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
tetracyclines spectrum:
Expanded gram-positive coverage (including MRSA) and gram-negative (NOT Pseudomonas)
Do tetracyclines cover pseudomonas?
no
Which tetracycline has anaerobic activty and works against VRE?
Tygacil
What conditions are tetracyclines good for?
bone and skin infections
What conditions are tetracyclines bad for?
bacteremia and urine infection
Tetracyclines AE
GI intolerances
Photosensitivity
Bone deformity and teeth staining
which tetracycline has more cases of vertigo?
Minocycline
Which tetracyline has higher levels of N/V?
Tygacil
Which groups are contraindicated for tetracyclines?
pregnant and children under 8
Macrolides (drugs)
Azithromycin
Clarithromycin
Macrolides route
Azithro - IV, PO
Clarithro - PO
Macrolides MOA
Inhibits protein synthesis via the 50S ribosomal subunit
Macrolides Spectrum:
- variable Streptococcus spp., H. influenzae, Moraxella catarrhalis, otherwise weak gram-negative coverage
- Respiratory pathogens that may cause CAP and other respiratory infections
- atypicals - mycoplasma pneumoniae and chlamydophilia pneumoniae
Which macrolide is used for chlamydia trachomitis
azythromycin
What is the post-antibiotic effect with macrolides?
Continues to work despite subtherapeutic concentrations
macrolides AE
GI upset, QTc prolongation
Should pts take macrolides with food?
yes; helps minimize GI upset
Why is Clarithromycin rarely used?
drug interactions (inhibits CYP 450 enzymes), increased GI intolerance and more frequent dosing
Sulfamethoxazole-trimethoprim (Bactrim®) route
IV and PO
Bactrim MOA
Inhibits DNA synthesis via inhibition of folic acid synthesis (synergistic activity as each component works in a different step)
Bactrim spectrum
Very broad, gram-negatives (NOT Pseudomonas aeruginosa) and gram-positives (including MRSA)
Bactrim bioavailabity
85% (IV and PO interchangable)
Bactrim contraindicated
patients with sulfa allergies
pregnant or trying
on warfarin
potassium issues
Use caution prescribing bactrim when
pt has hematological issues
renal disease
has used bactrim before (20% of ecoli are resistant)
Bactrim is dosed based on the ____________
trimethorprim
Bactrim indications
pneumonia, skin infections, UTI, bone infections
Bactrim AE
Skin reactions (can be very severe), neutropenia, nephrotoxicity, hyperkalemia
When to adjust bactrim?
renal dysfunction
Metronidazole (Flagyl®) route
– IV, PO
Metronidazole MOA
Damages DNA of the organism and leads to cell death
Metronidazole (Flagyl) Spectrum:
Anaerobic gram-negative organisms, Clostridium difficile (C.diff) which is a gram-positive anaerobic organism
Metronidazole (Flagyl) AE
GI upset, metallic taste, headache, dark urine, peripheral neuropathy
what happens when you mix Metronidazole (flagyl) and alcohol?
disulfram like reaction–extreme vomiting
Metronidazole (Flagyl) bioavailabiity
excellent - IV and PO interchangeable
gram pos antibiotics
vancomycin, linezolid, daptomycin
vanco MOA
Inhibits cell wall synthesis
vanco spectrum
gram pos only
drug of choice for MRSA
Vanco
When is vanco given IV?
pneumonia, CNS, UTI, bone, blood
When is vanco given PO?
Clostridium difficile infection (not absorbed systemically)
What must you do when administering IV vanco?
monitor drug levels for efficacy and toxicity
Vanco AE
Nephrotoxicity - high levels
Ototoxicity - very high levels
Red Man’s syndrome - with rapid infusion
What should you do when vanco pt gets red man syndrome?
slow the infusion time –it’s not an allergic reaction!
when is trough measurement taken for vanco
serum conc taken 30 minutes prior to the 4th dose
desired vanco concentrations for serious infections (blood and lung)
15 - 20 mcg/ml
desired vanco concnetrations for mild infections (skin and UTI)
10-15 mcg/ml
Linezolid route
IV and PO
LInezolid MOA
Inhibits protein synthesis
Linezolid spectrum
VERY broad gram-positive coverage including MRSA and VRE
No gram-negative coverage
Linezolid clinical uses
drug-resistant enterococcus (VRE), staphylococcal infections of the lungs, patients with vancomycin intolerance
Linezolid AE
Thrombocytopenia (use > 14 days) Drug interactions with SSRIs (may cause serotonin syndrome) Optic neuritis (use >28 days)
Linezolid contraindications
patients taking an MAO-I
Linezolid bioavailabity
100%
Daptomycin MOA
Causes rapid depolarization leading to inhibition of protein, DNA and RNA synthesis
Daptomycin Spectrum
Same as linezolid
Is Daptomycin available PO?
no
Daptomycin clinical Uses
Alternative agent to linezolid for resistant gram-positive infections and linezolid intolerance
NOT used to treat pneumonia (Inactivated by lung surfactant)
linezolid Adverse effects
myopathy
what to monitor on daptomycin
CPK
Pseudomonas aeruginosa agents
piperacillin/tazobactam ceftazidime carapenems (except ertrapenem) Levofloxacin Cipro
MRSA agents
Vanco Linezolid Daptomycin Tetracyclines Bactrim Ceftaroline
Antifungals
flucanozole
voriconazole
echinocandins
Does flucanazole have good bioavailability?
yes
What is the only azole that concentrates
well in the urine
fluconazole
Flucanazole indication
C. albicans infections (thrush, UTI, blood)
How often is flucanozole dosed for yeast infections?
one time
Drug of choice for invasive pulmonary aspergillosis
Voriconazole
Voriconazole has excellent distribution, except for __________
urine
Voricanazole route
IV and oral
Goal for voriconazole monitoring
2 - 5.5 mcg/ml
Voriconazole AE
visual disturbances and hallucinations
Azoles AE
increase QTc interval (except newest–isavunonazole)
liver injurry
All azoles can inhibit __________ leading to drug interactions
the CYP 450 enzyme system
Azoles can cause transient _______________
LFT elevations
Echinocandins (drugs)
Micafungin, caspofungin and anidulafungin
Echinocandins route
IV only
Echinocandins distribute well with the exception of ______ and ______
CNS, urine
Echinocandins is recommended for
coverage of candidemia in severely septic patients
Antivirals
Acyclovir
Valacyclovir
Oseltamivir (tamiflu)
Cyclovirs MOA
Terminates DNA replication
Which cyclovir is only PO?
valacyclovir (valtrex)
cycolivr side effects
headaceha and nausea
IV cycolivr potential AE
nephrotoxicity
Valacyclovir has a _____________ so it’s dosed less frequently
longer half life
Valacyclovir is a _____________ that’s converted to __________
prodrug, acyclovir
Oseltamivir (tamiflu) MOA
Treatment and/or prophylaxis via neuraminidase inhibition (halts replication)
Tamiflu dosing for treatment of flu
twice a day
tamiflu dosing for prophylaxis of flu
once a day
tamiflu side effects
nausea and vomiting
Empiric data
No culture data to guide antibiotic selection
Takes into account common pathogens
Takes into account patient history and local resistance
Definitive data
based on culture data
CAP Diagnosis
Fever Tachypnea Cough Sputum production (send for culture) ¤ Confusion Fatigue Chest X-ray showing infiltrate
In the elderly, _______may be the only initial symptom
of CAP
confusion
CAP usually straight forward diagnosis, except in those with ___________and_____________
structural lung disease, congestive heart failure
CAP first line treatment (uncomplicated)
Azithromycin OR doxycycline
CAP first line treatment (allergy or complicated)
Levofloxacin or Moxifloxacin
CAP treatment duration
5 days
Cystitis presentation
Urgency to urinate
Increased frequency of urination
Dysuria
Suprapubic pain/tenderness
Cystitis diagnosis
Urinalysis (UA) – sample of urine analyzed for bacteria, WBC,
inflammatory markers and organism growth
Urine Culture – Should be obtained if the UA is abnormal
Preferred Agents for cystitis
Nitrofurantoin (Macrobid®) – uncomplicated disease
Trimethoprim/sulfamethoxazole (Bactrim®)
Fosfomycin
Fluoroquinolones
Beta-lactams (amoxicillin-clavulanate, cefpodoxime)
Typical duration for cystitis treatment
3-5 days
____________ are NO LONGER recommended as first-line therapy for UTIs
Fluoroquinolones
drug for uncomplicated cystitis
Nitrofurantoin
What is the patient requirement for nitrofurantoin (macrobid)
CrCl > 40
Minimum days of treatment of Nitrofurantoin (macrobid)
5
Is nitrofurantoin (macrobid) safe in pregnancy?
yes
nitrofurantoin (macrobid) covers______
many gram negative organisms causing cystitis (eg E. coli)
Fosfomycin use
refractory cases of cystitis
Dosing for fosfomycin
one time (in uncomplicated disease)
Fosfomycin side effects
Diarrhea, nausea (more common)
Headache and dizziness
How often should a patient be prescribed Fosfomycin?
once or twice (base on cultures after)
Fosfomycin MOA
interferes with cell wall syntehsis
Sulfamethoxazole-trimethoprim (Bactrim®) for cystitis safe during pregnancy?
not in pregnancy
Levo/cipro (fluors) for cystitis
use in allergic patients or sever/refractory cases
Avoid in pregnancy
which fluor should be avoided for UTIs and why?
moxifloxacin because it has low urinary concentrations
Beta lactams for cystitis
Augmentin and oral cephs
ABSSSI drugs
Cephalexin Tetra Bactrim Clinda Linezolid Dalbavancin or ortiavancin
Last line ABSSI drug and why
Clinda, GI and C. Diff
Which ABSSI drug causes toxicites after two weeks?
linezolid
Good drug for MSSA and strep
cephalexin
Drug reserved for MRSA or VRE
linezolid
Cephalexin is dosed _____ times a day
4
Dalba/oritavancin is similar to __________
vancomycin
Dalba/oritavancin is useful for
ABSSI non-compliant pts or drug resistance
ABSSSI treatment duration
7-10 days
with minimal response to ABSSSI treatment consider
patient compliance
resistance to agent
source issues
When should we treat a URI with antibiotics?
Strep throat otitis externa (usually bacterial) Otitis media with pus Sinusitis with fever Worsening URI not treated may be bacterial
Strep treatment
Amoxicillin or augmentin in those with amox exposure
Treatment for CAP, inpatient
Ceftriaxone + Azithromycin
Treatment of CAP, inpatient with PCN allergy
Levofloxacin OR moxifloxacin
gram positive anaerobic organism
C Diff
which drugs are hepatically eliminated?
ceftriaxone
Anti-staph penicillins
Why would a patient need to switch from oxacillin to cefazolin?
hepatotoxicity
Which class of drug is inactivated by ESBLs?
3rd gen cephalosporins
Alternative to vanco
linezolid
which antibiotic can inhibit MAO?
linezolid
Daptomycin is not useful for_____________
pneumonia
The number given on an antibiogram indicates
percent susceptible
Of the azoles, only Flucanizole has adequate_________
urinary concentrations
All azoles can cause QTc prolongations except
isavunonazole
This azole can cause hallucinations
voriconazole
Fungins are part of this class
Echinocandins
Which ID drugs cause QT prolongation?
macrolides, azoles, fluoroquinolones
Which ID drugs can inhibit CYP 450 enzymes? (and therefore cause drug interactions?)
clarithromycin and azoles
Which ID drugs mess with the cell wall?
beta lactams and vancomycin
which ID drugs mess with protein?
tetracyclines, macrolides, linezolid
Which ID drugs mess with DNA?
Fluoros, Bactrim, Flagyl
Which drug is inactivated by lung surfactant?
Daptomycin
UTI drugs
Macrobid Bactrim Fosfomycin Fluoros Beta-Lactams—augmentin and cefpodoxime
Name 3 adverse effects of the Penicillin class
Hypersensitivity reactions - 10% of US population (esp. rash)
Almost all renally eliminated with two exceptions
GI intolerances such as diarrhea, usually more with oral agents
Name a cephalosporin that has a long half life, is highly protein bound and can be used to treat UTIs, Pneumonia, and Skin Infection
ceftriaxone
Way to remember pseudomonas aeruginosa
Zosyn Forts Maximize the Cipro Levo Penem
Zosyn, Fortaz (Ceftrazidime), Maxipime (Cefepime), Ciprofloxacin, Levofloxacin, carbaPenems (not ertapenem)
What’s used with vanco for c diff?
Flagyl