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
Most Resistant
Prions
Bacterial endospore
Mycobacteria
Cyst of protozoa
Active-stage protozoa
Gram-negative bacteria
Fungi Level
Nonenveloped viruses
of
Gram-positive bacteria
Enveloped viruses Susceptibility
Most Susceptible
 Measures of Effectiveness

measure of the
bactericidal activity
Phenol of a chemical
coefficient compound in
relation to phenol
(carbolic acid)
 Measures of Effectiveness

a coefficient greater
than 1.0 indicates
that the agent is
Phenol more effective than
coefficient phenol, and the
larger the ration,
the greater the
effectiveness
 Measures of Effectiveness

Example: Chloramine
S. aureus: 133.0
S. enterica: 100.0
Phenol
coefficient What is the phenol
coefficient of phenol
when used against
Staphylococcus?
 Measures of Effectiveness

measures efficacy of
Use-dilution disinfectants and
test antiseptics against
specific microbes
 Measures of Effectiveness

measures efficacy of
disinfectants and
antiseptics against
Use-dilution specific microbes:
test S. aureus
P. aeruginosa
S. cholerasuis
 Measures of Effectiveness

Process:

Researcher dips
Use-dilution several metal
test cylinders into broth
cultures of bacteria
and dries them at
37OC
 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

Used in teaching
laboratories to
Disk-Diffusion evaluate the efficacy
Method of chemical agents
 Measures of Effectiveness

Process:

A disk of filter paper

Disk-Diffusion is soaked with a
Method chemical and placed
on an agar plate
inoculated with the
test organism
 Measures of Effectiveness

A clear zone
representing
Disk-Diffusion inhibition of growth
Method can be seen around
the disk
Measures of Effectiveness

Disk-Diffusion Method
Measures of Effectiveness

realistic but time-

consuming method
In-use for determining the
test 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

Swabbing the
70% to 90% skin with alcohol
alcohol prior to an
injection
 Halogens

four very reactive, nonmetallic chemical

elements which are intermediate-level
antimicrobial chemicals
 Halogens

Effective Vegetative bacterial cells

Against Fungal cells

Fungal spores
Bacterial endospores
Protozoan cyst
Many viruses
Halogens
 Halogens

Iodine Chlorine

Bromine Fluorine
 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 iodine-containing
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
Ozone
peroxide

Peracetic
acid
 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
Formaldehyde
glutaraldehyde
 Gaseous agents

high-level chemical method that is used

to sterilize heat- and water-sensitive
objects
 Gaseous agents

Ethylene Propylene
oxide oxide

Beta-
propiolactone
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 Halogens
• Phenolics • Ethanol • Iodine
• Bisphenolics • Isopropanolol • Chlorine
• Bromine
• Fluorine

Oxidizing Agents Surfactants Heavy Metals

• Hydrogen Peroxide • Soap • Silver Nitrate
• Ozone • Silver Sulfadiazine
• Peracetic Acid • Thimerosal
• Copper

Aldehydes Gaseous Agents

• Glutaraldehyde • Ethylene Oxide
• Formaldehyde • 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 other microorganism
All antibiotics are antimicrobial
agents but not all antimicrobial
agents are antibiotics.
Definition of Terms

Antibiotics
Fungi source

Penicillin
Cephalosporin
Griseofulvin
 Definition of Terms

Antibiotics
Bacteria source

Gentamicin Bacitracin
Polymyxin Erythromycin
Streptomycin Chloramphenicol
Neomycin Rifampin
 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 first
antibiotic
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 infections
 Historical Notes

Gerhard Domagk

Protonsil was effective against

streptococcal infection in mice

Protonsil Sulfanilamide
 Historical Notes

Selman Waksman and colleagues

[isolated streptomycin]
[coined the word antibiotic]
Ideal qualities of an antimicrobial
agent

Kill or inhibit
Selective
growth of
toxicity
pathogens

Cause no Stable when

allergic stored in
reaction to solid or liquid
the host form
Ideal qualities of an antimicrobial
agent

Microbicidal
Not excessive
rather than
in cost
microbistatic

Remain in the Kill the

body long pathogens
enough to be before
effective 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]
[inhibition of enzyme activity]
 Antibacterial Agents

Inhibition of Cell Wall Synthesis

[considered to be bactericidal]
[has very little toxic effects to host cells]
[Penicillin]
[Cephalosporin]
[Bacitracin]
[Vancomycin]
[Antimycobacterial]
 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

Folic
PABA acid

Folic
Sulfa 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
Narrow-spectrum Broad-spectrum

Vancomycin Ampicillin
Colistin Chloramphenicol
Nalidixic acid Tetracycline
 Antibacterial Agents

Multidrug Therapy
the use of two or more drugs to kill all
pathogens

uses the principle of synergism

Example: DOTS (Direct Observed

Treatment Short-course)
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, temperature
 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

Acquisition
(conjugation,
Mutation
transduction,
transformation)

Change in cell
Change in drug Enzyme that destroys Multi-drug resistance
membrane
binding site or inactivates drug pumps
permeability
 DRUG

DRUG
BACTERIA

Change in Drug
Binding Site
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

ß-Lactamases
[enzymes that destroy ß-lactam ring]
Result: Resistance

Solution: Combine antibiotics with ß-

lactamase inhibitor

Example: Unasyn, Augmentin

 Drug Resistance

Superbugs
Methicillin- Methicillin- Vancomycin- Vancomycin-
resistant S. resistant S. intermediate resistant S.
aureus epidermidis S. aureus aureus
(MRSA) (MRSE) (VISA) (VRSA)
 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
ß-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