초록 ▼

The present invention is directed to methods of antimicrobial therapy for a patient infected with, or suspected of being infected with a microorganism that has mycolic acid structures in its outer membrane, said method comprising coadministering a betaine-like detergent and an antibiotic to said pat

The present invention is directed to methods of antimicrobial therapy for a patient infected with, or suspected of being infected with a microorganism that has mycolic acid structures in its outer membrane, said method comprising coadministering a betaine-like detergent and an antibiotic to said patient in an amount and for a length of time sufficient to kill said microorganism.

대표청구항 ▼

What is claimed is: 1. A method of antimicrobial therapy for a patient infected with, or suspected of being infected with, a microorganism that has mycolic acid structures in its outer membrane, said method comprising coadministering a betaine-like detergent and an antibiotic to said patient in an

What is claimed is: 1. A method of antimicrobial therapy for a patient infected with, or suspected of being infected with, a microorganism that has mycolic acid structures in its outer membrane, said method comprising coadministering a betaine-like detergent and an antibiotic to said patient in an amount and for a length of time sufficient to kill said microorganism. 2. The method of claim 1, wherein said betaine-like detergent is selected from the group consisting of a CB-like, SB-like, HSB-like, PB-like, StB-like, PhB-like, SoB-like, RevB-like, AO-like, cAB-like, and ImB-like detergent. 3. The method of claim 2, wherein said betaine-like detergent is said CB-like detergent. 4. The method of claim 3, wherein said CB-like detergent has the structure wherein R1 is C8-C22; α is--CH2--,--CH(OH)--,--(CO)--NH--CH 2CH2CH2--,--O--, or--C(O)--; n is 0 or 1; β is--N⊕,--P⊕--, or--S α--; R2 is--H,--CH3,--C2H5,--C3H7, or--C4H9; R3 is--H,--CH3,--C2H5,--C31H7, or--C4H9; R4 is--CH2--,--C2H4--,--C3H6--,--C4H8--,--C5H 10--,--C6H12--,--CH2--C6H 4--,--CmH2m--,--CH(OH)CH2CH2--,--CH2CH(OH)CH2--, or--CmH2m-1(OH)--where m is ≧1; and γ is COO⊖. 5. The method of claim 4, wherein said CB-like detergent is selected from the group consisting of N-(carboxymethyl)-N,N-dimethyl-1-hexadecanaminium, inner salt (CAS짰No. 693-33-4), cococarboxymethylbetaine and (CAS짰No. 68424-94-2), N-(carboxymethyl)-N,N-dimethyl-9-octadecen-1-aminium, inner salt (CAS짰No. 871-37-4), N-(carboxymethyl)-N,N-dimethyl-3-((1-oxooctadecyl)amino)-1-propanaminium, inner salt (CAS짰No. 6179-44-8), 3-amino-N(carboxymethyl)-N,N-dimethyl-1-propanaminium N-C8-C22 acyl derivatives, inner salt (CAS짰No. 84082-44-0), N-(carboxymethyl)-3-((12-hydroxy-1-oxo-9-octadecenyl)amino)-N,N-dimethyl-1-propanaminium, inner salt (CAS짰No. 71850-81-2), cocoamidopropyl carboxymethylbetaine (CAS짰No. 61789-39-7 and CAS짰No. 61789-40-0), N-(2-carboxyethyl)-N,N-dimethyl-1-dodecanaminium, inner salt (CAS짰No. 16527-85-8), N-(2-carboxyethyl)-N,N-dimethyl-1-tridecanaminium, inner salt (CAS짰No. 132621-79-5), N-(2-carboxyethyl)-N,N-dimethyl-1-tetradecanaminium, inner salt (CAS짰No. 69725-38-3), N-(2-carboxyethyl)-N,N-dimethyl-1-hexadecanaminium, inner salt (CAS짰No. 42416-43-3), N-(2-carboxyethyl)-N,N-dimethyl-1-octadecanaminium, inner salt (CAS짰No. 30612-73-8), N-dodecyl-beta-alanine (CAS짰No. 1462-54-0), N-(3-carboxypropyl)-N,N-dimethyl-1-undecanaminium, inner salt (CAS짰No. 150147-53-8), N-(3-carboxypropyl)-N,N-dimethyl-1-dodecanaminium, inner salt (CAS짰No. 15163-30-1), N-(3-carboxypropyl)-N,N-dimethyl-1-tetradecanaminium, inner salt (CAS짰No. 146959-90-2), N-(3-carboxypropyl)-N,N-dimethyl-1-pentadecanaminim, inner salt (CAS짰No. 146959-91-3), N-(3-carboxypropyl)-N,N-dimethyl-1-hexadecanaminium, inner salt (CAS짰No. 71695-32-4), N-(3-carboxypropyl)-N,N-dimethyl-1-octadecanaminium inner salt (CAS짰No. 78195-27-4), N-(4-carboxybutyl)-N,N-dimethyl-1-dodecanaminium, inner salt (CAS짰No. 120139-51-7), N-(5-carboxypentyl)-N,N-dimethyl-1-dodecanaminium, inner salt (CAS짰No. 76392-97-7), N-(5-carboxypentyl)-N,N-dimethyl-1-hexadecanaminium, inner salt (CAS짰No. 73565-98-7), N-(6-carboxyhexyl)-N,N-dimethyl-1-dodecanaminium, inner salt (CAS짰No. 132621-80-8), 4-carboxy-N-dodecyl-N,N-dimethyl-benzenemethanaminium, inner salt (CAS짰No. 71695-31-3), 2-carboxy-N-dodecyl-N,N-dimethyl-benzenemethanaminium, inner salt (CAS짰No. 71695-34-6), 4-carboxy-N-hexadecyl-N,N-dimethyl-benzenemethanaminium, inner salt (CAS짰No. 71695-33-5), 2-carboxy-N-hexadecyl-N,N-dimethyl-benzenemethanaminium, inner salt (CAS짰No. 71695-35-7), tallow glycinate (CAS짰No. 70750-46-8), soyamidopropyl carboxymethylbetaine, and babassuamidopropyl carboxymethylbetaine. 6. The method of claim 5, wherein said carboxybetaine is N-(3-carboxypropyl)-N,N-dimethyl-1-octadecanaminium, inner salt (CB-18) (CAS짰No. 78195-27-4). 7. The method of claim 2, wherein said betaine-like detergent is said SB-like detergent. 8. The method of claim 7, wherein said SB-like detergent is selected from the group consisting of SB-18, SB-16, SB-14 and SB-12. 9. The method of claim 8, wherein said SB-like detergent is SB-16. 10. The method of claim 8, wherein said SB-like detergent is SB-18. 11. The method of claim 2, wherein said betaine-like detergent is said SoB-like detergent. 12. The method of any one of claims 2-11, wherein said method comprises administering two or more betaine-like detergents to said patient. 13. The method of claim 1, wherein said antibiotic is a member of a class selected from the group consisting of a β-lactam antibiotic, an aminoglycoside, an aminocyclitol, a quinolone, a tetracycline, a macrolide, a lincosamide, a glycopeptide, a lipopeptide, a polypeptide antibiotic, a sulfonamide, trimethoprim, chloramphenicol, isoniazid, a nitroimidazole, a rifampin, a nitrofuran, methenamine, and nupirocin. 14. The method of claim 13, wherein said antibiotic is said β-lactam antibiotic. 15. The method of claim 14, wherein said β-lactam antibiotic is selected from the group consisting of penicillin, cephalosporin, monobactam and carbapenem antibiotics. 16. The method of claim 15, wherein said antibiotic is said penicillin. 17. The method of claim 16, wherein said penicillin is selected from the group consisting of azlocillin, methicillin, nafcillin, cloxacillin, dicloxacillin, oxacillin, ampicillin, bacampicillin, carbenicillin, ticarcillin, mezlocillin, penicillin, and piperacillin. 18. The method of claim 15, wherein said antibiotic is said cephalosporin. 19. The method of claim 18, wherein said cephalosporin is selected from the group consisting of cefoxitin, cefoperazone, ceftazidime, ceftriaxone, cefadroxil, cefazolin, cephalexin, cephaloridine, cephalothin, cephapirin, cephradine, cefaclor, cefamandole, cefonicid, ceforanide, cefprozil, cefuroxime, loracarbef, cefmetazole, cefotetan, cefixime, cefotaxime, cefpodoxime, and ceftizoxime. 20. The method of claim 19, wherein said cephalosporin is ceftriaxone. 21. The method of claim 15, wherein said antibiotic is said monobactam. 22. The method of claim 21, wherein said monobactam is aztreonam. 23. The method of claim 15, wherein said antibiotic is said carbapenem. 24. The method of claim 23, wherein said carbapenemis selected from the group consisting of imipenem, meropenem, panipenem, and biapenem. 25. The method of claim 24, wherein said carbapenem is imipenem. 26. The method of any one of claims 14-25, wherein said method further comprises administering a β-lactamase inhibitor to said patient. 27. The method of claim 26 wherein said β-lactamase inhibitor is selected from the group consisting of clavulanic acid, sulbactam, and tazobactam. 28. The method of claim 13, wherein said antibiotic is said aminoglycoside or said aminocyclitol. 29. The method of claim 28, wherein said aminoglycoside or aminocyclitol is selected from the group consisting of streptomycin, kanamycin, gentamicin, tobramycin, amikacin, sisomicin, netilmicin, neomycin, framycetin and paromomycin. 30. The method of claim 13, wherein said antibiotic is said quinolone. 31. The method of claim 30, wherein said quinolone is selected from the group consisting of naladixic acid, oxolinic acid, cinoxacin, flumequine, miloxacin, rosoxacin, pipemidic acid, norfloxacin, enoxacin, ciprofloxacin, ofloxacin, lomefloxacin, temafloxacin, fleroxacin, pefloxacin, amifloxacin, sparfloxacin, levofloxacin, clinafloxacin. 32. The method of claim 13, wherein said antibiotic is said tetracycline. 33. The method of claim 13, wherein said antibiotic is said macrolide. 34. The method of claim 33, wherein said macrolide is selected from the group consisting of erthromycin, oleandomycin, spiramycin, josamycin, rosaramicin, clarithromycin, azithromycin, dirithromycin, roxithromycin, flurithromycin, and rokitamycin. 35. The method of claim 13, wherein said antibiotic is said lincosamide. 36. The method of claim 13, wherein said antibiotic is said glycopeptide. 37. The method of claim 13, wherein said antibiotic is said lipopeptide. 38. The method of claim 13, wherein said antibiotic is said polypeptide antibiotic. 39. The method of claim 13, wherein said antibiotic is said sulfonamide. 40. The method of claim 13, wherein said antibiotic is said trimethoprim. 41. The method of claim 13, wherein said antibiotic is said chloramphenicol. 42. The method of claim 13, wherein said antibiotic is said isoniazid. 43. The method of claim 13, wherein said antibiotic is said nitroimidazole. 44. The method of claim 13, wherein said antibiotic is said rifampin. 45. The method of claim 44 wherein said rifampin is selected from the group consisting of rifampin, rifamycin SV rifamycin B (rifamide) and rifabutin. 46. The method of claim 45 wherein said rifampin is rifampin. 47. The method of claim 45 wherein said rifampin is rifabutin. 48. The method of claim 13, wherein said antibiotic is said nitrofuran. 49. The method of claim 13, wherein said antibiotic is said methenamine. 50. The method of claim 13, wherein said antibiotic is said mupirocin. 51. The method of claim 1, wherein said antibiotic is selected from the group consisting of amikacin, azithromycin, any β-lactam in combination with any of the β-lactamase inhibitors, capreomycin, cefnetazole, cefoxitin, ciprofloxacin, clarithromycin, clofazamine, cycloserine, dapsone, erythromycin, ethambutol, ethionamide, imipenem, isoniazid, kanamycin, minocycline, ofloxacin, para-amino salicylic acid, prothionamide, pyrazinamide, rifampin, rifabutin, sparfloxacin, sulfamethoxazole with trimethoprim, streptomycin, tetracycline, thiacetazole and viomycin. 52. The method of claim 1, wherein said patient is administered two antibiotics. 53. The method of claim 52, wherein said antibiotics are a sulfonamide and trimethoprim. 54. The method of claim 53, wherein said sulfonamide is sulfamethoxazole. 55. The method of claim 1, wherein said microorganism is a Mycobacterium. 56. The method of claim 55 wherein said Mycobacterium is selected from the group consisting of M. agri, M. abscessus, M. acetamidolyticum, M. africanum, M. aichiense, M. asiaticum, M. aurum, M. austroafricanum, M. avium, M. bovis, M. bovis (BCG), M. chelonae, M. chitae, M. chubuense, M. cookii, M. diernhoferi, M. duvaiji, M. fallax, M. farcinogenes, M. flavescens, M. fortuitum, M. gadium, M. gastri, M. gilvum, M. gordonae, M. haemophilum, M. intracellulare, M. kansasii, M. komossense, M. leprae, M. lepraemurium, M. marinum, M. malmoense, M. microti, M. moriokuense, M. necaurum, M. nonchromogenicum, M. obuense, M. parafortuitum, M. paratuberculosis, M. peregrinum, M. phlei, M. porcinum, M. poriferae, M. pulveris, M. rhodesiae, M. scrofulaceum, M. senegalense, M. shimoidei, M. simiae, M. smegmatis, M. sphagni, M. szulgai, M. terrae, M. thermoresistible, M. tokajense, M. triviale, M. tuberculosis, M. ulcerans, M. vaccae, M. xenopi. 57. The method of claim 56, wherein said Mycobacterium is a member of the Mycobacterium tuberculosis complex (MTB). 58. The method of claim 57, wherein said microorganism is said M. tuberculosis. 59. The method of claim 56, wherein said microorganism is a member of the Mycobacterium avium (MAC) complex. 60. The method of claim 56, wherein said microorganism is a member of the MAIS group. 61. The method of claim 56, wherein said microorganism is said M. ulcerans. 62. The method of claim 56, wherein said microorganism is said M. kansasii. 63. The method of claim 56, wherein said microorganism is said M. chelonae. 64. The method of claim 56, wherein said microorganism is said M. fortuitum.