Test 5

Antimicrobial drug

Drugs that target infectious microbes

Natural antimicrobials

Penicillin

Selective toxicity

The ability to effectively target the bacteria w/o damaging the cells of the host by Exploiting differences in structure and metabolism of microbes and host cells

Narrow spectrum

Targets narrow range of bacteria; pathogen’s identified

* gram positive

Or
* Gram Negative

Only

Broad spectrum

Targets wide variety of bacteria

* mixed infection
* Used to prevent infection after surgery

Superinfection

Secondary infection, protective microbiota are killed allowing for pathogenic one to take over

Superinfection in microbes is usually what

Endogenous - all ready inside body

C-diff

Normally found in body; can proliferate quickly in small amounts causing pseudomembranous colitis

Bactericidal

Anitmicrobial that is lethal to bacteria - cell lysis

Bacteriostatic

Inhibits growth but doe snot kill organism

Are intrinsically less permeable to many antibiotics b/c of outermembrane

Gram negative

What do hydrophilic drugs need to cross the outer membrane

Protein channel

Minimal inhibitory concentration

The lowest concentration that inhibits growth of a microorganism

Minimal bactericidal concentration

Lowest concentration that kills 99.9% of the population

The determined MIC is used to determine what

If a pathogen is susceptible or resistant to a drug

Susceptible

MIC of an organism can be achieved in the body of recommended doses

Resistant

MIC cannot be achieved

Etest

Plastic strip containing an antibiotic. Sone of inhibition is compared to concentration gradient strip

Microdilutions

Varied antibiotics can be done in a 96 well plate.

Kirby-Bauer disk diffusion assay

Swab lawn of bacteria on plates and place antibiotic disks to measure zone of inhibition and compare to standardized table to measure if it’s susceptible or resistant

* Smaller = resistant
* Larger= susceptible

what do antibiotics bind to

Proteins/ enzymes

Protein/enzymes examples to which antibiotics binds to

* transpeptidase
* DNA gyrase
* RNA polymerase
* Plasma membrane
* Ribosomes
* Specific enzymes in metabolic pathways

Tetracyclines

* Occur naturally from streptomyces
* Bind to 30S subunit
* Block tRNA’s association w/ribosome during translation
* Broad spectrum

Semisynthetic tetracyclines

* doxycycline
* Tigecycline

Aminoglycosides

Bind to 30S subunits and interfere with Codons and anticodons causing mismatch. Leads to cell death

Most commonly used aminoglycosides

* amikacin
* Gentamicin
* Tobraycin

**Beta lactam drugs**

* penecillins
* cephalosoporins
* carbapenems
* contain B- Lactam ring is recognized by enzyme blocking synthesis of peptidoglycan

Carbapenems

* last resort drug
* broad specturm
* more resistant to beta lactamase enzymes

penicillin binding proteins

transpeptidase enzyme that when binded to beta lactam it blocks crosslink b/w peptides and glycans.

vancomycin

large molecule that physically blocks new cell wall subunits from being incorporated into peptidoglycan

* works better w/ Gram (+)

protein biosynthesis inhibitor

target 30s or 50 s subunit of ribosome

* tetracyclines
* aminoglycosides
* chloramphenicol

\

macrolides- Erythromycin

* protein biosynthesis inhibitorbinds to 23s ribosomal RNA in 50s subunit blocking movement of tRNA along ribosome.

membrane function inhibitors

* polymyxins
* target outer membrane in gram (-) by interacting with LPS
* disrupts cell membrane
* not selectively toxic

fluroquinolones

* most widely used
* nucleic acid synthesis inhibitor -DNA Gyrase
* broad spectrum

rifampin

blocks transcription by binding to bacterial RNA polymerase

metabolic pathway inhibitors ( antimetabolites)

* competitive inhibitors - block enzyme activity
* sulfonamides
* selectively toxic
* trimethoprim- antibacterial synergy

BSL- 4

Contain highly infectious agents in a sealed lab with protective gear and ventilation. High risk for aersol contamination

BLS 3

microbes can cause lethal diseases thru respiratory transmission.

BSL 2

moderate risk to workers and environment, typically indigenous/ exotic,

BSL 1

don’t really cause disease healthy hosts, minimal risk

disinfection

reduces, destroys microbial load with heat or antimicrobial chemicals.

* chlorine bleach, phenol- lysol

sanitization

reduces microbial load to public safety levels with heat or antimicrobial chemicals

* detergants w/ phosphates, ammonium

sterilization

kill vegetative cells, endospores, and viruses with autoclave, chemicals, radiation

antispepsis

reduces microbial load on skin through applying antimicrobial chemical

* isopropyl alcohol
* iodine

dry heat

denatures protein= death 170 C for 2 hours

moist heat

penetrates cell better, autoclave, boiling, pasteruization

pasteurization

doesn’t sterilize but kills pathogens

boiling

doesn’t sterilize but kills most cells

refrigerating does what

0-7 C, inhibits metabolism to slow down growth

freezing

can stop metabolism and may kill sensitive microbes

desiccation (dehydrating)

effective for preservation because microbes need water for survival.

freeze drying/ lyophilization

rapidly frozen and places in vaccum so water is lost - better for quality of flavor

radiation

targets DNA to to kill/inhibit growth

ionizing

X-rays, gamma rays break backbone of DNA leading to lysis.

* used for sterilization of heat sensitive items.

Non ionizing

UV light can cause thymine diners in DNA which can lead to mutations- kills microbes

* effective for eater purification and food

Sonifications

Use of high frequency ultrasound waves to disrupt cell structures

* good for lysing cells in a lab or cleaning instruments q

Filtrations

Filters of various pore sizes some

* filter air/ liquid sensitive to heat

Phenolics

Inhibit microbial growth by denaturing proteins and disrupting membranes

* Lysol, triclosan ( hand soap)

Heavy metals

Can lead to irreversible inhibition making them effective at denaturing proteins and imparting cell function

Mercury

Used to treat syphilis - in some antiseptics - banned in USA

Silver

In catheters and bandages - use to apply to newborns

Copper, nickel, zinc

Coatings reduce spread of microbes - zinc oxide in topical ointments

Halogens

Disinfectants or antiseptics

* iodine
* Chlorine
* Fluorine

Iodine

Oxidizes biomolecules and destabilizes them

* topical tincture

Iodophor

Compound of iodine complexed with organic molecules such as providing-iodine

Sodium hypochlorite

In bleach, most common chlorine product

* organic materials inactive it

Chloramines

Stable and release chlorine over time, good for biofilm control

Fluorine

Treat dental cavities

Alcohol

Denature proteins, inhibit metabolism , disrupt membrane

* 70 % dilution is better than 100
* Doesn’t kill spores

Ethyl alcohol

60%-80% is Vivi ideal against enveloped viruses

Isopropyl alcohol

Rubbing alcohol, most common

Surfactants

Lower surface tension of water, distrust cel membrane - soap and detergents

Soap

Doesn’t kill or inhibit microbial growth are good at removing dirt - degerming

Detergents

Quaternary ammonium salts (quart), disrupt phospholipid bilayer - house hold cleaners

Bisbiguandides

Synthesized chemical that is used in antiseptics , disrupts cell membranes & is bacteriostatic at lower concentrations and bactericide at higher concentrations.

* chlorhexidine- surgical scrub

Alkylating agents

Can alter nitrogenous bases and incidents mutations

* formaldehyde fixes cadavers
* Glutaraldeyhde- sterilization - surfaces
* Ethylene oxide gaseous sterilization - heat sensitive items-

Peroxygens

Oxidizing agent - produces free radicals that damage biomolecules

* hydrogen peroxide
* Disinfect surfaces- gaseous agent to sterilize
* Skin antiseptic

Food preservatives

Nontoxic and metabolized

* sorbic acid


* Benzoic acid
* Propiocic acid

Sorbic acid

Inhibits various enzymes in metabolic processes

Benzoic acid

Naturally found in some fruits, berries , spices

Sulfanilamides

Synthetic drugs, structural analogous of PABA

* blocks biosynthesis of pyrimidines and purines - bacteriostatic

Trimethoprim

Synthetic drug, used in Combo with sulfa drugs = bactericidial

Eukaryotic microbes

Fungi, Protozoa, helminths - harder to find drugs that target these ( ergosterol - fungi)

Antiviral drugs

Are difficult to make because viruses are so simple and obligate Intracellular pathogens- they have target a step in viral replaiction

* inhibit nuclei acid synthesis
* Reverser transcriptase inhibitors
* Protease inhibitors
* Integrate inhibitor

Resistance mechanisms for antibiotic resistance

1) modified cell wall

2) efflux pump

3) modified drug target

4) hydrolysis by enzyme

Epidemiology

Study of how disease originates and spreads throughout a population

Descriptive epidemiology

Describes pattern of occurrence, focuses on person, place, time ,

Looks at data, helps generate hypothesis

Analytical epidemiology

Used to test hypothesis, Needs control group

* observational studies
* Clinical trials
* Uses results for recommendations for public health measures

Observational studies

Good for helping to determine risks factors or exposures associated with disease

Determinants

Causes/ factors of why who got sick

Case

Who has the disease

Control

Those who don’t have disease

Odds ratio

Odds that diseased ate particular food/

Odds that non diseased ate particular food

* ratio > 1 = higher odds of getting disease

Morbidity

State of being disease

Total morbidity

Number of individuals in a population

Morbidity rate

The # of sick individuals out of population

Prevalence

Proportion with particular Ilene in period of time

Incidence

Proportion of NEW cases in a period of time

Sporadic disease

Diseases seen on occasion en

Endemic disease

Constantly seen - flu