Table 1 Characteristics of studies included in the meta-analysis
Study, year | Country | Inclusion population | No. of patients | Disease severity | Respiratory comorbidities | Administration strategy | Antibiotic given (dose) | Device for drug delivery | Main outcomes | Quality assessment/Cochrane risk of biasa | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
(AS/IV) | AS | IV | AS | IV | AS | IV | |||||||
Observational studies | |||||||||||||
 Ghannam, 2009 [9] | USA | Gram-negative bacteria VAP | 16/16 | CPIS score: 7 ± 2.9 | CPIS score: 6 ± 1.8 | COPD: 3 | COPD: 6 | Substitution strategy | Colistin (100 mg every 8 h), tobramycin (300 mg b.i.d), gentamicin (100 mg t.i.d), and amikacin (100 mg t.i.d. or 300 mg b.i.d) | Amikacin (100 mg per 3 ml), gentamicin (40 mg per ml), and colistin (75 mg per 4 ml) | Jet nebulizer | Clinical recovery, microbiological eradication | 9 |
 Kofteridis, 2010 [10] | Greece | MDR VAP due to Gram-negative bacteria | 43/43 | APACHE II score: 16.95 ± 6.59 | APACHE II score: 17.74 ± 7.61 | COPD: 12 | COPD: 7 | Adjunctive strategy | Colistin (2 million IU b.i.d) | Colistin (3 million IU t.i.d) | Not described | Clinical recovery, microbiological eradication, all-cause mortality, nephrotoxicity | 9 |
 Korbila, 2010 [11] | Greece | Microbiologically documented VAP | 78/43 | APACHE II score: 17.4 ± 6 | APACHE II score: 19.2 ± 7 | Pulmonary: 17 | Pulmonary: 9 | Adjunctive strategy | Colistin (1 million IU) | Colistin (6.4 ± 2.3 million) | Ultrasonic nebulizer | Clinical recovery, mortality | 9 |
 Pérez-Pedrero, 2011 [12] | Spain | VAP due to multi-resistant Acinetobacter baumannii | 36/18 | APACHE II score: 11.2 ± 4.3 | APACHE II score: 12.8 ± 5.7 | Not described | Not described | Adjunctive strategy | Colistin (1 million every 8 h, 0.5 million every 8 h, or 1 million b.i.d) | Colistin (1 million every 8 h, 0.5 million every 8 h, or 1 million b.i.d) | Not described | Clinical recovery, microbiological eradication | 8 |
 Kalin, 2012 [13] | Turkey | VAP due to multi-resistant A. baumannii | 15/29 | APACHE II score: 22 | APACHE II score: 22 | COPD: 4 | COPD: 6 | Adjunctive strategy | Colistin (150 mg b.i.d) | Colistin (2.5 mg/kg b.i.d or every 6 h) | Not described | Clinical recovery, microbiological eradication, all-cause mortality, nephrotoxicity | 9 |
 Arnold, 2012 [25] | USA | Pseudomonas aeruginosa and A. baumannii VAP | 19/74 | APACHE II score: 17.5 ± 5.3 | APACHE II score: 21.4 ± 5.7 | Pulmonary: 22 | Pulmonary: 6 | Adjunctive strategy | Colistin (150 mg b.i.d) or tobramycin (300 mg b.i.d) | Standard IV antibiotics | Not described | All-cause mortality | 8 |
 Doshi, 2013 [14] | USA | MDR VAP due to Gram-negative bacteria | 44/51 | APACHE II score: 22.4 ± 7.1 | APACHE II score: 24 ± 6.9 | Not described | Not described | Adjunctive strategy | Colistin (75–150 mg b.i.d) | Colistin (2.5 mg/kg b.i.d) | Jet or vibrating mesh nebulizer | Clinical recovery, microbiological eradication, hospital mortality | 7 |
 Tumbarello, 2013 [15] | Italy | Patients with VAP caused by Acinetobacter, Pseudomonas, or Klebsiella | 104/104 | CPIS: 7.8 ± 1.2 | CPIS: 7.9 ± 1.3 | COPD: 21 | COPD: 28 | Adjunctive strategy | Colistin (1 million IU t.i.d) | Colistin (0.1 IU/kg every 8 to 12 h) | Jet or ultrasonic nebulizer | Clinical recovery, microbiological eradication, all-cause mortality, nephrotoxicity | 9 |
 Migiyama, 2017 [16] | Japan | ARDS patients with VAP caused by P. aeruginosa | 22/22 | APACHE II score: 26.2 ± 6.6 | APACHE II score: 24.5 ± 7.0 | Pulmonary: 6 | Pulmonary: 5 | Adjunctive strategy | Tobramycin (240 mg) | Tobramycin | Ultrasonic nebulizer | Clinical recovery, ICU mortality | 9 |
 Le Conte, 2000 [17] | France | Intubated and mechanically ventilated patients with nosocomial pneumonia | 21/17 | N/A | N/A | Not described | Not described | Adjunctive strategy | Tobramycin (6 mg/kg/day) | Betalactam and tobramycin | Pneumatic nebulizer | Clinical recovery, mortality | High |
 Hallal, 2007 [18] | USA | VAP caused by Pseudomonas or Acinetobacter | 5/5 | APACHE II score: 17 ± 1.26 | APACHE II score: 15 ± 3.3 | Not described | Not described | Substitution strategy | Tobramycin (300 mg b.i.d) | Betalactam and tobramycin | Jet nebulizer | Clinical recovery, nephrotoxicity | High |
 Rattanaumpawan, 2010 [19] | Thailand | Gram-negative bacteria VAP | 51/49 | APACHE II score: 19.1 ± 5.8 | APACHE II score: 18.5 ± 4.7 | Not described | Not described | Adjunctive strategy | Colistin (75 mg b.i.d) | Standard intravenous antibiotics | Jet or ultrasonic nebulizer | Clinical recovery, microbiological eradication, 28-day mortality, nephrotoxicity | High |
 Lu, 2011 [20] | France | VAP caused by Pseudomonas | 20/20 | CPIS score: 8 (7–8) | CPIS score: 9 (8–9) | COPD: 3 | COPD: 4 | Substitution strategy | Amikacin (25 mg/kg/day) | Amikacin (15 mg/kg/day) and ceftazidime (90 mg/kg/3 h) | Vibrating nebulizer | Clinical recovery, microbiological eradication, 28-day mortality | High |
 Niederman, 2012 [21] | France/Spain/USA | Mechanically ventilated patients with Gram-negative pneumonia | 46/22 | CPIS score: 6.8 (1.2) | CPIS score: 7 (1.2) | Not described | Not described | Adjunctive strategy | Amikacin (400 mg b.i.d or 400 mg/day) | Standard intravenous antibiotics | Vibrating mesh nebulizer | Clinical recovery, microbiological eradication, all-cause mortality, nephrotoxicity | Low |
 Palmer, 2014 [22] | USA | Patients with high risk for MDR organisms in the respiratory tract | 24/18 | APACHE II score: 20.96 ± 5.8 | APACHE II score: 14.4 ± 5.5 | COPD: 3 | COPD: 2 | Adjunctive strategy | Vancomycin (120 mg t.i.d), gentamicin sulfate (80 mg t.i.d), or amikacin (400 mg t.i.d) | Standard IV antibiotics | Jet nebulizer | Microbiological eradication, all-cause mortality | High |
 Abdellatif, 2016 [23] | Tunisia | Gram-negative bacteria VAP | 73/76 | SOFA score: 7.03 ± 3.8 | SOFA score: 6.5 ± 4.1 | Pulmonary: 32 | Pulmonary: 29 | Adjunctive strategy | Colistin (4 million IU t.i.d) | Imipenem (1 g t.i.d) | Ultrasonic vibrating plate nebulizer | Clinical recovery, 28-day mortality | Low |
 Kollef, 2017 [24] | USA | Gram-negative bacteria VAP | 71/72 | APACHE II score: 18.5 ± 5.6 | APACHE II score: 18.4 ± 5.9 | Not described | Not described | Adjunctive strategy | Amikacin (300 mg) and fosfomycin (120 mg) | Meropenem or imipenem | Vibrating plate electronic nebulizer | Clinical recovery, 28-day mortality | Low |