PTN - Antimicrobials (Drake) Flashcards
What is the difference between broad spectrum and narrow spectrum antibiotics?
Broad spectrum antibiotics work on a wide variety of different bacteria that are both gram positive and gram negative.
Narrow spectrum antibiotics target specific bacterial cell mechanisms, making them more effective against certain types of bacteria over others.
What is a porin and how does it contribute to antibiotic resistance?
A porin is a membrane transport protein that is used to excrete antibiotic drugs from the bacterial cell before they can induce their antimicrobial effect.
What are the major structural differences between Gram positive and Gram negative bacteria?
- Gram positive bacteria have one cell-membrane and a thick peptidoglycan layer
- They also contain teichoic and lipoteichoic acids, which act as exotoxins
- Gram negative bacteria have 2 cell membranes (an inner and an outer) and a thin peptidoglycan layer
- They have lipopolysaccharide (an endotoxin)
What are the 4 main targets of antibacterial drugs?
- Inhibition of bacterial cell wall synthesis
- Selective inhibition of prokaryotic DNA/mRNA/protein synthesis
- Inhibition of folate synthesis
- Cell membrane disruption
What is the minimum inhibitory concentration (MIC) and how is it calculated?
MIC is the concentration of antibacterial drug at which no visible growth of bacteria is evidenced.
This is calculated by doing a serial dilution of antibacterial concentrations in a nutrient broth. Bacteria cloud up the broth, so the tubes are examined for no cloudiness. The first dilution with no cloudiness is the MIC.
Simply reverse the dilution number to get the titer (ex: 1:20 dilution –> titer of 20)
You are working in a microbiology lab and are trying to determine the minimum inhibitory concetration (MIC) of penicillin on a strain of bacteria. You perform a serial dilution and your results are below. What is the dilution and titer of the MIC for this bacteria?
To determine the MIC, simply look for the first tube that appears clear.
In this case, the dilution is 1:8, so the titer is 8.
So the MIC is 8
What is the minimal bactericidal concentration (MBC) and his is it determined?
The MBC is the concentration of drug required to kill 99.9% of a certain type of bacteria (essentially a bacteriocide).
This is done by performing a serial dilution to determine the MIC. Next, culture broth with no visible growth in it is cultured on an agar plate. The dilution/titer that shows no growth on the agar is the MBC.
What does “time above MIC” mean in terms of an antibacterial drug?
The time that the drug is active
What are 3 pharmacokinetic factors to consider when deciding which antibacterial drug to prescribe?
- Location of infection - drug needs to be able to reach target
- Renal and hepatic function - alters drug clearance and metabolism
- Route of administration - how well the drug is absorbed via GI vs IV
What is time-dependent killing and what property is it commonly associated with?
Time dependent killing - bactericidal activity continues as long as the plasma concentration of drug is greater than MIC.
Commonly associated with cell wall synthesis inhibitors (penicillin, vancomycin, etc.)
What is concentration-dependent killing and what property is this associated with?
Concentration-dependent killing - rate and extent of killing increases as the peak drug concentration increases.
Associated with drugs that inhibit protein/DNA synthesis (aminoglycosides, fluoroquinolones, etc.)
What are some local host factors that should be considered when prescribing an antibacterial agent?
- Physical barriers - cell debris, biofilms
- Chemical factors - antimicrobial agents
- Pus inactivates aminoglycosides
- PABA inactivates sulfonamides
- Blood flow to site of infection - impaired flow limits penetration of antibiotic
True or False: Patients with neutropenia, AIDS, or other immune system disorders are typically not treated with bacteriostatic drugs.
True
Some of these drugs tend to impair the immune system when used at high doses.
True or False: Very young and very old patients respond atypically to certain bacteriostatic drugs.
True
Need to consider the patient’s age when determining which antibacterial drug to use.
What are 4 considerations that should be taken into account when prescribing pregnant women with antibacterial drugs?
- Altered volume of distribution - increaed blood volume
- Toxicity to mother - tetracyclines, erythromycin
- Toxicity to fetus - tetracyclines, aminoglycosides
- Transmission of drugs from mother to baby via breast feeding
What class of antibiotics is the most common type to cause drug allergic reactions?
Penicillins
What are 3 bacterial mechanisms of inherent drug resistance?
- Microbe lacks target for drug
- Modification of drug by microbial enzymes
- Lack of accumulation of drug - efflux pumps
What are the 4 primary mechanisms that allow bacteria to acquire resistance to antibiotics?
- Mutation of drug target - most common
- Transduction - transfer of drug resistance genes from one bacteria to another via bacteriophage
- Transformation - uptake by sensitive bacteria of drug resistance plasmids in the immediate environment
- Conjugation - passage of resistance genes from direct cell-cell contact
What are the 3 bacterial pathogens that are considered to be of urgent threat level by the CDC?
- C. difficile
- Carbapenem-resistant enterobacteriaceae (CRE)
- Drug-resistant Neisseria gonorrhea
What are some examples of misuse of antimicrobial agents that can lead to resistant bacteria?
- Using antibacterials on a viral infection
- Treating a fever of undetermined origin (in absence of signs of infection)
- Improper dosage
- Treating with drugs without draining an abscess
- Failure to ID organism and drug sensitivity
What is the most common reason to use antimicrobial prophylaxis?
Prevention of wound infections during surgery
Prophylaxis is also used for organ transplant patients, chemotherapy patients, patients with lesions predisposing endocarditis, and to prevent infection when a person is exposed to a pathogen (ex: gonorrhea)
What is the goal of treatment with multiple antimicrobial agents in patients with bacterial infections?
To prevent the emergence of antibacterial resistant bacteria
What are some disadvantages to treatment of bacterial infections with multiple drugs?
- Drug antagonism - when one drug inactivates the function of another drug
- Ex: giving a bacteriostatic drug with a bactericidal drug (these only kill dividing cells) - stopping cells from dividing limits function of bactericidal drug
- Unnecessary patient exposure - toxic side effects and the possibility of patient developing an allergy to the medication
What is a superinfection and how is it caused?
A superinfection is the emergence of resistant organisms after reduction of normal flora by antimicrobial agents.
Elimination of normal gut flora makes it easier for pathogens to invade and cause disease.
Examples of superinfecting bacteria: Staph. aureus, Candida albicans, and Clostridium difficile
What is a bacteriocin and what does it do?
Bacteriocins are substances made by commensal bacteria that prevent the growth of pathological organisms.
Elimination of bacteriocin production makes it easier for superinfections to occur.
True or False: The likelihood of superinfection is directly related to the width of antibacterial spectrum of the drug.
True
The broader spectrum of bacteria that are killed by the drug, the more likely that superinfection will occur because more bacteria will be erradicated.
What are 2 characteristics of an ideal antimicrobial drug?
- Cannot lead to resistance
- Does not disrupt patient’s health
How to beta-lactam antibiotics work to inhibit bacterial infections?
Beta-lactams inhibit bacterial cell wall synthesis
What is the advantage of using Penicillin V over Penicillin G?
Penicillin V (PenVK) is designed to be more stable in acidic environments, making it more easily absorbed in the gut.
Describe the process of peptidoglycan synthesis.
- Peptidoglycan are composed of monomeric subunits of amino acids within the cytoplasm
- These monomeric units are transported out of the cytoplasm and into the periplasmic space (space between cell membrane and peptidoglycan layer/outer membrane.
- These units are linked together via a process called transpeptidation
What is transpeptidation and which enzyme is responsible for this process?
Transpeptidation is the cross-linking of monomers of peptidoglycan to form the outer layer of gram positive and gram negative cells.
Enzyme: transpeptidase
What enzyme do penicillin drugs target and how do bacterial cells develop resistance to this class of drugs?
Transpeptidase
Penicillins inactivate transpeptidases, which prevents peptidoglycan from being cross-linked. This prevents cell wall formation.
Bacteria can develop penicillinases, which cleave penicillin and inactivate it.
What are the 5 penicillinase resistant penicillin drugs?
- Oxacillin
- Dicloxacillin
- Cloxacillin
- Nafcillin
- Methicillin
What are the 2 broad spectrum penicillins and what do they target?
- Amoxicillin
- Ampicillin
Target Gram negative bacteria
Describe the route of administration of cephalothin (a 1st generation cephalosporin) and its advantage over other first generation cephalosporins?
Cephalothin is a parenteral injection
Advantage: it is highly resistant to staphylococcal beta-lactamases
The other 1st gen cephalosporins are susceptible to beta-lactamases
Which type of bacteria are 1st generation cephalosporins best at treating? What about 2nd generation?
- 1st generation - treat gram positive bacteria
- Staph
- 2nd generation - treat gram negative bacteria
- H. influenza, Enterobacter, E. coli, Klebsiella
List the 3 types of 3rd generation cephalosporins. What are they good at treating?
- Cefotaxime
- Cefoperazone/Ceftazidime
- Ceftriaxone
Used to treat gonorrhea and Pseudomonas aeruginosa
What is the name of the 4th generation cephalosporin and what is it used to treat?
Cefepime
Used to treat gram negative organisms in vitro.
Highly resistant to beta-lactamases
What are carbapenems and what is their mechanism of action?
Carbapenems are non-penicillin, non-cephalosporin antibiotics.
They function by inhibiting beta-lactamases (same as penicillins and cephalosporins)
What is cilistatin and why is it used in conjunction with carbapenem drugs?
Cilistatin is a dehydropeptidase inhibitor.
Carbapenem drugs are hydrolyzed by dehydropeptidases in the kidney, making them more easily excreted in the urine.
Cilistatin increases the half-life of carbapenems.
What is the route of administration of carbapenem drugs and which types of bacteria do they work best on?
Parenteral injection
Work best on both gram positive and gram negative bacteria
Staph, strep, listeria, enterobacter, pseudomonas, etc.
How does vancomycin work and what type of bacteria is it most effective against?
Vancomycin binds D-ala-D-ala of monomers of peptidoglycan to inhibit cell wall polymerization.
Most effective against gram positive bacteria and penicillin resistant Staph aureus and strep.
Which antibiotic is MRSA most resistant to?
Erythromycin
Community acquired MRSA infections can be treated with which 3 drugs?
- Tetracyclines
- Clindamycin
- Co-trimoxazole (sulfamethoxazole + trimethoprim)
What is co-trimoxazole and why is it more beneficial than treating with a regular sulfonamide?
Co-trimoxazole = sulfamethoxazole + trimethoprim
Sulfamethoxazole inhibits dihydropteroate synthase, an enzyme that converts PABA into dihydropteroic acid (DHPA).
Trimethoprim inhibits the enzyme dihydrofolate reductase, an enzyme further down in the tetrahydrofolate synthesis pathway.
Using both prevents the possibility of a bacteria being resistant to one or the other.
