Meropenem-Vaborbactam vs. Piperacillin-Tazobactam in TANGO I (a Phase 3 Randomized, Double-blind Trial): Outcomes by Baseline MIC in Adults with Complicated Urinary Tract Infections or Acute Pyelonephritis
Abstract Background Meropenem-vaborbactam (M-V) is being developed for gram-negative infections, including complicated urinary tract infections (cUTIs) and multidrug-resistant bacterial infections. TANGO I was a Phase 3, multicenter, double-blind, randomized study of M-V vs. piperacillin-tazobactam...
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Published in | Open forum infectious diseases Vol. 4; no. suppl_1; p. S536 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
US
Oxford University Press
01.10.2017
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Online Access | Get full text |
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Summary: | Abstract
Background
Meropenem-vaborbactam (M-V) is being developed for gram-negative infections, including complicated urinary tract infections (cUTIs) and multidrug-resistant bacterial infections. TANGO I was a Phase 3, multicenter, double-blind, randomized study of M-V vs. piperacillin-tazobactam (P-T) for treatment of adults with cUTI/acute pyelonephritis (AP). Superiority of M-V over P-T at the FDA primary endpoint has been reported. The effect of baseline MICs of Enterobacteriaceae to both study drugs and by susceptibility vs. non-susceptibility to P-T on clinical/microbiological outcome at end of intravenous treatment (EOIVT) was investigated.
Methods
MICs were conducted on baseline urinary isolates using CLSI methods. Susceptibility to P-T was defined as MIC ≤16 µg/mL (FDA/CLSI).
Results
Of 550 subjects randomized, 374 (68.0%) were included in m-MITT (165/192 [85.9%] in M-V and 154/182 [84.6%] in P-T groups had baseline Enterobactericeae). Mean duration of IV therapy was 8 days. Clinical outcomes were >90% across all MICs (Table 1).
Conclusion
At EOIVT, clinical cure and microbial eradication rates were >90% for both groups with no trend in responses according to baseline study drug MIC. M-V is highly active against Enterobacteriaceae in vitro and in patients, and is a potential new treatment option for cUTI/AP.
Disclosures
T. J. Walsh, The Medicines Company: Consultant and Investigator, Consulting fee and Research grant; Astellas: Consultant and Investigator, Consulting fee and Research grant; Allergan: Consultant and Investigator, Consulting fee and Research grant; Merck: Consultant and Investigator, Consulting fee and Research grant; A. F. Shorr, Astellas Pharma Global Development, Inc: Consultant and Speaker’s Bureau, Consulting fee, Research support and Speaker honorarium; Cidara: Consultant, Consulting fee; Merck: Consultant, Scientific Advisor and Speaker’s Bureau, Research support and Speaker honorarium; T. M. File Jr., Allergan: Consultant, Consulting fee; Cempra: Consultant, Consulting fee; The Medicines Company: Consultant, Consulting fee; Merck: Consultant, Consulting fee; MotifBio: Consultant, Consulting fee; Pfizer: Consultant, Consulting fee; Paratek: Consultant, Consulting fee; Nabriva: Investigator, Research grant; J. S. Loutit, The Medicine’s Company: Employee and Shareholder, Salary; O. Lomovskaya, The Medicine’s Company: Employee and Shareholder, Salary; M. N. Dudley, The Medicine’s Company: Employee and Shareholder, Salary
Table 1.
Outcomes by Baseline MIC for Enterobacteriaceae at EOIVT (m-MITT)
M-V
P-T*
MIC
(µg/mL)
Clinical Cure
n/N’ (%)
Microbial Eradication
n/N’ (%)
MIC
(µg/mL)
Clinical Cure
n/N’ (%)
Microbial Eradication
n/N’ (%)
≤0.06
146/149 (98.0)
146/149 (98.0)
≤0.05
10/10 (100)
10/10 (100)
0.12
12/12 (100)
11/12 (91.7)
1
14/15 (93.3)
14/15 (93.3)
0.25
2/2 (100)
2/2 (100)
2
57/60 (95.0)
56/60 (93.3)
0.5
1/1 (100)
1/1 (100)
4
21/22 (95.5)
20/22 (90.9)
32
1/1 (100)
1/1 (100)
8
6/6 (100)
6/6 (100)
16
10/11 (90.9)
10/11 (90.9)
32
10/11 (90.9)
8/11 (72.7)
64
2/2 (100)
2/2 (100)
>64
17/17 (100)
16/17 (94.1)
Totals
162/165 (98.2)
161/165 (97.6)
147/154 (95.5)
142/154 (92.2)
*FDA/CLSI non-susceptibility breakpoint of Enterobacteriaceae to P-T is >16 µg/mL
Although 19.5% of baseline Enterobacteriaceae isolates were non-susceptible to P-T, clinical and microbiologic outcomes were similar for subjects with susceptible and non-susceptible isolates (p > 0.1). |
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ISSN: | 2328-8957 2328-8957 |
DOI: | 10.1093/ofid/ofx163.1396 |