Antibiotics for inhalation: how to do, dosage

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

At that time, antibiotics were administered intravenously, and their delivery directly to the respiratory tract was complicated by many factors, including the hyperosmolarity of the solutions and the lack of reliable nebulization systems – the conversion of the drug into an aerosol inhaled by patients. [ 2 ]

Indications antibiotics for inhalation

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

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

Antimicrobial inhalation treatment is appropriate for:

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

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

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

Studies of inhaled antibacterial therapy for respiratory diseases not associated with cystic fibrosis are 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);
• Zoteon Podhaler is a powder for inhalation in hard capsules (a Podhaler is included – a portable powder inhaler); TOBI is a solution for inhalation (in 5 ml ampoules);
• Colistin – powder (in 80 mg vials) for the preparation of inhalation solution;
• Ceftazidime - powder in vials (500, 1000, 2000) for the preparation of injection solution;
• Gentamicin – 4% injection solution in ampoules (1 or 2 ml), powder (in vials of 80 mg) for the preparation of injection solution.

The following antibacterial agents are currently used for inhalation:

• combination drug Fluimucil-Antibiotic IT (antibiotic thiamphenicol + mucolytic acetylcysteine);
• Tobramycin (other trade names, synonyms or analogues – Zoteon podhaler, TOBI, Bramitob);
• Colistin (Colistin sulfate, Colistad, Colistimethate sodium, Colistin Alvogen); [ 7 ], [ 8 ], [ 9 ]
• Ceftazidime (Zatsef, Sudocef, Ceftaridem, Ceftadim, Tizim);
• Gentamicin (Gentamicin sulfate, Garamycin, 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 the preparation of a solution (taken orally as an expectorant), and it does not contain an antibiotic. [ 10 ]

The nasal spray Rinofluimucil also does not have an antibacterial component: in addition to acetylcysteine, this remedy for a runny nose contains the sympathomimetic tuaminoheptane sulfate, which constricts blood vessels and relieves swelling of the mucous epithelium lining the nasal cavity.

Pharmacodynamics

The synthetic antibiotic Thiamphenicol (Thiomycetin, Thiofenicol, Dextrosulfenidol), which is part of Fluimucil-Antibiotic IT, is a bacteriostatic sulfonyl analogue of chloramphenicol and acts on gram-positive and gram-negative bacteria (Clostridium, Corynebacterium diphtheriae, Diplococcus pneumoniae, Staphylococcus albus, Streptococcus pyogenes, Bacteroides, Fusobacterium, Bordatella, Haemophilus, Neisseria, Shigella) by binding to the ribosomal subunits of bacteria and slowing down protein synthesis in their cells. In the USA and Great Britain, 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 process of production of peptide glycans of 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, Klebsiella and some other microorganisms. [ 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 when administered by aerosol.

Both the solution and powder of Tobramycin have similar pharmacokinetics: the antibiotic acts on the superficial tissues of the respiratory tract without accumulating in bronchial secretions; it 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 expectorated sputum, and the kidneys clear Colistin from the blood in about 8 hours. [ 15 ]

For Ceftazidime and Gentamicin used by inhalation, the pharmacokinetics are not indicated.

Dosing and administration

How to dilute Fluimucil-Antibiotic for inhalation is specified in the instructions for the drug: for 0.5 g of powder - one ampoule of solvent (4 ml). A single dose is 2 ml of the prepared solution, administered 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 IU, and the exact dosage is determined by the doctor.

Read also – Inhalations for bronchitis with a nebulizer

• Antibiotic for inhalation for children

Fluimucil-Antibiotic IT can be used for children from three years of age in half the dosage.

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

Use antibiotics for inhalation during pregnancy

Fluimucil-Antibiotic IT and Gentamicin are not used during pregnancy; Tobracin and Colistin can be prescribed only in cases where the expected benefit to the mother outweighs the risk to the fetus.

Ceftazidime is contraindicated in pregnant women during the first trimester, and in later stages the benefit/risk ratio should be considered.

Contraindications

In general, contraindications to the use of inhalation treatment include bleeding, coronary and cerebral vascular spasms, bullous emphysema of the lungs, gas accumulation in the pleural cavity, and lung tumors.

Fluimucil-Antibiotic is contraindicated in case of coughing up blood; decreased levels of red blood cells, white blood cells and platelets in the blood; exacerbation of gastric ulcer and/or duodenal ulcer.

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

Patients with bronchial asthma are not recommended to use Colistin, and those with renal insufficiency are not recommended to use Ceftazidime.

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

Side effects antibiotics for inhalation

When inhaling Fluimucil-Antibiotic, a reflex cough, bronchial spasm, runny rhinitis, inflammation of the oral mucosa, and nausea may occur.

Side effects of Tobramycin include temporary tinnitus, cough, shortness of breath, and bronchospasm; increased mucus production, nosebleeds, and hemoptysis may also occur.

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

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

Overdose

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

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

An overdose of Colistin is fraught with general weakness and dizziness; swallowing and speech disorders; paresis of the oculomotor muscles and deterioration of vision; convulsions and a comatose state requiring immediate resuscitation.

Interactions with other drugs

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

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 drugs containing ether, suxamethonium or tubocurarine; with antibiotics of the aminoglycoside and cephalosporin groups is unacceptable.

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

Storage conditions

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

Shelf life

The shelf life of Fluimucil-Antibiotic, Tobramycin, Gentamicin is 3 years, Colistin is 4 years, Ceftazidime is 2 years.

Reviews

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