Genomic Epidemiology of Methicillin-Resistant ...
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Background • Congregate settings such as urban jails may facilitate spread of MRSA 1,2 • Jails may be a location where individuals already colonized with MRSA (from preceding exposures) intermingle with other individuals, potentially augmenting spread of MRSA Methods • Study Setting: Cook County Jail in Chicago, IL which is one of the largest single-site jails in the US • Males were enrolled within 72 hours of jail intake • Surveillance cultures of the anterior nares, throat, and inguinal area were collected at entrance to the jail to determine the prevalence of MRSA colonization • Surveillance cultures were repeated at Day 30 for those who remained incarcerated to determine the rate of MRSA acquisition during incarceration • A survey was administered and chart review performed to identify predictors of MRSA acquisition • Whole genome sequencing was performed with integration of epidemiologic data Genomic Epidemiology of Methicillin-Resistant Staphylococcus aureus (MRSA) DURING Incarceration at a Large Inner-City Jail Kyle J. Popovich, MD MS, FIDSA 1,2 , Evan S Snitkin, PhD 3 , Stefan J Green, PhD 4 , Alla Aroutcheva, MD PhD 1,2 , Michael Schoeny 1 , PhD, Darjai Payne, BS MPH 1 , Stephanie N Thiede, BS 3 , Chad Zawitz, MD 5 , Bala Hota MD MPH 1 , Mary K Hayden, MD 1 , Robert A Weinstein MD 1,2 1 Rush University Medical Center, Chicago, IL, 2 Cook County Health and Hospitals System, Chicago, IL, 3 University of Michigan Medical Center, Ann Arbor, MI, 4 University of Illinois at Chicago, Chicago, IL, 5 Cermak Health Services, Chicago, IL Contact Information: Kyle Popovich, MD, MS, FIDSA Rush University Medical Center 600 S. Paulina St. Suite 143 Chicago, IL 60612 T: 312-942-4451 [email protected] Conclusions • There is a high burden of MRSA entering the jail (19% colonized at intake) • Genomic analysis of acquisition, intake, and clinical isolates suggests spread of incoming strains and possible networks of spread of prevalent MRSA strains during incarceration • Sharing of personal items during incarceration is associated with MRSA acquisition and could be a focus of an intervention • Future study of epidemiologic and location data may inform targeting of infection control interventions within the jail Results • 800 males enrolled (19% colonized with MRSA at intake) • 12 MRSA acquisitions detected at Day 30 (Table) • USA300 clinical isolates (mostly skin infections) may originate from transmission within the jail or perhaps be due to more virulent strains (Figure 1) • Sequenced clinical USA300 isolates were more likely to be genetically similar to each other in comparison to intake USA300 MRSA strains (p<0.001) (Figure 2) • 7/12 (58%) acquisition isolates were within 40 SNVs from another isolate that was sequenced (5 were similar to intake isolates and 2 were similar to clinical isolates) • Acquisition strains from those sharing personal items (versus not) tended to have closer genetic relatedness (19 SNVs versus 56 SNVs, p=0.22) References 1. MRSA skin or soft tissue infections in a state prison--Mississippi, 2000. MMWR. 2001;50(42):919-22. 2. Miller LG, Diep BA. Clinical practice: colonization, fomites, and virulence: rethinking the pathogenesis of community-associated MRSA infection. Clin Infect Dis. 2008;46(5):752-60. ***See poster 1229 and oral presentation number 159 for additional abstracts from this project Objective • To examine the rate of MRSA acquisition during incarceration • To characterize the genomic epidemiology of MRSA strains entering the jail, MRSA acquisition isolates, and archived clinical MRSA isolates from male detainees 1247 Table. Epidemiologic Predictors of MRSA Acquisition During Incarceration Epidemiologic Factor MRSA Acquisition (n=12) No MRSA Acquisition (n=131) OR 95% CI P value Exposures prior to incarceration History of Benzodiazepine use 5 (42%) 27 (21%) 2.75 0.81, 9.35 0.11 Heroin use in the past year 5 (42%) 21 (16%) 3.67 1.06, 12.68 0.04 Methamphetamine use 3 (25%) 23 (18%) 1.57 0.39, 6.23 0.53 Injection drug use in past year 2 (17%) 13 (10%) 1.82 0.36, 9.2 0.47 Homeless or unstable housing 7 (58%) 62 (47%) 1.67 0.51, 5.48 0.4 HIV infection 9 (75%) 91 (69%) 1.32 0.34, 5.13 0.69 Taking antiretrovirals a 3 (33%) 59 (66%) 0.26 0.06, 1.12 0.07 Exposures during incarceration Participating in drug treatment classes 4 (33%) 22 (17%) 2.48 0.69, 8.95 0.17 Sharing of personal items b 7 (58%) 29 (22%) 4.92 1.45, 16.67 0.01 Any skin infections during incarceration 1 (8%) 4 (3%) 2.89 0.3, 28.11 0.36 Visit to infirmary 4 (33%) 20 (15%) 2.77 0.76, 10.09 0.12 Number of times showered in the past week, mean (SD) 4.8 (1.8) 6 (2.7) 0.81 0.62, 1.07 0.13 a 143 reached the Day 30 study visit. There were 100 HIV-infected patients that reached Day 30 Study Visit; 9 HIV-infected patients acquired MRSA and 91 did not b Personal items shared by individuals who acquired MRSA included towel, toothpaste, uniform, and deodorant Frequency 0 100 200 300 400 500 0 10 20 30 40 Clinical Intake Genomic Distance Between Pairs Frequency Kolmogorov-Smirnov Test Comparing Distributions p < 0.001 Funding: NIAID R01 (Popovich-PI) Maximum likelihood tree generated by RAxML. Clusters with 90% bootstrap support are indicated by the grey circle. Highlighted labels indicate a 90% bootstrap-supported cluster with all intake or all clinical isolates (can also include acquisition isolates). Figure 2. Genomic Distance Between Pairs of USA300 MRSA Clinical Infection and Intake Colonization Isolates Distribution of SNV distances between closest-pairs within intake and clinical isolates. One-sided Kolmogorov-Smirnov test on the distribution of clinical vs. intake closest-pair SNV distances indicate that clinical isolates tend to have closer pairs than intake isolates. 126KP 22KP 621N 8256KP 463T 194N 76KP 8291KP 72KP 91KP 403N 50KP 79KP 113KP 165KP 133KP 181KP 545N 54KP 633N 44KP 21G 32KP 8177KP 412T 149KP 150KP 171KP 567G 151KP 7797KP 161KP 62KP 263N 114KP 166KP 179KP 112KP 797G 9KP 452N 31KP 7647KP 318T 123KP 182KP 131N 13-30N 7751KP 20KP 170KP 615-30N 424N 213-30N 130KP 168KP 326T 7696KP 8057KP 103G 19KP 37T 7453KP 731T 37KP 5KP 60KP 609-30G 36KP 670N 7643KP 179T 222-30T 69KP 87KP 17KP 7676KP 513N 339N 61KP 523N 13KP 7406KP 229N 669T 110KP 7693KP 35KP 582G 302T 7679KP 163KP 30KP 281N 205T 10KP 16KP 141KP 576N 127KP 443N 67KP 169KP 78KP 143KP 105KP 53KP 128KP 7580KP 187KP 21KP 82KP 176KP 7177KP 610N 58KP 7779KP 14KP 221N 57KP 7792KP 121KP 733N 264N 6KP 662T 122KP 116KP 678N 723N 74KP 276G 15KP 542G 292N 664G 7420KP 8157KP 139KP 106-30N 173KP 598N 25KP 106KP 8271KP 344N 56KP 38T 186KP 787N 96KP 4T 8205KP 45KP 8117KP 80G 563N 606N 189KP 118KP 239N 561N 165N 325N 705N 199-30N 137KP 108G 7725KP 66N 663T 20N 154KP 398N 498T 140KP 644-30G 99KP 377N 125KP 528G 607T 94KP 188KP 28KP 119KP 131KP 86KP 714-30N 55KP 7677KP 638N 77KP 7752KP 29KP 519N 178KP 580N 266G 192KP 127N 156KP 204N 91N 219T 336T 175N 134N 242T 39N 146KP 220N 117KP 138KP 185KP 3KP 34KP 7485KP 7489KP 307T 190T 27KP 153KP 70KP 177KP 160KP 85KP 81KP 115KP 299T 48N 651N 790G 384N 7577KP 100KP 52KP 657N 277T 667G 594T 779N 120KP 18N 104KP 159KP 7184KP 59KP 148KP 7644KP 109KP 134KP 135KP 18KP 172KP 97KP 526T 7418KP 178N 223T 8289KP 65N 33KP 49KP 66KP 320T 124KP 361N 472N 98KP Legend Acquisition Clinical Intake Pure Clinical Cluster* Pure Intake Cluster* Bootstrap > 90% scale: 0.001 Tree scale: 0.001 Figure 1. Genomic Epidemiology of USA300 MRSA Intake, Clinical, and Acquisition Isolates
Transcript of Genomic Epidemiology of Methicillin-Resistant ...
Background
• Congregate settings such as urban jails may facilitate spread of MRSA1,2
• Jails may be a location where individuals already colonized with MRSA (from preceding exposures) intermingle with other individuals, potentially augmenting spread of MRSA
Methods
• Study Setting: Cook County Jail in Chicago, IL which is one of the largest single-site jails in the US
• Males were enrolled within 72 hours of jail intake• Surveillance cultures of the anterior nares, throat, and
inguinal area were collected at entrance to the jail to determine the prevalence of MRSA colonization
• Surveillance cultures were repeated at Day 30 for those who remained incarcerated to determine the rate of MRSA acquisition during incarceration
• A survey was administered and chart review performed to identify predictors of MRSA acquisition
• Whole genome sequencing was performed with integration of epidemiologic data
Genomic Epidemiology of Methicillin-Resistant Staphylococcus aureus (MRSA) DURING Incarceration at a Large Inner-City Jail
Kyle J. Popovich, MD MS, FIDSA1,2, Evan S Snitkin, PhD3, Stefan J Green, PhD4, Alla Aroutcheva, MD PhD1,2, Michael Schoeny1, PhD, Darjai Payne, BS MPH1, Stephanie N Thiede, BS3, Chad Zawitz, MD5, Bala Hota MD MPH1, Mary K Hayden, MD1, Robert A Weinstein MD1,2
1Rush University Medical Center, Chicago, IL, 2Cook County Health and Hospitals System, Chicago, IL, 3University of Michigan Medical Center, Ann Arbor, MI, 4University of Illinois at Chicago, Chicago, IL, 5Cermak Health Services, Chicago, IL
Contact Information:Kyle Popovich, MD, MS, FIDSARush University Medical Center
600 S. Paulina St. Suite 143Chicago, IL 60612T: 312-942-4451
Conclusions
• There is a high burden of MRSA entering the jail (19% colonized at intake)
• Genomic analysis of acquisition, intake, and clinical isolates suggests spread of incoming strains and possible networks of spread of prevalent MRSA strains during incarceration
• Sharing of personal items during incarceration is associated with MRSA acquisition and could be a focus of an intervention
• Future study of epidemiologic and location data may inform targeting of infection control interventions within the jail
Results
• 800 males enrolled (19% colonized with MRSA at intake)• 12 MRSA acquisitions detected at Day 30 (Table)• USA300 clinical isolates (mostly skin infections) may
originate from transmission within the jail or perhaps be due to more virulent strains (Figure 1)
• Sequenced clinical USA300 isolates were more likely to be genetically similar to each other in comparison to intake USA300 MRSA strains (p<0.001) (Figure 2)
• 7/12 (58%) acquisition isolates were within 40 SNVs from another isolate that was sequenced (5 were similar to intake isolates and 2 were similar to clinical isolates)
• Acquisition strains from those sharing personal items (versus not) tended to have closer genetic relatedness (19 SNVs versus 56 SNVs, p=0.22)
References1. MRSA skin or soft tissue infections in a state prison--Mississippi, 2000. MMWR. 2001;50(42):919-22.2. Miller LG, Diep BA. Clinical practice: colonization, fomites, and virulence: rethinking the pathogenesis of
community-associated MRSA infection. Clin Infect Dis. 2008;46(5):752-60.
***See poster 1229 and oral presentation number 159 for additional abstracts from this project
Objective
• To examine the rate of MRSA acquisition during incarceration
• To characterize the genomic epidemiology of MRSA strains entering the jail, MRSA acquisition isolates, and archived clinical MRSA isolates from male detainees
1247
Table. Epidemiologic Predictors of MRSA Acquisition During IncarcerationEpidemiologicFactor MRSAAcquisition
(n=12)NoMRSAAcquisition(n=131) OR 95%CI Pvalue
ExposurespriortoincarcerationHistoryofBenzodiazepineuse 5(42%) 27(21%) 2.75 0.81,9.35 0.11Heroinuseinthepastyear 5(42%) 21(16%) 3.67 1.06,12.68 0.04Methamphetamineuse 3(25%) 23(18%) 1.57 0.39,6.23 0.53Injectiondruguseinpastyear 2(17%) 13(10%) 1.82 0.36,9.2 0.47Homelessorunstablehousing 7(58%) 62(47%) 1.67 0.51,5.48 0.4HIVinfection 9(75%) 91(69%) 1.32 0.34,5.13 0.69Takingantiretroviralsa 3(33%) 59(66%) 0.26 0.06,1.12 0.07
ExposuresduringincarcerationParticipatingindrugtreatmentclasses 4(33%) 22(17%) 2.48 0.69,8.95 0.17Sharingofpersonalitemsb 7(58%) 29(22%) 4.92 1.45,16.67 0.01Anyskininfectionsduringincarceration 1(8%) 4(3%) 2.89 0.3,28.11 0.36Visittoinfirmary 4(33%) 20(15%) 2.77 0.76,10.09 0.12Numberoftimesshoweredinthepastweek,mean(SD) 4.8(1.8) 6(2.7) 0.81 0.62,1.07 0.13
a143 reached the Day 30 study visit. There were 100 HIV-infected patients that reached Day 30 Study Visit; 9 HIV-infected patients acquired MRSA and 91 did notbPersonal items shared by individuals who acquired MRSA included towel, toothpaste, uniform, and deodorant
Closest Pair Clinical < Closest Pair Intake ? USA300 p_val= 7.67611578145617e−09
distance between closest pair
Freq
uenc
y
0 100 200 300 400 500
010
2030
40 ClinicalIntake
Genomic Distance Between Pairs
Freq
uenc
y
Kolmogorov-Smirnov TestComparing Distributions
p < 0.001
Funding: NIAID R01 (Popovich-PI)
Maximum likelihood tree generated by RAxML. Clusters with 90% bootstrap support are indicated by the grey circle. Highlighted labels indicate a 90% bootstrap-supported cluster with all intake or all clinical isolates (can also include acquisition isolates).
Figure 2. Genomic Distance Between Pairs of USA300 MRSA
Clinical Infection and Intake Colonization Isolates
Distribution of SNV distances between closest-pairs within intake and clinical isolates. One-sided Kolmogorov-Smirnov test on the distribution of clinical vs. intake closest-pair SNV distances indicate that clinical isolates tend to have closer pairs than intake isolates.
126KP
22KP
621N
8256KP463T
194N
76KP
8291KP
72KP
91KP
403N
50KP
79KP
113KP
165KP
133KP
181K
P
545N
54KP
633N
44KP21
G
32KP
8177
KP
412T
149K
P
150KP
171K
P
567G
151K
P
7797
KP
161K
P
62KP
263N
114KP
166KP
179KP
112KP
797G
9KP452N
31KP
7647
KP
318T
123KP
182KP
131N
13-30N
7751KP
20KP
170KP
615-30N
424N
213-30N
130K
P
168KP
326T
7696KP
8057KP
103G
19KP
37T
7453KP
731T
37KP
5KP
60KP
609-3
0G
36KP
670N
7643
KP
179T
222-
30T
69KP
87KP
17KP
7676
KP
513N
339N
61KP
523N
13KP
7406
KP
229N
669T
110KP
7693
KP
35KP
582G
302T
7679KP
163KP
30KP
281N
205T
10KP
16KP
141KP
576N
127KP
443N
67KP
169KP
78KP
143KP
105KP
53KP128KP
7580
KP
187KP
21KP
82KP
176K
P
7177KP
610N58K
P
7779KP
14K
P
221N
57KP
7792KP
121KP
733N
264N
6KP
662T
122KP
116K
P
678N
723N
74KP
276G15KP
542G
292N
664G
7420
KP 8157KP
139KP
106-30N
173KP
598N
25KP
106K
P
8271
KP
344N
56KP
38T
186KP787N
96KP
4T
8205KP
45KP
8117KP
80G
563N606N
189KP
118K
P
239N
561N
165N
325N
705N
199-30N
137KP
108G
7725KP
66N
663T
20N
154KP
398N
498T
140K
P
644-30G
99KP
377N
125K
P
528G
607T
94KP
188KP
28KP
119KP
131K
P
86KP
714-30N
55KP
7677KP
638N
77KP
7752KP
29KP
519N
178K
P
580N
266G
192KP
127N
156KP
204N
91N
219T
336T
175N 134N
242T
39N146KP
220N
117KP138K
P
185KP
3KP
34KP
7485KP
7489KP
307T
190T
27KP
153KP
70KP
177KP
160KP
85KP
81KP
115K
P
299T
48N
651N
790G
384N
7577KP
100KP
52KP
657N
277T
667G
594T779N
120KP
18N
104K
P
159KP
7184KP
59K
P
148KP
7644KP
109KP
134KP
135KP
18KP
172KP
97KP
526T
7418KP
178N
223T
8289KP
65N
33KP
49KP
66KP
320T
124K
P
361N
472N
98K
P
Legend
Acquisition
Clinical
Intake
Pure Clinical Cluster*
Pure Intake Cluster*
Bootstrap > 90%
Tree scale: 0.001
126KP
22KP
621N
8256KP463T
194N
76KP
8291KP
72KP
91KP
403N
50KP
79KP
113KP
165KP
133KP
181K
P
545N
54KP
633N
44KP21
G
32KP
8177
KP
412T
149K
P
150KP
171K
P
567G
151K
P
7797
KP
161K
P
62KP
263N
114KP
166KP
179KP
112KP
797G
9KP452N
31KP
7647
KP
318T
123KP
182KP
131N
13-30N
7751KP
20KP
170KP
615-30N
424N
213-30N
130K
P
168KP
326T
7696KP
8057KP
103G
19KP
37T
7453KP
731T
37KP
5KP
60KP
609-3
0G
36KP
670N
7643
KP
179T
222-
30T
69KP
87KP
17KP
7676
KP
513N
339N
61KP
523N
13KP
7406
KP
229N
669T
110KP
7693
KP
35KP
582G
302T
7679KP
163KP
30KP
281N
205T
10KP
16KP
141KP
576N
127KP
443N
67KP
169KP
78KP
143KP
105KP
53KP128KP
7580
KP
187KP
21KP
82KP
176K
P
7177KP
610N58K
P
7779KP
14K
P
221N
57KP
7792KP
121KP
733N
264N
6KP
662T
122KP
116K
P
678N
723N
74KP
276G
15KP
542G
292N
664G
7420
KP 8157KP
139KP
106-30N
173KP
598N
25KP
106K
P
8271
KP
344N
56KP
38T
186KP787N
96KP
4T
8205KP
45K
P
8117KP
80G
563N606N
189KP
118K
P
239N
561N
165N
325N
705N
199-30N
137KP
108G
7725KP
66N
663T
20N
154K
P
398N
498T
140K
P
644-30G
99KP
377N
125K
P
528G
607T
94KP
188KP
28KP
119KP
131K
P
86KP
714-30N
55KP
7677KP
638N
77KP
7752KP
29KP
519N
178K
P
580N
266G
192KP
127N
156KP
204N
91N
219T
336T
175N 134N
242T
39N146K
P
220N
117KP138K
P
185KP
3KP
34KP
7485KP
7489KP
307T
190T
27KP
153KP
70KP
177KP
160KP
85KP
81KP
115K
P
299T
48N
651N
790G
384N
7577KP
100KP
52KP
657N
277T
667G
594T779N
120KP
18N
104K
P
159KP
7184KP
59K
P
148KP
7644KP
109KP
134KP
135KP
18KP
172KP
97KP
526T
7418KP
178N
223T
8289KP
65N
33KP
49KP
66KP
320T
124K
P
361N
472N
98K
P
Legend
Acquisition
Clinical
Intake
Pure Clinical Cluster*
Pure Intake Cluster*
Bootstrap > 90%
Tree scale: 0.001
Figure 1. Genomic Epidemiology of USA300 MRSA Intake, Clinical, and Acquisition Isolates
