Evaluation of Amlodipine Inhibition and Antimicrobial Effects

Abstract

Antibiotic resistant pathogens is the an urgent challenge of the medicine field. To counter these pathogens, the antibiotic assisting drugs is an ideal choice. Assisting drugs can improve the efficiency of the treatment without further induce of antibiotic resistance. Amlodipine (AML) is one of the most common generic cardiovascular drug for lowering blood pressure. In previous studies, amlodipine was suggested to have some antibiotic properties. The MIC is not very low for amlodipine against these pathogens. However, the findings imply amlodipine potential to be repurposed as assisting drug and its inhibition of β-lactamase. To further discover and verify its potential of antimicrobial drug, amlodipine was tested for β-lactamase inhibition, and its synergistic effects were investigated against methicillin-resistant Staphylococcus aureus (MRSA). The compound was found to inhibit β-lactamase mixture (3 distinct species) in broad spectrum. Cephalosporins requires high concentration (>=64 ug/ml) to inhibit MRSA; combine both amlodipine and cephalosporins, the MIC only requires 8ug/ml (4 ug/ml amlodipine + 4 ug/ml Cefuroxime) in total, with FIC lower than 0.1 for strong synergistic effect. Both enzyme assay and bacterial tests indicate amlodipine as an ideal assisting drug for antibiotics; one of the mechanism is β-lactamase inhibition.

Inhaled Corticosteroids, Vitamin K Antagonists and Amlodipine Were Associated with an Increased Risk of Acute Periprosthetic Joint Infection in Patients with Total Hip Arthroplasty: A Retrospective Case–Cohort Study

“…In contrast to our hypothesis, we found amlodipine to be associated with an increased risk for PJI; this association remained after adjusting for possible confounders. Previously, Kumar et al (2003) and Yi et al (2019) found amlodipine to have antibacterial activity, and to inhibit a range of bacteria both in vitro and in vivo (animal models, white mice), and tested its potential as an antimicrobial drug [ 11 , 12 ]. Yi et al (2019) found that amlodipine exhibited inhibition of a wide range of β-lactamases and synergistic antimicrobial effects in combination with cephalosporines [ 12 ].…”

“…Previously, Kumar et al (2003) and Yi et al (2019) found amlodipine to have antibacterial activity, and to inhibit a range of bacteria both in vitro and in vivo (animal models, white mice), and tested its potential as an antimicrobial drug [ 11 , 12 ]. Yi et al (2019) found that amlodipine exhibited inhibition of a wide range of β-lactamases and synergistic antimicrobial effects in combination with cephalosporines [ 12 ]. Kumar et al (2003) found Staphylococcus aureus to be most sensitive towards amlodipine [ 11 ].…”

“…In contrast to the aforementioned potentially harmful drugs, in vitro studies suggest that cardiovascular drugs such as amlodipine and nifedipine might have antimicrobial properties, and therefore could be of value as antibiotic-assisting drugs [ 11 ]. For example, amlodipine was found to inhibit β-lactamase, and its synergistic effects were positively evaluated in methicillin-resistant Staphylococcus aureus [ 12 ]. In addition, it has been hypothesized that statins have a beneficial role in the treatment of infections [ 13 ].…”

Preoperative Risk Factors for Periprosthetic Joint Infection: A Narrative Review of the Literature

“…Regarding amlodipine, in vitro and in vivo animal studies suggest that it might have antibacterial properties inhibiting β-lactamase. Kumar et al [ 85 ] and Yi et al [ 86 ] found that amlodipine inhibits a variety of bacteria both in vitro and in vivo in animal models, but this effect has not been tested in humans. In contrast to previous in vitro and animal studies, Bruin et al [ 83 ] found an increased risk of PJI in patients taking amlodipine.…”