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Systematic review and meta-analysis of plant-derived antimicrobials in WHO priority pathogens


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Abstract

Background: Antimicrobial resistance (AMR) threatens the effective prevention and treatment of a growing range of infections and requires immediate intersectoral action. A report into the global burden of AMR estimated that AMR contributed to 700,000 deaths in 2016 and is expected to reach 10 million deaths annually by 2050. Plantderived antimicrobials (PDAms) have demonstrated the ability to combat multi-drugresistant (MDR) pathogens and hope exists that they may help control AMR. This review investigated and recorded the antimicrobial activity (AMA) of whole plant ethanolic and methanolic extracts in WHO priority pathogens (WHO PPs) reported between 2000 until present. The review collated studies on PDAms tested on WHO PP laboratory isolates, determined efficacious PDAms, and grouped PDAms by WHO PP and antimicrobial susceptibility test (AST). Methods: A comprehensive search of PubMed and Google databases using a combination of MeSH and free text terms was conducted from April 28th - May 8th 2020 of in-vitro studies determining the AMA of angiosperms in WHO PPs. Endpoints included minimum inhibitory concentration (MIC), zone of inhibition (ZOI) and half-maximal inhibitory concentration (IC50). This systematic review and meta-analysis was reported according to PRISMA guidelines. A modified STROBE-AMS checklist was applied to included studies. Limitations are that a double screening selection processis generally Scholar recommended. Results: Data were pooled and computed in a meta-analysis. Thirty-four studies on PDAmWHO priority specific data were identified. Effective PDAms were grouped by WHO PP and AST. PDAm activity was demonstrated in 50% of WHO PPs. Piper betle L. demonstrated the greatest AMA in six WHO PPs (50%). Methicillin-resistant Staphylococcus aureus (MRSA) was the most commonly studied WHO PP (69.6%), returning forty-three PDAms. No studies were returned on clarithromycin-resistant Helicobacter pylori, fluoroquinoloneresistant Campylobacter spp. fluoroquinolone-resistant Salmonellae, penicillin-nonsusceptible Streptococcus pneumoniae, ampicillin-resistant Haemophilus influenzae and fluoroquinolone-resistant Shigella spp. Conclusion: This synthesis of the available studies and identification of the quality data may help to inform and prioritise future research on PDAms in WHO PPs.

Keywords

AMA, antimicrobial activity; AMR, antimicrobial resistance; AMRIC, the antimicrobial resistance and infection control division; AMU, antimicrobial use; AB, antibiotics; AR, antibiotic resistance; AST, antimicrobial susceptibility testing; CPE, carbapenemaseproducing enterobacterales; CLSI, clinical and laboratory standards institute; CAM, complementary and alternative medicine; EUCAST, european committee on antimicrobial susceptibility testing; E. coli, ESBL-E.Escherichia coli; ESBL-E, extended-spectrum ?-lactamaseproducing enterobacterales; GPB, gram positive bacteria; GNB, gram negative bacteria; IC50, half maximal inhibitory concentration; HCAIs, healthcare associated infections; HPSC, health protection surveillance centre; MRSA, methicillin-resistant staphylococcus aureus; MIC, minimum inhibitory concentration; MBC, minimum bactericidal concentration; MDR, multidrug resistant; MDRO, multidrug resistant organisms; PDAms, plant-derived antimicrobials; QS, quorum sensing; R&D, research and development; RMAs, resistance-modifying agents; STROBE-AMS, STROBE for antimicrobial stewardship; SSIs, surgical site infections; VRE, vancomycin-resistant Enterococci; WHO, world health organisation; WHO PPs, WHO priority pathogens; ZOI, zone of inhibition

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