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

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

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

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

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)

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

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

Methods: Data Collection prospective, population based surveillance Ontario January, 1 1992 to Dec 31 2000 all 155 hospital laboratories largest outpatient laboratory annual audits of sterile site cultures

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

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

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

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

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

Invasive GAS Infections Ontario (1992 – 2000)

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%

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%

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

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

Post-Surgical Invasive GAS Infection

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 1992-2000 9,078, 303 1/100,000 surgeries

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

Types of Surgeries

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

Distribution of Onset # Cases Postoperative Day

Microbiologic Profile most common M-types M1 22.4% M12 16.5% M28 10.6% M4 5.9% more M12 infections (p=0.033) less M3 infections (p=0.014)

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

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

Peripartum Invasive GAS Infection peripartum invasive GAS infections 86 cases 4.1% of all invasive GAS infections total live births in Ontario 1992-2000 1,269,722 6.8 cases /100,000 live births

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)

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)

Microbiologic Profile most common M-types M28 33.8% M1 13.0% M4 13.0% M11 5.2% 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)

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

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%

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

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

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

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

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?

Infectious Syndromes

Mechanism of Soft Tissue Infection intravascular catheterization 16 other iatrogenic interventions 6 ulcers 5 trauma 2 burns 1 other recognized lesions 2 no predisposing factor 3

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

Comparative Mortality Rates NF Bacteremia Soft Tissue Respiratory All Diagnoses

Patient Characteristics older age 61.8 +/- 22.9 yrs vs. 45.4+/-27.6 yrs (p<0.001) higher rate of underlying illness 76.2% vs. 40.3%

Microbiologic Profile distribution similar to that of non-nosocomial invasive GAS infections most common M-types M1 20.0% M3 13.0% M12 11.0% M28 7.0% M4, M22, M62 4.0% each ?is the organism acquired in the hospital or the community?

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

Factors Influencing Mortality Post Surgical Peripartum Other All Nosocomial Categories

Age Category p<0.001

Sex

Delayed Antibiotic Use

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)

Mortality by Nosocomial Category p<0.001

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

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

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 11.5% within 6 months 23.8% within 12 months 39.0%

Likelihood of True Epidemiologic/Microbiologic Linkage probability that paired cases within same hospital are truly linked (by epidemiologic/microbiologic workup) <1 week 33.3% 1 week- 1 month 14.3% 1-3 months 0% 3-6 months 0% 6-12 months 0%

Nosocomial Invasive GAS Infections Involved in Outbreaks

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

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 (1985-88) 9/9 samples tested: M-NT, T28 linked to operating room technician with psoriatic scalp lesions

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

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

A Target for Intervention?

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)

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

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

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

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.