The present invention is directed to compounds of the formula

wherein Ri represents alkanoyl of C2-C1O which is unsubstituted, or which is substituted by a phenyl, or which is substituted on other than the a-carbon atom by an amino or protected amino group; benzoyl or substituted benzoyl bearing one or two substituents each of which is independently halo, loweralkyl of C1-C4, loweralkoxy of C1-C4 or phenyl;

an acyl derived from an a-amino acid or an acyl derived from a protected a-amino acid, said a-amino acid being selected from the group consisting of: alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, 3-phenylalanine, 3- (p-chlorophenyl) alanine, proline, serine, threonine, tryptophan and valine, in either D-or L-form; or an acyl derived from an a-amino acid as defined above which bears on the amine a substituent which is alkyl of C1-Clo, benzyl, phenylbenzyl, or p-chlorobenzyl, with the proviso that the acyl derived from N-methyl-D-leucine is excluded; R2 represents hydrogen, or epivancosaminyl of the formula

Wherein R2a represents hydrogen or-CH2-R3; and R3 represents hydrogen, alkyl of C1-Cll, alkyl of C1-Cll-R4, or (linker(0or1)-R4)0or1,R4- wherein each R4 is independently phenyl or phenyl substituted by one or two substituents, each of which is independently halo, loweralkyl of C1-C8, loweralkoxy of C1- C8, loweralkylthio of C1-C4, or trifluoromethyl, and "linker"is-0-,-CH2-, or-0- (CH2) n- wherein n is 1-3; and the pharmaceutically acceptable salts thereof.

When R1 represents alkanoyl of Cs-Cio, it can be a straight-chain alkanoyl, or it can be an alkanoyl which is branched to any degree. Likewise, when R3 represents alkyl of C1-Cll, it can be straight-chain or branched.

The compounds of the present invention are prepared from the corresponding"A82846B hexapeptides"of the formula:

wherein R2 is as defined above. These"A82846B hexapeptides"are so called because the normal Nl amino acid N-methyl-D-leucine, has been removed, reducing the number of amino acids in the parent glycopeptide from seven to six.

The compounds of the present invention are prepared by reacting an A82846B hexapeptide with an activated ester of an alkanoic acid of the desired acyl group R1. By "activated ester"is meant an ester which renders the carboxyl function more reactive to coupling with the amine of the A82846B hexapeptide. The reaction of the A82846B hexapeptide and activated ester is carried out in an organic solvent, suitably a polar solvent such as dimethylformamide, dimethyl sulfoxide, or a mixture of dimethylformamide and dimethyl sulfoxide. The reaction proceeds under temperatures of a wide range, such as 25° to 100° C., but is

preferably carried out at temperatures of about 25° to 35° C. Some of the desired product is produced shortly upon contacting the reactants, but higher yields are obtained with reaction times of from about 1 to about 24 hours, oftentimes from about 1 to about 5 hours. Isolation and purification are carried out under conventional procedures.

The starting A82846B hexapeptides are themselves synthesized from the parent glycopeptides:

wherein R2a is as defined above. This synthesis is by the "Edman degradation", a two-step process for the cleavage of the N-terminal residue of a peptide or protein. The above parent glycopeptide is first reacted with an isothiocyanate of the formula SCN-R5, to obtain an intermediate NLEU- (thiocarbamoyl)-A82846B compound of the formula

In the foregoing formula, R5 represents alkyl of Cl-Clo phenyl, naphthyl, or phenyl substituted by one or two substituents, each of which is independently halo, loweralkyl of C1-C4, loweralkoxy of C1-C4, benzyloxy, nitro, or wherein each R6 is independently loweralkyl of C1-C4.

This reaction is conveniently carried out in water with pyridine, at a temperature of 25°-30°C, employing a slight excess of the isothiocyanate reactant. The NLEU- (thiocarbamoyl) A82846B intermediate can be separated in conventional manner or can be employed after removal of

reaction solvent in the second step of the Edman degradation.

In the second step, the NLEU- (thiocarbamoyl) A82846B is reacted with an organic acid, preferably trifluoroacetic acid, in a non-polar solvent such a dichloromethane. The reaction proceeds at temperatures of from 0°C to 35°C but is preferably carried out at temperatures of from 0°C to 25°C.

The reaction is generally complete in several hours. The resulting hexapeptide product is separated and purified if desired in conventional procedures.

The second step of the Edman degradation can in some instances result in loss of the disaccharide epivancosamine.

Longer reaction times can be used to obtain the des- epivancosaminyl compound (R2=hydrogen).

Other variations at the disaccharide position of the molecule can be obtained in conventional procedures. As described above, the Edman degradation and subsequent acylation can be carried out with the naturally-occurring disaccharide (R2=epivancosaminyl with R2a=H) or with a disaccharide derivative (R2=epivancosaminyl with R2a=CH2-R3).

This approach to synthesis of the present compounds is illustrated by the preparations below of Examples 12 and 26.

However, it is also possible to prepare those claimed compounds with a disaccharide derivative (R2=epivancosaminyl with R2a=-CH2-R3) by first conducting the Edman degradation

and subsequent acylation on A82846B, with its naturally occurring R2=epivancosaminyl, and thereafter introducing the desired epivancosaminyl substituent-CH2-R3. This is illustrated by Examples 34 and 35.

Whether the-CH2-R3 substituent is introduced prior to Edman degradation and acylation, or after, the same conventional process is used. In this process, the substrate compound is reductively alkylated with the aldehyde suitable to introduce the desired-CH2-R3 group.

This process is taught in various references, see U. S.

5,591,714, and EPO 667,353.

The compounds of the present invention readily form salts, which can be prepared in conventional manner.

The following examples illustrate the preparation of the compounds of the present invention.

Preparation of NLEU- (phenylthiocarbamoyl)-NDISACC (p- (p-chlorophenyl) benzyl) A82846B NDISACC- (p- (p-Chlorophenyl) benzyl) A82846B trihydrochloride (100.0 mg, 0.0526 mmol) was dissolved in 10 ml H2O-pyridine (1: 1 v/v) and treated with phenyl isothiocyanate (0.010 ml, 0.083 mmol). The resulting mixture was stirred at room temperature for 1 hr at which time HPLC analysis indicated complete consumption of the starting material. The reaction mixture was concentrated in vacuo and the crude product was purified by preparative HPLC to give 76.6 mg (7601 yield) of the title compound. FAB-MS: calc. for Cg3H1o2Cl3NllO26S 1925.5, obtained 1928.5 (M+3).

Preparation of NDISACC _ (p- (p-chlorophenyl) benZyl)-<BR> <BR> <BR> <BR> <BR> desleucylA82846B from isolated thiourea A sample of the purified NLEU-(phenylthiocarbamoyl)- NDISACC_ (p- (p-chlorophenyl) benzyl) A82846B (63.3 mg, 0.0327 mmol) was suspended in 10 ml CH2C12, cooled to 0 °C, then treated with trifluoroacetic acid (0. 10 ml). After 1 hr the reaction mixture was warmed to room temperature and stirred an additional 2 hr. The solvent was removed in vacuo and the crude product was purified by preparative HPLC to give 25.3 mg (46W yield) of the title compound as a white powder.

FAB-MS: calc. for C79Hg4C13Ng02s 1663.5, obtained 1666.4 (M+3).

Preparation of NDISCC (p-phenylbenzyl) desleucylA82846B without isolation of thiourea intermediate NDISACC- (p-Phenylbenzyl) A82846B (41.0 mg, 0.0233 mmol) was dissolved in 4 ml H20-pyridine (1: 1 v/v) and treated with phenyl isothiocyanate (0.0040 ml, 0.033 mmol). The resulting mixture was stirred at room temperature for 3 hr at which time HPLC analysis indicated complete consumption of the starting material. The reaction mixture was concentrated in vacuo to give the crude thiourea intermediate as a white solid. The thiourea derivative was then suspended in 10 ml CH2Cl2, cooled to 0 °C, then treated with trifluoroacetic acid (0.25 ml). After 30 minutes the reaction mixture was warmed to room temperature and stirred an additional 1 hr. The solvent was removed in vacuo and

the crude product was purified by preparative HPLC to give 14.0 mg (37W yield) of the title compound as a white powder.

FAB-MS: calc. for C79H85Cl2NgO25 1629.5, obtained 1632.5 (M+3).

Preparation of Example 1 A sample of desleucylA82846B (101 mg, 0.0689 mmol) and the hydroxybenzotriazole hydrate active ester of 4- phenylbenzoic acid (47 mg, 0.149 mmol) was dissolved in 10 ml DMF. The resulting mixture was stirred at room temperature for 2 hours at which time HPLC analysis revealed complete consumption of the starting material. The reaction mixture was concentrated in vacuo and the crude product was purified by preparative HPLC to give 14 mg (12% yield) of Nl- (p-phenylbenzoyl) desleucylA82846B.

Preparation of Example 26 A sample of NDISACC- (p-phenylbenzyl) desleucylA82846B (140 mg, 0.0858 mmol) and the hydroxybenzotriazole hydrate active ester of N-BOC-D-proline (66 mg, 0.199 mmol) was dissolved in 12 ml DMF. The resulting mixture was stirred at room temperature for 1 hour at which time HPLC analysis revealed consumption of the starting material. The reaction mixture was concentrated in vacuo and the crude product purified by preparative HPLC to give 77.5 mg (496 yield) of Nl- (N-BOC-D-proline) derivative of NDISACC-( phenylbenzyl) desleucylA82846B.

Preparation of Example 12 A sample of purified Nl- (N-BOC-D-proline) derivative of NDISACC-(p-phenylbenzyl)(p-phenylbenzyl) desleucylA82846B (52.5 mg, 0.0287

mmol) was suspended in 9 ml CH2C12, cooled to 0° C, then treated with trifluoroacetic acid (0.5 ml). After 10 minutes the reaction mixture was warmed to room temperature and stirred for an additional 50 minutes. HPLC analysis revealed complete consumption of the starting material. The solvent was removed in vacuo, and the crude product was purified by preparative HPLC to give 15 mg (30% yield) of Nl-D-proline derivative of NDISACC-( phenylbenzyl) desleucylA82846B.

Preparation of Examples 34 and 35 A sample of N'-D-leucine derivative of desleucylA82846B (95 mg, 0.0602 mmol) and p-phenylbenzaldehyde (14 mg, 0.0768 mmol) was dissolved in 10 ml N, N-dimethylformamide (DMF) and 10 ml methanol (MeOH). The resulting mixture was heated to 75°C and stirred for 1 hour 15 minutes. At this time, sodium cyanoborohydride (26 mg, 0.413 mmol) was added and the reaction stirred at 75°C for another 1 hour 30 minutes at which time HPLC analysis revealed consumption of the starting material. The reaction mixture was concentrated in vacuo and the crude product purified by preparative HPLC to give 32 mg (30%) of N1-(N-p-phenylbenzyl)-D-leucine derivative of desleucylA82846B and 3 mg (2.60-.) of NDISACC-(p- phenylbenzyl)-N1-(N-p-phenylbenzyl)-D-leucine(N-p-phenylbenz yl)-D-leucine derivative of desleucylA82846B.

The HPLC procedures reported in these examples were as follows:

Analytical: Reactions were monitored by analytical HPLC using a Waters C18 yBondapak or Novapak C18 column (3.9x300 mm) and UV detection at 280 nm. Elution was accomplished with a linear gradient of 5% CH3CN-95 buffer to 80% CH3CN-20% buffer over 30 minutes. The buffer used was 0.5% triethylamine in water, adjusted to pH 3 with H3PO4- Preparative: Crude reaction mixtures were purified by preparative HPLC using a Waters C1s Nova-Pak column (40x300 mm) and W detection at 280 nm. Elution was accomplished with a linear gradient of 5% CH3CN-95o buffer to 80% CH3CN -20% buffer over 30 minutes. The buffer used was 0.5% triethylamine in water, adjusted to pH 3 with H3PO4. The desired fractions were subsequently desalted with a Waters Cl8 Sep-Pak (35 cc) followed by lyophilization.

Compounds were desalted as follows. A Waters Sep-Pak cartridge was pre-wet with methanol (2-3 column volumes) then conditioned with water (2-3 column volumes). The sample, dissolved in a minimum volume of water, was loaded onto the Sep-Pak column which was then washed with water (2- 3 column volumes) to remove the unwanted salts. The product was then eluted with an appropriate solvent system, typically 1: 1 CH3CN/H2O, CH3CN, and/or methanol. The organic solvent component was removed in vacuo and the resulting aqueous solution lyophilized to give the final product.

Representative compounds of the present invention are listed in the following tables: TABLE I: SIMPLE ACYL DERIVATIVES Example # FAB-MS M + X HPLC, min Compound Name 1 1644.2 1 14.7 N1-(p-phenylbenzoyl)desleucylA82846B 2 1667.4 2 17.3 N1-(8-phenyl-n-octanoyl)desleucylA82846B 3 1834.7 3 20.4 N1-(8-phenyl-n-octanoyl)-NDISACC-(p-phenylben@ desleucylA82846B 4 1564.4 3 11.0 N1-(4-methyl-n-pentanoyl)desleucylA82846B 5 1730.4 3 17.3 N1-(4-methyl-n-pentanoyl)-NDISACC-(p-phenylbe@ desleucylA82846B 6 1812.7 3 18.9 N1-(p-phenylbenzoyl)-NDISACC-(p-phenylbenzyl) desleucylA82846B 7 1764.4 0 18.7 N1-(4-methyl-n-pentanoyl)-NDISACC-[p(p- chlorophenyl)benzyl]desleucylA82846B 8 1868.5 3 23.0 N1-(8-phenyl-n-octanoyl)-NDISACC-[p-(p- chlorophenyl)benzyl]desleucylA82846B 9 1892.9 2 21.1 N1-[7-(tert-butoxycarboxamido)-n-heptanoyl]- [p-(p-chlorophenyl)benzyl]desleucylA82846B 10 1793.5 3 14.9 N1-(7-amino-n-heptanoyl)-NDISACC-[p-(p- chlorophenyl)benzyl]desleucylA82846B TABLE II: AMINO ACID DERIVATIVES Example # FAB-MS M + X HPLC, min Compound Name 11 1845.5 3 18.3 N1-(N-BOC-L-leucine) derivative of NDISACC-(p- phenylbenzyl)desleucylA82846B 12 1729.3 3 14.2 N1-D-proline derivative of NDISACC-(p- phenylbenzyl)desleucylA82846B 13 1745.4 3 14.2 N1-D-leucine derivative of NDISACC-(p- phenylbenzyl)desleucylA82846B 14 1679.6 3 13.3 N1-(N-BOC-D-leucine) derivative of desleucylA82846@ 15 1863.3 3 18.0 N1-(N-BOC-D-methionine) derivative of NDISACC-(p- phenylbenzyl)desleucylA82846B 16 1794.7 3 14.9 N1-(N,N'-DIBOC-D-lysine) derivative of desleucylA82@ 17 1579.2 3 8.5 N1-D-leucine derivative of desleucylA82846B 18 1845.5 3 18.3 N1-(N-BOC-D-leucine) derivative of NDISACC-(p- phenylbenzyl)desleucylA82846B 19 1960.4 3 19.2 N1-(N,N'-DIBOC-D-lysine) derivative of NDISACC-(p- phenylbenzyl)desleucylA82846B 20 1747.2 3 15.6 N1-[N-BOC-D-3-(p-chlorophenyl)alanine] derivative of desleucylA82846B 21 1913.5 3 19.6 N1-[N-BOC-D-3-(p-chlorophenyl)alanine] derivative of (p-phenylbenzyl)desleucylA82846B 22 1813.5 3 14.4 N1-[D-3-(p-chlorophenyl)alanine] derivative of NDISACC@ phenylbenzyl)desleucylA82846B TABLE II (continued) Example # FAB-MS M + X HPLC, min Compound Name 23 17604 3 12.9 N1-D-lysine derivative of NDISACC-(p- phenylbenzyl)desleucylA82846B 24 1663.1 3 11.6 N1-(N-BOC-D-proline) derivative of desleucylA82846@ 25 1919.3 4 18.7 N1-(N-BOC-D-tryptophan) derivative of NDISACC-(p- phenylbenzyl)desleucylA82846B 26 1830.1 3 17.7 N1-(N-BOC-D-proline) derivative of NDISACC-(p- phenylbenzyl)desleucylA82846B 27 1745.2 3 15.1 N1-L-leucine derivative of NDISACC-(p- phenylbenzyl)desleucylA82846B 28 1913.4 3 19.4 N1-[N-BOC-L-proline) derivative of NDISACC-(p- phenylbenzyl)desleucylA82846B 30 1960.5 3 19.1 N1-(N,N'-DIBOC-L-lysine) derivative of NDISACC-(p- phenylbenzyl)desleucylA82846B 31 1760.4 3 13.3 N1-L-lysine derivative of NDISACC-(p- phenylbenzyl)desleucylA82846B 32 1729.4 3 14.3 N1-L-proline derivative of NDISACC-(p- phenylbenzyl)desleucylA82846B 33 1813.3 3 16.2 N1-[L-3-(p-chlorophenyl)alanine] derivative of NDISACC@ phenylbenzyl)desleucylA82846B TABLE II (Continued) Example # FAB-MS M + X MPLC, min Compound Name 34 1745.4 3 13.3 N1-[N-(p-phenylbenzyl)-D-leucine] derivative of desleucylA82846B 35 1911.6 3 17.9 N1-[N-(p-phenylbenzyl)-D-leucine] derivativeof NDISACC@ phenylbenzyl)desleucylA82846B 36 1536.5 3 16.5 N1-(N-BOC-D-lucine) derivative of desepivancosaminyl@ desleucylA82846B 37 1436.3 3 9.1 N1-D-leucine derivative of desepivancosaminyl- desleucylA82846B 38 1747.4 3 14.5 N1-(N-n-hexyl-D-leucine) derivative of NDISACC-n-hexy@ desleucylA82846B 39 1661.7 1 11.0 N1-(N-n-hexyl-D-leucine) derivative of desleucylA8284@ 40 1727.3 3 14.8 N1-[N-BOC-N-methyl-D-phenylalanine) derivative of desleucylA82846B 41 1679.2 3 14.1 N1-(N-BOC-N-methyl-D-valine) derivative of desleucylA@ 42 1577.3 1 7.7 N1-(N-methyl-D-valine) derivative of desleucylA82846B

The compounds of the present invention are useful for the treatment of bacterial infections. Therefore, in another embodiment, the present invention is directed to a method for controlling a bacterial infection in a host animal, typically a warm-blooded animal, which comprises administering to the host animal an effective, antibacterial amount of a compound of the present invention. In this embodiment, the compounds can be used to control and treat infections due to various bacteria, but especially gram- positive bacteria. In a preferred embodiment, the compounds are used to control and treat infections due to bacteria resistant to existing antibacterials. For example, certain bacteria are resistant to methicillin, and yet others are resistant to vancomycin and/or teicoplanin. The present compounds provide a technique for controlling and treating infections due to such resistant bacterial species.

In carrying out this embodiment of the invention, the compounds of the present invention can be administered by any of the conventional techniques, including the oral route and parenteral routes such as intravenous and intramuscular.

The amount of compound to be employed is not critical and will vary depending on the particular compound employed, the route of administration, the severity of the infection, the interval between dosings, and other factors known to those skilled in the art. In general, a dose of from about 0.5 to about 100 mg/kg will be effective; and in many situations, lesser doses of from about 0.5 to about 50 mg/kg will be effective. A compound of the present invention can be administered in a single dose, but in the known manner of

antibacterial therapy, a compound of the present invention is typically administered repeatedly over a period of time, such as a matter of days or weeks, to ensure control of the bacterial infection.

Also in accordance with known antibacterial therapy, a compound of the present invention is typically formulated for convenient delivery of the requisite dose. Therefore, in another embodiment, the present invention is directed to a pharmaceutical formulation comprising a compound of the present invention, in combination with a pharmaceutically- acceptable carrier. Such carriers are well known for both oral and parenteral routes of delivery. In general, a formulation will comprise a compound of the present invention in a concentration of from about 0.1 to about 900 by weight, and often from about 1.0 to about 30.

The antibacterial efficacy of the present compounds is illustrated by Table III. The minimal inhibitory concentrations (MICs) were determined using a standard broth micro-dilution assay.

TABLE III: ACTIVITY OF SIMPLE ACYL DERIVATIVES* Example # Resistant Sensitive SA 446 SA 489 SA 447 SA X400 SA X778 SA 491 1 >128 4 1 0.5 0.25 0.5 0.125 0.5 2 >128 1.5 #.06 #.06 #.06 #.06 #.06 #.06 3 6.7 2.6 1 1 1 1 1 1 4 >128 4 1 0.5 1 0.25 0.5 0.125 5 27 0.44 0.125 0.125 #.06 #.06 0.125 #.06 6 38 3.5 1 2 2 1 0.5 0.5 7 3.4 0.22 0.5 1 0.5 0.5 1 0.125 8 4 2 16 8 8 8 4 4 9 4.8 0.66 2 1 2 2 1 1 10 5.7 0.57 Example # SA 1199A SH 105 SH 415 SE 270 EF 180 EF 180-1 EF 2041 EF 276 EG 245 1 #.06 2 4 0.5 64 0.125 0.125 0.125 2 2 #.06 1 8 0.125 8 #.06 #.06 #.06 0.25 3 0.5 1 2 1 1 #.06 0.5 0.5 2 4 0.5 0.25 16 0.5 >64 0.5 1 0.5 4 5 #.06 #.06 1 0.25 4 #.06 #.06 1 0.25 6 0.125 0.5 2 0.5 2 0.25 2 2 1 7 #.06 #.06 1 #.06 1 #.06 #.06 #.06 #.06 8 2 2 8 8 2 1 2 1 2 9 0.25 0.5 1 1 2 0.5 0.5 1 1 10 TABLE IV: ACTIVITY OF AMINO ACID DERIVATIVES* Example # Resistant Sensitive SA 446 SA 489 SA 447 SA X400 SA X778 SA 491 11 45 1.7 1 2 1 1 0.5 2 12 2.8 0.19 2 2 0.5 1 0.25 0.5 13 2.4 0.095 1 0.5 1 0.5 1 1 14 >128 6.1 15 27 1.2 1 1 1 1 0.5 1 16 >128 7 17 >32 0.5 0.5 0.06 0.5 0.06n 0.06 0.125 18 27 0.87 0.5 0.125 0.5 0.25 0.25 #.06 19 64 2.6 2 1 2 2 2 1 20 >128 2 0.5 #.06 0.25 #.06 0.25 #.06 21 11 1.5 0.5 0.25 0.5 0.5 0.5 0.5 Example # SA 1199A SH 105 SH 415 SE 270 EF 180 EF 180-1 EF 2041 EF 276 EG 24@ 11 1 0.5 1 0.5 8 0.25 1 2 1 12 0.25 0.125 0.25 0.125 1 #.06 0.25 1 0.25 13 0.25 1 0.5 0.25 0.25 #.06 #.06 0.5 #.06 14 15 0.125 1 1 0.25 8 #.06 0.25 0.5 1 16 17 #.06 0.5 1 0.25 1 #.06 #.06 0.06 0.06 18 no growth 1 1 0.25 2 0.5 #.06 0.5 1 19 no growth 4 4 2 8 1 0.5 2 2 20 no growth 8 16 0.125 16 0.25 #.06 0.125 0.5 21 no growth 2 2 0.5 1 0.5 0.5 1 1 TABLE IV (continued) Example # Resistant Sensitive SA 446 SA 489 SA 447 SA X400 SA X778 SA 491 22 6.7 0.66 1 1 1 0.5 1 0.5 23 2 0.29 1 0.5 1 2 2 0.5 24 >128 4 4 2 4 2 1 1 25 27 1.3 4 1 2 2 2 2 26 23 0.76 2 0.5 1 0.5 0.5 #.06 27 16 1 2 4 1 2 1 1 28 13 1.7 4 1 2 2 1 2 29 27 1.2 2 0.25 0.5 0.25 0.125 #.06 30 38 2.3 8 1 2 2 1 2 31 5.6 0.33 0.5 2 2 2 0.5 0.5 Example # SA 1199A SH 105 SH 415 SE 270 EF 180 EF 180-1 EF 2041 EF 276 EG 245@ 22 0.25 2 4 0.25 2 #.06 1 1 0.25 23 0.25 1 1 0.125 0.5 #.06 0.5 0.25 0.125 24 1 16 32 2 >64 1 1 1 8 25 0.5 2 4 2 8 #.06 1 2 2 26 0.125 1 2 0.25 4 #.06 0.25 1 0.5 27 0.5 0.125 2 0.25 4 0.25 1 1 0.5 28 1 2 4 1 2 0.5 2 1 2 29 #.06 0.125 0.5 #.06 4 #.06 0.125 0.25 2 30 1 2 2 1 0 0.5 1 2 2 31 0.25 0.5 2 0.5 1 0.25 1 2 0.5 TABLE IV (continued) Example # Resistant Sensitive SA 446 Sa 489 SA 447 SA X400 SA X778 SA 491 32 16 0.76 1 1 1 2 0.5 0.125 33 27 2.6 1 2 1 1 1 0.5 34 38 0.44 0.125 #.06 0.125 #.06#.06 #.06 35 4.8 0.66 2 2 2 2 1 1 36 >128 16 8 4 16 4 4 2 37 >32 0.87 0.5 0.25 1 0.25 0.25 0.5 38 6.7 0.19 1 0.25 1 1 0.5 #.06 39 45 0.38 #.06 #.06 0.5 #.06 #.06 #.06 40 >128 9.2 4 4 8 4 4 2 41 >128 84 32 16 32 16 8 4 42 128 0.66 0.5 0.5 0.5 0.5 2 1 Example # SA 1199A SH 105 SH 415 SE 270 EF 180 EF 180-1 EF 2041 EF 276 EG 24@ 32 #.06 0.125 0.5 0.125 2 0.125 1 2 0.5 33 0.25 0.5 0.5 0.25 4 0.5 2 4 1 34 #.06 #.06 4 0.25 2 #.06 0.25 #.06 #.06 35 1 0.5 2 1 1 0.25 0.5 1 1 36 4 2 >64 16 >64 4 8 4 16 37 0.125 0.25 4 0.5 >64 0.25 0.5 0.25 0.5 38 #.06 1 1 1 2 no growth #.06 0.25 0.5 39 #.06 0.5 2 0.25 2 no growth #.06 #.06 0.5 40 2 4 64 4 >64 4 2 1 16 41 8 16 64 8 >64 4 8 8 >64 42 0.5 1 1 64 *Abbreviations Organism Resistant Enterococcus faecium and faecalis (geometric mean of 4-6 isolates) Sensitive Enterococcus faecium and faecalis (geometric mean of 4-6 isolates) SA 446 Staphylococcus aureus 446 SA 489 Staphylococcus aureus 489 SA 447 Staphylococcus aureus 447 SA X400 Staphylococcus aureus X400 SA X778 Staphylococcus aureus X778 SA 491 Staphylococcus aureus 491 SA S13E Staphylococcus aureus S13E SA 1199 Staphylococcus aureus SA1199 SA 1199A Staphylococcus aureus SA1199A SH 105 Staphylococcus haemolyticus 105 SH 415 Staphylococcus haemolyticus 415 SE 270 Staphylococcus epidermidis 270 EF 180 Enterococcus faecium 180 EF 180-1 Enterococcus faecium 180-1 EF 2041 Enterococcus faecalis 2041 EF 276 Enterococcus faecalis 276 EG 245 Enterococcus gallinarum 245 HFRD Haemophilus influenzae RD EC 14 Escherichia coli EC14