Adv Pharm Final - ID Flashcards
GPC in clusters =
staph species
GPC in chains =
strep species
Gram-Positive Organisms of Importance
- Staphylococcus aureus–Methicillin-susceptible (MSSA) & Methicillin-resistant (MRSA)
- Streptococcus pneumoniae
- Streptococcus pyogenes (Group A Strep)
- Enterococcus faecalis and Enterococcus faecium
- Clostridium difficile (anaerobic organism)
Gram-Negative Organisms of Importance
- Escherichia coli (E. coli)
- Klebsiella pneumoniae
- Pseudomonas aeruginosa
- Bacteroides fragilis (anaerobic organism)
What do we look for on asusceptibility panel?
- Organism and drugs thatwere tested against it
- Minimum inhibitory concentration
- Interpretation from MIC
Minimum Inhibitory Concentration values determine
if sensitive, intermediate or resistant
Concentration-dependent
Greater bactericidal activity as drug concentration (Cmax) exceeds the MIC
Time-dependent
Greater bactericidal activity as drug concentration remains above the MIC
what family does penicillin belong to?
beta-lactam
penicillin MoA
Bind to penicillin binding proteins (PBPs) within the cell wall–>inhibiting cell wall synthesisa–>cell lysis–>destruction
What are natural penicillins?
Penicillin G, Penicillin V
Natural penicillin specturm
Staph aureus (penicillin-susceptible), Streptococcus spp., Syphilis
how much gram-negative activity with natural penicillins?
minimal to none
what was penicillin initally successful against?
skin infections
what is the drug of choice for syphillis?
penicillin
IV natural penicillin
Pencillin G
PO natural penicillin
Pen V
Does Pen V have good absorption?
no
Anti-Staphylococcal Penicillins
Oxacillin, Nafcillin, Dicloxacillin
Anti-Staphylococcal Penicillins Spectrum:
Methicillin-susceptible Staph aureus (MSSA)
Drug of choice for serious MSSA infections
Anti-Staphylococcal Penicillins
Anti-Staphylococcal Penicillins half life
dosed every 4 hours
where are Anti-Staphylococcal Penicillins cleared?
liver
are most beta lactams renally adjusted?
yes
Oral option of Anti-Staphylococcal Penicillins
dicloxacillin
Why isn’t dicloxacillin commonly used?
requires frequent dosing
What were Anti-Staphylococcal Penicillins Created to treat?
Penicillin-resistant Staph aureus
What was the original Anti-Staphylococcal Penicillin?
methicillin
Why was methicillin discontinued?
hepatotoxicity
Amino-penicillins
Amoxicillin (Amoxil®), Ampicillin
Amino-penicillins Spectrum:
Streptococcus spp., E. coli, Haemophilus influenzae, Enterococcus faecalis
are Amino-penicillins reliable for Staph aureus? Why/why not?
no–often resistant to becta-lactamase production
Ampicillin route
IV and PO - MAINLY IV
Amoxicillin route
PO
What penicillins are used for otitis media and pharyngitis?
Amino-penicillins
why aren’t amino-penicillins used for hosptial infections?
gram negatives are usually resistant
inactivated by beta-lactamases
What is a Beta-lactamase?
Enzyme that hydrolyzes the beta-lactam ring à antibiotic becomes inactive
Beta-lactamase Inhibitors (drugs)
Amoxicillin-clavulanate (Augmentin®)
Ampicillin-sulbactam (Unasyn®)
Piperacillin-tazobactam (Zosyn®)
Why were beta-lactamase inhibitors developed?
to inhibit the activity of simple beta-lactamases
Which beta-lactamase inhibitor is avail IV only?
zosyn and unasyn
which beta-lactamase inhibitor is avail PO only?
augmentin
useful action of beta-lactamase inhibitors
preserves/expands the activity of its counterpart
therapuetic use of beta-lactamase inhibitors
hospital infections (except c diff)
Which beta-lactamase inhibitor is associated with high rates of GI complaints?
Augmentin
Penicillin Class Adverse Effects
Hypersensitivity reactions (10%, usually rash) Almost all agents are renally eliminated (requires adjustments) GI intolerances (e.g. diarrhea)--mainly with oral agents
Which penicillins are hepatically eliminated?
Oxacillin, Nafcillin
Cephalosporins MoA
Inhibit cell wall synthesis
How are cephalasporings divided into generations
based on gram negative and gram positive coverage
Which generation of cephalasporin has the most gram-positive coverage?
first
Which generation of cephalasporin has the most gram-negative coverage?
fifth
Why where 3rd gen cephalasporins developed?
Developed to further expand gram-negative spectrum
First Generation Cephalosporins (drugs)
Cephalexin (Keflex®) – PO
Cefazolin (Acnef®) - IV
Which drug class is an alternative to anti-staphylococcal penicillin?
1st gen cephalosporins
1st gen cephalosporins Spectrum:
Streptococcus, Staph aureus (MSSA) – not MRSA
How often are 1st gen cephalosporins dosed?
3-4x a day
what are 1st gen cephalosporins commonly used for?
skin infections and propylaxis prior to surgeries
Third Generation Cephalosporins (drugs)
Ceftazidime
Ceftriaxone
Cefpodoxime
Cefdinir
Which 3rd gen cephalosporins are IV?
Ceftazidime and Ceftriaxone
Which 3rd gen cephalosporins are PO?
Cefpodoxime and Cefdinir
Third Generation Cephalosporins Spectrum:
Streptococcus spp., MSSA, E. coli, K. pneumoniae, Proteus spp.
Ceftriaxone dosing
once a day (for UTI, pneumonia, skin infections)/longer half life, very protein bound
3rd gen common indications
community- acquired pneumonia, skin, bacteremia, osteomyelitis, CNS infections
Fourth Generation Cephalosporins
Cefepime (Maxipime®)
Cefepime route
IV
4th gen ceph Spectrum:
Same as 3rd generation, + additional gram-negatives including Pseudomonas aeruginosa
4th gen ceph–cefepime is reserved for _____________
serious hospital-associated infections
Concern for ________________if 4th gen ceph not dosed properly
encephalopathy (including seizure)
highest risk for encephalopathy with 4th gen ceph
elderly and renal impairment
5th gen cephalosporin
Ceftaroline (Teflaro®)
Ceftaroline (5th gen) route
IV
Ceftaroline (5th gen ceph) spectrum
Covers methicillin-resistant Staph aureus (MRSA) by binding to PBP-2a
Does ceftaroline (5th gen ceph) cover Pseudomonas aeruginosa?
no
Which drug is approved for CAP and ABSSSI?
Ceftaroline (5th gen ceph)
Used off-label for bacteremia, endocarditis and osteomyelitis (as salvage therapy)?
Ceftaroline (5th gen ceph)
Cephalosporin AE
hypersensitivity
seizure if not dosed properly
When to request allergy test or discontinue ceph?
hives, swelling, anaphylaxis
What ceph has highest risk for seizure?
cefepime
CarbaPENEMs
Ertapenem
Meropenem
Imipenem/cilastatin
Doripenem
Carbapenem route
IV for all
Which carbapenem is also avail IM?
Ertapenem
Which class is broadest beta lactam class?
carbapenem
Which class is used as last-line options in gram-negative resistant infections
carbapenem
Carbapenem spectrum:
Streptococcus, MSSA, essentially all GNRs (including P. aeruginosa) and anaerobic gram-negatives
Which carbapenem does not cover psuedomonas?
ertapenem
Drug of choice for ESBL’s
Carbapenem
Which carbapenem has the highest risk for seizures?
Imipenem/cilastatin (Primaxin)
Which carbapenems are interchangeable?
Meropenem, doripenem, imipenem
Are carbapenems stable against many beta-lactamases?
yes
Fluoroquinolones (drugs)
ciprofloxacin
Levofloxacin
Moxifloxacin
fluoroquinolones route
IV and PO
fluoroquinolones MOA
Interferes with normal DNA processes by inhibiting DNA topoisomerases à leading to cell death
flouroquinolones spectrum:
Broad coverage including gram-positive (not MRSA) and gram-negatives
which fluor has poor streptococcus coverage?
Cipro
Do fluor have good bioavailabity?
yes! nearly 100%
Is there a problem of resistance development with fluor?
yes
Do fluor have good distrubtion among infection types?
yes used for nearly all infection types
Fluor AE
QTc prolongation
peripheral neuropathy
tendonitis
hyperglycemia
Fluor BBW:
Exacerbate myasthenia gravis, peripheral neuropathy, tendinitis
What pop are fluors contraindicated?
pregnant and kids
Tetracyclines (drugs)
doxycycline
minocycline
tigecycline
Tetracycline MOA
Inhibit protein synthesis by binding to the 30S ribosomal subunit and preventing tRNA from binding and forming aminoacid sequencing