Aerosolized Antibiotics in the Intensive Care Unit
Section snippets
Rationale for aerosolized antibiotic therapy in the ICU
The theoretical reasons for using targeted antimicrobial therapy in mechanically ventilated patients are compelling. With proper delivery, the drug is delivered directly to the site of infection, concentrations in the lung are high, and systemic toxicity is minimized.22, 29, 30, 31 Furthermore, the microflora of the gut is not altered, thus reducing the emergence of MDRO and infection with Clostridium difficile. The high antibiotic concentrations achieved with targeted therapy far exceed the
What are the current uncertainties about aerosolized therapy
Devices used for aerosolized delivery have never been held to the same rigorous FDA regulations to which medications are subject. Medications given intravenously with appropriate attention to dosing are not subject to large variability of concentrations in the blood stream. Unlike IV therapy, whereby dose is primarily related to concentration in the blood and the blood flow within the infected organ, aerosolized delivery depends on all the factors listed in Box 3. In addition to all these
Instillation
The earliest data about proximal concentrations of drug are from the trials in the 1960s to 1970s of instillation of aminoglycosides through the endotracheal tube or tracheostomy. As mentioned previously, tracheal aspirate concentrations were found to be 1000 times more than those of serum concentrations.20 More recently, Badia and colleagues,45 in a prospective, randomized, open-label trial in critically ill mechanically ventilated patients, compared instillation with aerosolization of 2
Clinical effects of aerosolized antibiotics
Aerosolized antibiotics have been used in trials to prevent VAP and in treatment protocols. The author focuses primarily on the treatment protocols but briefly summarizes the VAP prophylactic trials.
Are aerosolized antibiotics useful in treating VAT and/or VAP
At present, there are no large multisite investigations examining the effect of aerosolized antibiotics on VAP. Ioannidou and colleagues56 recently performed a meta-analysis on small RCTs done from 1950 to 2007 that compared topical administration (aerosolization or instillation) with or without concurrent usage of systemic antibiotics for the treatment of VAP. Of the 685 potential relevant articles, there were only 5 RCTs20, 57, 58, 59, 60 with a combined total of 176 patients suitable for
RCTs of aerosolized antibiotics for VAT or VAP
There have only been 4 randomized placebo-controlled studies with important positive clinical outcomes. A double-blind placebo-controlled phase 2 study of aerosolized amikacin delivered via vibrating mesh technology was given to 67 patients as adjunctive therapy in ventilated patients with gram-negative pneumonia. Systemic antibiotic therapy was given by the responsible clinician following ATS guidelines.34 Randomization was to aerosolized amikacin 400 mg daily with placebo (normal saline) 12
How do aerosolized antibiotics affect the emergence of bacterial resistance compared with systemic antibiotics
Increased bacterial resistance in the ICU has been shown to have a direct relationship to the amount of systemic antibiotics used.6 However, there have been little data in the recent literature analyzing the impact of aerosolized antibiotics on the emergence of resistance.
Indications for aerosolized antibiotics
There are no new consensus guidelines on the appropriate indications for aerosolized antibiotics since 2005. The current guidelines from the ATS state that “aerosolized antibiotics may also be useful to treat microorganisms that, on the basis of high minimum inhibitory concentration values, are ‘resistant’ to systemic therapy” but further studies are needed.1 So should adjunctive therapy remain the only indication or should the indication be extended to VAT? If VAT should be included, what
Summary
After 40 years of off-label use of aerosolized antibiotic in mechanically ventilated patients, with many promising results, there is neither consensus on the use of aerosolized antibiotics for VAT or VAP beyond the 2005 ATS guidelines nor any FDA-approved product for these diagnoses. There is, however, a growing body of data that suggest aerosolized antibiotics may have a role in the treatment of respiratory infection in the ICU. Three recent RCTs have shown positive clinical outcomes, with
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Cited by (31)
Metagenomic Analysis Reveals A Possible Association Between Respiratory Infection and Periodontitis
2022, Genomics, Proteomics and BioinformaticsCitation Excerpt :pgpB was the only ARG existing in periodontitis-associated pathogens with Ka/Ks > 1 in periodontitis patients and Ka/Ks < 1 in controls; this gene was identical in both the study by Wang et al. [24] and our data. Interestingly, Porphyromonas gingivalis could also cause pneumonia [10], and polymyxin B resisted by pgbB has already been widely used in pneumonia treatment [46]. It was supposed that selection pressure of pgpB is likely to be associated with both periodontitis and pneumonia.
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
2020, The Lancet Infectious DiseasesCitation Excerpt :Treatment can be unsuccessful if the alveolar concentrations of antibiotics that are needed to kill pathogens in the lungs are not achieved after intravenous administration,12 and safety concerns (such as neurotoxicity with β-lactams or ototoxicity and nephrotoxicity with aminoglycosides)2,12–14 prevent increased systemic dosing of some antibiotics to attain the alveolar concentrations required.15,16 Targeting the lungs with inhaled antibiotic therapy could address these issues by achieving high alveolar concentrations of antibiotics while minimising systemic exposure.16,17 Although not yet approved by the US Food and Drug Administration (FDA),12,16 clinical practice guidelines2 from 2016 support treatment with inhaled antibiotics when used adjunctively with systemic antibiotics (rather than systemic antibiotics alone) in patients with ventilator-associated pneumonia caused by Gram-negative bacilli that are susceptible to only aminoglycosides or polymyxins.
Optimizing Antibiotic Administration for Pneumonia
2018, Clinics in Chest MedicineCitation Excerpt :Aerosol administration has been investigated as a potential therapeutic optimization to target drug delivery to the lung and avoid the limitations of systemic IV administration.64 Aerosolized antibiotics could deliver a therapeutically effective drug concentration directly to the respiratory system and rapidly achieve eradication, while reducing drug resistance and systemic exposure to antibiotics.65 The most recent nebulizers have increased lung deposition of aerosolized antibiotic dose up to 60% compared with old nebulizers.66,67
New aerosol formulation to control ciprofloxacin pulmonary concentration
2018, Journal of Controlled ReleaseCitation Excerpt :The treatment of lung infections by direct aerosolization of antibiotic to the lung can lead to high pulmonary concentrations and an associated low systemic exposure. Also, this approach is expected to improve the treatment efficiency compared to oral or intravenous administrations [1–3]. However, for ciprofloxacin (CIP), which has a relatively high permeability through human bronchial epithelial cells (7.0 ± 0.2 × 10− 7 cm/s) [4,5] compared to antibacterials currently marketed for pulmonary inhalation (aztreonam (0.7 ± 0.2 × 10− 7 cm/s) [6] and colistin methanesulfonate (0.4 ± 0.2 × 10− 7 cm/s) [7]), a rapid decrease in extracellular CIP lung concentration was observed after aerosol administration in humans [8] and in rat [9].
Humidification and inhalation therapy
2013, Oh's Intensive Care Manual, Seventh Edition
Disclosure: Dr Lucy B Palmer and her associate Dr Gerald Smaldone have a patent with the Research Foundation of SUNY Stony Brook for the use endobronchial antibiotics, which is licensed to Nektar Therapeutics.