biostudies-literatureUnknown12She P<i>Klebsiella pneumoniae</i> has emerged as a major clinical and public health threat owing to the increasing prevalence of healthcare-associated infections caused by multidrug-resistant or extensively drug-resistant strains. However, increasing antibiotic resistance and the absence of clinically effective antimicrobial agents make combination therapy an urgent need. This study investigated the anti-microbial activity of SPR741, a polymyxin B derivative, in combination with macrolide antibiotics (erythromycin and clarithromycin), against extensively drug-resistant and pandrug-resistant <i>K. pneumoniae.</i> Monotherapy, double, and triple combination therapies were performed to identify the most effective treatment combination using <i>in vitro</i> checkerboard, time-killing kinetics. FurtFrontiers in cellular and infection microbiology858606https://www.ebi.ac.uk/biostudies/studies/S-EPMC8971605biostudies-literatureSPR741, Double- or Triple-Combined With Erythromycin and Clarithromycin, Combats Drug-Resistant <i>Klebsiella pneumoniae</i>, Its Biofilms, and Persister Cells.PMC8971605Xu LLiu YShe PLi YLi ZHussain ZLiu SWu YfalseSPR741, Double- or Triple-Combined With Erythromycin and Clarithromycin, Combats Drug-Resistant <i>Klebsiella pneumoniae</i>, Its Biofilms, and Persister Cells.<i>Klebsiella pneumoniae</i> has emerged as a major clinical and public health threat owing to the increasing prevalence of healthcare-associated infections caused by multidrug-resistant or extensively drug-resistant strains. However, increasing antibiotic resistance and the absence of clinically effective antimicrobial agents make combination therapy an urgent need. This study investigated the anti-microbial activity of SPR741, a polymyxin B derivative, in combination with macrolide antibiotics (erythromycin and clarithromycin), against extensively drug-resistant and pandrug-resistant <i>K. pneumoniae.</i> Monotherapy, double, and triple combination therapies were performed to identify the most effective treatment combination using <i>in vitro</i> checkerboard, time-killing kinetics. Furt2022-01-01T00:00:00Z20222025-04-04T19:10:17.831Z2025-04-04T19:10:17.831ZS-EPMC89716053537212410.3389/fcimb.2022.858606