Antimicrobial inhaled

Caution Dimethyl Dicarbonate is toxic if inhaled. Function Preservative antimicrobial. 

Soluble antimicrobial and fungicidal proteins produced by epithelial cells may cause direct killing of inhaled fungal spores. In addition, opsonizing soluble products may facilitate phagocytosis and killing of Aspergillus by alveolar... 

Recommended first line treatment -inhalational, GI, and oropharyngeal anthrax Ciprofloxacin (use in combination with one or two additional antimicrohials listed helow) IV treatment initially (400 mg q 12h) in combination with one or two additional antimicrobial/ Switch to oral dosing IV treatment initially when appropriate (10-15 mg/kg q 12 h) (500 mg PO BID) in combination with one or two additional antimicrobials Switch to oral when appropriate (500 mg PO BID) Same for adults ... 

Topical uses. Neomycin and framycetin, whilst too toxic for systemic use, are effective for topical treatment of infections of the conjunctiva or external ear. They are sometimes used in antimicrobial combinations selectively to decontaminate the bowel of patients who are to receive intense immunosuppressive therapy. Tobramycin is given by inhalation for therapy of infective exacerbations of cystic fibrosis. 

Microbiological protection of multiple-dose presentations such as liquid inhalations, nasal sprays, oral liquids, creams, and lotions is more complex. Once opened they are susceptible to microbiological contamination. If they are aqueous-based, they are in principle susceptible to proliferation of these new contaminants. To avoid this, they are formulated with antimicrobial agents or preservatives and are expected to be able to comply with preservative efficacy standards specified in the pharmacopeias. Preservative efficacy tests (not harmonized) are described in Section 51 of the USP and Section VIII. 14 of the PhEur (Fig. 3). 

Antimicrobial prophylaxis to prevent inhalational anthrax has been recommended for people potentially exposed to Bacillus anthracis as a result of recent bioterrorist attacks. Of 3428 people taking ciprofloxacin, 666 (19%) reported severe nausea, vomiting, diarrhea, or abdominal pain 484 (14%) reported fainting, lightheadedness, or dizziness 250 (7%) reported heartburn or acid reflux and 216 (6%) reported rashes, hives, or an itchy skin. Of those taking ciprofloxacin, 287 (8%) stopped taking it, 116 (3%) because of adverse events, 27 (1%) because of fear of possible adverse events, and 28 (1%) because they did not think it was needed (1-4). 

Cetylpyridinium chloride is a quaternary ammonium cationic surfactant, used in pharmaceutical and cosmetic formulations as an antimicrobial preservative see Section 10. It is used therapeutically as an antiseptic agent used alone or in combination with other drugs for oral and throat care used in nonparenteral formulations licensed in the UK and used in oral and inhalation preparations at concentrations of 0.02-1.5 mg (see Section 16). 

Sodium sulfite is used as an antioxidant in applications similar to those for sodium metabisulfite It is also an effective antimicrobial preservative, particularly against fungi at low pH (0.1% w/v of sodium sulfite is used). Sodium sulfite is used in cosmetics, food products, and pharmaceutical applications such as parenteral formulations, inhalations, oral formulations, and topical preparations. 

Sulfobutylether P-cyclodextrin can form noncovalent complexes with many types of compounds including small organic molecules, peptides, and proteins. It can also enhance their solubility and stability in water. The first application of sulfobutylether P-cyclodextrin was in injectable preparations it can also be used in oral solid and liquid dosage forms, and ophthalmic, inhalation, and intranasal formulations. Sulfobutylether P-cyclodextrin can function as an osmotic agent and/or a solubilizer for controlled-release delivery, and has antimicrobial preservative properties when present at sufficient concentrations. 

Comments the USP 28 (Suppl. 1.0) describes sterile water for inhalation as water purified by distillation or by reverse osmosis and rendered sterile. It contains no antimicrobial agents or other added substances, except where used in humidifiers or other similar devices, and where liable to contamination over a period of time. 

Inhalant bronchodilator therapy 313 Anti-inflammatory therapy 318 Antimicrobial therapy 322 References 324... 

Antimicrobial agents have been inhaled in human medicine for decades however, this practice has always been controversial. There are relatively few accepted indications for this mode of administration. The chronic administration of... 

Many of the medical products reviewed here find multiple applications. Thus procaine compounded with benzylpenicillin, penicillin G is an antimicrobial veterinary drug, approved in the US as a postexposure prophylaxis following inhalation of anthrax, providing that the strains do not have penicillin resistance. 

If blood cultures are positive for B. anthrads, treat with antimicrobials as for inhalational... 

Continued antimicrobial prophylaxis for inhalational anthrax for 60 days if aerosol exposure to B. anthrads is known or suspected (2). 

The inhalation of antimicrobial agents to treat infections in the lung has been of interest for decades [1], As early as the 1950s, extemporaneously prepared antimicrobial agents were aerosolized to treat pneumonia. These preparations were often crude and not well tolerated by patients. Dosage, formulation procedures, and stability assessment in these early reports were not consistent. Although some successes were reported, the potential benefit of this route of administration was not fully appreciated until the 1980s. 

A number of antibiotics have been used as aerosol therapies. Examples include beta lactam agents, polymycin antimicrobials, neomycin, gentamicin, and tobramycin. Many of the early efforts were reported as case studies, and observations and data regarding safety and efficacy were lacking. Controlled clinical trials were not conducted until the middle of the 1980s. More recent evaluations have focused on the role of inhaled tobramycin used as suppressive therapy for cystic fibrosis patients colonized with Pseudomonas aeruginosa. 

The search for useful inhaled antibiotics has been driven, in part, by a concern about the adequacy of systemic antimicrobial therapy for respiratory infections. Some agents, including aminoglycoside antibiotics, exhibit limited penetration into respiratory tract secretions. In fact, aminoglycosides may achieve sputum concentrations that are 12% of related serum concentrations. In addition, cystic fibrosis patients are often colonized with mucoid strains of Pseudomonas aeruginosa. This phenotype is associated with a further reduction in penetration of antibiotics. 

After deposition, antimicrobial therapies are cleared from the lung by various mechanisms, including mucociliary clearance, coughing, and absorption into the systemic circulation. The dmg is then metabolized or eliminated, depending on its properties. The systemic concentrations are severalfold less that what would be achieved with parenteral therapy and would not be expected to cause toxicity. However, more research is warranted to evaluate the impact of patient characteristics on systemic exposure to inhaled antimicrobial therapies. In the clinical trials of the commercially available inhaled tobramycin preparation, the mean concentration achieved one hour after inhalation was approximately 1 p,g/mL. 

Some progress has been made in developing alternative devices for the delivery of inhaled antimicrobial therapies. Colistin has been formulated in a dry powder inhaler and evaluated in healthy individuals and patients with cystic fibrosis [40]. Peak semm concentrations of colistin were 2.5-5 times higher when 25 mg of colistin sulfate dry powder was inhaled compared to 160 mg of colistin sulfomethate delivered by nebulization. Some patients experienced a decrease in pulmonary function and severe cough with the dry powder however, the investigators felt that this may be improved with a reduction in dose. 

Initial experiences with aerosolized antimicrobial therapies appeared in the literature more than 50 years ago. Until the early 1990s, the quality of the evidence supporting this strategy in the management of lung infections was poor. Recently, results from well-controlled clinical trials have established a role for inhaled antibiotics, particularly aminoglycosides, as suppressive therapy for patients with cystic fibrosis. Cyclic therapy with inhaled tobramycin reduces the frequency of pulmonary exacerbations and improves lung function. 

O Riordan TG. Inhaled antimicrobial therapy from cystic fibrosis to the flu. Respir Care 45(7) 836-845, 2000. 

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