Transcript Chemical Means of Microbial Control

Chemical Means of
Microbial Control
Nestor T. Hilvano, M.D., M.P.H.
Learning Objectives
You should be able to:
1.
Compare the types of disinfectant agents.
2.
Explain why 70% to 90% alcohols are more effective than pure alcohols.
3.
Compare and contrast formaldehyde and glutaraldehyde as antimicrobial
agents.
4.
Describe the types of antimicrobials and their use in environmental control
of microorganisms.
5.
List the mechanisms by which antimicrobial drugs affect the growth of
pathogens.
6.
Distinguish between narrow-spectrum and broad-spectrum drugs in terms
of targets and side effects.
7.
Compare and contrast Kirby-Bauer, Etest , MIC, and MBC tests.
8.
Discuss the advantages and disadvantages of the different routes of
administration of antimicrobial drugs.
9.
Identify three main categories of side effects of antimicrobial therapy.
10. List five ways by which microorganisms can be resistant to antimicrobal
drugs
11. Define cross resistance, and distinguish it from multiple resistance.
12. Describe four ways that development of resistance can be retarded
Chemical Method: Introduction
• Generally not intended to achieve sterilization; most
reduce (destroy/inhibit) microbes to safe levels
• An ideal disinfectants (on non-living surfaces) and/or
antiseptics (on skin/mucous membrane) kills microbes in
the shortest possible time
• Important criteria for use: concentration, whether the
agent is bactericidal or bacteriostatic, nature of material
to be treated (organic or not),temperature and pH of
chemical, and time available the agent will be left in
contact w/ the surface tested
• Phenol- first chemical used for disinfection by Joseph
Lister (1860); reference standard; used to disinfect urine,
feces, pus, and burns; skin irritants, corrosive
Disinfectants
1. Phenol and phenolics – denature proteins and
disrupt cell membranes; ex. lysol and triclosan
2. Alcohol – denature proteins and disrupt CM; 70% 90% aqueous solution are bactericidal, fungicidal, and
virucidal against enveloped viruses, but not effective
against endospores; ethanol, isopropanol
3. Halogens – nonmetallic chemical elements (iodine,
bromine, chlorine, and fluorine); disinfectants and
antiseptics to kill microbes in water or on medical
instruments or skin; bromine is more effective in hot
tubs than chlorine because it evaporates more slowly at
high temp.; betadine and isodyne (iodophors)
Exercises:
What chemical substance is most commonly used
disinfectant to kill microbes at the lowest level (near
zero)?
Disinfectants
4. Oxidizing agents – H2O2, ozone, and peracetic acid are
high level disinfectants and antiseptics that release O2
radicals; H2O2 is a poor antiseptic but a good disinfectant,
ozone also used to treat drinking water; benzoyl peroxide
(acne medication), peracetic acid (food industry, kills fungi
in 5 min).
5. Surfactants – surface active chemicals such as soaps and
detergents (quats/quarternary ammonium cpd.) which
disrupt cell membranes; low level disinfectants; cepacol
(mouth wash), zephiran
6. Heavy metals – low level disinfectants that denature
proteins; include arsenic, mercury, silver, copper, and zinc;
superceded by less toxic alternatives; silver still being
used in surgical dressings, burn creams, and catheters
Exercises:
What chemical agent is broken down by enzyme, catalase, into H2O
and O2 gas (causes wound to bubbles & removes microbes)?
Chemical Methods
7. Aldehydes - containing terminal – CHO groups; high
level disinfectants; cross link protein and DNA
- 2% glutaraldehyde solution and 37% aqueous solution of
formaldehyde (formalin) are used to disinfect or sterilize
medical/dental equipments and in embalming fluid.
8. Gaseous agents – used in plastic lab ware, artificial
heart valves, mattresses, and dried foods; ethylene oxide,
propylene oxide, and beta-propiolactone denature proteins
and DNA by cross link without harming inanimate objects;
gases are explosive and potentially carcinogenic
* Formalin hazards- exposure routes by inhalation, ingestion, skin/eye
contact; caused irritation of eyes, nose, throat, respiratory system;
cough, wheezing, discharge of tears, dermatitis
Food Preservatives
• Preserved foods by organic acids to maintain a
low microbial level
• SO2 in wines
• Sodium benzoate (benzoic acid) in cheese and
soft drinks
• Calcium proprionic acid prevents growth of
molds in bread and bakery products
• Nitrates in food (nitrosamines) = carcinogens)
Types of Antimicrobials
• Used to treat diseases
1. Antibiotics – produced naturally by microbes
2. Semisynthetics – chemically modified antibiotics
3. Synthetic – completely synthesized in the
laboratory
• Paul Ehrlich (1854-1915) – prod. arsenic cpds.
Effective against syphilis and trypanosome
parasites
• Alexander Fleming (1881-1955) – dev. earliest
form of penicillin
• Gerhard Domagk (1895-1964) – dev.
sulfanilamide
Mechanisms of Action of Antimicrobials
• Inhibition of C. Wall synthesis – by preventing
cross-linkage of NAM subunits leading to lysis
a)beta-lactams (penicillins and cephalosporins);
beta lactam rings bind to enzymes that cross link
NAM.
b)vancomycin and cycloserine disrupt cell wall
formation by interfering w/ alanine-alanine
bridges that link the NAM
c) INH and Ethambutol block mycolic acid synthesis
in cell walls of Mycobacteria
Considerations in use of antimicrobials
• Spectrum of action
- narrow spectrum (ex. penicillin)
- broad spectrum (ex. tetracycline)
• Efficacy – tests include:
1. diffusion susceptibility (Kirby-Bauer) test – zone
of inhibition
2. minimum inhibitory concentration (MIC) test –
quantify smallest amount of drug that inhibits
pathogen
3. minimum bactericidal concentration (MBC) test
Considerations in use of antimicrobials
• Routes of administration
- topical, oral, IM, or IV
• Safety and side effects:
- toxicity (effects on skull malformation; staining of
tooth enamel, etc.)
- Ex: toxicity of metronidazole, tetracycline
staining
- allergies
- disrupt normal
microbiota
Resistance to Antimicrobials Drugs
• Mutations of chromosomal genes or acquiring
resistance on R-plasmids (extrachomosomal
piece of DNA) via transformation, transduction,
or conjugation
• Mechanisms of resistance
1. producing enzymes (beta-lactamase)
2. inducing changes in cell membrane
3. altering drug’s receptor
4. altering cell’s metabolic pathways
5. pumping drug out of cell
• Multiple resistance – 3 or more drugs
• Cross resistance – drugs similar in structure
4 Ways to retard drug resistance
• Using high concentrations of drug for a
sufficient time
• Use combination of drugs
• Limiting use to necessary cases
• Developing new variations of existing
drugs
Homework
1. Define terms: surfactants, halogens, aldehydes,
antibiotics, cross resistance, multiple resistance,
narrow spectrum, broad spectrum, and toxicity.
2. Describe diffusion susceptibility test (KirbyBauer) of antimicrobials.
3. Explain how can you developed resistance to
penicillin drugs.
4. List the routes of drug administration.
5. Classify the types of chemical agents: lysol,
betadine, cephacol, benzoyl peroxide, formalin,
H2O2,and silver cream.