PROBLEMS ARISING WITH THE USE OF ANTIMICROBIALS

Toxicity A. Local B. Systemic
Hypersensitivity Reactions: It may be in the form of rashes, urticaria, fever, itching, exfoliative dermatitis, angioneurotic edema or rarely anaphylactic shock
Drug resistance: Natural or Acquired
Acquired resistance may be developed by mutation or gene transfer
Mutation is stable and heritable genetic change that occurs spontaneously and randomly among microorganisms

Mutation may be single step or mutistep
Gene transfer: from one organism to other organism occur by
Conjugation
Transduction
Transformation
Resistant organism may be of following types
Drug tolerant means that the organism has altered binding proteins so that an antimicrobial may not reach at the site of action e.g. Methicillin resistant Staphylococcus aureus (MRSA)
Drug destroying means organism is producing some enzyme that inactivate the antibiotic e.g. production of beta lactamases various bacterias
Drug impermeable means that bacteria have altered porin channels through which antibiotic enter into bacterial cell

SOURCES OF ANTIMICROBIALS

Fungi: Pn, Cephalosporin
Bacteria: Polymyxin B, Bacitracin
Actinomycetes: Aminoglycosides, Macrolides

TERMS RELATED TO ANTIMICROBIALS

Broad Spectrum: Agents which are active against more than one group or classes of microbes e.g. Tetracyclines which inhibit both gram positive as well as gram negative bacterias
Narrow Spectrum: Agents which are ative against only one group of microbes e.g. Penicillin G which is active only against gram positive bacteria
Bactericidal: Agents that kill the pathogenic microbes
Bacteriostatic: Agents which only inhibit the pathogenic microbes

MECHANISM OF ACTION

Agents that inhibit synthesis of bacterial cell walls e.g. Penicillins & Cephalosporin
Agents that act directly on the cell membrane of the microorganism, increasing permeability and leading to leakage of intracellular compounds, including detergents such as polymyxin; polyene antifungal agents (e.g., nystatin and amphotericin B) which bind to cell-wall sterols; and the lipopeptide daptomycin
Agents that disrupt function of 30S or 50S ribosomal subunits to reversibly inhibit protein synthesis, which generally are bacteriostatic (e.g., chloramphenicol, the tetracyclines, erythromycin, clindamycin, streptogramins, and linezolid)
Agents that bind to the 30S ribosomal subunit and alter protein synthesis, which generally are bactericidal (e.g., the aminoglycosides)


Agents that affect bacterial nucleic acid metabolism, such as the rifamycins (e.g., rifampin and rifabutin), which inhibit RNA polymerase, and the quinolones, which inhibit topoisomerases
Antimetabolites, including trimethoprim and the sulfonamides, which block essential enzymes of folate metabolism. There are several classes of antiviral agents
nucleic acid analogs, such as acyclovir or ganciclovir, which selectively inhibit viral DNA polymerase, and zidovudine or lamivudine, which inhibit HIV reverse transcriptase
non-nucleoside HIV reverse transcriptase inhibitors, such as nevirapine or efavirenz;
inhibitors of other essential viral enzymes, e.g., inhibitors of HIV protease or influenza neuraminidase;
fusion inhibitors such as enfuvirtide

CHEMICAL CLASSES OF ANTIMICROBIALS

Sulfonamides e.g. Dapsone
Diaminopyrimidines e.g. Trimethoprim
Quinolones e.g. Ciprofloxacin
Beta lactam antibiotic e.g. Penicillins, Cefalosporins
Tetracyclines e.g. Doxycyclines
Nitrobenzene derivative e.g. Chloramphanicol
Aminoglycosides e.g. Gentamycin
Macrolides: Erythromycin
Lincosamide: Clindamycin
Glycopeptide: Vancomycin
Oxazolidinone: Linezolid
Polypeptide : Polymyxin
Nitrofuran: Furazolidone
Nicotinic acid derivative: Isoniazid
Polyene: Nystatin
Azole: Ketoconazole
Others: Rifampin

Ideal Antibiotic

It must be able to reach the part of the human body where the infection is occurring
It should not cause the development of resistant forms of parasites

It should not produce undesirable side effects in the host such as allergic reaction, nerve damage or irritation of the kidneys and gastrointestinal tract


It should be given orally without inactivation by stomach acid, or by injection (parenterally) without binding to the blood proteins

Finally, it should have a high level of solubility in the body fluids and be possible to achieve concentrations in the tissue or blood, which are sufficiently high to inhibit or kill the infectious agent.

Antimicrobial Agents

Antimicrobial agents are among the most commonly used and misused of all drugs.
Antibiotics are antibacterial substances produced by various species of microorganisms (bacteria, fungi, and actinomycetes) that suppress the growth of other microorganisms.
The term Antimicrobial agent (AMA) is used to designate synthetic as well as naturally obtained drugs that attenuate microorganism
Chemotherapy is the treatment of systemic infections with specific drugs that selectively suppress the infecting microorganism without significantly affecting the host
Due to analogy b/w the malignant cell & the pathogenic microbes, T/t of neoplastic diseases with drugs is also called chemotherapy