Non-Antibiotic Antimicrobial Agents Disinfectants, Antiseptics, Sanitizers and

Preservatives Prepared by :

Microbiology and Immunology Department

1. Definitions of Non-Antibiotic Antimicrobial Agents:

q  Disinfectant: A chemical compound which kill

microorganisms on non-living surfaces.

q  Antiseptic: A chemical compound which inhibit or kill

microorganisms on living surfaces.

q  Sanitizer: A chemical compound which reduce the level of

contamination to normal hygienic levels.

q  Preservative: A chemical compound added to a product to kill

all microorganisms and extend the shelf life time of the

preparation.

Sometimes the same compound is used as antiseptic in low concentration and disinfectant in high concentration.

2. Mode of Action of Non-Antibiotic Antimicrobials:

2.A Interaction with the cell wall: - Low concentrations of formalin, glutaraldehyde, phenol, mercuric chloride, sodium hypochlorite and thiomersal, breaks cell wall of bacteria or inhibits the enzymes of cell wall synthesis especially Gram-positive. -Glutaraldehyde provides irreversible cross linking with the cell wall.

2.B Interaction with the cytoplasmic membrane: a- Membrane permeability: Quaternary ammonium compounds (cetrimide), chlorhexidine, phenol and alcohol, causes a leakage of cell. b- Inhibition of energy processes: 2,4- dinitrophenol, phenoxy ethanol and certain anilides uncouple oxidation from phosphorylation by rendering the membrane permeable to protons inhibiting active transport.

c- Action on membrane enzymes: -­‐Chlorhexidine inhibit both membrane-bound and soluble adenosine triphosphatase (ATPase). -Hexachlorophene inhibits part of the membrane- bound electron transport chain. -Mercury-containing antibacterials inhibit membrane enzymes, which contain thiol (-SH) groups.

2.C Interaction with the cytoplasm: a- Irreversible coagulation of cytoplasmic constituents:

clorhexidine, hexachlorophene, glutaraldehyde, phenols, “Ag” , “Cu” salts. b- Effects on (inactivation of) cytoplasmic enzymes:

-Chorine , hypochlorite and iodine affect the thiole (-SH) groups. -Formaldhye, sulpher dioxide and glutaraldhyde affect amino (-NH2) groups.

c- Effect on nucleic acid: -Acridines affect DNA and RNA polymerases. d-Ribosomes:

- H2O2 and p-chloromercuric benzoate dissociate the 70S ribosome

I- Phenols: - Coal tar preparations:

Black fluid: is a solubilized crude phenol while White fluid is emulsifying phenolic compounds. * Both white and black fluid are used for disinfection of drains and veterinary medicine. Lysol: is a mixture of cresols solubilized with soap. Sudol: devoid of cresols but rich in xylenols and ethyl phenols. - Non-coal tar phenols:

Hexylresorcinol: It is used in glycerol as a skin antiseptic and in lozenges and medicated sweets for the treatment of throat infections. II- Organic and Inorganic Acids: Preservatives in foods and pharmaceutical products. They were also used for topical treatment of fungal infections as Acetic acid, Propionic acid, Sorbic acid, Lactic acid (air disinfectant), benzoic acid, esters of para-hydroxy-benzoic acid (parabins) important pharmaceutical and cosmetic preservative.

III- Alcohols: Bactericidal at high concentration due to protein denaturation, also may disrupt the function and structure of cytoplasmic membrane causing lyses of the bacterial cell. Bacteriostatic action at low concentration due to the interference with cell metabolism.

IV- Heavy metals: - They react with protein and enzyme -SH group and inactivate them. Mercury compounds: They are bacteriostatic or fungistatic. Its activity is enhanced by addition of alcohol. Used as skin antiseptic.

V- Biguanides - Chlorhexidine: at low concentrations, affect membrane enzymes (bacteriostatic). At higher concentrations, coagulate cytoplasmic constituents (bactericidal). - It is used in combination with cetyltrimethyl ammonium bromide as a topical antiseptic (Savlon).

VI- Surface Active Agents: A) Cationic agents: quaternary ammonium compounds QACs e.g. cetrimide, benzalkonium chloride. They are very useful disinfectants but not as detergents B) Anionic agents: e.g. soaps and sodium lauryl sulfate. (detergents but not as disinfectants) C) Non-ionic agents: (Tweens) D) Amphoteric agents: e.g. dodecyl β-alanine. (detergent and bactericidal).

VII-Antimicrobial Dyes: Acridines: - Acridines compete with H+ ions for anionic sites on the bacterial cell also affect DNA. - They are relatively slow in their action and are non sporicidal. Used as local antiseptic for application to wounds and burns, and in selective medium.

VIII- Aldehydes: Used for sterilization 1. Glutaraldehyde: - Used for sterilization of certain types of medical equipment since it is non-corrosive to metals, rubber and lenses. 2. Formaldehyde: - Used as a disinfectant in both liquid and gaseous states. - Formaldehyde is used in the production of certain types of viral vaccines e.g. the inactivated polio vaccines.

IX- Halogens: 1. Chlorine and hypochlorites: Used as skin and surgical antiseptic, wound dressings and disinfection of contaminated drinking water. Disadvantages: Hypochlorites have irritant and bleaching effects to skin and tissues. 2. Iodine and iodophores: Uses: domestic antiseptic. Disadvantages: staining and irritation of skin, However iodophores are washable.

5. Classification of disinfectants

Disinfectants could be classified into 3 levels High level (H) : Bactericide, fungicide, virucide and sporicidal also T.B cidal. Intermediate level (I): Bactericide, fungicide, virucide, T.B. cidal but not sporicidal at practical concentration and time. Low level (L): No effect on T.B. or spores (acts only on vegetative cells and viruses).

Class Activity

Organic matter Antagonized by

QACS L ++++ Soaps and anionic SAA

Chlorhexidine L ++++ Soaps and anionic SAA

Heavy metals L ++++ -SH containing compounds

Phenol L + Cationic SAA

Lysol – Sudol I ++ Cationic SAA

White – black fluid I +++ Cationic SAA

Chlorinated phenol I ++++ Cationic SAA

Alcohols I + -

Glutaraldehyde H - -

Formaldehyde H ++ -

Chlorine compounds H ++++ -

Iodine compounds H ++++ -

6. Hospital Disinfection Policy 1. Critical objects: (must be sterile) -Surgical instruments - Sutures and dressing - Catheters.

- Glutaraldehyde or ethylene oxide could be used. 2. Semicritical objects: (at least disinfected) -Cystoscopes – endoscopes –Bronchoscopes - Thermometers.

- QACs, chlorhexidine + alcohol, lysol or sudol could be used. 3. Non-critical objects: Only need hygienic conditions as they may be a source for nosocomial infections (hospital infections). *Direct contact: nurses, physicians, and visitors.

- Alcohols, QACs, chlorhexidine, or iodophores could be used. * Indirect contact: bed pans, urinals …… etc

- Phenolics, hypochlorites or formalin could be used. * Surfaces: trolleys, basins .... etc.

- Phenolics or hypochlorites could be used. * Food articles: forks, spoons, dishes ... etc.

- Washing with water and soap is sufficient.

7. PRESERVATIVES -Pharmaceutical preparations may be attacked by M.O.s during storage or upon use. It is intended to kill or inhibit any contaminating microorganism.

Microbial contamination of pharmaceuticals results in: 1- Degradation of the active ingredients. 2- Infection to the patient who is already immunocompromized Pharmaceutical preparations, which require a preservative are divided into two groups: 1- Sterile products: - Eye drops and multi-dose parentals. The function of the preservative is to maintain sterility. 2- Non-sterile products : -Preparations intended for oral or external use. The function of a preservative to prevent the growth of microorganisms.

Characteristics of an ideal preservative

1. Compatible with the ingredients of the preparation.

2. Compatible with soaps and detergents.

3. Non-irritant, non-toxic, non-corrosive, non-carcinogenic and of no

offensive odor.

4.  Miscible with water and cheap.

5.  Stable and effective at low concentration.

6. Rapid in action at room temperature in the presence of organic

matter.

7. Have a wide spectrum of activity against microorganisms and spores.

8. Biocidal and active in the presence of large number of microorganisms.

9. Resist the attack of microorganisms.