Methods of treating bacterial infections
Methods of treating or ameliorating urinary tract infection (UTI), including complicated urinary tract infection (cUTI) and acute pyelonephritis (AP), comprising administering a composition comprising a cyclic boronic acid ester vaborbactam in combination with meropenem are disclosed herewith.
1 . A method of treating or ameliorating complicated urinary tract infection (cUTI) or acute pyelonephritis (AP) in a subject in need thereof, comprising administering a combination of an amount of vaborbactam or a pharmaceutically acceptable salt thereof and an amount of meropenem to the subject, wherein the subject has a Charlson comorbidity score equal to or greater than 3.
2 . The method of claim 1 , wherein the subject is suffering from cUTI.
3 . The method of claim 1 , wherein the subject is suffering from AP.
4 . The method of claim 1 , wherein the subject is also suffering from concomitant bacteremia.
5 . The method of claim 1 , wherein the administration continues for at least five days.
6 . The method of claim 1 , wherein the subject is a female.
7 . The method of claim 1 , wherein the subject has a creatinine clearance rate of equal to or greater than 40 mL/min.
8 . The method of claim 1 , wherein the subject has a creatinine clearance rate of equal to or greater than 30 mL/min.
9 . The method of claim 1 , wherein the subject has a systemic inflammatory response syndrome (SIRS).
10 . A method of treating or ameliorating complicated urinary tract infection (cUTI) or acute pyelonephritis (AP) in a subject in need thereof, comprising:
selecting for treatment a subject having a systemic inflammatory response syndrome (SIRS) who is also suffering from cUTI or AP; and
administering a combination of an amount of vaborbactam or a pharmaceutically acceptable salt thereof and an amount of meropenem to the subject, wherein the subject has a Charlson comorbidity score equal to or greater than 3.
11 . The method of claim 10 , wherein the subject has one or more of the following characteristics at the time of treatment: body temperature less than 36° C. or more than 38° C., heart rate more than 90 bpm, respiratory rate greater than 20 breaths/min, an arterial partial pressure of carbon dioxide less than 4.3 kPa (32 mmHg), white blood cell count more than 12,000 cells/mm 3 or less than 4,000 cells/mm 3 , or the presence of greater than 10% immature neutrophils.
12 . A method of treating or ameliorating complicated urinary tract infection (cUTI) or acute pyelonephritis (AP) in a subject in need thereof, comprising:
selecting for treatment a subject having a Charlson comorbidity score of equal to or greater than 3, who is also suffering from cUTI or AP; and
administering a combination of an amount of vaborbactam or a pharmaceutically acceptable salt thereof and an amount of meropenem to the subject.
13 . The method of claim 12 , wherein the subject is also suffering from concomitant bacteremia.
14 . The method of claim 12 , wherein the administration continues for at least five days.
15 . The method of claim 12 , wherein the subject has a creatinine clearance rate of equal to or greater than 40 mL/min.
16 . The method of claim 12 , wherein the subject has a creatinine clearance rate of equal to or greater than 30 mL/min.
17 . The method of claim 1 , wherein the cUTI or AP is caused by a baseline pathogen selected from the group consisting of E. coli, K. pneumoniae, Enterococcus faecalis, Proteus mirabilis, Enterobacter cloacae species complex, and P. aeruginosa , or combinations thereof.
18 . A method of treating or ameliorating a serious infection due to carbapenem-resistant enterobacteriaceae (CRE) in a subject in need thereof, comprising:
selecting for treatment a subject having a CRE infection that requires at least 7 days of treatment with intravenous antibiotics; and
administering a combination of an amount of vaborbactam or a pharmaceutically acceptable salt thereof and an amount of meropenem to the subject.
19 . The method of claim 18 , wherein the CRE infection is selected from the group consisting of cUTI, AP, cIAI, HABP, VABP, and bacteremia, and combinations thereof.
20 . The method of claim 18 , wherein the method provides less adverse events in the treatment of the CRE infection as compared to a subject treated with best available therapy.
21 . The method of claim 18 , wherein the method provides a higher success rate in the treatment of the CRE infection as compared to a subject treated with best available therapy.
22 . The method of claim 21 , wherein the best available therapy is selected from the group consisting of ciprofloxacin, polymyxin B, colistin, amikacin, meropenem, gentamicin, ertapenem, tigecycline, and ceftazidime-avibactam, and combinations thereof.
23 . The method of claim 18 , wherein the subject has a Charlson comorbidity score of equal to or greater than 3.
24 . The method of claim 23 , wherein the subject has a Charlson comorbidity score of equal to or greater than 5.
25 . The method of claim 18 , wherein the subject has a systemic inflammatory response syndrome (SIRS).
26 . The method of claim 18 , wherein the amount of vaborbactam or the pharmaceutically acceptable salt thereof is about 2 g.
27 . The method of claim 18 , wherein the amount of meropenem is about 2 g.
28 . The method of claim 18 , wherein the combination is administered at least once per day.
29 . The method of claim 28 , wherein the combination is administered every 8 hours.
30 . The method of claim 18 , wherein the administration is by intravenous infusion.
31 . The method of claim 30 , wherein the intravenous infusion is completed is about 3 hours.
32 . The method of claim 18 , wherein vaborbactam or the pharmaceutically acceptable salt thereof is administered prior or subsequent to meropenem.
33 . The method of claim 18 , wherein vaborbactam or the pharmaceutically acceptable salt thereof and meropenem are in a single dosage form.
34 . The method of claim 18 , further comprises administering one or more additional medicaments selected from the group consisting of an antibacterial agent, antifungal agent, an antiviral agent, an anti-inflammatory agent, and an anti-allergic agent, and combinations thereof.
35 . The method of claim 10 , wherein the subject is also suffering from concomitant bacteremia.
36 . The method of claim 10 , wherein the administration continues for at least five days.
37 . The method of claim 10 , wherein the subject has a creatinine clearance rate of equal to or greater than 40 mL/min.
38 . The method of claim 10 , wherein the subject has a creatinine clearance rate of equal to or greater than 30 mL/min.
39 . The method of claim 10 , wherein the cUTI or AP is caused by a baseline pathogen selected from the group consisting of E. coli, K. pneumoniae, Enterococcus faecalis, Proteus mirabilis, Enterobacter cloacae species complex, and P. aeruginosa , or combinations thereof.
40 . The method of claim 12 , wherein the cUTI or AP is caused by a baseline pathogen selected from the group consisting of E. coli, K. pneumoniae, Enterococcus faecalis, Proteus mirabilis, Enterobacter cloacae species complex, and P. aeruginosa , or combinations thereof.
41 . The method of claim 21 , wherein the best available therapy is selected from the group consisting of ciprofloxacin, polymyxin B, colistin, amikacin, meropenem, gentamicin, ertapenem, tigecycline, and ceftazidime-avibactam, and combinations thereof.
42 . The method of claim 1 , wherein the amount of vaborbactam or the pharmaceutically acceptable salt thereof is about 2 g.
43 . The method of claim 1 , wherein the amount of meropenem is about 2 g.
44 . The method of claim 1 , wherein the combination is administered at least once per day.
45 . The method of claim 44 , wherein the combination is administered every 8 hours.
46 . The method of claim 1 , wherein the administration is by intravenous infusion.
47 . The method of claim 46 , wherein the intravenous infusion is completed in about 3 hours.
48 . The method of claim 1 , wherein vaborbactam or the pharmaceutically acceptable salt thereof is administered prior or subsequent to meropenem.
49 . The method of claim 1 , wherein vaborbactam or the pharmaceutically acceptable salt thereof and meropenem are in a single dosage form.
50 . The method of claim 1 , further comprises administering one or more additional medicaments selected from the group consisting of an antibacterial agent, antifungal agent, an antiviral agent, an anti-inflammatory agent, and an anti-allergic agent, and combinations thereof.
51 . The method of claim 10 , wherein the amount of vaborbactam or the pharmaceutically acceptable salt thereof is about 2 g.
52 . The method of claim 10 , wherein the amount of meropenem is about 2 g.
53 . The method of claim 10 , wherein the combination is administered at least once per day.
54 . The method of claim 53 , wherein the combination is administered every 8 hours.
55 . The method of claim 10 , wherein the administration is by intravenous infusion.
56 . The method of claim 55 , wherein the intravenous infusion is completed in about 3 hours.
57 . The method of claim 10 , wherein vaborbactam or the pharmaceutically acceptable salt thereof is administered prior or subsequent to meropenem.
58 . The method of claim 10 , wherein vaborbactam or the pharmaceutically acceptable salt thereof and meropenem are in a single dosage form.
59 . The method of claim 10 , further comprises administering one or more additional medicaments selected from the group consisting of an antibacterial agent, antifungal agent, an antiviral agent, an anti-inflammatory agent, and an anti-allergic agent, and combinations thereof.
60 . The method of claim 12 , wherein the amount of vaborbactam or the pharmaceutically acceptable salt thereof is about 2 g.
61 . The method of claim 12 , wherein the amount of meropenem is about 2 g.
62 . The method of claim 12 , wherein the combination is administered at least once per day.
63 . The method of claim 62 , wherein the combination is administered every 8 hours.
64 . The method of claim 12 , wherein the administration is by intravenous infusion.
65 . The method of claim 64 , wherein the intravenous infusion is completed in about 3 hours.
66 . The method of claim 12 , wherein vaborbactam or the pharmaceutically acceptable salt thereof is administered prior or subsequent to meropenem.
67 . The method of claim 12 , wherein vaborbactam or the pharmaceutically acceptable salt thereof and meropenem are in a single dosage form.
68 . The method of claim 12 , further comprises administering one or more additional medicaments selected from the group consisting of an antibacterial agent, antifungal agent, an antiviral agent, an anti-inflammatory agent, and an anti-allergic agent, and combinations thereof.
69 . The method of claim 1 , wherein the subject is a human suffering from moderate or severe liver disease.