1. MRSA Update 2013 David K. Hong, MD Pediatrics/Infectious Diseases &
Immunology/Allergy
Santa Clara Valley Medical Center
Stanford University Medical School

2. Objectives
1. Review the increase in community-associated MRSA infections in the last decade 2. Describe the unique infectious complications in neonates 3. Discuss strategies for effective treatment and prevention of MRSA infections

4. 10 day old ex36wk male presents to urgent care clinic with this rash
Late-preterm, previously healthy male neonate with CA S aureus localized groin pustulosis.
Fortunov R M et al. Pediatrics 2007;120:

5. What is MRSA?

6. Staphylococcus aureus
Staphyle – “grape”; aureus – “gold”
Coagulase positive

7. Staphylococcus aureus
Staphyle – “grape”; aureus – “gold”
Coagulase positive
Coagulase-negative staph
are usually non-pathogenic

8. Staphylococcus aureus
Staphyle – “grape”; aureus – “gold”
Coagulase positive
Coagulase-negative staph
are usually non-pathogenic
Catalase positive
Turns H2O2 into H20 and O2

9. Some definitions MRSA – methicillin-resistant S. aureus
HA-MRSA – healthcare associated MRSA
- MRSA infection occurring within 12 months of hospitalization
- Nosocomial infection
- Usually has multidrug resistance
CA-MRSA – community associated MRSA
- MRSA infection in the absence of healthcare exposure
- Associated with skin and soft-tissue infections (SSTI)

10. More definitions
SCCmec - Staphylococcal Cassette Chromosome mec or SCCmec (I-V) is a resistance island or cassette in the chromosome that encodes for methicillin resistance Mec gene - Methicillin resistance: mec gene encodes for production of penicillin binding protein 2A (PBP2A) USA300 - Dominant CA-MRSA strain in U.S. causing increase in SSTI PVL – Panton Valentine Leukocidin

11. Panton Valentine Leukocidin
Cytotoxin that causes white cell destruction and tissue necrosis
Commonly present in SCCmec type IV and V (CA-MRSA strains)
Can be also present in MSSA strains
Associated with skin and soft tissue infections and necrotizing pneumonia
S. aureus has many other virulence factors that may modulate infection

12. Committee on Infectious Diseases et al. Red Book Online 653-668

14. Evolution of Resistance
Drug
Year
Introduced
Time to R
25%R
Hospitals
25% R
Comm.
Penicillin
1941
1-2 yrs
6 yrs
15-20 yrs
Methicillin
1961
1 yr
25-30
40-50
Vanco
1956
40 yr ?
Chambers, HF EID 2001

15. Resistance
Penicillin resistance: Gene for penicillin resistance is carried on a plasmid
Encodes for a penicillinase
About 80-90% of S. aureus isolates are R to penicillin

16. The -lactam ring R= Penicillin G (benzylpenicillin)
Beta-lactamase cuts the ring here R=
Penicillin G (benzylpenicillin)

17. R
Staph
-lactamase X
Cephalosporin +
Clavulanate
Amoxicillin

18. MRSA Methicillin-resistance is NOT due to a super-powerful -lactamase
mecA gene - PBP2a - altered penicillin-binding protein that has low affinity to -lactams

19. MRSA Resistance
Peptidoglycan cell wall x
Beta lactam abx
PBP2A
PBP

20. MLS Resistance Mechanisms
in S. aureus
Macrolides (e.g., erythromycin)
Lincosamides (e.g., clindamycin)
Streptogramin B
Protein
synthesis
erm
msrA
Ribosome
Efflux pump
Methylase
All MLS antibiotics bind basically the same target site on the ribosome in the bacterial cell. This inhibits protein synthesis.
Resistance in staph in encoded by two major mechanisms:
erm (erythromycin resistance/ribosome mechanism) gene: this gene encodes a methylase that affects the target binding site on the ribosome. Methylase is an enzyme that adds a methyl group to the ribosome which methylates the binding site and blocks the binding of all MLS antibiotics.
msrA (methionine sulfoxide reductase) gene: this gene encodes an efflux pump which pumps macrolides (only) out the the bacterial cell before they can bind to the ribosome target site. Bacteria will still be susceptible to lincosamides (clindamycin) and streptogramin B (synercid is a comination of streptogramin A and B)
Macrolides
Lincosamides
Streptogramin B
Macrolides

21. A note about Clindamycin Resistance Testing

22. All politics is local… microbiology
About 20 – 40% of S. aureus is MRSA in our area
About 50 – 87% of MRSA is clindamycin sensitive

23. Rates of all Staphylococcus aureus infections, of methicillin-resistant S. aureus (MRSA) infections, and of methicillin-susceptible S. aureus (MSSA) infections in 33 US children's hospitals from 2002 to 2007.
Rates of all Staphylococcus aureus infections, of methicillin-resistant S. aureus (MRSA) infections, and of methicillin-susceptible S. aureus (MSSA) infections in 33 US children's hospitals from 2002 to 2007.
Gerber J S et al. Clin Infect Dis. 2009;49:65-71
© 2009 by the Infectious Diseases Society of America

24. Staphylococcus aureus and MRSA bacteremia/meningitis in NICUs
Shane AL et al, Pediatrics Apr;129(4):e914-22

25. Clone USA300 is remarkably similar from different patients
Kennedy AD et al, PNAS 2008 Jan 29;105(4):

26. No difference in mortality between MSSA and MRSA
Pathogenicity based on virulence factors not necessarily antibiotic resistance patterns
Shane AL et al, Pediatrics Apr;129(4):e914-22

27. MRSA Colonization 1/3 of people have S. aureus in their nose
~2% carry MRSA

28. Risk factors for Colonization and Infection
Very young children or the elderly
Athletes
Lower SE
Pet owners and veterinarians
Prisoners
Nail biters
Health care exposure
Health care workers
Race

29. Impact of methicillin-resistant Staphylococcus aureus (MRSA) colonization on risk of subsequent infection in critically ill children.
Impact of methicillin-resistant Staphylococcus aureus (MRSA) colonization on risk of subsequent infection in critically ill children. The risk of developing a subsequent MRSA infection was compared for children with and without MRSA colonization at time of admission to the pediatric intensive care unit. Patients were monitored for an infection during their hospitalization and after hospital discharge.
Milstone A M et al. Clin Infect Dis. 2011;53:
© The Author Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please

30. California state law SB 1058 - passed in 2008
- requires MRSA screening (nasal swab) for following patients
ICU admissions – including NICUs
Inpatient hemodialysis patients
patients discharged from general acute care hospital within 30 ays of admission to SHC
Transfers from a skilled nursing facility (SNF)

31. Overlap of nares, oropharynx, and inguinal colonization among the 542 Staphylococcus aureus–colonized subjects from our total population of 1162 persons of households of persons with a recent S. aureus skin infection.
Overlap of nares, oropharynx, and inguinal colonization among the 542 Staphylococcus aureus–colonized subjects from our total population of 1162 persons of households of persons with a recent S. aureus skin infection. Each circle size is proportional to the amount of S. aureus detected at that given anatomic site. Of note, nares-only surveys would have missed 48% of S. aureus–colonized persons.
Miller L G et al. Clin Infect Dis. 2012;cid.cis213
© The Author Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please

32. Infants with MRSA infection commonly have mothers colonized with MRSA
MRSA colonization in neonates
25/35 (71%) case
4/19 (21%) control
Fortunov Pediatr Infect Dis J Jan;30(1):74-6.

33. Infants with MRSA infection commonly have mothers colonized with MRSA
MRSA colonization in moms
12/35 (34%) case
1/19 (5%) control
Fortunov Pediatr Infect Dis J Jan;30(1):74-6.

34. Infants with MRSA infection commonly have mothers colonized with MRSA
8/34 (24%) identical maternal nasal and neonatal clinical isolate
Fortunov Pediatr Infect Dis J Jan;30(1):74-6.

35. Infants with MRSA infection commonly have mothers colonized with MRSA
21/34 (62%) identical
neonatal nasal and neonatal clinical isolate
Fortunov Pediatr Infect Dis J Jan;30(1):74-6.

36. Infants with MRSA infection commonly have mothers colonized with MRSA
6/25 (17%) identical maternal nasal, neonatal nasal, and neonatal clinical isolate
Fortunov Pediatr Infect Dis J Jan;30(1):74-6.

37. Late-preterm, previously healthy male neonate with
CA S aureus localized groin pustulosis.
at Texas Children’s
Term and late-preterm <30 days
43 pustulosis – none had invasive disease
68 cellulitis/abscess – 3 had bacteremia or CSF pleocytosis
15 invasive infections
Late-preterm, previously healthy male neonate with CA S aureus localized groin pustulosis.
Fortunov R M et al. Pediatrics 2007;120:
©2007 by American Academy of Pediatrics

38. Treatment of MRSA in Neonates
IV Vancomycin
Clindamycin or linezolid if a non-endovascular infection
For mild cases with localized disease: Topical treatment with mupirocin may be adequate in full term neonates and young infants.

39. What about Vancomycin?
Don’t use it for MSSA infections – it does NOT work as well as beta lactam antibiotics.
Change to appropriate therapy as soon as susceptibility data is available

40. Do not use Vancomycin for Methicillin-sensitive S. aureus (MSSA)
Chang FY etl al, Medicine (Baltimore) Sep;82(5):333-9

41. Decolonization Nasal decolonization with mupirocin BID for 5-10 days
Topical body decolonization with either chlorhexidine for 5-14 days or bleach baths (1/4 cup per ¼ tub). Bleach baths are given for 15 minutes semi-weekly for 3 months

42. Decolonization
Systemic antibiotics are recommended for treatment of active infection only
Only in select circumstances is an oral antibiotic plus rifampin recommended for decolonization (CIII)
If household transmission is suspected, personal and environmental measures are recommended for contacts.

43. Decolonization
Systemic antibiotics are recommended for treatment of active infection only
Only in select circumstances is an oral antibiotic plus rifampin recommended for decolonization (CIII)
If household transmission is suspected, personal and environmental measures are recommended for contacts.

44. Decolonization
Shown to be effective in the short-term in reducing nasal carriage of MRSA
Re-colonization is common
Rates of SSTI are still high even when decolonized
Fritz SA et al, Infect Control Hosp Epidemiol Sep;32(9):872-80

45. Decolonization regimens used in NICUs – unclear benefit
Milstone AM et al, Infection Control and Hospital Epidemiology , Vol. 31, No. 7 (July 2010), pp

46. Prevention - Hand washing works!
Pittet D et al, Lancet Oct 14;356(9238):

47. Summary
MRSA colonization and infection has been on the rise in the community even without exposure to healthcare facilities
Both methicillin-resistant and –sensitive S. aureus can cause similar disease due to the sharing of virulence factors
Patients colonized with S. aureus are more likely to have S. aureus infections
Decolonization can work in the short term but the long-term effects are unknown