Abstract
New regimens based on 2 or more novel agents are sought to shorten or to simplify treatment of tuberculosis (TB), including drug-resistant forms. Prior studies showed that the novel combinations of bedaquiline (BDQ) plus pretomanid (PMD) plus pyrazinamide (PZA) and PMD plus moxifloxacin (MXF) plus PZA shortened the treatment duration necessary to prevent relapse by 2 to 3 months and 1 to 2 months, respectively, compared with the current first-line regimen, in a murine TB model. These 3-drug combinations are now being studied in clinical trials. Here, the 4-drug combination of BDQPMDMXFPZA was compared to its 3-drug component regimens and different treatment durations of PZA and MXF were explored, to identify the optimal regimens and treatment times and to estimate the likelihood of success against drug-resistant strains. BDQPMDMXFPZA rendered all mice relapse-free after 2 months of treatment. PZA administration could be discontinued after the first month of treatment without worsening outcomes, whereas the absence of MXF, PZA, or BDQ administration from the beginning necessitated approximately 0.5, 1, or 2 months, respectively, of additional treatment to attain the same outcome.
| Original language | English (US) |
|---|---|
| Article number | e00913-17 |
| Journal | Antimicrobial Agents and Chemotherapy |
| Volume | 61 |
| Issue number | 9 |
| DOIs | |
| State | Published - Sep 1 2017 |
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Keywords
- Bedaquliine
- Mouse
- Moxifloxacin
- Mycobacterium tuberculosis
- Pretomanid
- Pyrazinamide
ASJC Scopus subject areas
- Pharmacology
- Pharmacology (medical)
- Infectious Diseases
Cite this
Bactericidal and sterilizing activity of a novel regimen with bedaquiline, pretomanid, moxifloxacin, and pyrazinamide in a murine model of tuberculosis. / Li, Si Yang; Tasneen, Rokeya; Tyagi, Sandeep; Soni, Heena; Converse, Paul J.; Mdluli, Khisimuzi; Nuermberger, Eric.
In: Antimicrobial Agents and Chemotherapy, Vol. 61, No. 9, e00913-17, 01.09.2017.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Bactericidal and sterilizing activity of a novel regimen with bedaquiline, pretomanid, moxifloxacin, and pyrazinamide in a murine model of tuberculosis
AU - Li, Si Yang
AU - Tasneen, Rokeya
AU - Tyagi, Sandeep
AU - Soni, Heena
AU - Converse, Paul J.
AU - Mdluli, Khisimuzi
AU - Nuermberger, Eric
PY - 2017/9/1
Y1 - 2017/9/1
N2 - New regimens based on 2 or more novel agents are sought to shorten or to simplify treatment of tuberculosis (TB), including drug-resistant forms. Prior studies showed that the novel combinations of bedaquiline (BDQ) plus pretomanid (PMD) plus pyrazinamide (PZA) and PMD plus moxifloxacin (MXF) plus PZA shortened the treatment duration necessary to prevent relapse by 2 to 3 months and 1 to 2 months, respectively, compared with the current first-line regimen, in a murine TB model. These 3-drug combinations are now being studied in clinical trials. Here, the 4-drug combination of BDQPMDMXFPZA was compared to its 3-drug component regimens and different treatment durations of PZA and MXF were explored, to identify the optimal regimens and treatment times and to estimate the likelihood of success against drug-resistant strains. BDQPMDMXFPZA rendered all mice relapse-free after 2 months of treatment. PZA administration could be discontinued after the first month of treatment without worsening outcomes, whereas the absence of MXF, PZA, or BDQ administration from the beginning necessitated approximately 0.5, 1, or 2 months, respectively, of additional treatment to attain the same outcome.
AB - New regimens based on 2 or more novel agents are sought to shorten or to simplify treatment of tuberculosis (TB), including drug-resistant forms. Prior studies showed that the novel combinations of bedaquiline (BDQ) plus pretomanid (PMD) plus pyrazinamide (PZA) and PMD plus moxifloxacin (MXF) plus PZA shortened the treatment duration necessary to prevent relapse by 2 to 3 months and 1 to 2 months, respectively, compared with the current first-line regimen, in a murine TB model. These 3-drug combinations are now being studied in clinical trials. Here, the 4-drug combination of BDQPMDMXFPZA was compared to its 3-drug component regimens and different treatment durations of PZA and MXF were explored, to identify the optimal regimens and treatment times and to estimate the likelihood of success against drug-resistant strains. BDQPMDMXFPZA rendered all mice relapse-free after 2 months of treatment. PZA administration could be discontinued after the first month of treatment without worsening outcomes, whereas the absence of MXF, PZA, or BDQ administration from the beginning necessitated approximately 0.5, 1, or 2 months, respectively, of additional treatment to attain the same outcome.
KW - Bedaquliine
KW - Mouse
KW - Moxifloxacin
KW - Mycobacterium tuberculosis
KW - Pretomanid
KW - Pyrazinamide
UR - http://www.scopus.com/inward/record.url?scp=85028317237&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85028317237&partnerID=8YFLogxK
U2 - 10.1128/AAC.00913-17
DO - 10.1128/AAC.00913-17
M3 - Article
C2 - 28630203
AN - SCOPUS:85028317237
VL - 61
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
SN - 0066-4804
IS - 9
M1 - e00913-17
ER -