Pharmaceutical Microbiology Lecture 1 PDF

MICROBIOLOGY AND IMMUNOLOGY DEP. Fall 2024 - 2025 Pharmaceutical Microbiology PM 502 Lecture 1 Control of microbial growth  Lecture Outline In vivo microbial growth control Antimicrobial agents Antibacterial - Antiviral – Antifungal -...

MICROBIOLOGY AND IMMUNOLOGY DEP. Fall 2024 - 2025 Pharmaceutical Microbiology PM 502 Lecture 1 Control of microbial growth  Lecture Outline In vivo microbial growth control Antimicrobial agents Antibacterial - Antiviral – Antifungal - Anti-tubercular - Antiparasitic – Anthelmintic. Antibiotics Vs Chemotherapeutic agents Classification of antimicrobial agents Source, Spectrum, Function, Chemical structure, Mechanism of action Characteristics of an ideal Antimicrobial agent Factors Affecting the Choice of Antimicrobial Agents  Historical Background Bacterial diseases were a leading cause of death earlier in this century (diphtheria, pneumonia, and tuberculosis) and since 1619, quinine was used for treatment of malaria. Moreover, treatment of sexually transmitted diseases such as syphilis and gonorrhea required long periods and was toxic to patients. e.g. Organic arsenic compounds (Salvarsan, 1909). Red Azo dye (prontosil) was used for streptococcal infections. In 1928, Sir Alexander Fleming discovered the world's first effective antibiotic substance, which he named penicillin. Sulfa drugs were discovered by Domagk in 1935.  Discovery of Penicillin (First beta-lactam drug) Discovered in 1928. While working in his lab, trying to kill a deadly bacteria, he noticed a blue mold growing on the dish. He learned that it was the mold Penicillum Notatum. Penicillin is produced by this mold. Noticed that the bacteria that he inoculated did not grow around the mold.  How it is was Developed ▪ For 9 years, nobody could purify the Penicillum Notatum to get the pure penicillin. ▪ Finally, in 1938, a team of Oxford University Scientists, headed by Howard Florey and Ernst B. Chain helped to develop penicillin and produced benzyl penicillin on industrial scale. What are antibiotics? They are naturally occurring microbial products; which can inhibit or kill microorganisms at a very low concentration. In other words an antibiotic is a substance that produced naturally by one microorganism and can inhibit or destroy other microorganism. (However, some antibiotics are now produced wholly or partly by chemical synthesis). ▪ Microbial Death: In bacteria, death could be defined as the potential inability to multiply and not the lack of active metabolism. (Microbial death is an exponential or logarithmic process as microbial growth).  Antibiotic versus Antimicrobial chemotherapeutic agent The difference in these terms is based upon two things: 1. Their source (natural or synthetic) 2. The type of organism against which it is effective (bacteria, fungi, virus, parasite). Antimicrobial agent is any substance inhibiting the growth of any microorganism (bacteria, fungi, virus, parasite) and its original source may be natural or synthetic. Antibiotic is an antimicrobial agent which was originally produced from microorganism (natural) and can kill or inhibit the growth of other microorganisms. Antimicrobial Chemotherapeutic agent is a synthetic substance (drug) with similar antimicrobial activity to that of an antibiotic. e.g. Sulphonamides - Quinolones and Fluoroquinolones –Imidazoles (Metronidazole). EXAMPLES Penicillin, Chloramphenicol, Aminoglycosides : -Antimicrobial -Antibiotic (from natural source) -Antibacterial (effective against bacteria) Sulphonamides, Quinolones: - Antimicrobial chemotherapeutics - Antibacterial - (but not antibiotics) Metrinidazole: -Antimicrobial chemotherapeutic -Antibacteria -Antiprotozoal Ivermectin: anthelmintic, antibiotic (as its original source is microorganism) but not antibacterial (as not effective against bacteria)  Classification of antimicrobial agents A) According to the microorganisms they act upon: Antibacterial agents (against bacteria: G+, G- &/or special groups). Antifungal or Antimycotic agents (against fungi). Antiviral agents (against viruses). Antimycobacterial or Antituberculous (against mycobacteria). Antiparasitic agents ( Antiprotozoa and Anthelmintics) (against protozoa and helminths=worms) B) According to their source: Natural: antibiotics obtained naturally from microorganisms. Example, penicillin from Penicillium species, streptomycin from Steptomyces species. Semi-synthetic antibiotics: are the products of chemical manipulation of naturally occurring compounds (ex. Methicillin, Aminopenicillins). Synthetic antibiotics: some naturally occuring antibiotics are produced by chemical reactions. ex. Penicillin basic structure is synthesized from the amino acids valine and cysteine. While, pure synthetic antimicrobial agents are sulphonamides, quinolones and imidazoles.  Microbial sources Antibiotic Bacteria (Gram-positive) Sources Bacillus subtilis Bacitracin of some Bacillus polymixa Polymyxin naturally Chromobacteria occurring Chromobacterium violaceum Azetronam antibiotics Actinomycetes Micromonospora purpurea Gentamicin Streptomyces parvulus Actinomycin D Streptomyces erythreus Erythromycin Streptomyces Streptomyces noursei Nystatin Streptomyces mediterranei Rifamycin Streptomyces griseus Streptomycin Streptomyces rimosus Tetracycline Streptomyces orientalis Vancomycin Streptomyces venezuelae Chloramphenicol Fungi Cephalosporium acremonium Cephalosporines Penicillium griseofulvum Griseofluvin Penicillium chrysogenum Penicillin C) According to their spectrum of action: Spectrum: Range of bacteria against which the antibacterial agent is typically active. 1) Narrow spectrum agents (against single or limited groups) For example, isoniazid is active only against Mycobacterium tuberculosis, penicillins only against Gram positive species, while polymyxin is active only against Gram negative species. 2) Extended spectrum agents (Gram-positive and some Gram-negative bacteria). Example: Ampicillin 3) Broad Spectrum agents (affects a wide variety of bacterial species). Example tetracycline, Chloramphenicol, fluoroquinolones, carbapenems, ….) D) Classification according to their function: either bactericidal or bacteriostatic. ▪ Suffixes: Cidal: Kills Static: Fix, Stable (Inhibit) Bactericidal Bacteriostatic Refers to antibiotics that kill bacteria. Refers to antibiotics that inhibit growth of bacteria. Action is irreversible. Action is reversible. Do not work with immune system of the host.( Requires immune system of the host. Not suitable suitable for immunosuppressed patients. for immunosuppressed patients. Examples: Penicillins Examples:Tetracyclines Cephalosporins Chloramphenicol Monobactams Macrolides Carbapenems Sulphonamides Aminoglycosides Trimethoprim Vancomycin Fluoroquinolones Metronidazole  Based on function Bacteriostatic Bactericidal Based on their spectrum of action Narrow Broad-spectrum Spectrum  E) Classification according to their chemical structure: 1. β-lactam antibiotics: 2. Aminoglycosides i) Penicillins 3. Tetracyclines (four cyclic rings) ii) Cephalosporins 4. Macrolides iii) Carbapenems e.g. imipenem, meropenem 5. Glycopeptides (vancomycin, teicoplanin) iv) Monobactams e.g. aztreonam 6. Polypeptides ( polymyxin, bacitracin) v) Clavams e.g. clavulanic acid ( Beta- 7. Rifamycins lactamase inhibitor). 8. Lincomycin and clindamycin vi) Penicillanic acid sulphone e.g. 9. Polyenes ( antifungal) ( Nystatin, amphotericin) tazobactam, sulbactam. 10. Synthetic antimicrobial agents Sulphonamides Quinolones (Nalidixic acid, ciprofloxacin, levofloxacin) Imidazoles (Metronidazole - antibacterial & β-lactam ring antiprotozoal), Mebendazole- antihelmintic), (Clotrimazole, Ketoconazole, Miconazole – antifungal). Oxazolidinone (Linzolid)  III. Classification according to mode of action: I. Inhibitors of Cell wall Synthesis II. Inhibititors of the cell membrane structure or function III. Inhibitors of protein synthesis IV. Inhibitors of Nucleic acid synthesis a-Inhibitors of DNA replication b-Inhibitors of RNA synthesis V. Inhibitors of key metabolic pathways as Folate metabolism (Antimetabolites) a-Inhibition of Pteroic acid sythetase b-Inhibition of dihydrofolate reductase The characteristics of the ideal antimicrobial drug: 1) Selectively toxic: They have the ability to kill or inhibit an invading microorganism without harming the cells of the host. 2) Microbicidal rather than microbiostatic: Bactericidal: Any substance that kills the microbes irreversibly. Bacteriostatic: Any substance that inhibits the growth (proliferation) of microbes. 3) Broad spectrum rather than narrow spectrum. Effects of bactericidal and bacteriostatic Although broad spectrum antimicrobial agents is one of the drugs on the growth of bacteria in vitro. causes of eliciting bacterial resistance. 4) Remains potent long enough to act and is not broken down or excreted prematurely. 5) Doesn’t lead to the development of antimicrobial resistance Antimicrobial resistance is an adaptive response in which microorganisms begin to tolerate an amount of drug that used to be inhibitory. 6) Remains active in tissues and body fluids. 7) Readily delivered to the site of infection. 8) Does not disrupt the host’s health by causing allergies or predisposing the host to other infections. 9) Moderately priced. In short, the perfect drug does not exist, but by balancing drug characteristics against one another, a satisfactory compromise can be achieved.  Factors Affecting the Choice of Antimicrobial Agents The following factors should be considered when prescribing antibiotics ❑ Factors concerning patient and factors concerning the drug. I. The patient: II. The Drug: Age Identify the organism and sensitivity to antimicrobials. Renal and hepatic function Choose a narrow spectrum antimicrobial if possible. Antimicrobial (drug) allergies If female (pregnancy, or taking The dosage and route of administration will depend the contraceptive pill) on the severity of the infection. Patient obedience Plasma levels should be the minimum required to Severity of infection counteract the infection (MIC). The presence of pus or abscesses may inhibit the effectiveness of the drug.