Infectious Diseases - Antibiotic Resistance Flashcards
cfr gene
cfr gene = chloramphenicol/ florpenicol resistant
Seen in some staph to make resistant to LINEZOLID
VRE is most commonly faecium or faecalis?
Faecium is more commonly resistant
VRE: which genotype is most common?
In South Australia: Van B
In Eastern Australia and USA: Van A
What are the mechanisms for antibiotic resistance?
Tranduction (bacterial specific viruses transfer DNA between closely related bacteria)
Transformation (parts of DNA taken up by bacterium from external environment)
Conjugation (direct cell-cell contact between bacteria)
What are the ESKAPE organisms?
= highly resistant species
Enterococcus Faecium Staph Aureus Klebsiella pneumonia Acinetobacter baumanii Pseudomonas aeruginosa Enterobacter sp.
Which Ambler Class of Beta Lactamases are structurally unrelated to PBPs and what mineral are they dependent on?
Class A
Zinc-dependent
Class A Beta Lactamases
- examples?
- what additional therapy do they lend themselves to?
ESBLs
Carbapenemases
Penicillinases
Inhibited by clavulanate (beta lactamase inhibitors) which get preferentially hydrolised instead of antibiotics
Class B Beta Lactamases
- examples?
- inhibited by what?
Metalloenzymes
Broadest spectrum (hydrolise ALL beta lactamases except aztreonam)
Inhibited by chelating agents
Class C Beta Lactamases
- examples?
AmpC enzymes which preferentially hydrolyse cephalosporins and are NOT inhibited by clavulanate
What are ESCAPPM Organisms?
Chromosomally mediated beta lactamases:
Enterobacter sp Serratia sp Citrobacter sp Acinetobacter sp Pseudomonas aeruginosa Proteus vulgaris Morganella morganii
Which organisms have ESBL?
How do you treat them?
E coli and Klebsiella most commonly
(also in Enterobacter and Acinetobacter)
Treat with meropenem, irtapenem and cotrimoxazole
What does NDM-1 do?
How do you treat?
Encodes carbapenemases
In klebsiella and E coli
Treat with polymyxins and tigecycline
Risk factors for NDM-1 organism?
Travel
Hospitalisations
Puddles and tap water
Sweedish backpackers
A question mentions sweedish backpackers and puddles…what antibiotic resistance mechanism do you suspect?
NDM-1
What is KPC antibiotic resistance?
KPC encodes a carbapenemase produced by Klebsiella
Gene is blaKPC
Variable resistance to colistin
What gene encodes KPC?
blaKPC
What is GelE antibiotic resistance mechanism?
E faecalis produces metalloproteinase GelE which degrades E cadherin.
Some bacteria are resistant via altered binding sites. Describe these four mechanisms
1) Altered ribosomal target site
ie: resistance to streptomycin (30s)
resistance to erythromycin (50s)
cfr gene (chloramphenicol/florpenicol resistance) in some staph which make them resistant to linezolid
2) Altered cell wall precursor targets
ie: VRE
3) Altered target enzymes
ie: altered PBPs in penicillin resistant strep pneumonia
4) Altered protection of target sites
How does VRE make antibiotic resistance?
VRE (mainly Enterococcus faecium, not faecalis)
substitutes D-lac for D-alanine in lipid 11
Other forms replace D-ala with D-serine which reduces vancomycin efficacy
How is VRE resistance obtained by bacteria?
Plasmid or transposins
In SA what type of VRE do we have?
Which is more common in Eastern states?
Usually Van-B type of VRE in SA
But most commonly in Eastern states and USA is Van-A
Relationship between Van A VRE and teicoplanin?
Van A is ALWAYS resistant to teicoplanin, and is induced by glycopeptides like teicoplanin
How do we treat VRE?
Treat with amoxicillin (faecalis often sensitive, NOT faecium)
Linezolid Teicoplanin (but ONLY if Van B) Synercid (ONLY faecium) Daptomycin Fosfomycin
What is optrA gene?
optrA gene found in E faecalis and E faecium results in OXAZOLIDIONE resistance
What is NORSA?
Community-acquired, non-multiresistant oxacillin-resistant Staphylococcus aureus (NORSA)
Causes necrotizing pneumonia and skin infections
- usually sensitive to clindamycin, bactrim, macrolides and gentamicin
What is the mechanism by which MRSA is resistant?
MRSA is due to mecA gene encoding PBP2a protein with low affinity for beta lactam antibiotics
What is VISA MRSA?
How do you treat it?
When is it more commonly encountered?
MRSA with reduced vancomycin sensitivity
Associated with thickened cell wall containing vanc-binding dipeptides which detain the drug (so more targets for D-ala-D-ala)
Treat with linezolid or rifampicin
Especially in dialysis or Left Ventricular Devices
What are the anti-MRSA cephalosporins?
Ceftaroline and Ceftobiprole
What are the new MRSA treatments?
DALBAVANCIN: noninferior to vanc followed by linezolid
TELAVANCIN
TEDIZOLID = oxazolidinone with less haem adverse effects
What is CRE?
How do you treat?
= carbapenam resistant enterobacteriae
ie: E coli, klebsiella, salmonella, shigella, enterobacter
Treat with colistin, tigecycline or fosfomycin
What creates colistin resistance?
mcr-1 gene (plasmid mediated) in enterobacteriae
adds phosphoethanolamine to lipid A in colistin
What is most commonly carbepenem resistant?
Acinetobacter baumanii
What mechanisms create ANTIBIOTIC RESISTANCE via DECREASED PERMEABILITY?
Outer membrane permeability:
- ie mutations causing loss of porins
Inner membrane permeability
- ie aminoglycoside resistance
What antibiotics are susceptible to ANTIBIOTIC RESISTANCE via ACTIVE EFFLUX?
Linezolid
- natural lack of activity of linezolid against gram negatives is due to efflux pump
Tetracyclines
- resistance in gram negatives due to efflux of tetracyclines
Macrolides and Streptogramins
- in some strains of s pneumonia, strep pyogenes, staph aureus and strep epidermidis
Beta lactams
- in pseudomonas
Fluoroquinolones
- in enteric bacteria and staph
What is the c diff hypervirulent strain?
B1/NAP1/027 is resistant to fluoroquinolones
What is GYR mutation?
GYR mutation in E coli resistant to cipro
