1. Hospital Acquired Group A Streptococcal Infections What have we learned? Nov. 20, 2008 Nick Daneman Division of Infectious Diseases Sunnybrook Health Sciences Centre

2. Invasive Group A Streptococcus: Dramatic Illness

7. Invasive Group A Streptococcus: Dramatic Outbreaks 75 CASES, 10 DEATHS

8. Invasive Group A Streptococcus: Dramatic Hospital Outbreaks 3 year outbreak of Group A Streptococcal surgical site infections Mastro NEJM 1990 56 Cases of Group A Streptococcal infection in a nursery Nelson J. Ped. 1976

9. 1 nosocomial case: –enhanced surveillance –isolate storage 2 nosocomial cases within 6months: –typing of isolates –if same strain: epidemiologic investigation culture health care workers CID 2002

10. expert opinion review of a handful of literature outbreaks CID 2002

11. Objectives describe hospital acquired cases of invasive group A streptococcal infections in Ontario describe hospital outbreaks of invasive group A streptococcal infections –in Ontario prospective surveillance –systematic review of the literature provide evidence-based recommendations

12. Methods: Prospective Surveillance Ontario Group A Strep Study Group population-based surveillance Ontario (population 11,000,000) 1992 - 2000 all invasive isolates microbiology labs –all Ontario hospitals –largest outpatient microbiology lab

13. Methods: Definitions invasive –group A streptococcus from a sterile site hospital acquired –neither present nor incubating at admission outbreak –> 2 cases of culture confirmed, symptomatic GAS infection –epidemiologically linked –caused by same M, T type –indistinguishable by PFGE

14. Methods: Literature Review MEDLINE database, 1966-2004 search terms “Streptococcus pyogenes” OR “group A streptococcus” OR “group A streptococcal” nosocomial OR outbreak OR cross-transmission review of reference lists manuscripts reviewed by 2 investigators

15. Objectives describe hospital acquired cases of invasive group A streptococcal infections in Ontario describe hospital outbreaks of invasive group A streptococcal infections –in Ontario prospective surveillance –systematic review of the literature evidence based recommendations

16. CID 2005

17. Ontario Prospective Surveillance 1992- 2000 2,351 invasive group A strep infections 291 (12.4%) hospital-acquired 86 postpartum infections 109 non-surgical, non-obstetrical 96 surgical site infections

18. Hospital-acquired cases

19. Differences cannot be explained by M-types

20. Group A Strep Surgical Site Infections 96 cases out of 9,078,030 surgical admissions =1.1 cases / 100,000 surgical admissions entire range of surgical procedures –digestive tract 28% –musculoskeletal 24% –cardiovascular 9% –nervous system 11% –skin and soft tissue 9% –urogyne 8% –…

21. Timing of Invasive Group A Streptococcal Surgical Site Infections median = 5d

22. Group A Strep Postpartum infections 86 cases out of 1,269,722 live births =0.7 cases / 10,000 live births ~ 1/10 as common as neonatal group B strep infections but these were infections of mothers (only 2 newborn cases, both non-invasive)

23. Post-partum M28 association

24. M28 predominated in CDC postpartum surveillance 1 also predominates in perineal infection in children 2 express surface protein (R28) related to cell-surface molecules in Group B Strep which enhance binding to cervical epithelium 1. Chuang CID 2002; 2. Mogielnicki Ped 2000; 3. Stalhammar MM 1990

25. Group A Strep Non-surgical, non-obstetrical infections 109 cases 40% of all cases –(despite no mention in nosocomial group A strep guidelines) time of onset: –median 10.5 days –range 2d to >1 year ?community or nosocomial acquisition?

26. Group A Strep Non-surgical, non-obstetrical infections most common syndromes –primary bacteremia 33% –non-necrotizing soft tissue infection 32% –lower respiratory tract infection 21% –necrotizing fasciitis 6% 32 / 35 skin infections were associated with pre- existing skin breakdown –IV lines (16), G-tubes /tracheostomy (6), chronic ulcers (5), trauma (2), burns (1), other lesions (2)

27. Risk factors for mortality among hospital-acquired cases

28. Objectives describe hospital acquired cases of invasive group A streptococcal infections in Ontario describe hospital outbreaks of invasive group A streptococcal infections –in Ontario prospective surveillance –systematic review of the literature recommendations

30. Complementary methods Literature Review Prospective Surveillance Publication bias Hawthorne effects

31. Number of Outbreaks Literature 66 publications 60 available61 outbreaks Surveillance 2,351 invasive cases 291 nosocomial 29 outbreak-linked (20 outbreaks)

32. Outbreak Magnitude Literature Review Prospective Surveillance p Median cases (range) 10 (2-56) 2 (2-10) <0.001 Median duration (range) 30d (1-1095) 6d (1-30) <0.001

33. Outbreak Patient Composition

34. Outbreak Initiation: Index Cases 3/4 of indexes cases = nosocomial cases two other sources of outbreaks: –ill health care workers 5 literature outbreaks* –community-acquired cases 9 of 11 admitted to ICU 5 of 9 necrotizing fasciitis† * DiPersio 1996, Holloway 1967, Kakis 2002, Lannigan 1985, Nicolle 1986, Schwartz 1992 †Burnett 1990, Decker 1985, Ejlertsen 2001, Quinn 1965, Walter 1974

35. Outbreak Initiation: Rapid Tempo median interval between first two cases –literature outbreaks: 2.0d –surveillance outbreaks: 4.5d interval between first two cases <1 month in 80 of 81 outbreaks

36. Outbreak Propagation patient to patient47% colonized health care worker27% environmental9% mixed6% insufficient information11%

37. Outbreak Propagation: Colonized Health Care Workers Colonized health care worker Patient-to-Patient/Environmental

38. Outbreak Propagation: Colonized Health Care Workers site of health care worker colonization –31 pharyngeal only –10 anal –2 vaginal –5 skin

39. Outbreak Propagation: Environmental sources bidet hand shower vinyl sheet airflow mattress multidose vaccine vials (3) food borne outbreak (1) Claesson 1985, Decker 1976, Gordon 1994, Reid 1983, Rutihauser 1999, Decker 1985

40. Outbreak Termination: Treatment of Colonized HCWs data from 24 literature outbreaks first regimen usually successful: –pharyngeal carriage only:9/9 (100%) –nonpharyngeal carriage:11/15 (73%) 4 failures * –2 ongoing transmission –2 late relapses (4mos and 15mos) all ultimately successfully eradicated * Berkelman 1982, McIntyre 1968, Schaffner 1969, Viglionese 1991

41. Outbreak Termination: Patient to Patient Transmission multifaceted control measures required 1st attempt usually unsuccessful (14/25) most effective control measures –ward closure (86% success) –mass treatment/prophylaxis (69% success)

42. 5 Recommendations

43. #1: Target all Nosocomial Cases Hospitalized CID 2002

44. #2: Isolation of Necrotizing Fasciitis 11 community acquired index cases majority due to necrotizing fasciitis admitted to intensive care unit  isolate necrotizing fasciitis on admission (pending cultures)

45. #3: immediate investigations current guidelines for single case: –enhanced surveillance + isolate storage short interval between first cases (2-4d) will not prevent second case majority of outbreaks only 2 cases therefore, preemptive investigations

46. #4 One month ceiling current guidelines for 2 cases in 6 months: –type isolates; if same strain: epidemiologic investigations culturing health care workers virtually no outbreaks with initial interval >1month limit investigations to cases within 1 month

47. #5: Tailor Investigation by Ward health care worker carriers broad epi search for linked staff cultures –throat, anal, vaginal, skin test of cure for non- pharyngeal carriers patient and environmental reservoirs multifaceted infection control strategies –isolation/cohorting –disinfection –sterilization –ward closure –mass treatment Surgery/Labour & DeliveryMiscellaneous Wards

48. Summary 12% of invasive group A streptococcal infections are hospital-acquired three groups with different characteristics and outcomes –surgical (1/100,000 surgeries) –postpartum (0.7/10,000 births) –non-surgical/obstetrical (largest group)

49. Summary 10% of hospital-acquired cases are associated with outbreaks –90% of hospital-acquired cases are sporadic when outbreaks do occur they are smaller and shorter than those in the literature

50. Summary these complementary data sources lead to 5 recommendations: –1: include all hospital cases in guidelines –2: isolate necrotizing fasciitis –3: immediate investigations after 1 case –4: one month ceiling for linked cases –5: tailor investigations & management to ward

51. Acknowledgements Dr. Allison McGeer Dr. Donald Low Karen Green Ontario Group A Streptococcal Study Group