Your browser doesn't support javascript.
loading
The use of dual ß-lactams to restore susceptibility of Mycobacterium avium complex.
Al-Jabri, Maha Y; Dousa, Khalid M; Wilson, Brigid M; Bonomo, Robert A.
Afiliación
  • Al-Jabri MY; Division of Infectious Diseases and HIV Medicine, Department of Medicine, University Hospitals-Cleveland Medical Center, Cleveland, OH, USA.
  • Dousa KM; Department of Medicine, Case Western Reserve University, Cleveland, OH, USA.
  • Wilson BM; Department of Medicine, Case Western Reserve University, Cleveland, OH, USA.
  • Bonomo RA; Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Geriatric Research Education and Clinical Center (GRECC), VA Northeast Ohio Healthcare System, 10701 East Boulevard, Cleveland, OH 44106, USA.
JAC Antimicrob Resist ; 6(5): dlae142, 2024 Oct.
Article en En | MEDLINE | ID: mdl-39281290
ABSTRACT

Background:

The Mycobacterium avium complex (MAC) are non-tuberculous mycobacteria responsible for chronic and debilitating conditions. Guideline-recommended therapy for MAC is a combination of clarithromycin/azithromycin, ethambutol and a rifamycin. However, culture conversion rates with this regimen are 67%. Alternative treatment options are needed. Recent findings of ß-lactam combinations in the treatment of other mycobacterial diseases have been promising. The proposed mechanism is an additive inhibition of multiple enzymes in the peptidoglycan synthesis pathway by the ß-lactam combinations. Given the similarity in cell wall structures of MAC and M. abscessus, we hypothesize that using dual ß-lactams will result in interruption of peptidoglycan synthesis in MAC and reduction of MIC. In this study, we sought to determine the MIC of meropenem in combination with ceftaroline, cefdinir and cefuroxime in MAC.

Methods:

A total of 31 clinical MAC isolates were used for susceptibility testing using broth microdilution method. MICs were tested for meropenem, ceftaroline, cefdinir and cefuroxime, alone, as well as combinations of meropenem plus ceftaroline, cefdinir, or cefuroxime.

Results:

In vitro MAC susceptibility to meropenem was significantly enhanced with the addition of ceftaroline, cefdinir, and cefuroxime. This effect was most significant with addition of ceftaroline and cefdinir, with a change of meropenem MIC50/MIC90 from 16/32 to 0.125/0.5 and 0.125/4 mg/L, respectively (P value ≤0.0001, Wilcoxon signed-rank test).

Conclusions:

This study demonstrates that the susceptibility of MAC to meropenem is restored with the addition of ceftaroline and cefdinir. These findings underscore the potential effectiveness of combining ß-lactams as an alternative therapeutic strategy for MAC infections.
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: JAC Antimicrob Resist Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: JAC Antimicrob Resist Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido