Antibiotics for inhalation: how to do, dosage

Inhalation antimicrobial therapy, when antibiotics are used for inhalation - one of the parenteral methods of drug administration, began to be used in the middle of the last century. [1]

Then they used antibiotics for intravenous administration, and their delivery directly to the respiratory tract was hampered by many factors, including the hyperosmolarity of solutions and the lack of reliable spray systems - the transformation of the drug into an aerosol inhaled by patients. [2]

Indications Antibiotics for inhalation

Like systemic  antibiotics for bronchitis , an antibiotic for inhalation for bronchitis (acute or chronic), tracheobronchitis, or an antibiotic for inhalation for coughing are prescribed only in cases of bacterial origin of respiratory diseases provoked by Staphylococcus aureus, Streptococcus pneumoniae and Moraxella catarrhalis and other pathogenic pathogenic microorganisms, accompanied by an increased formation of bronchial secretions of a purulent-mucous nature. [3]

Therefore, before prescribing antibacterial drugs, it is necessary to identify  antibodies to streptococci A, B, C, D, F, G in the blood  and make a  bacterioscopic sputum analysis .

Antimicrobial inhalation treatment is advisable for:

• - staphylococcal or streptococcal bronchopneumonia;
• - infectious exacerbation of chronic obstructive pulmonary disease (COPD);
• - bacterial apical  pleural empyema ;
• - tonsillopharyngitis, sinusitis and sinusitis caused by microbial infection. Antibiotic for inhalation for sinusitis, see material -  Antibiotics for sinusitis .

Injectable drugs Gentamicin, Tobramycin, Ceftazidime are used for inhalation with nebulizers for lesions of bronchopulmonary tissues and bronchiectasis associated with  nosocomial pneumonia  or mechanical ventilation (ALV). [4]

After a series of randomized clinical trials, the FDA, and later the European Medicines Agency, approved the use of inhaled Tobramycin in patients with complicated Pseudomonas aeruginosa cystic fibrosis of the bronchi and lungs with  cystic fibrosis . According to some reports, colonization of P. Aeruginosa is found in almost 27% of children with this hereditary systemic pathology and in 80% of patients aged 25-35 years. [5]

The study of inhaled antibiotic therapy for respiratory diseases not associated with cystic fibrosis is ongoing. [6]

Release form

• Fluimucil-Antibiotic IT - lyophilized powder in vials (plus solvent in 4 ml ampoules);
• Tobramycin - powder in vials of 80 mg; 4% solution in ampoules (1 or 2 ml);
• Bramitob - solution for inhalation (in ampoules of 4 ml); TOBI - solution for inhalation in ampoules (5 ml each);
• Zoteon podhaler - powder for inhalation in hard capsules (podhaler - portable powder inhaler is attached); TOBI - solution for inhalation (in ampoules of 5 ml);
• Colistin - powder (in vials of 80 mg) for the preparation of an inhalation solution;
• Ceftazidime - powder in vials (500, 1000, 2000) for the preparation of an injection solution;
• Gentamicin - 4% solution for injection in ampoules (1 or 2 ml), powder (in vials of 80 mg) for preparing an injection solution.

Currently, the following antibacterial agents are used by inhalation:

• the combined preparation Fluimucil-Antibiotic IT (antibiotic thiamphenicol + mucolytic acetylcysteine thinning phlegm);
• Tobramycin (other trade names, synonyms or analogs - Zoteon podhaler, TOBI, Bramitob);
• Colistin (Colistin sulfate, Colistad, Colistimetat sodium, Colistin Alvogen); [7],  [8], [9]
• Ceftazidim (Zatsef, Sudocef, Ceftaridem, Ceftadim, Tizim);
• Gentamicin (Gentamicin sulfate, Garamicin, Geomycin, Miramycin).

It should be borne in mind that simply Fluimucil for inhalation with a nebulizer is an injection solution of acetylcysteine in ampoules or granules for preparing a solution (taken orally as an expectorant), and there is no antibiotic in it. [10]

Also, the nasal spray Rinofluimucil does not have an antibacterial component: in addition to acetylcysteine, this remedy for the common cold contains the sympathomimetic tuaminoheptane sulfate, which constricts the vessels and relieves swelling of the mucous epithelium lining the nasal cavity.

Pharmacodynamics

The synthetic antibiotic Tiamphenicol (Thiomycetin, Thiofenicol, Dextrosulfenidol), which is part of Fluimucil-Antibiotic IT, belongs to the bacteriostatic sulfonyl analogs of chloramphenicol and acts on gram-positive and gram-negative bacteria (Clostridium, Corynebacterium dipcohumeus albumen, Bacterus Bacterus Bacterium, Bacterus Bacterus Bacterus, Bacterus Bacterus, Haemophilus, Neisseria, Shigella) by binding to the ribosomal subunits of bacteria and slowing down protein synthesis in their cells. In the US and UK, this antibiotic is classified as a veterinary drug). [11]

The drugs Tobramycin and Gentamicin belong to the group of aminoglycoside antibiotics and act similarly to thiamphenicol - inhibiting the production of peptidoglycans from the bacterial cell walls. [12]

The pharmacodynamics of the polymyxin antibiotic Colistin, produced by the bacterium Bacillus polymyxa, as well as the third generation cephalosporin Ceftazidime, is based on the destruction of the cell membranes of microbes, mainly Pseudomonas aeruginosa, Haemophilus influenzae, Enterobacter, Klebsorganiella and some others. [13]

Pharmacokinetics

After thiamphenicol Fluimucil-Antibiotic enters the respiratory tract, it penetrates the mucous membranes, but the official instructions do not specify the distribution and excretion of this antibiotic with an aerosol method of application.

Both the solution and the powder of Tobramycin have similar pharmacokinetics: the antibiotic acts on the surface tissues of the respiratory tract, without accumulating in bronchial secretions; is not transformed into metabolites and is excreted from the body by the kidneys.   [14]

Colistin is characterized by penetration into the bloodstream (no more than 2%) and accumulation in the pulmonary surfactant (almost 15% of the administered drug) and bronchial secretions. The drug is excreted unchanged with the coughing up sputum, and the kidneys clear the blood from Colistin in about 8 hours. [15]

For ceftazidimi and gentamicin used by inhalation, pharmacokinetics are not indicated. 

Dosing and administration

How to dilute Fluimucil-Antibiotic for inhalation is indicated in the instructions for the preparation: for 0.5 g of powder - one ampoule of solvent (4 ml). A single dose is 2 ml of the prepared solution, injected with a nebulizer no more than twice a day.

The dose of Tobramycin solution is determined by the doctor; the daily dose of Zoteon Podhaler is four capsules, the interval between inhalations is 6-12 hours, the course of treatment is four weeks.

The daily dose of Colistin ranges from 2-6 million units, and the exact dosage is determined by the doctor.

Read also -  Inhalation for bronchitis with a nebulizer

• Inhalation antibiotic for children

Fluimucil-Antibiotic IT is allowed to be used in children from the age of three at a half dosage.

Tobramycin and Colistin are not used in children under six years of age, and Ceftazidime and Gentamicin in pediatrics are used only in severe cases and for health reasons.

Use Antibiotics for inhalation during pregnancy

Fluimucil-Antibiotic IT and Gentamicin are not used during gestation; Tobracin and Colistin can be prescribed only in cases where the expected benefit to the mother is higher than the threat to the fetus.

Ceftazidime is prohibited for pregnant women in the first trimester, and at a later date, the balance of benefits and risks should be taken into account.

Contraindications

In general, contraindications to the use of an inhalation method of treatment include bleeding, coronary and cerebral vascular spasms, bullous emphysema of the lungs, accumulation of gases in the pleural cavity, and neoplastic formations of the lungs.

Fluimucil-Antibiotic is contraindicated for coughing up blood; a lowered level of red blood cells, leukocytes and platelets in the blood; exacerbation of stomach and / or duodenal ulcers.

In case of hypersensitivity to aminoglycosides, Tobramycin and its analogs are not prescribed.

Colistin is not recommended for patients with bronchial asthma, and Ceftazidime for those with renal insufficiency.

The list of contraindications for Gentamicin includes inflammation of the auditory nerve, azotemia, and a tendency to allergic reactions.

Side effects Antibiotics for inhalation

Inhalation of Fluimucil-Antibiotic may cause reflex cough, bronchial spasm, liquid rhinitis, inflammation of the mucous membrane in the mouth, and nausea.

Side effects of Tobramycin are manifested by temporary tinnitus, cough, shortness of breath and bronchospasm; also, the amount of sputum may increase, nosebleeds and hemoptysis may occur.

When using Colistin or Ceftazidime, you may experience: dizziness, shortness of breath, increased cough, bronchospasm, nausea, skin rashes and even Quincke's edema.

The most common side effects of Gentamicin are hearing damage and kidney damage.

Overdose

In case of an overdose of Fluimucil-Antibiotic, Ceftazidime or Gentamicin, an increase in the side effects of these drugs is noted.

Exceeding the permissible dose of Tobramycin leads to deterioration of the kidneys, vestibular apparatus, hearing impairment, weakening of the tone of the diaphragm and rib muscles.

And an overdose of Colistin is fraught with general weakness and dizziness; swallowing and speech disorders; paresis of the oculomotor muscles and visual impairment; convulsions and coma requiring immediate resuscitation.

Interactions with other drugs

The instructions note the incompatibility of Fluimucil-Antibiotic with sulfonamides, analgin, amidopyrine, butadione, cytostatic drugs and other cough suppressants.

Tobramycin, Zoteon Podhaler, etc. Should not be used together with diuretics and other antibiotics of the aminoglycoside and macrolide groups, as well as immunosuppressive drugs.

Interaction of Colistin with preparations containing ether, suxamethonium or tubocurarine is unacceptable; with antibiotics of the aminoglycoside group and cephalosporins.

Ceftazidime is absolutely incompatible with heparin preparations and any aminoglycoside antibiotics.

Storage conditions

All listed medicines should be stored at normal room temperature, and TOBI inhalation solution should be stored in a dark place at t ≤ + 8 ° C.

Shelf life

Shelf life of Fluimucil-Antibiotic, Tobramycin, Gentamicin - 3 years, Colistin - 4 years, Ceftazidime - 2 years.

Reviews

The reviews of practicing otolaryngologists and pulmonologists regarding inhalation of antibiotics are ambiguous, but doctors are unanimous that this method of administering antimicrobial drugs gives fewer side effects affecting the functions of the kidneys, liver and intestines than intravenous or oral administration of drugs of this pharmacological group.