Drug-resistant Staphylococcus aureus

Question 1

The rise of resistant S. aureus

Answer 1

1946: 6% produced penicillinases
1948: >50% of hospital S. aureus is pen resistant (now its more like 90%)
Chromaphenicol, erythromycin, streptomycin & tetracycline were active at first.
1961: First MRSA discovered

Question 2

Mechanisms of resistance to beta-lactams:

Answer 2

S. aureus uses 4 PBPs (1, 2, 3 & 4) to catalyse PG cross-linking.
MRSA has an extra component, PBP2’ or 2a, with low affinity for all beta-lactams at therapeutic levels.
PBP2a encoded by mecA gene that is carried by large sections of chromosomally inserted DNA.
These inserts are called stapylococci cassette chromosome mec (SCC mec)

Question 3

mecA gene

Answer 3

This gene doesnt allow the ringlike structure of penicillin-like antibiotics to bind to the transpeptidases that help form the peptidoglycan. The gene codes for the protein PBP2a.
mecA-containng DNA is mobile but not readily transmissible- however some horizontal transfer must occur. It’s possible that the evolution of MRSA predated introduction of antistaphylococcal penicillins.

Question 4

The rise of MRSA & EMRSA

Answer 4

MRSA initially spread rapidy, then delcined in the 70s/80s due to gentamicin and better infection control
Gentamicin resistant MRSA a problem by mid 80s.
Epidemic MRSA 1 strain (EMRSA-1) occured widely but EMRSA-15 and 16 accounted for about 95% of strains isolated by 2000, but 16 has now declined.
Its not especially resistant but its often associated with severe infections, especially bacteraemias because it possesses more or different toxins.

Question 5

Possible reasons why EMRSA strains were particularly successful

Answer 5

greater adhesive properties
lower infected dose
better survival capacity on inatimate objects
Increased nosocomal spread
increased use of fluoroquinolones
Increased number of MRSA patients

Question 6

Clinical therapy of healthcare associated MRSA infections.

Answer 6

Mainstays- vancomycin & teicoplanin
alternatives- fusidic acid & rifampicin in combination
mupirocin for superficial infections or to eliminate carriage before surgery.
Trimethoprim used for UTIs
Aminoglycosides used as prophylaxis but has potential for oto- and nephro- toxicity
Daptomycin for bacteraemia- can cause skeletal muscle necrosis

Question 7

Reduced susceptibility to glycopeptides:

Answer 7

First vancomycin-reistant enterococci reported in 1986
MRSA has excessive cell wall precursors & enzymes involved in cell wall production leading to a thickened cell wall which might sequester glycopeptides
The Japaense strain Mu50 has accelerated PG synthesis and thickened cell walls with reduced cross-linking

Question 8

Vancomycin-RSA

Answer 8

vanA gene present, probably transferred from a GRE strain, via transposon/plasmid, from same patient, 14 cases of VRSA in USA since 2000 and 1 in Europe 2013.
All but one were CC5 strain

Question 9

The brighter side:

Answer 9

MRSA deaths fell 20% from 2011 to 2012, has now fallen by more than 75% since 08.

Question 10

What’s next for MRSA?

Answer 10

Deadly strain of MRSA which can lead to flesh eating form of pneumonia has emerged.
Only 2 confirmed cases in UK.
Often contracted in the community.
A new strain has been found on the isle of man called MRSA USA 300.

Question 11

Community acquired MRSA

Answer 11

emerging cause of infections in non-healthcare setting
Can cause fatal necrotising pneumonia in children and serious necrotising soft-tissue infection.
Transmits through skin-skin contact
common features of CA-MRSA are presence of the Panton-Valentine leukocidin (PVL) gene and the methicillin-resistance locus SCCmec IV.
All have so far been +ve for beta-lactamase and assumed to be resistant to all beta-lactams. Tend to be more susceptible to other anti-staphylococcal agents. than HAMRSA. Mortality rates are low, with most deaths in patients with necrotising pneumonia
Therapy for CA-MRSA infection is with vancomycin, teicoplanin, daptomycin and linezolid.

Question 12

Hospital MRSA vs Community MRSA

Answer 12

HA-MRSA usually typical with the elderly or ill patients, CA-MRSA usually with young, healthy people.
Infection site of HAMRSA usually bacteraemia with no obvious infection site, with CAMRSA there is a predilecition for skin and soft tissue, producing cellulite and abscesses. May cause necrotising community acquired pneumonia. In HAMRSA, community spread is usually limited, PVL gene is usually missing. In CAMRSA, community spread occurs easily, with PVL genes often present, predisposing to necrotising soft tissue or lung infection

Question 13

Diagnosis & management of PVL staphylococcus aureus;

Characteristics of infection
Risk groups & factors
How to reduce spread

Answer 13

Reccurent skin infections include boils, cutaneous lesions and carbuncles.
Invasive infections include necrotising pneumoina after a flu-like illness, necrotising fasciitis.
Factors: contaminated items, close cantact, crowding
Groups: Prisons, Gyms, Military, close contact sports.
Stop spread by covering infected wounds and change dressing regularly, do not touch or squeeze skin lesions. regularly wash hands. general cleanliness

Question 14

Livestock-associated MRSA

Answer 14

Found in pigs in Netherlands in 2003
An increase in transmission of MRSA from colonised animals is being seen
Occupational risk for those working with livestock (abbatoir workers and vets)
LR-MRSA usually contain SSCmeciV but majority so far don’t have PVL