Nebulized antibiotics

The use of the aerosol route for delivery of antibiotics for pulmonary infections remains controversial. The majority of pediatric studies have been conducted in children with cystic fibrosis. In these patients distribution of the antibiotic to the desired tissue site is impeded because of the viscosity of the sputum in patients with acute exacerbations of their pulmonary infections [91,92], Long-term studies have demonstrated preventive benefits of aerosolized antibiotics in children with cystic fibrosis who are colonizing Pseudomonas aeruginosa in their lungs but are not acutely ill [93,94], Cyclic administration of tobramycin administered by nebulizer has received FDA approval [95],... 

Patients suffering from cystic fibrosis often use various aerosolized drugs. To reduce the viscosity of the mucus in the airways, recombinant human deoxyribonuclease is used. This enzyme is the first recombinant protein that has been developed for specific delivery to the lungs via the airways. It has a local action on the mucus in the airways and its absorption is minimal. Another drug that decreases the viscosity of the mucus is acetylcysteine. Aerosolized antibiotics are a further group of therapeutics that is widely used by cystic fibrosis patients. Solutions of antibiotics like tobramycin or colistin are used in nebulizers to prevent exacerbation of the disease. Pentamidine has been used for the prophylaxis of Pneumocystis pneumonia in patients infected with HIV virus, while chronic rejection of lung transplants provided a reason to develop an aerosol formulation of cyclosporine A. 

Warming may have a beneficial effect. For instance, the temperature of fluids atomized in air-jet nebulizers decreases by approximately 10-15°C during use, resulting in bronchoconstriction in some asthma suffers.Bronchoconstriction, which is most marked at 5°C, disappears at 37°C and thus may be minimized by using an ultrasonic device. Furthermore, when solutions of drugs with low solubility are to be nebulized, ultrasonic nebulizers, which warm the solutions, may be preferable to air-jet devices, which cool them and may cause precipitation. However, the heat generated may harm heat-labile materials such as diethylenetriaminepentoacetic acid ( mTc-/DTPA), " proteins, and some antibiotic solutions. Thus, ultrasonic nebulizers are specifically prohibited for aero-solization of recombinant human deoxyribonuclease (rhDNase). ... 

In a randomized comparison of nebulized tobramycin and nebulized colistin in patients with cystic fibrosis, 26 of 53 patients treated with tobramycin had at least one respiratory adverse event, most commonly pharyngitis (3). In 520 patients, inhaled tobramycin (300 mg bd for three 28-day cycles, each cycle being separated by a 28-day period of no treatment) was compared with placebo. Respiratory function was significantly improved as early as the second week and remained so for the rest of the study, even dnring periods withont aerosol treatment. There was also a parallel rednetion in the relative risk of hospitalization, the number of days of hospitalization, and the number of days of intravenous antibiotic treatment (4). 

Smith A, Ramsey B 1995 Aerosol administration of antibiotics. Respiration 62(suppl 1) 19-24 Soma L, Beech J, Gerber N 1987 Effects of cromolyn in horses with chronic obstructive pulmonary disease. Veterinary Research Communications 11 339-344 Sustronck B, Deprez P, Muylle E 1995 Evaluation of nebulization of sodium ceftiofur in the treatment of experimental Pasteurella haemolytica bronchopneumonia in calves. Research in Veterinary Science 59 267-271... 

Pulmozyme is approved for use in the treatment of CF patients, in conjunction with stitndurd thcr.ipies. to reduce the frequency of re.spinitory infections requiring parenteral antibiotics and to improve pulmonary function. Tbc do.se is delivered at a level of 2.. mg daily with a nebulizer. Pulmo-/.yme is not a replacement for antibiotics, bronchodilators. and daily physical therapy. 

Duma.se alpha is indicated for the treatment of cystic fibrosis in conjunction with other available therapies, such as antibiotics, brunchodilators, and corticosteroids. Adult dosage is 2.S mg inhaled once daily, administered via a recommended nebulizer. Dornase alpha. should not be mixed or diluted with other agents in the nebulizer becau.se of the possibility of adverse physicochemical changes that may affect activity. Common adverse effects include sure throat. hoarsene.s.s. and facial edema. 

Mukhopadhyay S, Singh M, Cater JI, Ogston S, Franklin M, Olver RE. Nebulized antipseudomonas antibiotic therapy in cystic fibrosis a meta-analysis of benefits and risks. Thorax 51 364-368, 1996. 

For many drugs, the optimum site of action remains unknown, and the dose of many therapeutic agents may be less pertinent than their delivery profile down the tracheobronchial tree. Whereas it is likely that steroid therapy for asthma is best delivered to the larger airways, antibiotics for cystic fibrosis may need to be delivered to the more distal airways and alveoli. However, further improvements in aerosol and nebulizer technologies may be required before antiinflammatory agents can be effectively delivered to the periphery of the lung. 

Devadason 8G, Everard ML, Linto JM, Le 8ouef PN. Comparison of drug delivery from conventional versus Venturi nebulizers. Eur Respir J 1997 10 2479-2483. Wilson D, Bumiston M, Moya E, Parkin A, 8mye 8, Robinson P, et al. Improvement of nebulised antibiotic delivery in cystic fibrosis. Arch Dis Child 1999 80 348-352. 

High performance liquid chromatography is well established as a tool for the separation of mixtures of labile biological substances, but its combination with mass spectrometry (LC/MS) remains fraught with difficulties as a valid analytical procedure. Several new types of direct liquid introduction interfaces (as opposed to transport interfaces) have been developed recently and appear to offer promise for the future. The thermospray interface 44) has been used successfully for amino acids, small peptides, nucleosides, antibiotics and glucuronides. The spectra are the relatively simple ones commonly obtained from soft ionization methods and resemble those obtained by FABMS. A gas nebulizer interface has enabled representative spectra (resembling those generated from DCI) to be... 

Antibiotic concentrations in respiratory secretions following systemic administration (oral or parenteral) may be inadequate for rapid treatment of airway disease such as tracheitis or bronchitis (71). Administration of antibiotics by aerosol has been used successfully and safely in children with cystic fibrosis and in infants and children who have endotracheal or tracheostomy tubes (72-74). Nebulization of antibiotic solutions allows delivery of high concentrations of antibiotics (10-40 times greater than following parenteral... 

Hung JCC, Hambelton G, Super M. Evaluation of two commercial jet nebulizers and three compressors for the nebulization of antibiotics. Arch Dis Child 1994 71 335-338. 

Nebulization of antibiotics in cystic fibrosis has also been reviewed (162). For P-lactams, an improvement in pulmonary function was demonstrated with carbenicillin (163). For polymyxin, colistin alone (164), or in conjunction with oral ciprofloxacin (165), there was a decrease in the rate of decline in pulmonary function and in the Ifequency of P. aeruginosa recovered from respiratory tract secretions. Antibiotics of this class have been reported to cause bronchospasm and respiratory failure (166). Aminoglycosides have been administered as aerosols since 1950, and they have demonstrated improvement of pulmonary function, decreased sputum bacterial density, no ototoxicity or renal toxicity, and according to Smith and Ramsey (162), they are of clinical benefit for patients with cystic... 

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