycin, wherein:
(a) the surfactant consists of palmitoleic acid;
(b) the aminoglycoside antibiotic comprises streptomycin, kanamycin A, amikacin, dibekacin, sisomicin, netilmicin, neomycin B, neomycin C, neomycin E, or any combination thereof;
(c) the surfactant synergizes with the aminoglycoside antibiotic or vancomycin to decrease the MIC of the aminoglycoside antibiotic or vancomycin;
wherein the bacterial infection comprising a biofilm is caused by a gram-positive bacteria; and
wherein the risk of recurrence of a bacterial infection is reduced.
3 . A method of disrupting a biofilm, comprising contacting the biofilm with an effective amount of a surfactant and at least one of an aminoglycoside antibiotic or vancomycin, wherein:
(a) the surfactant consists of palmitoleic acid;
(b) the aminoglycoside antibiotic comprises streptomycin, kanamycin A, amikacin, dibekacin, sisomicin, netilmicin, neomycin B, neomycin C, neomycin E, or any combination thereof;
(c) the surfactant synergizes with the aminoglycoside antibiotic or vancomycin to decrease the MIC of the aminoglycoside antibiotic or vancomycin;
wherein the biofilm is from a gram-positive bacteria; and
wherein the biofilm is disrupted.
4 . The method of claim 1 , wherein the bacteria is antibiotic resistant or antibiotic tolerant.
5 . The method of claim 1 , wherein the bacteria is Staphylococcus aureus.
6 . The method of claim 5 , wherein the bacteria is methicillin-resistant Staphylococcus aureus.
7 . The method of claim 1 , wherein the surfactant and the aminoglycoside antibiotic or vancomycin are administered simultaneously.
8 . The method of claim 1 , wherein the surfactant and the aminoglycoside antibiotic or vancomycin are administered sequentially.
9 . The method of claim 2 , wherein the bacteria is antibiotic resistant or antibiotic tolerant.
10 . The method of claim 2 , wherein the bacteria is Staphylococcus aureus.
11 . The method of claim 10 , wherein the bacteria is methicillin-resistant Staphylococcus aureus.
12 . The method of claim 2 , wherein the surfactant and the aminoglycoside antibiotic or vancomycin are administered simultaneously.
13 . The method of claim 2 , wherein the surfactant and the aminoglycoside antibiotic or vancomycin are administered sequentially.
14 . The method of claim 3 , wherein the bacteria is antibiotic resistant or antibiotic tolerant.
15 . The method of claim 3 , wherein the bacteria is Staphylococcus aureus.
16 . The method of claim 15 , wherein the bacteria is methicillin-resistant Staphylococcus aureus.
17 . The method of claim 3 , wherein the surfactant and the aminoglycoside antibiotic or vancomycin are administered simultaneously.
18 . The method of claim 3 , wherein the surfactant and the aminoglycoside antibiotic or vancomycin are administered sequentially.