Antibiotics By: Noor Hisham Al-Atraqchi M.Sc. pharmacognosy

Definition Antibiotics are chemical substances produced by a microorganism, that has the capacity, in low concentration, to inhibit or kill, selectively, other microorganisms. The term antibiotic is now used to include anti-infective produced from synthetic or semi synthetic compounds. The term antibiotic may be used interchangeably with term antibacterial . However, it is incorrect to use the term antibiotic when referring to antiviral, antifungal and antiprotozoal agents.

History of Antibiotics The first antibiotic to be discovered was penicillin, a natural product of Penicillinum mold . Alexander Fleming 1928 observed inhibition of Staphylococci on an ager plate contaminated by a Penicillinum mold , there was a halo of inhibited bacterial growth around the mold. Fleming concluded that the mold was releasing a substance that was suppressing the growth & lysing the bacteria. The antibiotic substance, named penicillin, was not purified until the 1940s (by Florey and Chain), just in time to be used at the end of the second world war.

Penicilium notatum

Criteria that determine the effectiveness of antimicrobial agents Selective destruction of the microorganism. Antimicrobial substances should have a specific action against molecules or enzymes or metabolism of the microorganism only. No or rare side effects on the host

Natural sources of antibiotics Most antibiotics in clinical use are of bacterial or fungal origin. Among the bacteria, the genus Streptomyces is the largest source of antibiotics, they produce antibiotics like streptomycin, chloramphenicol, chlortetracycline , erythromycin and neomycin Cyanobacteria: mostly produce toxins that kill higher organisms. Fungi: e.g: penicillin produced by the genera “penicillium notatum and P. chrysogenum . Cyanobacteria

Sources of antibiotics

How the microorganisms produce antibiotics ?

Primary metabolism is the metabolism of energy production for the cell, the primary metabolites are produced during active growth ,e.g: alcohol, lactic acid Secondary metabolism regards the production of metabolites that are not used in energy production .The metabolite is being utilized as a defense mechanism against other microorganisms in the environment.

Natural antibiotics made by microbes as products of their secondary metabolic pathways . Secondary metabolites are not essential for growth and reproduction. The pathways for synthesis of antibiotics are turned off during growth phase (lag phase) when there is abundance of nutrients . Secondary metabolites are produced in stationary phase, they are only produced in times of stress when resources are low and the organism must produce these compounds to kill off its competitors to allow it to survive, e.g: penicillin, streptomycin. These information are important for the industrial preparation of antibiotics from the natural sources.

Non microbial sources of antibiotics Lichens: Many of these appear to owe their bacteriostatic and antifungal properties to usnic acid or vulpinic acid. Order Coniferae. Various essential oils from Pinus spp. Marine organisms Plants/insects Monocotyledons,e.g: Fresh garlic owes its antibiotic action to alliine. A sulphur-containing amino acid; ginger has antibacterial properties aloe vera gel.

Non microbial sources of antibiotics Dicotyledons. examples o f this group are: the sesquiterpen ketones of hops (humulene and lupulene) Mastic gum is effective in the treatment of gastric ulcers and has been shown to be active in low doses against Helicobactor pylori . Cinnamon extracts have been shown to inhibit the growth and urease activity of the same organisim. (Helicobactor pylori).

Types of Antibiotics according to the source Natural antibiotic agents: metabolic products produced by microorganisms ,e.g: Penicillium notatum-penicillin Streptomyces spp.-streptomycin Semi-synthetic antibiotic agents: chemically modified natural agents (large group of modern antibiotics). Synthetic antibiotic agents: chemically related to the natural antibiotics but completely industrially manufactured.

Classification of antibiotics Based on chemical structure : Beta lactam antibiotics - penicillins, cephalosporins Aminoglycosides: streptomycin, gentamycin, amikacin. Macrolides : erythromycin, azithromycin Tetracyclines - oxytetracycline, doxycycline Sulfonamides : Sulfadiazine, paraaminosalicylic acid (PAS) Quinolones: Norfloxacin, Ciprofloxacin Diaminopyrimidines: Trimethoprim, Pyrimethamine Nitrobenzene : chloramphenicol.

Classification of antibiotics Antibiotics can be classified according to their Spectrum of activity: Narrow-spectrum antibiotics: chemotherapeutic agents acting only on a single or a limited group of microorganisms, For example, penicillin G is active against gram positive bacteria. Broad-spectrum antibiotics: drugs that affect a wide variety of microbial species and are referred to as broad-spectrum antibiotics, such as tetracycline which is active against gram negative and gram positive bacteria.

Classification of antibiotics Antibiotics can be classified according to their mechanism of action :

bacteriostatic vs bacteriocidal Bacteriostatic antibiotics: arrest the growth and replication of bacteria, thus limiting the spread of infection until the immune system attacks, immobilizes, and eliminates the pathogen. Bactericidal antibiotics : kill bacteria at drug serum levels achievable in the patient. Because of their more aggressive antibiotic action, bactericidal agents are often the drugs of choice in seriously ill and immunocompromised patients.

Complications of antibiotics therapy Hypersensitivity: the penicillins, despite their almost absolute selective microbial toxicity, can cause serious hypersensitivity problems, ranging from urticaria (hives) to anaphylactic shock. Direct toxicity :High serum levels of certain antibiotics may cause toxicity by directly affecting cellular processes in the host. For example, aminoglycosides can cause ototoxicity. Superinfections: antibiotic therapy, particularly with broad-spectrum antimicrobials or combinations of agents, can lead to alterations of the normal microbial flora of the upper respiratory, oral, intestinal, and genitourinary tracts, permitting the overgrowth of opportunistic organisms, especially fungi or resistant bacteria.

Resistance to Antibiotic Therapy: The widespread and indiscriminate used of antibiotics together with poor hygiene resulted in that many pathogenic organisms have acquired resistance to specific antibiotic and these strains particularley evident in the hospital environments . Development of resistant strains : Production of enzymes that can destroy antibiotics. Rsistance genes e.g: in plasmids, transferred from one bacterial cell to the other. Modifications of the target.