Antimicrobial Chemotherapy Antibiotics Drug Resistance of Bacteria Vinnitsa

Antimicrobial Chemotherapy. Antibiotics. Drug Resistance of Bacteria Vinnitsa National Pirogov Memorial Medical University / Department of microbiology

Chemotherapy and chemotherapeutic agents Chemotherapy Chemotherapeutic agents Antibiotics Chemotherapeutic index

Development of chemotherapy ¡ ¡ ¡ Paul Erlich found that dye Trypan Red was active against the trypanosome (causative agent of African sleeping sickness) in 1904 In 1910 P. Erlich discovered the arsenical compounds and one of their was active against the syphilis spirochete (later was called Salvarsan) Cherhard Domagk discovered sulfonamides (red streptocide) that were effective for treatment of streptococci and staphylococci infections in 1935 (Nobel Prize in 1939) In 1929 A. Fleming got penicillin, a first antibiotic In 1939 penicillin was produced and purified by chemists H. Flory and E. Chain (A. Fleming, H. Flory and E. Chain received the Nobel Prize in 1945) Selman Waksman announced in 1944 that he had found a new antibiotic streptomycin (he received Nobel Prize in 1952)

Chemotherapeutic Index (CTI) ¡

Classification of chemotherapeutic agents according to target (general microbial group they act against) Antimicrobial drugs ¡ Antiviral drugs ¡ Antifungal drugs ¡ Antiprotozoan drugs ¡ Antitumoral drugs ¡

Classification of chemotherapeutic agents l l l Narrow-spectrum drugs Broad-spectrum drugs Specific-spectrum drugs (antituberculous, antiviral, etc. )

Classification of chemotherapeutic agents ¡ Due to their total effect: l l ¡ With cidal action With static action Due to their manufacture : l l l Natural Semi synthetic Synthetic

Chemical classification of CTD ¡ ¡ ¡ Heavy metal derivates Sulfonamides Diaminopyrimidins Analogs of iso-nicotinic acid Nitrofuran derivatives Quinolones Chinoxalines Oxychinolones Azoles Metronidazole Alkaloid preparations Chinine derivate

Antibiotics ¡ According to origin antibiotics are subdivided into next groups: l l l Antibiotics produced by fungi. Antibiotics produced by actinomycetes. Antibiotics produced by bacteria Plant antibiotics (phytoncides) Animal antibiotics (lysozyme, interferons)

Mechanism of antibiotic action l l Cell wall synthesis inhibitors Protein synthesis inhibitors Cell membrane disruptors Nucleic acid synthesis inhibitors

Antibiotic action onto bacterial cell

Chemical antibiotics classification l l l l Penicillins Cephalosporins Carbapinems Monobactams Vancomycin Bacitracin Cycloserine Antitumoral antibiotics l l l l Aminoglycosides Tetracyclines Macrolides Chloramphenicol Linezolid Rifampin Polymyxin Polyenes

Chemical structure of β-lactams Penicillin nucleus Monobactam nucleus Cephalosporin nucleus Carbapenem nucleus

B-lactams influence onto bacterial cell wall

Chemical structure of gentamicin Chemical structure of chloramphenicol Chemical structure of a tetracycline Chemical structure of lincomycin

Action of aminoglycosides onto protein synthesis

Determination of antimicrobial effectiveness of chemotherapeutic agents ¡ ¡ Dilution susceptibility tests Disk diffusion tests E-tests Accelerated tests

Broth dilution test

Disk diffusion test

Side effects of chemotherapy Allergic response ¡ Toxic effects ¡ Disbacteriosis ¡ Inhibition of immune system ¡ Embryotoxic action ¡ Formation of the drug resistance ¡

Resistance to antimicrobial drugs ¡ Natural ¡ Acquired (mutation and genetic recombination)