TsEFALOSPORYNY — group of natural antibiotics, and also the semi-synthetic drugs received at chemical transformation of 7-aminotsefalosporanovy acid or 7-aminodezatsetoksitsefalospora-new acid; belong to r-lakta-mothers (r-lactamides). C. along with penicillin (see) and aminoglycosides (see. And ntibiotik, t. 10, additional materials) are one of the largest groups of antibiotics including many drugs which found a wedge, use.
Discovery of cephalosporins is connected with allocation in 1945 by the ital. researcher G. Brotzu of a strain of a fungus of Cephalosporium acremoni-um (on modern classification of Acremonium chrysogenum). In 1955 English researchers Newton and Eybrekhem (G. Newton, E. P. Abraham) was received cephalosporin C as a product of biosynthesis of this fungus. Afterwards it was established that representatives of many other species of microorganisms form the substances relating to group C. Multistage process of full chemical synthesis of cephalosporin C was carried out by Vudvord (R. Century of Woodward) awarded in 1965. A Nobel Prize for works on synthesis of biologically important organic compounds. Cephalosporin C as independent drug did not find medical application. In I960 Mr. R. Morin developed a method of receiving 7-aminotsefalosporanovy to - you (7-ATsK) therefore an opportunity for creation of unlimited number of semi-synthetic C appeared. Other direction in receiving C. chemical synthesis on the basis of transformations was 7-aminodezatsetoksitsefalosporanovy to - you (7-ADTsK), received from bin-zilpenitsillina.
C. — antibiotics of a broad spectrum of activity, have resistance to various types a r-varnish-tamaz (except tsefalosporinaz, to-rye hydrolyze certain C.), the expressed bactericidal effect, well get into fabrics and liquids of an organism. The mechanism of antibacterial action of these antibiotics is similar to that at penicillin — is caused by suppression of synthesis of a cell wall of bacteria.
C. appoint in the presence of contraindications for use of other antibiotics, first of all on-lusintetichesky penicillin (see), aminoglycosides or their combinations, including in cases of hypersensitivity to penicillin.
(Classical) — the first drugs which received use in clinic distinguish cephalosporins I of generation; the cephalosporins II and III of generations different from cephalosporins I of generation bigger activity concerning gram-negative bacteria, bigger stability to action r-laktamaz.
Cephalosporins I of generation include cefalotin, cefalexin, Cefaloridinum (tseporin), cefazolin (Kefzolum), tsefaloglitsin, etc. In the USSR are issued cefalotin and tsefaleksinony the wide experience of use of cefazolin and Cefaloridinum is accumulated Now. The last drug has no advantages in comparison with cefalotin, but is characterized by the expressed nephrotoxicity and in the majority of the countries is not applied. Cefazolin is optimum drug from cephalosporins I of generation. Against nek-ry gram-negative bacteria it surpasses cefalotin in pharmacokinetic parameters and activity a little. The main cephalosporins I of generation which are the most widely applied in medicine are cefalotin and tsefaleksinony
Cefalotin (Cephalotin, Ke-flin) — sodium salt 7-[(2 thienyl) acetamido] - tsefalosporanovy to - you. Total formula: C16H15N2Na06S2, molecular weight (weight) 396,4. White crystal powder, well water soluble. It is active concerning the majority of the gram-positive cocci which are forming and not forming r-lactamelements (except enterococci). It is steady against action staphylococcal r-lakta-mazy, collapses under influence r-laktamaz, the gram-negative bacteria formed by antibiotikorezistentny strains. More than 50% of strains of colibacilli, bacteria of group of a klebsiyell — an en-terobakter are steady against cefalotin, completely rezistentna to it of sulfurs radio sets, tsitrobakter, pseudo-monads, providention, indolpositive proteas. Stability to cefalotin of gram-negative microorganisms develops quickly, gram-positive — slowly. Partial cross resistance of gram-negative bacteria to ampicillin and cefalotin is observed.
Cefalotin is not soaked up at intake. At parenteral use the greatest concentration of drug in blood serum is found in 30 min. — 1 hour after intramuscular introduction and in 15 min. — after intravenous. Therapeutic concentration of cefalotin in blood are maintained within 3 — 4 hours, the antibiotic for 50 — 70% communicates serum proteins. Cefalotin is well soaked up and distributed in an organism, it is found in high concentration in kidneys, in pleural, peritoneal and synovial exudates, in smaller quantities — in a bronchial secret and a prostate; practically does not get through a blood-brain barrier (see). Cefalotin (in an active form and partially in the form of inactive metabolites) is removed from an organism of hl. obr. kidneys by canalicular secretion. The antibiotic is partially excreted by a liver and it is found in bile in therapeutic concentration.
of the Indication to use of cefalotin the same, as for polusinteti-chesky penicillin (see). Cefalotin is applied to treatment of infections of the respiratory and urinary tract, contaminated wounds, burns and various other pyoinflammatory diseases caused by sensitive microorganisms. The antibiotic is applied at sepsis, peritonitis. Owing to its high resistance to a staphylococcal penicillinase cefalotin is effective at the infections caused by penitsillinazoobrazuyushchy stafilokokka.
Cefalotin is entered by hl. obr. intravenously. Intramuscular administration of drug is applied seldom. At the infections caused by gram-positive microorganisms, the daily dose makes 2 — 3 g, gram-negative — 4 —, in case of a heavy generalized infection of 10 g and more. The drug is administered by bucketed 4 — 6 hours.
By-effects at use of cefalotin are observed seldom. Allergic reactions (skin rashes, an eosinophilia) arise at 1 — 5% of patients. Only at 5 — 10% of patients with a cross allergy to penicillin the heavy allergic phenomena can develop (a small tortoiseshell, a Quincke's disease, in rare instances — an acute anaphylaxis). At introduction of the daily doses exceeding 10 g the nephrotoxic phenomena can sometimes be observed.
Form of release: the bottles containing 0,5 g, 1 g and 2 g of drug.
Cefalexin (Cephalexin, Keflex, Ceporex, Oracef). 7 (B-a-amino-a-fenilatsetamido) - Z-metil-Z-tsefem-
4-carboxylic to - that. Total formula: C16H17N304S-H20, molecular weight (weight) 347,7. Crystal powder, white with a yellowish shade, water soluble. Possesses the wide range of antimicrobic action close to cefalotin, however it is characterized by smaller activity in the relation of both gram-positive, and gram-negative microorganisms. Cefalexin is steady against action staphylococcal r-lactamelements and is active against the stafilokokk producing (3 lactamelements. The majority of strains of aerobic streptococci is sensitive to cefalexin, however enterococci are steady against it. Are moderately sensitive to cefalexin of a clostridium and listeriya, gonokokka, meningokokka, peptokok-ka and peptostreptokokka. Bacteroides fragilis are steady against cefalexin, bacteria of the sort Fusobacterium and the sort Veillonella — are sensitive. Drug resistance develops slowly.
At intake more than 90% of cefalexin are soaked up. Drug is found in high concentration in kidneys and a liver, gets into pulmonary fabric, it is found in a pancreas. Cefalexin is emitted with kidneys in not changed look and it is found in high concentration in urine that defines high performance of an antibiotic at diseases of kidneys and urinary tract. Drug does not get through a blood-brain barrier.
Indications to use of cefalexin are close to indications for other cephalosporins. Drug is generally used in out-patient practice at moderately severe infections. Cefalexin is applied inside in the daily dose
of 1 — 2 — 4 g (divided into 4 receptions).
By-effects at treatment by cefalexin are shown by nausea, vomiting, abdominal pains, is rare — diarrhea. Allergic reactions (rashes, urticaria, it is rare — a Quincke's disease), a cross (incomplete) allergy with drugs of group of penicillin are possible.
Form of release: capsules on 0,25 g or in the form of powder in the banks from orange glass with a capacity of 150 ml containing drug together with fillers gross weight on 35 g (on 2,5 g of active agent).
Cephalosporins II of generation include tsefamandol, tsefuroksy, etc. Drugs of this group are much stabler concerning the penicillinases formed by various microorganisms. tsefamandol surpasses cefalotin concerning a hemophilic stick and enterobakteriya in a degree of activity. On pharmacokinetic properties it is comparable with cefalotin.
Tsefuroksim holds average position in group C. on stability to r-lactamelements, it is active concerning gonokokk, indolpolozhi-telny protiums and a hemophilic stick. Drug is longer in comparison with other antibiotics of this group remains in blood.
Tsefamandol and tsefuroksy are widely applied at treatment of hospital infections of various etiology (see. Intrahospital infections) except for the infections caused by pseudo-monads. Tsefamandol is highly active concerning stafilokokk, except having multiple resistance. Cephalosporins II of generation are well transferred and can be appointed the patient with an allergy to penicillin. Intravenous administration of these drugs is successfully applied to prevention of postoperative purulent complications.
Cephalosporins III of generation.
Carry anti-bio tics of a broad spectrum of activity to this group (to tsefotak-these, tsefoperazon, a ceftazidime, tsef-tizoksy, tsefzulodin, a tseftriak-dream), highly active concerning aerobic and anaerobic gram-negative microorganisms. In the USSR from cephalosporins III of generation apply tsefotaksy.
Tsefotaksim possesses the expressed action concerning enterobakteriya, gonokokk, hemophilic sticks, moderately aerobic and anaerobic, is active concerning pyocyanic sticks and stafilokokk. According to pharmacokinetic characteristics tsefotaksy it is close to cefalotin. Drug is well transferred by patients.
Tsefoperazon is highly active concerning the majority of enterobakteriya, is moderately active concerning gram-positive anaerobe bacterias and pyocyanic sticks, is not active at the infections caused by V. fragilis. The antibiotic in high concentration is found in blood and is allocated preferential with bile. Drug gives good therapeutic effect, however in some cases diarrhea, obviously, connected with dysbacteriosis (see) is noted.
The ceftazidime, as well as tsefotaksy and tsefoperazon, possesses a wide range of antimicrobic action, especially concerning gram-negative anaerobic sticks. The antibiotic exceeds all other C. on action on pseudo-monads.
Tseftizoksim is characterized by the expressed activity against the majority of enterobakteriya and V. of fragilis. According to pharmacokinetic and pharmacological characteristics it is similar to other cephalosporins III of generation.
Tsefzulodin differs in the expressed activity concerning pyocyanic sticks (see), but poorly affects other representatives of gram-negative microorganisms.
On physical. - to chemical properties and a range of antibacterial action cephalosporins III of generation are close adjoined by derivatives tsefamitsi-is new — tseftriakson and a moxalactam. Tseftriakson possesses the prolonged action and is very long and in high concentration remains in an organism. The moxalactam is characterized by very wide range of antimicrobic action covering gram-negative microorganisms, both aerobic, and anaerobic, surpassing other antibiotics in action on V. fragilis; it is active against pyocyanic sticks; it is steady against r-lactamelements. The moxalactam in high concentration is found in blood, gets through a blood-brain barrier. The moxalactam for treatment of various forms of meningitis is especially perspective.
SITE 189 Bibliogrnavashins. M and F about m and - N and I. P. Rational antibioticotherapia, M., 1982; they, Some results and perspectives of development of researches in the field of semi-synthobiotics, Antibiotics, t. 29, No. 2, page 136, 1984; Chemistry and biology of | 3-lactam antibiotics, ed. by R. B. Morin a. M. Gorman, v., N. Y. a. o., 1982. S. M. Navashin.