The 22 reference contexts in paper A. Yakovlev Yu, N. Gushchina N., A. Niyazmatov A., R. Zatsev M, E. Golubtsova Yu, M. Ryabikova A., А. Яковлев Ю., Н. Гущина Н., А. Ниязматов А., Р. Зайцев М, Е. Голубцова Ю., М. Рябикова А. (2013) “Ранняя оценка эффективности антибактериальной терапии нозокомиальной пневмонии путем количественного определения липополисахарида // Early Evaluation of the Efficiency of Antibiotic Therapy for Nosocomial Pneumonia by Quantifying Lipopolysaccharide” / spz:neicon:reanimatology:y:2013:i:6:p:45

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    Introduction One percent of hospital patients suffer from the nosocomial pneumonia (NP) that is developed in 20% of mechanically ventilated patients. NP increases the risk of death and requires considerable treatment expenses
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    [1—4]
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    . The most frequent causes of NP are infections evoked by gram-negative (Pseudomonas aeruginosa, Acinetobacter spiralis., Klebsiella spiralis. etc.) and gram-positive (Staphylococcus aureus) microorganisms multiresistant to antibacterial drugs (ABD) [5].
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    The most frequent causes of NP are infections evoked by gram-negative (Pseudomonas aeruginosa, Acinetobacter spiralis., Klebsiella spiralis. etc.) and gram-positive (Staphylococcus aureus) microorganisms multiresistant to antibacterial drugs (ABD)
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    [5]
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    . The diversity of «problem» bacteria causing nosocomial infections and high lethality are due to inadequacy of ABD use or delay in ABD administration. These obstacles are usually circumventing by the use of evidencebased regimens of treatment with those ABD that are active against most actual germs and capable to overcome resistance mechanisms of hospital fl
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    These obstacles are usually circumventing by the use of evidencebased regimens of treatment with those ABD that are active against most actual germs and capable to overcome resistance mechanisms of hospital flora
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    [6]
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    . This is considered as a reason for a deescalation therapy [7—9]. Clinical and economical consequences of multiresistance of bacteria to ABD and lack of new ABD active against those pathogens stimulated the inhalationt use of ABD [10], the efficacy of which was proved in cystic fibrosis patients [11, 12].
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    971
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    These obstacles are usually circumventing by the use of evidencebased regimens of treatment with those ABD that are active against most actual germs and capable to overcome resistance mechanisms of hospital flora [6]. This is considered as a reason for a deescalation therapy
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    [7—9]
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    . Clinical and economical consequences of multiresistance of bacteria to ABD and lack of new ABD active against those pathogens stimulated the inhalationt use of ABD [10], the efficacy of which was proved in cystic fibrosis patients [11, 12].
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    1163
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    This is considered as a reason for a deescalation therapy [7—9]. Clinical and economical consequences of multiresistance of bacteria to ABD and lack of new ABD active against those pathogens stimulated the inhalationt use of ABD
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    [10]
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    , the efficacy of which was proved in cystic fibrosis patients [11, 12]. Inhalation allows maintaining the high concentration of the medication in the infection area [13] resulting in better bacterial killing [14, 15] and lowing both systemic absorption of medication and toxicity [16].
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    1231
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    Clinical and economical consequences of multiresistance of bacteria to ABD and lack of new ABD active against those pathogens stimulated the inhalationt use of ABD [10], the efficacy of which was proved in cystic fibrosis patients
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    [11, 12]
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    . Inhalation allows maintaining the high concentration of the medication in the infection area [13] resulting in better bacterial killing [14, 15] and lowing both systemic absorption of medication and toxicity [16].
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    1341
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    Clinical and economical consequences of multiresistance of bacteria to ABD and lack of new ABD active against those pathogens stimulated the inhalationt use of ABD [10], the efficacy of which was proved in cystic fibrosis patients [11, 12]. Inhalation allows maintaining the high concentration of the medication in the infection area
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    [13]
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    resulting in better bacterial killing [14, 15] and lowing both systemic absorption of medication and toxicity [16]. Recently conducted pilot studies have demonstrated the efficiency of combining the systemic antibacterial therapy with inhalations.
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    1383
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    and economical consequences of multiresistance of bacteria to ABD and lack of new ABD active against those pathogens stimulated the inhalationt use of ABD [10], the efficacy of which was proved in cystic fibrosis patients [11, 12]. Inhalation allows maintaining the high concentration of the medication in the infection area [13] resulting in better bacterial killing
    Exact
    [14, 15]
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    and lowing both systemic absorption of medication and toxicity [16]. Recently conducted pilot studies have demonstrated the efficiency of combining the systemic antibacterial therapy with inhalations.
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    1454
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    Inhalation allows maintaining the high concentration of the medication in the infection area [13] resulting in better bacterial killing [14, 15] and lowing both systemic absorption of medication and toxicity
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    [16]
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    . Recently conducted pilot studies have demonstrated the efficiency of combining the systemic antibacterial therapy with inhalations. The combination therapy improved therapeutic efficacy with low toxic effects in patients [17—21].
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    1704
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    Recently conducted pilot studies have demonstrated the efficiency of combining the systemic antibacterial therapy with inhalations. The combination therapy improved therapeutic efficacy with low toxic effects in patients
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    [17—21]
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    . Numerous studies had demonstrated the advantages of inhaled tobramycin versus intravenous mode in severe NP cases [22—26]. Until today the estimation of the antibacterial therapy effectiveness is based on clinical parameters (body temperature, leukocytosis, somatic status) that are available for analysis after 48—72 hours of beginning of the therapy [7, 27].
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    The combination therapy improved therapeutic efficacy with low toxic effects in patients [17—21]. Numerous studies had demonstrated the advantages of inhaled tobramycin versus intravenous mode in severe NP cases
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    [22—26]
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    . Until today the estimation of the antibacterial therapy effectiveness is based on clinical parameters (body temperature, leukocytosis, somatic status) that are available for analysis after 48—72 hours of beginning of the therapy [7, 27].
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    2083
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    Until today the estimation of the antibacterial therapy effectiveness is based on clinical parameters (body temperature, leukocytosis, somatic status) that are available for analysis after 48—72 hours of beginning of the therapy
    Exact
    [7, 27]
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    . Methods of early bacterial identification in concert with the estimation of antibiotic sensitivity might have limited availability due to technological problems and high cost of analyzing equipment and operating materials.
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    5039
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    Earlier studies showed an increase in LPS binding protein and endotoxin concentrations in patients with severe pneumonia, however, the dynamics of these molecules during the antibacterial therapy was not evaluated
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    [28, 29]
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    . Analysis of the arterial-venous difference of gram-negative bacteria LPS level might provide information on detoxifying activities of the lungs detoxicant activity as well as on the site of the gram-negative infection in the pulmonary circuit.
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    7383
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    Inhaled tobramycin was employed as the main medication due to absence of other sites of infection and because of proved fast and equal diffusion through lung tissue regardless the initial ventilation-perfusion imbalance
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    [30]
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    . There were no cases of microflora resistance against the applied ABD found. Initial microbiological inoculation showed no significant difference between the groups. Patients that had gram-positive microflora in culture sputum in combination with gram-negative microorganisms were excluded from the study. 22 patients were transferred from intensive care departments of other hospi
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    11320
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    In future the administration of bronchial spasmolytics and early aminophylline inhalation prevented similar complications. There was no cases of ototoxicity or nephrotoxicity when employing the inhaled tobramycin. LPS (endotoxin, O-antigen) is a membrane structural component of all gram-negative bacteria
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    [31]
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    . The structural alterations of a bacterial membrane results in endotoxemia since one bacteria contain up to 3 500 000 LPS molecules. High activity of carbapenems and aminoglycosides (especially tobramycin and amikacin) against non-fermenting gramnegative flora leads to rapid killing of germs [32].
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    11635
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    The structural alterations of a bacterial membrane results in endotoxemia since one bacteria contain up to 3 500 000 LPS molecules. High activity of carbapenems and aminoglycosides (especially tobramycin and amikacin) against non-fermenting gramnegative flora leads to rapid killing of germs
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    [32]
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    . This results in a release of large number of LPS molecules into microenvironment and arterial blood stream thus providing potential benefit to employ these consequences in developing method for express evaluation of effectiveness of antibacterial therapy.
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    13037
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    faster germ-killig effect in sputum and bronchial/alveolar microenvironment because the intravenous injections of ABD accumulation of the active substance there is delayed due to due to alterations of drug distribution in tissues. These findings have been proved indirectly in numerous papers demonstrating clinical advantages of inhalations compared to intravenous therapy
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    [19, 21, 33]
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    . In our study high clinical effectiveness of the employed therapies has been demonstrated, however, any significant proof of inhalations advantages in terms of influence on titers of microorganisms in sputum has not been achieved.
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    13493
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    Aerosol aminoglycosides therapy is carried on easily by the patients and results in high concentration of the medication in lung tissue. At the same time their serum concentration is not intense
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    [33, 34]
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    . This improves therapy effectiveness, its safety and decreases side effects and adverse experiences. Only few such incident have been noted in present similar studies. It is unacceptable to employ intravenous and other forms of ABD for inhalations due to common complications (bronchial and glottic spasm, coughing, damages in the mouth, gorge, trachea and bronchi, breast
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    13948
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    It is unacceptable to employ intravenous and other forms of ABD for inhalations due to common complications (bronchial and glottic spasm, coughing, damages in the mouth, gorge, trachea and bronchi, breast pain) that may defame new therapy development
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    [35]
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    . It is known that after the first tobramycin inhalation its concentration in lungs of cystic fibrosis patients quickly reached maximum therapeutic means that 25-fold exceeded the minimum inhibitory concentration for Pseudomonas sp. remaining at a minimum concentration in blood [36].
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    14245
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    It is known that after the first tobramycin inhalation its concentration in lungs of cystic fibrosis patients quickly reached maximum therapeutic means that 25-fold exceeded the minimum inhibitory concentration for Pseudomonas sp. remaining at a minimum concentration in blood
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    [36]
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    . The same results were collected after examination of a lung cancer patient who had been receiving inhalant tobramycin before pulmonectomy [37]. This was also true for other studied antibiotics that required high concentration of ABD for effective killing of germs [38, 39].
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    14401
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    concentration in lungs of cystic fibrosis patients quickly reached maximum therapeutic means that 25-fold exceeded the minimum inhibitory concentration for Pseudomonas sp. remaining at a minimum concentration in blood [36]. The same results were collected after examination of a lung cancer patient who had been receiving inhalant tobramycin before pulmonectomy
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    [37]
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    . This was also true for other studied antibiotics that required high concentration of ABD for effective killing of germs [38, 39]. It is believed that further improvements in treatment with ABD through employing the inhaled forms of ABD might stem from the decrease of proinflammatory cytokines produced by neutrophils and macrophages (interleukine 1β, tumor necrosis factor α
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    14961
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    that further improvements in treatment with ABD through employing the inhaled forms of ABD might stem from the decrease of proinflammatory cytokines produced by neutrophils and macrophages (interleukine 1β, tumor necrosis factor αetc.) as well as from the manipulating of the release of molecules of intracellular adhesion 1 (sICAM-I) reducing the neutrophilous elastase
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    [21]
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    . Conclusion 1. After the beginning of the systemic or inhalation antibacterial therapy in patients with NP LPS level is increased in arterial blood. This quantitative pattern seems to be an early candidate biomarker of ABD efficacy in a particular patient.
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