Abstract
Linezolid is a synthetic oxazolydinone active against multi-resistant Gram-positive cocci that inhibits proteins synthesis by interacting with the 50S ribosomal subunit. Although linezolid-resistant strains are infrequent, several outbreaks have been recently described, associated with prolonged treatment with the antibiotic. As an alternative to monotherapy, the combination of different antibiotics is a commonly used option to prevent the selection of resistant strains. In this work, we evaluated combinations of linezolid with classic and new aminoglycosides (amikacin, gentamicin and plazomicin), carbapenems (doripenem, imipenem and meropenem) and fosfomycin on several linezolid- and methicillin-resistant strains of Staphylococcus aureus and S. epidermidis, isolated in a hospital intensive care unit in Madrid, Spain. Using checkerboard and time-kill assays, interesting synergistic effects were encountered for the combination of linezolid with imipenem in all the staphylococcal strains, and for linezolid–doripenem in S.epidermidis isolates. The combination of plazomicin seemed to also have a good synergistic or partially synergistic activity against most of the isolates. None of the combinations assayed showed an antagonistic effect.
Highlights
Antibiotic resistance is considered a major global public health problem and constitutes a challenge for the treatment of infections caused by multi-drug-resistant microorganisms
S. aureus strains were resistant to gentamicin and fosfomycin and showed elevated minimum inhibitory concentration (MIC) values for carbapenems
The studied S. epidermidis strains were resistant to amikacin and gentamicin
Summary
Antibiotic resistance is considered a major global public health problem and constitutes a challenge for the treatment of infections caused by multi-drug-resistant microorganisms. Linezolid is a synthetic oxazolidinone active against multi-resistant Gram-positive cocci and is one of the recommended treatments for pneumonia, bacteremia or central nervous system and soft tissue infections [4]. Antibiotics 2020, 9, 496 by interacting with the peptidyl transferase center of the 50S ribosomal subunit [5]. It shows good pharmacokinetic/pharmacodynamical properties and excellent oral bioavailability, and it appears to reduce biofilm formation by staphylococci [6,7]. Linezolid resistance is based on mutations in several 23S rRNA positions, including conserved nucleotides at the antibiotic binding pocket and other nucleotides, and the mutation
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