Use of Aerosolized Aminoglycosides in the Treatment of Gram-Negative Ventilator-Associated Pneumonia

Mohr, Alicia M.; Sifri, Ziad C.; Horng, Helen; Sadek, Ragui; Savetamal, Alisa; Hauser, Carl J.; Livingston, David H.

doi:10.1089/sur.2006.041

Cited by 23 publications

(15 citation statements)

References 27 publications

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“…No adverse events were reported in this evaluation, and all patients were weaned from mechanical ventilation. Notably, 56% of patients in this study had been treated for a prior episode of VAP before inclusion in this analysis (289).…”

Section: Nosocomial Pneumoniamentioning

confidence: 99%

Inhaled Antibiotics for Gram-Negative Respiratory Infections

et al. 2016

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SUMMARYGram-negative organisms comprise a large portion of the pathogens responsible for lower respiratory tract infections, especially those that are nosocomially acquired, and the rate of antibiotic resistance among these organisms continues to rise. Systemically administered antibiotics used to treat these infections often have poor penetration into the lung parenchyma and narrow therapeutic windows between efficacy and toxicity. The use of inhaled antibiotics allows for maximization of target site concentrations and optimization of pharmacokinetic/pharmacodynamic indices while minimizing systemic exposure and toxicity. This review is a comprehensive discussion of formulation and drug delivery aspects,in vitroand microbiological considerations, pharmacokinetics, and clinical outcomes with inhaled antibiotics as they apply to disease states other than cystic fibrosis. In reviewing the literature surrounding the use of inhaled antibiotics, we also highlight the complexities related to this route of administration and the shortcomings in the available evidence. The lack of novel anti-Gram-negative antibiotics in the developmental pipeline will encourage the innovative use of our existing agents, and the inhaled route is one that deserves to be further studied and adopted in the clinical arena.

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Section: Nosocomial Pneumoniamentioning

confidence: 99%

Inhaled Antibiotics for Gram-Negative Respiratory Infections

et al. 2016

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“…65 In particular, the efficiency of vibrating mesh nebulizer technology may be an important step in advancing aerosolized antibiotic therapy. 57 Several small RCTs, as well as uncontrolled studies, [66][67][68][69][70][71][72][73][74][75][76][77] have been published (Table 3). Although not uniformly unambiguous, many of these studies suggest that aerosolized antibiotics maybe a more effective strategy to treat VAP and VAT.…”

Section: Aerosolized Antibioticsmentioning

confidence: 99%

Adjunct Therapies During Mechanical Ventilation: Airway Clearance Techniques, Therapeutic Aerosols, and GasesDiscussion

Kallet

2013

Respir Care

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Mechanically ventilated patients in respiratory failure often require adjunct therapies to address special needs such as inhaled drug delivery to alleviate airway obstruction, treat pulmonary infection, or stabilize gas exchange, or therapies that enhance pulmonary hygiene. These therapies generally are supportive in nature rather than curative. Currently, most lack high-level evidence supporting their routine use. This overview describes the rationale and examines the evidence supporting adjunctive therapies during mechanical ventilation. Both mechanistic and clinical research suggests that intrapulmonary percussive ventilation may enhance pulmonary secretion mobilization and might reverse atelectasis. However, its impact on outcomes such ICU stay is uncertain. The most crucial issue is whether aerosolized antibiotics should be used to treat ventilatorassociated pneumonia, particularly when caused by multi-drug resistant pathogens. There is encouraging evidence from several studies supporting its use, at least in individual cases of pneumonia non-responsive to systemic antibiotic therapy. Inhaled pulmonary vasodilators provide at least short-term improvement in oxygenation and may be useful in stabilizing pulmonary gas exchange in complex management situations. Small uncontrolled studies suggest aerosolized heparin with N-acetylcysteine might break down pulmonary casts and relieve airway obstruction in patients with severe inhalation injury. Similar low-level evidence suggests that heliox is effective in reducing airway pressure and improving ventilation in various forms of lower airway obstruction. These therapies generally are supportive and may facilitate patient management. However, because they have not been shown to improve patient outcomes, it behooves clinicians to use these therapies parsimoniously and to monitor their effectiveness carefully. Key words: high-frequency percussive ventilation; intrapulmonary percussive ventilation; inhaled nitric oxide; aerosolized prostacyclin; aerosolized heparin; metered-dose inhalers; heliox.

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“…Mohr et al retrospectively reviewed 22 patients with VAP that received tobramycin 300 mg inhaled twice daily (n ¼ 16) or amikacin 400 mg-1000 mg inhaled twice daily (n ¼ 6), and there were no reported renal or pulmonary toxicities. 108 The pharmacokinetics of inhaled and intravenous amikacin have also been studied in a simulated mechanical ventilation model in healthy participants. 110 Intravenous doses of amikacin 15 mg/kg were compared to nebulized amikacin in 40, 50, and 60 mg/kg doses, and the resulting peak serum concentrations were 48 mcg/mL, 8.2 mcg/mL, 9.2 mcg/mL, and 9.2 mcg/mL, respectively.…”

Section: Lungsmentioning

confidence: 99%

Management of Aminoglycosides in the Intensive Care Unit

Radigan

Gilchrist

Miller

2010

J Intensive Care Med

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Antibacterial resistance is increasing throughout the world, while the development of new agents is slowly progressing. In addition, the increasing prevalence of fluoroquinolone resistance may force many practitioners to choose an aminoglycoside agent in gram-negative regimens. Aminoglycosides are bactericidal agents with potent activity against gram-negative infections and activity against gram-positive infections when added to a cell wall active antimicrobial-based regimen. These agents may be dosed multiple times a day or consolidated as high-dose, extended-interval dosing to maximize pharmacokinetic and pharmacodynamic properties to achieve possible improved efficacy with reduced toxicity. Clinical application includes the treatment of bacteremia, endocarditis, health-care and nosocomial pneumonias, intra-abdominal infections, and others. Nephrotoxicity and ototoxicity are potential risks of aminoglycoside therapy that may be minimized with serum monitoring and short courses of therapy.

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Use of Aerosolized Aminoglycosides in the Treatment of Gram-Negative Ventilator-Associated Pneumonia

Cited by 23 publications

References 27 publications

Inhaled Antibiotics for Gram-Negative Respiratory Infections

Inhaled Antibiotics for Gram-Negative Respiratory Infections

Adjunct Therapies During Mechanical Ventilation: Airway Clearance Techniques, Therapeutic Aerosols, and GasesDiscussion

Management of Aminoglycosides in the Intensive Care Unit

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