The emergence of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKp) is a new threat to healthcare. In this study, we analyzed nine CR-hvKp isolates of different sequence-types (ST) recovered from patients with nosocomial infections in two hospitals in Saint Petersburg. Whole-genome sequencing showed that eight of them harbored large mosaic plasmids carrying resistance to carbapenems and hypervirulence simultaneously, and four different types of hybrid plasmids were identified. BLAST analysis showed a high identity with two hybrid plasmids originating in the UK and Czech Republic. We demonstrated that hybrid plasmids emerged due to the acquisition of resistance genes by virulent plasmids. Moreover, one of the hybrid plasmids carried a novel New Delhi metallo-beta-lactamase (NDM) variant, differing from NDM-1 by one amino acid substitution (D130N), which did not provide significant evolutionary advantages compared to NDM-1. The discovery of structurally similar plasmids in geographically distant regions suggests that the actual distribution of hybrid plasmids carrying virulence and resistance genes is much wider than expected.
An Escherichia coli sequence type 31 isolate co-harbouring mcr-1 and bla NDM-1 genes on the plasmids of Incl2 and IncC groups, respectively, was recovered from a newborn with ventilator-associated pneumonia in Moscow, Russia. The convergence of polymyxin and carbapenem resistance and its expansion beyond Southeast Asia is a serious threat to human health.
Escherichia coli isolates from various sources from 2018 to 2019 were included in the study. Mcr-1 genes were found in two of 105 animal strains (2%) and seven of 928 human strains (0.8%). All mcr-1-positive strains showed a low level of resistance to colistin (MIC ranged from 4 to 8 µg/ml). Both strains isolated from animals remained sensitive to betalactam antibiotics and did not contain beta-lactamase genes. Beta-lactamases were absent only in one of the strains isolated from humans. Four strains were resistant to cephalosporins with sensitivity to carbapenems and carried class A (blaCTX-M-15 or blaCTX-M-1) or class C (blaCMY-2) extended-spectrum beta-lactamases genes. One strain showed resistance to cephalosporins and meropenem and contained four beta-lactamase genes: blaNDM-1, blaCTX-M-15, blaTEM-1B, and blaCMY-6. Only one strain isolated from animals remained sensitive to ciprofloxacin, the rest showed high level of resistance, had amino acid substitutions in the DNA gyrase genes or mutations leading to overexpression of the mdfA gene. In terms of resistance to aminoglycosides, the strains varied widely and carried up to four aminoglycoside-modifying enzyme genes. One strain isolated from humans showed resistance to tigecycline, but no genes conferring resistance to this antibiotic were found. The data obtained substantiate the need for extended studies on the molecular epidemiology of associated resistance to polymyxins and beta-lactams.
OXA-48 carbapenemases are frequently expressed by Klebsiella pneumoniae clinical isolates; they decrease the effectiveness of carbapenem therapy, particularly with meropenem. Among these isolates, meropenem-susceptible carbapenemase-producers may show decreased meropenem effectiveness. However, the probability of the emergence of resistance in susceptible carbapenemase-producing isolates and its dependence on specific K. pneumoniae meropenem MICs is not completely known. It is also not completely clear what resistance patterns will be exhibited by these bacteria exposed to meropenem, if they would follow the patterns of non-beta-lactamase-producing bacteria and other than beta-lactams antibiotics. These issues might be clarified if patterns of meropenem resistance related to the mutant selection window (MSW) hypothesis. To test the applicability of the MSW hypothesis to meropenem, OXA-48-carbapenemase-producing K. pneumoniae clinical isolates with MICs in a 64-fold range (from susceptible to resistant) were exposed to meropenem in a hollow-fiber infection model; epithelial lining fluid meropenem pharmacokinetics were simulated following administration of 2 grams every 8 hours in a 3-hour infusion. Strong bell-shaped relationships between the meropenem daily dose infused to the model as related to the specific isolate MIC and both the antimicrobial effect and the emergence of resistance were observed. The applicability of the MSW hypothesis to meropenem and carbapenemase producing K. pneumoniae was confirmed. Low meropenem efficacy indicates very careful prescribing of meropenem to treat K. pneumoniae infections when the causative isolate is confirmed as an OXA-48-carbapenemase producer.
Today, fur farming continues to incur huge losses because of the Aleutian mink disease. Frequently, the pathogen enters the territory of farms together with newly imported mink livestock, which is why the applied immunoelectroosmophoresis reaction has low efficiency if the antibodies have not yet reached a certain level. So for this reason, the problem of accurate and early diagnosis of viral plasmocytosis in newly imported quarantine livestock becomes urgent. The study was carried out using PCR diagnostics of fecal samples from a newly imported population of minks of 30-day age in the fur farm of the North-Western region. Before taking fecal samples, all animals were examined by clinical methods. PCR diagnostics was performed using a set of reagents «Test system "ABN"» according to the manufacturer's instructions. According to the results of the experiment, it was found that out of 40 selected animals without clinical signs of the disease, 29 managed to detect the DNA of the causative agent of viral plasmocytosis. Thus, the use of PCR diagnostics as a method of identifying the Aleutian mink disease virus for newly imported livestock will prevent the development and spread of the disease already at its early stages.
The rapid spread of gram-negative bacteria resistance to carbapenems due to the production of carbapenemases requires new treatment options. The activity of carbapenem antibiotic biapenem, recently registered in Russia, against producers of various carbapenemases was studied in comparison with other antibiotics of this group. Among NDM-type carbapenemase producers, 77.8% demonstrated clinical susceptibility to biapenem; 50.3% and 21.1% of isolates were susceptible to meropenem and imipenem, respectively. Among the producers of OXA-48-type carbapenemases, 82,6%, 60,9%, and 65,2% of isolates demonstrated susceptibility to biapenem, imipenem, and meropenem, respectively.Producers of KPC-type carbapenemases were 100% resistant to all carbapenems. The introduction of biapenem will significantly expand the possibilities of treating severe infections caused by carbapenemase producers.
Lipoglycopeptide antibiotics are semi-synthetic derivatives of glycopeptides and are characterized by a pronounced bactericidal activity against gram-positive pathogens. The aim of the study was comparative assessment of the sensitivity of gram-positive clinical isolates to lipoglycopeptide antibiotics (telavancin, dalbavancin, oritavancin). The following isolates were included in the work: methicillin-resistant Staphylococcus aureus (MRSA, n=780), methicillin-resistant coagulase-negative Staphylococcus spp. (MRCoNS, n=163), and vancomycin-resistant Enterococcus faecium (VREf, n=93). Serial dilutions were used to assess sensitivity with the addition of 0.002% polysorbate 80 to the medium. Lipoglycopeptides showed more pronounced antibacterial activity against MRSA compared to vancomycin, teicoplanin, and daptomycin, and had a MIC₅₀/MIC₉₀ (µg/ml): for telavancin — 0.06 /0.125, for dalbavancin — 0.016/0.06, and for oritavancin — 0.06/0.125. A trend towards an increase in the MIC of lipoglycopeptides and daptomycin was established in MRSA with the MIC of 2 µg/ml for vancomycin, the proportion of which was 13%. For MRCoNS, MIC₅₀ and MIC₉₀ of lipoglycopeptides did not exceed 0.06 µg/ml and 0.125 µg/ml, respectively. Oritavancin showed strong activity against VREf at MIC range of 0.03 µg/ml to 0.5 µg/ml, and at MIC₉₀ of 0.25 µg/ml. Thus, lipoglycopeptide antibiotics are a plausible alternative to vancomycin and daptomycin; they are characterized by pronounced activity and can be used to treat severe forms of staphylococcal infections.
Vancomycin and daptomycin are first-line drugs for the treatment of complicated methicillin-resistant Staphylococcus aureus (MRSA) infections, including bacteremia. However, their effectiveness is limited not only by their resistance to each antibiotic but also by their associated resistance to both drugs. It is unknown whether novel lipoglycopeptides can overcome this associated resistance. Resistant derivatives from five S. aureus strains were obtained during adaptive laboratory evolution with vancomycin and daptomycin. Both parental and derivative strains were subjected to susceptibility testing, population analysis profiles, measurements of growth rate and autolytic activity, and whole-genome sequencing. Regardless of whether vancomycin or daptomycin was selected, most of the derivatives were characterized by a reduced susceptibility to daptomycin, vancomycin, telavancin, dalbavancin, and oritavancin. Resistance to induced autolysis was observed in all derivatives. Daptomycin resistance was associated with a significant reduction in growth rate. Resistance to vancomycin was mainly associated with mutations in the genes responsible for cell wall biosynthesis, and resistance to daptomycin was associated with mutations in the genes responsible for phospholipid biosynthesis and glycerol metabolism. However, mutations in walK and mprF were detected in derivatives selected for both antibiotics.
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