ABSTRACT
Frequency of bacterial co-infections among patients with COVID-19 is not high, and over-prescribing of antibiotics may contribute the selection of resistant strains of enterobacteria and gram-negative non-fermenting bacteria. The aim of the study was to assess the local features of antibiotic resistance of K. pneumoniae and its genetic mechanisms against background of the COVID-19 infection pandemic. Material and methods. There was selected 37 carbapenem-resistant K. pneumoniae strains isolated in 2016, 2017 and 2020 from hospitalized patients, including 15 strains, isolated from patients with COVID-19 infection. Minimal inhibitory concentrations (MICs) of meropenem and colistin were determined by broth microdilution method. Determination of MICs of eravacycline, ceftazidime/avibactam, meropenem/vaborbactam, imipenem/relebactam was performed using Sensititre diagnostic system on EUMDROXF plates. Susceptibility to 11 combinations of 2 antibiotics was detected by modified method of multiply combination bactericidal testing. For 4 K. pneumoniae strains high-throughput sequencing was performed, followed with the subsequent search for determinants of antibiotic resistance and virulence, assessment of plasmid profiles. Results. All strains were resistant to meropenem (MIC50 32 mg/l, MIC90 128 mg/l) and produced KPC and OXA-48 carbapenemases. Strains isolated in 2016-2017 were susceptible to colistin (MIC <=2 mg/l), in 2020 only 26.7% of the strains retained their susceptibility (MIC50 64 mg/l, MIC90 256 mg/l). Susceptibility to combinations of two antibiotics with colistin included reduced from 84.6-100% in 2016-2017 till 26.6-66.7% in 2020. The strains isolated in 2020 retained their susceptibility to ceftazidime/avibactam (MIC <=1 mg/l). 5 strains resistant to cefiderocol with a MIC 8 mg/l were identified. Strains 2564 and 3125 isolated in 2020 from sputum of patients with COVID-19 infection belonged to different sequence-types (ST12 and ST23) and contained the blaOXA-48 carbapenemase gene, additionally strain 2564 contained the blaKPC-27carbapenemase gene. Resistance to colistin was caused by inactivation of the mgrB genes due to insertion of IS1 and IS5-like transposons. Conclusion. The performed genetic studies demonstrate a diversity of mechanisms of antibiotic resistance in K. pneumoniae leading to the formation of resistance including to antibiotics that haven't been used in Belarus till now.Copyright © 2021 Geotar Media Publishing Group. All Rights Reserved.
ABSTRACT
Background. Multiple studies have shown that antibiotic utilization increased during the COVID-19 pandemic. However, the impact of this increased utilization has not been well established. The aim of this study is to describe the trends in minimum inhibitory concentrations for various antibiotics against common gram-negative pathogens observed since the start of the COVID-19 pandemic as compared to previous years. Methods. This retrospective study was conducted at the Memphis VA. All respiratory, urine, and blood culture MicroScan results run from October 2017-March 2021 were analyzed. Only inpatient and emergency department data was included. The MIC50 and MIC90 of seven antibiotics for four of the most common pathogens were trended by quarterly intervals. Results. MIC50 and MIC90 were compared using standardized breakpoints. As compared to previous years, Pseudomonas aeruginosa was noted to have the most sustained increase in MIC90 across various antibiotics. In the last 3 quarters of the study time frame, piperacillin-tazobactam mean MIC90 increased from 32 to 64, cefepime from 8 to > 16, and meropenem from 4 to > 8. Escherichia coli had a sustained increase in ceftriaxone MIC90 from < 1 to > 8 in the final quarter of 2020 and beginning of 2021. Klebsiella pneumonia was also found to have a sustained increase in cefepime mean MIC90 from < 1 to > 16 during the year of 2020, with return to previous MIC90 the following quarters. Conclusion. Previous studies have clearly demonstrated a widespread increase in antibiotic utilization during the COVID era. Our study demonstrates how even short-term increases in antibiotic use can lead to shifts in MIC, if not outright resistance. This was demonstrated across multiple common gram-negative pathogens and to various broad-spectrum antibiotics which were commonly used more frequently during COVID-19. Further analysis will be needed to determine whether these trends continue or whether the decrease in antibiotic utilization in the recent months will lead to similar decrease in MIC.
ABSTRACT
Ceftriaxone has been a part of therapeutic regime for combating some of the most aggressive bacterial infections in the last few decades. However, increasing bacterial resistance towards ceftriaxone and other third generation cephalosporin antibiotics has raised serious clinical concerns especially due to their misuse in the COVID-19 era. Advancement in nanotechnology has converted nano-therapeutic vision into a plausible reality with better targeting and reduced drug consumption. Thus, in the present study, gold nanoparticles (GNPs) were synthesized by using ceftriaxone antibiotic that acts as a reducing as well as capping agent. Ceftriaxone-loaded GNPs (CGNPs) were initially characterized by UV-visible spectroscopy, DLS, Zeta potential, Electron microscopy and FT-IR. However, a TEM micrograph showed a uniform size of 21 ± 1 nm for the synthesized CGNPs. Further, both (CGNPs) and pure ceftriaxone were examined for their efficacy against Escherichia coli, Staphylococcus aureus, Salmonella abony and Klebsiella pneumoniae. CGNPs showed MIC50 as 1.39, 1.6, 1.1 and 0.9 µg/mL against E. coli, S. aureus, S. abony and K. pneumoniae, respectively. Interestingly, CGNPs showed two times better efficacy when compared with pure ceftriaxone against the tested bacterial strains. Restoring the potential of unresponsive or less efficient ceftriaxone via gold nanoformulations is the most alluring concept of the whole study. Moreover, applicability of the findings from bench to bedside needs further validation.