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Background  The recent rise and spread of carbapenem-resistant pathogens pose an urgent threat to public health and has fueled the search for new therapies. Localized delivery of topical antibiotics is an alternative for the treatment of infected wounds caused by drug-resistant pathogens. In this study, we aimed to develop antimicrobial-loaded hydrogels for topical treatment of wound infections in a murine skin wound infection.    Results  Paenipeptin analogue 1, a linear lipopeptide, potentiated clarithromycin against multidrug-resistant  Acinetobacter baumannii ,  Enterobacter cloacae ,  Escherichia coli , and  Klebsiella pneumoniae . Enzymatically-crosslinked gelatin hydrogels were developed to encapsulate paenipeptin analogue 1 and clarithromycin. The encapsulated antimicrobials were gradually released from hydrogels during incubation, reaching 75.43 and 53.66% for paenipeptin and clarithromycin, respectively, at 24 h. The antimicrobial-loaded hydrogels containing paenipeptin and clarithromycin synergistically resulted in 5-log reduction in carbapenem-resistant  A. baumannii  within 6 h in vitro. Moreover, the antimicrobial-loaded hydrogels reduced 3.6- and 2.5-log of carbapenem-resistant  A. baumannii  when treated at 4 or 20 h post infection, respectively, in a murine skin wound infection.    Conclusions  Enzymatically-crosslinked gelatin hydrogels loaded with paenipeptin analogue 1 and clarithromycin exhibited potent therapeutic efficacy against carbapenem-resistant  A. baumannii  in murine skin wound infection.    Supplementary Information  The online version contains supplementary material available at 10.1186/s12866-021-02383-z.

bmc microbiology

Enzymatically-crosslinked gelatin hydrogels containing paenipeptin and clarithromycin against carbapenem-resistant pathogen in murine skin wound infection