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COMBINATION THERAPY WITH AMIDINE SUBSTITUTED beta-LACTAM COMPOUNDS AND beta-LACTAMASE INHIBITORS FOR INFECTIONS WITH ANTIBIOTIC RESISTANT BACTERIAL STRAINS

A technology of lactamase and inhibitor, applied in the field of beta-lactam compounds, can solve problems such as multi-drug resistance and rare infection

Inactive Publication Date: 2019-10-08
AICURIS GMBH & CO KG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Infections caused by New Delhi metallo-(NDM) beta-lactamase producers are relatively rare; however, these isolates are highly multidrug resistant [12]

Method used

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  • COMBINATION THERAPY WITH AMIDINE SUBSTITUTED beta-LACTAM COMPOUNDS AND beta-LACTAMASE INHIBITORS FOR INFECTIONS WITH ANTIBIOTIC RESISTANT BACTERIAL STRAINS
  • COMBINATION THERAPY WITH AMIDINE SUBSTITUTED beta-LACTAM COMPOUNDS AND beta-LACTAMASE INHIBITORS FOR INFECTIONS WITH ANTIBIOTIC RESISTANT BACTERIAL STRAINS
  • COMBINATION THERAPY WITH AMIDINE SUBSTITUTED beta-LACTAM COMPOUNDS AND beta-LACTAMASE INHIBITORS FOR INFECTIONS WITH ANTIBIOTIC RESISTANT BACTERIAL STRAINS

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0124] Compounds of formula (I-a, I-c, I-e and I-g) alone and in combination with clavulanic acid, tazobactam or sulbactam and alone and in combination with clavulanic acid, tazobactam or sulbactam The activity of the reference antibiotics against ESBL producing strains with β-lactamases belonging to different families (Table 1). Aztreonam was chosen as a reference for marketed monobactam antibiotics, ceftazidime as a reference for marketed cephalosporins, and piperacillin as a reference for marketed penicillin antibiotics (the latter can also be compared with BLI tazobactam obtained in combination).

[0125] Table 1 – Effects in ESBL producing strains

[0126]

[0127]

Embodiment 2

[0129] Analysis of compounds (I-a, I-c, I-e and I-g) in combination with clavulanic acid, tazobactam or sulbactam in strains producing ESBL and a different class of second β-lactamase. For clinical strains producing ESBLs and a second β-lactamase of a different class, it was surprisingly found that compounds of formula (I-a, I-c, I-e and I-g) + tazoba The combination of sulbactam or the compound of formula (I-a, I-c, I-e and I-g) + clavulanic acid or the combination of compound of formula (I-a, I-c, I-e and I-g) + sulbactam compared with the combination of the corresponding BLI The reference antibiotics all showed lower MICs.

[0130] Table 2 – Effects in ESBL+AmpC (Category C) co-producing strains

[0131]

[0132]

[0133] Table 3 – Effects in ESBL+KPC (class A carbapenemase) co-producing strains

[0134]

[0135]

[0136] Table 4 – Effects in ESBL+OXA-48 (D-class carbapenemase) co-producing strains

[0137]

[0138]

[0139] Table 5 – Effects in E...

Embodiment 3

[0143] Time-kill kinetics of E. cloacae (E. cloacae) 23 (SHV-12) were produced using Compound I-g alone and in combination with 4 μg / mL tazobactam or 2 μg / mL clavulanic acid, The results are shown in figure 1 middle.

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Abstract

This invention relates to beta-lactam compounds in combination with further drugs, e.g. beta-lactamase inhibitors (BLIs), for use in the treatment and prophylaxis of infections caused by resistant bacteria.

Description

technical field [0001] The present invention relates to β-lactam compounds in combination with other drugs such as β-lactamase inhibitors (BLIs) for the treatment and prevention of infections caused by drug-resistant bacteria. Background technique [0002] Public health experts and officials consider the emergence and spread of antibiotic-resistant bacteria to be one of the major public health challenges of the 21st century. Although not a new phenomenon per se, the spread of antibiotic-resistant bacteria has reached unprecedented levels. Although most drug-resistant isolates still occur in hospital settings, physicians and epidemiologists are encountering increasing numbers of drug-resistant bacteria in the community, among people with no previous health care exposure. [0003] The number of patients dying from untreatable nosocomial infections continues to increase. Treatment options are particularly limited for infections caused by multidrug-resistant Gram-negative path...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D417/12A61K31/427A61P31/04
CPCC07D417/12A61P31/04A61P43/00Y02A50/30A61K31/427A61K31/424A61K31/43A61K31/431A61K31/454A61K45/06
Inventor 伊瑞斯·维甘德强·旺丹妮拉·M·劳施
Owner AICURIS GMBH & CO KG
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