MRSA International Lessons Learned

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MRSA International Lessons Learned?

• Michael Millar
• Barts and the London NHS Trust
• UK

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Meticillin-resistant Staphylococcus aureus

• Resistant to ß-lactam antibiotics
• (penicillins, cephalosporins, carbapenems)
• Staphylococcal cassette chromosome (SCCmec)
  inserted in to MSSA ? MRSA
• The mecA gene ? PBP2A, which has a reduced
  affinity for ß-lactam antibiotics
• MRSA can still synthesise a cell wall in the
  presence of ß-lactam antibiotics

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Staphylococcus aureus infection

• Staphylococcus aureus has been and remains a
  common cause of wound, biomedical device
  associated and blood stream infection
• MRSA infection is (still) most commonly
  hospital-acquired and arises post-procedure

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What have we learned?

• Antibiotic resistant S.aureus are bad for
  patients because
• Current preventive and treatment strategies for
  Staphylococcus aureus infection are compromised
  by the emergence of antibiotic resistant strains

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What have we learned?

• Better diagnostics
• Better treatments
• Better understanding of pathogenesis
• and of epidemiology
• Better prevention??

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What have we learned?

• MRSA can be controlled
• Contrast Denmark in 1970 with today
• Variation in prevalence country to country
• Variation within country
• (Prevalence 3 Perth, 35 Sydney)

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Hajo Grundmann et al., Emergence and
resurgence of meticillin-resistant Staphylococcus
aureus as a public-health threat. Lancet 2006
368 87485
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Global burden of MRSA

• MRSA is at present the most commonly identified
  antibiotic-resistant pathogen in many parts of
  the world, including Europe,
• the Americas, North Africa, Middle-East, and
  East Asia
• Grundmann et al.
• Lancet 368 874-885, 2006

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What have we learned?

• Dictionary Definition of
• Learned
• gained much knowledge
• acquired skill by study, instruction or
  experience?

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MRSA some gaps in what we have learned

• Which control strategies are most cost-effective?
• How to change human behaviour?
• How to predict the future?

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What have we learned?

• We hardly need to call readers attention to
  the thousands of articles published over the last
  three decades about epidemiological and
  microbiological aspects of MRSA. Yet uncertainty
  remains about the best approach to prevent and
  control this worldwide plague
• Harbarth Pittet
• Lancet Infect Dis 5661-2. 2005

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MRSA some gaps in what we have learned

• Which control strategies are effective and which
  are the most cost-effective?
• Screening (/- rapid testing)
• Decontamination
• Isolation
• Information/knowledge/understanding
• Hand-washing
• Antibiotic policies/restriction(s)
• Probiotics

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MRSA some gaps in what we have learned

• How do we change human behaviour?
• If we know that we have a problem and
• we know what to do to prevent or control the
  problem then why dont we do it?
• This problem applies at all levels
• national to individual
• Contrast Holland with UK
• Variation in hand hygiene practices

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MRSA in the USA

• Given the considerable body of evidence that
  screening cultures, when combined with contact
  precautions, are beneficial and cost-effective,
  it is disconcerting that only 30 (of ID
  physicians) worked in facilities where screening
  cultures are routinely done
• Boyce. Lancet Infect Dis 5 653-4, 2005

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MRSA in Holland

• there have been neither legal nor ethical qualms
  about the Dutch search, isolate, and destroy
  strategy., all see the value in prevention
• the experience is almost invariably one of
  excellent cooperation, and most people involved
  enjoy the process of working for the greater
  good
• Vandenbrouke-Grauls
• Lancet Infect Dis 5 660-1, 2005

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MRSA in the UK

• Problem with MRSA recognised very late
• Mandatory reporting of MRSA blood stream
  infections since April 2001
• Targets for reductions of gt50 by 2008
• Enhanced surveillance since 2006
• Increasing regulation

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Mandatory MRSA bacteraemia surveillance trends
(Apr 2001 September 2005)
Red significant above line
increase Blue not significant below line
decrease
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Mandatory MRSA bacteraemia surveillance trends
(Apr 2001 September 2005)
Red significant above line
increase Blue not significant below line
decrease
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MRSA in Finland

• Ten fold increase in MRSA isolates from 1997-2004
  (1458 isolates)
• Problems in elderly care settings and community
• Increased emphasis on control since 2005 ?
  reduced numbers of isolates
• 30 of MRSA were CA-MRSA in 2005
• Newer epidemic strains non-multiresistant with
  SCCmec types IV, V, or nontypeable
• (from Vainio et al. ESCMID, April 2007)

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MRSA some gaps in what we have learned

• How to predict the future?
• How much of a threat are Community MRSA and is
  there a historical parallel with penicillin
  resistant MSSA?
• Will VRSA become common-place?
• Are local solutions going to succeed in the face
  of a global pandemic?

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BSAC Working party definitions (consultation)

• CA-MRSA are MRSA strains isolated from patients
  in an outpatient or community setting, or within
  48 hours of hospital admission, who have no
  previous history of MRSA infection or
  colonisation, no history of hospitalisation,
  surgery, dialysis or residence in a long term
  care facility within one year of the MRSA culture
  date, and absence of an indwelling catheter or
  percutaneous device at the time of culture.
• HA-MRSA are MRSA strains that are transmitted to
  and circulate between individuals who have had
  contact with health care facilities.

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Mode of action of PVL
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How CA MRSA evolves
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Proposed definitions of CA-MRSA. BC Millar et
al., JHI 2007
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Figure 1. Overall rate of hospital-onset
methicillin-resistant Staphylococcus aureus
bacteremia for the period 20002006. Rates of
infection with community genotype (CG) and
hospital genotype (HG) strains, as inferred by
the phenotypic rule (see Methods), are shown.
From Popovich et al. CID 46 787-794, 2008
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MRSA - what we have learned

• Staphylococcus aureus is an adaptable pathogen
• Antibiotic resistance is probably only one
  manifestation of recent adaptations
• Hospital MRSA can be controlled, although the
  most cost-effective strategy for control remains
  uncertain

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MRSA rates vary

• Why?
• .uneven control and isolation measures, hand
  hygiene practices, antibiotic prescribing
  behaviours, and allocation of resources. Cultural
  and economic factors pervade all aspects of MRSA
  control, which can only be successful if strict
  measures and policies are installed at an early
  stage of MRSA dissemination..
• Harbath and Pittet, Lancet, 2005

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MRSA control

• Screening combined with actions to control
  dissemination
• Decontamination
• Cohorting / isolation
• Hand hygiene
• Information
• Antibiotic policies

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The precautionary principle

• When there are threats of serious or
  irreversible consequences, lack of full
  scientific certainty shall not be used as a
  reason for postponing cost-effective measures to
  control the spread of disease
• Perhaps a principle that should be adopted
  globally with respect to MRSA control?