Inhaled Antimicrobials for Ventilator-Associated Pneumonia: Practical Aspects

Poulakou, Garyfallia; Matthaiou, Dimitrios K.; Nicolau, David P.; Siakallis, Georgios; Dimοpoulos, George

doi:10.1007/s40265-017-0787-0

Cited by 7 publications

(6 citation statements)

References 92 publications

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“…The appropriate aerosolized antibiotic remains a matter of controversy, and the most studied are colistin and aminoglycosides. The selection of the aerosolized antibiotic should encompass several properties and characteristics to achieve maximum effectiveness including: 1) activity against the causative pathogen; 2) physical properties to ensure maximal pulmonary delivery and minimal extrapulmonary loss; and 3) the achievement of adequate concentrations in the lung well above the pathogen’s minimum inhibitory concentration, taking into account the need for the prevention of resistance and the presence of biofilm [ 29 ].…”

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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“…Irritation and airway inflammatory reaction may lead to cough, bronchospasm, bronchoconstriction-wheezing, desaturation, and even hypoxemia. Among inhaled antibiotics, colistin is more responsible for these effects [60,61]. The preceding administration of an aerosolized β-agonist might decrease the incidence of bronchospasm occurrence.…”

Section: Adverse Effects Of the Aerosolized Antibiotic Therapiesmentioning

confidence: 99%

“…Occlusion of the ventilation circuit, usually resulting from obstruction of the expiratory filter, may have very serious consequences, including cardiac arrest. Therefore, monitoring of the peak airway pressure during antibiotic administration is valuable, and the expiratory filter could be exchanged after each treatment session [60,62].…”

Section: Adverse Effects Of the Aerosolized Antibiotic Therapiesmentioning

confidence: 99%

Aerosolized Antibiotics to Manage Ventilator-Associated Infections: A Comprehensive Review

et al. 2023

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Background: Ventilator-associated lower respiratory tract infectious complications in critically ill patients cover a wide spectrum of one disease process (respiratory infection), initiating from tracheal tube and/or tracheobronchial colonization, to ventilator associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP). VAP occurence has been associated with increased intensive care unit (ICU) morbidity (ventilator days, as well as length of ICU and hospital stay) and ICU mortality. Therefore, treatments that aim at VAP/VAT incidence reduction are a high priority. Aim: The aim of the present review is to discuss the current literature concerning two major aspects: (a) can aerosolized antibiotics (AA) administered in a pre-emptive way prevent the occurrence of ventilator-associated infections? and (b) can VAT treatment with aerosolized avert the potential evolution to VAP? Results: There were identified eight studies that provided data on the use of aerosolized antibiotics for the prevention of VAT/VAP. Most of them report favorable data on reducing the colonisation rate and the progression to VAP/VAT. Another four studies dealt with the treatment of VAT/VAP. The results support the decrease in the incidence to VAP transition and/or the improvement in signs and symptoms of VAP. Moreover, there are concise reports on higher cure rates and microbiological eradication in patients treated with aerosolized antibiotics. Yet, differences in the delivery modality adopted and resistance emergence issues preclude the generalisability of the results. Conclusion: Aerosolized antibiotic therapy can be used to manage ventilator-associated infections, especially those with difficult to treat resistance. The limited clinical data raise the need for large randomized controlled trials to confirm the benefits of AA and to evaluate the impact on antibiotic selection pressure.

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“…A major complication is occlusion of the flow meter or the expiratory filter, which could have very serious consequences, including cardiac arrest. 52,63,64 It is therefore necessary to check the peak airway pressure during antibiotic administration and exchange the expiratory filter after each treatment session. 52 Some adverse effects are due to direct exposure of the lung tissues to the antibiotic aerosol.…”

Section: Limitations and Barriers To Use Of Aerosolized Antibioticsmentioning

confidence: 99%

“…These local side effects include cough, dysphonia, throat irritation, bronchoconstriction, bronchospasm, and even hypoxemia. 49,63,65 The occurrence of bronchospasm could be mitigated by administration of an aerosolized ␤-agonist. 49,52 However, if this strategy is unsuccessful, aerosolized antibiotics may have to be discontinued.…”

Section: Limitations and Barriers To Use Of Aerosolized Antibioticsmentioning

confidence: 99%

Aerosolized Antibiotics for Treatment of Pneumonia in Mechanically Ventilated Subjects

2019

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Mechanical ventilation is a well-established and commonly employed modality of treatment for critically ill patients in the ICU. Pneumonia is a frequent complication in mechanically ventilated patients. Patients who develop ventilator-associated pneumonia (VAP) incur higher medical costs, have prolonged ICU and hospital stays, and have increased mortality risk. There is growing interest in finding new treatment modalities for this condition because the success rate for treating VAP with systemic antibiotics continues to be < 70%. Accordingly, clinicians are reevaluating the role of aerosolized antibiotics, either as a sole therapy or as adjuncts to systemic antibiotics, in an attempt to improve clinical outcomes in patients with VAP. There are several clinical settings in which aerosolized antibiotics could be used for treating pneumonia, including their use for prevention, as monotherapy, as adjunctive therapy with systemic antibiotics, and for treatment of extensively drug-resistant or pan drug-resistant pathogens. However, aerosolized antibiotics have not been uniformly effective for improving clinical outcomes of patients with VAP, and local and systemic side effects could complicate their use. Moreover, many questions about aerosolized antibiotics, such as optimal formulations and dosage and treatment regimens, remain unanswered and warrant future investigations.

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Inhaled Antimicrobials for Ventilator-Associated Pneumonia: Practical Aspects

Cited by 7 publications

References 92 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

Aerosolized Antibiotics to Manage Ventilator-Associated Infections: A Comprehensive Review

Aerosolized Antibiotics for Treatment of Pneumonia in Mechanically Ventilated Subjects

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