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Manganese complex [Mn(CO)3(tpa-κ3N)]Br increases antibiotic sensitivity in multidrug resistant Streptococcus pneumoniae.

Abstract：

OBJECTIVES:The emergence of multidrug-resistance (MDR) in Streptococcus pneumoniae clones and non-vaccine serotypes necessitate the development of novel treatment strategies. This work aimed to determine the efficacy of the Mn complex [Mn(CO)3(tpa-κ3N)]Br against clinically important MDR strains of S. pneumoniae. METHODS:Twenty MDR clinicalS. pneumoniae strains were included in this study. Minimum inhibitory concentrations (MICs) of [Mn(CO)3(tpa-κ3N)]Br were determined via broth microdilution alone and in combination with other antimicrobial agents using checkerboard assays and/or disc diffusion tests. In vitro efficacy was assessed by time-kill assays while in vivo efficacy was tested using the insect model Galleria mellonella. RESULTS:[Mn(CO)3(tpa-κ3N)]Br showed moderate in vitro efficacy against S. pneumoniae coupled with bactericidal activity. Checkerboard and disc diffusion assays showed synergy between [Mn(CO)3(tpa-κ3N)]Br and tetracycline, and the combination of both agents caused rapid kill-kinetics and reduced the MIC below the susceptibility breakpoint of 1 mg/L even for tetracycline-resistant strains of S. pneumoniae. Similar results were observed for the erythromycin- and the co-trimoxazole-Mn complex combination. In the G. mellonella infection model, mortality and morbidity rates at 96 h were significantly lower in larvae treated with [Mn(CO)3(tpa-κ3N)]Br than phosphate buffered saline, while treatment with the tetracycline-Mn complex combination was superior to monotherapy, resulting in significantly lower mortality and morbidity rates (p < 0.049). CONCLUSIONS:We show that [Mn(CO)3(tpa-κ3N)]Br has in vitro and in vivo antibacterial activity against clinically relevant strains of S. pneumoniae and has the potential to be used in combination with currently available antibiotics to increase their effectiveness against MDR S. pneumoniae.

journal_name

J Glob Antimicrob Resist

journal_title

Journal of global antimicrobial resistance

authors

Liakopoulos A,La Ragione RM,Nagel C,Schatzschneider U,Rozen DE,Betts JW

doi

10.1016/j.jgar.2020.04.031

subject

Has Abstract

pub_date

2020-09-01 00:00:00

pages

594-597

eissn

2213-7165

issn

2213-7173

pii

S2213-7165(20)30124-7

journal_volume

pub_type

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Manganese complex [Mn(CO)3(tpa-κ3N)]Br increases antibiotic sensitivity in multidrug resistant Streptococcus pneumoniae.