Infectious diseases 2 - Overview part 1

Question 1

What are general mechanisms of antibiotic resistance?

Answer 1

Antibiotic inactivation
Alteration of Ab target
Decreased uptake

Question 2

What are genetic mechanisms of resistance in bacteria?

Answer 2

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

Question 3

What is conjugation?

Answer 3

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

Question 4

What is transformation?

Answer 4

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

Question 5

What is transduction?

Answer 5

Transfer of resistance genes via bacetriophages

Question 6

What is NORSA?

Answer 6

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

Question 7

What are definitions of MRSA/VISA/VRSA?

Answer 7

MRSA/VSSA MIC =16ug/ml

Question 8

What are features of hVISA

Answer 8

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

Question 9

In what patients is VISA assocaited?

Answer 9

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

Question 10

How is VISA detected clinically?

Answer 10

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

Question 11

What are features of VRSA?

Answer 11

rare

assoc with VAN genes from VRE

Question 12

What are features of VRE?

Answer 12

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

Question 13

What are features of Van A?

Answer 13

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

Question 14

What are features of Van B?

Answer 14

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

Question 15

What are treatment options of VRE?

Answer 15

Linezolid (neutropenias post 2/52 Rx)
Tigecycline
Daptomycin

Question 16

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

Answer 16

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

Question 17

What are features of pneumococcal resistance?

Answer 17

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

Question 18

What are beta lactam enzyme classes?

Answer 18

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

Question 19

What are bacteria associated with inducible beta-lactamase?

Answer 19

AmpC gene

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

Question 20

What are features of ESBL producing bacteria?

Answer 20

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

Question 21

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

Answer 21

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

Question 22

What are features of linezolid?

Answer 22

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

Question 23

What are features of daptomycin?

Answer 23

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

Question 24

What are features of tigecycline?

Answer 24

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

Question 25

What are features of ceftaroline?

Answer 25

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

Question 26

What are features of colistin?

Answer 26

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

Question 27

What are features of fosfomycin?

Answer 27

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

Question 28

What are features of moxifloxacin?

Answer 28

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