Higher Tobramycin concentration and vibrating mesh technology can shorten antibiotic treatment time in cystic fibrosis

Abstract

Poor adherence to recommended therapy in cystic fibrosis (CF) is often because of the time demands of therapy. Tobramycin (TOBI®, 300 mg at 60 mg/ml) inhaled from the PARI LC PLUS® nebulizer requires about 20 min. This study determined if equivalent levels of pulmonary deposition could be achieved in shorter time using 1.5 ml of 100 mg/ml tobramycin solution delivered by an investigational eFlow® nebulizer. Sixteen males with stable CF, 8 children and 8 adults, and an FEV(1) > 45% predicted inhaled both preparations on two occasions with (99m) Tc-DTPA added to the tobramycin. Blood samples were taken for quantification of tobramycin in the serum. The PARI LC PLUS® delivered 45.4 (39.3-51.6), mean and 95% CI, mg to the lungs in 17.0 ± 2.5 min (mean ± SD) with serum levels of 1,089 ± 388 µg/L. The investigational eFlow® delivered 46.3(40.3-51.7) mg in 4.0 ± 1.0 min with blood levels of 909 ± 458 µg/L. Only the time of delivery was significantly different with P < 0.0001 (paired t-test). Tolerability of the treatment was comparable for both inhalation regimes, but the shorter treatment was preferred by all patients. These results demonstrate the possibility of delivering equivalent levels of tobramycin much faster into the lungs of CF patients when using eFlow®, a very efficient electronic nebulizer.

Radioaerosol Pulmonary Deposition Using Mesh and Jet Nebulizers During Noninvasive Ventilation in Healthy Subjects

“…A piezo element converts electricity to mechanical vibration of the mesh at 128 kHz (one-tenth frequency of ultrasonic nebulizers), creating a micro-pumping action that extrudes fluid through the small holes in the membrane, breaking fluid from the apertures into a stream of precise droplets. 11,[15][16][17][18] The vibrating mesh nebulizer has been associated with production of precise particle sizes without adding gas flow into the ventilator circuit and a low residual volume of drug remaining after nebulization is complete. 11,15 This type of nebulizer has been shown to be promising in providing greater inhaled and pulmonary deposition compared with jet nebulizers during conventional mechanical ventilation using both in vitro and animal models.…”

Respiratory System Deposition with a Novel Aerosol Delivery System in Spontaneously Breathing Healthy Adults

“…18 Roughly 15% of the 300 mg charge dose in a 5 mL volume deposited in the lungs in a study including both adults and children, and is roughly the same as a 4 mL charge delivered by the Pari LC Star in adults. 16 Importantly, this device is orders of magnitude more efficient than an unvented jet nebulizer with a face mask.…”

“…Second, toward the end of nebulization sputtering occurs and the production progressively falls. 18 On the other hand, a vibrating-mesh nebulizer extrudes the drug solution through microscopic pores at a constant rate, with minimal chance for evaporation in the small holding chamber, so the rate of lung deposition and the osmolarity should be constant, providing the pattern of ventilation is constant. 11 Furthermore, most vibrating-mesh systems have a controller that indicates when nebulization has ceased, allowing the session to be terminated or, alternatively, the nebulizer refilled.…”

“…Greater details of these calculations have been published recently in both healthy adults 11,16,17 and children and adults with lung disease. 18 If MgSO 4 had been used instead of saline, the total amount of counts in the nebulizer prior to nebulization would represent 600 mg of MgSO 4 in 6 mL of a 100 mg/mL solution. Hence, the total counts in the nebulizer prior to nebulization, divided by 600 mg, gives the counts per mg of MgSO 4 .…”

Fungal contamination of nebuliser devices used by people with cystic fibrosis

“…This dependence on time consuming regimens increases treatment burden and often impacts on adherence. The introduction of devices such as the e Flow® and iNeb® have helped to reduce some of this burden by improved portability, usability and speed of administration (1). Despite these changes adherence to treatment and nebuliser hygiene can remain low (2,3).…”