Infectious Diseases I: background and ABX by drug class Flashcards
how to determine if infection present?
fever, elevated WBC, site specific stuff
Diagnostic findings such as culture results, X-rays, etc
ABX selection based on…..
infection site and likely organisms
infection severity and risk of MDR
abx spectrum of activity & ability to penetrate site of infection
pt characteristics = age, allergies, renal/hepatic function etc
Txm guidelines
Gram + organisms stain…
purple or bluish from crystal violet stain and have a thick cell wall
Gram - organisms stain…
pink or reddish and have thin cell wall
Gram + clusters
Staph
Gram + pairs/chains
Strep or Enterococcus
Gram + rods
Listeria monocytogenes
Corynebacterim
Gram + anaerobes
Clostridium, C.Dif, P. Strep, P. acnes
Atypicals that won’t stain
Chlamydia
Legionella
Mycoplasma pneumo
Mycobacterium tuberculosis
Gram - Cocci
Neisseria
Gram - Rods, colonize gut “Enteric”
Proteus mirabilis
E. coli
Klebsiella
Serratia
Enterobacter
Citrobacter
Gram - Rods, dont colonize gut
Psuedomonoas
H influ
Providencia
Gram - Coccobacilli
Acinetobacter
Bordetella pertussis
M.Catarrhalis
Gram - Anaerobes
B. fragilis
Prevotella
Example of antibiotic synergy
Beta-lactams and aminoglycosides, used for certain gram + invasive infections
A + B > A alone + B alone
Intrinsic resistance
natural resistance
Selection pressure resistance
occurs when abx kills susceptible bacteria, leaving behind more resistant bacteria
Acquired resistance
DNA containing resistance transferred between bacteria
Enzyme inactivation resistance
bacteria produces enzymes that will break down the antibiotics
Overgrowth of C.diff can occur when….
abx kills too much of healthy gut flora
leading to CDI = C.diff infection
Highest risk ABX for C.diff?
broad-spectrum penicillins
cephalosporins
quinolones
carbapenems
Clindamycin**
How do beta-lactams work?
inhibit bacterial cell wall synthesis by binding to penicillin-binding proteins.
prevents final step of peptidoglycan synthesis
What can increase levels of beta-lactams?
Probenecid, sometimes used intentionally for severe infections
Beta-latams effect on warfarin?
can inc anticoagulant effect, except nafcillin/dicloxacillin
Pen G benzathine boxed warning?
dont use IV
Which penicillins should not be used in CrCl < 30ml/min?
extended release oral forms, like Augmenting XR or Amox/clav 875mg
Side effects with penicillins?
Seizures (w/ accumulation & incorrect dose), GI upset, diarrhea, rash, allergic reactions
Why isn’t oral ampicillin used?
poor bioavailability
ampicillin and ampicillin/sulbactam (Unasyn) should only be diluted in….
NS
Penicillin VK is first line for…
strep and mild nonpurluent skin infections
Amoxicillin is first line for….
acute Otis media
drug of choice for infective endocarditis prophylaxis before dental procedure
amox/clav is first line for….
for acute Otis media and bacterial sinusitis
use lowest dose of clavulanate to dec diarrhea
which penicillin is active against pseudomonas?
pip/tazo (zosyn)
which penicillin is drug of choice for syphilis?
penicillin G benzathine
1st gen cephalosporin spectrum of activity
good against gram + cocci
MSSA
dec gram - activity compared to 2/3/4th gen
2nd gen cephalosporin spectrum of activity
gram + and increased gram - activity over previous generations
Which beta-lactam covers MRSA?
Ceftaroline (5th gen)
which cephalosporin should be separated from drugs that decrease stomach acid
Cefuroxime
cefpodoxime
cefdinir
should be operated by 2 hours from short-acting antacids
H2RAs and PPIs should be avoided
Ceftriaxone should be avoided when using the same line as….
calcium containing IV fluids
Carbapenems provide no coverage against….
atypical pathogens
MRSA
VRE
C.dif
Stenotrophomonas
Ertapenem is different from other carbapenems as it has no activity against….
pseudomonas
acinetobacter
enterococcus
Aztreonam info
no cross reactivity with beta-lactam, used when allergy present
doesnt cover gram +/anaerobes but does cover many gram -/pseudomonas
Aminoglycoside info
usually used for synergy
2 dosing strategies
2 Dosing strategies for Aminoglycosides
traditional = lower dose, more frequent
Extended interval = higher dose for higher peak, less frequent
Benefits of using extended dosing interval aminoglycosides
lower risk of nephrotoxicity
less accumulation
decreased cost
hasn’t been shown to be clinically superior tho
Aminoglycoside Boxed warnings
Nephrotoxicity, ototoxicity, neuromuscular blockade n respiratory paralysis. avoid with other nephrotoxic drugs
Aminoglycoside warnings
caution in impaired renal function and elderly patients
Dosing for aminoglycosides?
use TBW if < IDW, use TBW if weight normal and use ABW if obese
Genta/tobra = lower doses for gram +, higher dose for gram neg infection
Quinolone MOA
inhibit bacterial DNA topoisomerase IV and DNA gyrase
Do quinolones have concentration dependent activity?
Yes
Which quinolones are “respiratory”?
Levofloxacin and Moxifloxacin due to enhanced coverage of S.pneumoniae and atypical pathogens
Which quinolones have enhanced gram - activity?
ciprofloaxin and levofloxacin, also coverage against pseudomonas (can be used in combo w/ beta-lactam or as mono if susceptible)
Which quinolone cant be used for UTI?
Moxifloxacin = doesnt conc in urine
but can be used for polymicrobial infections (intra-ab), no renal adjustment req
Which quinolone is active against MRSA?
Delafloxacin
preferred if treating skin infections suspected to be caused by MRSA
Quinolone boxed warnings
Tendon inflammation/rupture
Peripheral neuropathy
CNS effects
CI of ciprofloxacin
dont take with tizanidine
Quinolone QT prolongation risk
Highest = moxi > levo > cipro
dont use in pts with known prolongation
Warnings for quinolones
Dont use kids/pregnant/breastfeeding
Hypo/Hyperglycemia
Psychiatric disturbances
photosensitivity
Quinolone side effects
N/D
HA
dizziness
SJS/TEN
Quinolone drug interactions
Antacids n other polyvalent cations = can chelate, dont take together
phosphate binders = separate by 2hrs before/after
inc effect of warfarin, diabetes drugs
Macrolide MOA
bind to 50S ribosomal subunits, inhibit RNA-dependent protein synthesis
Macrolides excellent coverage of….
atypical
used for community acquired RTI and some STI
Clarithromycin/Erythromycin CI
lovastatin n simvastatin
caution with warfarin other blood thinners
Macrolide warnings
QT prolongation
Hepatotoxicity
Macrolide SE?
GI upset (erythromycin used specifically for motility), rare but SJS/TEN
Tetracycline MOA
inhibit protein synthesis by reversibly binding to 30S ribosomal subunit
Which tetracycline has broadest indications?
Doxy - RTI, ticks, STI, mild CA-MRSA skin and VRE UTI
Tetracycline warnings
Photosensitivity
Children < 8, preg/breastfeeding = teeth/bones
** Minocycline = DILE = drug-induced lupus **
Doxycycline notes
sit atleast for 30min after, take w/ 8oz water for all tetracyclines
Tetracycline SE/Monitoring
N/V/D
monitor LFT, renal function, CBC
Tetracycline DI
Antacids n polyvalent cations separate by 2hr before or 4hrs after
SMX/TMP MOA
SMX = inhibits dihydrofolic acid formation, interfere with bacteria folic acid synthesis
TMP = inhibits dihydrogolic acid reduction, interfere with folic acid pathway
SMX/TMP CI
sulfa allergy
SMX/TMP warnings
Skin reaction = SJS/TEN, TTP
Hemolytic anemia = dont use G6PD deficiency
dont use preg unless benefit> risk
SMX/TMP side effects
photosensitivity
inc potassium
crystalluria = take w/ 8oz water
SMX/TMP drug interactions
inc INR if used w/ warfarin
risk of hyperkalemia inc if on ACE/ARB
can inc toxic effects of methotrexate
Vanco MOA
inhibit bacterial cell wall synthesis by binding to D-alanyl-D-alanine
covers gram +, including MRSA but not VRE
Vanco warnings
Oto/nephrotoxicity = caution when used with other agents
PO only used C.diff not systemic infections
Vanc infusion reaction if too fast infusion
Vanco monitoring
Renal function
Drug lvls
AUC/MIC ratio or steady state troughs
Lipoglycopeptides MOA
inhibit bacterial cell wall synthesis by binding D-alanyl-D-alanine and disrupting cell membrane/changing permeability
have concentration dependent activity
Telavancin boxed warning
Fetal risk = preg test before starting
nephrotoxicity = inc mortality CrCl < 50
Telavancin and oritavancin CI
Tela = dont use UFH same time, dont use in QT prolonged pts
Orit = dont use UFH 120hrs (5 days) after
can affect PT/INR/aPTT falsely
Daptomycin MOA
inhibits all intracellular replication processes by causing rapid depolarization
concentration dependent activity against most gram +, including MRSA n VRE, no gram - activity
Daptomycin warnings
myopathy n rhabdo
false inc INR/PT
cant use for pneumonia, inactivated by surfactant in lungs
additive muscle tox when used with statins
Daptomycin monitoring
CPK weekly (can cause inc)
Oxazolidinones MOA (Linezolid and tedizolid)
bind to 50S subunit and inhibit translation/protein synthesis
similar to vanc coverage, but also VRE
CI for Linezolid/Tedizolid
dont use within 2 weeks of MOAi
** avoid tyramine containing foods **
Warnings for Linezolid/Tedizolid
duration-related myelosuppression when used > 14 days
optic neuropathy when used > 28 days
** dont shake Linezolid suspension **
Linezolid/Tedizolid SE
dec platelets
monitor weekly CBC/visual function
Quinupristin/Dalfopristin (streptogramin) MOA
inhibits protein synthesis by binding 50S ribosomal subunit
not well tolerated, used for VRE infections
Quinupristin/Dalfopristin (streptogramin) SE/notes
** D5W only **
infusion reactions, arthralgia/myalgias, hyperbilirubinemia
Tigecycline MOA
binds to 30S ribosomal subunit n inhibits protein synthesis
broad spec against gram -/+, no activity against 3 P (pseudo/proteus/providencia)
Tigecycline boxed warning
inc risk of death, only used when other txm cant
Tigecycline Notes
dont use blood stream infections
should be yellow-orange when recon**
Polymixins generally used for….
MDR gram - infection due to risk of toxicities
Polymixin B boxed warnings
nephrotoxicity = dose dependent
neurotoxicity, can result in respiratory neuromuscular blockade
nephrotoxicity inc if used with other drugs
Colistimethate warning/notes
prodrug converted to colistin
Dose-dependent nephrotoxicity
neurotoxicity
Chloramphenicol MOA
reversibly binds 50S subunit of bacterial ribosome, inhibiting protein synthesis
Chloramphenicol Boxed warnings
Serious and fatal blood dyscrasias
Chloramphenicol Warnings
Gray syndrome w/ high serum levels
Montior CBC at baseline and Q 2 days during therapy
Clindamycin MOA
reversibly binds 50S subunit, inhibiting protein synthesis
Clindamycin boxed warning
C.diff
Clindamycin SE and notes
N/V/D
induction test (D-test) should be performed
Metronidazole MOA
cause loss of DNA structure and strand breakage, resulting in inhibition of protein synthesis
Metronidazole CI
1st trimester pregnancy
alc during or within 3 days of txm stop
Metronidazole SE
metallic taste, furry tongue, dark urine
Metronidazole DI
dont use with alc during and 3 days after stopping txm
can inc INR in pts on warfarin
Lefamulin (Xenleta) info
Avoid in preg, QT prolongation
approved for CAP
Rifaximin (Xifaxan) info
used off-label C.diff and hepatic encephalopathy
Fosfomycin info
used for uncomplicated UTI - female
1 dose regimen
Nitrofurantoin info
used for uncomplicated UTI - covers VRE/E.coli/Klebsiella
CI in CrCl < 60
dont use G6PD deficiency
SE = GI upset - take with food, brown urine,
Mupirocin nasal ointment uses
to get rid of MRSA colonization
