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Chemical Structure| 161715-21-5 Chemical Structure| 161715-21-5

Structure of Tebipenem
CAS No.: 161715-21-5

Chemical Structure| 161715-21-5

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Tebipenem is a broad-spectrum antibiotic, from the carbapenem subgroup of β-lactam antibiotics.

Synonyms: LJC 11036

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Quan, Diana H ; Wang, Trixie ; Martinez, Elena ; Kim, Hanna Y ; Sintchenko, Vitali ; Britton, Warwick J , et al.

Abstract: The significant global impact of tuberculosis (TB) on human health is exacerbated by the increasing prevalence of multidrug resistant tuberculosis (MDR-TB) and the challenges of novel drug discovery for the treatment of drug-susceptible and drug-resistant strains of M. tuberculosis. Rifampicin is a key first-line TB drug and rifampicin resistance is a major obstacle to treating MDR-TB. Utilising existing antimicrobial drugs to supplement combination therapy and overcome rifampicin resistance is a promising solution due to their widespread availability and proven clinical safety profile. Therefore, this study aimed to explore the feasibility of using beta-lactam/beta-lactamase inhibitor combinations with rifampicin to inhibit the growth of multidrug-resistant M. tuberculosis. Based on inhibitory concentration (IC), oral bioavailability, pricing, commercial availability, five beta-lactams and the beta-lactamase inhibitor, clavulanate, were selected for testing. These were combined with rifampicin for in vitro testing against Mycobacterium tuberculosis H37Rv. Resazurin assays and colony forming unit (CFU) enumeration were used to quantify drug efficacy, Chou-Talalay calculations were performed to identify drug synergy and Chou-Martin calculations were performed to quantify drug dose reduction index (DRI). The combination of tebipenem-clavulanate/rifampicin and cephradine-clavulanate/rifampicin were found to be synergistic and highly effective against clinical isolates of MDR-TB, overcoming rifampicin resistance in vitro. Beta-lactam synergy may provide viable combination therapies with rifampicin to address the issue of drug resistance in TB.

Keywords: Tuberculosis ; Drug resistance ; Beta-lactam ; Beta-lactamase inhibitor

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Quan, Diana H ; Wang, Trixie ; Martinez, Elena ; Kim, Hannah Y ; Sintchenko, Vitali ; Britton, Warwick J , et al.

Abstract: Background: The enormous burden of tuberculosis (TB) worldwide is a major challenge to human health, but the costs and risks associated with novel drug discovery have limited treatment options for patients. Repurposing existing antimicrobial drugs offers a promising avenue to expand TB treatment possibilities. This study aimed to explore the activity and synergy of beta- lactams in combination with a beta-lactamase inhibitor, which have been underutilised in TB treatment to date. Methods: Based on inhibitory concentration, oral bioavailability and commercial availability, seven beta-lactams (cefadroxil, , cephradine, cephalexin, cefdinir, V, flucloxacillin), two beta-lactamase inhibitors (avibactam and clavulanate), and three second- line TB drugs (moxifloxacin, and linezolid) were selected for combination in vitro testing against Mycobacterium tuberculosis H37Rv. assays and colony forming unit (CFU) enumeration were used to quantify drug efficacy, Chou-Talalay calculations were performed to identify drug synergy and Chou-Martin calculations were performed to quantify drug dose index (DRI). Results: The order of activity of beta-lactams was > > cephradine > cephalexin > cefdinir > V > flucloxacillin. The addition of clavulanate improved beta-lactam activity to a greater degree than the addition of avibactam. As a result, avibactam was excluded from further investigations, which focused on clavulanate. Synergy was demonstrated for cefdinir/cephradine, cefadroxil/tebipenem, cefadroxil/penicillin V, cefadroxil/cefdinir, cephalexin/tebipenem, cephalexin/penicillin V, cephalexin/cefdinir, cephalexin/cephradine and cefadroxil/cephalexin, all with clavulanate. However, combining beta-lactams with , or resulted in antagonistic effects, except for the combinations of V/levofloxacin, V/moxifloxacin and cefdinir/moxifloxacin. Conclusions: Beta-lactam synergy may provide viable combination therapies for the treatment of TB.

Keywords: tuberculosis, beta-lactam, synergy, combination therapy

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Sayed, Alaa R. M. ; Shah, Nirav R. ; Basso, Kari B. ; Kamat, Manasi ; Jiao, Yuanyuan ; Moya, Bartolome , et al.

Abstract: Mycobacterium abscessus causes serious infections that often require over 18 mo of antibiotic combination therapy. There is no standard regimen for the treatment of M. abscessus infections, and the multitude of combinations that have been used clin. have had low success rates and high rates of toxicities. With β-lactam antibiotics being safe, double β-lactam and β-lactam/β-lactamase inhibitor combinations are of interest for improving the treatment of M. abscessus infections and minimizing toxicity. However, a mechanistic approach for building these combinations is lacking since little is known about which penicillin-binding protein (PBP) target receptors are inactivated by different β-lactams in M. abscessus. We determined the preferred PBP targets of 13 β-lactams and 2 β-lactamase inhibitors in two M. abscessus strains and identified PBP sequences by proteomics. The Bocillin FL binding assay was used to determine the β-lactam concentrations that half-maximally inhibited Bocillin binding (50% inhibitory concentrations [IC50s]). Principal component anal. identified four clusters of PBP occupancy patterns. Carbapenems inactivated all PBPs at low concentrations (0.016 to 0.5 mg/L) (cluster 1). Cephalosporins (cluster 2) inactivated PonA2, PonA1, and PbpA at low (0.031 to 1 mg/L) (ceftriaxone and cefotaxime) or intermediate (0.35 to 16 mg/L) (ceftazidime and cefoxitin) concentrations Sulbactam, aztreonam, carumonam, mecillinam, and avibactam (cluster 3) inactivated the same PBPs as cephalosporins but required higher concentrations Other penicillins (cluster 4) specifically targeted PbpA at 2 to 16 mg/L. Carbapenems, ceftriaxone, and cefotaxime were the most promising β-lactams since they inactivated most or all PBPs at clin. relevant concentrations These first PBP occupancy patterns in M. abscessus provide a mechanistic foundation for selecting and optimizing safe and effective combination therapies with β-lactams.

Keywords: Mycobacterium abscessus ; PbpA ; PonA1 ; PonA2 ; beta-lactams ; cell wall biosynthesis ; drug-resistant bacteria ; penicillin-binding proteins ; principal component analysis ; receptor binding

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Alternative Products

Product Details of Tebipenem

CAS No. :161715-21-5
Formula : C16H21N3O4S2
M.W : 383.49
SMILES Code : O=C(C(N12)=C(SC3CN(C4=NCCS4)C3)[C@H](C)[C@]2([H])[C@@H]([C@H](O)C)C1=O)O
Synonyms :
LJC 11036
MDL No. :MFCD00936545
InChI Key :GXXLUDOKHXEFBQ-YJFSRANCSA-N
Pubchem ID :9800194

Safety of Tebipenem

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Isoform Comparison

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.61mL

0.52mL

0.26mL

13.04mL

2.61mL

1.30mL

26.08mL

5.22mL

2.61mL

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