Antimicrobial agents Flashcards
Mechanism of action and resistance
These agents cause cell lysis, thus killing bacteria. These agents “attack” microbes by affecting the cell wall, lipids, enzymes, or protein synthesis within the cell – sometimes even completing a combination of these mechanisms
Bactericidal agents
- By disrupting the cell wall structure of existing cells and inhibiting the formation of new cells, bactericidal substances cause bacterial cells to die off, therefore decreasing the amount found in the individual affected.
These agents cause cell lysis, thus killing bacteria. These agents “attack” microbes by affecting the cell wall, lipids, enzymes, or protein synthesis within the cell – sometimes even completing a combination of these mechanisms
Bactericidal agents
- By disrupting the cell wall structure of existing cells and inhibiting the formation of new cells, bactericidal substances cause bacterial cells to die off, therefore decreasing the amount found in the individual affected.
These agents inhibit the growth and multiplications of bacterial cells, rather than directly killing them.
Bacteriostatic agents.
-they can achieve this by obstructing the metabolic mechanisms of the bacterial cell, in most cases targeting the protein synthesis. While doing this does not cause outright cell death, it does effectively inhibit further growth and DNA replication of the bacterial cells.
Examples of bactericidal agents
- Penicillin, cephalosporins, and vancomycin
Examples of bacteriostatic agents
- Tetracycline, sulfonamides, and erythromycin
Antibacterial agents can be categorized into two spectrum: _______ and ________
-Narrow and Broad spectrum
These refer to antibiotics with limited spectrum and target only few types of bacteria
e.g: Penicillin G which is effective against gram negative bacteria only
-Narrow spectrum antibiotics
also Vancomycin since it is a very large molecule it cannot penetrate the outer membrane of gram-positive bacteria so it is also effective only in gram negative bacteria
These antibiotics have an antimicrobial spectrum which includes some gram-positive and some gram-negative organisms, as well as certain rickettsiae, larger viruses, protozoa, and pleuropneumonia-like organisms. Antibiotics with a wide range effect
Broad spectrum antibiotics
True or false: Narrow-spectrum antibiotics are more likely to lead to bacteria that resist drugs. This leads to infections that last longer and cost more to treat.
False.
-it should be broad spectrum antibiotics
True or false: Broad spectrum antibiotics may inhibit and destroy normal flora — a new infection may appear (superinfection) as a result of antibiotic treatment
True
Aminoglycosides, 2nd and 3rd generation cephalosporins, and quinolones are examples of what type of antibiotic?
-Broad spectrum antibiotics
Antibiotics mechanism of action targets:
- bacterial cell wall biosynthesis
- cell membrane function
- protein synthesis
- RNA and DNA synthesis
- Metabolic processes
An antimicrobial agent that binds enzymes transpeptidase/ penicillin binding proteins. They contain 4-membered nitrogen-containing beta-lactam ring at the core of their structure.
Beta-Lactams
Give the 4 beta-lactam class
- Penicillin, Cephalosporins, Monobactam, and Carbapenems
Penicillin were found to inhibit the growth of what bacteria?
Streptococcus aureus
- discovered by Alexendar Fleming in 1928
On what year do humans first started the use of Penicillin?
1941
- from the mold penicillum notatum
To be effective Penicillin must:
- penetrate the bacterial cell wall
- keep its beta-lactam ring intact
- binds to transpeptidase
How can bacteria develop resistanc to penicillins?
- by producing penicillinase that binds to C-N bond of the beta-lactam ring
What bacterial structure provide antibiotics resistance gene to the cell?
- Plasmids
The “first true antibiotic”
Penicillin
- Fleming discovered that the mold penicillum notatum can inhibit S. aureus
These antibiotics are structurally similar to penicillin but can more withstand the action of beta-lactamase and are more modifiable
Cephalosporins
-Beta-lactams bind to and block the activity of enzymes responsible for making peptidoglycan, resulting in cell wall death.
What is beta-lactamase? and how do they inactivate antibiotics?
Beta-lactamases are enzymes produced by bacteria that provide multi- resistance to β-lactam antibiotics
-The beta-lactamase enzymes inactivate beta-lactam antibiotics by hydrolyzing the peptide bond of the characteristic four-membered beta-lactam ring rendering the antibiotic ineffective.
This antibiotic only has 1 beat-lactam ring, its ring is alone and not fused to another ring (in contrast to other beta-lactams which have at least two rings).
Monobactam
- can kill tough hospital acquired, MDR bacteria
This antibiotics can work only against aerobic gram-negative bacteria. They are actually referred to as “magic bullet” for gram-negative aerobic bacteria.
Monobactam
Type of antibiotic given as initial treatment for px with infectious diseases
Broad-spectrum antibiotics
Type of antibiotics given to px that has an infectious diseases with known organism
Narrow spectrum
-given when test result us already out and the organism is already identified
Characteristic of antimicrobial agents
- Must be in active form
- must be able to achieve concentration at the site of infection that is higher than the pathogens’s MIC to be effective
- must jave selective toxicity
The lowest concentration of drug that inhibits the bacteria.
It is the lowest concentration of an antimicrobial that will inhibit the visible growth of a microorganism after overnight incubation
MIC- minimum inhibitory concentration
It is the study of a drug’s molecular, biochemical, and physiologic effects or actions. It answers the questions
“What the drug does to the body?”
- Pharmacodynamics
The study of how the body process the drugs. It answers the question
“what the body does to the drugs”
Pharmacokinetics
Classification of antimicrobial drugs according to nature
- Natural drugs
- Semi synthetic drugs
- Synthetic drugs
Drugs produced by bacteria or fungi
ex. bacitracin, erythromycin, vancomycin, penicillin, tetracyline
-Natural drugs
These are modified natural drugs with added chemicals
ex: ampicillin, carbenicillin, and methicillin
Semi-sybthetic drugs
These are chemically-produced drugs
ex: sulfonamides, isoniazid, ciprofloxacin, and dapsone
Synthetic ic drugs
These are the most selective antibiotics according to mode of action with a high therapeutic index.
Note: TI means the quantitative measurement of the relative safety of drugs.
-Cell wall inhibitors antibiotics
Formula for therapeutic index
Note: the larger the TI the safer the drugs is
TI = TD 50
————–
ED 50
in which TD refers to- toxicity dose
ED refers to - effectivity dose
An enzyme also called as penicillin binding protein
Transpeptidase enzyme
- which is necessary for cell wall synthesis. It also helps bacteria to form cross-linking between each peptide chains.
What substance is found in the cell wall of gram positive bacteria and are composed of polymers of either glycerol phosphate and ribitol phosphate. They are also involved in attachment of bacteria to mucosal cells.
Teichoic acid
- Teichoic acids (TAs) are specific polymers on Gram-positive bacterial cell surfaces and are not found in Gram-negative bacterial cells
Process of Beta-Lactam inhibition
Beta lactam
| ring attached to PBP or transpeptidase enzyme
↓
Interference with transpeptidation
↓
Inhibition of cell wall synthesis
↓
Unstable cell wall
↓
Autolysis due to osmotic pressure
↓
Cell deathRefers to an enzyme which can inactivate penicillin, produced by certain bacteria. These are bacteria that breaks the lactam ring of beta-lactam classes
Penicillinase
- e.g. B-lactamase
Common resistance mechanism of bacteria to beta-lactam antibiotics
-production of enzymes such as b-lactamase or penicillinase
What do beta-lactams inhibit?
inhibits transpeptidation
How do bacitracin inhibit bacterial growth?
inhibits synthesis of peptidoglycan precursors.
How do vancomycin inhibits bacterial cell growth?
-they inhibit translocation and elongation of peptidoglycan
Target site for protein synthesis inhibitors
- Ribosomes
2 ribosomal sub units of prokaryotic organism
- 30S and 50S subunit
These type of antibiotic inhibitors binds with a 30s and 50s subunit that results in the misreading of mRNA and thus interferes with aminoacyl-tRNA binding.
Protein synthesis inhibitors
- always halt the growth of microorganism
- bacteriostatic in nature
Main side effect of aminoglycosides
this include: gentamicin, kanamycin, neomycin, streptomycin, tobramycin
Deafness and loss of balance
Antibiotics usually used to treat typhoid fever, meningitis, and some anaerobic organism.
-Chloramphenicol
Primary side effects of chloramphenicol
Temporary or permanent depression of bone marrow resulting to Aplastic anemia and Leukopenia
Increase dosage of tetracycline may lead to _______ and ______ damage or even ______ of the teeth among children
- Hepatic and kidney
- yellowing of teeth
Type of antibiotic according to mechanism of action that primarily target DNA metabolism. Antibiotics that targets organism before translation.
Nucleic Acid Synthesis Inhibitors
A type of nucleic acid inhibitor antibiotic that inhibit RNA POLYMERASE
Rifampicin
-indirectly stops protein production
A type of nucleic acid inhibitor antibiotic that interferes with DNA gyrase (G-) and Topoisomerase IV (G+)
The enzymes mentioned are necessary for DNA replication ,recombination, and repair.
- Flouroquinolones
e. g. Ofloxacin and Ciprofloxacin
A type of nucleic acid inhibitor antibiotic that disrupts DNA process and is effective against anaerobic bacteria
Metronidazole
Type of antibiotics that disrupts cell membrane function, once the cell membrane is disrupted. It increase permeability resulting to autolysis and cell death.
Cell membrane inhibitors
A cell membrane inhibitor that is effective against gram-negative bacteria such as Pseudomonas aeruginosa
-Polymyxin B nd E
A cell membrane inhibitor that is effective against gram-negative bacteria such as Pseudomonas aeruginosa
- Polymyxin B nd E
- acts as detergents interacting with phospholipids in cell membrane to increase permeability.
A cell membrane inhibitor that is effective against gram-positive bacteria like MRSA and VRSA
Daptomycin
- exerts antimicorbial effect by binding and disrupting gram- positive bacteria
A type of metabolite inhibitor antibiotics that inhibits FOLIC acid metabolism and has high therapeutic index.
It targets the enzyme dihydropteroate synthetase
-Sulfamethoxazole (SMXZ)
A type of metabolite inhibitor antibiotics that blocks the enzyme dihydrofolate reductase which is necessary in the formation of DNA
- Trimepthoprim
- usually mixed w/ sulfonamides which enhance activity against bacteria.
A type of metabolite inhibitor antibiotics that interferes CORD factor synthesis found in mycolic acid
-Isoniazid
MALT = Proteins synthesis
Macrolides- Aminoglycosides- Lincosamides- Tetracycline
Genral Antibiotic classes
“Antibiotics Can Terminate Protein Synthesis For Microbial Cells Like Germs”
Aminoglycosides- Cephalosporins- Tetracyclin- Penicillins-Sulfonamides- Fluoroquinolones- Macrolides-Carbapenems- Lincosamides- Glycopeptides
It is a result of both use and overuse of antimicrobial agents
Antibiotic Residtance
Two types of antimicrobial resistance
Intrinsic and Acquired resistance
Refers to the type of antibiotic resistance in which the organism already had inherent characteristic enabling it to be resistant to certain antimicrobials even before antibiotic use.
Intrinsic Resistance
Characteristic of Intrinsic Resistance
- already included in the normal genetic structure of the organism
- depends on the hydrophobic and hydrophilic nature of antibiotic
- Impermiability of antibiotic to cell wall
- Pass vertically into the new cell
- Predictable
- Naturally and consistently inherited
Refers to the type of antibiotic resistance which is necessitated by prior exposure to the antimicrobial agent. Usually results from altered cellular physiology and structure caused by changes in microorganism genetic make-up.
Characteristics:
- present only on certain isolates different from the parental strain
- Unpredictable
Acquired Resistance
Primary reason as to why laboratory methods are necessary to detect resistance pattern which are known as antimicrobial susceptibility profile in clinical isolates
Unpredictability of acquired resistance
Common methods for an organism to attain acquired resistance
-chromosomal mutations, transformation, and recombination
Bacterial resistance to beta- lactams may be mediated by:
- enzymatic destruction (production of b-lactamase)
- altered target - resulting low affinity
- Decreased uptake or increase efflux of drugs
In gram positive bacteria, B-lactamase is secreted as?
Exoenzymes
- offering less protection to organism (kay sa gawas man na produce)
In gram negative bacteria, B-lactamase are found in?
Periplasmic space
4 categories of Beta-lactamases
- Class A,B, C, and D enzymes
type of B-lactamase enzyme that is SERINE peptidases and is usually carried by plasmids .
Class A and D enzymes
type of B-lactamase enzyme that is CEPHALOSPORINASE and is usually located within and integron
Class C enzyme
type of B-lactamase enzyme that is METALLO-BETA LACTAMASES and is usually located within and integron
Class B enzyme
These are inhibitor drugs that are co-administered with beta-lactam antimicrobials to prevent antimicrobial resistance by inhibiting serine beta-lactamases, which are enzymes that inactivate the beta-lactam ring, which is a common chemical structure to all beta-lactam antimicrobials.lactamase
Note: these combination is effective only against organism that produce beta-lactamase
B-lactamas inhibitors
e.g. Clavulanic acid, sulbactan, and tazobactam
Are rapidly evolving group of beta-lactamases which shares the ability to hydrolyze 3rd generation cephalosporins and aztreonam but are inhibited by clavulinic acid.
Extended spectrum B-lactamases (ESBLs)
Antibiotic drugs that is used for treatment of Extended spectrum b-lactamases because they are active against it
Carbapenems
For screening of Extended spectrum b-lactamases it should b resistant to antibiotics such as:
- Ceftazidime, Cefotaxime, Cefpodoxime
What confirms ESBLs production of bacteria in culture plate
-Synergy or key-hole phenomenon between antibiotic drugs
It is a circular area around the spot of the antibiotic in which the bacteria colonies do not grow. This can be used to measure the susceptibility of the bacteria to wards the antibiotic.
Zone of inhibition / Zone of no growth
- key hole phenomenon
Measurement necessary for it to be deemed as positive for ESBLs.
≥5 mm enhancement with Clavunilic combination
