Affiliation:
1. Laboratorio de Bacteriología, Departamento de Bioquímica Clínica – INFIBIOC, Hospital de Clínicas José de San Martín, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Avenida Córdoba 2351, Buenos Aires, Argentina
Abstract
The emergence of metallo-β-lactamase (MBL)-producing
Enterobacterales
, mainly New Delhi metallo-β-lactamase (NDM), represents a clinical threat due to the limited therapeutic alternatives. Aztreonam (AZT) is stable to MBLs, but most MBL-producing
Enterobacterales
isolates usually co-harbour other β-lactamases that confer resistance to AZT and, consequently, its use is restricted in these isolates. We compared the ability of sulbactam (SUL), tazobactam (TAZ), clavulanic acid (CLA) and avibactam (AVI) to restore the AZT activity in MBL-producing AZT-resistant
Enterobacterales
isolates. A collection of 64 NDM-producing AZT-resistant
Enterobacterales
from five hospitals in Buenos Aires city, Argentina, were studied during the period July–December 2020. MICs were determined using the agar dilution method with Mueller–Hinton agar according to Clinical and Laboratory Standards Institute (CLSI) recommendations. AVI, SUL and TAZ were used at a fixed concentration of 4 mg l−1, whereas CLA was used at a fixed concentration of 2 mg l−1. A screening method based on disc diffusion to evaluate this synergy was also conducted. Detection of bla
KPC, bla
OXA, bla
NDM, bla
VIM,
bla
CTXM-1, bla
PER-2 and bla
CIT was performed by PCR. The AZT-AVI combination restored the AZT activity in 98.4 % of AZT-resistant strains, whereas CLA, TAZ and SUL did so in 70.3, 15.6 and 12.5 %, respectively, in isolates co-harbouring extended-spectrum β-lactamases, but were inactive in isolates harbouring AmpC-type enzymes and/or KPC. The synergy screening test showed an excellent negative predictive value to confirm the absence of synergy, but positive results should be confirmed by a quantitative method. The excellent in vitro performance of the AZT-CLA combination represents a much more economical alternative to AZT-AVI, which could be of use in the treatment of MBL-producing, AZT-resistant
Enterobacterales
.
Funder
Secretaria de Ciencia y Tecnica, Universidad de Buenos Aires
Subject
Microbiology (medical),General Medicine,Microbiology