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Chemical

Methods of
Microbial Growth
Control

Factors that affect chemical


agents

Prior cleaning of objects


Organic load
Bioburden
Concentration

Factors that affect chemical


agents

Contact time
Physical nature
Temperature
pH

Factors that affect chemical


agents

Stronger and more effective


antimicrobial chemical agents
are of limited usefulness

Bacterial
Most
Resistant

endospore
Mycobacteria
Cyst of protozoa
Active-stage
protozoa
Gram-negative
bacteria
Fungi
Nonenveloped
viruses
Gram-positive

Most

Level
of
Susceptib
ility

Measures of Effectiveness

Phenol
coefficient

measure of the
bactericidal
activity of a
chemical
compound in
relation to
phenol (carbolic

Measures of Effectiveness

Phenol
coefficient

a coefficient
greater than 1.0
indicates that
the agent is
more effective
than phenol,
and the larger
the ration, the

Measures of Effectiveness

Phenol
coefficient

Example:
Chloramine
S. aureus: 133.0
S. enterica:
100.0
What is the
phenol

Measures of Effectiveness

Use-dilution
test

measures
efficacy of
disinfectants
and antiseptics
against specific
microbes

Measures of Effectiveness

Use-dilution
test

measures
efficacy of
disinfectants
and antiseptics
against specific
microbes:
S. aureus
P. aeruginosa

Measures of Effectiveness
Process:

Use-dilution
test

Researcher dips
several metal
cylinders into
broth cultures of
bacteria and
dries them at

Measures of Effectiveness
Immerse dried cylinder into
disinfectants of different dilutions

Rinse with water after 10 minutes to


remove excess chemicals

48 hours of incubation

Measures of Effectiveness

DiskDiffusion
Method

Used in
teaching
laboratories to
evaluate the
efficacy of
chemical agents

Measures of Effectiveness
Process:

DiskDiffusion
Method

A disk of filter
paper is soaked
with a chemical
and placed on
an agar plate
inoculated with

Measures of Effectiveness

DiskDiffusion
Method

A clear zone
representing
inhibition of
growth can be
seen around the
disk

Measures of Effectiveness

Disk-Diffusion Method

Measures of Effectiveness

In-use
test

realistic but
time-consuming
method for
determining the
efficacy of a
chemical

TYPES OF
DISINFECTANTS

Phenol and Phenolics


Phenolics

compounds derived from


phenol molecules that have
been chemically modified by
the addition of halogens or
organic functional groups

Phenol and Phenolics


Bisphenolics

composed of two covalently


linked phenolics such as
hexacholorophene,
orthophenylphenol and
triclosan

Phenol and Phenolics


Action

intermediate- to low-level
disinfectants that denature
proteins and disrupt cell
membranes

Phenol and Phenolics


Advantage

effective even in the presence


of contaminating organic
material and remain active on
surfaces for a prolonged period

Phenol and Phenolics


Disadvantage

disagreeable odor and possible


side effects

Alcohols
Alcohol

intermediate-level disinfectants
which is effective as
bactericidal, fungicidal, and
virucidal but ineffective against
fungal spores or bacterial
endospores

Alcohols
Action

denature proteins and disrupt


cytoplasmic membranes

Alcohols
Advantage

leaves no residue

Alcohols
Disadvantage

they may not contact microbes


long enough to be effective

Alcohols
Examples of Use

70% to 90%
alcohol

Alcohols
Examples of Use

70% to 90%
alcohol

Swabbing
the skin with
alcohol prior
to an
injection

Halogens
four very reactive, nonmetallic
chemical elements which are
intermediate-level antimicrobial
chemicals

Halogens

Effecti
ve
Agains
t

Vegetative bacterial
cells
Fungal cells
Fungal spores
Bacterial endospores
Protozoan cyst
Many viruses

Halogens

Halogens

Iodine

Chlorin
e

Bromin
e

Fluorin
e

Halogens
Action

exact action is unknown but is


thought to participate in
denaturation

Halogens
Iodine

iodine tablets

Halogens
Medical Use

disinfectant, usually 2-7%


potassium iodide or sodium
iodide, and elemental iodine,
dissolved in a mixture of
ethanol and water (tincture)

Halogens
Medical Use

as an iodophor: an iodinecontaining organic compound


that slowly releases iodine

Halogens
Medical Use

Surgery
Burns
Injections

Halogens
Chlorine

chlorine tablets

Halogens
Chlorine compounds

Calcium hypochlorite
Sodium hypochlorite
Chlorine dioxide
Chloramine

Halogens
Bromine

effective disinfectant in hot


tubs because it evaporates
more slowly than chlorine at
high temperatures
very good alternative to
chlorine

Halogens
Fluorine

antibacterial in drinking water


and toothpaste

Oxidizing agents
high-level disinfectants and
antiseptics that are particularly
effective against anaerobic
microorganisms

Oxidizing agents
Hydrogen
peroxide

Peracetic
acid

Ozone

Surfactants
surface active chemicals that
reduce the surface tension of
solvents thus the solvent
becomes more effective at
dissolving solute molecule

Surfactants
Soap

one end of a soap molecule is


hydrophobic and the other end
is hydrophilic

Heavy metals
low-level bacteriostatic and
fungistatic agents

Heavy metals

Silver nitrate
Silver sulfadiazine
Thimerosal
Copper

Aldehydes
2% solution
glutaraldeh
yde

Formaldehy
de

Gaseous agents
high-level chemical method
that is used to sterilize heatand water-sensitive objects

Gaseous agents

Ethylene
oxide

Propylene
oxide

Betapropiolacto
ne

Characteristics of an ideal
chemical agent
Must kill pathogens within
a reasonable period and in
specified concentration

Characteristics of an ideal
chemical agent
Not toxic to human tissues
and not corrosive and not
destructive to materials

Characteristics of an ideal
chemical agent

Must be soluble to water


and easy to apply

Characteristics of an ideal
chemical agent

Inexpensive and easy to


prepare for use

Characteristics of an ideal
chemical agent

It must be stable

Characteristics of an ideal
chemical agent
It must be fast-acting and
have a broad antimicrobial
spectrum

RECAP
Phenols

Alcohols

Phenolics
Bisphenolics

Halogens

Ethanol
Isopropanolol

Iodine
Chlorine
Bromine
Fluorine

Oxidizing Agents

Surfactants

Heavy Metals

Hydrogen Peroxide
Ozone
Peracetic Acid

Soap

Silver Nitrate
Silver Sulfadiazine
Thimerosal
Copper

Aldehydes

Gaseous Agents

Glutaraldehyde
Formaldehyde

Ethylene Oxide
Propylene Oxide
Beta-propiolactone

Antimicrobial
Agents to
Control Microbial
Growth In Vivo

Definition of Terms
Chemotherapy
use of any chemical to treat any
disease
Chemotherapeutic agent
any drug used to treat any
condition

Definition of Terms
Antimicrobial agent
any drug used to treat infectious
diseases
Antibiotics
substance produced by
microorganisms that is effective
in killing or inhibiting the growth of

All antibiotics are


antimicrobial agents but
not all antimicrobial
agents are antibiotics.

Definition of Terms
Antibiotics
Fungi source
Penicillin
Cephalospori
n
Griseofulvin

Definition of Terms
Bacteria
source

Antibiotics

Gentamicin

Bacitracin

Polymyxin

Erythromycin
Chlorampheni
col
Rifampin

Streptomycin
Neomycin

Historical Notes
Ipecac aided in the
treatment of dysentery
Quinine extract aided in
the treatment of malaria

Historical Notes
Paul Ehrlich
magic bullet
Compound 606 |
Salvarsan|
arsphenamine
used in the treatment of
syphilis
Rosaniline
used to treat of African
trypanosomiasis

Historical Notes
Alexander
Fleming
Scottish
bacteriologist who
accidentally
discovered the

A: Colonies of
Staphylococcus
aureus
B: Area of
antibiotic activity
C: Colony of
Penicillium
notatum

Historical Notes
Sir Howard
Walter Florey &
Ernst Boris Chain
purified penicillin
and demonstrated
its effectiveness in
the treatment of
various bacterial

Historical Notes
Gerhard Domagk
Protonsil was effective against
streptococcal infection in mice
Protonsil

Sulfanilami
de

Historical Notes
Selman Waksman and
colleagues
[isolated streptomycin]
[coined the word antibiotic]

Ideal qualities of an
antimicrobial agent
Kill or
inhibit
growth of
pathogens

Selective
toxicity

Cause no
allergic
reaction to
the host

Stable
when
stored in
solid or
liquid form

Ideal qualities of an
antimicrobial agent
Microbicid
al rather
Not
than
excessive
microbistat
in cost
ic in
Remain
the body
Kill the
long
pathogens
enough to
before
be
mutation

Antibacterial Agents
constitute the greatest number
and diversity of antimicrobial
agents

Antibacterial Agents
Actions

[inhibition of cell wall


synthesis]
[damage to cell membrane]
[inhibition of nucleic acid
synthesis]
[inhibition of protein
synthesis]

Antibacterial Agents
Inhibition of Cell Wall
Synthesis
[considered
to be bactericidal]

[has very little toxic effects to


host cells]
[Penicillin]
[Cephalosporin]
[Bacitracin]
[Vancomycin]

Antibacterial Agents
Inhibition of Enzyme Activity

sulfonamide, a bacteriostatic
and competitive inhibitor,
inhibits production of folic acid
in those bacteria that require
para-aminobenzoic acid
[Trimethoprim]

Antibacterial Agents
Inhibition of Enzyme Activity

PAB
A
Sulfa

Folic
acid
Folic
acid

Antibacterial Agents
Damage to Cell Membrane

[bactericidal]
[bring about changes in the
permeability of plasma
membrane]
[Polymyxin]

Antibacterial Agents
Inhibition of Nucleic Acid
Synthesis
[interfere with
the processes of

DNA replication]
[limited usefulness]
[Rifampin]
[Quinolone (nalidixic acid and
ciprofloxacin)]

Antibacterial Agents
Inhibition of Protein Synthesis

[interferes with the production


of ribosomes]
[Chloramphenicol]
[Erythromycin]
[Streptomycin]
[Tetracycline]

Antibacterial Agents
Spectrum of Activity
range of different microbial types
they affect

Narrowspectrum

Broadspectrum

Vancomycin
Colistin
Nalidixic acid

Ampicillin
Chloramphenicol
Tetracycline

Antibacterial Agents
Multidrug Therapy

the use of two or more drugs


to kill all pathogens
uses the principle of
synergism
Example: DOTS (Direct

R.I.P.E.S.
Rifampicin
Isoniazid
Pyrazinamide
Ethambutol
Streptomycin

General considerations for


antibiotics
Monitor for superinfections
Evaluate renal/liver function
Do not store in medicine cabinet
Inform provider prior to taking
other
meds
Cultures
prior to initial dose
Ask about allergy
Take full course of the drug
Evaluate cultures, WBC,

Antifungal Agents
Actions

[bind with cell membrane


sterol]
[interfere with sterol
synthesis]
[block mitosis or nucleic
acid synthesis]

Antifungal Agents
Bind with cell membrane sterol

[causes cell membrane to be


excessively permeable]
Nystatin and Amphotericin B

Antifungal Agents
Interfere with sterol synthesis

[causes cell membrane to be


excessively permeable]
Clotrimazole and Miconazole

Antifungal Agents
Block mitosis or nucleic acid
synthesis
[interferes
with the

biosynthesis of RNA]
Griseofulvin and 5-flucytosine

Antiprotozoal Agents
Action

[interfering with DNA and RNA


synthesis]
[interfering with protozoal
metabolism]

Antiviral Agents
Action

[inhibit viral replication within


the cell]

Antiviral Agents
Zidovudine (AZT)
[first antiviral effective against
HIV]

DRUG RESISTANCE

Drug Resistance
INTRINSIC RESISTANCE
versus
ACQUIRED RESISTANCE

Drug Resistance
Intrinsic resistance
[naturally resistant to an
antimicrobial agent]

Drug Resistance
Acquired
Resistance

Mutation

Change in drug
binding site

Change in cell
membrane
permeability

Acquisition
(conjugation,
transduction,
transformation)

Enzyme that
destroys or
inactivates drug

Multi-drug
resistance pumps

DRU
G

BACTE
RIA

Change in Drug
Binding Site

DRU
G

BACTERIA

BACTERIA

Change in Cell
Membrane
Permeability

Drug Resistance
Acquired resistance
[Acquisition of genes]
Conjugation: Bacterial sex
Transformation: DNA capture
from solution
Transduction: Case of Piggyback
DNA

Drug Resistance
-Lactamases
[enzymes that destroy -lactam
ring]
Result: Resistance
Solution: Combine antibiotics
with lactamase inhibitor

Drug Resistance

Superbugs
Methicilli
Vancomy
Methicilli
nVancomy
cinnresistant
cinintermedi
resistant
S.
resistant
ate S.
S. aureus epidermi
S. aureus
aureus
(MRSA)
dis
(VRSA)
(VISA)
(MRSE)

Drug Resistance

Superbugs
Vancomycin-resistant
Enterococcus spp. (VRE)
[resistant to most
antienterococcal drugs]
[common cause of nosocomial
UTI]

Drug Resistance

Superbugs
Multidrug-resistant M.
tuberculosis (MRTB)
[patients with this strain may
have a lung or section of the lung
removed]

Drug Resistance

Superbugs
-Lactamase-producing strains of
Streptococcus pneumoniae and
Haemophilus influenzae

Drug Resistance
Empirical Therapy
[therapy initiated by a clinician
before laboratory results are
available]

Undesirable effects of
antimicrobial agents
Resistance
Allergy development
Toxicity
Superinfection

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