Effect of polymyxin B combined with novel β-lactam/β-lactamase inhibitor combinations on biofilms of polymyxin B-resistant bacteria
10.12138/j.issn.1671-9638.20256729
- VernacularTitle:多黏菌素B联合新型β-内酰胺酶抑制剂复方制剂对耐多黏菌素B细菌生物膜的影响
- Author:
Miaomei TIAN
1
;
Siwei GUO
;
Bingqian YAN
;
Rong JIANG
;
Bing XU
;
Xin LI
Author Information
1. 长沙市第三医院药学部,湖南 长沙 410015;抗耐药微生物药物湖南省重点实验室,湖南长沙 410015
- Publication Type:Journal Article
- Keywords:
biofilm;
Pseudomonas aeruginosa;
Klebsiella pneumoniae;
polymyxin B;
novel β-lactam/β-lactamase inhibitor combinations
- From:
Chinese Journal of Infection Control
2025;24(1):58-66
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the activity and mechanism of polymyxin B combined with novel β-lactam/β-lac-tamase inhibitor combinations on biofilm of polymyxin B-resistant Pseudomonas aeruginosa and Klebsiella pneumo-niae.Methods The minimum inhibitory concentration(MIC),minimum biofilm inhibitory concentration(MBIC),and minimum biofilm eradication concentration(MBEC)of all antimicrobial agents were determined by micro-broth dilution method and MBECTM assay.The crystal violet staining method was adopted to evaluate the effect of poly-myxin B combined with cefepime/avibactam,ceftazidime/avibactam,meropenem/avibactam,aztreonam/avibactam,meropenem/vaborbactam,and imipenem/relebactam at sub-MIC doses on inhibition of biofilm formation and eradi-cation of mature biofilm.The best combination scheme for anti-biofilm activity was screened out,and anti-biofilm mechanism of this combination scheme was preliminarily explored with phenol-sulfuric acid method,bacterial motili-ty test,and quorum sensing inhibition test.Results The MBIC and MBEC of all antimicrobial agents were higher than MIC.The combination regimen based on polymyxin B could inhibit the formation of biofilms and eradicate ma-ture biofilm in Pseudomonas aeruginosa and Klebsiella pneumoniae.The combination of polymyxin B with cefepime/avibactam had the highest inhibition and eradication rates,ranging 67.99％-90.16％and 58.26％-63.86％,respectively.The combination of polymyxin B and cefepime/avibactam could inhibit the extracellular poly-saccharides of Klebsiella pneumoniae,with inhibition rates of 34.04％-61.10％,this combination could also re-duce the swimming and twitching motility diameters of bacteria.Cefepime/avibactam monotherapy on quorum sen-sing signaling molecules presented concentration dependent inhibitory effect,and when combined with polymyxin B,the inhibitory effect was consistent with that of monotherapy.Conclusion Polymyxin B and cefepime/avibactam may be potential scheme for clinical treatment for severe biofilm-associated infection caused by polymyxin B-resistant strains,and their mechanisms may be related to the inhibition of bacterial extracellular polysaccharides and motility.
