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The use of aminoglycosides in patients with cystic fibrosis

Improvements in the quality of medical care and the emergence of effective antibacterial drugs have increased the life expectancy of patients with cystic fibrosis. Aminoglycosides are widely used in the treatment of this category of patients, however, the potential toxicity of this group of drugs requires careful monitoring of the safety of their use. The British antibiotic group Cystic Fibrosis Charity Foundation and the North American Cystic Fibrosis Foundation offer recommendations on the use of aminoglycosides in patients with cystic fibrosis.

The use of aminoglycosides in this category of patients is due to activity against Pseudomonas aeruginosa, to synergy with beta-lactams and to high concentrations in sputum. Given the repeated and repeated cycles of prescribing antibiotics in patients with cystic fibrosis, highly effective drugs with minimal cumulative toxicity should be used.

Aminoglycosides are characterized by oto-, vestibulo- and nephrotoxicity. An early sign of ototoxicity is an increase in the hearing perception threshold to 25 decibels. This level of hearing loss does not affect speech perception and is generally not found in patients. However, early detection of an increased hearing threshold is crucial to preventing clinically significant hearing loss. The development of vestibulotoxicity is unpredictable, but it usually occurs with the use of high doses, rapid intravenous administration of aminoglycosides, the simultaneous use of other nephrotoxic drugs, as well as in patients with history of dizziness.

Nephrotoxicity is assessed by serum creatinine, urea and electrolyte concentrations, however, none of these indicators is a marker for early manifestations of renal failure. Each cystic fibrosis patient receiving aminoglycosides must calculate the creatinine clearance, since the serum creatinine content depends on muscle mass, which is reduced in this category of patients.

A single administration of the entire daily dose of aminoglycosides in many studies has shown equal efficacy and less or equal safety compared to traditional triple administration. However, the results of a meta-analysis showed the lack of benefits of a single administration of aminoglycosides in patients with cystic fibrosis. Therefore, before obtaining new data in patients with cystic fibrosis, it is advisable to use the traditional three-stage dosage.

The UK Cystic Fibrosis Foundation Antibiotic Group recommends close monitoring of kidney function, as patients with this condition receive repeated treatments of potentially toxic drugs, including aminoglycosides. At the same time, there are no clear recommendations on this subject, except that intravenous administration should determine the maximum and residual levels of aminoglycosides.

The North American Cystic Fibrosis Foundation recommends monitoring the general analysis of urine, residual nitrogen, and serum creatinine after each intravenous administration of aminoglycosides. It is recommended to assess renal function at the start of treatment, then at the second and at the end of the second week of intravenous administration of aminoglycosides in all patients with cystic fibrosis, as well as to determine the maximum and residual concentrations medication.

It is necessary to carefully examine all patients who complain of changes in hearing and vestibular function during treatment. Significant hearing loss was recorded after 20 treatment cycles with aminoglycosides. However, all patients who have received at least 10 intravenous cycles of aminoglycosides require an audiometric assessment.

It should be noted that patients with cystic fibrosis generally tolerate repeated cycles of aminoglycosides, the frequency of nephro- and ototoxicity is lower than in the general population. At the same time, it is important to identify the first effects of toxicity before their clinical manifestation. Unfortunately, there is currently no method to reliably determine this in all patients. Currently, all patients should use standard methods of audiometry and kidney function assessment to reduce the risk of long-term complications in this category of patients.

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