Abstract
Treatment of multidrug resistant bacterial infections has been a great challenge globally. Previous studies including our study have highlighted the use of celecoxib, a non-steroidal anti-inflammatory drug in combination with antibiotic has decreased the minimal inhibitory concentration to limit Staphylococcus aureus infection. However, the efficacy of this combinatorial treatment against various pathogenic bacteria is not determined. Therefore, we have evaluated the potential use of celecoxib in combination with low doses of antibiotic in limiting Gram-positive and Gram-negative bacteria in vivo in murine polymicrobial sepsis developed by cecum ligation and puncture (CLP) method and against clinically isolated human ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species). The in vivo results clearly demonstrated a significant reduction in the bacterial load in different organs and in the inflammatory markers such as COX-2 and NF-κB via activation of SIRT1 in mice treated with imipenem, a choice of antibiotic for polymicrobial sepsis treatment. Combinatorial treatment of ampicillin and celecoxib was effective on clinical isolates of ESKAPE pathogens, 45% of tested clinical isolates showed more than 50% reduction in the colony forming units when compared to ampicillin alone. In conclusion, this non-traditional treatment strategy might be effective in clinic to reduce the dose of antibiotic to treat drug-resistant bacterial infections.
Highlights
Multidrug resistance is an adaptation of bacteria for its survival (Sorlozano et al, 2014)
First to confirm the presence of bacterial load in various organs of cecum ligation and puncture (CLP) mice, Gram staining was carried out using liver and spleen tissue homogenate and the results indicated the presence of both Gram-positive and Gram-negative bacteria and most of them were cocci (Figure 1A)
Our study results imply that celecoxib is effective in controlling inflammatory response by the activation of SIRT1, inhibiting inflammatory protein COX-2, and Nuclear Factor-κB (NF-κB) pathways in polymicrobial sepsis murine model and helping antibiotic in clearing the bacterial load
Summary
Multidrug resistance is an adaptation of bacteria for its survival (Sorlozano et al, 2014). The cost and time involved in the development of new drug for the treatment of such “superbugs” is very huge which is soon followed by the development of resistance to the new antibiotic. In this context, Celecoxib Enhances Antibiotic Potency finding a non-traditional treatment strategy consisting of combination of an antibiotic targeting bacteria and a non-antibiotic agent that does not have any target in bacteria but helps in improving host response or potentiating antibiotic activity even at low doses of antibiotic is preferred (Wang et al, 2015). The efficacy of such treatment strategy on various pathogens causing clinical and economic burden needs to be evaluated
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