Efficacy of Aerosolized Tobramycin in Patients with Cystic Fibrosis

Ramsey, Bonnie W.; Dorkin, Henry L.; Eisenberg, Jay D.; Gibson, Ronald L.; Harwood, Ivan R.; Kravitz, Richard M.; Schidlow, Daniel V.; Wilmott, Robert W.; Astley, Susan J.; McBurnie, Mary Ann; Wentz, Kim R.; Smith, Arnold L.

doi:10.1056/nejm199306173282403

Cited by 429 publications

(235 citation statements)

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“…9 Experimental and clinical data support the delivery of antibiotics to the respiratory tract. 25,[27][28][29][30] In addition, there is evidence that direct pulmonary exposure to aminoglycosides protects lung epithelial cells against http://www.pediatrics.org/cgi/content/full/100/5/e5oxidant injury. 31 Aerolized aminoglycosides have yielded inconsistent yet encouraging results for patients with cystic fibrosis.…”

Section: Discussionmentioning

confidence: 99%

“…31 Aerolized aminoglycosides have yielded inconsistent yet encouraging results for patients with cystic fibrosis. 29 Ramsey et al 30 have shown safety and efficacy with short-term administration of aerosolized tobramycin in stable cystic fibrosis patients using 1800 mg/day, which can be up to 5 to 10 times the IV dose. A prevailing problem when evaluating the usefulness of aerosol therapy is the estimation of the dose of medication actually delivered to the patient's lungs, which depends on many variables including nebulizer type and output, particle size, and patient breathing pattern.…”

Section: Discussionmentioning

confidence: 99%

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Pulmonary Administration of Gentamicin During Liquid Ventilation in a Newborn Lamb Lung Injury Model

et al. 1997

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ABSTRACT. Objectives. Newborns with pulmonary infection frequently present with acute lung injury leading to ventilation/perfusion abnormalities in which intravenous delivery of antibiotics to the lung can be suboptimal. Tidal liquid ventilation (TLV) has been shown to be an effective means for delivering drugs directly to the pulmonary system. The objective of this study was to compare, with lung injury, antibiotic delivery achieved by conventional techniques (gas ventilation and intravenous gentamicin) with that using pulmonary administration of drug (PAD) during TLV.Methods. Twelve newborn lambs with an acid lung injury were randomized to receive gentamicin either intravenously during gas ventilation or via PAD during TLV using LiquiVent (Alliance Pharmaceutical Corporation, San Diego, CA, and Hoechst-Marion Roussel, Bridgewater, NJ) perfluorochemical. Gentamicin (5 mg/ kg) was administered over 1 minute, and serum levels were obtained at 15-minute intervals. Arterial blood gases and pulmonary mechanics were measured. Ventilation efficiency index and arterial/alveolar oxygen ratio were calculated. Lung-tissue gentamicin levels were measured 4 hours after administration and corrected to dry weight.Results. Serum gentamicin levels were similar in both groups. Lung gentamicin levels ( g/g) were significantly higher for TLV. Also, TLV resulted in significantly more of the total delivered dose in the lung after 4 hours. Ventilation efficiency index and arterial/alveolar oxygen ratios were significantly higher for TLV.Conclusions. In this lung injury model, both methods achieved equivalent serum gentamicin levels with higher lung levels using PAD during TLV. This study suggests that TLV may provide an effective vehicle for gentamicin delivery in infants with severe pulmonary infection and ventilation/perfusion abnormalities. Pediatrics 1997; 100(5). URL: http://www.pediatrics.org/cgi/content/full/ 100/5/e5; perfluorochemical, liquid ventilation, gentamicin, newborn, lung injury, pulmonary administration of drug, antibiotic, intratracheal.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Pulmonary Administration of Gentamicin During Liquid Ventilation in a Newborn Lamb Lung Injury Model

et al. 1997

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“…In the first large study demonstrating the efficacy of inhaled tobramycin in 72 CF patients [39], tobramycin was delivered to the lungs using an ultrasonic nebuliser (UltraNeb 99/100). In two other clinical trials performed later with 520 CF patients [40], TNS was delivered using the PARI LC PLUS nebuliser and the Pulmo-Aide compressor.…”

Section: Page 8 Of 30mentioning

confidence: 99%

“…Finally, in a smaller, placebo-controlled study, the PARI BOY ® jet nebuliser/compressor system was used [41]. It is of interest that the type of nebuliser used in the Phase III clinical trials [39,40] affected the choice of nebuliser in other studies with scope other than device testing [42][43][44].…”

Section: Page 8 Of 30mentioning

confidence: 99%

“…Motivated by the disadvantages of the ultrasonic nebuliser used in the first study (increased cost and maintenance problems) [39], a multicentre, randomised study performed in 1997 in 68 CF patients [13] compared the effectiveness and safety of the abovementioned ultrasonic nebuliser with two jet nebuliser systems. The study found 93% and 87% of patients using the Sidestream ® and the PARI LC nebulisers, respectively, had adequate peak sputum tobramycin concentrations.…”

Section: Page 8 Of 30mentioning

confidence: 99%

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Pulmonary drug delivery systems for antimicrobial agents: facts and myths

Falagas

Michalopoulos

Metaxas

2010

International Journal of Antimicrobial Agents

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To cite this version:Matthew E. Falagas, Argyris Michalopoulos, Eugenios I. Metaxas. Pulmonary drug delivery systems for antimicrobial agents: facts and myths. International Journal of Antimicrobial Agents, Elsevier, 2009, 35 (2) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Effect of nebulizer type and antibiotic concentration on device performance

et al. 1997

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We compared the performance of selected ultrasonic and jet nebulizers when aerosolizing several antibiotic formulations to determine optimum combinations for delivery of a respirable antibiotic aerosol. Three ultrasonic devices were tested: the UltraNeb 99/100®, the UltraAIR® and the Aerosonic®. The reusable jet nebulizers were the Dura ProNeb®, Pari‐LL® and the Sidestream®. The six disposable jet nebulizers were Marquest Acorn II®, Hudson T Updraft® II, Baxter MistyNeb®, Pari‐LC®, Pari IS‐2®, and a disposable Sidestream®. Each jet was tested with four compressors: a DeVilbiss AP‐50®, a Pulmo‐Aide®, a DuraNeb® and a PariMaster®. All nebulizing systems were initially tested with normal saline. From the initial data, six jet nebulizers and one ultrasonic device were tested with varying concentrations of tobramycin, gentamicin, ceftazidime, ciprofloxacin and colistin. Output was assessed by measuring volume (milliliters per minute), and amount of drug (milligrams per minute) nebulized. We then measured mean particle size of the antibiotic aerosol with seven jet nebulizers and two different compressors, Pulmo‐Aide® and PariMaster®, and two ultrasonic devices. The rate of nebulization of saline and antibiotic solutions (milliliters per minute) was greater with the ultrasonic device(s) than all jet nebulizer systems tested. Increasing the reservoir antibiotic concentration increased the drug output (milligrams per minute) with the jet nebulizers to a maximum, followed by decreasing output. When antibiotic concentrations were increased the output decreased more precipitously with the ultrasonic devices than with the jet nebulizers. At the highest antibiotic concentrations tested, the ultrasonic devices had the lowest output. Particle size distribution was most dependent on the specific jet device, with particle size distribution less affected by a specific antibiotic or its concentration. Higher reservoir concentrations can be utilized for increasing output of respirable antibiotic aerosols by jet nebulizers. We conclude that antibiotic output is dependent upon both the nebulizing system and the reservoir concentration of antibiotic. Pediatr Pulmonol. 1997; 23:249–260. © 1997 Wiley‐Liss, Inc.

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Efficacy of Aerosolized Tobramycin in Patients with Cystic Fibrosis

Abstract: The short-term aerosol administration of a high dose of tobramycin in patients with clinically stable cystic fibrosis is an efficacious and safe treatment for endobronchial infection with P. aeruginosa.

Cited by 429 publications

References 27 publications

Pulmonary Administration of Gentamicin During Liquid Ventilation in a Newborn Lamb Lung Injury Model

Pulmonary Administration of Gentamicin During Liquid Ventilation in a Newborn Lamb Lung Injury Model

Pulmonary drug delivery systems for antimicrobial agents: facts and myths

Effect of nebulizer type and antibiotic concentration on device performance

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