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Antibiotic resistance
Lecture 16
26
Pharmacology
Professional
03/07/2013

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Term
What are the stages of S. aureus colonization?
Definition
Intermittent and long term
Decolonization: mupirocin and chlorhexidine body wash
**Colonization leads to infections, esp in the immunocompromised: diabetes, IVDU, dialysis, surgery, HIV
Term
How is S. aureus transmitted?
Definition
- hands of healthcare workers
- Outbreaks: a single carrier or environment
- Person to person transmission occurs
Term
What is the agr gene?
Definition
Controls virulence in S. aureus. 4 groups:
- 1: HA-MRSA
- 2: VISA
- 3: CA-MRSA
- 4: exfoliatin-producing strain
Term
What toxins are expressed by S. aureus?
Definition
- Alpha toxin
- Beta toxin
- Enterotoxin (A-K) - causes toxic shock syndrome toxin (TSST-1)
- Virulence factor panton-valentine Leukocidin (PVL) - seen in CA-MRSA
Term
What is "classic" MRSA?
Definition
HA-MRSA. But it has now migrated to community
**At risk: in hospital, nursing home, surgery, dialysis, IVDU, previous antibiotics, underlying conditions
Term
What is mecA?
Definition
A gene on S. aureus that encodes for resistance on PBP2a
**Alters PBP2 to 2a - loss of affinity for methicillin
Term
What SCCmec genes encode for HA-MRSA?
Definition
I - lacks other resistant genes
II - multiple non-beta lactam resistance
III - associated w/ MDR
Term
What SCCmec genes are associated with CA-MRSA?
Definition
IV - Resistance to beta lactams
V - lacks other abx resistant genes
Term
How does a bacteria become resistant to vancomycin?
Definition
Cell wall is thickened
**MIC breakpoint has gone DOWN across the board
Term
What is hVISA?
Definition
Heteroresistant Vanc-Intermediate S. aureus - susceptible but contain populations which are resistant. Associated w/ tx failure and reversion
**VISA mortality > MRSA
Term
What is VISA?
Definition
Vanc-Intermediate S. aureus. Has a thicker cell wall/less PG cross links. Incr in false D-ala binding sites - Decr in PBPs.
**MIC - 4-8
Term
What is VRSA?
Definition
Conjugative transfer of VanA from enterococcus to S. aureus - in vitro, not clinically.
Term
Who is at risk for CA-MRSA?
Definition
Prisoners
Competition sports
Urban men/men
Daycare
Term
What are typical of CA-MRSA infections?
Definition
- Broader susceptibility profiles
- Usually resistant to Emycin
- Typically a soft tissue infection
**"Spider bite"
Term
What are typical treatment options for CA-MRSA?
Definition
- 1st line - bactrim or clinda
- 2nd line - Vanc, linezolid, Dapt, Synercid, Teicoplanin
- Wash w/ povidone or chlorhexidene
- Mupirocin to decolonize
Term
What factors lead to gram(-) resistance?
Definition
- Enzyme degradation - hydrolysis of AG and beta lactams. Metallobetalactamases
- Binding site mutation - Most common mutation for FQNs
- Decreased permeability - loss of outer membrane protein such as OprD in P. aerug
- Pumps - porins - MexAB-OprM
Term
What do the TEM and SHV genes do?
Definition
pick up an extra amino acid - knock out P. aerug covering penicillins and some cefs. EBSL +/-
**ampC knocks out Zosyn
Term
How does bacteria load affect MIC?
Definition
Higher load = drug becomes ineffective. Beta lactams especially known for this.
- At a higher inoculum, MIC increased for cefepime and Zosyn. Cefepime increases mortality when used all the time
Term
What can be used for ESBL-Klebsiella?
Definition
Tigecycline - but it's a static drug and can lead to relapse. Can also use Colistin
**Mutating to CRE - really bad.
Term
What is OprD responsible for?
Definition
Porins in P. aerug. Loss of porins = reduced uptake of antibiotics
**Zosyn is the only drug above 90% susceptibility
Term
What are common mutations in Acinetobacter?
Definition
- OprD - porin loss
- TEM/SHV EBSLs
- Metallo-betalactamase
- ampC is VERY common - no Zosyn
**Only Imipenem and tobra still in the 90's%
Term
What antibiotic is used in HIGH DOSE for acinetobacter?
Definition
Ampicillin/Sulbactem
Term
What are the NDM-1 metallo-betalactamases?
Definition
- Klebsiela, E. cloacae, E. coli
- Resistance to ALL beta lactams, including carbapenems (except aztreonam)
- Risk factors: Hospitalized in pakistan/india
Term
What are the 3 basic principles of appropriate antimicrobial therapy?
Definition
1) Establish a diagnosis BEFORE initiating antibiotics. Involves tests, C&S, other evaluation
2) Initiate proper empiric therapy - broad spectrum, parenteral, appropriately aggressive
3) De-escalate when possible - narrow as possible
Term
What is resistance surveillance?
Definition
- Monte carlo predictions. Higher dose = more success
- Protocols aid in stewardship
Term
When can short course therapy be used?
Definition
gram(+)
Leads to relapse in gram(-)
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