Linezolid (Linezolid)

In an open study, among severely ill patients with intravascular catheter-associated infections, mortality was increased in patients who received linezolid, compared with patients receiving vancomycin / dicloxacillin / oxacillin [78/363 (21.5%) versus 58/363 (16.0%)]. The main factor influencing mortality was the gram-positive pathogen of infection at the initial stage. The mortality rate was similar among patients whose infections were caused only by Gram-positive microorganisms, but was significantly higher in the linezolid group when other microorganisms were detected or could not be detected at the initial stage. The greatest imbalance was noted during treatment and within 7 days after the end of antibiotic therapy. In many patients linezolid groups were detected during the study of Gram-negative microorganisms, and they died from infection caused by Gram-negative microorganisms or polymicrobial infections. Therefore, in case of complicated skin and soft tissue infections, linezolid should be used in patients with known or possible co-infection with Gram-negative microorganisms, only if there are no alternative treatment options. In these cases, additional application of drugs acting on gram negative microflora is shown simultaneously.

In some patients taking linezolid, reversible myelosuppression may develop (with anemia, thrombocytopenia, leukopenia and pancytopenia), depending on the duration of therapy. In elderly patients, the risk of developing this condition is also increased. Thrombocytopenia occurred more often in patients with severe renal failure, regardless of the patient's hemodialysis. Therefore, in the course of treatment, it is necessary to monitor blood values ​​in patients with an increased risk of bleeding, myelosuppression in anamnesis, and simultaneous use of drugs that reduce hemoglobin or platelet count and / or their functional properties, with severe renal failure, and in patients taking linezolid more than 2 weeks. Linezolid these patients are only used when it is possible to carefully monitor the level of hemoglobin, the number of leukocytes and platelets. If during treatment with linezolid develops marked myelosuppression, treatment should be discontinued unless continuation of therapy is considered absolutely necessary.In this case, intensive monitoring of blood counts and appropriate treatment is necessary. In addition, it is recommended that a blood test (including, more specifically, the level of hemoglobin, platelet count and leukocyte count (with calculation of the leukocyte formula)) be performed weekly in patients receiving linezolid regardless of the initial blood test. A higher incidence of severe anemia was observed in patients who received linezolid more than the maximum recommended duration of 28 days. These patients were more likely to require a blood transfusion. Cases of sideroblastic anemia were registered in the post-marketing period. In most cases, the duration of linezolid therapy exceeded 28 days. In most patients, the manifestations were completely or partially reversible after discontinuation of treatment with linezolid with / without specific treatment for anemia.

In patients taking antibacterial drugs, including linezolid, should take into account the risk of developing pseudomembranous colitis of varying severity. The cases of diarrhea associated with Clostridium difficile have been reported in connection with the use of almost all antibacterial drugs, including linezolid. The severity of diarrhea can range from mild to severe forms.Treatment with antibacterial drugs disrupts the normal intestinal microflora, which leads to excess growth of Clostridium difficile. Clostridium difficile produces toxins A and B, which lead to the development of diarrhea associated with Clostridium difficile. Excessive toxins produced by Clostridium difficile strains can cause an increase in mortality among patients, since such infections can be resistant to antimicrobial therapy, and may require a colonectomy. The possibility of developing diarrhea associated with Clostridium difficile should be considered in all patients with diarrhea following the use of antibiotics. Careful medical supervision for 2 months is necessary for patients who have experienced diarrhea associated with Clostridium difficile after the administration of antibacterial drugs.

When symptoms of impaired visual function appear, such as changes in visual acuity, changes in color perception, blurred vision, visual field defects, it is recommended that you urgently consult an ophthalmologist for advice. Monitor visual function in all patients taking linezolid for a long time (more than 28 days), as well as for all patients with newly appeared symptoms of visual disturbances, regardless of the duration of therapy.In the case of peripheral neuropathy and optic nerve neuropathy, the risk / benefit ratio of linezolid therapy in these patients should be assessed. The risk of developing neuropathy is higher if linezolid It is used in patients who are currently using or who have recently taken antimycobacterial drugs for the treatment of tuberculosis.

In connection with the use of linezolid, lactoacidosis was reported. Patients who experience repeated nausea or vomiting with linezolid, abdominal pain, unexplained acidosis, or a decrease in the concentration of bicarbonate anions, require close monitoring by the physician.

Linezolid inhibits the synthesis of the mitochondrial protein. Side effects, such as, lactic acidosis, anemia and neuropathy (peripheral or optic nerve), can result from this inhibition; these effects are more common when the drug is used more than 28 days.

Cramping was reported in patients taking linezolid, and in most cases in the history there was an indication of convulsions or the presence of risk factors for their development.Patients need to collect a detailed history of previous episodes of seizures.

If the drug is to be used in combination with selective serotonin reuptake inhibitors, patients should be monitored continuously to identify signs and symptoms of serotonin syndrome, such as cognitive impairment, hyperpyrexia, hyperreflexia, and impaired coordination of movements. If these symptoms appear, you should cancel one or both of the drugs taken. When discontinuing the use of a serotonergic drug, symptoms of the withdrawal syndrome may be observed.

There have been reports of reversible surface changes in tooth enamel staining with linezolid. These changes in staining were removed by professional dental cleaning.

There were reported cases of symptomatic hypoglycemia in patients with diabetes mellitus who received linezolid simultaneously with insulin or hypoglycemic drugs. Although a causal relationship between the use of linezolid and the development of hypoglycemia has been established, patients with diabetes should be warned about the possibility of developing hypoglycemia.In case of hypoglycaemia, correction of insulin dose / hypoglycemic drugs or cancellation of linezolid is necessary.

Patients should be advised not to take large amounts of food containing tyramine (such as red wine, old cheese, some alcoholic beverages, minced meat).

Clinical studies that studied the effect of linezolid on the normal microflora of the human body were not carried out.

The use of antibacterial drugs can sometimes lead to an increased growth of microorganisms that are not susceptible to it. In clinical studies, it was shown that approximately 3% of patients receiving recommended doses of linezolid developed candidiasis associated with taking antibiotics. If superinfections occur against the background of linezolid, appropriate medical measures should be taken.

Clinical researches

The safety and efficacy of linezolid for more than 28 days have not been established.

In controlled clinical trials, patients with "diabetic foot" syndrome, bedsores or ischemic impairment, severe burns or gangrenous lesions did not participate.Thus, the experience of using linezolid in the therapy of these conditions is limited.