МИКРОБИОЛОГИЧЕСКАЯ ЭФФЕКТИВНОСТЬ КОМБИНАЦИЙ АНТИБИОТИКОВ В ОТНОШЕНИИ ИНВАЗИВНЫХ ШТАММОВ KLEBSIELLA PNEUMONIAE

Введение. Комбинированная антибиотикотерапия – основной способ лечения инфекций, вызванных антибиотикорезистентными бактериями. Цель исследования – выявить комбинации антибиотиков с синергидной активностью в отношении инвазивных экстремально-антибиотикорезистентных штаммов K.pneumoniae, продуцирующих карбапенемазы. Материал и методы. Для 12 инвазивных штаммов K.pneumoniae, продуцирующих карбапенемазы KPC, OXA-48 и NDM, определены минимальные подавляющие концентрации антибиотиков. Определение чувствительности к комбинациям антибиотиков выполнено модифицированным диско-диффузионным методом. Результаты. Отмечен эффект потенцирования колистина азтреонамом (58,3% штаммов), азитромицином (33,3%), кларитромицином (41,7%), рифампицином (33,3%), доксициклином (50,0%). Показана высокая микробиологическая эффективность цефтазидима/авибактама в отношении всех продуцентов карбапенемаз KPC и OXA-48. Для продуцентов MBL NDM выявлен синергидный эффект комбинации цефтазидима/авибактама и азтреонама с восстановлением чувствительности. Выводы. Полученные результаты открывают перспективы для комбинированной терапии инфекций кровотока, вызванных XDR-штаммами K.pneumoniae

Антибактериальное покрытие имплантатов на основе полиметилметакрилатного костного цемента in vitro и in vivo

Nowadays, the infection recurrence rate in osteomyelitis is still high. New hardware not only allowing one to stabilize bone fragments, but also having antibacterial activity seems to be an extremely useful and promising task. The goal of the study was to assess the effectiveness of use of an antibacterial coating based on polymethylmethacrylate cement in experiment and in infected nonunions of long tubular bones of the lower limbs. Bone cement-based coatings impregnated with antibiotics were formed on titanium plates. A plate rinse was carried out; antibiotic concentrations in the rinsed solutions were estimated by a serial broth microdilution method. The antibacterial activity of 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. Clinical part. The study included 70 patients divided into 2 groups: osteosynthesis with antibacterial-coated interlocking nail (40 patients, main group) and osteosynthesis with an external fixation device (30 patients, control group) comparable in age, sex and disease duration. The effectiveness of the antibacterial coating was analyzed by the duration of systemic use of antibiotics and infection recurrence rate. The concentrations of meropenem and phosphomycin in the rinsed solutions obtained at one-fold and two-fold treatments were sufficient to suppress the growth of control strains. Vancomycin-containing samples possessed sufficient antibacterial activity against both methicillin-sensitive (MSSA) and methicillin-resistant (MRSA) S. aureus strains, double rinse of the samples eliminated their bactericidal properties. The duration of systemic antibacterial therapy in the main group was statistically significantly lower than in the control group (U = 77.5, p < 0.001), and in the main group the infection recurrence rate was lower than 32.5 % vs. 86.7 % (χ2 = 20.39, p < 0.001). The PMMA-based coating impregnated with phosphomycin, meropenem or vancomycin possesses sufficient and long-lasting antibacterial activity, mainly against antibiotic-sensitive strains. An adequate use of such a coating in clinical practice allows one to obtain the desired result of treatment.Частота рецидивов после костных инфекций в настоящее время высока. Создание конструкции, которая не только позволяет стабилизировать костные отломки, но и обладает антибактериальной активностью, представляется чрезвычайно актуальной и перспективной задачей. Цель исследования – оценить эффективность применения антибактериального покрытия на основе полиметилметакрилатного цемента в эксперименте и при инфицированных несращениях длинных трубчатых костей нижних конечностей. На титановых пластинах сформированы покрытия из костного цемента, импрегнированного антибиотиками. Выполнена отмывка пластин методом последовательных микроразведений в бульоне, оценена концентрация антибиотиков в отмывочных растворах. Антибактериальная активность образцов в отношении чувствительных и множественно-резистентных штаммов S. aureus и P. aeruginosa оценена двуслойным агаровым методом. В исследование включены 70 пациентов, разделенных на 2 группы: остеосинтез стержнем с блокированием и антибактериальным покрытием (40 пациентов, основная группа) и остеосинтез аппаратом внешней фиксации (30 пациентов, контрольная группа), сопоставимые по возрасту, полу и продолжительности заболевания. Эффективность антибактериального покрытия анализировали по продолжительности системного применения антибактериальных препаратов и наличию рецидивов инфекции. Концентрации меропенема и фосфомицина в отмывочных растворах, полученных при однократной и двукратной обработке образцов, были достаточными для подавления роста контрольных штаммов. Ванкомицин-содержащие образцы обладали достаточной антибактериальной активностью в отношении как метициллинчувствительного (MSSA), так и метициллинрезистентного (MRSA) штаммов S. aureus, двукратная отмывка образцов устраняла их бактерицидные свойства. Продолжительность системной антибактериальной терапии в основной группе была статистически значимо меньше, чем в контрольной (U = 77,5, p < 0,001), также в основной группе наблюдалось меньше рецидивов инфекции 32,5 % vs. 86,7 % (χ2 = 20,39; p < 0,001). Покрытия из костного цемента, импрегнированного фосфомицином, меропенемом или ванкомицином, обладают достаточной и длительной антибактериальной активностью, проявляющейся главным образом в отношении антибиотикочувствительных штаммов. Адекватное применение такого покрытия в клинической практике позволяет получить желаемый результат лечения

МЕХАНИЗМ ФОРМИРОВАНИЯ ПОЛИЛАКТИДНЫХ ПОКРЫТИЙ ИЗ АКТИВНОЙ ГАЗОВОЙ ФАЗЫ

The mechanism of deposition of a poly-L-lactide film from the active gas phase has been shown to be associated with destructing a macromolecule into large fragments rather than with depolymerizing a poly-L-lactide film to a monomer followed by its polycondensation on substrate. The transformation of the initial polymer powder into a thin film under the great energetic effect is accompanied by decreasing the molecule mass, while the D-isomer content increases from 4 to 12 %. In so doing, not only the phase state of the polymer changes from semi-crystalline to amorphous one, but the poly-L-lactide relaxation state is transformed from glass to rubber one; these changes could promote an accelerated release of different biocide additives from the film.Методами спектроскопии ЯМР 1 H и 13С и поляриметрии установлено, что при формировании тонких пленок поли-L-лактида путем осаждения из активной газовой фазы происходит деструкция исходного полимера до крупных фрагментов с сохранением полимерного состояния вещества. Одновременно конфигурационные превращения макромолекулы приводят к увеличению содержания в ней D-звеньев с 4 до 12 мол. %, в результате чего исходный аморфно-кристаллический полимер превращается в аморфный. Переход поли-L-лактида в тонкопленочное состояние сопровождается изменением не только фазового, но и релаксационного состояния полимера, что является дополнительной причиной ускорения высвобождения из пленки биоцидных добавок

Antibacterial Activity of Antibiotic-Impregnated Bone Cement Based Coatings Against Microorganisms with Different Antibiotic Resistance Levels

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

Prevalence of carbapenemase-producing <i>Klebsiella pneumoniae</i> in the Gomel Region

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

Coatings Based on Two-Dimensionally Ordered Linear Chain Carbon for Protection of Titanium Implants from Microbial Colonization

Purpose of the study – to evaluate the antibacterial activity and biological compatibility of alloy coatings based on two-dimensionally ordered linear chain carbon (TDOLCC).Materials and Methods. Coatings based on TDOLCC were synthesized using alloying additions like nitrogen (TDOLCC+N) and silver (TDOLCC+Ag) on the surfaces of titanium plates and polystyrene plates by the ion-stimulated carbon condensation in a vacuum. The authors examined the superficial bactericidal activity of the coatings and its resistance to mechanical effects. Coated plates were evaluated in respect of rate of microbial biofilms formation by clinical isolates with multiple and extreme antibiotic resistance. Specimens were colored with crystal violet solution to visualize the biofilms. Cytotoxic effect of coatings was evaluated in respect of primary culture of fibroblasts and keratinocyte cell line HaCaT.Results. The authors observed pronounced superficial bactericidal effect of TDOLCC+Ag coating in respect of microorganisms of several taxonomic groups independently of their resistance to antibacterial drugs. TDOLCC+Ag coating proved capable to completely prevent microbial biofilm formation by antibiotic resistant clinical isolates of S. aureus and P. aeruginosa. Silvercontaining coating demonstrated mechanical resistance and preservation of close to baseline level of superficial bactericidal activity even after lengthy abrasion treatment. TDOLCC based coatings did not cause any cytotoxic effects. Structure of monolayers formed in cavities coated by TDOLCC+N and TDOLCC+Ag was indistinguishable from the monolayers in cavities of control plates

Long-term dissemination of CTX-M-5-producing hypermutable Salmonella enterica serovar typhimurium sequence type 328 strains in Russia, Belarus, and Kazakhstan

In this paper, we present evidence of long-term circulation of cefotaxime-resistant clonally related Salmonella enterica serovar Typhimurium strains over a broad geographic area. The genetic relatedness of 88 isolates collected from multiple outbreaks and sporadic cases of nosocomial salmonellosis in various parts of Russia, Belarus, and Kazakhstan from 1996 to 2009 was established by multilocus tandem-repeat analysis (MLVA) and multilocus sequence typing (MLST). The isolates belong to sequence type 328 (ST328) and produce CTX-M-5 β-lactamase, whose gene is carried by highly related non-self-conjugative but mobilizable plasmids. Resistance to nalidixic acid and low-level resistance to ciprofloxacin is present in 37 (42%) of the isolates and in all cases is determined by various single point mutations in the gyrA gene quinolone resistance-determining region (QRDR). Isolates of the described clonal group exhibit a hypermutable phenotype that probably facilitates independent acquisition of quinolone resistance mutations. Copyright © 2014 American Society for Microbiology. All Rights Reserved