Photoactivatable antimicrobial agents and therapeutic and diagnostic methods of using same

Patent metadata

Field	Value
Publication number	US-9828622-B2
Application number	US-99099709-A
Country	US
Kind code	B2
Filing date	May 5, 2009
Priority date	May 5, 2008
Publication date	Nov 28, 2017
Grant date	Nov 28, 2017

Abstract

The present invention provides photosensitizer compounds for use in detecting beta-lactamase activity. Methods and kits that utilize the photosensitizer compounds of the invention for the detection of, quantitation of, and classification or typing of microbial beta-lactamases.

First claim

What is claimed is:

1. A method of measuring susceptibility of beta-lactamase secreting bacteria in a sample to a beta-lactam antibiotic, wherein, the method comprises:
(a) contacting the sample with:
(i) a composition comprising a cephalosporin linker compound linked with two benzophenothiazinium chloride (EtNBS) fluorophores (standard); and
(ii) a composition comprising the beta-lactam antibiotic and the cephalosporin linker compound linked with two EtNBS fluorophores (test sample),
wherein, the EtNBS fluorophores are (Z)-5-((9-(diethylamino)-5H-benzo[a]phenothiazin-5-ylidene)amino)pentanoic acid (EtNBS-COOH) derived fluorophores;
(b) light-activating the standard and the test compositions to produce a fluorescence signal;
(c) quantifying the fluorescence signal with a detector to obtain result;
(d) comparing the test result to the standard result; and
(e) if the amount of the measured fluorescence in the test sample is less than the amount of measured fluorescence in the standard sample, then the β-lactamase secreting bacteria is determined to be susceptible to the β-lactam antibiotic.

2. The method of claim 1 , wherein, the EtNBS fluorophores are conjugated to the cephalosporin linker via amide bond.

3. The method of claim 2 , wherein at least one fluorophore is bound at the 3′ position of the cephalosporin linker.

4. The method of claim 3 , wherein, the cephalosporin linker compound linked with two EtNBS fluorophores is a compound of the structure:

Assignees

• Hasan Tayyaba
• Sallum Ulysses W
• Verma Sarika
• Nau Gerard
• Massachusetts Gen Hospital

Inventors

• Hasan Tayyaba
• Sallum Ulysses W
• Verma Sarika
• Nau Gerard

Classifications

• G01N2333/986

  acting on amide bonds in cyclic amides (3.5.2), e.g. beta-lactamase (penicillinase, 3.5.2.6), creatinine amidohydrolase (creatininase, EC 3.5.2.10), N-methylhydantoinase (3.5.2.6) · CPC title

• C12Q1/34 Primary

  involving hydrolase · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• G01N33/542

  with steric inhibition or signal modification, e.g. fluorescent quenching · CPC title

• G01N33/56911

  Bacteria · CPC title