LAB 15 -Antimicrobials Flashcards
CLSI warnings - the following combos may appear active in vitro but are not effective clinically and should NOT be reported as susceptible
Salmonella, Shigella sp = 1st and 2nd gen cephalosporins, cephamycins, and aminoglycosides
oxacillin-resistant Staph sp. = penicillins, b lactam/ b lactamase inhibitor combinations, anti-staphylococcal cephems, and carbapenems
Enterococcus sp = aminoglycosides (except high concentrations), cephalosporins, clindamycin, and SXT
amikacin
aminoglycoside
vancomycin
glycopeptides
naladixic acid
quinolones
erythromycin
macrolides
(only GP)
cefuroxime
cephalosporins
Ciprofloxacin
quinolones
Meropenem
Carbapenems
Co-trimoxazole
sulfonamides
cephalothin
cephalossporin
gentamicin
aminogycside
tobramycin
aminoglycoside
ampicillin
penicillins
clindamycin
lincosamides
imipenem
carbapenem
cell wall synthesis antimicrobials
beta lactams
vancomycin
protein synthesis antimicrobials
aminoglycosides
tetracylines
chloramphenicol
macrolides
lincosamides
oxazolidinones
streptogramins
DNA and RNA synthesis antimicrobials
fluoroquinolones
rifamycins (RNA)
metronidazole (DNA)
metabolic pathways antimicrobials
sulfonamides
trimethoprim
nitrofurantoin
cell membrane and integrity antimicrobials
polymyxin B
Colistin
Daptomycin
beta-lactams
bind th enzyme inhibiting transpeptidation and inhibit cell wall synthesis (interferes with peptidoglycan cross-linking
vancomycin
- a glycopeptide
- bind the end of the peptidoglycan interfering with transpeptidation, inhibition of cell wall synthesis and growth
how do sulfonamides and trimethoprim work together?
inhibit folic acid production at two different spots on the pathway
how does Nitrofurantoin inhibit metabolic pathways?
it binds to ribosomal proteins and rRNA to affect the folic acid pathway
beta lactams “rules”
- penicillins = BLNGP and GNDC; unable to penetrate outer mem of most gnb
- cephalosporins = diff generations have diff spectrums
- carbapenems = very broad spectrum to cover many GP and GN organisms
- monobactams = effective against GN other than strict anaerobes
the different beta lactam antibiotics differ by …
the structures that are linked to b-lactam ring
glycopeptides rules
- aeorbic GP
- similar to BLs
- since targeting cell wall through peptidoglycan, no human toxicity
- do not pass into CSF, cannot be taken orally
- saved for serious infections
- GN resistant bc OM is impermeable to large size of molecules
aminoglycosides rules
mostly aerobic and facultative GNB
transported into bacteria using oxidative metabolism so cant use with anaerobes or organisms that can only metabolize fermentatively (NO STREP)
- Enterobacteriaecea and P. aeruginosa
- serious infections with GP organisms but will be paired with another drug
- Enterococcus at high concentration (Gent Synergy)
tetracyclines rules
broad spectrum, toxic
- GN and GP
- toxic toward developing teeth and bones
- NOT for children
macrolides rules
GP only; erythromycin commonly tested
- tested for GP only (erythromycin)
- may be used for some ‘special’ GN like Neisseria, Bordetella, Chlamydia
lincosamide rules
- clindamycin = similar to eryhtro + GN anaerobes
- often used if anaerobe infection/co-infection
- associated with C.diff infection due to activity against GN anaerobes so clear out large amounts of gut flora
antibiotic associated with C. diff
lincosamide
(clindamycin)
quinolones rules
wide rang of aerobic and facultative anaerobes
- includes fluoroquinolones (cipro, levofloxacin, etc.)
- affects DNA replication
- can be taken orally
- concentrates well in urine
sulfonamides/SXT
- work at different points of folate pathway; often paired for better killing power
- toxicity not a concern bc we ingest folate
- common for UTIs as it concentrates in urine
- can be taken orally
VRE drug
linezolid
MRSA gene
MecA codes for PBP change (PBP2A and PBP2A’)
MRSA test
cefox disc
may require oxacillin Etest if vitek MIC is low
T or F. When screening for MRSA, patients not treated
T!
nose and groin to chromagar
just a carrier; not causing infection
positive pts put under precautions by infection control so doesn’t spread
why is cefoxitin used to ID clox resistance?
better inducer of MecA resistance than oxacillin or other
hetero population is common with this
MRSA
can make ID difficult
some colonies S and some R
incubating cefox testing at 35C can help enhance MecA resistance
VRE gene
VanA and VanB (passed on by plasmids; not VanC though!)
alteration of vancomycin binding site
VRE screening
rectal on VRE chromagar
VRE clinical
any site; urine most common
VRE clinical
any site; urine most common
how to test for VRE
Vancomycin Etest for confirmation
highest MIC
256 ug/mL
VISA/VRSA
VISA = thickening of cell wall
VRSA = VanA from VRE (keep MRSA and VRE patients away)
why do we carefully monitor Vancomycin results on MRSA
in case of VRSA emergencw
how to test for VISA/VRSA
vanc E test to confim MIC as automated susceptibility testing does not accurately pick up resistance in Staph
beta-lactamase
- H. influenzae resistant to ampicillin
- class A - basic penicillinase (TEM-1)
- enzyme that hydrolyzes balctam ring
- Haemophilus, Neisseria, M. catarhalis, B. fragilis
- cefinase or nitrocefin as constitutive enzyme
b lactamase class A
basic and weak
only R to amp, amox, penicillin
other penicillins (clox, ox, meth) not affected
NOTE: why we treat clox for S. aureus bc usually BLP
drug of choice for H. influenzae
ampicillin
but if BLP … can’t use it so we don’t even test amp for BLP H. influenza
clavulanic acid
beta lactamase inhibitor; ‘suicide inhibitor’
- substrate so enzyme is used up.. leaving antimicrobial to be effective against the organism
- AMOX (AMC) is tested with clavulanate; BLP amp will be reported as R so test AMC instead
ESBL
- E. coli R to 3rd gen cephalosporins
- class A - basic penicilllinase
- extended-spectrum = effective on more rings
- plasmid-mediated = IC concern
- ESBL disc test
- concern in Enterobacteriaceae
- we don’t screen but if any 3rd gen cephalosporin comes up R, then testing required
ESBL disc test… why not nitrocefin?
this is not constitutive, it’s inducible!! must be growing in presence of 3rd gen to produce enzyme
EXBL disc test
paired discs used
one disc has 3rd gen cephalosporin (Cepofoxime, Cefotaxime, Ceftazidime)
AND a 3rd gen cephalosporin with clavulanic acid
5mm diff between two discs
MBL
- class B - requies zinc for action; ‘metallo’
- found in GNB - Enterobacteriaceae, P. aeruginosa, Acinetobacter
- R to all b-lactams including carbapenems
- three main types = VIM, IMP, NDM
screening for MBL
chromagar (CRE) used sparingly when requested
any site resistant to 3d gen cephalosporin and carbapenem
require further testing
MBL??
how to test for MBL
MAST discs; b lactamase inhibitor has no use here
KESC group
Klebsiella, Enterobacter, Serratia, Citrobacter
KESC group
Klebsiella, Enterobacter, Serratia, Citrobacter
MBL ID
double disc test
- one disc with mero
- one disc with mero + MBL inhibitor (dipicolinic acid or DPA)
if zon > or = 5mm = MBL!
DPA
MBL inhibitor; helps with ID
GNB with carbapenem reisstance, which is only antibiotic sens
colistin
colistin resistance
- MCR-1 mobilized colistin resistance
- modified target site
- plasmid-mediated so IC Concern
- Enterobacteriaceae often from livestock/food animals
how to identify colistin resistance
PCR to ID MCR-1 gene
intrinsically resistance to colistin
PMP group and Serratia = does not need further ID of MC-1
ICR
inducible clindamycin resistance
- some S. aureus resistant to clinda, not all inducible
- erm gene = constitutive and inducible resistance
- may test sens in vitro but treatment fails in vivo
ICR organisms
S. aureus, B-hem Strep, anaerobic GPC
how to test ICR
if Erythromycin I/R and Clinda = S = further testing necessary =Double Disc test or D test (2 discs specific distance and incubated overnight)
- if flattening = resistance induced; clinda R
- if circular zone = negative = clinda S
D test
used to identify inducible resistance but does not mean pt has to b on both antibiotics for clinda to be R
organism will quickly demonstrate resistance in patient when exposed to clinda for treatment alone
