Pharm 262: Antibiotics. 1 Pharmaceutical Microbiology II DR. C. AGYARE

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1 Pharm 262: 1 Pharmaceutical Microbiology II Antibiotics DR. C. AGYARE

2 Reference Books 2 HUGO, W.B., RUSSELL, A.D. Pharmaceutical Microbiology. 6 th Ed. Malden, MA: Blackwell Science, WALSH, G. Biopharmaceuticals: Biochemistry and Biotechnology. 2 nd Ed. New York: Wiley, 2003.

3 Course content/learning outcomes 3 Definitions of antibiotics Classification of antibiotics Mode of actions of antibiotics Antimicrobial spectrum Few significant/major sides effects

4 Chemotherapy 4 Chemotherapy is the treatment or prevention of disease with chemicals The term was coined by Paul Ehrlich The definition has been expanded to include antibiotics. The term now is widely applied to treatment of cancer

5 Antibiotics Antibiotics are natural antibacterial substances produced by microorganisms (bacteria, fungi, and actinomycetes) Extended to include synthetic antimicrobial agents, such as sulfonamides and quinolones. Antibiotics differ markedly in physical, chemical, and pharmacological properties, in antimicrobial spectra, and in mechanisms of action. Knowledge of molecular mechanisms of bacterial replication has greatly facilitated rational development of compounds that can interfere with their replication. 5

6 History of Antibiotics The antibacterial effect of penicillin was discovered by Alexander Fleming in Fleming had devoted much of his career to finding methods for treating wound infections. A fungal colony grew as a contaminant on an agar plate streaked with Staphylococcus aureus. The bacterial colonies around the fungus were transparent A fungal metabolite may be responsible The substance was named penicillin, because the fungal contaminant was identified as Penicillium notatum.

7 History of antibiotics I 7 In 1941, Florey and Chain managed to produce the antibiotic on an industrial scale. Penicillin was originally obtained, as a mixture of Penicillins known as F, G, X, and K, from the mould Penicillium notatum. Better yields were achieved using P. chrysogenum. The (earlier) natural penicillins, were produced by adding side chain precursors to the fermentation medium. Benzylpenicillin (penicillin G) was selectively produced by adding the precursor phenylacetic acid Phenoxymethylpenicillin (penicillin V) was produced by adding phenoxymethyl acetic acid.

8 History of antibiotics II 8 The discovery of penicillin led to the search for other antibiotic-producing microorganisms, especially from soil environments. Streptomycin - Streptomyces griseus (soil actinomycete) Cephalosporins - Cephalosporium acremonium Griseofulvin - Penicillium griseofulvum Chloramphenicol - Streptomyces venezuelae

9 History of antibiotics III In 1935, Domagk discovered that prontosil A dye, could protect mice against several thousand times the lethal dose of haemolytic streptococci and was also effective against infections in man. 9

10 Some Clinically Important Antibiotics Antibiotic Producer organism Activity Site or mode of action Penicillin Penicillium chrysogenum Gram-positive bacteria Cephalosporium Cephalosporin Broad spectrum acremonium Wall synthesis Wall synthesis Griseofulvin Penicillium griseofulvum Dermatophytic fungi Microtubules Bacitracin Polymyxin B Bacillus subtilis Bacillus polymyxa Gram-positive bacteria Gram-negative bacteria Wall synthesis 10 Cell membrane Amphotericin B Streptomyces nodosus Fungi Cell membrane Erythromycin Streptomyces erythreus Gram-positive bacteria Protein synthesis Neomycin Streptomyces fradiae Broad spectrum Protein synthesis Streptomycin Streptomyces griseus Gram-negative bacteria Protein synthesis Tetracycline Streptomyces rimosus Broad spectrum Protein synthesis Vancomycin Gentamicin Rifamycin Streptomyces orientalis Micromonospora purpurea Streptomyces Gram-positive bacteria Broad spectrum Wall synthesis Protein synthesis

11 11

12 Susceptibility of microorganisms to antimicrobial agents Successful antimicrobial therapy of an infection ultimately depends on the concentration of antibiotic at the site of infection. 12 This concentration must be sufficient to inhibit growth of the offending microorganism. If host defences are intact and active, a minimum inhibitory effect, such as that provided by bacteriostatic agents may be sufficient. If host defences are impaired, bactericidal effect may be required to eradicate the infection.

13 13

14 Selective toxicity 14 Depends on there being exploitable biochemical differences between the parasite/microbial cell and the host. This is because only compounds with selective toxicity can be used clinically. In practice, this is expressed in terms of the therapeutic index - the ratio of the toxic dose to the therapeutic dose. The larger the index, the better is its therapeutic value.

15 Nosocomial infections 15 Result from pathogens that develop within a hospital or other type of clinical care facility and are acquired by patients while they are in the facility. Most nosocomial infections become clinically apparent while patients are still hospitalized However, disease onset can occur after patients have been discharged. Infections that are incubating when patients are admitted to a hospital are not nosocomial; they are community acquired.

16 Super infection (Supra-infection) 16 Is usually attributed to the suppression of antibiotic-sensitive microorganisms which normally provide natural competition to prevent the unlimited multiplication of antibiotic-resistant microorganisms. The administration of broad spectrum antibiotics, especially by mouth, may result in supra-infection with Candida and other yeasts, filamentous fungi And resistant Gram-negative bacteria, affecting the mouth, gastro-intestinal tract, or upper respiratory tract. Co-infection?????

17 Thanks for your attention 17

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