Antibiotics

Chemotherapeutic drugs Chemotherapeutic agents – drugs acting on microorganisms inside of macroorganism

Differences of chemotherapeutic drugs Operate, basically on microbes inside of organism Possess selective action (toxic on microorganism and little or not toxic for macroorganism) System action is priority

The basic methodical principles of chemotherapy To choose correctly chemotherapeutic agents taking into consideration of the bacterial diagnosis and sensitivity of microorganism to drugs A choice of rational routs of administration

The basic methodical principles of chemotherapy The early beginning of treatment An empirical selection of drugs The optimal dose for creating a sufficient antimicrobial concentration

The basic methodical principles of chemotherapy complex treatment monitoring of treatment sufficient duration of treatment a rational combination of chemotherapeutic agents

Antibiotics Antibiotics – substances which selectively and effectively act on harmful microbes, not mentioning thus the cells are useful and important for the macroorganism.

Uniqueness of antibiotics The action is directed only at the pathogen agent

Classification ( according to mechanism of action ) Mechanism of action Antibiotics Inhibit cell wall synthesis PenicillinsCephalosporinsMonobactamsCarbapenems Glycopeptides

Classification (according to mechanism of action) Mechanism of action Antibiotics Impairment of permeability of the cytoplasmic membrane Polimixins

Classification (according to mechanism of action) Mechanism of action Antibiotics Inhibit protein synthesis on the ribosomes ChloramphenicolTetracyclinesMacrolidesLincomycinAminoglycosides

Classification (according to mechanism of action) Mechanism of action Antibiotics Inhibit nucleonic acid synthesis Rifampicin

Classification (according to type of action): BactericidalPenicillinsCephalosporinsAminoglycosidesRifampicinPolimixinsBacteriostaticMacrolidesTetracyclines Lincomycin Chloramphenicol

Classification (according to spectrum of action): Narrow spectrum – biosynthetic penicillins, polimixins, polyene Broad spectrum – Tetracyclines, ChloramphenicolCephalosporins Broad spectrum – Tetracyclines, Chloramphenicol Cephalosporins Medium spectrum Macrolides Lincomycin

Penicillins Operating component of molecule of penicilline has betalactam ring (betalactam drugs)

The mechanism of action inhibit synthesis of bacterial cell wall due to suppression of transpeptidase and disturb a synthesis of peptidoglycan in the cell wall. Act on microbes in a stage of growth - young growing microorganisms are more sensitive to penicillin than old ones

Penicillins Type of action bactericidal Toxicity insignificant

biosynthetic penicillins Type of action - Bactericidal

The spectrum of action The narrow spectrum of action: mainly on gram-positive bacteria (staphylococci, streptococci, pneumococci), gram-negative bacteria (meningococci, gonococci) tetanus bacillus, diphtheria bacillus, spirochete

Preparations 1. Natural (biosynthetic) penicillins: benzylpenicillin (penicillin G) benzylpenicillins: Sodium Benzyl penicillin, Potassium Benzyl penicillin phenoxymethylpenicillin (penicillin V) phenoxymethylpenicillin (penicillin V) The spectrum of action is similar to penicillin, but is accepted orally, is acid resistant.

long-acting preparations: novocain salt of benzylpenicillin (benzylpenicillin procain) (duration of action 12 hours); bicillins: bicillins: bicillin-1 (benzatyn benzylpenicillin), bicillin-5.

Indications to use: for treatment of infectious-inflammatory diseases caused microorganisms are sensitive to penicillin

The main side effects: allergic reaction anaphylactic shock disorders of electrolyte balance neurotoxic reactions (in using of big doses) – encephalopathy (hyperreflexia, seizures, hallucinations, coma)

semisynthetic penicillins Aminopenicillins - unlike biosynthetic penicillins have the broad spectrum of action. Ampicillin has a broad spectrum of action and it is acid-resistant

semisynthetic penicillins amoxicillin is combined penicillin of broad spectrum of action and acid- resistant In 2,5 times it is better absorbed in oral administration. It is not used in intestinal infections.

semisynthetic penicillins Охасillin. It is effective concerning polyresistant St. aureus (РRSA) Spectrum of action The narrow spectrum of action: gram-positive bacteria (staphylococci, streptococci, pneumococci), gram-negative bacteria (meningococci, gonococci) diphtheria bacillus, staphylococci which produce β- lactamases Spectrum of action The narrow spectrum of action: gram-positive bacteria (staphylococci, streptococci, pneumococci), gram-negative bacteria (meningococci, gonococci) diphtheria bacillus, staphylococci which produce β- lactamases

for treatment of infectious-inflammatory diseases caused microorganisms are sensitive to oхасillin

semisynthetic penicillins Carboxypenicillins (antipseudomonas penicillins) carbenicillin ureidopenicillins (antipseudomonas penicillins)

semisynthetic penicillins Carboxy- and ureidopenicillins have a broad spectrum of action including Enterobacter.

semisynthetic penicillins Combinations of penicillins with inhibitors of β- lactamases: – ampicillin/sulbactam – amoxicillin /clavulanate

Cephalosporins Type of action - Bactericidal. The broad spectrum of action: mainly on gram- negative bacteria but depends from generation Operating component of molecule of cephalosporins has betalactam ring (betalactam drugs)

Cephalosporins The mechanism of action inhibit synthesis of cell wall of bacteria Major side effects : nephrotoxicity, hemopoesis disturbances, allergy

Cephalosporins Cephalosporins of I generation. Серhazolin (for parenteral administration), Сеphalexin (orally) Spectrum of action: gram-positive and gram-negative cocci, activity on gram- negative bacteria is moderated.

Cephalosporins of I generation - - resistant to beta-lactamases, are not resistant to cephalosporinase Gram-positive bacteria (pneumococci, streptococci, staphylococci) - Gram-negative bacteria (Escherichia coli, Klebsiella pneumonia, Proteus mirabilis) - no effect on Pseudomonas aeruginosa, Proteus, Bacteroides

Cephalosporins of II generations. Cefamandole, Сеfuroxim (for parenteral administration), Cefaclor (orally) Spectrum of action - Spectrum of action - I generation + Enterobacter, proteus - - Less effective against gram-positive cocci - - No effect on Pseudomonas aeruginosa

Cephalosporins of III generations Сеfotaxim, Ceftazidime, Ceftriaxone Are even more active rather gram- negative bacteria and are more stable to β-lactamases.

Cephalosporins of III generations - - Wider spectrum of action, especially as against gram-negative bacteria - - Gram-positive bacteria (pneumococci, streptococci, staphylococci) - Gram-negative bacteria (Escherichia coli, Klebsiella pneumonia, Proteus mirabilis) - - Pseudomonas aeruginosa, Proteus, Bacteroides Pass through the blood-brain barrier

Cephalosporins of IV generations Cefpirom A broad spectrum of action, act on pseudomonas, are stable to β- lactamases. On the same activity as carbapenems.

Cephalosporins of IV generations Broader spectrum of action than the preparations of the 3rd generation - - Are more effective against Gram-positive cocci - - Highly active against Pseudomonas aeruginosa, gram-negative bacteria

Side effects: allergic reactions, including cross allergy with penicillins Nephrotoxicity (accumulation in epithilial cells of kidney canalicules) Granulocytopenia Hemorrhages (inhibition of synthesis of factors of blood coagulation in liver) – cephalosporins ІІІ disbacteriosis, superinfection

Irritation of mucous membrane of digestive tract infiltrates after intromuscular introduction infiltrates after intromuscular introduction phlebitis after inrtavenous introduction

Side effects: Encephalopathy (hyperreflexia, seizures, coma) Encephalopathy (hyperreflexia, seizures, coma)

Monocyclic β-lactams (Monobactams) Operating component of molecule of monobactams has betalactam ring (betalactam drugs) Operating component of molecule of monobactams has betalactam ring (betalactam drugs) The mechanism of action: inhibition synthesis of bacterial wall. Spectrum of action: gram-negative bacteria, including P. aeruginosa, salmonellas, shigells, H. inuenzae, gonococci and meningococci.

Monocyclic β-lactams (Monobactams) Type of action – Bactericidal Side effects: hepatotoxicity, enterotoxicity.

Aztreonam. Preparations of reserve. Action spectrum - Gram (-) bacteria, including Escherichia coli, Clebsiellas, Proteus, Haemophilus influenzae (activity is equal to the activity of cephaloporins of third generation) Indication to use: sepsis, infection of urinary tract, soft tissues, meningitis and others (often combined with aminoglycosides, clindamycin, metronidazole, vankomycin).

Carbapenems Operating component of molecule of carbapenems has betalactam ring (betalactam drugs) Operating component of molecule of carbapenems has betalactam ring (betalactam drugs) Are highly tolerant to action of bacterial β-lactamases. Spectrum of action is widest, including staphylococcus, enterococcus (but not S. faecium), anaerobe, except C. difcile.

Carbapenems Imipenem+cilastatin Side effects: neurotoxicity Meropenem Meropenem Antibiotics of reserve Indication to use: sepsis, infections of a small pelvis, endocarditic, pneumonia, abscess of lung

Glycopeptides Operating component of molecule of glycopeptides has betalactam ring (betalactam drugs) Operating component of molecule of glycopeptides has betalactam ring (betalactam drugs)Vancomycin The mechanism of action: inhibition of synthesis cell wall and damage of penetration cytoplasmic membrane of bacteria.

Glycopeptides Type of action bactericidal. Spectrum of action is narrow: is active only on gram-positive bacteria. Spectrum of action is narrow: is active only on gram-positive bacteria. Side effects: ototoxicity in mainly in older persons and in disorder of kidneys function, nephrotoxicity, hyperemia of skin especially by quick introduction.

Aminoglycosides All of them contain amino sugars The mechanism of action: suppression of protein synthesis on the level of bacteria ribosomes. Spectrum of action is wide, including pathogen of plague, brucellosis, tuberculosis.

Aminoglycosides 1 generation Streptomycin Streptomycin Canamycin Canamycin Neomycin Neomycin Monomycin Monomycin 2 generation Gentamycin Gentamycin 3 generation Amicacin Amicacin Tobramycin Tobramycin Sizomycin Sizomycin 4 generation Netilmycin Netilmycin

Aminoglycosides Broad spectrum of action Highly active against gram-negative microorganisms Streptomycin, canamycin active against Mycobacterium tuberculosis

Aminoglycosides inhibit protein synthesis Mechanism of action - inhibit protein synthesis on ribosomes - High doses - inhibit the permeability of the cytoplasmic membrane Type of action - bactericidal

Aminoglycosides Administered parenterally Act only extracellularly Resistance of microorganisms has developed rapidly

Aminoglycosides Indications to use: sepsis unclear etiology, infectious endocarditis, pyelonephritis, infections of a small pelvis, septic arthritis The main side effects: The main side effects: nephrotoxicity nephrotoxicity ototoxicity ototoxicity neuromuscular block

Aminoglycosides Streptomycin. High ototoxicity, hearing disorder, at long-standing use in high dozes deafness can developed. It is active against mycobacteria tuberculosis.

Aminoglycosides Canamycin. It is the least toxic. It is active against mycobacteria tuberculosis. Gentamycin. The basic aminoglycoside of II generation. More toxic than canamycin. Amycacin. Is used for treatment of hospital infections

Aminoglycosides Side effects: nephrotoxicity, neurotoxicity, myoneural blockade, hematotoxicity, but only in parenteral introduction. Leuko-, thrombocytopenia, hemmorhages, hemolisis Allergic reactions

M Macrolides Macrolides14 members15 members16 members Natural Erythromy- cin Oleandomy- cin Spiramycin Josamycin Midecamy- cin Semisynthe tic Roxithromy- cin Clarithromy- cin Azithromy -cin Midecamy- cin acetate

Macrolides Contain a macrocyclic lactone ring linked by various sugars Reserve antibiotics, resistance of microorganisms has developed fast. The average spectrum: gram positive cocci, pathogenic spirochetes, gram negative cocci, pathogenic anaerobes rikketsii, Chlamydia, Mycoplasma, Legionella Mechanism of action - inhibit protein synthesis on ribosomes

Macrolides Type of action is bacteriostatic Creating high concentrations of antibiotic Creating high intracellular concentrations of antibiotic Immune stimulating effect Antiinflammatory action Have a low toxicity to the macroorganism

Macrolides erythromycin, oleandomycin, roxithromycin, spiramycin, clarythromicin Indications to use: Indications to use: infections of respiratory tract, diphtheria, syphilis, staphylococcus skin infections, soft tissues, stomach ulcer.

Side effects Dispeptic disorders, disbacteriosis, superinfection Cholestasis, cholestatic jaundice (erythromycin) Depression of liver microsome enzyme activity (erythromycin, oleandomycin can not be combined with theophylline, ergot alkaloids, carbamazepine) Development of resistance in process of treatment Development of resistance in process of treatment

Azithromycin Azithromycin Azithromycin. Duration of action – 24 hours. Therapeutic action has been last for 5 days after abolition (postantibiotic effect). Indications to use: infections of respiratory tract, diphtheria, syphilis, staphylococcus skin infections, soft tissues, stomach ulcer.

Azithromycin is 2-4 times less active on the effect of erythromycin on Staphylococcus and Streptococcus Creating high intracellular concentrations of antibiotic times higher than in blood plasma, especially as in macrophages and fibroblasts The average spectrum: gram positive cocci, pathogenic spirochetes, gram negative cocci, pathogenic anaerobes rikketsii, Chlamydia, Mycoplasma, Legionella Mechanism of action - inhibit protein synthesis on ribosomes

Polymyxin M The mechanism of action: damage cytoplasmic membranes of bacteria. Type of action bactericidal. Spectrum of action - narrow: gram- negative bacteria, except proteus. They are not absorbed from GIТ, act in empty space of GIТ.

Polymyxin M Side effects: nephrotoxicity, neurotoxicity, myoneural blockade, hematotoxicity, but only in parenteral introduction. Indication to use: inward in acute intestinal infections, locally in wound pseudomonas infections, including burns.

Tetracycline The mechanism of action: inhibition protein synthesis on the level of bacteria ribosomes, but not less important party of their effect are formation of complexes with metals and influence on binding of calcium, magnesium and manganese in cell

Tetracycline Type of action bacteriostatic. Broad spectrum of action: cocci, Rickettsia, brucella, separate large viruses, and also protozoas (amoebas, trichomonads).

Tetracycline natural: Tetracycline, oxytetracycline. semisynthetic: metacycline, doxycycline Indication to use: Chlamidia trachomatis infections, specially dangerous infections, syphilis, stomach ulcer, ricketsiosis Chlamidia trachomatis infections, specially dangerous infections, syphilis, stomach ulcer, ricketsiosis

Tetracycline Dispeptic disorders, stomatitis, glositis,esophagitis, pruritus etc. Disbacteriosis and superinfection with Candida fungi, proteus, pseudomonadas or staphylococci. Disbacteriosis and superinfection with Candida fungi, proteus, pseudomonadas or staphylococci.Photodermatosis. Liver toxicity.

Absorbtion by bones and teeth of a featus or a child: hipoplasia of dental enamel, disorder of teeth formation, tendency for caries. Antianabolic action, damage of kidneys (when using tetracyclines with long termed storage, using big doses). Tetracyclines contrindicates for children under the age of 8-12, during pregnancy, liver diseases, kidney insufficiency

tetracyclines

Lincosamines - lincomycin The mechanism of action: inhibition protein synthesis on the level of bacteria ribosomes. Type of action bacteriostatic. Spectrum of action - moderate: on gram-positive bacteria and anaerobe. Are capable to collect in bone and cartilaginous tissues.

Lincosamines - lincomycin Indication to use: infections of the lower respiratory tract, bones, joints, bodies of small pelvis Side effects: of pseudomembranous colitis. dyspepsia and dysbacteriosis

Chloramphenicol The mechanism of action: Inhibit a protein synthesis on the level of bacteria ribosomes. Spectrum of action Broad spectrum of action Acts on bacteria which are stable to penicillin Acts on bacteria which are stable to penicillin

Chloramphenicol Type of action: pneumococcusmeningococcus H. inuenzaе bactericidal on the others bacteriostatic Penetrates through blood-brain barrier

Indications to use: meningitis, typhoid fever, paratyphoid fever, brucellosis, tularemia

Side effects of chloramphenicol hematotoxicity Hypochrome and aplastic anemia, granulocytopenia, thrombocytopenia «grey baby syndrome» in newborn depression of cardiovascular activity (up to collapse, heart failure) hepatotoxicity neurotoxicity hepatotoxicity neurotoxicity dyspepsia dyspepsia disbacteriosis and superinfection