Micro ch. 10-15

Goals of antibacterial treatment

• disrupt/prevent bacterial infection without affecting the host too much

• kill micro bacteria

Ideal drug

• not toxic to host cell

• relatively soluble

• does not lead to antimicrobial resistance

Three factors needed to be known before therapy

1. identity of microorganism

2. how susceptible is the the microorganism to drugs

3. what is the condition of the person infected?

Methods for testing antimicrobial susceptibility

Disc diffusion test/ Kirby-Bauer, tube dilution test

Disc diffusion/ Kirby-Bauer test

looks at region of bacteria diffusion into media, small discs of antibacterial put onto medium, once incubated the "zone of inhibition" surround the disc is measured and compared with a standard of each drug

Tube dilution test

antimicrobial is diluted serially in tubes of broth and inoculated with a pure culture, once incubated it is examined for growth

Minimum Inhibitory Concentration

the smallest concentration (highest dilution) of a drug that visibly inhibits growth

Therapeutic Index

ratio of the dose of the drug that is toxic to humans compared to its minimum effective dose ------> the smaller the ration the greater for potential toxic drug reactions ------> drug with highest TI has the widest margin of safety

Failure of Antimicrobial treatment due to

1. Delivery of drug (able to reach target site)

2. resistance

3. what if it is polymicrobial?

4. consistent with treatment

Goal of antimicrobial drugs

• Disrupting, inhibit

• interfere

• destroy

• selectively toxic

Broad Spectrum drugs

drugs that target a wide range of microbes

Narrow Spectrum drugs

drugs that target a small range/few microbes

Drug classifications

1. targets cell wall

2. targets protein synthesis

3. targets folic acid synthesis

4. target cytoplasmic or cell membrane

Drugs that target cell wall

penicillin, cephalusporins

Drugs that target protein synthesis

2 types: aminoglycosides, tetracyclines

Aminoglycosides

insert on sites on the 30S subunit and cause the misreading of mRNA, leads to abnormal proteins

Tetracyclines

block the attachment of tRNA on the A acceptor site and stop further protein synthesis

Drugs that target folic acid synthesis

sulfonamides

Sulfonamides

interferes with folate metabolism by blocking ezymes

Drugs that target cell membrane

polymyxins

Polymyxins

interact with membrane phospholipids to break them down

Biofilm treatment strategies

1. interrupting quorum sensing pathways

2. adding DNAse to antibiotic acids penetration through extracellular debris

3. interpreting devices with antibiotics prior to implantation

Some antibiotics cause:

biofilms to form at a higher rate than they normally would

Vaccines prevent

measles, mumps, hepatitus

Virus diseases that need more effective medication s

aids, influenza, common cold

Drug resistance

an adaptive response in which microorganisms begin to tolerate an amount of drug that would normally be inhibited

microbes become resistant to a drug after

1. spontaneous mutations in critical chromosomal genes

2. acquisition of entire new genes or sets of genes via horizontal transfer from another species

Mechanisms of drug resistance

1. targets the drug: production of lactum ring inactivates penicillin

2. alters its target/shape so antibiotic cannot recognize it

3. efflux pumps: pumps drugs out of bacteria

4. change in enzymatic pathway

Probiotics

preparations of live micro-bacterium fed to animals and humans to improve intestinal biota

Prebiotic

nutrients that encourage growth of beneficial microbes of the intestine

Fecal transplant

treats reoccurent clostridiods difficile infection and ulcerative colitis; transfers feces from healthy via colonoscopy

Colonization

resident microbiota

Infection

microbes get past barrier

Disease

deviation from health

Infectious disease

pathogenic state

Contamination

excessive amount of growth

Pathogen

a microbe whose relationship is with its host parasitic and results in infection and disease

Pathogenicity

an organism's potential to cause disease

True pathogens

capable of causing a disease in a healthy organism

Opportunistic pathogens

has potential to cause harm but relies on compromised immune system

Virulence

relatively severity of disease by a particular microbe; degree of pathogenicity

Virulence factor determined by:

1. establish

2. cause

Virulence factor

a microbes structures or capabilities that allow it to establish itself in a host and cause damage

Polymicrobial Infections

majority of infections are polymicrobial with contributions from more than one microbe

Exogenous

microbe introduced from outside

Endogenous

microbe introduced from inside

Steps to becoming established

1. portal of Entry

2. attaching to host cell

3. surviving host defense

4. causing disease

5. Vacating the host- portals of exit

Portal of entry

the route that a microbe takes to enter the tissues of the body to initiate an infection

• pathogens specifically adapted to specific portal of entry but pathogens can enter more than one portal

Infectious dose

the minimum number of microbes necessary to cause an infection to proceed; microorganisms with smaller infectious doses have greater virulence

attaching to the host cell

Adhesion: process by which microbes gain a more stable foothold on host tissues

Causing disease

three ways: directly, indirectly, epigenetic changes

Directly

actin of exoenzymes, toxins

Exoenzymes

enzymes secreted by microbe that break down and inflict damages on tissues; dissolves the hosts defense barriers to promote the spread of disease to the other tissue

Toxins

a specific chemical product of microbes that is poisonous to other organisms

Toxin types

Neurotoxins: act on nervous system Enterotoxins: act on intestine Hemotoxins: lyse red blood cells Nephrotoxins: damage to kidney Endotoxins Exotoxins

Indirectly

inducing the hosts defense (immune response)

Epigenetic changes

environmental changes that changes the way the genes work

Distribution of pathogen

localized infection, systemic infection

Localized infection

microbe limited to small area

Systemic infection

agent spread throughout the body

Causing Disease warning signals

sign symptom syndrome

Sign

objective evidence of disease as noted by an observer

Symptom

subjective evidence of disease as sensed by the patient

Syndrome

a disease identified by a certain complex of signals and symptoms

Portal of exit

specific venue by which pathogens exit; shed through secretion, excretion, discharge, or sloughed tissue

Major portals of exit

coughing, sneezing insect bite skin cells open lesions urine feces removal of blood

Stages of infection and disease

incubation period prodromal stage acute phase convalescent period continuation period

Incubation period

the period from the initial contact with an infectious agent to the appearance of the first symptoms

Prodromal stage

a short period incubation; indicates onset of disease

Acute phase

specific signs and symptoms are seen and pathogen is at peak activity

Convalescent period

phase which either the organism linger after symptoms subside or the symptoms continue after the organism is no longer detectable

Reservoir

primary habitat in the natural world from which a pathogen originates

Transmitter

indiviual or object from which an infection is acquired

Vertical transmission

transmission if ro parent to offspring via the ovum, sperm, or milk

Horizontal transmission

disease is spread through a population from one infected indiviual to another; 3 types

3 types of horizontal transmission

direct transmission indirect transmission vector transmission

Formite

form of indirect transmission from an inanimate object

Vehicle

form of indirect transmission from natural non-living material like air, water, soil, and food

HAI

infectious diseases acquired or developed during a hospital or health car facility stay

Factors tied to HAI

patients collection points lowered defenses acquisition

Successful identification and treatment relies on

1. asceptic

2. sterile

Asceptic

free from contamination caused by harmful bacteria, viruses, and other

Phenotypic methods

observing traits an organism is expressing, examining microbe appearance and behavior, immediate direct examination of the specimen

Phenotypic examination

enzymatic activities physical conditions antibiotics chemical composition

Phenotypic method that does not require cultivation

direct examination

Direct examination

microscopy of patient specimens (after staining)

Phenotypic method that requires cultivation

selective/differential growth biochemical testing susceptibility testing Phage typing

Selective/differential growth

identifies characteristics such as colony, appearance, motility, gas requirements

Biochemical testing

growth detects the prescence of microbes of enzymes, creating metabolic fingerprint

Susceptibility testing

detects a pattern of antimicrobial susceptibility to identify microbe; useful in determining what drugs will be used for treatment, used during pathogen identification

Phage typing

testing bacterial sensitivity to phages by determining its lyse

Phenotypic method drawbacks 1

it has to be cultured

Phenotypic method drawbacks 2

multiple infections

Phenotypic method drawbacks 3

non-culture

Phenotypic method drawbacks 4

easy misidentify: can go undetected

Phenotypic method drawbacks 5

takes longer

Dichotomous key

flowchart leading to identification; combines results of gram staining, growth on differential media, and enzymatic testing

Sensitivity

high, low; the levels you can detect and their variations

Specificity

the ability to target one specific target and that one only

Immunological methods

involves in vitro testing serum, urine, cerebrospinal fluid, whole tissues, and saliva for the presence of specific antibodies