Antibacterial Activity of LCB10-0200 against Klebsiella pneumoniae.

Sang-Hun Oh,Young-Lag Cho,Hee-Soo Park,Jin-Hwan Kwak,Young-Rok Kim,Kyu-Man Oh

doi:10.3390/antibiotics10101185

Sang-Hun Oh, Young-Lag Cho + Show 4 more

Open Access

https://doi.org/10.3390/antibiotics10101185

Copy DOI

Abstract

Klebsiella pneumoniae is one of the important clinical organisms that causes various infectious diseases, including urinary tract infections, necrotizing pneumonia, and surgical wound infections. The increase in the incidence of multidrug-resistance K. pneumoniae is a major problem in public healthcare. Therefore, a novel antibacterial agent is needed to treat this pathogen. Here, we studied the in vitro and in vivo activities of a novel antibiotic LCB10-0200, a siderophore-conjugated cephalosporin, against clinical isolates of K. pneumoniae. In vitro susceptibility study found that LCB10-0200 showed potent antibacterial activity against K. pneumoniae, including the beta-lactamase producing strains. The in vivo efficacy of LCB10-0200 was examined in three different mouse infection models, including systemic, thigh, and urinary tract infections. LCB10-0200 showed more potent in vivo activity than ceftazidime in the three in vivo models against the drug-susceptible and drug-resistant K. pneumoniae strains. Taken together, these results show that LCB10-0200 is a potential antibacterial agent to treat infection caused by K. pneumoniae.

Highlights

Klebsiella pneumoniae, an opportunistic pathogenic bacterium belonging to the Enterobacteriaceae group, can cause various infectious diseases in immunocompromised individuals [1,2]
Most antimicrobial agents are currently ineffective in treating infections caused by these bacterial species because they are considered multidrug-resistant (MDR) pathogens and are on their way to becoming pan-drug resistant strains, which means that they show resistance to more than seven antibiotics simultaneously [6,7]
LCB10-0200 (MIC range, 1–>32 mg/L) was more active than ceftazidime and ciprofloxacin against K. pneumoniae. These results demonstrated that LCB10-0200 has potent activities against K. pneumoniae

Summary

Introduction

Klebsiella pneumoniae, an opportunistic pathogenic bacterium belonging to the Enterobacteriaceae group, can cause various infectious diseases in immunocompromised individuals [1,2]. The in vivo activity of LCB10-0200 against K. pneumoniae was compared with that of ceftazidime using a mouse systemic infection model (Table 3). In this experiment, ceftazidime—susceptible and -resistant K. pneumoniae were used. In the urine infection mouse model, LCB10-0200 showed potent antibacterial activity against ceftazidime—resistant K. pneumoniae strains (Figure 3). LCB10-0200 showed potent activity against K. pneumoniae strains in a systemic infection mouse model (Table 3). The results of the previous hERG toxicity test confirmed that there was no toxicity at the highest concentration (300 μM) in the experiment [20] Taken together, these results show the potential of LCB10-0200 as a therapeutic agent for beta-lactamase-producing K. pneumoniae strains. Future studies will be carried out to better understand the mechanism of action of LCB01-0200 against Gram—negative bacteria, including P. aeruginosa and K. pneumoniae

Antimicrobial Agents and Bacterial Strains

Systemic Infection Mouse Model

Thigh Infection Mouse Model

Urinary Tract Infection Mouse Model

Findings

Conclusions