The 51 references with 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

Total in-text references: 1
  1. In-text reference with the coordinate start=1760
    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.

2

Total in-text references: 1
  1. In-text reference with the coordinate start=2635
    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.

3

Total in-text references: 1
  1. In-text reference with the coordinate start=2635
    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.

4

Total in-text references: 1
  1. In-text reference with the coordinate start=2635
    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.

5

Total in-text references: 1
  1. In-text reference with the coordinate start=2635
    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.

6

Total in-text references: 1
  1. In-text reference with the coordinate start=3765
    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].

7

Total in-text references: 2
  1. In-text reference with the coordinate start=3765
    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].

  2. In-text reference with the coordinate start=6176
    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.

8

Total in-text references: 3
  1. In-text reference with the coordinate start=3765
    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].

  2. In-text reference with the coordinate start=4019
    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.

  3. In-text reference with the coordinate start=5459
    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.

9

Total in-text references: 4
  1. In-text reference with the coordinate start=4688
    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].

  2. In-text reference with the coordinate start=4969
    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.

  3. In-text reference with the coordinate start=5459
    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.

  4. In-text reference with the coordinate start=6176
    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.

10

Total in-text references: 1
  1. In-text reference with the coordinate start=4688
    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].

11

Total in-text references: 3
  1. In-text reference with the coordinate start=4688
    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].

  2. In-text reference with the coordinate start=8865
    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

  3. In-text reference with the coordinate start=13311
    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].

12

Total in-text references: 3
  1. In-text reference with the coordinate start=4688
    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].

  2. In-text reference with the coordinate start=8865
    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

  3. In-text reference with the coordinate start=13311
    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].

13

Total in-text references: 3
  1. In-text reference with the coordinate start=4688
    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].

  2. In-text reference with the coordinate start=8865
    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

  3. In-text reference with the coordinate start=13311
    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].

14

Total in-text references: 1
  1. In-text reference with the coordinate start=6176
    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.

15

Total in-text references: 1
  1. In-text reference with the coordinate start=6176
    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.

16

Total in-text references: 1
  1. In-text reference with the coordinate start=6762
    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
    . Inhaled antibiotics in modern medicine [22] 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.

17

Total in-text references: 1
  1. In-text reference with the coordinate start=8724
    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].

18

Total in-text references: 1
  1. In-text reference with the coordinate start=8724
    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].

19

Total in-text references: 2
  1. In-text reference with the coordinate start=8724
    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].

  2. In-text reference with the coordinate start=14380
    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].

20

Total in-text references: 3
  1. In-text reference with the coordinate start=8724
    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].

  2. In-text reference with the coordinate start=9823
    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.

  3. In-text reference with the coordinate start=14380
    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].

21

Total in-text references: 3
  1. In-text reference with the coordinate start=8724
    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].

  2. In-text reference with the coordinate start=9823
    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.

  3. In-text reference with the coordinate start=14380
    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].

22

Total in-text references: 9
  1. In-text reference with the coordinate start=6807
    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 [16]. Inhaled antibiotics in modern medicine
    Exact
    [22]
    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.

  2. In-text reference with the coordinate start=8724
    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].

  3. In-text reference with the coordinate start=9874
    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.

  4. In-text reference with the coordinate start=13618
    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.

  5. In-text reference with the coordinate start=14107
    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].

  6. In-text reference with the coordinate start=14380
    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].

  7. In-text reference with the coordinate start=14594
    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.

  8. In-text reference with the coordinate start=15564
    Prefix
    Only special preparations for inhalation must be used to prevent these complications. Inhaled antibiotics and nebulizers are expensive, their use is associated with the environment pollution and resistance formation
    Exact
    [22, 50]
    Suffix
    . Formation of microbial resistance is still a problem, but as it has been mentioned, the rate of resistance formation is lower in IA than in intravenous antibiotics. The informativity of sputum microbiology decreases in IA use: the absence of microbes in sputum does not mean their absence in distal parts of tracheobronchial tree and in alveoli.

  9. In-text reference with the coordinate start=16018
    Prefix
    The informativity of sputum microbiology decreases in IA use: the absence of microbes in sputum does not mean their absence in distal parts of tracheobronchial tree and in alveoli. There are currently no inhaled anti-gram-positive antibiotics
    Exact
    [22, 50]
    Suffix
    . Thus, the use of IA in combination with the intravenous administration is an efficient and safe treatment modality for severe NP caused by gram-negative strains. In spite of low evidence for this treatment method, the current situation of high microbial resistance and no perspectives of new antibiotics development rises the significance of this treatment modality.

23

Total in-text references: 2
  1. In-text reference with the coordinate start=8865
    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

  2. In-text reference with the coordinate start=11870
    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.

24

Total in-text references: 1
  1. In-text reference with the coordinate start=8865
    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

25

Total in-text references: 1
  1. In-text reference with the coordinate start=8865
    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

26

Total in-text references: 1
  1. In-text reference with the coordinate start=8865
    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

27

Total in-text references: 2
  1. In-text reference with the coordinate start=8865
    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

  2. In-text reference with the coordinate start=10793
    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.

28

Total in-text references: 2
  1. In-text reference with the coordinate start=8865
    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

  2. In-text reference with the coordinate start=10793
    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.

29

Total in-text references: 3
  1. In-text reference with the coordinate start=8865
    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

  2. In-text reference with the coordinate start=9061
    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.

  3. In-text reference with the coordinate start=10793
    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.

30

Total in-text references: 3
  1. In-text reference with the coordinate start=8865
    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

  2. In-text reference with the coordinate start=9061
    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.

  3. In-text reference with the coordinate start=10793
    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.

31

Total in-text references: 3
  1. In-text reference with the coordinate start=8865
    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

  2. In-text reference with the coordinate start=9061
    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.

  3. In-text reference with the coordinate start=11981
    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.

32

Total in-text references: 3
  1. In-text reference with the coordinate start=8865
    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

  2. In-text reference with the coordinate start=9061
    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.

  3. In-text reference with the coordinate start=10793
    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.

33

Total in-text references: 2
  1. In-text reference with the coordinate start=8865
    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

  2. In-text reference with the coordinate start=10793
    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.

34

Total in-text references: 1
  1. In-text reference with the coordinate start=8865
    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

35

Total in-text references: 1
  1. In-text reference with the coordinate start=8865
    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

36

Total in-text references: 2
  1. In-text reference with the coordinate start=8865
    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

  2. In-text reference with the coordinate start=10793
    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.

37

Total in-text references: 1
  1. In-text reference with the coordinate start=8865
    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

38

Total in-text references: 1
  1. In-text reference with the coordinate start=8865
    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

39

Total in-text references: 1
  1. In-text reference with the coordinate start=8865
    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

40

Total in-text references: 1
  1. In-text reference with the coordinate start=9100
    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].

41

Total in-text references: 2
  1. In-text reference with the coordinate start=9122
    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].

  2. In-text reference with the coordinate start=11499
    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].

42

Total in-text references: 1
  1. In-text reference with the coordinate start=9157
    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].

43

Total in-text references: 1
  1. In-text reference with the coordinate start=9175
    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].

44

Total in-text references: 1
  1. In-text reference with the coordinate start=9270
    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].

45

Total in-text references: 1
  1. In-text reference with the coordinate start=9270
    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].

46

Total in-text references: 1
  1. In-text reference with the coordinate start=9495
    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).

47

Total in-text references: 1
  1. In-text reference with the coordinate start=9823
    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.

48

Total in-text references: 1
  1. In-text reference with the coordinate start=10793
    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.

49

Total in-text references: 1
  1. In-text reference with the coordinate start=11746
    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].

50

Total in-text references: 4
  1. In-text reference with the coordinate start=14380
    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].

  2. In-text reference with the coordinate start=14594
    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.

  3. In-text reference with the coordinate start=15564
    Prefix
    Only special preparations for inhalation must be used to prevent these complications. Inhaled antibiotics and nebulizers are expensive, their use is associated with the environment pollution and resistance formation
    Exact
    [22, 50]
    Suffix
    . Formation of microbial resistance is still a problem, but as it has been mentioned, the rate of resistance formation is lower in IA than in intravenous antibiotics. The informativity of sputum microbiology decreases in IA use: the absence of microbes in sputum does not mean their absence in distal parts of tracheobronchial tree and in alveoli.

  4. In-text reference with the coordinate start=16018
    Prefix
    The informativity of sputum microbiology decreases in IA use: the absence of microbes in sputum does not mean their absence in distal parts of tracheobronchial tree and in alveoli. There are currently no inhaled anti-gram-positive antibiotics
    Exact
    [22, 50]
    Suffix
    . Thus, the use of IA in combination with the intravenous administration is an efficient and safe treatment modality for severe NP caused by gram-negative strains. In spite of low evidence for this treatment method, the current situation of high microbial resistance and no perspectives of new antibiotics development rises the significance of this treatment modality.

51

Total in-text references: 1
  1. In-text reference with the coordinate start=14594
    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.