Should Aerosolized Antibiotics Be Used to Treat Ventilator-Associated Pneumonia?

Zhang, Changsheng; Berra, Lorenzo; Klompas, Michael

doi:10.4187/respcare.04748

Cited by 10 publications

(11 citation statements)

References 70 publications

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“…Aerosolized antibiotics may be a useful treatment since aerosolization directly targets the airways and localizes the drug to the pulmonary parenchyma, thus bypassing the poor lung penetration of many antibiotics. Aerosolized antibiotics therefore make it possible to achieve high local antibiotic concentrations relative to an organism’s minimum inhibitory concentration while concurrently minimizing systemic toxicities by concentrating antibiotics in the lungs rather than spreading them throughout the body [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Aerosolized antibiotics for ventilator-associated pneumonia: a pairwise and Bayesian network meta-analysis

Che

et al. 2018

Crit Care

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BackgroundAerosolized antibiotics have been proposed as a novel and promising treatment option for the treatment of ventilator-associated pneumonia (VAP). However, the optimum aerosolized antibiotics for VAP remain uncertain.MethodsWe included studies from two systematic reviews and searched PubMed, EMBASE, and Cochrane databases for other studies. Eligible studies included randomized controlled trials and observational studies. Extracted data were analyzed by pairwise and network meta-analysis.ResultsEight observational and eight randomized studies were identified for this analysis. By pairwise meta-analysis using intravenous antibiotics as the reference, patients treated with aerosolized antibiotics were associated with significantly higher rates of clinical recovery (risk ratio (RR) 1.21, 95% confidence interval (CI) 1.09–1.34; P = 0.001) and microbiological eradication (RR 1.42, 95% CI 1.22–1.650; P < 0.0001). There were no significant differences in the risks of mortality (RR 0.88, 95% CI 0.74–1.04; P = 0.127) or nephrotoxicity (RR 1.00, 95% CI 0.72–1.39; P = 0.995). Using network meta-analysis, clinical recovery benefits were seen only with aerosolized tobramycin and colistin (especially tobramycin), and microbiological eradication benefits were seen only with colistin. Aerosolized tobramycin was also associated with significantly lower mortality when compared with aerosolized amikacin and colistin and intravenous antibiotics. The assessment of rank probabilities indicated aerosolized tobramycin presented the greatest likelihood of having benefits for clinical recovery and mortality, and aerosolized colistin presented the best benefits for microbiological eradication.ConclusionsAerosolized antibiotics appear to be a useful treatment for VAP with respect to clinical recovery and microbiological eradication, and do not increase mortality or nephrotoxicity risks. Our network meta-analysis in patients with VAP suggests that clinical recovery benefits are associated with aerosolized tobramycin and colistin (especially tobramycin), microbiological eradication with aerosolized colistin, and survival with aerosolized tobramycin, mostly based on observational studies. Due to the low levels of evidence, definitive recommendations cannot be made before additional, large randomized studies are carried out.Electronic supplementary materialThe online version of this article (10.1186/s13054-018-2106-x) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Aerosolized antibiotics for ventilator-associated pneumonia: a pairwise and Bayesian network meta-analysis

Che

et al. 2018

Crit Care

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“…Aerosolised antibiotics have been widely used for the treatment of multidrug-resistant nosocomial pneumonia because of its high concentration in lung tissue and favourable safety profiles [8]. A recently published guideline proposed the use of adjunctive aerosolised antibiotics in patients with nosocomial pneumonia due to multidrug-resistant Gram-negative bacilli [1].…”

Section: Introductionmentioning

confidence: 99%

Pilot Study of Aerosolised Plus Intravenous Vancomycin in Mechanically Ventilated Patients with Methicillin-Resistant Staphylococcus Aureus Pneumonia

Cho

Kim

Yang

et al. 2020

JCM

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Treatment of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia in critically ill patients remains unsatisfactory. This pilot study aimed to evaluate the clinical outcomes of aerosolised vancomycin in addition to intravenous administration in this setting. This was a prospective, noncomparative, phase II trial. Patients receiving mechanical ventilation for >48 h in intensive care units (ICUs) were screened; those receiving intravenous vancomycin for MRSA pneumonia were enrolled. Patients received aerosolised vancomycin (250 mg every 12 h for five days) via a vibrating mesh nebuliser. The primary outcome was treatment success (clinical cure or improvement) at the conclusion of antibiotic treatment. Vancomycin concentrations were measured in bronchoalveolar lavage fluid according to administration time. Twenty patients were enrolled (median age 75 years and 13 (65%) men; 18 (90%) cases with nosocomial pneumonia). Thirteen patients (65%) showed clinical cure or improvement. Microbiological eradication of MRSA was confirmed in 14 patients (70%). ICU and hospital mortality rates were 30% and 35%, respectively. Maximum aerosolised vancomycin concentration was observed 4-5 h after nebulising (98.75 ± 21.79 mcg/mL). No additional systemic adverse effects occurred following aerosol vancomycin treatment. Aerosolised vancomycin combination therapy may be an alternative treatment for patients with severe MRSA pneumonia receiving mechanical ventilation (ClinicalTrials.gov number, NCT01925066).

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“…Nebulized antibiotics can increase the concentration of local antibiotics and signi cantly enhance the antibacterial effect. At the same time, nebulization makes the antibiotics con ned in the lungs, which can reduce the occurrence of systemic toxicity [27]. According to current clinical practical applications, the choice of nebulizer, the setting of the pipeline, and the setting of the ventilator parameters will affect the concentration of the drug in the lung tissue, the loss of drug delivery, and systemic side effects.…”

Section: Discussionmentioning

confidence: 99%

Basic Treatment Combined With Atomized Inhalation of Amikacin for Ventilator-associated Pneumonia: A Meta-analysis of Randomized Controlled Trials

Huang¹,

Feng²,

Guo³

et al. 2021

Preprint

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Background: Compared with single intravenous therapy, nebulized amikacin combined with intravenous therapy can significantly benefit ventilator-associated pneumonia (VAP). However, the existing literature provides controversial conclusions. Methods: We systematically searched PubMed, Embase, Cochrane, CNKI, VIP, and Wanfang databases (without language restriction) for randomized controlled trials (RCTs) involving atomization inhalation of amikacin in the treatment of VAP published before October 2020. Literature screening, data extraction, and quality evaluation were performed according to the preferred reporting items for systematic reviews and meta-analyses guidelines. Results : A total of 9 RCTs were found eligible and included in our analysis (1162 patients with VAP). The results of this meta-analysis showed a significant benefit of combination treatment for improving the clinical cure (odds ratio, 2.40; 95% CI, 1.50–3.84; p = 0.006), Pathogen clearance rate (odds ratio, 3.46; 95% CI, 2.41–4.97; p <0.001), bronchospasm rate (odds ratio, 2.82; 95% CI, 1.38–5.78; p = 0.005) and Clinical pulmonary Infection Score (CPIS) (MD,-0.90; 95% CI, -1.23 to -0.57; p<0.001), No significant difference was found in 28-day mortality (odds ratio, 1.15; 95%CI, 0.81–1.63; p = 0.45) and renal impairment (odds ratio, 0.88; 95% CI, 0.60–1.30; p = 0.53). Conclusion : The addition of atomization inhalation of amikacin to intravenous antibiotics treatment in VAP patients significantly improves the clinical cure rate and pathogen clearance rate, t can also help reduce the 28-day mortality, bronchospasm rate and CPIS outcome. In addition, the combination has no significant difference in the rate of renal impairment over the conventional intravenous treatment.

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Should Aerosolized Antibiotics Be Used to Treat Ventilator-Associated Pneumonia?

Cited by 10 publications

References 70 publications

Aerosolized antibiotics for ventilator-associated pneumonia: a pairwise and Bayesian network meta-analysis

Aerosolized antibiotics for ventilator-associated pneumonia: a pairwise and Bayesian network meta-analysis

Pilot Study of Aerosolised Plus Intravenous Vancomycin in Mechanically Ventilated Patients with Methicillin-Resistant Staphylococcus Aureus Pneumonia

Basic Treatment Combined With Atomized Inhalation of Amikacin for Ventilator-associated Pneumonia: A Meta-analysis of Randomized Controlled Trials

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