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ANTIMICROBIAL AGENTS. By. Dr. Emad AbdElhameed Morad. Lecturer of Medical Microbiology and Immunology. Definitions. Antibiotic: substance of microbial origin with antimicrobial activity against other organisms. Chemotherapeutic agents: synthetic drugs with antimicrobial activity.
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ANTIMICROBIAL AGENTS By Dr. Emad AbdElhameed Morad Lecturer of Medical Microbiology and Immunology
Definitions • Antibiotic: substance of microbial originwith antimicrobial activity against other organisms. • Chemotherapeutic agents: synthetic drugs with antimicrobial activity. • Bactericidal agents: drugs which kill and destroy the bacteria. • Bacteriostatic agents: drugs which inhibit the growth and multiplication of bacteria without killing them.
Ideal antimicrobial agent • Selective toxicity:harmful to the bacteria and non toxic to the host cells. • Broad spectrum:affect a variety of bacteria both Gram positive and Gram negative. • Bactericidal better than bacteriostatic. • Diffusible to distant body areas with slow rate of excretion. • Bacteria do not develop resistance to it.
Mechanisms of action of antimicrobial agents • Inhibition of cell wall synthesis: penicillin and cephalosporin. • Inhibition of cell membrane function: polymyxins, amphotericin-B, nystatin and colistin. • Inhibition of protein synthesis:chloramphenicol, tetracycline and aminoglycosides (amikacin and gentamicin). • Inhibition of nucleic acid synthesis: • DNA inhibition by inhibiting DNA gyrase enzyme: quinolones. • RNA inhibition by inhibiting RNA polymerase enzyme: rifampicin. • Competitive inhibition: sulphonamides compete with para-amino-benzoic acid (PABA) for the active site of the enzyme involved in folic acid synthesis.
Choice of antimicrobial agent • Choice of the antimicrobial agent depends on: In-vitro tests of bacterial sensitivity to antibiotics Empirical use of antibiotics OR Using antibiotics without in-vitro tests Disc diffusion method Dilution method Closed lesions with no available sample such as brain abscess While waiting for the in-vitro sensitivity result
Antimicrobial drug combination • In severe infections of unknown organism. • In mixed infections with organisms that have different antibiotic sensitivities. • To avoid development of resistant strains especially with prolonged course of treatment as in tuberculosis. • For complete eradication of the organism to avoid occurrence of complications. • Synergism:the combined effect of a pair of antimicrobial agents is greater than the sum of the two drugs acting separately such as use of penicillin and gentamicin (1+1=>2).
Chemoprophylaxis • Definition: • Means administration of antimicrobial drugs to prevent infection (before the development of a disease). • Examples: • A single large dose of amoxycillin given immediatelybefore dental procedures for patients with congenital or rheumatic heart disease to prevent endocarditis. • Administration of broad spectrum bactericidal drug before until after major surgical procedures.
Complications of antimicrobial agents • Drug toxicity: • Chloramphenicol cause bone marrow inhibition. • Aminoglycosides are nephrotoxic. • Streptomycin is ototoxic. • Tetracycline causes teeth deformity and liver damage. • Hypersensitivity: • Some antimicrobials act as haptens. • When they bind to host tissue proteins, they become antigenic and stimulate exaggerated immune response leading to tissue damage.
Superinfection: • During treatment with a broad spectrum antibiotic, susceptible members of normal flora at different body sites are killed. • This will result in biological imbalance. • Bacteria resistant to the antibiotic used will cause superinfection: • Candida may cause oral thrush. • Clostridium defficile and staphylococci cause enterocolitis. • Development of drug resistance: • The emergence of resistant mutants is encouraged by: • Inadequate dosage or duration of chemotherapy. • Presence of a closed focus of infection. • Abuse of antibiotics without in-vitro sensitivity testing.
Mechanisms of antimicrobial resistance • Bacteria produce enzymesthat inactivate the drug. • Beta-lactamase enzymes cleaves the β-lactam ring in penicillins and cephalosporins. • Bacteria decrease their permeability to the drug. • Streptococci resist aminoglycosides by this mechanism. • Bacteria alter the target site for drug action. • Resistance to aminoglycosides is associated with alteration in 30S subunit of the bacterial ribosome.
Development of alternative pathway to bypass the pathway inhibited by the drug. • Bacteria resistant to sulphonamides utilize the folic acid with no need for PABA. • Bacteria actively pump the drug out using efflux pump. • Note that • Genes mediating resistance of bacteria to antibiotics are frequently carried on plasmids. • Plasmids could be transmitted between bacterial cells by three methods spreading the resistance between bacteria: • Transformation:uptake of free DNA liberated from lysed bacterial cells. • Conjugation: transfer is mediated through sex pilus. • Transduction: transfer is done by bacteriophages.
To limit the bacterial resistance to antibiotics • Antibiotics should be prescribed only after doing in-vitro antibiotic sensitivity testing. • However, empirical antibiotic treatment is indicated in certain situations. • Moreover, pay attention to prescribe the proper antibiotic in the proper dose and for the proper duration.
