POLYMYXINS — the antibiotics produced by cultures of spore-forming bacteria of Bacillus polymyxa, Bacillus circulans, Bacillus colistinus.
Items — various antibacterial substances close on biol, to action, designated by letters A, B, C, D, E and M. V to medical practice apply polymyxins B, E and M.
Hydrochlorides and sulfates of polymyxins are crystal substances which are quickly dissolved in water to concentration of 40%, is moderate — in alcohol, are not dissolved in acetone and ether. The bases of polymyxins are practically not dissolved in water, are stable at pH within 2,0 — 7,0, even during the heating. At more acid and more alkaline pH values there is their loss biol, activities during 36 hours at the room temperature. Pepsin, trypsin, erepsin and Pancreatinum do not inactivate the Item.
Polymyxin B (Polymyxin, Aerosporin) is received at biosynthesis of cells you. polymyxa in 1947. Yellowish hygroscopic crystal powder, slightly bitter taste. Total formula C 56 H 96-98 O 13 N 16 , molecular weight (weight) 1201 — 1203.
Polymyxin E — colistin (Colomycin, Colimycin, Belkomycin) — is received at biosynthesis of cells you. colistinus in 1950. White hygroscopic crystal powder of bitterish taste. Total formula C45H85O10N13, molecular weight 969.
Polimiksinm is received at biosynthesis of cells you. polymyxa in 1954. White hygroscopic crystal powder, sweetish and bitterish taste. Total formula C 51 H 96 N 16 O 14 , molecular weight of 1185.
Different types of P. possess close antibiotic (hl. obr. bactericidal) activity, having the damaging effect on a cytoplasmic membrane of bacteria. Are active concerning the majority of gram-negative bacteria, except for bacteria of the sort Proteus. Concerning nek-ry gram-negative bacteria, especially Pseudomonas aeruginosa, P. surpass many widely applied antibiotics in the activity. Pneumococci, streptococci, enterococci, meningokokk, clostridiums, causative agents of tuberculosis, diphtheria, etc. are steady against P.'s action staphylococcus. The strains having resistance to one of P., a .ustoychiva and to others. Increase in resistance to P. is noted rather seldom and happens slowly. Action on vnekletochno the located bacteria is characteristic of polymyxins.
Items are not soaked up from intestines, their introduction is inside possible at treatment of nek-ry went. - kish. diseases. The item, except for polymyxin M., is recommended to be entered intramusculary. In this case they quickly come to blood and are slowly removed with urine. Various dosage forms of P. apply a method of intracavitary introduction of P. Imeyutsya to use inside, intramusculary, intralyumbalno, in a pleural cavity in the form of aerosols also. Intravenous administration of P. is shown at severe forms of diseases.
Use of polymyxins in clinic. Items possess rather narrow action spectrum and nppi the infections caused by a pyocyanic stick and also klebsiyella-m, pasterellam, an enterobakter, brucellas are effective. The main indications to P.'s use are the diseases caused by Ps. aeruginosa and Klebsiella (in particular, pneumonia, abscesses of lungs, meningitis, sepsis). At P.'s kolibakterioza apply only in case of inefficiency of other antibiotics. The most effective antibiotic from group P. is polymyxin E (colistin). It is applied inside in a dose of 250 mg a day to adults. To children it is appointed depending on age in doses: till 1 year on 3 mg/kg; from 1 year to 12 years of 125 mg a day. Intramusculary apply kolistimetat sodium (1,5 — 2 mg/kg a day), at a heavy current double a dose. Perhaps intravenous administration of an antibiotic in the specified dosages, at Krom is created the increased concentration of polymyxin E in blood.
Polymyxin B is used in the same purposes, as polymyxin E. Polymyxin B is applied inside and parenterally. Inside daily doses for children make: for babies of 20 mg/kg; for children up to 2 years of 150 mg; from 2 to 5 years of 150 — 200 mg (on 3 receptions). The adult enter 300 — 400 laid down in days (on 3 — 4 receptions). Intramusculary an antibiotic appoint in the form of sulfate in a dose 1,5 — 2,5 mg/kg a day (to 3 — 4 introductions).
Polymyxin M is applied at inertly current local processes (infected burns, decubituses, necrotic ulcers, etc.) in the form of ointments and solutions. Ointment contains an antibiotic in a dose of 2 mg on 1 g of an ointment basis and is applied daily (the daily dose shall not exceed 1,5 — 2 mg/kg). Inside the daily dose for adults makes 200 — 300 mg (on 4 — 6 receptions); for children up to 3 — 4 years of 10 mg/kg of body weight, from 5 to 12 years of 150 mg. Parenteral administration of polymyxin M is not allowed.
Absolute contraindications to P.'s use do not exist. Items with care apply at severe defeats of c. N of page and kidneys. Items can cause nevrol, disturbances (a dysarthtia, a lack of coordination of movements, an asynergia, an ataxy). These symptoms arise in 5 — 7 days after an initiation of treatment and pass later 1 — 2 day after drug withdrawal. Disturbance of gait and coordination of movements is possible that demands P.'s use in the conditions of a hospital.
Toxic damage of kidneys is characterized by an albuminuria (see. Proteinuria ), hamaturia (see), a cylindruria (see. Urine ), which develop later 1 — 2 week after an initiation of treatment. Similar changes are connected with toxic defeat of tubules and are exposed to involution in 7 — 10 days after drug withdrawal. A wedge, manifestations at the same time are absent.
Allergic reactions (see. Allergy ) can be shown by paresthesias and hypesthesias in lips, a pilar part of the head, the person and in extremities; also dizziness, nausea, weakness are observed. Polymorphic rash develops seldom. Local irritant action of P. is insignificant. At use in P. can make sick, pains in epigastric area, vomiting, ponosa. Side effect of P. is minimum at observance of a dosage of 2,5 mg/kg of body weight at parenteral administration and 20 mg/kg at appointment inside within 10 — 14 days.
See also Antibiotics .
Bibliography: Arnaudov G. D. Medicinal therapy, the lane with bolg., page 385, Sofia, 1975; Navashin S. M. and Fomina I. P. Reference book on antibiotics, page 245, M., 1974; Panaite-sku G. and Popescu E. Modern medicamentous pathology, the lane from Romanians., page 116, M., 1976; Shemyakin M. M., etc. Chemistry of antibiotics, t. 2, page 1089, M., 1961.
V. R. Sobolev; S. P. Burgayeov (wedge.).