Multidrug resistant Enterobacteriaeceae as a serious noscomial threat Flashcards
Discuss the nosocomial threat of enterobacteriaceae
70% of all UTIs
40% pneumoniase
20% of all bactaraemias
10% of endocarditis
WHat is the most common nosocomial infection in the UK
E.Coli –> most are UTIs plus 15,000 Bactaraemias per year and 30% of all Surgical site infections!
What is not far behind E.Coli in terms of nosocomial infections
Klebsiella Pneumonia –> less common in faeces but it is more resistant to antibiotics. Can also cause pneumonias in ICUs but isnt as important as the NFGNBs.
Name some imporant less virulent enterbacteriaceae for nosocomial infections
Citrobacter and Enterbacter
Cause opportunistic infections particulalry in children/neonates
Meningitis adn brain absceses
BUt causing an increasing number of bactaraemias in the UK
What is the definition of ESBLs
A bush class 2e enzyme Molecular class A Hydrolyse 3rd generation cephalosporins BUT not cephamycins and are sensitive to clavulanic acid
What used to be the most predominant cause of ESBLs and what is it now
Used to be TEM and SHV
Now thought to be due to CTX-M
Where has CTX-M originiated from
From Kluvera species. Kluvera is an enteric bacteria hence has spread to E. Coli easily
What species are ESBLs most common in
Klebsiella, K. Pneumoniae and E. Coli
Describe the mobilisation of CTX-M
It is a composite transposon that uses insertion sequences to mobilise the chromosomal gene
The insertion sequence needs only a week match between IRR and IRL
Hence the transposon needs just a single copy of insertion sequence element to mobilise as the trasnpose enzyme detects the IRL but is very unspecific for IRR
What IS and transposon has been seen in plasmics for CTX-M
IS26 insertion into ISEcp1B
What CTX is predominant in humans and animasl
CTX-M15 humans
CTX-M14 in animals
Are AmpC Beta lactamsases ESBLS
NO
What is the definition of an AmpC Beta lactamses
Bush Class I Enzymes
Molecular class C enzymes
Hydrolyse all penicillins, 3rd generation cephalosporins AND cephamycins and Monobactams. Insensitive to clavulanic acid!
What are AmpC Beta lactamases still susceptible to
4th generation cephalosporins
ALSO the newer beta-lactamse inhibitors of avibactam and vaborbactam have inhibitory activity against them
How can E.Coli get carbapenemase resistance
Upregulation of Amp C
Normally AmpC is expressed at low levels in E. Coli due to a weak promoter and an attenuator HOWEVER mutations in either of them can increase. Need mutations in both to get high level resistance
Describe inducible AmpC beta lactamases and how they arose
The increasing use of cephalosporins fuelled a rise in inducible, chromosomally encoded AmpC i.e. Citrobacter and enterobacter!
Selection of thes AmpC hyperproducing mutatns of citrobacter and enterbacter can result in resistanct
How did AmpC mobilise
Mobilised onto plasmids from ACromonas and Enterbacteriaeceae species
Thought to be via ISECp, the same as CTX-M
Now present in Non-AmpC producers e.g. Salmonella and Klebsiella and also low level AmpC Producers e.g. E. COli
What is MDR
Resistance to at least 3 entirely different calsses of drugs!
What organisms do MDR plasmids generally occur in
Mainly in enterbacteriaceae –> mainly linekd to complex class I Integraons e.g. carrying ESBL, Qnr and aminohlycoside resistance genes
Describe MDR ESBL plasmids and complex class I integrons
They are large plasmids carrying multple resistance mechanisms
Also carry resistance to things other than antibitoics e.g. heavy metals sch as silver
What is method of produc range resistance inetnerbacteria
Efflux pumps e.g. AcrAB-TolC pump
The overproduction of what pump in enterbacteriaceae conveys resistance to fluorquinolones
AcrAB-TolC –> also gives protection against other antimicrobials dies and disinfectants
In other bacteria e.g. Klebsiella it also gives resistance against tetracyclines
What usually controls the expression of AcrAB-TolC
AcrR represses it –> but can be activated by point mutations or insertional activation with an IS element or a binding site mutations
What else can also causes AcrAB-TolC overproduction
MarA –> an acivator of acrAB Expression –> however MarR usually regulates MarA level –> mutation in MarR can activate it!
