Weeks 1 & 2: Antibiotics Flashcards
do positive cultures indicate an infection?
no, not sole criteria for diagnosing an infection. could be contamination (improper site prep). colonization (bacteria/fungus present but not causing active disease)
what other things should you think about regarding an infection?
-related symptoms. Vital Signs: fever, hypotension. Labs: leukocytosis, leukopenia. Imagine: CXR, CT
what do you often see colonized, but no infection?
candida
what color corresponds to what type of bacteria on Gram stain?
purple: Gram Positive. pink: Gram negative
what does aerobic mean?
requires O2 for growth
what does cocci mean?
sphere
example of aerobic gram + cocci clusters, coagulase +
S. aureus (MRSA, MSSA)
example of aerobic gram + cocci clusters, coagulase -
S. epidermidis, S. haemolyticus, S. lugdunensis
what is coagulase?
it’s an enzyme
example of aerobic gram positive diplococcus quellung +
S. pneumoniae
example of aerobic gram positive cocci chains, PNA FISH +
E. faecium, E. faecalis
example of aerobic gram positive cocci chains, PNA FISH -
Streptoccus app.
what is PNA FISH
molecular assay
aerobic gram positive large bacilli
Bacillus spp
aerobic gram positive cocco bacillus
listeria monocytogenes, Lactobacillus spp.
aerobic gram positive bacilli, small pleomorphic
Corynebacterium spp.
aerobic gram positive bacilli branching filaments
Nocardia spp. Streptomyces spp.
anaerobic gram positive bacilli, large
Clostridium spp.
anaerobic gram positive bacilli, small, pleomorphic
P. acnes, Actinomyces spp.
anaerobic gram positive cocci
Peptostreptococcus spp.
where is coliform bacteria found?
in the gut/colon
Aerobic gram negative bacillus lactose fermenter
Escherichia coli, Klebsiella spp, Enterobacter spp., Serratia spp., Citrobacter spp., Proteus spp.,
aerobic gram negative bacillus non lactose fermenter, oxidase +
Pseudomonas spp. Aeromonas spp. Vibrio spp.
aerobic gram negative bacillus non lactose fermenter oxidase -
Acinetobacter spp. Stenotrophomonas spp. Burkholderia spp. Shigella spp. Salmonella spp.
aerobic gram negative diplococci
N. meningitis, N. gonorrhoeae, Moraxella catarrhalis
aerobic gram negative cocci-bacillus
Haemophilus influenzae, Acinetobacter spp., Eikenella, Kingella, Aggregatibacter, Cardiobacterium
anaerobic gram negative bacilli
Bacteroides spp., Fusobacterium spp., Prevotella spp.
anaerobic gram negative cocci
veillonella spp.
what is the qualitative way for sensitivity testing?
disk diffusion. it does not provide MIC, it only labels sample as susceptible or resistant
what is the quantitative way for sensitivity testing
minimum inhibitory concentration (MIC) method. performed by utilizing an automated system (BD Phoenix)
what is MIC?
the lowest concentration of antibiotic which inhibits the growth of the bacterium
how does JHH determine susceptibilities?
microbiology lab uses standard reference methods for determining susceptibilities (CLSI)
what does resistant mean?
growth not inhibited by usually achievable concentrations at normal doses
what does intermediate mean re: antibiotics
antibiotic level can usually be obtained in the tissue or blood, but response may be diminished
what does susceptible mean?
strain can be treated with antibiotic at recommended doses and schedules. useful to know when treating an organism in an area that is difficult to penetrate (CSF, osteomyelitis)
what is time dependent killing
how long you have to maintain level above MIC. (TIME > MIC).
what antibiotics work via time dependent killing
b-lactams, macrolides, clindamycin, glycopeptides, tetracyclines, oxazolidones
what is concentration dependent killing
Cmax/MIC or AUC/MIC. the max concentration you can achieve in the blood.
what antibiotics work via concentration dependent killing
aminoglycosides, fluoroquinolones, daptomycin, colistin
what is synergy
marked increased killing
example of synergy?
beta lactam + aminoglycoside
what is additive
increased killing
example of additive?
beta lactam + fluoroquinolone
what is antagonism
decreased killing
example of antagonism
double beta lactam
what is indifference
no difference in killing
example of indifferences
pip/tazo+metronidazole. both kill the same bacteria.
what are beta lactams
penicillins (IV/PO), cephalosporins (IV/PO), carbapenems (IV), monobactam (IV)
what is the mechanism of action for beta lactams
interferes w/ cell wall synthesis by preventing cross linking of peptidoglycan
spectrum of activity for natural PCN
non-PCNase producing gram positives (streptococci, staphylococcus aureus, Coagulase negative staph, enterococcus). Oral anaerobes (some clostridium) actinomycetes. T. palladum (syphilis)
spectrum of activity for PCNase resistant PCN
enhanced activity against staph aureus (MRSA). decreased activity against streptococcus. lacks activity against enterococcus
spectrum of activity for amino PCNs
same as natural PCN. enhance activity against listeria and enterococcus. Enhanced activity against listeria and enterococcus. enhanced activity against gram-negatives ( E. coli, proteus, haemophilus)
ureidopenicillin, spectrum of activity
enhanced gram negative activity ( E. coli, Pseudomonas, Enterobacter, Proteus, Providencia) decreased activity against enterococcus)
spectrum of activity for PCN + beta lactamase inhibitor
enhanced activity against staph aureus. Activity against Haemophilus, Moraxella, E. Coli. Klebisella and enterobacteriacae. Piperacillin-tazobactam is only one w/ activity against pseudomonas
which PCN + beta lactase has activity against Pseudomonas?
piperacillin-tazobactam.
reaction to PCN
hypersensitivity reactions, interstitial nephritis, gastrointestinal (n/v/d, pseudomembranous colitis) hematologic (anemia, neutropenia, thrombocytopenia)
which PCN has hepatotoxicity?
oxacillin, increase LFTs. less w/ nafcililin
what PCN causes electrolyte abnormalities?
PCN G since it has to be bound to a salt (Na or K)
do PCN need to be renal dosed?
yes, they are all renal cleared and need to be adjusted for renal insufficiency
which PCN doesn’t need to be renally dosed
dicloxacillin, oxacillin
how many generations of cephalosporins?
5!
spectrum of activity of 1st generation cephlasporin, cefazolin
MSSA, streptococci, limited gram negative.
spectrum of activity for 2nd generation cephalosporins, cefoxitin/cefuroxime, cefotetan?
MSSA, streptococci, Haemophilus, Moraxella, Neisseria spp.
spectrum of activity for 3rd generation cephalosporin, ceftriaxone?
decreased activity against MSSA, streptococci, enhanced gram negative activity (E.coli, Klbsiella, Proteus, Citrobacter, Serratia)
what does ceftazidime work against?
pseudomonas
spectrum of activity for 4th generation cephalosporins, cefepime
MSSA, streptococci, pseudomonas
what is 5th generation cephalosporin good against?
skin/soft tissue infections, CAP
spectrum of activity of 5th generation cephalosporin, ceftaroline.
streptococci. MRSA/MSSA
clinical use of 1st generation cephalosporins?
surgical prophylaxis, skin/soft tissue infections, UTIs
clinical use of 2nd generation cephalosporins
surgical prophylaxis
clinical use of 3rd generation cephalosporins
CAP, meningitis, endocarditis, STDs
clinical use of 4th generation cephalosporins
neutropenic fever, UTIs HAP, VAP, Meningitis, broad spectrum
clinical use of 5th generation cephalosporins
skin & soft tissue infections, CAP
how are cephalosporins elminated?
renally
do you need to dose adjust cephalosporins for renal insufficiency
yes! except ceftriaxone
how does food change bioavailability of cephalosporins
bioavailability usually enhanced w/ food d/t the acid production
are first generation cephalosporins good for meningitis?
no b/c they don’t cross the blood brain barrier.
safety concerns for cephalosporins
generally well tolerated, common: hypersensitivity, GI upset, Rare: neutropenia, thrombocytopenia, interstitial nephritis.
examples of carbapenems
meropenem, ertapenem, imipenem/cilastatin, doripenem.
spectrum of activity for carbapenems
MSSA, strep pneumoniae, many gram-negative rods (including multi-drug resistant gram negatives). anaerobes (B. fragilis). does not cover MRSA, VRE
ertapenem does not cover….
pseudomonas spp. or acinetobacter spp.
characteristics of imipenem
hydrolyzed by renal dihydropeptiase to a toxic metabolite. that’s why cilastatian is included b/c it inhibits dihydropeptiase. need to dose adjust for renal insufficiency.
safety of carbapenems
generally well tolerated. Rare: seizures, neutropenia, thrombocytopenia, interstitial nephritis.
spectrum of activity for monobactams (ex: aztreonam)
gram negative aeroobes, fair coverage for Pseudomonas, NO COVERAGE for gram positive or anaerobic.
what’s good about aztreonam (a monobactam, part of the beta lactam family)
weakly immunogenic so can be used in patients w/ a true PCN allergy
clinical use of aztreonam?
alternative empiric therapy for gram negative coverage.
what family is colistin part of
polymixin E antibiotic
how many forms is colistin available in?
2 forms: colistin sulfate (topical) & Colistimethate sodium (IV)
mechanism of action of Colistin?
disrupts gram negative bacteria outer membrane by displacing divalent cations (Mg, Ca) from membrane lipids
spectrum of activity for Colistin?
only gram negative bacilli: MDR Pseudomonas, Acinetobacter, E Coli, Klebsiella, Enterobacter
what does Colistin not protect against?
Gram positive and gram negative cocci are naturally resistant
what are resistance issues for Colistin?
-has been reported worldwide to P. aeruginosa, A baumanni, K pneumonia w & w/o previous exposure to Colistin -heteroresistance reported as well -resistence has been linked to inadequate dosing -has been suggested to be relative to environment, low Mg concentrations, low pH, high iron concentrations
mechanism of action for colistin?
reduced binding affinity - not fully understood.
clinical use for colistin
Salvage therapy for MDR gram negative organisms.
safety issues of colistin
neuro: dizziness, paresthesia, vertigo, confusion, visual disturbances, ataxia renal: ATN reported in 20-25% w/ older formulation, but lower in recent reports
how can you tell if colistin is dosed high enough?
ataxia. neuropathy can develop that is not reversable
mechanism of action of oxazolidinones
inhibits protein synthesis by inhibiting initiation complex 50s rRNA and 30S
what family does linezolid belong?
oxazolidinones
what is the spectrum for oxazolidinones
E. faecalis, E. faecium (including VRE), S. aureus (including MRSA), coagulase-negative staphylococci (MRSE), S. pneumoniae, Nocardia, Mycobacteria (TB and other Non TB microbacterimum) not active against gram negative organisms
clinical use of linezolid
VRE infections, MRSA pneumonia in patients failing vancomycin
safety of linezolid
reversible bone marrow suppression; thrombocytopenia & leukopenia - resolves w/ discontinuation reversible optic neuritis & irreversible sensory motor polyneuropathy (with prolonged therapy > 28 days) Serotonin syndrome when administered w/ serotonergic agents (controversial)
which is better, vancomycin or linezolid
in the long term it doesn’t matter
dosing guidelines for vancomycin
slowly bactericidal (compared to beta lactams
when do you get a trough for vancomycin?
prior to 4th dose.
what should trough levels of vancomycin be?
15-20 mg/L (assuming MIC < 1 mg/L)
loading dose of vancomycin
25-30 mg/kg
when do you see nephrotoxicity with vancomyocin?
when co-administered w/ aminoglycosied
when is vancomycin resistane?
when trough levels are < 10
mechanism of action for clindamycin
inhibiting bacterial protein synthesis by binding to 50s ribosomal subunit
absorption & CSF penetration for clindamycin
good oral absorption (90%) but poor CSF penetration
spectrum of clindamycin
gram positive aerobes & anaerobes including community acquired MRSA, MSSA w exception of Enterococcus
many gram negative anaerobes
clinical use of clindamycin
provides anaerobic coverage for intra abdominal or pulmonary infections
skin & soft tissue community acquired MRSA, MSSA strep
necrotizing fascitis group A strep
alternative PCP, toxoplasmosis, malaria
used for dental prophylaxis
safety concerns for clindamycin
c. difficile pseudomembranous colitis / GI issues: N/V
incidence of C difficile is greater with PO vs IV
mechanism of action for fluoroquinolones
inhibit bacterial topoisomerases IV and DNA gyrase to inhibit DNA replecation & bacterial growth
examples of fluoroquinolones
norfloxacin, ciprofloxacin, moxifloxacin, ofloxacin, levofloxacin, gemifloxacin
what causes the difference in the fluoroquinolones?
substituions at positions on the core quinolong structure affects type and thus specrtum of activity
spectrum of activity for fluoroquinolones
- gram negatives including Enterbactericeae spp.
- pseudomonas - use ciprofloxacin & levoflxacin only
- gram positives (Streptococcus - S. pneumo & S. viridans) Staphylococcal spp.
- moxifloxacin, levofloxacin, gemifloxacin
- ciprofloxacin limited activity f/t resistance
- atypical organism
- anaerobes, tb, mycobacteria
clinical use of fluoroquinolones
- second line agent in patients with peicillin allergies
- CAP & URI - avoid ciprofloxacin d/t unreliable activity against gram positive organisms except VAP/HAP when used in combo w/ gram positive agent
- UTIs/prostatitis
- avoid moxifloxacin d/t poor renal penetration and inadequat urinary concentration
- intra abdominal infections
- infectious diarrhea
- second line agent for treatment of pulmonary TB
safety concerns for fluoroquinolones
- GI upset
- CNS: HA, insomnia, dizzines
- photosensitivity
- prolonged QT interval
- glucose dysregulation
- pseudomembranous colitis (C difficile)
- ******connetive tissue damage
- black box warning for tendon injury
- teratogen/impaired cartilage development - have to stop if have cartilage injury while one it & cant receive it again
- interstitial nephritis - rare
mechanism of action for macrolides
inhibit RNA dependent protein synthesis by reversibly binding to 50S ribosomal subunit
examples of macrolides
azithromycin, clarithrmycin, erythromycin
spectrum of activity for macrolides
gram postive MSSA, S. pneumoniae, S. pyogenes
gram negatives: H. influenzae, M. catarrhalis, N gonorrhoeae
atypicals - mycoplasma
non TB mycobacteria
H. pyloria
emergence of resistance limits macroline use
possesses anti-inflammatory properties - good for CF patients, lung transplant recipients
clinical use of macrolides - clarithromycin & azithromycin
community aquired pneumonia
COPD exacerbations
pharyngitis, tonsillitis, acute otitis media, acute sinusitis
myobacterium avium complex - first line
lyme disease (early)
clinical use of macrolides - erythromycin & azithromycin
chlamydia trachomatis infections (cervicitis, urethritis)
infectious diarrhea (salmonella typhi, shigella)
campylobacter jejuni assocaited diarrhea - first line
what to use for helicobacter pylori infection?
clarithromycin
what antibiotic can you use as a motility agent (hint it’s a macrolide)
erythromycin
name a tetracycline?
tigecycline
what is tigecycline?
a derivative of minocycline
what is good/bad about tigecycline?
low concentrations in the blood - so don’t use for bactermia
it goes into the tissues
spectrum for tigecycline?
gram positive organisms (MRSA, MSSA, VRE)
gram negative organisms (Citrobacter freundii, E. coli, Klebsiella spp, acinetobacter baumanii)
anaerobes
DOES NOT COVER: pseudomonas spp., proteus spp., providentia spp. (the three P’s)
clinical use of tigecycline
intra-abdominal infections in patients with contraindications to both beta-lactams and fluoroquinolones
infections d/t MDR gram negative organisms including acinetobacter spp. (MDR aAb) & Stenotrophomonas maltophilia, non-TB mycobacteria
safety issues w/ tigecycline
nausea, vomiting, diarrhea, pacreatitis
what are considerations for antibiotics?
host factors:
age, body weight, volume of distribution, renal function (CVVHD, HD), allergy history
infection factors:
location of infection, organisms (gram positive vs gram negative vs fungal vs other), resistance profile, mechanisms of action
antibiotic factors:
frequency of administration, time dependent killing, concentration dependent killing, tissue penetration, renally cleared vs hepatic, drug/drug interactions
information on host factors for antibiotics
use the Cockcroft-Gault equation
weight
volume of distribution: higher volume of distribution in critically ill patient
Allergy history: IgE mediated vs non-IgE vs ‘intolerance’
use skin testing for IgE mediated PCN allergy & possibly desentizie
infection factors for antibiotics
location of infection
organism: gram positive vs. gram negative vs. fungal vs viral
resistance profile: MRSA (VISA, VRSA). VRE (liver failure/transplant), MDR GNR (Acinetobacter, Klebsiella, Pseudomonas)
Mechanism of resistance: Gene vs plasmid (transmissibility) & ESBL, NDM-1 (carbapenamase producer)
CNS ICU infections
meningitis/encephalitis
shunt infections
post op infections
respiratory icu infections
pneumona (CAP, VAP, HCAP), viral, fungal
transplant
cardiovascular icu infections
endocarditis, vascular graft infections, device infections (ICD, LVAD)
transplant
GI ICU infections
spontaneous (perforation, rupture, peritonitis)
post op
c. difficile colitis
transplant
genitourinary ICU infections
urosepsis
pyelonephritis
transplant
musculoskeletal ICU infections
necrotizing fascitis
time dependent antibiotics
beta lactams
carbapenems
linezolid
erythromycin
clarithromycin
lincosamides
concentration dependent antibiotics
aminoglycosides
metronidazole
fluroquinolones
telithromycin
daptomycin
quinupristin/dalfopristin
concentration dependent with time dependence
fluroquinolones
aminoglycoside
azithromycin
tetracyclines
glycopeptides
tigecycline
quinupristin/dalfopristin
linezolid
antibiotics with good tissue penetration
CNS infection: PCN, 3rd generation cephalosporin, linezolid, flagyl
Pulmonary infections: beta lactams, fluoroquinolones, linezolid
GU infections: kidney: fluoroquinolones, 3rd generation cephalosporins; bladder: fluroquinolones, cephalosporins (IV), aminoglycosides
antibiotics with poor tissue penetration
CNS infection: vancomycin, PCN+Beta lactamase inhibitor, 1st generations cephalosporin, aminoglycosides
pulmonary infections: aminoglycosides
GU infection: moxifloxacin (not adequate urine levels)
