Novel combination and use

Abstract

The present invention relates to the use of one or more compounds selected from the following: caffeic acid, thymol, aspirin, benzydamine hydrochloride, diclofenac sodium, flurbiprofen, ibuprofen, indomethacin, trifluoperazine hydrochloride, chlorprothixene hydrochloride, triflupromazine hydrochloride, suloctidil, thioridazine hydrochloride, dichlorophen, saccharin and piroxicam, in combination with a polymyxin selected from colistin or polymyxin B or a pharmaceutically acceptable derivative thereof, for use in the treatment of a microbial infection, and in particular for killing clinically latent microorganisms associated with microbial infections. The invention also provides a combination comprising suloctidil or a pharmaceutically acceptable derivative or prodrug thereof, and a polymyxin selected from polymyxin E and polymyxin B or a pharmaceutically acceptable derivative thereof. This combination is particularly useful for the treatment and/or prevention of microbial infections.

1 - 17 . (canceled) 
     
     
         18 . A method of treating a microbial infection, wherein the method comprises administering to a mammal, one or more compounds selected from the following: caffeic acid, thymol, aspirin, benzydamine hydrochloride, diclofenac sodium, flurbiprofen, ibuprofen, indomethacin, trifluoperazine hydrochloride, chlorprothixene hydrochloride, triflupromazine hydrochloride, thioridazine hydrochloride, dichlorophen, saccharin and piroxicam, in combination with a polymyxin selected from colistin or polymyxin B or a pharmaceutically acceptable derivative thereof. 
     
     
         19 . The method according to  claim 18 , wherein the method comprises killing multiplying, non-multiplying and/or clinically latent microorganisms associated with the microbial infection. 
     
     
         20 . The method according to  claim 19 , wherein the polymyxin is colistin or a pharmaceutically acceptable derivative thereof. 
     
     
         21 . The method according to  claim 18 , wherein the infection is a bacterial infection. 
     
     
         22 . The method according to  claim 21 , wherein the bacterial infection is caused by  E. coli , Enterobacteriaceae,  Haemophilis influenzae , Mycobacteria or  Klebsiella.    
     
     
         23 . The method according to  claim 22 , wherein the infection is caused by  E. coli  or  Klebsiella.    
     
     
         24 . The method according to  claim 23 , wherein the infection is caused by a drug-resistant strain. 
     
     
         25 . The method according to  claim 24 , wherein the infection is caused by a carbapenemase-resistant strain or “extended spectrum β-lactamase” (ESPL) strain. 
     
     
         26 . The method according to  claim 25 , wherein the infection is caused by New Delhi Metallo-beta-lactamase-1 (NDM-1) resistant Klebs. Pneumonia or NDM-1  E. coli.    
     
     
         27 . The method according to  claim 18  for the treatment of tuberculosis, anthrax, abscesses, acne vulgaris, actinomycosis, asthma, bacilliary dysentry, bacterial conjunctivitis, bacterial keratitis, bacterial vaginosis, botulism, Buruli ulcer, bone and joint infections, bronchitis (acute or chronic), brucellosis, burn wounds, cat scratch fever, cellulitis, chancroid, cholangitis, cholecystitis, cutaneous diphtheria, cystic fibrosis, cystitis, diffuse panbronchiolitis, diphtheria, dental caries, diseases of the upper respiratory tract, eczema, empymea, endocarditis, endometritis, enteric fever, enteritis, epididymitis, epiglottitis, erysipelis, erysipclas, erysipeloid, erythrasma, eye infections, furuncles,  gardnerella  vaginitis, gastrointestinal infections (gastroenteritis), genital infections, gingivitis, gonorrhoea, granuloma inguinale, Haverhill fever, infected burns, infections following dental operations, infections in the oral region, infections associated with prostheses, intraabdominal abscesses, Legionnaire's disease, leprosy, leptospirosis, listeriosis, liver abscesses, Lyme disease, lymphogranuloma venerium, mastitis, mastoiditis, meningitis and infections of the nervous system, mycetoma, nocardiosis, non-specific urethritis, opthalmia, osteomyelitis, otitis, orchitis, pancreatitis, paronychia, pelveoperitonitis, peritonitis, peritonitis with appendicitis, pharyngitis, phlegmons, pinta, plague, pleural effusion, pneumonia, postoperative wound infections, postoperative gas gangrene, prostatitis, pseudo-membranous colitis, psittacosis, pulmonary emphysema, pyelonephritis, pyoderma, Q fever, rat-bite fever, reticulosis, ricin poisoning, Ritter's disease,  salmonellosis , salpingitis, septic arthritis, septic infections, septicameia, sinusitis, skin infections, syphilis, systemic infections, tonsillitis, toxic shock syndrome, trachoma, tularaemia, typhoid, typhus, urethritis, wound infections, yaws, aspergillosis, candidiasis, cryptococcosis, favus, histoplasmosis, intertrigo, mucormycosis, tinea, onychomycosis,  pityriasis versicolor , ringworm and sporotrichosis; or infections with MSSA, MRSA,  Staph. epidermidis, Strept. agalactiae , Strept.  pyogenes, Escherichia coli, Klebs. pneumoniae, Klebs. oxytoca, Pr. mirabilis, Pr. rettgeri, Pr. vulgaris, Haemophilis influenzae, Enterococcus faecalis  or  Enterococcus faecium.    
     
     
         28 . A pharmaceutical composition comprising one or more compounds selected from the following: caffeic acid, thymol, aspirin, benzydamine hydrochloride, diclofenac sodium, flurbiprofen, ibuprofen, indomethacin, trifluoperazine hydrochloride, chlorprothixene hydrochloride, triflupromazine hydrochloride, suloctidil, thioridazine hydrochloride, dichlorophen, saccharin and piroxicam, in combination with a polymyxin selected from colistin or polymyxin B or a pharmaceutically acceptable derivative thereof, and a pharmaceutically acceptable adjuvant, diluent or carrier. 
     
     
         29 . A product comprising one or more compounds selected from the following: caffeic acid, thymol, aspirin, benzydamine hydrochloride, diclofenac sodium, flurbiprofen, ibuprofen, indomethacin, trifluoperazine hydrochloride, chlorprothixene hydrochloride, triflupromazine hydrochloride, suloctidil, thioridazine hydrochloride, dichlorophen, saccharin and piroxicam, in combination with a polymyxin selected from colistin or polymyxin B or a pharmaceutically acceptable derivative thereof, as a combined preparation for simultaneous, separate or sequential use in treating a microbial infection. 
     
     
         30 . The product according to  claim 29  for killing clinically latent microorganisms associated with the microbial infection.