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Last Updated: March 28, 2024

Claims for Patent: 10,183,034


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Summary for Patent: 10,183,034
Title:Therapeutic uses of pharmaceutical compositions comprising cyclic boronic acid ester derivatives
Abstract: Disclosed herein are antimicrobial compounds compositions, pharmaceutical compositions, the use and preparation thereof. Some embodiments relate to cyclic boronic acid ester derivatives and their use as therapeutic agents.
Inventor(s): Hirst; Gavin (San Diego, CA), Reddy; Raja (San Diego, CA), Hecker; Scott (Del Mar, CA), Totrov; Maxim (San Diego, CA), Griffith; David C. (San Marcos, CA), Rodny; Olga (Mill Valley, CA), Dudley; Michael N. (San Diego, CA), Boyer; Serge (San Diego, CA)
Assignee: Rempex Pharmaceuticals, Inc. (Lincolnshire, IL)
Application Number:15/935,782
Patent Claims: 1. A method of treating a bacterial infection in a subject comprising administering to the subject an effective amount of a compound of Formula (I) in combination with an additional medicament selected from the group consisting of an antibacterial agent, antifungal agent, an antiviral agent, an anti-inflammatory agent, or an anti-allergic agent, wherein Formula (I) has the structure: ##STR00209## or a pharmaceutically acceptable salt thereof, wherein: Y is a 1-4 atom alkylene or 2-4 atom alkenylene linker, optionally substituted by one or more substituents selected from the group consisting of Cl, F, CN, CF.sub.3, --R.sup.9, --OR.sup.9, --C(.dbd.O)NR.sup.9R.sup.10, and --C(.dbd.O)OR.sup.9, wherein said alkylene or alkenylene linker is optionally fused to an optionally substituted aryl, optionally substituted heteroaryl, optionally substituted carbocyclyl, or optionally substituted heterocyclyl; R.sup.1 is selected from a group consisting of --C.sub.1-9alkyl, --C.sub.2-9alkenyl, --C.sub.2-9alkynyl, --NR.sup.9R.sup.10, --C.sub.1-9alkylR.sup.11, --C.sub.2-9alkenylR.sup.11, --C.sub.2-9alkynylR.sup.11, -carbocyclyl-R.sup.11, --CH(OH)C.sub.1-9alkylR.sup.9, --CH(OH)C.sub.2-9alkenylR.sup.9, --CH(OH)C.sub.2-9alkynylR.sup.9, --CH(OH)carbocyclyl-R.sup.9, --C(.dbd.O)R.sup.9, --C(.dbd.O)C.sub.1-9alkylR.sup.9, --C(.dbd.O)C.sub.2-9alkenylR.sup.9, --C(.dbd.O)C.sub.2-9alkynylR.sup.9, --C(.dbd.O)C.sub.2-9carbocyclyl-R.sup.9, --C(.dbd.O)NR.sup.9R.sup.10, --N(R.sup.9)C(.dbd.O)R.sup.9, --N(R.sup.9)C(.dbd.O)NR.sup.9R.sup.10, --N(R.sup.9)C(.dbd.O)OR.sup.9, --N(R.sup.9)C(.dbd.O)C(.dbd.NR.sup.10)R.sup.9, --N(R.sup.9)C(.dbd.O)C(.dbd.CR.sup.9R.sup.10)R.sup.9, --N(R.sup.9)C(.dbd.O)C.sub.1-4alkylN(R.sup.9)C(.dbd.O)R.sup.9, --N(R.sup.9)C(.dbd.NR.sup.10)R.sup.9, --C(.dbd.NR.sup.10)NR.sup.9R.sup.10, --N.dbd.C(R.sup.9)NR.sup.9R.sup.10, --N(R.sup.9)SO.sub.2R.sup.9, --N(R.sup.9)SO.sub.2NR.sup.9R.sup.10, --N.dbd.CHR.sup.9, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted carbocyclyl, and optionally substituted heterocyclyl; R.sup.6 is selected from a group consisting of H, --C.sub.1-9alkyl, C.sub.2-9alkenyl, --C.sub.2-9alkynyl, carbocyclyl, --C.sub.1-9alkylR.sup.11, --C.sub.2-9alkenylR.sup.11, --C.sub.2-9alkynylR.sup.11, carbocyclyl-R.sup.11, --C(.dbd.O)OR.sup.9, --C.sub.1-9alkylCO.sub.2R.sup.9, --C.sub.2-9alkenylCO.sub.2R.sup.9, --C.sub.2-9alkynylCO.sub.2R.sup.9, and -carbocyclyl-CO.sub.2R.sup.9, or alternatively: (i) R.sup.6 and an R.sup.7 are taken together with the atoms to which they are attached to form an optionally substituted carbocyclyl or optionally substituted heterocyclyl, or (ii) R.sup.6 is absent when the carbon to which it is attached is a ring atom in an aryl or heteroaryl ring; each R.sup.7 is independently selected from a group consisting of H, halo, --C.sub.1-9alkyl, --C.sub.2-9alkenyl, --C.sub.2-9alkynyl, --NR.sup.9R.sup.10, --OR.sup.9, --C.sub.1-9alkylCO.sub.2R.sup.9, --C.sub.2-9alkenylCO.sub.2R.sup.9, --C.sub.2-9alkynylCO.sub.2R.sup.9, and -carbocyclyl-CO.sub.2R.sup.9, or independently: (i) R.sup.6 and an R.sup.7 are taken together with the atoms to which they are attached to form an optionally substituted carbocyclyl or optionally substituted heterocyclyl, or (ii) R.sup.7 and an R.sup.8 are taken together with the atoms to which they are attached to form an optionally substituted carbocyclyl or optionally substituted heterocyclyl; each R.sup.8 is independently selected from a group consisting of H, halo, --C.sub.1-9alkyl, --C.sub.2-9alkenyl, --C.sub.2-9alkynyl, --NR.sup.9R.sup.10, --OR.sup.9, --C.sub.1-9alkylCO.sub.2R.sup.9, --C.sub.2-9alkenylCO.sub.2R.sup.9, --C.sub.2-9alkynylCO.sub.2R.sup.9, -carbocyclyl-CO.sub.2R.sup.9, or independently: (i) an R.sup.7 and an R.sup.8 are taken together with the atoms to which they are attached to form an optionally substituted carbocyclyl or optionally substituted heterocyclyl, (ii) a geminal R.sup.7 and R.sup.8 together form --C.sub.2-9 alkenylenylCO.sub.2R.sup.9, or (iii) each R.sup.8 attached to a ring atom forming part of an optionally substituted aryl is absent; each R.sup.9 is independently selected from a group consisting of H, --C.sub.1-9alkyl, C.sub.2-9alkenyl, --C.sub.2-9alkynyl, carbocyclyl, --C.sub.1-9alkylR.sup.11, --C.sub.2-9alkenylR.sup.11, --C.sub.2-9alkynylR.sup.11, -carbocyclyl-R.sup.11, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted carbocyclyl, and optionally substituted heterocyclyl; each R.sup.10 is independently selected from a group consisting of H, --C.sub.1-9alkyl, --OR.sup.9, --CH(.dbd.NH), --C(.dbd.O)OR.sup.9, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted carbocyclyl, and optionally substituted heterocyclyl; each R.sup.11 is independently selected from a group consisting of optionally substituted aryl, optionally substituted heteroaryl, optionally substituted carbocyclyl, and optionally substituted heterocyclyl; X is selected from a group consisting of --CO.sub.2R.sup.12, and a carboxylic acid isostere; R.sup.12 is selected from a group consisting of H, C.sub.1-9alkyl, --(CH.sub.2).sub.0-3--R.sub.11, --C(R.sup.13).sub.2OC(O)C.sub.1-9alkyl, --C(R.sup.13).sub.2OC(O)R.sup.11, --C(R.sup.13).sub.2OC(O)OC.sub.1-9alkyl and --C(R.sup.13).sub.2OC(O)OR.sup.11; each R.sup.13 is independently selected from a group consisting of H and C.sub.1-4alkyl; and m is independently zero or an integer from 1 to 2, wherein each C.sub.1-9alkyl, C.sub.2-9alkenyl, and C.sub.2-9alkynyl is independently optionally substituted.

2. The method of claim 1, wherein the compound has the structure of formula II: ##STR00210## or a pharmaceutically acceptable salt thereof, wherein: the bond represented by a dashed and solid line represents a bond selected from the group consisting of a single bond and a double bond with the proviso that the dashed and solid line can only be a double bond when n is 1; R.sup.1 is selected from a group consisting of --NR.sup.9R.sup.10, --C.sub.1-9alkylR.sup.11, --C.sub.2-9alkenylR.sup.11, --C.sub.2-9alkynylR.sup.11, -carbocyclyl-R.sup.11, --CH(OH)C.sub.1-9alkylR.sup.9, --CH(OH)C.sub.2-9alkenylR.sup.9, --CH(OH)C.sub.2-9alkynylR.sup.9, --CH(OH)carbocyclyl-R.sup.9, --C(.dbd.O)R.sup.9, --C(.dbd.O)C.sub.1-9alkylR.sup.9, --C(.dbd.O)C.sub.2-9alkenylR.sup.9, --C(.dbd.O)C.sub.2-9alkynylR.sup.9, --C(.dbd.O)C.sub.2-9carbocyclyl-R.sup.9, --C(.dbd.O)NR.sup.9R.sup.10, --N(R.sup.9)C(.dbd.O)R.sup.9, --N(R.sup.9)C(.dbd.O)NR.sup.9R.sup.10, --N(R.sup.9)C(.dbd.O)OR.sup.9, --N(R.sup.9)C(.dbd.O)C(.dbd.NR.sup.10)R.sup.9, --N(R.sup.9)C(.dbd.O)C(.dbd.CR.sup.9R.sup.10)R.sup.9, --N(R.sup.9)C(.dbd.O)C.sub.1-4alkylN(R.sup.9)C(.dbd.O)R.sup.9, --N(R.sup.9)C(.dbd.NR.sup.10)R.sup.9, --C(NR.sup.10)NR.sup.9R.sup.10, --N.dbd.C(R.sup.9)NR.sup.9R.sup.10, --N(R.sup.9)SO.sub.2R.sup.9, --N(R.sup.9)SO.sub.2NR.sup.9R.sup.10, --N.dbd.CHR.sup.9, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted carbocyclyl, and optionally substituted heterocyclyl; R.sup.2 and R.sup.4 are independently selected from a group consisting of H, Cl, F, CN, CF.sub.3, --R.sup.9, --OR.sup.9, --C(.dbd.O)NR.sup.9R.sup.10, and --C(.dbd.O)OR.sup.9; R.sup.3 and R.sup.5 are independently selected from a group consisting of H, Cl, F, CN, CF.sub.3, --R.sup.9, --OR.sup.9, --C(.dbd.O)NR.sup.9R.sup.10, and --C(.dbd.O)OR.sup.9, with the proviso that if the bond represented by a dashed and solid line is a double bond then R.sup.3 and R.sup.5 are absent; R.sup.6 is selected from a group consisting of H, --C.sub.1-9alkyl, C.sub.2-9alkenyl, --C.sub.2-9alkynyl, --C.sub.1-9alkylR.sup.11, --C.sub.2-9alkenylR.sup.11, --C.sub.2-9alkynylR.sup.11, --C(.dbd.O)OR.sup.9, and --C.sub.1-9alkylCO.sub.2R.sup.9, --C.sub.2-9alkenylCO.sub.2R.sup.9, and --C.sub.2-9alkynylCO.sub.2R.sup.9; each R.sup.7 is independently selected from a group consisting of H, --NR.sup.9R.sup.10, --OR.sup.9, and --C.sub.1-9alkylCO.sub.2R.sup.9, --C.sub.2-9alkenylCO.sub.2R.sup.9, and --C.sub.2-9alkynylCO.sub.2R.sup.9; each R.sup.8 is independently selected from a group consisting of H, --NR.sup.9R.sup.10, --OR.sup.9, and --C.sub.1-9alkylCO.sub.2R.sup.9, --C.sub.2-9alkenylCO.sub.2R.sup.9, and --C.sub.2-9alkynylCO.sub.2R.sup.9; each R.sup.9 is independently selected from a group consisting of H, --C.sub.1-9alkyl, C.sub.2-9alkenyl, --C.sub.2-9alkynyl, --C.sub.1-9alkylR.sup.11, --C.sub.2-9alkenylR.sup.11, --C.sub.2-9alkynylR.sup.11, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted --(CH.sub.2).sub.0-3carbocyclyl, and optionally substituted heterocyclyl; each R.sup.10 is independently selected from a group consisting of H, --C.sub.1-9alkyl, --OR.sup.9, --CH(.dbd.NH), optionally substituted aryl, optionally substituted heteroaryl, optionally substituted carbocyclyl, and optionally substituted heterocyclyl; X is --CO.sub.2H; and n is independently zero or an integer from 1 to 2.

3. The method of claim 2, wherein n is 1.

4. The method of claim 2, wherein R.sup.2, R.sup.3, R.sup.4, and R.sup.5 are hydrogen.

5. The method of claim 1, wherein the compound has the structure of formula IIIa, IIIb, IVa, IVb, or IVc: ##STR00211## or a pharmaceutically acceptable salt thereof, wherein: the bond represented by a dashed and solid line represents a bond selected from the group consisting of a single bond and a double bond; each R.sup.2 and R.sup.4 are independently selected from a group consisting of H, Cl, F, CN, CF.sub.3, --R.sup.9, --OR.sup.9, --C(.dbd.O)NR.sup.9R.sup.10, and --C(.dbd.O)OR.sup.9; and each R.sup.3 and R.sup.5 are independently selected from a group consisting of H, Cl, F, CN, CF.sub.3, --R.sup.9, --OR.sup.9, --C(.dbd.O)NR.sup.9R.sup.10, and --C(.dbd.O)OR.sup.9, with the proviso that if the bond represented by a dashed and solid line is a double bond then R.sup.3 and R.sup.5 are absent.

6. The method of claim 1, wherein R.sup.1 is --NHC(.dbd.O)C.sub.1-9alkylR.sup.11.

7. The method of claim 6, wherein R.sup.11 is optionally substituted aryl or optionally substituted heteroaryl.

8. The method of claim 7, wherein R.sup.11 is thien-2-yl.

9. The method of claim 1, wherein m is 1.

10. The method of claim 1, wherein R.sup.6 and each R.sup.7 and R.sup.8 is hydrogen.

11. The method of claim 1, wherein X is --CO.sub.2H.

12. The method of claim 1, wherein the compounds has the structure selected from the group consisting of: ##STR00212## ##STR00213## ##STR00214## ##STR00215## ##STR00216## ##STR00217## ##STR00218## ##STR00219## ##STR00220## ##STR00221## ##STR00222## ##STR00223## ##STR00224## ##STR00225## ##STR00226## or a pharmaceutically acceptable salt thereof.

13. The method of claim 1, wherein the compound is: ##STR00227## or a pharmaceutically acceptable salt thereof.

14. The method of claim 1, wherein the additional medicament is a .beta.-lactam antibacterial agent.

15. The method of claim 14, wherein the .beta.-lactam antibacterial agent is a carbapenem selected from the group consisting of simipenem, biapenem, doripenem, meropenem, and ertapenem.

16. The method of claim 15, wherein the carbapenem is meropenem.

17. The method of claim 14, wherein the .beta.-lactam antibacterial agent is selected from the group consisting of Amoxicillin, Ampicillin, Pivampicillin, Hetacillin, Bacampicillin, Metampicillin, Talampicillin, Epicillin, Carbenicillin, Carindacillin, Ticarcillin, Temocillin, Azlocillin, Piperacillin, Mezlocillin, Mecillinam, Pivmecillinam, Sulbenicillin, Benzylpenicillin (G), Clometocillin, Benzathine benzylpenicillin, Procaine benzylpenicillin, Azidocillin, Penamecillin, Phenoxymethylpenicillin (V), Propicillin, Benzathine phenoxymethylpenicillin, Pheneticillin, Cloxacillin, Dicloxacillin, Flucloxacillin, Oxacillin, Meticillin, Nafcillin, Faropenem, Biapenem, Doripenem, Ertapenem, Imipenem, Meropenem, Panipenem, Tomopenem, Razupenem, Cefazolin, Cefacetrile, Cefadroxil, Cefalexin, Cefaloglycin, Cefalonium, Cefaloridine, Cefalotin, Cefapirin, Cefatrizine, Cefazedone, Cefazaflur, Cefradine, Cefroxadine, Ceftezole, Cefaclor, Cefamandole, Cefminox, Cefonicid, Ceforanide, Cefotiam, Cefprozil, Cefbuperazone, Cefuroxime, Cefuzonam, Cefoxitin, Cefotetan, Cefmetazole, Loracarbef, Cefixime, Ceftazidime, Ceftriaxone, Cefcapene, Cefdaloxime, Cefdinir, Cefditoren, Cefetamet, Cefmenoxime, Cefodizime, Cefoperazone, Cefotaxime, Cefpimizole, Cefpiramide, Cefpodoxime, Cefsulodin, Cefteram, Ceftibuten, Ceftiolene, Ceftizoxime, Flomoxef, Latamoxef, Cefepime, Cefozopran, Cefpirome, Cefquinome, Ceftobiprole, Ceftaroline, CXA-101, RWJ-54428, RWJ-333441, ME1036, BAL30072, BAL19764, Ceftiofur, Cefquinome, Cefovecin, Aztreonam, Tigemonam, Carumonam, RWJ-442831, RWJ-333441, and RWJ-333442.

18. The method of claim 1, wherein the bacterial infection comprises a bacteria selected from the group consisting of Acinetobacter baumannii, Acinetobacter calcoaceticus, Acinetobacter haemolyticus, Aeromonas hydrophilia, Bacteroides uniformis, Bacteroides 3452A homology group, Bacteroides distasonis, Bacteroides eggerthii, Bacteroides fragilis, Bacteroides ovalus, Bacteroides splanchnicus, Bacteroides thetaiotaomicron, Bacteroides vulgatus, Bordetella bronchiseptica, Bordetella parapertussis, Bordetella pertussis, Borrelia burgdorferi, Branhamella catarrhalis, Burkholderia cepacia, Campylobacter coli, Campylobacter fetus, Campylobacter jejuni, Citrobacter freundii, Clostridium difficile, Corynebacterium diphtheriae, Corynebacterium ulcerans, Enterobacter aerogenes, Enterobacter cloacae, Enterococcus faecalis, Enterococcus faecium, Escherichia coli, Francisella tularensis, Gardnerella vaginalis, Haemophilus ducreyi, Haemophilus haemolyticus, Haemophilus influenzae, Haemophilus parahaemolyticus, Haemophilus parainfluenzae, Helicobacter pylori, Kingella, Klebsiella oxytoca, Klebsiella pneumoniae, Legionella pneumophila, Listeria monocytogenes, Moraxella, Morganella morganii, Mycobacterium avium, Mycobacterium intracellulare, Mycobacterium leprae, Mycobacterium tuberculosis, Neisseria gonorrhoeae, Neisseria meningitidis, Pasteurella haemolytica, Pasteurella multocida, Proteus mirabilis, Proteus vulgaris, Providencia alcalifaciens, Providencia rettgeri, Providencia stuartii, Pseudomonas acidovorans, Pseudomonas aeruginosa, Pseudomonas alcaligenes, Pseudomonas fluorescens, Pseudomonas putida, Salmonella enteritidis, Salmonella paratyphi, Salmonella typhi, Salmonella typhimurium, Serratia marcescens, Shigella dysenteriae, Shigella flexneri, Shigella sonnei, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus hyicus subsp. hyicus, Staphylococcus intermedius, Staphylococcus saccharolyticus, Staphylococcus saprophyticus, Stenotrophomonas maltophilia, Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes, Vibrio cholerae, Vibrio parahaemolyticus, Yersinia enterocolitica, Yersinia intermedia, Yersinia pestis, and Yersinia pseudotuberculosis.

19. The method of claim 1, wherein the administration is intravenous.

20. The method of claim 1, wherein the compound and the additional medicament are administered concurrently.

21. The method of claim 1, wherein the subject is human.

22. A method of treating a bacterial infection in a subject comprising administering to the subject an effective amount of a compound in combination with meropenem, wherein the compound has the structure: ##STR00228## or a pharmaceutically acceptable salt thereof.

23. The method of claim 22, comprising administering a pharmaceutical composition that comprises the compound, meropenem, and sodium carbonate to the subject.

24. The method of claim 22, wherein the bacterial infection comprises a bacteria selected from the group consisting of Acinetobacter baumannii, Acinetobacter calcoaceticus, Acinetobacter haemolyticus, Aeromonas hydrophilia, Bacteroides uniformis, Bacteroides 3452A homology group, Bacteroides distasonis, Bacteroides eggerthii, Bacteroides fragilis, Bacteroides ovalus, Bacteroides splanchnicus, Bacteroides thetaiotaomicron, Bacteroides vulgatus, Bordetella bronchiseptica, Bordetella parapertussis, Bordetella pertussis, Borrelia burgdorferi, Branhamella catarrhalis, Burkholderia cepacia, Campylobacter coli, Campylobacter fetus, Campylobacter jejuni, Citrobacter freundii, Clostridium difficile, Corynebacterium diphtheriae, Corynebacterium ulcerans, Enterobacter aerogenes, Enterobacter cloacae, Enterococcus faecalis, Enterococcus faecium, Escherichia coli, Francisella tularensis, Gardnerella vaginalis, Haemophilus ducreyi, Haemophilus haemolyticus, Haemophilus influenzae, Haemophilus parahaemolyticus, Haemophilus parainfluenzae, Helicobacter pylori, Kingella, Klebsiella oxytoca, Klebsiella pneumoniae, Legionella pneumophila, Listeria monocytogenes, Moraxella, Morganella morganii, Mycobacterium avium, Mycobacterium intracellulare, Mycobacterium leprae, Mycobacterium tuberculosis, Neisseria gonorrhoeae, Neisseria meningitidis, Pasteurella haemolytica, Pasteurella multocida, Proteus mirabilis, Proteus vulgaris, Providencia alcalifaciens, Providencia rettgeri, Providencia stuartii, Pseudomonas acidovorans, Pseudomonas aeruginosa, Pseudomonas alcaligenes, Pseudomonas fluorescens, Pseudomonas putida, Salmonella enteritidis, Salmonella paratyphi, Salmonella typhi, Salmonella typhimurium, Serratia marcescens, Shigella dysenteriae, Shigella flexneri, Shigella sonnei, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus hyicus subsp. hyicus, Staphylococcus intermedius, Staphylococcus saccharolyticus, Staphylococcus saprophyticus, Stenotrophomonas maltophilia, Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes, Vibrio cholerae, Vibrio parahaemolyticus, Yersinia enterocolitica, Yersinia intermedia, Yersinia pestis, and Yersinia pseudotuberculosis.

25. The method of claim 22, wherein the administration is intravenous.

26. The method of claim 22, wherein the compound and meropenem are administered concurrently.

27. The method of claim 22, wherein the subject is human.

28. A method of treating a bacterial infection in a human subject comprising administering an effective amount of a pharmaceutical composition to the subject, the pharmaceutical composition comprising a compound, meropenem, sodium carbonate and saline, wherein the administration is intravenous, wherein the compound has the structure: ##STR00229## or a pharmaceutically acceptable salt thereof.

29. The method of claim 28, wherein the bacterial infection comprises a bacteria selected from the group consisting of Acinetobacter baumannii, Acinetobacter calcoaceticus, Acinetobacter haemolyticus, Aeromonas hydrophilia, Bacteroides uniformis, Bacteroides 3452A homology group, Bacteroides distasonis, Bacteroides eggerthii, Bacteroides fragilis, Bacteroides ovalus, Bacteroides splanchnicus, Bacteroides thetaiotaomicron, Bacteroides vulgatus, Bordetella bronchiseptica, Bordetella parapertussis, Bordetella pertussis, Borrelia burgdorferi, Branhamella catarrhalis, Burkholderia cepacia, Campylobacter coli, Campylobacter fetus, Campylobacter jejuni, Citrobacter freundii, Clostridium difficile, Corynebacterium diphtheriae, Corynebacterium ulcerans, Enterobacter aerogenes, Enterobacter cloacae, Enterococcus faecalis, Enterococcus faecium, Escherichia coli, Francisella tularensis, Gardnerella vaginalis, Haemophilus ducreyi, Haemophilus haemolyticus, Haemophilus influenzae, Haemophilus parahaemolyticus, Haemophilus parainfluenzae, Helicobacter pylori, Kingella, Klebsiella oxytoca, Klebsiella pneumoniae, Legionella pneumophila, Listeria monocytogenes, Moraxella, Morganella morganii, Mycobacterium avium, Mycobacterium intracellulare, Mycobacterium leprae, Mycobacterium tuberculosis, Neisseria gonorrhoeae, Neisseria meningitidis, Pasteurella haemolytica, Pasteurella multocida, Proteus mirabilis, Proteus vulgaris, Providencia alcalifaciens, Providencia rettgeri, Providencia stuartii, Pseudomonas acidovorans, Pseudomonas aeruginosa, Pseudomonas alcaligenes, Pseudomonas fluorescens, Pseudomonas putida, Salmonella enteritidis, Salmonella paratyphi, Salmonella typhi, Salmonella typhimurium, Serratia marcescens, Shigella dysenteriae, Shigella flexneri, Shigella sonnei, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus hyicus subsp. hyicus, Staphylococcus intermedius, Staphylococcus saccharolyticus, Staphylococcus saprophyticus, Stenotrophomonas maltophilia, Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes, Vibrio cholerae, Vibrio parahaemolyticus, Yersinia enterocolitica, Yersinia intermedia, Yersinia pestis, and Yersinia pseudotuberculosis.

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