Upload
noah-mccormick
View
212
Download
2
Embed Size (px)
Citation preview
Community-Associated Methicillin-Resistant Staphylococcus aureus
Ruth Lynfield, M.D.
Minnesota Department of Health
Chambers, EID 7:178-182, 2001
Time required for prevalence rates of resistance to reach 25% in hospitals
Drug
Year Drug Introduced
Years to Report of
Resistance
Years Until 25%
Rate in Hospitals
Years Until 25% Rate in Community
Penicillin 1941 1-2 6 15-20
Methicillin1961 <1 25-30
40-50 (projected)
Emergence of Resistance in S. aureus
Methicillin Resistance in S. aureus
• mecA confers resistance to penicillins and cephalosporins
• mecA is part of the staphylococcal cassette chromosome mec (SCCmec), a mobile genetic element (21-67 kb in size) that may also contain genes that confer resistance to non-beta-lactam antimicrobials
• SCCmec has been classified into 5 main types based on polymorphisms in its conserved genes
Staphylococcal Cassette Staphylococcal Cassette Chromosome Chromosome mec mec TypesTypes
Oliveira et al., Lancet ID, 2002
SCCmec type I - Archaic clone
SCCmec type IV - Pediatric clone
orfXRJLJ
mecR1HVR
dcsccrAB4 IS1272
SCCmec type II - NY/Japan clone
SCCmec type IIIA - Brazilian clone
SCCmec type III - Hungarian clone
orfXRJ
pls
LJmecR1
HVRdcs
ccrAB1 IS1272
orfXRJ
pls
LJmecR1 HVR dcs
pUB110ccrAB1 IS1272
SCCmec type IA - Iberian clone
orfXpT181 pI258 Tn554
LJ RJipsccrAB
Tn554ccrAB3 mecImecR1 HVR
pUB110ccrAB2kdp
LJ RJorfX
HVRdcsmecI
mecR1Tn554 mecImecR1 HVR
pI258 Tn554
LJ RJccrAB orfX
Tn554ccrAB3 mecImecR1 HVR
10 Kb
mecA
IS431
LJ - chromosomal left junctionRJ - chromosomal right junction
Background: Healthcare-associated (HA) MRSA
• Leading cause of nosocomial pneumonia, surgical wound infection, and bloodstream infection
• Established risk factors include
– Current or recent hospitalization
– Residence in long-term care facilities
– Dialysis
• Typical resistance profile
– Resistant to many antimicrobials in addition to beta-lactams
Community-Associated Methicillin-Resistant Staphylococcus aureus (CA-MRSA)
Reports began in 1980s of MRSA occurring in the community in patients without established risk factors – Younger patients – Indigenous peoples and racial minorities – Skin infections common– Outbreaks:
• Injection drug users• Players of close-contact sports • Prison/jail inmates• Group Homes (developmentally disabled)• Men who have sex with men
CA-MRSA
• Isolates typically susceptible to most antimicrobial classes other than beta-lactams
• Isolates differ by PFGE from HA-MRSA
• Isolates have different SCCmec types from HA-MRSA
• Isolates have been identified that are highly related to MSSA except for SCCmec element*
• Although most infections associated with CA-MRSA have been skin and soft tissue, some infections have been very severe including necrotizing pneumonia and other life-threatening infections
* Fey. Antimic Agents Chem. 2003; 47: 196-203.Mongkolrattanothai. Clin Infec Dis. 2003: 37: 1050-8.
CA-MRSA in Minnesota
• 1997- Minnesota Department of Health (MDH) received reports of MRSA infections in young, previously healthy individuals
• Reported four pediatric deaths due to MRSA infection (MMWR, August 20, 1999)
Four Pediatric Deaths, CA-MRSA Minnesota and North Dakota, 1997-99
Clonal group A
Clonal group A
Clonal group A (MW2)
Clonal group APFGE
T/S, tet, cip, gent, ery,
clind, vanc
T/S, tet, cip, gent, ery,
clind, vanc
T/S, tet, cip, gent, ery,
clind, vanc
T/S, tet, cip, gent, ery,
clind, vanc
Antimicrobial
susceptibility
Necrotizing pneumonia/
sepsis
Necrotizing pneumonia/
sepsisSepsis
Septic joint, pneumonia/ empyema Syndrome
WhiteWhiteAmerican
IndianAfrican
AmericanRace
MaleFemaleFemaleFemaleGender
12 months13 years16 months7 yearsAge
Case 4Case 3Case 2Case 1
CA-MRSA in Minnesota
Minnesota Communicable Disease Reporting rule amended in 1999:
– All cases of serious illness or death due to CA-MRSA reportable
– Sentinel sites were required to report all cases of MRSA
Minnesota Definition of CA-MRSA Used in Prospective Surveillance
• Positive culture for MRSA obtained within 48 hours of admission (if hospitalized)
• No history of hospitalization in past year
• No history of surgery in past year
• No history of long-term care in past year
• No history of dialysis in past year
• No permanent indwelling catheters or percutaneous medical devices
• No prior history of MRSA infection or colonization
MRSA patients
Community-onset, no risk factors documented in medical record
Healthcare-associated
•Hospital-acquired
•Community-onset with Risk factors
Risk factors (-)
Medical record review
Risk factors (+)
Risk factors (-)
No interviewRisk factors (+)
Telephone interview Indeterminate
Community-associated
Minnesota MRSA SurveillanceMinnesota MRSA Surveillance
Prospective MRSA Surveillance: Methods, MN, 2000
• 12 sentinel hospitals selected to represent different geographic regions (6 metro area, 6 greater MN) reported all cases MRSA
• Patient information was collected and MRSA isolates were obtained for all cases (HA and CA-MRSA)
• Presumptive CA-MRSA patients were interviewed to verify that they met the CA-MRSA case definition
Minnesota MRSA Surveillance Methods: Laboratory
• MRSA isolates from sentinel sites sent to MDH Laboratory
• All CA-MRSA isolates tested
• 25% of HA-MRSA isolates from each site randomly selected for testing
• Isolates confirmed as S. aureus (tube coagulase)
• Antimicrobial susceptibility testing (including oxacillin) by broth micro-dilution
• PFGE subtyping
• 26 CA and 26 HA-MRSA isolates characterized for toxins
Minnesota MRSA Surveillance Results: 2000
• 4,612 patients with S. aureus identified at 10 sentinel sites in 2000 (total number S. aureus unavailable at two sites)
• 1100 (25%) were MRSA (range 10-49%)
– 937 (85%) were HA-MRSA
– 131 (12%) were CA-MRSA (range 4-50%) after patient interview*
– 32 (3%) not enough information to classify
*13% of presumptive CA-MRSA cases were reclassified as HA-MRSA after interview
Age and Culture Sites of CA-MRSA Cases, MN, 2000
CA-MRSA
(n = 131)
HA-MRSA
(n = 937) p-value
Age (median) 23 years 68 years <0.05
Culture site No. (%) No. (%)
Skin 98 (75) 343 (36) <0.05
Respiratory 8 ( 6) 205 (22) <0.05
Blood 5 ( 4) 83 ( 9) NS
Urine 1 ( 1) 185 (20) <0.05
Other 10 (7) 110 (12) NS
CA and HA-MRSA PFGE Subtype Patterns, Minnesota, 2000
Healthcare-associated (clonal group H)
Community-associated (clonal group A)
PFGE Relatedness of CA and HA-MRSA Isolates to Reference Strain, MN, 2000
Number of Bands Different from MRSA Reference Strain
Nu
mb
er o
f Is
ola
tes
0
10
20
30
40
50
60
70
80
90
100
110
120
130
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
15%35%50%70%90%100%
Clonal Group A
Community-associated (n=106)
Healthcare-associated (n=211)
Relatedness to Reference Strain
(MW2)
30%
70%
Beta-lactamOther
Initial Empiric Treatment of CA-MRSA Infections, MN, 2000 (n = 92)
Susceptibility of CA and HA-MRSA Isolates by Antimicrobial
Agent, MN, 2000
0%
20%
40%
60%
80%
100%
CIP CLI ERY GENT TMP/SMX TET RIF VAN
Antimicrobial
% S
us
ce
pti
ble
CA-MRSA (n=106)
HA-MRSA (n=211)
p<0.001 p<0.001 p<0.001
p=0.001
79
16
83
21
44
9
94
80
9590 92 92
96 94100100
Trends in Antimicrobial Susceptibility of CA-MRSA Isolates, MN, 1996-2001
• No significant change in susceptibilities to tetracycline, TMP-SMX, gentamicin, or rifampin
• Susceptibility decreased over time:
– Ciprofloxacin: 92% to 77%, x2 trend=15.3, p<0.001
– Clindamycin: 90% to 80%, x2 trend=4.1, p<0.05
– Erythromycin: 70% to 39%, x2 trend=14.8, p<0.001
erm msrA
Macrolides (e.g., erythromycin) Lincosamides (e.g., clindamycin) Streptogramin B
Methylase
MacrolidesLincosamidesStreptogramin B
Macrolides
Efflux pump
Macrolide Resistance Mechanisms in S. aureus
Ribosome
Proteinsynthesis