Intro to Antimicrobials - Ported from yr I PBD decks. Flashcards
Ok, so we are going to run through the drug list, shall we begin?
What are the broad categories of drugs we were presented?
For example, the first one was Natural Penicillins.
Now, you try!
(there are a lot. Just try to get the 15 bolded ones. These categories have drugs in them that Dr. Kinder listed in RED as must knows)
- Natural penicillins
- Anti-staphylococcal Penicillins
- Aminopenicillins
- Anti-pseudomonal Penicillins
- First Gen Cephalosporins
- Second gen cephalosporins
- Third gen cephalosporins
- Fourth gen cephalosporins
- Carbapenems
- Monobactams
- B-Lactamase inhibitors
- Glycopeptides
- Lipopeptides
- Fluoroquinolones
- Aminoglycosides
- Tetracyclines/glycyclines
- Macrolides/Ketolides
- Lincosamides
- Oxazolidinones
- Metronidazole
- Sulfonamides/Trimethoprim
- Antivirals
- Antifungals
What is the natural penicillin we must know?
Penicillin G
(IV, IM)
What is the anti-staphylococcal penicillin we must know?
Nafcillin
(IV, IM)
What are the aminopenicillins (2) we must know?
Ampicillin (PO, IV, IM)
Amoxicillin (PO)
What first gen. cephalosporin must we know?
Cephalexin [Keflex] (PO)
What 3rd gen cephalosporin must we know?
Ceftriaxone [Rocephin] (IV, IM)
Which Beta-lactamase inhibitors must we know?
Amoxicillin-clavulanic acid [Augmentin] (PO)
What glycopeptide drug must we know?
Vancomycin (PO, IV)
Which fluoroquinolone must we know?
Ciprofloxacin [Cipro] (PO, IV, topical)
What aminoglycoside must we know?
Gentamicin (IV, IM, topical)
What Tetracyclines/Glycylcyclines do we need to know?
Doxycycline
(PO, IV)
What macrolide/ketolide must we know?
Azithromycin [Zithromax, Z-pak] (PO, IV, topical)
What lincosamide must we know?
Clindamycin [Cleocin] (PO, IV, IM, topical)
What is the trade name for metronidazole?
Flagyl
What antiviral do we need to know?
Acyclovir (PO, IV, topical)
What antifungals must we know? (2)
Fluconazole [Diflucan] (PO, IV)
Amphotericin B (IV)
Via what route of administration would you use vancomycin to treat a C. diff infection?
Oral administration
Over use of antimicrobials has proven a major problem. When considering wether to use antimicrobial therapy, what are six questions you should consider before prescribing?
- Is an antimicrobial indicated based on clinical findings?
- Have appropriate cultures been obtained?
- What is the most likely causative organism?
- What must be done to prevent secondary exposure?
- Is there clinical evidence or established guidelines that have determined antimicrobial therapy provides a clinical benefit?
What are the five types of therapy we can employ using antimicrobials?
- Prophylactic Therapy
- Preemptive Therapy
- Empiric Therapy
- Definitive Therapy
- Post-Treatment Suppressive Therapy
Describe the purpose of prophylactic therapy.
Prevent infection or prevent dangerous disease in those already infected.
Describe preemptive antimicrobial therapy
Early, targeted therapy in high risk patients who are asymptomatic but have become infected
Describe empiric therapy
Provide therapy to a symptomatic patient without identification of infecting organism
What is definitive therapy?
Infecting organism now known. Antibiotics streamlined based on susceptibility. Duration of therapy limited to appropriate length.
Describe Post-Treatment Suppressive Therapy.
Antimicrobial coverage at lower dose when infection has not been completely eradicated
Name the type of therapy appropriate in this situation.
A 50 yo male presents to his PCP with dyspnea, fever, and cough. Community-acquired pneumonia is suspected.
Empiric therapy - The physician shoul initiate the appropriate therapy to cover the most likely infecting organisms.
An 18 yo female is admitted to the hospital with a diagnosis of meningococcal meningitis. She lives in the dorms and is only one month into her freshman year of college.
What kind of therapeutic approach is appropriate for maintaining the health of any close contacts she might have, including her roommate?
Prophylactic therapy: Her roommate and other “close contacts” must receive antibiotic therapy to prevent infection.
What kind of therapy is best suited to this scenario?
A 45 yo female, undergoing 3x weekly dialysis, presents with fever and fatigue. Blood cultures reveal gram-positive cocci on gram stain and Staphylococcus is suspected. Sensitivity tests are performed with clear results.
Definitive therapy: At this point the organism is identified and the appropriate antibiotics are determined, the physician can narrow the spectrum of coverage.
What type of therapy is called for in this situation?
A 75 yo male presents to his PCP for follow-up of prosthetic hip joint infection. Review of his drug list reveals continued low dose antimicrobial therapy. Hip prosthesis was unable to be removed and replaced during hospitalization.
This patient should be on post-treatment suppressive therapy
An 8 yo male presents to the ED with a perforated appendix. What kind of antimicrobial therapy is appropriate for this patient?
Preemptive therapy: Antibiotics are initiated pre-operatively to reduce risk of intra-abdominal abscess and surgical wound infection.
What is the most valuable, time tested method for immediate ID of bacteria
Gram stain
In gram negative bacteria, what connects the outer membrane to the peptidoglycan layers?
Lipoprotein
What chemical feature gives peptidoglycan its rigid stability?
What enzyme is involved in its creation?
why is this important clinically?
terminal D-alanine cross linking
transpeptidase
it is the target of B-lactam antibiotics
Which layer is LPS found in?
Which layer is transpeptidase found in?
Gram Negative
Outer membrane
inner membrane
What is a Minimum Inhibitory Concentration?
How do we use this data between various species?
(MIC): lowest concentration of drug required to inhibit VISIBLE growth
MICs are not directly compared between species.
Breakpoints established by CLSI are used to classify degree of susceptibility/resistance, and this is compared.
Describe the serial dilution testing.
What is it for?
Why is it done?
Susceptibility testing
Describe the disk diffusion testing.
What is it for?
Why is it done?
Susceptibility Testing
What is an “Antibiogram”, and how can it help you, clinically?
Institutions keep tabs on the susceptibility & resistance patterns of local pathogenic strains.
Will help you decide which antibiotics to use based on these local patterns
What is this graph showing?
time dependent killing
what is this graph showing?
concentration dependent killing
What is the difference between “broad-spectrum” and “extended-spectrum”
Both cover gram positive and negative, but “broad-spectrum” has more coverage of gram negatives than “extended spectrum” does
Describe the two general types of bacteriocidal agents
Concentration-dependent killing: rate and extent of killing increase with increasing drug concentrations
Time-dependent killing: activity continues as long as serum concentration above minimum bactericidal concentration
What are the sites of action of antibacterial drugs?
Cell wall synthesis
Cell membrane synthesis
Protein synthesis
Nucleic acid metabolism
Function of topoisomerases
Folate synthesis
What is the mechanism of action for B lactam antibiotics?
Time-dependent
structural analogs of D-Alanine
covalently bind transpeptidases (AKA penicillin-binding proteins)
inhibit the last transpeptidation step in cell wall synthesis
what is an example of antibiotic synergy we should be aware of?
Gentamicin – ineffective against enterococci in the absence of a cell-wall inhibitor
Combining penicillin with gentamicin leads to bactericidal activity
Are protein synthesis inhibitors generally bacteriocidal or bacteriostatic?
bacteriostatic
Why is antibiotic selective toxicity important?
This property is what allows us to use toxic agents medicinally - they are much more toxic to bacteria than they are to us.
What are the B lactam antibiotic groups?
Penicillins
Cephalosporins
Monobactam
Carbapenems
Kinder says focus on Penicillins & Cephalosporins
Ok so now for the really hard cards not the childs play we have seen before.
What natural penicillin do we have to know and what does it treat?
What is a narrow spectrum penicillin that treats staph?
Penicillin G, treats strep and is narrow spectrum
Nafcillin
Ampicillin and amoxicillin treat what?
+
Extended; gram-positive and gram-negative (H. influenzae, E. coli, P. mirabilis), Listeria, enterococci
HELPS kill enterococci
What is the MOA of fluoroquinolone?
Is it time or concentration dependant?
targets bacterial DNA gyrase & topoisomerase IV. Prevents relaxation of positive supercoils
Concentration
What are some adverse effects of penicillins?
When can no B-lactam be given?
Allergic reactions (0.7-10%)
Anaphylaxis (0.004-0.04%)
Nausea, vomiting, mild to severe diarrhea
Pseudomembranous colitis
If anaphylaxis occurs no B-lactam can be given
What is a first gen cephalosporin that covers gram positives?
What is a good third gen cephalospirin and what does it hit?
Cephalexin
Ceftriaxone-
Less active against gram-positive; good activity against gram-negative infections (Klebsiella, Enterobacter, Proteus, Serratia, Haemophilus), ceftriaxone drug of choice for gonorrhea
What are some adverse effects of cephalosporins?
Diarrhea
1% cross reactivity with penicillins.
Why do we give B-lactamase inhibitors?
give an example of one.
Because some organisms destroy B-lactam rings so to make the drug effective that must be inhibited
Clavulonic acid
What is the MOA of vancomyocin?
Spectrum?
inhibits cell wall synthesis binding with high affinity to D-Ala-D-Ala terminal of cell wall precursor units
broad gram-positive (including resistant organisms); Clostridium difficile, with what stipulation?
What adverse effects can vanco have, what should you do if they appear?
Adverse effects: red-man syndrome (histamine release), ototoxicity, nephrotoxicity
Slow down rate of drug
What is a fluoroquinolone we should know?
Spectrum?
Why is it contraindiated in children?
Ciprofloxacin,
Spectrum: broad gram-negative, S. aureus (not MRSA), limited coverage of Streptococcus spp [exception – covered by “respiratory FQ’s” (levofloxacin, moxifloxacin)]
Because of achilles tendon rupture, also see other adverse effects
GI distress, CNS, photosensitivity
What is the MOA of acyclovir?
What is it against?
Competes with deoxyGTP for DNA polymerase; causes DNA chain termination
Viruses
Ok so we have azoles and Ampotericin B as antifungals, what are their MOAs
Azoles
•Reduce production of ergosterol
Amphotericin B
•Forms pores in cell membrane
Gentamicin is a aminoglycoside, what is its MOA
Spectrum (What else can it kill if combined with what drug)
aDVERSE effects?
What is a requirement of the drug?
Concentration dependent, binds 30S ribosomal subunit, interferes with initiation of protein syn,causes misreading of nRNA (this by the way makes it not only a syn inhibitor but also cidal)
aerobic gram neg bacteria (will kill gram pos in the presence of a B-lactam)
ototoxicity, nephrotoxicity
Require oxygen and energy to be transported into bacteria
Name a tetracyclin you should know?
MOA
Spectrum
Doxycycline
bacteriostatic; binds 30S ribosomal subunit; prevents access of aminoacyl tRNA to acceptor (A) site
broad gram-positive and –negative; Rickettsia, Coxiella burnetii, Borrelia burgdorferi (Lyme’s disease)
Tetracyclines have what adverse effects?
This makes them contraindicated for what group?
photosensitivity, teeth discoloration
Children- because of the kelation of Ca ions (teeth)
Name a good macrolide?
MOA
Spectrum
Adverse effects
azithromycin
bacteriostatic; binds 50S ribosomal subunit; inhibits translocation
aerobic gram-positive, some gram-negative
Arrhythmia, QT prolongation (important)
What is the MOA of clinamycin?
Spectrum
Adverse effects?
binds 50S ribosomal subunit; inhibits translocation
pneumococci, S. pyogenes, viridans Streptococci, MSSA, anaerobes (B. fragilis)
pseudomembranous colitis (0.01-10%)
So to sum up run through the protein syn inhibitors again on your own
Aminoglycosides (gentamicin)
Bind 30S subunit; prevents formation of initiation complex; causes misreading
Tetracyclines (doxycycline)
Binds 30S subunit; prevents access of aminoacyl tRNA to A site
Macrolides (azithromycin)
Binds 50S subunit; inhibits translocation
Clindamycin
Binds 50S subunit; inhibits translocation
What is the MOA of metronidazole?
Spectrum
Adverse effects
nitro radical anions interact with DNA; cause DNA damage
anaerobes; Clostridium difficile, trichomoniasis, amebiasis, giardiasis
Adverse effects: disulfiram-effect- this means you will be really sick if you drink alcohol while taking this drug
Amphotericin B does have some adverse effects, what are they?
Amphotericin B adverse effects: infusion related (fever, chills, vomiting, headache) and cumulative toxicity
