Inhaled antibiotics for treatment and prevention of ventilator-associated pneumonia. Narrative review

Shunsuke Kondo, Joshua Garcia, Austin Corpuz, Yusuke Hirao, Brent Tatsuno

Cite

Kondo S, Garcia J, Corpuz A, Hirao Y, Tatsuno B. Inhaled antibiotics for treatment and prevention of ventilator-associated pneumonia. Narrative review. J Mech Vent 2025; 6(4):160-167.

Metrics

361 Downloads

Abstract

Background

Ventilator-associated pneumonia (VAP) remains a common and serious complication among patients receiving invasive mechanical ventilation. Inhaled antibiotics have been proposed as a strategy to either prevent or treat VAP by achieving high local concentrations in the lung with minimal systemic toxicity. However, their clinical benefit and optimal use remain uncertain.

Objective

This review aims to summarize current evidence on the use of inhaled antibiotics for both the prevention and treatment of VAP, identify existing knowledge gaps, and suggest directions for future research.

Methods

A narrative synthesis was conducted based on a comprehensive review of randomized controlled trials, meta-analyses, and observational studies published up to 2024. Particular attention is given to antibiotic class, delivery method, patient outcomes, safety, and microbial resistance.

Findings

Several high-quality studies suggest that prophylactic inhaled antibiotics, especially aminoglycosides such as amikacin, significantly reduce the incidence of VAP without increasing adverse events or multidrug resistance. Nonetheless, consistent improvements in mortality, ICU length of stay, or duration of mechanical ventilation have not been demonstrated. In the treatment context, inhaled antibiotics are frequently used as adjunctive therapy for multidrug-resistant Gram-negative pathogens, although robust RCT evidence remains limited. Key challenges include heterogeneity in study design, delivery devices, antibiotic regimens, and diagnostic definitions of VAP.

Conclusions

Inhaled antibiotics appear effective in preventing VAP, particularly when delivered via modern nebulization systems. However, their role in improving patient-centered outcomes and in the treatment of established VAP requires further clarification. Future research should focus on standardized protocols, long-term safety monitoring, and identifying patient subgroups most likely to benefit. Well-designed trials powered for clinical outcomes are essential to support the broader integration of inhaled antibiotics into VAP management strategies.

Keywords:  Ventilator associated pneumonia, inhaled antibiotics, mechanical ventilation

References

1. Wong FJ, Dudney T, Dhand R. Aerosolized Antibiotics for Treatment of Pneumonia in Mechanically Ventilated Subjects. Respir Care 2019; 64(8):962-979.
https://doi.org/10.4187/respcare.07024
PMid:31346071
2. Kallet RH. Adjunct therapies during mechanical ventilation: Airway clearance techniques, therapeutic aerosols, and gases. Respir Care 2013; 58(6):1053-1073.
https://doi.org/10.4187/respcare.02217
PMid:23709200
3. Palmer LB. Aerosolized antibiotics in critically ill ventilated patients. Curr Opin Crit Care 2009; 15(5):413-418.
https://doi.org/10.1097/MCC.0b013e328330abcf
PMid:19657273
4. Michalopoulos AS, Falagas ME. Inhaled antibiotics in mechanically ventilated patients. Minerva Anestesiol 2013; 80(2):236-244.
5. Li J, Lyu S, Luo J, et al. Prophylactic antibiotics delivered via the respiratory tract to reduce ventilator-associated pneumonia: A systematic review, network meta-analysis, and trial sequential analysis of randomized controlled trials. Crit Care Med 2024; 52(10):1612-1623.
https://doi.org/10.1097/CCM.0000000000006323
PMid:38722206
6. Yuan X, Feng Y, Wan J, et al. Effect of nebulised inhalation of antibiotics on preventing ventilator-associated pneumonia in critically ill patients: a systematic review and meta-analysis. BMJ Open 2025;15(5):e093868.
https://doi.org/10.1136/bmjopen-2024-093868
PMid:40449947 PMCid:PMC12142166
7. Kollef MH, Hamilton CW, Ernst FR. Economic Impact of Ventilator-Associated Pneumonia in a large matched cohort. Infect Control. 2012; 33(3):250-256.
https://doi.org/10.1086/664049
PMid:22314062
8. Liu C, Zhang YT, Peng ZY, et al. Aerosolized amikacin as adjunctive therapy of ventilator-associated pneumonia caused by multidrug-resistant gram-negative bacteria: A single-center randomized controlled trial. Chin Méd J 2017; 130(10):1196-1201.
https://doi.org/10.4103/0366-6999.205846
PMid:28485320 PMCid:PMC5443026
9. Niederman MS. Adjunctive nebulized antibiotics: What is their place in icu infections? Front Med 2019;6:99.
https://doi.org/10.3389/fmed.2019.00099
PMid:31139628 PMCid:PMC6517749
10. Hassan NA, Awdallah FF, Abbassi MM, et al. Nebulized versus IV amikacin as adjunctive antibiotic for hospital and ventilator-acquired pneumonia postcardiac surgeries. Crit Care Med 2018; 46(1):45-52.
https://doi.org/10.1097/CCM.0000000000002695
PMid:28857848
11. Boisson M, Jacobs M, Grégoire N, et al. Comparison of intrapulmonary and systemic pharmacokinetics of Colistin methanesulfonate (cms) and colistin after aerosol delivery and intravenous administration of CMS in critically ill patients. Antimicrob Agents Chemother 2014; 58(12):7331-7339.
https://doi.org/10.1128/AAC.03510-14
PMid:25267660 PMCid:PMC4249558
12. Min KL, Son ES, Kim JS, et al. Risk factors of colistin safety according to administration routes: Intravenous and aerosolized colistin. PLoS ONE 2018; 13(11):e0207588.
https://doi.org/10.1371/journal.pone.0207588
PMid:30462703 PMCid:PMC6248982
13. Rello J, Rouby JJ, Sole-Lleonart C, et al. Key considerations on nebulization of antimicrobial agents to mechanically ventilated patients. Clin Microbiol Infect 2017; 23(9):640-646.
https://doi.org/10.1016/j.cmi.2017.03.018
PMid:28347790
14. Kalil AC, Metersky ML, Klompas M, et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis 2016; 63(5):e61-e111.
https://doi.org/10.1093/cid/ciw353
PMid:27418577 PMCid:PMC4981759
15. Sella N, Pettenuzzo T, Cassai AD, et al. Inhaled antibiotics for treating pneumonia in invasively ventilated patients in intensive care unit: a meta-analysis of randomized clinical trials with trial sequential analysis. Crit Care 2024; 28(1):387.
https://doi.org/10.1186/s13054-024-05159-9
PMid:39587607 PMCid:PMC11587605
16. Zhang Z, Li H, Hu Y, et al. The efficacy and safety of inhaled antibiotics for pneumonia: A systematic review and meta-analysis. Pulm Pharmacol Ther 2024; 86:102315.
https://doi.org/10.1016/j.pupt.2024.102315
PMid:39009240
17. Buendía JA, Patiño DG, Salazar AFZ. Efficacy of adjunctive inhaled colistin and tobramycin for ventilator-associated pneumonia: systematic review and meta-analysis. BMC Pulm Med 2024; 24(1):213.
https://doi.org/10.1186/s12890-024-03032-7
PMid:38698403 PMCid:PMC11064396
18. Hsu WH, Wu JY, Shiau BW, et al. The preventive effect of inhaled antibiotic against ventilator-associated pneumonia: A systematic review and meta-analysis. Int J Antimicrob Agents 2024; 64(5):107324.
https://doi.org/10.1016/j.ijantimicag.2024.107324
PMid:39244163
19. Ehrmann S, Barbier F, Demiselle J, et al. Inhaled amikacin to prevent ventilator-associated pneumonia. N Engl J Med 2023; 389(22):2052-2062.
https://doi.org/10.1056/NEJMoa2310307
PMid:37888914
20. Gao M, Yu X, Liu X, et al. Effects of prophylactic nebulized antibiotics on the prevention of ICU-acquired pneumonia: a systematic review and meta-analysis. PeerJ 2024; 12:e18686.
https://doi.org/10.7717/peerj.18686
PMid:39686984 PMCid:PMC11648687
21. Jung YJ, Kim EJ, Choi YH. Aerosolized antibiotics in the treatment of hospital-acquired pneumonia/ventilator-associated pneumonia. Korean J Intern Med 2021; 37(1):1-12.
https://doi.org/10.3904/kjim.2021.277
PMid:34666432 PMCid:PMC8747925
22. Carmeli Y, Troillet N, Karchmer AW, et al. Health and economic outcomes of antibiotic resistance in Pseudomonas Aeruginosa. Arch Intern Med 1999; 159(10):1127-1132.
https://doi.org/10.1001/archinte.159.10.1127
PMid:10335691
23. Lu Q, Yang J, Liu Z, et al. Nebulized ceftazidime and amikacin in ventilator-associated pneumonia caused by Pseudomonas Aeruginosa. Am J Respir Crit Care Med 2011; 184(1):106-115.
https://doi.org/10.1164/rccm.201011-1894OC
PMid:21474643
24. Palmer LB, Smaldone GC. Reduction of bacterial resistance with inhaled antibiotics in the intensive care unit. Am J Respir Crit Care Med 2014; 189(10):1225-1233.
https://doi.org/10.1164/rccm.201312-2161OC
PMid:24646034
25. Ramsey BW, Pepe MS, Quan JM, et al. Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. N Engl J Med 1999; 340(1):23-30.
https://doi.org/10.1056/NEJM199901073400104
PMid:9878641
26. Konstan MW, Geller DE, Minić P, et al. Tobramycin inhalation powder for P. aeruginosa infection in cystic fibrosis: The EVOLVE trial. Pediatr Pulmonol 2011; 46(3):230-238.
https://doi.org/10.1002/ppul.21356
PMid:20963831 PMCid:PMC4112574
27. Assael BM, Pressler T, Bilton D, et al. Inhaled aztreonam lysine vs. inhaled tobramycin in cystic fibrosis: A comparative efficacy trial. J Cyst Fibros 2013; 12(2):130-140.
https://doi.org/10.1016/j.jcf.2012.07.006
PMid:22985692
28. Bilton D, Pressler T, Fajac I, et al. Amikacin liposome inhalation suspension for chronic Pseudomonas aeruginosa infection in cystic fibrosis. J Cyst Fibros 2020; 19(2):284-291.
https://doi.org/10.1016/j.jcf.2019.08.001
PMid:31451351 PMCid:PMC9078215
29. Hancock REW, Speert DP. Antibiotic resistance in Pseudomonas aeruginosa: mechanisms and impact on treatment. Drug Resist Updat 2000; 3(4):247-255.
https://doi.org/10.1054/drup.2000.0152
PMid:11498392
30. Kollef MH, Ricard JD, Roux D, et al. A Randomized trial of the amikacin fosfomycin inhalation system for the adjunctive therapy of gram-negative ventilator-associated pneumonia IASIS Trial. Chest 2017; 151(6):1239-1246.
https://doi.org/10.1016/j.chest.2016.11.026
PMid:27890714
31. Olofsson SK, Cars O. Optimizing drug exposure to minimize selection of antibiotic resistance. Clin Infect Dis 2007; 45(Supplement_2):S129-S136.
https://doi.org/10.1086/519256
PMid:17683017
32. Dalhoff A. Pharmacokinetics and pharmacodynamics of aerosolized antibacterial agents in chronically infected cystic fibrosis patients. Clin Microbiol Rev 2014; 27(4):753-782.
https://doi.org/10.1128/CMR.00022-14
PMid:25278574 PMCid:PMC4187638
33. Soares A, Alexandre K, Etienne M. Tolerance and persistence of pseudomonas aeruginosa in biofilms exposed to antibiotics: Molecular mechanisms, antibiotic strategies and therapeutic perspectives. Front Microbiol 2020; 11:2057.
https://doi.org/10.3389/fmicb.2020.02057
PMid:32973737 PMCid:PMC7481396
34. Motos A, Yang H, Bassi GL, et al. Inhaled amikacin for pneumonia treatment and dissemination prevention: an experimental model of severe monolateral Pseudomonas aeruginosa pneumonia. Crit Care 2023; 27(1):60.
https://doi.org/10.1186/s13054-023-04331-x
PMid:36788582 PMCid:PMC9930251