Exam 2 Flashcards

Antoni Van Leeuwenhoek

Father of Microbiology

Kochs’s Postulates

1. The microorganisms must be found in abundance in all organisms suffering from the disease, but should not be found in healthy organisms

2. The microorgansim must be isolated from a disease organisism and grown in a pure culture

3. The culutured microorganism should cause disease when introduced into a health organism

4. The microorgansim must be reisolated from the inoculated diseased experimental host and identified as being identical to the originial specific causative agent

Gerhard Domagk

Prontosil

What does prontosil Cure

streptococcal infections

Sir Alexander Fleming

penicillin

what does mold secreting penicillin kill

staphylococci

Selman Abraham Waksman

streptomyces

What does streptomycin kill

Mycobacterium tuberculosis

Giuseppe Brotzu

discovered original cephalosporin (Cephalosporium

acremonium) from sewer outfall

Is there an ecological rationale for production of antibiotics by microbes?

Antibiotic resistance

When germs develop the ability to defeat the antibiotics designed to kill them, one of the greatest global heath challenges of modern time

Antibiotic Resistance infections affect

1. Sepsis Treatment

2. Surgery

3. Chronic conditions (ex, diabetes)

4. Organ transplants

5. Dialysis for advanced kidney disease

6. Cancer Care

Carbapenem-Resistant Enterobacteriaceae

Are a major concern for patients in healthcare facilities. Some bacteria in this family are resistant to nearly all antibiotics , leaving. more toxic or less effective treatment oprions

How do CRE spread antibiotic resistance?

They can carry mobile genetic elements that are easily shared between bacteria

Plasmids

Circles of DNA that can move between cells

Transpoons

small pieces of DNA that can go into and change the overall DNA of a cell. These can move from chromosomes (which carry all essential genes for germ survival) to plasmids and back

Phages

Viruses that attack germs and carry DNA from germ to germ

Transduction

Resistant genes can be transfered from one germ to another via phages

Conjugation

Resistant genes can be transfered between germs when they connect

Transformation

Resistant genes released from nearby live or dead germs can be picked up directly from another germ

Antibiotic Resistance Mechanisms

1. Antibiotic degrading enzyme

2. Antibiotic Alterning Enzyme

3. Antibiotic efflux pump

Example of a drug class affected by antibiotic degrading enzymes

Beta-Lactams

Example of a drug class affected by antibiotic altering enzyme

Aminoglycosides

Example of a drug class affected by an antibiotic efflux pump

tetracyclines

What is a biofilm?

A biofilm is a community of bacteria encased in a self-produced extracellular matrix that adheres to surfaces and protects bacteria from external threats, including antibiotics.

How does a biofilm contribute to antibiotic resistance?

Biofilms act as a protective barrier, preventing antibiotics from penetrating and reaching bacteria, leading to increased resistance.

Kirby-Bauer Assay

A standardized method used to test bacterial sensitivity to antibiotics by measuring the zone of inhibition around antibiotic-impregnated discs on an agar plate.

How is the Broth Dilution Assay performed?

Bacteria are inoculated into tubes or wells containing liquid media with serially diluted concentrations of an antibiotic, then incubated and observed for growth.

MIC - Minimum Inhibitory Concentration

Lowest concentration of a drug that results in no visible growth of the bacteria

MBC - Minimum Bactericidal Concentration

Lowest concentration of the drug that kills 99.9% of bacteria cells in original inoculum

Bacteriostatic activity

An antibacterial drug that stops the growth of a pathogen but does NOT kill it at the site of infection after a therapeutic dose

Bactericidal Activity

An antibacterial drug that kills a pathogen at the site of infection after a therapeutic dose

Five major pathways/targets of clinically used antibacterial drugs

1. Inhibition of cell wall synthesis

2. Inhibition of protein synthesis

3. Inhibition of DNA or RNA synthesis

4. Inhibition of folate synthesis

5. Membrane distribution

Sulfonamides

Inhibitors of folic acid biosythnesis in bacteria

Sulfonamides MOA

inhibit dihydropteroate synthase

what does dihydropteroate synthase do

an enzyme necessary for folic acid biosynthesis

why is Tetrahydrofolate important

it is an essential coenzyme for the synthesis of thymidine, purines, and certain amino acidcs

What do sulfonamides mimic

PABA

Monotherapy of sulfonamide are

Bacteriostatic

Common allergic reactions to sulfonamides

Hypersensitivity reactions (rash, photosensitivity, drug fever)

Sulfadiazine

broad spectrum activity against Gram (+) and Gam (-) bacteria, toxoplasmosis, poorly soluble in urine and can cause crystalluria

Sulfamethoxazone

Used only in synergistic combination therapy with trimethoprim. Combination is known as co-trimoxzole or TMP-SMX

Trimethoprim (TMP)

Inhibitor of folate biosynthesis

trimethoprim MOA

inhibits bacterial dihydrofolate reductase (DHFR) thus halting folate biosynthesis. Folate is needed for DNA synthesis.

Basis for Selectivity (trimethoprim)

Differences between bacterial and mamalian DHFR.

Trimethoprim - Resistance Mechanisms

1. Alteration of DHFR (weaker binding of TMP)

2. Increased DHFR production in bacteria cell

3. TMP does not penetrate into Pseudomonas aeruginosa cells

Trimethoprim & Sulfamethoxazole

Bactrim

Trimethoprim & Sulfamethoxazole

Formulated in a 1:5 ratio (TMP:SMX) to

produce a serum concentration of 1:20

Is TMP-SMX bactericidal or bacteriostatic

Bactericidal - Synergy from inhibiting two enzymes in same pathway

What is the brand name for TMP-SMX

Bactrim

How is TMP-SMX formulated

1:5 ratio (TMP:SMX)

What serum concentration does TMP-SMX produce

1:20

What are indications for TMP-SMX

Uncoomplicated lower UTIs (cystitis), MRSA (cellulitis)

How is the TMP-SMX Oral bioavailability

Excellent

TMP-SMX has signfigant drug intraction with

warfarin

A common side effect of TMP-SMX is

RASH (due to SMX)

Quinolones

Inhibitors of DNA Gyrase and Topoisomerase IV

First Gerneation Quinolone also called

Nalidixic Acid

First geranation Quinolones have low or high potency

Low potency

First gerneation quinolones are indicated for

Gram negative urinary tract infections

Seconnd genration quinolones (biocehmistry)

Fluroine atom at the C-6 Position which incrase the spectrim of activity (gram + and gram negative)

What is DNA gyrase needed for

to help unqind the supercoils

MA of quinolones

inhibit the nicking and closing activeties at DNA gyrase. At higher concenrtations they block the decatenating activity of toposiomerase

What happens when winding and unwiding of DNA is impated

DNA cannot be properly stored, replicated, repaired and trasncribed

IMPORANT: Quinolones have chemical icompatabilties with

Chelate polyvalent metals (ca2+, Mg2+, A3+, Fe2+) and form less water soluble complexes which ddecrease oral bioavibility, thereby losing potency

Quinolones and what are contraindicated

co-adminstration with antacids and after consuking dair products

What is the bassi of selectivity of quinolones

Human toposiomerase II is insensitive to uinolones at noraml achievalbe dosese

Bacteria resistance to quinolones

Binding site modifications, efflux pumps

What is the brand name for ciprofloxacin

Cipro

Compared to other fluorquionones ciproflacxin has the ____ activity against aerobic gram - organisims

MOST; ciprofloxacin (cipro) most active fluroquinlone agaisnt aerobic gram (-) organsisms

Is ciprofloxacin active against anerobic organsims

NO ciprofloxacin is not active agaisnt anaerobic organsims

Is hte plasma pritein bidning of cirpofloxacin low or high

low

Cirpofxacin is widely distributed into

most tissues

What is the brand name of ofloxacin

Floxcin

What is the aboslute bioavailabilty of ofloxacin

roughly 98 percent

Compared to ciprofloxacin ofloxacin is _____ potent compared

Less, ofloxacin is less potent than ciprofloxacin against most gram (-) bacteria

What is ofloxacin generally used to treat,

Mild to moderate urinary UTI, prostatitis, Lower respiratory tract infections, and skin infections

What are teh brand names of levofloxacin

Iquix, Levaquin, Quixin

Levoflxacin is

optically active L-isomer of ofloxacin

Levofloxacin exhbits

post antigbitoic effect (APE) against amny patherogens: organisms may not redsuke grwoth for about 0.5 - 4 hrs after exposrue to levofloxacin, despire undetectrable drug levels

MOA of nitrfuranotin

DNA damaging agent

Nitrofurantoin is used for

Limited to infections of the lower urinary tract (baldder, cystiis)

What is the concentration of ntrifuratoin in the urin

200 μg/mL

Who should avoid nitrofurantoin

Patientts with renal dysfunction due to insufficeint accumulation of drug

What does nitrofurantoin do to the urine

Colors the urine brown

MOA Summary

Sulfonamides: block biosyntheiss of terrahydrofolate by inhibiting the nexyme dihydropteroate synthase

Trimethoprim: inhibits biosynthesis of tetrahydrofolate by bidning to the enzyme tetrahydrofolate reductase

Fluroquinolones: Inhibitors of DNA gyrase and topoisomerase IV

Nitrfurantoin: Generates reactive species that lead to DNA damage

What is the main resistance mechansims for the for beta-lactam antibiotic famalines

The penicillins are incctivted bt amidases and lactamases

Penicillin binding proteins (PBS) have two crucial enxu,atic activeis for th sutnehsus of peptidogylane where

transpetidase (TP) that cross-links amino acid side chains

Glucosyltransferase (GT) that links subunits of the glycopetide polymer

Beta lactams inhibit peptidogylcan syntehsis by

bidning to transpeptidase

The biculic Beta-lactam structure mimics

D-alanul-D-alaanine

Beta-lactams onhbit peptidoglycan sytnehsis by covalenting bindign to

the transpeptidase at hte same stie that bidns to D-alanyl-D-alanine

What is penicillin G called

Benzylpenicillin

Penicillin G is primaruly active against

gram (+) cocci

procaine and benzathine saltes of penicillin G

water insoluble used for repositoruy pruposes follwing intramuscual injection when long term delivery is desired

Origin of b-Lactam Allergenicity

Haptenic reaction with host protein

porins are protiens that form channles providing

hydrophilic access

Penicllinase resitent, paternal penicllins

Methicillin

Nefecillin

Penicillinase resistant oral penicllins

cloxacillin, dicloxacilloin

Pencillinase sesnitve - braod spectrim oral penicllins

Ampicillin

Amoxicillin

Penicillnase senstive braod sepctrum parenteral penicllins

Ticarcilln

Piperacillin