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INFECTION

Flora

Resident flora
always present, usually without altering the clients
health.
Includes bacteria, fungi, protozoa, viruses and
arthropods
large intestine has the highest numbers of
bacteria.
Internal organs and tissues and fluids are microbefree.
benefit host by preventing overgrowth of harmful
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microbes microbial antagonism.

PATHOGENICITY AND VIRULENCE


Pathogensdisease-producing
microorganisms.
Pathogenicityability of microorganism to
produce disease.
Virulence is a quantitative measure of
pathogenicity and is measured by the number of
organisms required to cause disease

Signs and Symptoms


Sign objective evidence of disease as
noted by an observer
fever, septicemia, chest sounds, rash,
leukocytosis, antibodies

Symptom subjective evidence of


disease as sensed by the patient
chills, pain, ache, nausea, itching,
headache. fatigue
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Infectious Disease Classifications


A. Symptomology changes in body function
resulting from infectious diseases.
1. asymptomatic without symptoms.
Detection based on positive blood test
indicating presence of antibodies.
Insidious infection if damaging host tissues
without symptoms, Ex. Pelvic Inflammatory
Disease. Etiology: Chlamydia, or Neisseria
gonorrhea.

2. Subjective symptoms malaise, a general


feeling of discomfort.
3. Objective symptoms observable and
measured conditions. Ex. Rash size and
color, body temperature, and extent of
lymphadenopathy (lymph node swelling).

Distribution of pathogen
Infections often described according to distribution within
the body
Localized
Infection limited to small area
Example = boil
Systemic or generalized
Agent has spread or disseminated throughout the body
Example = measles
Toxemia
Toxins circulating in blood
Viremia
Viruses circulating in blood
Septicemia
Acute life-threatening illness causes by infectious agent or its products
circulating in blood

Duration of Symptoms
Acute
Symptoms have rapid
onset and last only short
time

Chronic
Symptoms develop slowly
and persist

Latent
Infection never completely
eliminated
Infection becomes reactive

Infection Process
Six elements must be present for infection to occur:
Infectious agent
Reservoir
Exit
Method of transportation
Entrance
Host

Requirement for an Infectious Dose


(ID)
Minimum number of microbes required
for infection to proceed
Microbes with small IDs have greater
virulence.
Lack of ID will not result in infection.

12

The Chain
of
Infection

Generalized Stages of Infection


1. Entry of Pathogen
Portal of Entry

2. Colonization
Usually at the site of entry

3. Incubation Period
Asymptomatic period
Between the initial contact with the
microbe and the appearance of the first
symptoms

Generalized Stages of Infection


4. Prodromal Symptoms
Initial Symptoms

5. Invasive period
Increasing Severity of Symptoms
Fever
Inflammation and Swelling
Tissue Damage
Infection May Spread to Other Sites

Generalized Stages of Infection


6. Decline of Infection
5. Convalescence

PORTAL OF EXIT
How infectious agent leaves the reservoir:
Sputum.
Semen, vaginal secretions, and urine.
Saliva and feces.
Blood.
Draining wounds.
Tears.

Method of Transmission
Once a microorganism has exited a reservoir there
are many vehicles.
These vehicles are called contaminated, soiled or
stained.

MODES OF TRANSMISSION
Movement of infectious agent from reservoir or
source through portal of exit to portal of entry of
susceptible host:
Contact transmission.
Airborne transmission.
Vehicle transmission.(Water,food)
Vector-borne transmission. (Mechanical, Biological)

Flies defecate, vomit, feed

Zoonoses
diseases transmitted directly from animals to humans, or indirectly
from animals by insect vectors. ex. Malaria and Yellow Fever have
a monkey reservoir. Wild and domestic animals are carriers for
many human infectious diseases. Zoonoses include diseases
transmitted by feathers, hides, or furs to humans.

PORTAL OF ENTRY
How an infectious agent enters the host:
Integumentary system.
Respiratory tract.
Genitourinary tract.
Gastrointestinal tract.
Circulatory system.
Transplacental.

Entrance of Microorganisms
Once an organism has exited one host and been transmitted,
it must find a way to enter a susceptible host.
When a hosts defense mechanisms are reduced, there is a
greater chance of the organism to enter.

FACTORS AFFECTING SUSCEPTIBILITY


TO INFECTION

Age
Concurrent diseases
Stress
Immunization/vaccination status
Lifestyle and occupation
Nutritional status
Heredity

The Process of Infection and Disease


4 distinct stages of clinical infections:
incubation period - time from initial contact with the
infectious agent to the appearance of first symptoms;
agent is multiplying but damage is insufficient to cause
symptoms; several hours to several years
prodromal stage vague feelings of discomfort;
nonspecific complaints
period of invasion multiplies at high levels,
becomes well established; more specific signs and
symptoms
convalescent period as person begins to respond to
the infection, symptoms decline
25

Infectious Disease Stages


1.
2.
3.
4.

Incubation Period no symptoms


Prodromal period subjective symptoms
Period of Invasion objective symptoms
Convalescence decrease to subjective or
no symptoms.

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Attaching to the Host


Adhesion microbes gain a stable
foothold at the portal of entry;
dependent on binding between specific
molecules on host and pathogen
fimbrae
flagella
adhesive slimes or capsules
cilia
suckers
hooks
barbs

28

SEVEN MECHANISMS OF
PATHOGENESIS
1. Maintain a reservoir in humans
(carriers), animals (zooneses), water,
soil, dust etc.
2. Adherance hooks, spikes, tacky chems
3. Anti-phagocytic properties: capsule,
Wax D, M-protein in Streptococcus
pyogenes, and antigenic drift in
Influenza (virus), Neisseria (bacteria),
and Trypanosomes (protozoan).

4. EXOENZYMES secreted by pathogens


a. Hemolysin lysis of erythrocytes (RBC)
b. Leukocidin degrades lysosomes, the digestive
vacuole found in phagocytes. Staph. aureus.
c. Coagulase clots blood Staph aureus.
d. Streptokinase dissolves clots ex. Strep. and
Staph.
e. Hyaluronidase hydrolyzes the glue that holds
cells together, I.e. the dermis to the epidermis.
Leaves tissues black. ex. Clostridium perfringens
causes gas gangrene.

f. Collagenase degrades collagen, Strep.


pyogenes (necrotizing faciitis)
g. Urease ex. Helicobacter pylori survives at
low stomach pH. Causes ulcers.
h. Neisseria gonorrhea degrades imunoglobulin
(IgA) found in mucous rendering its antibody
activity to be lost.

5. SIDEROPHORES
Most pathogens obtain iron from the host by
secreting these low molecular weight proteins
into the blood which strip iron from
transferrin, a glycoprotein in the blood.

Exotoxins Endotoxins

Secreted to attack
specific targets
Toxic in small
amounts
Polypeptide
composition
Unstable at 60 C
Convert to toxoid
Stimulate antitoxins
No fever

Found in cell wall of gram bacteria


Released on cell lysis
Toxic in high doses
Lipopolysaccharide composition
Stable at 60 C
Do not convert to toxoid
Do not stimulate antitoxins
Fever

Body Defenses Overview


1st line of defense (physical, chemical and genetic
barriers)
2nd line of defense (Inflammation, Interferons,
Phagocytosis) (linked to 3rd)
3rd line of defense (Immune response)

NONSPECIFIC IMMUNE DEFENSE


Protects host from all microorganisms;
does not depend on prior exposure to antigen:
Skin and normal flora.
Mucous membranes.
Coughing, sneezing, and tearing reflexes.
Elimination and acidic environment.
Inflammation.

SPECIFIC IMMUNE DEFENSE


Response specific to an invading antigen.
Acquired immunityprotects individual
against future invasions of already
experienced antigens.
Vaccinationan inoculation with a vaccine
to produce immunity against specific
diseases.

Mechanisms of Viral Pathogenesis


Binding to host cells and invasion
All viruses have surface proteins to interact with specific
host cell receptors
Once attached, viruses are taken up through receptor
mediated endocytosis or membrane fusion
Membrane fusion occurs in enveloped viruses

Viruses released from infected cell may infect new cell


or disseminate into bloodstream

Mechanisms of Viral Pathogenesis

Avoiding immune responses

Avoiding antiviral effects of interferon


Interferons alter regulatory responses of cell in event of viral
infection
Helps limit viral replication
Some viruses encode specific proteins to interrupt inhibition of viral
replication

Regulation of host cell death by viruses


Kill host after production of large numbers of viral copies
Allows spread to other cells

Viruses prevent apoptosis


Inhibits protein that regulates apoptosis

Block antigen presentation of MHC class I


No sign of infection

Cause production of counterfit MHC class I molecules


All appears well

Mechanisms of Viral Pathogenesis


Avoiding immune responses
Antibodies and viruses
Antibodies interact with extracellular viruses only
To avoid antibody exposure some viruses develop mechanisms to directly
transfer from one cell to immediate neighbor

Viruses can remain intracellular by forcing neighboring cells to


fuse in the formation of syncytium
Viruses can modify viral surface antigens
Viruses replicate and change faster than the human body can replicate
antibody

Mechanisms of Viral Pathogenesis

What is Sterilization?
Sterilization (in Microbiology) :
1. To completely remove all kinds of microbes (bacteria,
mycobacteria, viruses, & fungi) by physical or chemical
methods.
2. Effective to kill bacterium spores
3. Sterilant: material or method used to remove or kill all
microbes

Methods of sterilization (I)

Methods of sterilization (II)

Pros & Cons of Sterilants


1. Steam (Moist) & Dry Heat => the most common methods for most materials.
Cons: NO good for heat-senstive, toxic or volatile chemicals
2. Filtration => remove bacteria and fungi from air or solutions
eg: HEPA (High-Efficiency Particular Air) filters
Cons: unable to remove viruses and some small bacteria (microplasma)
3. Ethylene oxide => the most common gas vapor sterilant
Cons: (1) flammable & explosive (2) potential carcinogenic
4. Formaldehyde gas => carcinogenic

Pros & Cons of Sterilants


1. Plasma gas => Hydrogen peroxide

Reactive free radicals


Microwave - or radio-freq energy

=> No Toxic byproducts


=> may replace many applications for ethylene oxide
Cons: NOT good for materials absorbing or reacting with
H2O2
2. Peracetic acid => an oxidizing agent w/ good activity
=> end products nontoxic
3. Glutaraldehyde => Not safe

What is Disinfection?
Disinfection (in Microbiology) :
1. To kill most of microbial forms except some resistant organisms or
bacterium spores
2. Categorizing: High-level sterilization
Intermediate-level
Low level

Not effective for


all bacteria
or spores

3. Disinfectant: a substance or method used to kill microbes on


surfaces

High-level disinfectants
Used for items involved in invasive procedures but NOT withstand
sterilization, e.g. Endoscopes, Surgical instruments

Intermediate-level disinfectants
Used for cleaning surface or instruments without bacterial
spores and highly resilient organism, eg. Laryngoscopes,
Anesthesia breathing circuitsetc

Low-level disinfectants
Used to treat noncritical instruments and devices, not
penetrating into mucosa surfaces or sterile tissues

Considerations of Disinfection
Effectiveness of disinfectants is influenced by
1. Nature of the item to be disinfected
2. Number and resilience of the contaminants
3. Amount of organic material present
4. Type and concentration of disinfectant
5. Duration and temperature of exposure

Antisepsis & Antiseptic agents


1. Use of chemical agents on skin or living tissues to inhibit
or eliminate microbes
2. Antiseptic agents are selected for their safety & efficacy

Physical methods

(moist heat, dry heat, filtration, radiation)


Moist heat
Boiling: boiling for 10 min => Kill most vegetative forms of bacteria
Longer time => Kill spores
Addition of 2% Na2CO3 or 0.1% NaOH => enhance
destruction of spores and prevent rusting of the metal wares.
Low temperature disinfection (Pasteurization): 62-65 oC for 30 min.
or 71.5 oC for 15 sec. This is mainly used for disinfection of milk.
Autoclave: 121-132 oC for 15 min or longer => Kill both the
vegetative
and spore forms of the bacteria.
=> Use Bacillius stearothermophilus spores to monitor the
effectiveness of Autoclave

Back

B. stearothermophilus spores

Dry heat
Dry oven: 160 oC for 2 hrs or 171 oC for 1 hr. (B. subtilis)
Flaming; incineration

Radiation
UV-light: UV-radiation causes
damage to DNA.
Ionizing radiation: less applicable.

Filtration
The pore size for filtering bacteria,
yeasts, and fungi is in the range of
0.22-0.45 mm (filtration membranes
are most popular for this purpose).
HEPA filters

Antibacterial agents
1. A useful chemotherapeutic agent should have in vivo
effectiveness and selective toxicity.
2. Modes of action of the chemotherapeutic agents
Inhibition of:
cell wall synthesis
protein synthesis
nucleic acid synthesis
(cell membrane function)

Sites of Action of Antibacterial


Chemical Agents

Disruption
of cell wall

Sites of antibiotic
activity

Penicillins
Produced by Penicillium chrysogenum
Modifications:
decrease acid lability;
increase absorption;
resistant to penicillinase;
broader spectrum (e.g., ampicillin).
-lactamase inhibitors: bind -lactamases irreversibly;
combined use with some penicillins to increase
effectiveness.
Modifications of cephalosporins were to expand their
spectra or increase their stability to -lactamases.

Vancomycin
A complex glycopeptide produced by Streptomyces orientalis
Interacts with D-ala-D-ala termini of the pentapeptide side chains
Inactive for gram-negative bacteria
Some enterococci have acquired resistance to vancomycin
The resistance genes are carried on plasmids

Polymyxins
1. Cyclic polypeptides (from Bacillus polymyxa)
2. Insert into bacteria outer membrane by interacting with LPS and
phospholipids increase cell permeability bacterial cell death
3. Most Active for gram-negative bacteria, because Gram-pos bacteria
have no outer member
4. Nephrotoxic
5. External treatment of localized infection and oral administration to
sterilize the gut

Drug resistance of the microbes


Mechanisms
1. Producing enzymes that degrade or modify the active drugs;
2. Decreasing drug entry;
3. Increasing drug efflux;
4. Increasing the amount of target enzyme;
5. Decreasing affinity of target for drug;
6. Developing an altered metabolic pathway that bypass the
reaction inhibited by the drug.

Dangers of indiscriminate use of antibiotics


1. Development of drug resistance.
2. Superinfection" resulting from changes in the normal flora of the
body.
3. Masking serious infection without eradicating it.
4. Drug toxicity.
5. Widespread sensitization of the population with resulting
hypersensitivity, anaphylaxis, rashes, fever, blood disorders,
cholestatic hepatitis, and perhaps collagen-vascular diseases.

Genetic origin of drug resistance

Chromosomal
Extrachromosomal
(e.g., R plasmids)
Can be transferred
by conjugation,
transformation, and
transduction.

A general rule in antimicrobial therapy


give a sufficiently large amount of an effective
drug as early as possible and continue treatment
long enough to ensure eradication of infection,
but give an antimicrobial drug only when it is
indicated by rational choice.

Disinfection and Sterilization of


Patient-Care Equipment

Recommendations

Cleaning
All objects to be disinfected or sterilized should first be
thoroughly cleaned to remove all organic matter (blood
and tissue) and other residue.
Indications for Sterilization and High-Level
Disinfection
Critical medical devices or patient-care equipment
that enter normally sterile tissue or the vascular
system or through which blood flows should be
subjected to a sterilization procedure before each
use.
Laparoscopes, arthroscopes, and other scopes that
enter normally sterile tissue should be subjected to a
sterilization procedure before each use; if this is not
feasible, they should receive at least high-level
disinfection.

Treatment of Infection
Pathogen

Drug and Mechanism of Action

Bacterial

Antibacterial, antibiotic- attacks the


cell wall, membrane permeability,
or cellular protein synthesis

Virus

Antiviral- decrease reproduction


but can not destroy virus

Fungi

Antifungal interfere with cell


division or cell membrane
permeability

Breaking the Chain of Infection


Universal Precautions
All bodily fluids, blood and wastes are considered
infected
Gloves and appropriate protective apparel are then
used to reduce the transmission of organisms in either
direction, that is, from patient to caregiver and from
caregiver to patient

Breaking the Chain of Infection

Reservoir and sources of infection need to be located and removed


Refrain from traveling when actively infected
Monitor through lab testing for persistent signs of infection
Minimize potential for infection through correct cough/sneeze technique (sleeve,
covering nose/mouth)
Use protection when mode of transmission is known (e.g., condoms, PPE)
Perform frequent hand washing
Disinfect and dispose of equipment/supplies using techniques to minimize
spread of disease
Maintain immunizations and ensure booster to maintain adequate host
resistance

Breaking the Chain of Infection


Sterilization
Use of heat or burning to destroy microorganisms

Disinfectants
chemical solutions that are known to destroy microorganisms or their
toxins on inanimate objects.

Antiseptics
chemicals applied to the skin that do not usually cause tissue
damage, such as isopropyl alcohol-70%; generally affects organisms
on the surface

Breaking the Chain of Infection

Dr. Earle Spaulding


You

can clean without


disinfecting, but you cannot
disinfect without cleaning

75

Basic elements

Cleaning
Disinfecting
Packaging
Sterilizing
Storage

76

Cleaning

Remove all visible soil


Decrease the bioburden
Increase workers safety
Do early in process to avoid dried on materials.
Safe compounds
NOT intended to disinfect or sterilize

77

How to
Mechanical process
Friction
Detergent
Make fats soluble or isolate

Carrier (water)
Detailed
Use standard process
Monitor activity
Use only the very best products
78

Essential components
Surfactant decreases surface tension permitting
water and detergent to disperse throughout area.
Precipitants condense metallic ions to prevent
them from effecting process.
Chemical buffers maintain the pH of the
cleaning solution to maximize the effect of the
detergent.

79

Other cleaning agents


Enzymes dissolve protein (organic matter)
Lipase (fat)
Protease (protein)
Amylase (starch)

80

TYPES OF MATERIALS CLEANED

A. Aluminum
low alkaline detergent.
manually cleaning use a motion in the direction of the grain, rather than a circular
motion against the grain.

B. Glassware
washed with low alkaline detergent.
Rinse with large amounts of water.
final rinse, use distilled water, or demineralized water.

C. Rubber goods
should be scrubbed thoroughly with soft fiber brush
detergent should be low alkaline.
Thorough rinsing is essential, and followed by air-drying.

D. Stainless steel is to be washed, rinsed, and dried as soon as possible,


using a low alkaline detergent
81

Disinfecting
A process that eliminates living pathogenic
microorganisms on inanimate objects
Does not work on most virus
Does not work on most spores
Does not work on prion?
May have other limits (high level vs. low level)

82

Characteristics of a disinfectant

Broad kill spectrum


Not affected by environment (pH)
Not toxic
Mix with available water (hardness)
Stable (evaporation)
Wont harm target surfaces (metal, fabric)

83

Important disinfecting thoughts

Proper dilution more is not better!


Employee safety
Environmental safety
Exposure limits (Permissible exposure level)
Compatibility (gloves, basins, other products)
[chlorine and ammonia]

84

Different types (US)


Phenolic gold standard
Smells like a hospital
Toxicity
Wont kill spores

Quaternary ammonium
Specific pathogen approvals (read the label!)
Affected by water hardness
Affected by bioburden
85

Halogens
Iodine (Iodophore)
Good killer usable in food preparation
Inactivated by organic materials (blood)
Stains

Chlorine
Good killer usable in food preparation
Inactivated by organic materials (blood)
Corrosive
Bleach!
86

Other products
Chloramine-T
Retains more chlorine
More bactericidal

Alcohol
Not sporicidal
Flammable
Incompatible with many items

87

Other products
Aldehydes
Gluteraldehyde

Good product, sporicidal; tuberculocidal; viricidal


Characteristic unpleasant odor
Environmental issues
Toxicity
Exposure levels
Clean-up requirements

88

Newer products
Hydrogen peroxide
Oxidizer (may harm some instruments)
Reverts to hydrogen and oxygen (safe?)

Peracetic acid
Rapid action but smells bad (vinegar)
Works in presence of organic materials

89

Sterilization

Steam
Dry Heat
Ethylene Oxide
Gluteraldehyde
Peracetic Acid
Plasma Gas (vapourized hydrogen peroxide)

90

The Action of Antimicrobial Drugs

Figure 20.2

The Inhibition of Protein Synthesis by Antibiotics

Figure 20.4

Inhibitors of Cell Wall Synthesis

Penicillin
Natural penicillins
Semisynthetic penicillins
Extended-spectrum penicillins

Inhibitors of Cell Wall Synthesis


Cephalosporins
First-generation: Narrow spectrum, gram-positive
Second-generation: Extended spectrum includes
gram-negative
Third-generation: Includes pseudomonads;
injected
Fourth-generation: Oral

Inhibitors of Cell Wall Synthesis


Polypeptide antibiotics
Bacitracin
Topical application
Against gram-positives

Vancomycin
Glycopeptide
Important "last line" against antibiotic-resistant
S. aureus

Inhibitors of Cell Wall Synthesis


Antimycobacterial antibiotics
Isoniazid (INH)
Inhibits mycolic acid synthesis

Ethambutol
Inhibits incorporation of mycolic acid

Inhibitors of Protein Synthesis


Chloramphenicol
Broad spectrum
Binds 50S subunit; inhibits peptide bond formation

Figure 20.10

Inhibitors of Protein Synthesis


Aminoglycosides
Streptomycin, neomycin, gentamycin
Broad spectrum
Changes shape of 30S subunit

Inhibitors of Protein Synthesis


Tetracyclines
Broad spectrum
Interferes with tRNA attachment

Figure 20.11

Inhibitors of Protein Synthesis


Streptogramins
Gram-positives
Binds 50S subunit; inhibits translation

Inhibitors of Protein Synthesis


Macrolides
Gram-positives
Binds 50S; prevents translocation

Figure 20.12

Inhibitors of Protein Synthesis


Oxazolidinones
Linezolid
Gram-positives
Binds 50S subunit; prevents formation of 70S ribosome

Injury to the Plasma Membrane


Polymyxin B
Topical
Combined with bacitracin and neomycin in
over-the-counter preparation

Inhibitors of Nucleic Acid Synthesis


Rifamycin
Inhibits RNA synthesis
Antituberculosis

Quinolones and fluoroquinolones


Nalidixic acid: Urinary infections
Ciprofloxacin
Inhibits DNA gyrase
Urinary tract infections

Competitive Inhibitors
Sulfonamides (sulfa drugs)
Inhibit folic acid synthesis
Broad spectrum

Figure 5.7b

Figure 20.13

Antifungal Drugs
Inhibition of ergosterol synthesis
Polyenes
Amphotericin B

Figure 20.14

Antifungal Drugs
Inhibition of cell wall synthesis
Echinocandins
Inhibit synthesis of -glucan
Cancidas is used against Candida and
Pneumocystis

Antifungal Drugs
Azoles
Miconazole
Triazoles

Allylamines
For azole-resistant
infections

Figure 20.15

Inhibition of Nucleic Acids


Flucytocine
Cytosine analog interferes with RNA synthesis

Pentamidine isethionate
Anti-Pneumocystis; may bind DNA

Other Antifungal Drugs


Griseofulvin
Inhibits microtubule formation
Superficial dermatophytes

Tolnaftate
Action unknown

Antiviral Drugs
Nucleoside and nucleotide analogs

Figure 20.16a

Antiviral Drugs
Protease inhibitors
Indinavir: HIV

Integrase inhibitors
HIV

Inhibit attachment
Zanamivir: Influenza
Block CCR5: HIV

Inhibit uncoating
Amantadine: Influenza

Enzyme Inhibitors
Fusion inhibitors
Enfuvirtide: HIV

Inhibit attachment
Zanamivir: Influenza

Inhibit uncoating
Amantadine: Influenza

Interferons
Prevent spread of viruses to new cells
Alpha interferon: Viral hepatitis

Imiquimod
Promotes interferon production

Antiprotozoan Drugs
Chloroquine
Inhibits DNA synthesis
Malaria

Diiodohydroxyquin
Unknown mode of action
Amoebic diseases

Antiprotozoan Drugs
Metronidazole
Damages DNA
Entamoeba, Trichomonas

Nitazoxanide
Interferes with metabolism of anaerobes

Antihelminthic Drugs
Niclosamide
Prevents ATP generation
Tapeworms

Praziquantel
Alters membrane
permeability
Flatworms

Figure 12.26

Antihelminthic Drugs
Mebendazole
Inhibits nutrient
absorption
Intestinal roundworms

Ivermectin
Paralyzes worm
Intestinal roundworms

Figure 12.28a

Resistance to Antibiotics

Figure 20.20

Antibiotic Resistance
A variety of mutations can lead to antibiotic
resistance
Mechanisms of antibiotic resistance
1.
2.
3.
4.

Enzymatic destruction of drug


Prevention of penetration of drug
Alteration of drug's target site
Rapid ejection of the drug

Resistance genes are often on plasmids or


transposons that can be transferred between
bacteria

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