Infectious diseases 2 - Overview part 1 Flashcards Preview

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1
Q

What are general mechanisms of antibiotic resistance?

A

Antibiotic inactivation
Alteration of Ab target
Decreased uptake

2
Q

What are genetic mechanisms of resistance in bacteria?

A

Spontaneous DNA mutations (SNPs)
- no cost to bacteria, permanent resistance
Acquisition of new DNA
- bacteriophages - plasmids - transposons
- energy cost - must reproduce both nuclear and plasmid DNA, can be reduced in frequency with reduced selection pressure

3
Q

What is conjugation?

A

transfer of DNA from mobile plasmid via pilus to other bacteria (From relaxosome to transferosome)

4
Q

What is transformation?

A

Release DNA from lysed cells incorporated back into the new bacterial chromosome

5
Q

What is transduction?

A

Transfer of resistance genes via bacetriophages

6
Q

What is NORSA?

A

Non-multiply resistant, oxacillin resistant S. aureus

  • skin infections and necrotising pneuimonia
  • necrotising Fasciitis, rapidly progressive septicaemia, osteomyeltitis
  • often susceptible to clindamycin, co-trimoxazole, macrolides, gentamicin
  • panton-valentine leucocidin associated with virulence
  • pore forming cytotoxin
7
Q

What are definitions of MRSA/VISA/VRSA?

A

MRSA/VSSA MIC =16ug/ml

8
Q

What are features of hVISA

A

heterogenous MRSA with minority VISA
MIC usually 1-2
ASsoc with thickened cell wall - D-Ala-D-Ala
vancomycin failures common
treat wtih linezolid, tigecycline, rifampicin/fusidate, ceftaroline

9
Q

In what patients is VISA assocaited?

A

mainly in dialysis patients, or those with infected foreign bodies
also associated with thickened cell wall

10
Q

How is VISA detected clinically?

A

poor response to gylcopeptide Antibiotics despite appropriate dosing and debulking
prolonged positive cultures
dialysis patients receving prolonged courses of glycopeptide antibiotics

11
Q

What are features of VRSA?

A

rare

assoc with VAN genes from VRE

12
Q

What are features of VRE?

A

E. faecalis and E. faecium generally
Contain Van A, B +/- others
Vancomycin resistance gene cluster
- change D-ala-D-ala to D-ala-D-lac - no vanc binding
- eliminates any produced D-ala-D-ala
- dipeptidase to cleave D-ala-D-ala
Can transfer resistance genes to staphs in vitro

13
Q

What are features of Van A?

A

High level resistance (>64), teicoplanin resistant, inducible

14
Q

What are features of Van B?

A

Lower level resistance (4-32), no teicoplanin resistance, inducible

15
Q

What are treatment options of VRE?

A

Linezolid (neutropenias post 2/52 Rx)
Tigecycline
Daptomycin

16
Q

What are features of non-penicillin susceptible S. pneumoniae?

A

caused by altered penicillin binding proteins (not beta lactamase)
RFs - children, day care centres, recent Ab use (azithro)

PSSP MIC =8

meningitis MIC =0.12

17
Q

What are features of pneumococcal resistance?

A

Pen-resistance often confers other resistance - macrolides, cephalosporins, quinolones
Rates of PISP/PRSP vary around the world (Spain, USA, Hungary, France, Greece)
generally only relevant for meningitis and OM

18
Q

What are beta lactam enzyme classes?

A

A - penicillinases (TEM, SHV, CTX-M)
B - Metalloenzymes (NDM, VIM, IMP)
C - cephalosporinases (AmpC)
D - oxacillinases (OXA)

19
Q

What are bacteria associated with inducible beta-lactamase?

A

AmpC gene

  • > ESCAPPM
  • Enterobacter
  • Serratia marcescens
  • Citrobacter freundii
  • Acinetobacter
  • Providencia spp.
  • Proteus
  • (SOME Pseudomonas)
  • Morganella morganii
20
Q

What are features of ESBL producing bacteria?

A

mutations in existing b-lactamase genes (TEM, SHV) - plasmid mediated transfer
Spread from person to person, and by antibiotic pressure
Klebsiella, E. coli, Salmonella, Proteus, Enterobacter, Citrobacter, Serratia, Pseudomonas
Treat with - carbepenems, colistin, amikacin
may appear treatable in vitro with 3rd gen cephalosporins
Linked to fluoroquinolone use

21
Q

What are features of Class B - metallo-beta-lactamases?

A

Zn dependent
Pseudomonas, acinetobacter
plasmid mediated usually - hydrolyses all b-lactams except aztreonam
hydrolyses all carbapenems

22
Q

What are features of linezolid?

A

good activity against G+ (plus mycobacteria and nocardia)
good tissue penetration and B/A
totally synthetic, nil pre-existing resistance
no clear advantage over vanc
SE: GIT, cytopenias, neuropathy, MAO-inhibition
Avoid SSRIs, tramadol

23
Q

What are features of daptomycin?

A

Cyclic lipopeptide
bacterial activity against most Gram positives
similar to glycopeptides + VRE
? use in VISA, VRSA
inhibited by surfactant - not in pneumonia
Binds to cell membrane and leads to inhibition of synthesis of DNA, RNA and protein - bacteriacidal

24
Q

What are features of tigecycline?

A
derivative of minocycline
protein synthesis inhibitor
bacteriostatic
Low MICs for MRSA, MSSA, VISA, VRE
active against many gram negatives
(not pseudomonas, possesses an efflux pump)
BUT - MICs similar to serum levels
25
Q

What are features of ceftaroline?

A

Novel cephalosporin - active against MRSA
Not great for VRE
Similar to cefepime for gram negs (not for ESBLS)
mainly for pneumonia and soft tissue infections

26
Q

What are features of colistin?

A

binds to lipopolysaccharides and phospholipids in outer cell membrane - disrupts membrane and causes leakage and cell death.
renal and neurotoxicity
resistance via change in outer membrane
active: pseudomonas, acinetobacter, e. coli, some enterobacter, klebsiella, salmoneall
non-active: burkholderia cepacia, serratia, proteus, providencia, morganella, G-C, gram +ves

27
Q

What are features of fosfomycin?

A

inhibits MurA enzyme
bacteriacidal
inhibits cell wall biogenesis
mainly for resistant UTIs (G-, G+, not pseudomonas)

28
Q

What are features of moxifloxacin?

A
very broad spectum
MSSA, NORSA, Streps, many gram -ves, anaerobes, legionalla, leprosy, TB
Good tissue penetration and B/A
Two step resistance (c.f. 1 for cipro)
C.difficile
QT prolongation