These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: In Vitro Activity of β-Lactams in Combination with β-Lactamase Inhibitors against Multidrug-Resistant Mycobacterium tuberculosis Isolates.
    Author: Zhang D, Wang Y, Lu J, Pang Y.
    Journal: Antimicrob Agents Chemother; 2016 Jan; 60(1):393-9. PubMed ID: 26525785.
    Abstract:
    The combination of β-lactams and β-lactamase inhibitors has been shown to have potent in vitro activity against multidrug-resistant tuberculosis (MDR-TB) isolates. In order to identify the most potent β-lactam-β-lactamase inhibitor combination against MDR-TB, we selected nine β-lactams and three β-lactamase inhibitors, which belong to different subgroups. A total of 121 MDR-TB strains were included in this study. Out of the β-lactams used herein, biapenem was the most effective against MDR-TB and had an MIC50 value of 8 μg/ml. However, after the addition of clavulanate or sulbactam, meropenem exhibited the most potent anti-MDR-TB activity with an MIC50 value of 4 μg/ml. For meropenem, 76 (62.8%), 41 (33.9%), and 22 (18.2%) of the 121 MDR-TB strains were subjected to a synergistic effect when the drug was combined with sulbactam, tazobactam, or clavulanate, respectively. Further statistical analysis revealed that significantly more strains experienced a synergistic effect when exposed to the combination of meropenem with sulbactam than when exposed to meropenem in combination with tazobactam or clavulanate, respectively (P < 0.01). In addition, a total of 10.7% (13/121) of isolates harbored mutations in the blaC gene, with two different nucleotide substitutions: AGT333AGG and ATC786ATT. For the strains with a Ser111Arg substitution in BlaC, a better synergistic effect was observed in the meropenem-clavulanate and in the amoxicillin-clavulanate combinations than that in a synonymous single nucleotide polymorphism (SNP) group. In conclusion, our findings demonstrate that the combination of meropenem and sulbactam shows the most potent activity against MDR-TB isolates. In addition, the Ser111Arg substitution of BlaC may be associated with an increased susceptibility of MDR-TB isolates to meropenem and amoxicillin in the presence of clavulanate.
    [Abstract] [Full Text] [Related] [New Search]