Red Book - Abx Resistance

Question 1

Mechanisms of antibiotic resistance to bacteria

Answer 1

INTRINSIC or ACQUIRED

Intrinsic - Lack of an actual molecular target
Lack of a transport mechanism for Abx to enter
Membrane is impermeable (gram neg cell wall is thick)

Acquired - Drug is inactivated (e.g. the beta lactamases)#
Reduced permeability (pseudomonas has a thick wall AND loss of porins)
Efflux of drugs - Gram negs can actively pump Abx back out
(pseudomonas can pump penicillin/cefs)
Altered molecular target/create an alternative pathway
(MRSA makes an low affinitity penicillin binding protein)
(VRE has genetic alteration to alter cell wall substates)

Question 2

How may bacteria acquire resistance

Answer 2

Intrinsic - Innate resistance

Sporadic mutation

Horizontal gene transfer

Question 3

List the ways horizontal gene transfer may occur

Answer 3

Transformation - Free DNA from lysed bacteria

Transduction - Bacteriophages (viruses) transfer DNA from one bact to another

Conjugation - Plasmids require direct contact of two bacteria

Transposition - Use of TRANSPOSONS (small bacterial segement of DNA, move between plasmids or chromosomes)

Question 4

Why is ABx resistance an issue in ITU

Answer 4

Use of broad spec Abx –> selection pressure

Patietns are immunocompromised

Many invasive devices bypass normal defences

Potential for cross contamination

Question 5

How can we minimised resistance (list the principles)

Answer 5

Antimicrobial Stewardship

Local Guidance

Aim to get micro sample BEFORE starting empirical tx

Rigourous infection control

SSD??

Question 6

Principles of Abx stewardship

Answer 6

Collect dose, drug, indication and duration
Close monitoring
De-escalate ASAP
Short a course as possible
Cycling Abx
Avoid those likely to cause c.diff

Question 7

Describe the principles of using local guidance

Answer 7

Knowing/suspecting the site of infeciton
Is it community of nosocomial
Recent Abx use
Local common organisms

Question 8

Infection control measrues

Answer 8

Side rooms with resistant organisms
Barrier nursing
Alcohol gel
Hand washing
Audits

Question 9

Describe SDD

Answer 9

Use of non-absorbable Abx oral and enteral plus short term iv

Reduce prevent colonisation or overgrowth of pathogenic commensual

Examples:
Tobramycin topical
Polymixin E (colistin)
Amphotericin B

Systemic cefuroxime

Vanc in MRSA

Reduces VAP and bacteraemia
Conflicting evidence over whether it causes resistance

Question 10

Describe MRSA

Answer 10

MEC-A gene by transposons codes for a low affinity binding protein for penicillin in cell wall

Eradicated with MUPIROCIN nasal and Chorhex wash

Treatment - glycopeptides (vanc)
2nd line - linezolid

Question 11

What is PVL

Answer 11

Panton Valentine Leucocidin

Present in community acquired MRSA

Causes necrotising skin/soft tissue infections and pneumonia

Tx - linezolid, rifampicin, clindamycyin
+ IvIG

Question 12

What is c.difficile

Answer 12

Gram positive spore forming anaerobic bacillus

Toxin A - enterotoxin - causes bowel fluid sequestriation
Toxin B - cytotoxin - detected with CDT testing

Increased with use of broad spec Abx

Hand washing (alcohol doesnt kill spores)

1: oral metronidazole (or IV)
2) Oral vanc

Question 13

What is VRE

Answer 13

Vancomicin resistant enterococci

Gram positve coccus (y-haemolytic)

E. faecalis is sensitive
E. faecium is resistant

Six different resistant genes render multi drug resistance

Tx - linezolid/daptomicin

Question 14

Pseudomonas

Answer 14

Gram neg bacillus

Easily resistant

Forms biofilms

Commonest cause of late onset VAP

Tx - tazoxin, ceftazedine, gent (usually as a dual therapy)

Question 15

Treatment of ESBL

Answer 15

Mero