ESBL. antimicrobial R Flashcards
What are the 2 main categories of resistance?
- Intrinsic- normal genetic,structural, physiological state of a microbe, natural and inherited. predictable for some bacterial groups- pseudonomads R to augmentin
- Acquired- successful genetic mutation
- Acquisition of genes from other organism(s) via gene transfer - Combination of a mutation and gene transfer
Genetic changes lead to altered cellular physiology and structure
Horizontal Gene transfer- describe conjungation, transduction and transformation
conjungation- by plasmids or transposon
transduction- by bacteriophage
transformation - direct transfer of DNA between compatible species
What is the antibiotic creed MINDME
Microbilology guides therapy wherever possible
Indications should be evidence based
Narrowest spectrum required
Dosage appropriate to the site and type of infection
minimise duration of therapy
ensure monotherapy in most cases
How can B lactamases be mediated?
By plasmid or chromosome
Production/Expression
- May be secreted into the surrounding environment e.g. S. aureus
- Cell bound in most Gram negatives
* Only become effective
once antimicrobial enters the cell wall
- Inducible (e.g. S. aureus)
* Onlyproducediforganismisexposedtoab-lactamantimicrobialinitsenvironment
- Constitutive (most Gram negatives)
* Producedconstantlywhetherthereisademandornot
- Constitutive-Inducible – constant low-level production with induced production of higher levels when required/exposed to a b-lactam antimicrobial in its environment
TEM 1, 2, SHV-1 B lactamases - how can they be mediated?
where is tem 1 and 2 commonly found?
what does it mean tem 1 and 2 in terms of R and S?
All three are chromosomal OR plasmid mediated
All three have constitutive OR inducible expression
Tem 1 and 2 Present in many Gram-negative organisms (very common) - Enterobacteria (Enterobacteriaceae)
- Haemophilus influenzae
- Neisseria gonorrhoea
Resistance to 1GC (exception is cephalexin), 2GC and penicillins (including AMX, AMP)
* Susceptible to 3GC and 4GC
* Enzymes are inhibited by clavulanic acid, tazobactam, sulbactam, avibactam, vaborbactam
where is SHV1 mainly found
what is it S and R to?
Klebsiella pneumoniae but can be detected in other organisms
Confers resistance to ampicillin and 1GC (exception is cephalexin)
* Susceptible to 2GC, 3GC and 4GC
* Inhibited by clavulanic acid, tazobactam, sulbactam, avibactam, vaborbactam
R to only AMP disc= production of what, a query …
Resistance to only the ampicillin disc indicates the production of a penicillinase ? TEM1, TEM 2, SHV1
What are ESBL’s?
where were they first detected?
are they plasmid or chromosomal borne?
what are its enzymes susceptible to?
extended spectrum b-lactamases are enzymes that encode resistance to:the penicillins,cephalosporins(1GC,
2GC) including the extended-spectrum cephalosporins (3GC AND 4GC) and aztreonam
Klebsiella , Germany 1983
Plasmid borne (can be transferred to other organisms for genetic resistance)
These enzymes are susceptible to the b-lactam inhibitors:
* Clavulanic acid* Tazobactam* Sulbactam
* Avibactam* Vaborbactam* ? Durlobactam
what are some types of esbls
how is it mediated and what is it susceptible to?
which carbapenams can we use to treat them
Some ESBL’s are genetic point mutations of TEM-1 or TEM-2 and SHV-1
Other ESBLs include the CTX-M family (160+) – more common than TEM/SHV- Plasmid acquired resistance from chromosomal genes of Kluyvera species
Some OXA enzymes (usually found in GPC, AA mutation in enzyme provides ESBL)
Predominantly plasmid mediated with constitutive expression (NOT chromosomal)
* All are susceptible to Augmentin (AMC) – amoxycillin + clavulanic acid
Can also treat ESBL producing organisms with carbapenems
- The following are used in Australia (all IV)
- Meropenem (MEM)
- Ertapenem (ETP)
- Doripenem (DOR)
- Imipenem is not prescribed in Aust. – due to CSF problems
community isolates usually Susceptible to:
- Amoxycillin/Clavulanate (Augmentin)
- Cephalosporins
Resistance typically to :
- Ampicillin/Amoxycillin
Multiple antibiotic resistance is readily acquired and common in hospital isolates
- Frequently produce (_______)
Note the _____ effect (synergism) between (AMC and CTX) and (AMC and ATM)
Klebsiella pneumoniae
ESBL, keyhole effect
How do we generally detect ESBL in lab? 2 steps
how can we also test using MIC?
First: detect reduced susceptibility to Extended Spectrum b-lactams (3GC) and/or aztreonam - i.e., either completely R or a borderline zone around these disc(s) - possible resistance to CTX (a 3GC), possible resistance to aztreonam (ATM)
Second : demonstrate inhibition of resistance by an inhibitor such as clavulanic acid – seen as a “keyhole effect” with double disc methods
Can be tested using E-test double ended strips (compare MIC of antimicrobials with/without inhibitor)
- Can be tested using broth dilution in micro titre tray (compare MIC of antimicrobials with/without inhibitor)
Calculation of the number of fold difference
MIC without inhibitor divided by MIC with inhibitor = fold x difference- if greater than 8 fold increase or 3x dilutions= ESBL
How to detect ESBL with microtitre tray?
Wells containing bacterial growth have a cell pellet
* The MIC is the lowest concentration of an antibiotic that has no visible growth (no pellet), usually units are ug/mL (same for e test)
What is AMPC b lactamases?
how are they mediated?
WHat can type 1 cephalosporinases or class c cephalosporinases mediate R to, is induced and inhibited by?
clinically important cephalosporinases encoded on the chromosomes of many of the Enterobacteriaceae and a few other organisms, where they mediate resistance to cephalothin, cefazolin, cefoxitin, most penicillins, and β-lactamase inhibitor-β-lactam combinations
Chromosome OR Plasmid mediated
- Inducible expression when encoded on chromosome (IC)(ESCHAPM group)
- Constitutive expression when encoded on a plasmid (CP)
- Inducible expression encoded by a plasmid is rare
Type 1 cephalosporinases or Class C cephalosporinase
- Can mediate resistance to all b-lactams (Pc’s, 1-2-GC) except 4GC and the carbapenems (depends on organism)
- Can be induced by imipenem (and not meropenem) – hence the use of IMP discs
- Inhibited by aztreonam but not clavulanic acid, tazobactam, sulbactam, avibactam, vaborbactam
What organisms produce AMPC B lactamases? ESCHApPM
E entertobacter (E. cloacae, E. aerogenes)
S serratia marcescens
C citrobacter freundii
H hafnia alvei
A aeromonas (all species except A. sobria, A. veronii) –
designated as ‘A1’ enzyme in Aeromonas
proteus
P providencia (P. stuartii, P. rettgeri)
M morganella morganii
