The 31 reference contexts in paper A. Kuzovlev N., V. Moroz V., A. Golubev M., S. Polovnikov G., А. Кузовлев Н, В. Мороз В, А. Голубев М, С. Половников Г. (2013) “Ингаляционные антибиотики в лечении тяжелой нозокомиальной пневмонии // Inhaled Antibiotics in the Treatment of Nosocomial Pneumonia” / spz:neicon:reanimatology:y:2013:i:6:p:61

  1. Start
    470
    Prefix
    pneumonia (NP) — is a disease associated with a formation of new focal and infiltrative changes on the chest X-ray 48 hrs after the hospitalization along with the clinical data confirming their infectious nature (fever, purulent sputum or purulent discharge from the tracheobronchial tree, leukocytosis, etc.), excluding infections which were incubated on the admission
    Exact
    [1]
    Suffix
    . Nosocomial pneumonia — is the most prevalent intensive care unit infection. The high prevalence of NP is due to the widespread and irrational use of antibiotics and artificial pulmonary ventilation.
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  2. Start
    1337
    Prefix
    Nosocomial pneumonia significantly deteriorates the course of any disease, increase the duration of intensive care unit stay by 4,3—6,1 days and mortality. The attributable mortality of NP is between 5,8 to 27%
    Exact
    [2—5]
    Suffix
    . The pathogenesis of NP in critically ill patients is based on an imbalance between the lung protective mechanisms and microbial aggression. The lung can be infected either exogenously or endogenously.
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  3. Start
    3766
    Prefix
    Translocation of opportunistic microbes from the intestines is the other important pathogenetic factor of NP. Exogenous acquisition of NP may occur from the air, medical gases, respiratory devices, microbiota of medical personnel and other patients etc.
    Exact
    [6—8]
    Suffix
    The proved methods of NP prophylaxis in the intensive care unit include the 300 elevation of head, an early removal of nasogastric tubes, a continuous subglottic aspiration and a regular oral cleaning with watery chlorhexidine [8].
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  4. Start
    4020
    Prefix
    acquisition of NP may occur from the air, medical gases, respiratory devices, microbiota of medical personnel and other patients etc. [6—8] The proved methods of NP prophylaxis in the intensive care unit include the 300 elevation of head, an early removal of nasogastric tubes, a continuous subglottic aspiration and a regular oral cleaning with watery chlorhexidine
    Exact
    [8]
    Suffix
    . The key etiological agents of NP are cassociations of multiresistant gram-negative (Pseudomonas aeruginosa, Acinetobacterspp., Klebsiella pneumonia) and grampositive (Staphylococcus aureus) strains.
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  5. Start
    4689
    Prefix
    Associations of 3—4 multiresistant strains of Pseudomonas aeruginosa (70—80%), Acinetobacter baumanii/calcoaceticus (70—90%), Klebsilella pneumonia (30—40%), Proteus mirabilis (20—25%) were detected in our investigation; gram-positive strains were detected in 10—15% of patients (Staphylococcus aureusMRSA, Enterococcus faecalis, Enterococcus faecium)
    Exact
    [9—13]
    Suffix
    . Rational antibiotic therapy is the background of NP treatment. Intravenous carbapenems, cephalosporins III— IV generations, protected anti-pseudomonal penicillines, aminoglycosides, fluoroquinolones, glycopeptides and their combinations are recommended for NP treatment [9].
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  6. Start
    4970
    Prefix
    Intravenous carbapenems, cephalosporins III— IV generations, protected anti-pseudomonal penicillines, aminoglycosides, fluoroquinolones, glycopeptides and their combinations are recommended for NP treatment
    Exact
    [9]
    Suffix
    . Early start of antibiotics improves outcomes, but the mortality and microbial resistance still remain extremely high. The problem of microbial resistance to the majority of antibiotics is of great significance.
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  7. Start
    5460
    Prefix
    Pseudomonas aeruginosa, Acinetobacter spp., Burkholderiaspp., Stenotrophomonasspp., have a natural property to form biolayers, which protect them against the immune system and antibiotics. There are currently no perspectives of producing new classes of antibiotics
    Exact
    [8—9]
    Suffix
    . In view of the abovementioned special regimens of antibiotic therapy are recommended: increase of doses, continuous infusions, etc. Randomized controlled trial shows that continuous infusion of piperacillin/tazobactam and carbapenems decreases the mortality in NP.
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  8. Start
    6177
    Prefix
    Increasing daily doses of antibiotics is related to a risk of selection of multiresistant strains, side-effects and superinfection. Theferore inhaled antibiotics (IA) as an adjunct to systemic ones present a good treatment modality
    Exact
    [7, 9, 14—15]
    Suffix
    . Inhaled antibiotics The inhaled root has long been used to administer various medicines: antibiotics, antifungals, antimycobacterials, immune supressors, insulin, vaccines, nitrous oxide, interferones, furosemide, in genotherapy of some diseases.
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  9. Start
    6763
    Prefix
    Ehrmann S. et al. showed that 99% of German doctors use some inhaled preparations, 43% of them use nebulizers (55% — jet, 44% — ultrasound, 14% — mesh nebulizers). Eighty percent of them use inhaled colistin in their daily practice, and 30% use inhaled antibiotics minimum 2 times a year
    Exact
    [16]
    Suffix
    . AntibioticArea of implementationDosage AMINOGLYCOSIDES AmikacinExacerbation of bronchoectatic disease, mycobacterial infections.500 mg BID GentamycinExacerbation of bronchoectatic disease.80 mg BID TobramycinCystic fibrosis — prophylaxis and treatment of exacerbations.300 mg BID Treatment of nosocomial pneumonia.
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  10. Start
    8030
    Prefix
    B Prophylaxis of invasive aspergillosis in oncohematology.12,5 mg liposomal2 times/week for 2 days OTHERS ColistinCystic fibrosis — prophylaxis and treatment of exacerbations.1—2 million IU BID Treatment of nosocomial pneumonia. Continuous therapy of bronchoectatic disease PentamidinProphylaxis of Pneumocystis spp. pneumonia in HIV patients300 mg/month Inhaled antibiotics in modern medicine
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    [22]
    Suffix
    www.niiorramn.ru Inhaled colistin, tobramycin, cephalosporins, amphotericin B, pentamydin have been used for prophylaxis and treatment of various infections for more than 50 years now. Modern nebulizers help to administer nearly 50—70% of IA dose directly into the infection focus.
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  11. Start
    8725
    Prefix
    It is noteworthy that in this case the local sputum concentration of antibiotics is significantly higher that after the intravenous administration, which is important when treating multiresistant strains and preventing the formation of resistance. Inhaled administration of antibiotics is related to less systemic toxicity and a profound action on biolayers
    Exact
    [17—22]
    Suffix
    . Inhaled colistin and inhaled aminoglycosides are the most frequently used IA in pulmonology and intensive care medicine [11—13, 23—39]. Aminoglycosides are the most suitable antibiotics for inhalation because they are bactericidial and concentration-dependant (high concentration for a short period of time) [29—32].
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  12. Start
    8866
    Prefix
    Inhaled administration of antibiotics is related to less systemic toxicity and a profound action on biolayers [17—22]. Inhaled colistin and inhaled aminoglycosides are the most frequently used IA in pulmonology and intensive care medicine
    Exact
    [11—13, 23—39]
    Suffix
    . Aminoglycosides are the most suitable antibiotics for inhalation because they are bactericidial and concentration-dependant (high concentration for a short period of time) [29—32]. Also inhaled fluoroquinolones [40], cephalosporines [41], liposomal aminoglycosides [42]; aztreonam [43], combinations (fosfomycin/tobramycin, colitin/tobramycin, ciprofloxacin/colistin) [44—45
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  13. Start
    9062
    Prefix
    Inhaled colistin and inhaled aminoglycosides are the most frequently used IA in pulmonology and intensive care medicine [11—13, 23—39]. Aminoglycosides are the most suitable antibiotics for inhalation because they are bactericidial and concentration-dependant (high concentration for a short period of time)
    Exact
    [29—32]
    Suffix
    . Also inhaled fluoroquinolones [40], cephalosporines [41], liposomal aminoglycosides [42]; aztreonam [43], combinations (fosfomycin/tobramycin, colitin/tobramycin, ciprofloxacin/colistin) [44—45] are used.
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  14. Start
    9101
    Prefix
    Aminoglycosides are the most suitable antibiotics for inhalation because they are bactericidial and concentration-dependant (high concentration for a short period of time) [29—32]. Also inhaled fluoroquinolones
    Exact
    [40]
    Suffix
    , cephalosporines [41], liposomal aminoglycosides [42]; aztreonam [43], combinations (fosfomycin/tobramycin, colitin/tobramycin, ciprofloxacin/colistin) [44—45] are used. Inhaled fosfomycin is active against both gram-negatives and grampositives, but it is strongly recommended to combine it with other antibiotics to prevent a rapid resistance formation [46].
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  15. Start
    9123
    Prefix
    Aminoglycosides are the most suitable antibiotics for inhalation because they are bactericidial and concentration-dependant (high concentration for a short period of time) [29—32]. Also inhaled fluoroquinolones [40], cephalosporines
    Exact
    [41]
    Suffix
    , liposomal aminoglycosides [42]; aztreonam [43], combinations (fosfomycin/tobramycin, colitin/tobramycin, ciprofloxacin/colistin) [44—45] are used. Inhaled fosfomycin is active against both gram-negatives and grampositives, but it is strongly recommended to combine it with other antibiotics to prevent a rapid resistance formation [46].
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  16. Start
    9158
    Prefix
    Aminoglycosides are the most suitable antibiotics for inhalation because they are bactericidial and concentration-dependant (high concentration for a short period of time) [29—32]. Also inhaled fluoroquinolones [40], cephalosporines [41], liposomal aminoglycosides
    Exact
    [42]
    Suffix
    ; aztreonam [43], combinations (fosfomycin/tobramycin, colitin/tobramycin, ciprofloxacin/colistin) [44—45] are used. Inhaled fosfomycin is active against both gram-negatives and grampositives, but it is strongly recommended to combine it with other antibiotics to prevent a rapid resistance formation [46].
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  17. Start
    9176
    Prefix
    Aminoglycosides are the most suitable antibiotics for inhalation because they are bactericidial and concentration-dependant (high concentration for a short period of time) [29—32]. Also inhaled fluoroquinolones [40], cephalosporines [41], liposomal aminoglycosides [42]; aztreonam
    Exact
    [43]
    Suffix
    , combinations (fosfomycin/tobramycin, colitin/tobramycin, ciprofloxacin/colistin) [44—45] are used. Inhaled fosfomycin is active against both gram-negatives and grampositives, but it is strongly recommended to combine it with other antibiotics to prevent a rapid resistance formation [46].
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  18. Start
    9271
    Prefix
    Also inhaled fluoroquinolones [40], cephalosporines [41], liposomal aminoglycosides [42]; aztreonam [43], combinations (fosfomycin/tobramycin, colitin/tobramycin, ciprofloxacin/colistin)
    Exact
    [44—45]
    Suffix
    are used. Inhaled fosfomycin is active against both gram-negatives and grampositives, but it is strongly recommended to combine it with other antibiotics to prevent a rapid resistance formation [46].
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  19. Start
    9496
    Prefix
    Inhaled fosfomycin is active against both gram-negatives and grampositives, but it is strongly recommended to combine it with other antibiotics to prevent a rapid resistance formation
    Exact
    [46]
    Suffix
    . It is inexpedient to use inhaled beta-lactames, because they are concentration-dependant antibiotics, and therefore multiple inhalations will be required (e.g. every 3 hrs for ceftazidime).
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  20. Start
    9824
    Prefix
    It is inexpedient to use inhaled beta-lactames, because they are concentration-dependant antibiotics, and therefore multiple inhalations will be required (e.g. every 3 hrs for ceftazidime). Carbapenems when inhaled induce allergic reaction: inhaled doripenem study was stopped at stage one due to this reason
    Exact
    [20—21, 47]
    Suffix
    . Table deals with the currently used IA [22]. The majority of IA are used to treat acute and chronic pseudomonal infection in cystic fibrosis and bronchoectatic disease. Chronic preudomonal infection in cystic fibrosis increases mortality.
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  21. Start
    9875
    Prefix
    It is inexpedient to use inhaled beta-lactames, because they are concentration-dependant antibiotics, and therefore multiple inhalations will be required (e.g. every 3 hrs for ceftazidime). Carbapenems when inhaled induce allergic reaction: inhaled doripenem study was stopped at stage one due to this reason [20—21, 47]. Table deals with the currently used IA
    Exact
    [22]
    Suffix
    . The majority of IA are used to treat acute and chronic pseudomonal infection in cystic fibrosis and bronchoectatic disease. Chronic preudomonal infection in cystic fibrosis increases mortality.
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  22. Start
    10794
    Prefix
    But the recent meta-analysis shows that there are currently no evident data to support IA use in cystic fibrosis. Moreover, the increase of the prevalence of colistin and aminoglycoside resistant strains of Pseudomonas aeruginosaand gram-positive microbes is detected in cystic fibrosis patients
    Exact
    [27—30, 32—33, 36, 48]
    Suffix
    . There were no randomized multicenter trials of IA use in NP. Several small trials proved that IA in combination with systemic antibiotics decrease the symptoms of NP, facilitate weaning from ventilator, decrease the sputum microbes titer.
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  23. Start
    11500
    Prefix
    It is noteworthy that IA in this study were used as a monotherapy (ceftazidime 15 mg/kg every 3 hrs., amikacin 25 mg/kg/day). Several cases of exhalation filter obstruction were detected
    Exact
    [41]
    Suffix
    . The same group of authors proved later the same efficacy of inhaled colistin and combination of intravenous beta-lactames and aminoglycosides in NP patients caused by Pseudomonas aeruginosa and Acinetobacter baumanii [49].
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  24. Start
    11747
    Prefix
    The same group of authors proved later the same efficacy of inhaled colistin and combination of intravenous beta-lactames and aminoglycosides in NP patients caused by Pseudomonas aeruginosa and Acinetobacter baumanii
    Exact
    [49]
    Suffix
    . Korbila I. et al. showed more rapid NP resolution in combination of inhaled and intravenous forms of colistin [23]. Arnold H. et al. in the retrospective trial showed a higher survival in NP patients treated with IT [31].
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  25. Start
    11871
    Prefix
    The same group of authors proved later the same efficacy of inhaled colistin and combination of intravenous beta-lactames and aminoglycosides in NP patients caused by Pseudomonas aeruginosa and Acinetobacter baumanii [49]. Korbila I. et al. showed more rapid NP resolution in combination of inhaled and intravenous forms of colistin
    Exact
    [23]
    Suffix
    . Arnold H. et al. in the retrospective trial showed a higher survival in NP patients treated with IT [31]. All the abovementioned trials showed a low threshold of resistance emergence and low incidence of side effects in IA use.
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  26. Start
    11982
    Prefix
    Korbila I. et al. showed more rapid NP resolution in combination of inhaled and intravenous forms of colistin [23]. Arnold H. et al. in the retrospective trial showed a higher survival in NP patients treated with IT
    Exact
    [31]
    Suffix
    . All the abovementioned trials showed a low threshold of resistance emergence and low incidence of side effects in IA use. Our data on the inhaled tobramycin use in septic patients with NP proved its efficacy and safety: decrease of systemic inflammation and acute respiratory insufficiency signs 2,3±1,2 after the treatment onset.
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  27. Start
    13312
    Prefix
    The treatment with IT made it possible to wean 30% of patients on the day 5,2±1,7. Hearing loss and tinnitus was detected only in 2 patients in our study. There were no cases of bronchospasm or kidney dysfunction in our study, which is in accordance with the other trials
    Exact
    [11—13]
    Suffix
    . Only special preparations for inhalation and modern nebulizers must be used for an effective treatment with IA. The preparation for inhalation use should not contain some conservatives and should not be hyperosmolar, should be pH neutral and contain chlorides to prevent bronchospasm and cough [22].
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  28. Start
    13619
    Prefix
    Only special preparations for inhalation and modern nebulizers must be used for an effective treatment with IA. The preparation for inhalation use should not contain some conservatives and should not be hyperosmolar, should be pH neutral and contain chlorides to prevent bronchospasm and cough
    Exact
    [22]
    Suffix
    . Mesh nebulizers are most suitable for IA administration. This type of nebulizers forms 2.1 μm particles and provides a delivery of 5—70% of drug dose into the lungs; temperature of preparation remains constant during the aerosol formation; the air flow minimally affects the ventilation parameters; constant humidification of air can be continued.
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  29. Start
    14108
    Prefix
    forms 2.1 μm particles and provides a delivery of 5—70% of drug dose into the lungs; temperature of preparation remains constant during the aerosol formation; the air flow minimally affects the ventilation parameters; constant humidification of air can be continued. Instillation of antibiotics through the intubation or tracheostomic tube is ineffective and must never be used
    Exact
    [22]
    Suffix
    . Inhaled antibiotics are not used as a monotherapy without the systemic antibiotics, because their absorbtion into the blood is low (2—4%) and not sufficient to treat the concomitant extrapulmonary infections and moreover insufficient to reach the alveoli [19—22, 50].
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  30. Start
    14381
    Prefix
    Inhaled antibiotics are not used as a monotherapy without the systemic antibiotics, because their absorbtion into the blood is low (2—4%) and not sufficient to treat the concomitant extrapulmonary infections and moreover insufficient to reach the alveoli
    Exact
    [19—22, 50]
    Suffix
    . But we have a clinical experience of an effective monotherapy with IT in a patient with severe allergic reaction to systemic antibiotics. Currently it is not recommended to use IA for the NP prophylaxis [22, 50—51].
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  31. Start
    14595
    Prefix
    But we have a clinical experience of an effective monotherapy with IT in a patient with severe allergic reaction to systemic antibiotics. Currently it is not recommended to use IA for the NP prophylaxis
    Exact
    [22, 50—51]
    Suffix
    . Use of IA is related to some problems. The penetration of IA into the obstructed airways is deteriorated. A possible inactivation of IA in sputum should be taken into account. This effect is mostly profound in aminoglycosides.
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