Antibiotic resistance has become a major issue in public health especially for one of the most used antibiotics; the third-generation cephalosporins. one of the main resistance mechanisms in Enterobacteriaceae, is the production of extended-Spectrum β-lactamases. Here, we demonstrated that the oligonucleotide therapy is an efficient approach to reduce the resistance of bacteria to antibiotic treatment. Lipid oligonucleotides (LONs) were proved to be efficient strategies in both delivering the oligonucleotide sequences in the prokaryotic cells and decreasing the Minimum inhibitory concentration of resistant bacteria to a third generation cephalosporin, the ceftriaxone. Accordingly, we demonstrated the strong antimicrobial potential of this Lon strategy targeting the ß-lactamase activity on both clinical and laboratory strains. our results support the concept that the self-delivery of oligonucleotide sequences via lipid conjugation may be extended to other antimicrobial drugs, which opens novel ways to struggle against the antibiotic resistance.
Our experimental data demonstrate for the first time, to our knowledge, the mobilization of a β-lactamase gene mediated by a member of the IS91 family and highlight the important role of this mobile genetic element in the spread of antibiotic resistance genes.
Background
Description and comparison of bacterial characteristics of ventilator-associated pneumonia (VAP) between critically ill intensive care unit (ICU) patients with COVID-19-positive, COVID + ; and non-COVID-19, COVID-.
Methods
Retrospective, observational, multicenter study that focused on French patients during the first wave of the pandemic (March–April 2020).
Results
935 patients with identification of at least one bacteriologically proven VAP were included (including 802 COVID +). Among Gram-positive bacteria, S. aureus accounted for more than two-thirds of the bacteria involved, followed by Streptococcaceae and enterococci without difference between clinical groups regarding antibiotic resistance. Among Gram-negative bacteria, Klebsiella spp. was the most frequently observed bacterial genus in both groups, with K. oxytoca overrepresented in the COVID- group (14.3% vs. 5.3%; p < 0.05). Cotrimoxazole-resistant bacteria were over-observed in the COVID + group (18.5% vs. 6.1%; p <0.05), and after stratification for K. pneumoniae (39.6% vs. 0%; p <0.05). In contrast, overrepresentation of aminoglycoside-resistant strains was observed in the COVID- group (20% vs. 13.9%; p < 0.01). Pseudomonas sp. was more frequently isolated from COVID + VAPs (23.9% vs. 16.7%; p <0.01) but in COVID- showed more carbapenem resistance (11.1% vs. 0.8%; p <0.05) and greater resistance to at least two aminoglycosides (11.8% vs. 1.4%; p < 0.05) and to quinolones (53.6% vs. 7.0%; p <0.05). These patients were more frequently infected with multidrug-resistant bacteria than COVID + (40.1% vs. 13.8%; p < 0.01).
Conclusions
The present study demonstrated that the bacterial epidemiology and antibiotic resistance of VAP in COVID + is different from that of COVID- patients. These features call for further study to tailor antibiotic therapies in VAP patients.
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