How to Use Nebulized Antibiotics in Severe Respiratory Infections
Abstract
:1. Introduction
1.1. Pharmacodynamic Targets to Treat Severe Infections
1.2. Nebulized Antibiotics: Technical Issues
1.3. Existing Evidence on the Efficacy of Inhaled Antibiotics
1.3.1. Ceftazidime
1.3.2. Fosfomycin
1.3.3. Amikacin and Tobramycin
1.3.4. Colistin
1.3.5. Vancomycin
1.4. Adverse Effects of Nebulized Antibiotics
2. Conclusions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Palmer, L.B. Aerosolized Antibiotics in the Intensive Care Unit. Clin. Chest Med. 2011, 32, 559–574. [Google Scholar] [CrossRef]
- Bergmans, D.C.; Bonten, M.J.; Gaillard, C.A.; Van Tiel, F.H.; Van Der Geest, S.; De Leeuw, P.W.; Stobberingh, E. Indications for antibiotic use in ICU patients: A one-year prospective surveillance. J. Antimicrob. Chemother. 1997, 39, 527–535. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kollef, M.H.; Hamilton, C.W.; Ernst, F.R. Economic Impact of Ventilator-Associated Pneumonia in a Large Matched Cohort. Infect. Control Hosp. Epidemiol. 2012, 33, 250–256. [Google Scholar] [CrossRef] [PubMed]
- Safdar, N.; Dezfulian, C.; Collard, H.R.; Saint, S. Clinical and economic consequences of ventilator-associated pneumonia: A systematic review. Crit. Care Med. 2005, 33, 2184–2193. [Google Scholar] [CrossRef] [PubMed]
- Warren, D.K.; Shukla, S.J.; Olsen, M.A.; Kollef, M.H.; Hollenbeak, C.S.; Cox, M.J.; Cohen, M.M.; Fraser, V.J. Outcome and attributable cost of ventilator-associated pneumonia among intensive care unit patients in a suburban medical center. Crit. Care Med. 2003, 31, 1312–1317. [Google Scholar] [CrossRef]
- Nguile-Makao, M.; Zahar, J.R.; Français, A.; Tabah, A.; Garrouste-Orgeas, M.; Allaouchiche, B.; Goldgran-Toledano, D.; Azoulay, E.; Adrie, C.; Jamali, S.; et al. Attributable mortality of ventilator-associated pneumonia: Respective impact of main characteristics at ICU admission and VAP onset using conditional logistic regression and multi-state models. Intensive Care Med. 2010, 36, 781–789. [Google Scholar] [CrossRef]
- Trouillet, J.-L.; Chastre, J.; Vuagnat, A.; Joly-Guillou, M.-L.; Combaux, D.; Dombret, M.-C.; Gibert, C. Ventilator-associated Pneumonia Caused by Potentially Drug-resistant Bacteria. Am. J. Respir. Crit. Care Med. 1998, 157, 531–539. [Google Scholar] [CrossRef]
- Palmer, L.B.; Smaldone, G.C. Reduction of Bacterial Resistance with Inhaled Antibiotics in the Intensive Care Unit. Am. J. Respir. Crit. Care Med. 2014, 189, 1225–1233. [Google Scholar] [CrossRef]
- Rodvold, K.A.; George, J.M.; Yoo, L. Penetration of Anti-Infective Agents into Pulmonary Epithelial Lining Fluid. Clin. Pharmacokinet. 2011, 50, 637–664. [Google Scholar] [CrossRef]
- Imberti, R.; Cusato, M.; Villani, P.; Carnevale, L.; Iotti, G.A.; Langer, M.; Regazzi, M. Steady-State Pharmacokinetics and BAL Concentration of Colistin in Critically Ill Patients After IV Colistin Methanesulfonate Administration. Chest 2010, 138, 1333–1339. [Google Scholar] [CrossRef]
- Boselli, E.; Breilh, D.; Djabarouti, S.; Guillaume, C.; Rimmelé, T.; Gordien, J.-B.; Xuereb, F.; Saux, M.-C.; Allaouchiche, B. Reliability of mini-bronchoalveolar lavage for the measurement of epithelial lining fluid concentrations of tobramycin in critically ill patients. Intensive Care Med. 2007, 33, 1519–1523. [Google Scholar] [CrossRef] [PubMed]
- Carcas, A.; Garciasatue, J.; Zapater, P.; Friasiniesta, J. Tobramycin penetration into epithelial lining fluid of patients with pneumonia. Clin. Pharmacol. Ther. 1999, 65, 245–250. [Google Scholar] [CrossRef]
- Cruciani, M.; Gatti, G.; Lazzarini, L.; Furlan, G.; Broccali, G.; Malena, M.; Franchini, C.; Concia, E. Penetration of vancomycin into human lung tissue. J. Antimicrob. Chemother. 1996, 38, 865–869. [Google Scholar] [CrossRef] [PubMed]
- Lamer, C.; de Beco, V.; Soler, P.; Calvat, S.; Fagon, J.Y.; Dombret, M.C.; Farinotti, R.; Chastre, J.; Gibert, C. Analysis of vancomycin entry into pulmonary lining fluid by bronchoalveolar lavage in critically ill patients. Antimicrob. Agents Chemother. 1993, 37, 281–286. [Google Scholar] [CrossRef] [Green Version]
- Lu, Q.; Girardi, C.; Zhang, M.; Bouhemad, B.; Louchahi, K.; Petitjean, O.; Wallet, F.; Becquemin, M.-H.; Le Naour, G.; Marquette, C.H.; et al. Nebulized and intravenous colistin in experimental pneumonia caused by Pseudomonas aeruginosa. Intensive Care Med. 2010, 36, 1147–1155. [Google Scholar] [CrossRef]
- Valcke, Y.; Pauwels, R.; Van der Straeten, M. Pharmacokinetics of antibiotics in the lungs. Eur. Respir. J. 1990, 3, 715–722. [Google Scholar] [CrossRef]
- Nicasio, A.M.; Eagye, K.J.; Nicolau, D.P.; Shore, E.; Palter, M.; Pepe, J.; Kuti, J.L. Pharmacodynamic-based clinical pathway for empiric antibiotic choice in patients with ventilator-associated pneumonia. J. Crit. Care 2010, 25, 69–77. [Google Scholar] [CrossRef] [PubMed]
- Neuhauser, M.M.; Weinstein, R.A.; Rydman, R.; Danziger, L.H.; Karam, G.; Quinn, J.P. Antibiotic Resistance Among Gram-Negative Bacilli in US Intensive Care Units: Implications for Fluoroquinolone Use. JAMA 2003, 289, 885. [Google Scholar] [CrossRef]
- Souli, M.; Galani, I.; Giamarellou, H. Emergence of extensively drug-resistant and pandrug-resistant Gram-negative bacilli in Europe. Eurosurveillance 2008, 13, 19045. [Google Scholar] [CrossRef]
- Chung, D.R.; Song, J.-H.; Kim, S.H.; Thamlikitkul, V.; Huang, S.-G.; Wang, H.; So, T.M.-K.; Yasin, R.M.D.; Hsueh, P.-R.; Carlos, C.C.; et al. High Prevalence of Multidrug-Resistant Nonfermenters in Hospital-acquired Pneumonia in Asia. Am. J. Respir. Crit. Care Med. 2011, 184, 1409–1417. [Google Scholar] [CrossRef]
- Kwa, A.L.H.; Loh, C.; Low, J.G.H.; Kurup, A.; Tam, V.H. Nebulized Colistin in the Treatment of Pneumonia Due to Multidrug-Resistant Acinetobacter baumannii and Pseudomonas aeruginosa. Clin. Infect. Dis. 2005, 41, 754–757. [Google Scholar] [CrossRef]
- Solé-Lleonart, C.; Rouby, J.-J.; Chastre, J.; Poulakou, G.; Palmer, L.B.; Blot, S.; Felton, T.; Bassetti, M.; Luyt, C.-E.; Pereira, J.M.; et al. Intratracheal Administration of Antimicrobial Agents in Mechanically Ventilated Adults: An International Survey on Delivery Practices and Safety. Respir. Care 2016, 61, 1008–1014. [Google Scholar] [PubMed] [Green Version]
- de Jesús Valle, M.J.; López, F.G.; Hurlé, A.D.G.; Navarro, A.S. Pulmonary versus Systemic Delivery of Antibiotics: Comparison of Vancomycin Dispositions in the Isolated Rat Lung. Antimicrob. Agents Chemother. 2007, 51, 3771–3774. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Goldstein, I.; Wallet, F.; Nicolas-Robin, A.; Ferrari, F.; Marquette, C.H.; Rouby, J.J. Lung Deposition and Efficiency of Nebulized Amikacin during Escherichia coli Pneumonia in Ventilated Piglets. Am. J. Respir. Crit. Care Med. 2002, 166, 1375–1381. [Google Scholar] [CrossRef] [PubMed]
- Montgomery, A.B.; Vallance, S.; Abuan, T.; Tservistas, M.; Davies, A. A Randomized Double-Blind Placebo-Controlled Dose-Escalation Phase 1 Study of Aerosolized Amikacin and Fosfomycin Delivered via the PARI Investigational eFlow® Inline Nebulizer System in Mechanically Ventilated Patients. J. Aerosol. Med. Pulm. Drug Deliv. 2014, 27, 441–448. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Luyt, C.-E.; Clavel, M.; Guntupalli, K.; Johannigman, J.; Kennedy, J.I.; Wood, C.; Corkery, K.; Gribben, D.; Chastre, J. Pharmacokinetics and lung delivery of PDDS-aerosolized amikacin (NKTR-061) in intubated and mechanically ventilated patients with nosocomial pneumonia. Crit. Care 2009, 13, R200. [Google Scholar] [CrossRef] [Green Version]
- Niederman, M.S.; Chastre, J.; Corkery, K.; Fink, J.B.; Luyt, C.E.; García, M.S. BAY41-6551 achieves bactericidal tracheal aspirate amikacin concentrations in mechanically ventilated patients with Gram-negative pneumonia. Intensive Care Med. 2012, 38, 263–271. [Google Scholar] [CrossRef]
- Morais, C.L.D.M.; Nascimento, J.W.L.; Ribeiro, A.C.; Cortinez, L.I.; Carmona, M.J.C.; Maia, D.R.R.; Monsel, A.; Auler, J.O.C., Jr.; Rouby, J.J.; Otsuki, D.A. Nebulization of Vancomycin Provides Higher Lung Tissue Concentrations than Intravenous Administration in Ventilated Female Piglets with Healthy Lungs. Anesthesiology 2020, 132, 1516–1527. [Google Scholar] [CrossRef]
- Kyriakoudi, A.; Pontikis, K.; Valsami, G.; Avgeropoulou, S.; Neroutsos, E.; Christodoulou, E.; Moraitou, E.; Markantonis, S.L.; Dokoumetzidis, A.; Rello, J.; et al. Pharmacokinetic Characteristics of Nebulized Colistimethate Sodium Using Two Different Types of Nebulizers in Critically Ill Patients with Ventilator-Associated Respiratory Infections. Antibiotics 2022, 11, 1528. [Google Scholar] [CrossRef]
- Rouby, J.J.; Monsel, A. Nebulized Antibiotics. Anesthesiology 2019, 131, 229–232. [Google Scholar] [CrossRef]
- Dhanani, J.; Roberts, J.A.; Chew, M.; Lipman, J.; Boots, R.J.; Paterson, D.L.; Fraser, J.F. Antimicrobial chemotherapy and lung microdialysis: A review. Int. J. Antimicrob. Agents 2010, 36, 491–500. [Google Scholar] [CrossRef] [PubMed]
- Heffernan, A.J.; Sime, F.B.; Lipman, J.; Dhanani, J.; Andrews, K.; Ellwood, D.; Grimwood, K.; Roberts, J.A. Intrapulmonary pharmacokinetics of antibiotics used to treat nosocomial pneumonia caused by Gram-negative bacilli: A systematic review. Int. J. Antimicrob. Agents 2019, 53, 234–245. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Labiris, N.R.; Dolovich, M.B. Pulmonary drug delivery. Part I: Physiological factors affecting therapeutic effectiveness of aerosolized medications: Physiological factors affecting the effectiveness of inhaled drugs. Br. J. Clin. Pharmacol. 2003, 56, 588–599. [Google Scholar] [PubMed]
- Brain, J.D.; Valberg, P.A. Deposition of Aerosol in the Respiratory Tract. Am. Rev. Respir. Dis. 1979, 120, 1325–1373. [Google Scholar] [PubMed]
- Harvey, C.J.; O’Doherty, M.J.; Page, C.J.; Thomas, S.H.L.; Nunan, T.O.; Treacher, D.F. Comparison of jet and ultrasonic nebulizer pulmonary aerosol deposition during mechanical ventilation. Eur. Respir. J. 1997, 10, 905–909. [Google Scholar] [CrossRef]
- Ari, A.; Atalay, O.T.; Harwood, R.; Sheard, M.M.; Aljamhan, E.A.; Fink, J.B. Influence of Nebulizer Type, Position, and Bias Flow on Aerosol Drug Delivery in Simulated Pediatric and Adult Lung Models During Mechanical Ventilation. Respir. Care 2010, 55, 845–851. [Google Scholar]
- Rello, J.; Rouby, J.; Sole-Lleonart, C.; Chastre, J.; Blot, S.; Luyt, C.; Riera, J.; Vos, M.; Monsel, A.; Dhanani, J.; et al. Key considerations on nebulization of antimicrobial agents to mechanically ventilated patients. Clin. Microbiol. Infect. 2017, 23, 640–646. [Google Scholar] [CrossRef] [Green Version]
- Ferrari, F.; Lu, Q.; Girardi, C.; Petitjean, O.; Marquette, C.H.; Wallet, F.; Rouby, J.J.; the Experimental ICU Study Group. Nebulized ceftazidime in experimental pneumonia caused by partially resistant Pseudomonas aeruginosa. Intensive Care Med. 2009, 35, 1792–1800. [Google Scholar] [CrossRef]
- Lu, Q.; Yang, J.; Liu, Z.; Gutierrez, C.; Aymard, G.; Rouby, J.-J.; the Nebulized Antibiotics Study Group. Nebulized Ceftazidime and Amikacin in Ventilator-associated Pneumonia Caused by Pseudomonas aeruginosa. Am. J. Respir. Crit. Care Med. 2011, 184, 106–115. [Google Scholar] [CrossRef] [Green Version]
- Bassi, G.L.; Motos, A.; Fernandez-Barat, L.; Xiol, E.A.; Chiurazzi, C.; Senussi, T.; Saco, M.A.; Fuster, C.; Carbonara, M.; Bobi, J.; et al. Nebulized Amikacin and Fosfomycin for Severe Pseudomonas aeruginosa Pneumonia: An Experimental Study. Crit. Care Med. 2019, 47, e470–e477. [Google Scholar] [CrossRef]
- Mohr, A.M.; Sifri, Z.C.; Horng, H.S.; Sadek, R.; Savetamal, A.; Hauser, C.J.; Livingston, D.H. Use of Aerosolized Aminoglycosides in the Treatment of Gram-Negative Ventilator-Associated Pneumonia. Surg. Infect. 2007, 8, 349–358. [Google Scholar] [CrossRef] [PubMed]
- Niederman, M.S.; Alder, J.; Bassetti, M.; Boateng, F.; Cao, B.; Corkery, K.; Dhand, R.; Kaye, K.S.; Lawatscheck, R.; McLeroth, P.; et al. Inhaled amikacin adjunctive to intravenous standard-of-care antibiotics in mechanically ventilated patients with Gram-negative pneumonia (INHALE): A double-blind, randomised, placebo-controlled, phase 3, superiority trial. Lancet Infect. Dis. 2020, 20, 330–340. [Google Scholar] [CrossRef]
- Stokker, J.; Karami, M.; Hoek, R.; Gommers, D.; van der Eerden, M. Effect of adjunctive tobramycin inhalation versus placebo on early clinical response in the treatment of ventilator-associated pneumonia: The VAPORISE randomized-controlled trial. Intensive Care Med. 2020, 46, 546–548. [Google Scholar] [CrossRef] [PubMed]
- Hassan, N.A.; Awdallah, F.F.; Abbassi, M.M.; Sabry, N.A. Nebulized Versus IV Amikacin as Adjunctive Antibiotic for Hospital and Ventilator-Acquired Pneumonia Postcardiac Surgeries: A Randomized Controlled Trial. Crit. Care Med. 2018, 46, 45–52. [Google Scholar] [CrossRef] [PubMed]
- Arnold, H.M.; Sawyer, A.M.; Kollef, M.H. Use of Adjunctive Aerosolized Antimicrobial Therapy in the Treatment of Pseudomonas aeruginosa and Acinetobacter baumannii Ventilator-Associated Pneumonia. Respir. Care 2012, 57, 1226–1233. [Google Scholar] [CrossRef] [Green Version]
- Czosnowski, Q.A.; Wood, G.C.; Magnotti, L.J.; Croce, M.A.; Swanson, J.M.; Boucher, B.A.; Fabian, T.C. Adjunctive Aerosolized Antibiotics for Treatment of Ventilator-Associated Pneumonia. Pharmacotherapy 2009, 29, 1054–1060. [Google Scholar] [CrossRef]
- Ghannam, D.E.; Rodriguez, G.H.; Raad, I.I.; Safdar, A. Inhaled aminoglycosides in cancer patients with ventilator-associated Gram-negative bacterial pneumonia: Safety and feasibility in the era of escalating drug resistance. Eur. J. Clin. Microbiol. Infect. Dis. 2009, 28, 253–259. [Google Scholar] [CrossRef]
- Hallal, A.; Cohn, S.M.; Namias, N.; Habib, F.; Baracco, G.; Manning, R.J.; Crookes, B.; Schulman, C.I. Aerosolized Tobramycin in The Treatment of Ventilator-Associated Pneumonia: A Pilot Study. Surg. Infect. 2007, 8, 73–82. [Google Scholar] [CrossRef]
- Kollef, M.H.; Ricard, J.-D.; Roux, D.; Francois, B.; Ischaki, E.; Rozgonyi, Z.; Boulain, T.; Ivanyi, Z.; János, G.; Garot, D.; et al. A Randomized Trial of the Amikacin Fosfomycin Inhalation System for the Adjunctive Therapy of Gram-Negative Ventilator-Associated Pneumonia. Chest 2017, 151, 1239–1246. [Google Scholar] [CrossRef]
- Zhu, Y.; Monsel, A.; Roberts, J.A.; Pontikis, K.; Mimoz, O.; Rello, J.; Qu, J.; Rouby, J.-J.; on behalf of the European Investigator Network for Nebulized Antibiotics in Ventilator-Associated Pneumonia. Nebulized Colistin in Ventilator-Associated Pneumonia and Tracheobronchitis: Historical Background, Pharmacokinetics and Perspectives. Microorganisms 2021, 9, 1154. [Google Scholar] [CrossRef]
- Lin, C.C.; Liu, T.C.; Kuo, C.F.; Liu, C.P.; Lee, C.M. Aerosolized Colistin for the Treatment of Multidrug-resistant Acinetobacter baumannii Pneumonia: Experience in a Tertiary Care Hospital in Northern Taiwan. J. Microbiol. Immunol. Infect. 2010, 43, 323–331. [Google Scholar] [CrossRef]
- Korbila, I.P.; Michalopoulos, A.; Rafailidis, P.I.; Nikita, D.; Samonis, G.; Falagas, M.E. Inhaled colistin as adjunctive therapy to intravenous colistin for the treatment of microbiologically documented ventilator-associated pneumonia: A comparative cohort study. Clin. Microbiol. Infect. 2010, 16, 1230–1236. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Naesens, R.; Vlieghe, E.; Verbrugghe, W.; Jorens, P.; Ieven, M. A retrospective observational study on the efficacy of colistin by inhalation as compared to parenteral administration for the treatment of nosocomial pneumonia associated with multidrug-resistant Pseudomonas aeruginosa. BMC Infect. Dis. 2011, 11, 317. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Motaouakkil, S.; Charra, B.; Hachimi, A.; Nejmi, H.; Benslama, A.; Elmdaghri, N.; Belabbes, H.; Benbachir, M. Colistin and rifampicin in the treatment of nosocomial infections from multiresistant Acinetobacter baumannii. J. Infect. 2006, 53, 274–278. [Google Scholar] [CrossRef] [PubMed]
- Kofteridis, D.P.; Alexopoulou, C.; Valachis, A.; Maraki, S.; Dimopoulou, D.; Georgopoulos, D.; Samonis, G. Aerosolized plus Intravenous Colistin versus Intravenous Colistin Alone for the Treatment of Ventilator-Associated Pneumonia: A Matched Case-Control Study. Clin. Infect. Dis. 2010, 51, 1238–1244. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lu, Q.; Zahr, N.; Rouby, J.J. Efficacy of High-dose Nebulized Colistin in Ventilator- associated Pneumonia Caused by Multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii. Anesthesiology 2012, 117, 1335–1347. [Google Scholar] [CrossRef] [Green Version]
- Athanassa, Z.E.; Markantonis, S.L.; Fousteri, M.-Z.F.; Myrianthefs, P.M.; Boutzouka, E.G.; Tsakris, A.; Baltopoulos, G.J. Pharmacokinetics of inhaled colistimethate sodium (CMS) in mechanically ventilated critically ill patients. Intensive Care Med. 2012, 38, 1779–1786. [Google Scholar] [CrossRef] [PubMed]
- Kalin, G.; Alp, E.; Demiraslan, H.; Doganay, M.; Coskun, R.; Gündogan, K. Use of high-dose IV and aerosolized colistin for the treatment of multidrug-resistant Acinetobacter baumannii ventilator-associated pneumonia: Do we really need this treatment? J. Infect. Chemother. 2012, 18, 872–877. [Google Scholar] [CrossRef] [PubMed]
- Kuo, S.-C.; Lee, Y.-T.; Yang, S.-P.; Chen, C.-P.; Chen, T.-L.; Hsieh, S.-L.; Siu, L.-K.; Fung, C.-P. Eradication of multidrug-resistant Acinetobacter baumannii from the respiratory tract with inhaled colistin methanesulfonate: A matched case-control study. Clin. Microbiol. Infect. 2012, 18, 870–876. [Google Scholar] [CrossRef] [Green Version]
- Tumbarello, M.; De Pascale, G.; Trecarichi, E.; De Martino, S.; Bello, G.; Maviglia, R.; Spanu, T.; Antonelli, M. Effect of Aerosolized Colistin as Adjunctive Treatment on the Outcomes of Microbiologically Documented Ventilator-Associated Pneumonia Caused by Colistin-Only Susceptible Gram-Negative Bacteria. Chest 2013, 144, 1768–1775. [Google Scholar] [CrossRef] [PubMed]
- Amin, M.; Rashad, A.; Fouad, A.; Azeem, A.A. Re-emerging of colistin for treatment of nosocomial pneumonia due to gram negative multi-drug resistant pathogens in critically ill patients. Egypt J. Chest Dis. Tuberc. 2013, 62, 447–451. [Google Scholar] [CrossRef]
- Doshi, N.M.; Cook, C.H.; Mount, K.L.; Stawicki, S.P.; Frazee, E.N.; Personett, H.A.; Schramm, G.E.; Arnold, H.M.; Murphy, C.V. Adjunctive aerosolized colistin for multi-drug resistant gram-negative pneumonia in the critically ill: A retrospective study. BMC Anesthesiol. 2013, 13, 45. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Maskin, L.P.; Setten, M.; Rodríguez, P.O.; Bonelli, I.; Attie, S.; Stryjewski, M.E.; Valentini, R. Inhaled colistimethate sodium in ventilator-associated tracheobronchitis due to multidrug-resistant Gram-negative bacteria. Int. J. Antimicrob. Agents 2015, 45, 199–200. [Google Scholar] [CrossRef] [PubMed]
- Choi, H.K.; Kim, Y.K.; Kim, H.Y.; Uh, Y. Inhaled Colistin for Treatment of Pneumonia due to Colistin-Only-Susceptible Acinetobacter baumannii. Yonsei Med. J. 2014, 55, 118. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hsieh, T.C.; Chen, F.L.; Ou, T.Y.; Jean, S.S.; Lee, W.S. Role of aerosolized colistin methanesulfonate therapy for extensively-drug-resistant Acinetobacter baumannii complex pneumonia and airway colonization. J. Microbiol. Immunol. Infect. 2016, 49, 523–530. [Google Scholar] [CrossRef] [Green Version]
- Abdellatif, S.; Trifi, A.; Daly, F.; Mahjoub, K.; Nasri, R.; Ben Lakhal, S. Efficacy and toxicity of aerosolised colistin in ventilator-associated pneumonia: A prospective, randomised trial. Ann. Intensive Care 2016, 6, 26. [Google Scholar] [CrossRef] [Green Version]
- Jang, J.Y.; Kwon, H.Y.; Choi, E.H.; Lee, W.Y.; Shim, H.; Bae, K.S. Efficacy and toxicity of high-dose nebulized colistin for critically ill surgical patients with ventilator-associated pneumonia caused by multidrug-resistant Acinetobacter baumannii. J. Crit. Care 2017, 40, 251–256. [Google Scholar] [CrossRef]
- Khorvash, F.; Yaghoubi, S.; Farsaei, S.; Ataei, B.; Hakamifard, A.; Mohajeri, F.; Gudarzi, M. Comparison of two therapeutic approaches for the management of ventilator-associated pneumonia due to multidrug-resistant Acinetobacter: A randomized clinical trial study. J. Immunoass. Immunochem. 2020, 41, 97–105. [Google Scholar] [CrossRef]
- Kim, Y.K.; Lee, J.H.; Lee, H.-K.; Chung, B.C.; Yu, S.J.; Lee, H.-Y.; Park, J.-H.; Kim, S.; Kim, H.-K.; Kiem, S.; et al. Efficacy of nebulized colistin-based therapy without concurrent intravenous colistin for ventilator-associated pneumonia caused by carbapenem-resistant Acinetobacter baumannii. J. Thorac. Dis. 2017, 9, 555–567. [Google Scholar] [CrossRef] [Green Version]
- Benítez-Cano, A.; De Antonio-Cuscó, M.; Luque, S.; Sorlí, L.; Carazo, J.; Ramos, I.; Bermejo, S.; Campillo, N.; Horcajada, J.P.; Samsó, E.; et al. Systemic pharmacokinetics and safety of high doses of nebulized colistimethate sodium in critically ill patients with hospital-acquired and ventilator-associated pneumonia. J. Antimicrob. Chemother. 2019, 74, 3268–3273. [Google Scholar] [CrossRef]
- Rattanaumpawan, P.; Lorsutthitham, J.; Ungprasert, P.; Angkasekwinai, N.; Thamlikitkul, V. Randomized controlled trial of nebulized colistimethate sodium as adjunctive therapy of ventilator-associated pneumonia caused by Gram-negative bacteria. J. Antimicrob. Chemother. 2010, 65, 2645–2649. [Google Scholar] [CrossRef] [PubMed]
- Korkmaz Ekren, P.; Toreyin, N.; Sayiner, A.; Bacakoglu, F. The Role of Aerolized Colistin in the Treatment of Hospital-Acquired Pneumonia: Experience of Multicenter From Turkey. Crit. Care Med. 2016, 44, e304. [Google Scholar] [CrossRef] [PubMed]
- Vardakas, K.Z.; Mavroudis, A.D.; Georgiou, M.; Falagas, M.E. Intravenous plus inhaled versus intravenous colistin monotherapy for lower respiratory tract infections: A systematic review and meta-analysis. J. Infect. 2018, 76, 321–327. [Google Scholar] [CrossRef] [PubMed]
- Valachis, A.; Samonis, G.; Kofteridis, D.P. The Role of Aerosolized Colistin in the Treatment of Ventilator-Associated Pneumonia: A Systematic Review and Metaanalysis. Crit. Care Med. 2015, 43, 527–533. [Google Scholar] [CrossRef] [PubMed]
- Liu, D.; Zhang, J.; Liu, H.X.; Zhu, Y.G.; Qu, J.M. Intravenous combined with aerosolised polymyxin versus intravenous polymyxin alone in the treatment of pneumonia caused by multidrug-resistant pathogens: A systematic review and meta-analysis. Int. J. Antimicrob. Agents 2015, 46, 603–609. [Google Scholar] [CrossRef]
- Vardakas, K.Z.; Voulgaris, G.L.; Samonis, G.; Falagas, M.E. Inhaled colistin monotherapy for respiratory tract infections in adults without cystic fibrosis: A systematic review and meta-analysis. Int. J. Antimicrob. Agents 2018, 51, 1–9. [Google Scholar] [CrossRef] [PubMed]
- Wenisch, C.; Laferl, H.; Szell, M.; Smolle, K.H.; Grisold, A.; Bertha, G.; Krause, R. A Holistic Approach to MRSA Eradication in Critically Ill Patients with MRSA Pneumonia. Infection 2006, 34, 148–154. [Google Scholar] [CrossRef]
- Palmer, L.B.; Smaldone, G.C.; Chen, J.J.; Baram, D.; Duan, T.; Monteforte, M.; Varela, M.; Tempone, A.K.; O’Riordan, T.; Daroowalla, F.; et al. Aerosolized antibiotics and ventilator-associated tracheobronchitis in the intensive care unit. Crit. Care Med. 2008, 36, 2008–2013. [Google Scholar] [CrossRef]
- Cho, J.Y.; Kim, H.-S.; Yang, H.-J.; Lee, Y.J.; Park, J.S.; Yoon, H.I.; Bin Kim, H.; Yim, J.-J.; Lee, J.-H.; Lee, C.-T.; et al. Pilot Study of Aerosolised Plus Intravenous Vancomycin in Mechanically Ventilated Patients with Methicillin-Resistant Staphylococcus Aureus Pneumonia. J. Clin. Med. 2020, 9, 476. [Google Scholar] [CrossRef] [Green Version]
- Wunderink, R.G.; Niederman, M.S.; Kollef, M.H.; Shorr, A.F.; Kunkel, M.J.; Baruch, A.; McGee, W.T.; Reisman, A.; Chastre, J. Linezolid in Methicillin-Resistant Staphylococcus aureus Nosocomial Pneumonia: A Randomized, Controlled Study. Clin. Infect. Dis. 2012, 54, 621–629. [Google Scholar] [CrossRef] [Green Version]
- Solé-Lleonart, C.; Rouby, J.-J.; Blot, S.; Poulakou, G.; Chastre, J.; Palmer, L.B.; Bassetti, M.; Luyt, C.-E.; Pereira, J.M.; Riera, J.; et al. Nebulization of Antiinfective Agents in Invasively Mechanically Ventilated Adults. Anesthesiology 2017, 126, 890–908. [Google Scholar] [CrossRef] [PubMed]
- Kahler, D.A.; Schowengerdt, K.O.; Fricker, F.J.; Mansfield, M.; Visner, G.A.; Faro, A. Toxic Serum Trough Concentrations After Administration of Nebulized Tobramycin. Pharmacotherapy 2003, 23, 543–545. [Google Scholar] [CrossRef] [PubMed]
- Stass, H.; Corkery, K.; Gribben, D.; Eldon, M.A. Pharmacokinetics and Tolerability of BAY41-6551 in Subjects with Chronic Kidney Disease. J. Aerosol. Med. Pulm. Drug Deliv. 2011, 24, 191–199. [Google Scholar] [CrossRef] [PubMed]
- Yang, J.W.; Fan, L.C.; Lu, H.W.; Miao, X.Y.; Mao, B.; Xu, J.F. Efficacy and safety of long-term inhaled antibiotic for patients with noncystic fibrosis bronchiectasis: A meta-analysis: Inhaled antibiotics for bronchiectasis. Clin. Respir. J. 2016, 10, 731–739. [Google Scholar] [CrossRef] [PubMed]
- Brodt, A.M.; Stovold, E.; Zhang, L. Inhaled antibiotics for stable non-cystic fibrosis bronchiectasis: A systematic review. Eur. Respir. J. 2014, 44, 382–393. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rello, J.; Solé-Lleonart, C.; Rouby, J.-J.; Chastre, J.; Blot, S.; Poulakou, G.; Luyt, C.-E.; Riera, J.; Palmer, L.; Pereira, J.; et al. Use of nebulized antimicrobials for the treatment of respiratory infections in invasively mechanically ventilated adults: A position paper from the European Society of Clinical Microbiology and Infectious Diseases. Clin. Microbiol. Infect. 2017, 23, 629–639. [Google Scholar] [CrossRef] [Green Version]
- Michalopoulos, A.; Kasiakou, S.K.; Falagas, M.E. The significance of different formulations of aerosolized colistin. Crit. Care 2005, 9, 417. [Google Scholar] [CrossRef] [Green Version]
- Kalil, A.C.; Metersky, M.L.; Klompas, M.; Muscedere, J.; Sweeney, D.A.; Palmer, L.B.; Napolitano, L.M.; O’Grady, N.P.; Bartlett, J.G.; Carratalà, J.; 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, e61–e111. [Google Scholar] [CrossRef]
IASIIASIS [49] | INHALE [42] | VAPORISE [43] | |
---|---|---|---|
Type of study | Randomized, double-blind, placebo-controlled, phase 2, multicenter study | Randomized, double-blind, placebo-controlled, phase 3, multicenter study | Randomized, double-blind, placebo-controlled, single-center study; terminated prematurely due to insufficient inclusion |
Number of patients | 143 | 712 | 26 |
VAP pathogens | MDR GNB (29% placebo group–45% treatment group) | MDR GNB (44% placebo group–49% treatment group) | MDR GNB (0%) |
Placebo group | IV-lactam + nebulized saline | IV-lactam + IV fluoroquinolone or amikacin + nebulized saline | IV-lactam + IV fluoroquinolone + nebulized saline |
Treatment group | IV-lactam + nebulized amikacin/fosfomycin | IV-lactam + IV fluoroquinolone or amikacin + nebulized amikacin | IV-lactam + nebulized tobramycin |
Doses of nebulized antibiotics | Amikacin 300 mg + fosfomycin 120 mg every 12 h for 10 days | Amikacin 400 mg every 12 h for 10 days | Tobramycin 300 mg every 12 h for 8 days |
Type of nebulizer | Non-synchronized mesh nebulizer | Synchronized inhalation mesh nebulizer | Non-synchronized mesh nebulizer |
Ventilator setting optimization | No | No | No |
Primary aim | Change in CPIS after 10 days of treatment | Mortality at Days 28–32 | Treatment failure at Day 4 |
Results | No difference between groups (p = 0.70) | 77% placebo group vs. 75% treatment group | 31% treatment group vs. 62% placebo group |
Mortality rate | At Day 28: 24% treatment group vs. 17% placebo group (p = 0.32) | No difference in survival (77% placebo group vs. 75% treatment group) | At Day 30: no difference (31% in both groups) |
Adverse events | Comparable in both groups | Comparable in both groups (84% placebo group vs. 84% treatment group) | NR |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Gorham, J.; Taccone, F.S.; Hites, M. How to Use Nebulized Antibiotics in Severe Respiratory Infections. Antibiotics 2023, 12, 267. https://doi.org/10.3390/antibiotics12020267
Gorham J, Taccone FS, Hites M. How to Use Nebulized Antibiotics in Severe Respiratory Infections. Antibiotics. 2023; 12(2):267. https://doi.org/10.3390/antibiotics12020267
Chicago/Turabian StyleGorham, Julie, Fabio S. Taccone, and Maya Hites. 2023. "How to Use Nebulized Antibiotics in Severe Respiratory Infections" Antibiotics 12, no. 2: 267. https://doi.org/10.3390/antibiotics12020267
APA StyleGorham, J., Taccone, F. S., & Hites, M. (2023). How to Use Nebulized Antibiotics in Severe Respiratory Infections. Antibiotics, 12(2), 267. https://doi.org/10.3390/antibiotics12020267