USE OF THIAMPHENICOL FOR THE PREPARATION OF PHARMACEUTICAL COMPOSITIONS USEFUL IN THE TREATMENT OF VANCOMYCIN-INTERMEDIATES AND MULTIRESISTANT <i>STAPHYLOCOCCI</i> INFECTIONS

Abstract: Use of thiamphenicol or derivatives thereof for the preparation of pharmaceutical compositions useful for the treatment of vancomycin-intermediates and multiresistant <i>Staphylococci</i> infections, is described.

Description: "Use of thiamphenicol for the preparation of pharmaceutical compositions useful in the treatment of vancomycin-intermediates and multiresistant Staphylococci infections" * ****************************** The present invention relates to the use of thiamphenicol for the preparation of pharmaceutical compositions useful in the treatment of vancomycin-intermediates and multiresistant Staphylococci infections The broad use of antibiotics has significantly increased the number of resistant microorganisms which are more and more associated to seπous pathological states and to mortality among hospitalized patients In particular, duπng the last years, the onset of hospital infections caused by strains of Staphylococci, in particular Staphylococcus aureus, with an intermediate susceptibility, I e reduced, to vancomycin (VISA) and other glycopeptides (GISA), has been more and more frequently supported by documentary evidence These pathogenic strains are generally resistant also to most antibiotics of frequent therapeutical use such as, for example, β- lactames, macrohdes, tetracychnes and quinolones The characteπstics of a significant number of these strains have been widely descπbed by Tenover et al in Journal of Chmical Microbiology, Apr 1998, pages 1020-1027 Most of the strams of Staphilococci GISA or GISS studied by Tenover et al in the above mentioned article, are susceptible to the treatment with tπmetopπm-sulphametoxazole association and to the treatment with πphampine while only some strains are susceptible to other antibiotics such as tetracycline, chloramphenicol, gentamicm and ciprofloxacm The speed and the frequency of the occurrence of phenomena of reduced susceptibility to those antibiotics up to now proposed for the treatment of infections caused by strams of vancomycin-intermediates and multiresistant Staphylococci, make the identification of other antibiotics effective in this kind of infections, particularly interesting Thiamphenicol (The Merck Index, XII ed . No 9436. page 1587) is a known antibiotic used for the treatment of Gram-positive and Gram-negative bacteπal infection In particular, the activity of thiamphenicol toward many strains of Staphylococci has been supported by documentary evidence in literature [see for example Kayser et al , Postgraduate Medical Journal, 1974, 50(Suppl 5), 79-83], nevertheless underlining that in vitro thiamphenicol is from 2 to 4 times less active than chloramphenicol We have now found that thiamphenicol is particularly effective in the treatment of infections due to strains of Staphylococci vancomycin-intermediates and multiresistant It is therefore an object of the present invention, the use of thiamphenicol for the preparation of pharmaceutical composition useful in the treatment of vancomycin-intermediates and multiresistant Staphylococci infections Particularly preferred is the use of thiamphenicol for the preparation of a pharmaceutical composition useful for the treatment of vancomycin-intermediates Staphylococci infections The pharmaceutical compositions useful in the present invention are compositions for enteral or parenteral use containing thiamphenicol or deπvatives thereof such as, for example, thiamphenicol ghcinate and salts thereof The amount of active ingredient, expressed as thiamphenicol, contained m the pharmaceutical composition may change depending on the administration way and to the seπousness of the infection but is generally compπsed between 250 mg and 5000 mg per dose, more preferably between 500 mg and 3000 mg The pharmaceutical compositions can be in a solid or liquid form, suitable for administenng by mjectable, oral or aerosol route Preferred are the pharmaceutical compositions suitable for administenng by mjectable route, both endovenous and intramuscular Particularly suitable are the pharmaceutical compositions already on the market with the trademark GLITISOL ® The thiamphenicol efficacy with regard to strams of vancomycin-intermediates (VISA) and multiresistant Staphylococcus aureus has been demonstrated in vitro by calculating the MIC (Mimmum Inhibitory Concentration) It is important to underlme that the activity of thiamphenicol resulted to be comparable to that as of cloramphenicol well known to be more effective than thiamphenicol against Staphylococci With the aim to better illustrate the present invention the following example is now given Example 1 MIC Determination The MICs of thiamphenicol and of other antibiotics was obtained by using the method proposed by NCCLS (National Committee for Clinical Laboratory Standards, 1999). Various antibiotic concentrations were added to bacteria in exponental growth (final inoculum 5 x 10 5 ml/cell); dilution in MHb (cation-supplemented Mueller-Hinton broth) and distribution on a microplate by using an automatic diluting machine Biomek 1000 (Beckman, USA). MHb charged with 2% NaCl was used to test the methicillin activity. The antibiotic concentration which hinders a visible growth after 18-24 hours of incubation at 37°C, was registered as MIC. S. aureus ATCC 29213 was used as quality control strain. The obtained results are reported in the following tables. Table 1 MIC of thiamphenicol and of others comparative antibiotics against S. aureus vancomycin- intermediates and multiresistant strains Met-R: methicillin resistants * breakpoints suggested in NCCLS (1999) for Staphylococci, in mg/1: chloramphenicol, <8; vancomicine, <4; teicoplanin, <8; methicillin, <8; erythromycin, <0.5; clindamycin, <0.5. Table 2 MIC (mg/1) of thiamphenicol and other comparative antibiotics Table 2 (continued) Thia thiamphenicol, Clo cloramphenicol, Van vancomycine, Tei teicoplanme, Met methiciUine, Ery erythromycin, Cl clindamycin, Oxa oxacillin, Cip ciprofloxacin, Fos fosfomycin, Gm gentamicm, Rif nfampicm, SXT co-tπmoxazole, Dox doxycyclme

Claims: Claims 1) Use of thiamphenicol for the preparation of a pharmaceutical composition useful for the treatment of vancomycin-intermediates and multiresistant Staphylococci infections 2) Use accordmg to claim 1 wherein thiamphenicol is used as thiamphenicol glicinate or salts thereof 3) Use accordmg to claim 1 wherein the pharmaceutical composition is suitable for mjectable administration 4) Use accordmg to claim 1 wherein the amount of thiamphenicol is compπsed between 250 mg and 5000 mg

Inventors: LICCIARDELLO LUCIANO, UNGHERI DOMENICO, LICCIARDELLO, LUCIANO, UNGHERI, DOMENICO
Applicants: LICCIARDELLO LUCIANO, UNGHERI DOMENICO, ZAMBON SPA, LICCIARDELLO, LUCIANO, UNGHERI, DOMENICO, ZAMBON GROUP S.P.A.
Application year: 2001
Main classification: A61K31
IPC codes: A61K31, A61P31