In vitro activity of polymyxin B in combination with meropenem, amikacin and gentamicin against Klebsiella pneumoniae clinical isolates co-harbouring aminoglycoside-modifying enzymes, blaNDM-1 and blaKPC-2

• Published in: Journal of global antimicrobial resistance. Vol. 22; pp. 511 - 514
• Main Authors: Firmo, Elza Ferreira, Oliveira Júnior, Jorge Belém, Scavuzzi, Alexsandra Maria Lima, Alves, Luis Carlos, Brayner, Fábio André, Veras, Dyana Leal, Lopes, Ana Catarina de Souza
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01-09-2020; Elsevier
• Subjects: Amikacin; Carbapenemase; Gentamicin; Meropenem; Polymyxin B; Synergy; Carbapenemase; Synergy; Meropenem; Amikacin; Polymyxin B; Gentamicin
• ISSN: 2213-7165; 2213-7173
• DOI: 10.1016/j.jgar.2020.04.014

•The monotherapy fail to prevent the regrowth of of K. pneumoniae carrying blaKPC-2 and blaNDM-1.•PMB/MEM and PMB/AMK combinations are synergistic and maintain bactericidal activity.•Bactericidal activity of combinations was observed using subinhibitory concentrations.
Multidrug-resistant Klebsiella pneumoniae carrying blaNDM-1 and blaKPC-2 genes are a worldwide concern for which combination antimicrobial therapy may be the only viable option. The aim of this study was to investigate the in vitro activity of combinations of polymyxin B (PMB) with meropenem (MEM), amikacin (AMK) and gentamicin (GEN) at subinhibitory concentrations against two K. pneumoniae clinical isolates co-harbouring blaNDM-1, blaKPC-2 and aminoglycoside-modifying enzymes and resistant to PMB.
Synergy and bactericidal activity were evaluated by chequerboard and time–kill assays against two PMB-resistantK. pneumoniae clinical isolates carrying the blaNDM-1, blaKPC-2, aac(3)-IIa, aac(6ʹ)-Ib, aph(3ʹ)-VI and ant(2ʹʹ)-Ia genes. Five combinations of PMB, MEM, AMK and GEN were evaluated.
The PMB/MEM and PMB/AMK combinations proved to be the best options against isolate K7R2, mainly because they demonstrated bactericidal activity when using subinhibitory concentrations of these antimicrobials. However, none of the studied combinations was bactericidal against isolate K11R2.
The combinations used in this study showed synergy against NDM-and KPC-producing isolates but, given their bactericidal activity, the combinations of PMB/MEM and PMB/AMK were the most active against one isolate. It can also be concluded that the antimicrobials to which the bacteria were resistant could form part of combination therapy.