The rapid emergence of antibiotic-resistant bacterial "superbugs" with concomitant treatment failure and high mortality rates presents a severe threat to global health. The superbug risk is further exacerbated by chronic infections generated from antibiotic-resistant biofilms that render them refractory to available treatments. We hypothesized that efficient antimicrobial agents could be generated through careful engineering of hydrophobic and cationic domains in a synthetic semirigid polymer scaffold, mirroring and amplifying attributes of antimicrobial peptides. We report the creation of polymeric nanoparticles with highly efficient antimicrobial properties. These nanoparticles eradicate biofilms with low toxicity to mammalian cells and feature unprecedented therapeutic indices against red blood cells. Most notably, bacterial resistance toward these nanoparticles was not observed after 20 serial passages, in stark contrast to clinically relevant antibiotics where significant resistance occurred after only a few passages.
The Spectra Optia CMNC device using lower centrifugal force (PF4·0) showed similar target cell yield and composition as well as collection efficiencies with superior performance parameters and lower PLT contamination compared to the MNC setting.
Objective.
To reveal antibiotics being capable of potentiating the antimicrobial activity of colistin against multidrug- and extensively drug-resistant strains of Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa.
Materials and Methods.
The minimum inhibitory concentrations (MIC) of colistin alone and in combination with fixed concentrations of antibiotics of different groups were determined for 272 multidrug- and extensively drug-resistant strains of K. pneumoniae, A. baumannii and P. aeruginosa. Bactericidal activity of colistin, carbapenems, clarithromycin and their combinations were also determined at fixed PK/PD breakpoint concentrations of antibiotics.
Results.
Potentiation of colistin antibacterial activity in the presence of fixed concentration of rifampicin (0.5 mg/L) was observed as a 4–16-fold MIC decrease for K. pneumoniae and A. baumannii. In the presence of fixed concentrations of azithromycin (2 mg/L) or clarithromycin (1 mg/L), the colistin MICs decreased 64–512 times for K. pneumoniae, 4–32 times for A. baumannii, 16–64 times for P. aeruginosa. Two- or more-fold reduction of MIC of colistin in the presence of 1 mg/L clarithromycin was observed for 85.2% of K. pneumoniae, 86.3% of A. baumannii and 60.2% of P. aeruginosa strains. In the presence of 1 mg/L clarithromycin and 8 mg/L meropenem, the potentiation effect was enhanced and was observed for an even larger percent of isolates: 96.1% K. pneumoniae, 98.0% A. baumannii and 61.3% P. aeruginosa. Colistin-based combinations with clarithromycin-meropenem and clarithromycin-doripenem were bactericidal against most isolates of A. baumannii and P. aeruginosa (91.4–100%), and against colistin-sensitive K. pneumoniae (95.3%) and colistin-resistant K. pneumoniae (79.1%).
Conclusions.
The ability of macrolides to significantly potentiate the colistin antimicrobial activity against both colistin-sensitive and colistin-resistant strains of K. pneumoniae, A. baumannii and P. aeruginosa was shown. This potentiation effect was enhanced in the presence of carbapenems. The most potent bactericidal activity was revealed with dual and triple combinations of colistin-clarithromycin and colistinclarithromycin-carbapenems.
Aim. Within the microbiological monitoring program, to study the prevalence of carbapenemase-producing K. pneumoniae in the healthcare organizations of the Gomel region and assess their level of resistance to antibacterial drugs. Materials and methods. For 91 clinical isolates of Klebsiella pneumoniae with multiple antibiotic resistance, isolated in Gomel and Gomel region, carbapenemase genes were detected by real-time PCR and sensitivity to antibacterial drugs was determined. Results. 68 carbapenemase producers were revealed: KPC — 1 isolate, OXA-48 — 47 isolates, NDM — 20 isolates. Carbapenemase producers were found in 11 Gomel health organizations and 8 central district hospitals of the regional centers of the Gomel region. All of them had an associated resistance to most antibiotics and retained sensitivity to colistin (91.2% sensitive isolates) and tigecycline (98.5%). Conclusion. The spread of carbapenemase-producing K. pneumoniae isolates in healthcare organizations makes it very difficult to conduct effective antibiotic therapy for patients and requires the introduction of appropriate infection control measures aimed at limiting their circulation in the hospital environment.
Purpose — to evaluate the presence and duration of antibiotic activity of antibiotic-impregnated bone cement based coatings samples against antibiotic-sensitive and antibiotic-resistant microorganisms.Material and Methods. Bone cement based coatings impregnated with antibiotics (gentamycin, vancomycin, colistin, meropenem, fosfomycin) are formed on titanium (Ti) plates. A plate rinse was carried out; antibiotic concentrations in the rinsed solutions were estimated by a serial broth microdilution method. Antibacterial activity of the control and rinsed samples against the antibiotic-sensitive and multiple-antibiotic-resistant Staphylococcus aureus and Pseudomonas aeruginosa strains was estimated by a bilayer agar method.Results. The meropenem and fosfomycin concentrations in the rinsed solutions obtained at a one-fold (16 μg/ml for both antibiotics) and two-fold treatment (2 μg/ml for meropenem and 8 μg/ml for fosfomycin) were sufficient to suppress the growth of the control strains. One-fold rinse of samples with colistin eliminated their antibacterial activity completely. The marked activity of the samples with meropenem and fosfomycin persisted against the antibiotic-sensitive P. aeruginosa ATCC 27853 strain after 2 rinse cycles; single-rinsed samples with fosfomycin also maintained the activity against the extensively antibioticresistant P. aeruginosa BP-150 strain. Vancomycin-containing samples possessed the sufficient antibacterial activity against both methicillin-sensitive (MSSA) and methicillin-resistant (MRSA) S. aureus strains; two-fold rinse of the samples eliminated their bactericidal properties.Conclusion. Bone cement based coatings impregnated with fosfomycin and meropenem possess the most marked and long-lasting antibacterial activity, manifested mainly against the antibiotic-sensitive strains.
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