1. Nosocomial Invasive Group A Streptococcal Infections
Nick Daneman
PGY-2, Internal Medicine, University of Toronto

2. Presentation Overview
brief background literature
objectives and methods
results and discussion
nosocomial vs non-nosocomial invasive GAS infections
heterogeneous nosocomial categories
post-surgical infections
peripartum infections
other nosocomial GAS infections
factors influencing mortality
cross-transmission
conclusions

3. Invasive Group A Streptococcal Infections
resurgence in invasive Group A Streptococcal (GAS) infections in last 2 decades
prompted numerous large hospital-based and population-based case series

4. Invasive GAS Infections: Case Series
>40 large case series of invasive GAS infections since 1985
significant proportion of cases have been nosocomial
range: 5.4 to 39%
median: 13.5%
no analysis of nosocomial subgroup

5. Nosocomial Outbreaks
literature confined to retrospective reports of outbreaks
51 outbreaks described
wide array of clinical settings
surgery, peripartum, burn units, ICU, …
large numbers of patients involved
range 2 to 25
mean 9
health care workers as carriers
sites of colonization (pharyngeal, nasal, anal, vaginal)

6. after single case identified:
CDC Recommendations for Prevention of Invasive GAS Disease among Postpartum and Surgical Patients
CID Oct. 2002
after single case identified:
enhanced surveillance
storage of GAS isolates from index patient and any additional cases
after second case identified:
epidemiologic links sought
microbiologic links determined
culture specimens obtained from health care workers

7. Objectives
1) to provide the first prospective description of invasive nosocomial group A streptococcal infections
2) to evaluate the risk of cross-transmission within the hospital setting

8. Methods: Data Collection
prospective, population based surveillance
Ontario
January, to Dec
all 155 hospital laboratories
largest outpatient laboratory
annual audits of sterile site cultures

9. Definitions invasive group A streptococcal (GAS) infection
isolation of GAS from a normally sterile body site
nosocomial infection
disease neither present nor incubating at the time of admission
surgical site infection (NNIS definition)
occurring within 30d of operation, or within 1 year if implanted material

10. Definitions peripartum GAS infections outbreak
all nosocomial unless signs or symptoms of disease evident prior to delivery
outbreak
2 or more cases of disease linked by epidemiologic and microbiologic investigations

11. Microbiologic/Laboratory Methods
M - protein, T-agglutination typing at National Centre for Streptococcus in Edmonton, Alberta
pulse field gel electrophoresis used to evaluate epidemiologically associated cases

12. Statistical Analysis
surveillance data double-entered, stored, sorted and analyzed via SAS statistical software
differences in group proportions analyzed by chi-square/Fisher’s two-tailed test
differences in group means analyzed by Student’s t-test

13. Results nosocomial vs non-nosocomial invasive GAS infections
heterogeneous nosocomial categories
post-surgical infections
peripartum infections
other nosocomial GAS infections
factors influencing mortality
cross-transmission

14. Invasive GAS Infections Ontario (1992 – 2000)

15. Nosocomial vs. Non-Nosocomial GAS infections
Chi-sq /Ttest
Sex (%M)
36.9%
54.0%
p<0.001
Age
-children <17
-adults
-elderly >65
7.6%
60.5%
31.9%
21.5%
48.2%
30.4%
Underlying
Illness
42.2%
40.4%
p=0.554
Chicken Pox
0.0%
4.8%

16. Nosocomial vs. Non-Nosocomial GAS infections
Chi-sq /Ttest
Necrotizing
Fasciitis (NF)
5.7%
11.8%
p<0.001
Streptococcal Toxic Shock Syndrome (STSS)
7.7%
13.7%
p=0.004
Mtype 1 or 3
22.2%
35.5%

17. Nosocomial vs. Non-Nosocomial GAS infections
Chi-sq /Ttest
Requiring Surgical Intervention
25.4%
38.0%
p<0.001
ICU admission
21.5%
27.8%
p=0.029
Mortality at 30 days
16.2%
15.1%
p=0.640

18. Nosocomial Categories
Post-surgical
95 cases
Peripartum
86 cases
Other
109 cases

19. Post-Surgical Invasive GAS Infection

20. Post-surgical Invasive GAS infection
post-surgical invasive GAS infections
95 cases
4.5% of all invasive GAS infections
3 fold higher rate than estimated by CDC
total surgeries in Ontario
9,078, 303
1/100,000 surgeries

21. Types of Surgeries digestive system (27.6%)
musculoskeletal system (23.7%)
nervous system (10.5%)
cardiovascular system (9.2%)
integumentary system (9.3%)
female genital system (5.3%)
male genital, ENT, endocrine, ophthalmologic, respiratory, urinary

22. Types of Surgeries

23. Time of Onset median onset = postoperative day #5 30.9% within 2 days
timing did not significantly influence mortality

24. Distribution of Onset
# Cases
Postoperative Day

25. Microbiologic Profile
most common M-types
M %
M %
M %
M4 5.9%
more M12 infections (p=0.033)
less M3 infections (p=0.014)

26. Outcomes icu admission 27.6% mechanical ventilation 20.5%
30 day mortality 8.4%

27. Summary GAS is a rare but important cause of post-surgical infection
can affect any organ system
both minor and major procedures
wide distribution of onset

28. Peripartum Invasive GAS Infection
peripartum invasive GAS infections
86 cases
4.1% of all invasive GAS infections
total live births in Ontario
1,269,722
6.8 cases /100,000 live births

29. Patient Population different gender distribution
all women
different age distribution
all adults
less underlying illness
2.3% vs 39.8% non-nosocomial infection (p=0.001)

30. Illness Profile no necrotizing fasciitis low rate of STSS
0.0% vs. 11.7% non-nosocomial (p=0.002)
low rate of STSS
2.4% vs. 13.6% non-nosocomial (p=0.015)

31. Microbiologic Profile
most common M-types
M %
M %
M %
M %
more M28 (p=0.001) and M4 infections (p=0.001)
less M1 (p=0.005), M3 (p=0.003) and M12 infections (p=0.034)

32. Outcomes icu admission 11.3% mechanical ventilation 1.3%
30 day mortality 1.2%

33. Comparison to other Women of Childbearing Age
Peripartum Cases
Women of Childbearing Age
Rate of underlying illness
2.3%
26.8%
Mortality
1.2%
7.8%

34. CDC surveillance Ontario CDC 1995-2000 Number of cases 86 87
Proportion of GAS cases
4.1%
2.2%
Rate/1000
live births
0.07
0.06
Mortality
1/86
3/87
#1 Mtype
M28

35. Summary relatively common obstetrical problem (0.07/1000 live births)
better prognosis than all other categories of invasive GAS infection
lower burden of underlying illness
different microbiologic profile

36. Other Invasive GAS Infections (non-surgical, non-obstetrical)

37. Non-surgical, non-obstetrical invasive GAS infections
109 nosocomial cases were neither surgical nor peripartum
this group of infections has never been characterized

38. Time of Onset
time from admission to documentation of invasive GAS infection
median: 10.5 days
mode: 3 days
17/109 (15%) occurred after 2 mos of hospitalization
?is the organism acquired in the hospital or the community?

39. Infectious Syndromes

40. Mechanism of Soft Tissue Infection
intravascular catheterization 16
other iatrogenic interventions 6
ulcers
trauma
burns
other recognized lesions 2
no predisposing factor 3

41. Comparative Mortality rates
Infectious
Syndrome
Nosocomial
(non-surgical,
non-peripartum)
Non-Nosocomial
Chi-square
Primary Bacteremia
42.9%
24.2%
0.019
Soft Tissue
Infection
20.6%
10.2%
0.056
Necrotizing Fasciitis
56.5%
32.9%
0.024
Respiratory
66.7%
23.9%
0.017
All Diagnoses
37.0%
15.2%
0.001

42. Comparative Mortality RatesNF
Bacteremia
Soft Tissue
Respiratory
All Diagnoses

43. Patient Characteristics
older age
61.8 +/ yrs vs /-27.6 yrs
(p<0.001)
higher rate of underlying illness
76.2% vs. 40.3%

44. Microbiologic Profile
distribution similar to that of non-nosocomial invasive GAS infections
most common M-types
M %
M %
M %
M %
M4, M22, M % each
?is the organism acquired in the hospital or the community?

45. Summary
a large group of nosocomial invasive GAS infections occur in non-surgical, non-obstetrical settings
widely varied
time of onset
mechanisms of infection
infectious syndromes
poor outcome compared with non-nosocomial GAS infections
older, sicker patient population

46. Factors Influencing Mortality
Post Surgical
Peripartum
Other
All Nosocomial Categories

47. Age Category
p<0.001

48. Sex

49. Delayed Antibiotic Use

50. Delayed Antibiotic Use
<24h vs. >24h
10.6% vs. 27.0% mortality (p=0.012)
<48h vs. >48h
11.2% vs. 30.8% mortality (p=0.009)

51. Mortality by Nosocomial Category
p<0.001

52. Other Factors Influencing Mortality
any underlying illness OR 7.3
cardiac disease OR 6.3
kidney disease OR 19.7
malignancy OR 2.4
necrotizing fasciitis OR 5.0
STSS OR 10.4
M1 or M3

53. Cross-Transmission temporal clustering prevalence of true outbreaks
comparison of sporadic and outbreak linked cases
size of outbreaks
a target for intervention

54. Temporal Clustering of Nosocomial Invasive GAS infections
given one nosocomial invasive GAS infection, the probability of an ensuing infection within the same hospital:
within 1 week 4.0%
within 1 month 6.5%
within 3 months %
within 6 months %
within 12 months %

55. Likelihood of True Epidemiologic/Microbiologic Linkage
probability that paired cases within same hospital are truly linked (by epidemiologic/microbiologic workup)
<1 week %
1 week- 1 month 14.3%
1-3 months 0%
3-6 months 0%
6-12 months 0%

56. Nosocomial Invasive GAS Infections Involved in Outbreaks

57. Comparison of Sporadic and Outbreak-linked Cases
no significant differences in
patient characteristics (age, sex, illness)
nosocomial category
presence of necrotizing fasciitis
presence of STSS
icu admissions
mortality

58. Magnitude of Outbreaks
reported nosocomial outbreaks are large
mean 9 patients
several outbreaks involving more than 10 pts
e.g. Mastro et al., NEJM Oct.4, 1990
20 post-surgical invasive GAS infections
3 year period ( )
9/9 samples tested: M-NT, T28
linked to operating room technician with psoriatic scalp lesions

59. Magnitude of Outbreaks
in our study, “outbreaks” very small:
15 involve only 2 cases
4 involve > 2 cases
0 involve >5 cases
why smaller outbreaks?
modern infection control practices
literature bias towards dramatic outbreaks

60. A Target for Intervention
most outbreaks involve only 2 cases
greatest yield = preventing the second case
widespread investigations and chemoprophylaxis not economically feasible
target cases at high risk of secondary nosocomial transmission

61. A Target for Intervention?

62. High Risk for Transmission: NF in the ICU
4 community-acquired invasive GAS infections caused secondary nosocomial transmission
4/2032 (0.2%)
3 involved NF in ICU setting
3/136 (2.2%)
1 did not involve NF or ICU setting
1/1975 (0.05%)
(p<0.001)

63. Summary
unrelated nosocomial invasive GAS infections are frequently clustered in time & space
substantial likelihood of 2 cases being causally linked if they occur within 1 month
investigators must think laterally
index and secondary cases
linked to invasive and non-invasive cases
linked to nosocomial and community acquired cases
similar characteristics to sporadic cases
outbreaks usually limited to 2 cases
potential benefit to isolation and prophylaxis when necrotizing fasciitis case admitted to icu

64. Conclusions
first descriptive analysis of nosocomial invasive GAS infections
differ from non-nosocomial infections
heterogeneous group
post surgical infections
diverse surgeries and time of onset
peripartum infections
common, excellent prognosis
non-surgical, non-obstetrical infections
varied onset, syndromes, mechanism of infection
poor prognosis

65. Conclusions nosocomial outbreaks true outbreaks are common
barriers to detection
temporal clustering of unrelated cases
cross-transmission between community and nosocomial cases
similarities between sporadic and linked cases
small size of outbreaks
best target for prevention may be preventing first transmission from high risk cases

66. Acknowledgements Karen Green Dr. D. Low Dr. A McGeer
Toronto Invasive Bacterial Disease Network
We thank the microbiology laboratories, infection control practitioners, and physicians across Ontario without whose time, effort, and enthusiasm this surveillance would not be possible and the many staff members of the Ontario Ministry of Health and public health departments across Ontario who have supported this study.