Streptococcal Toxic Shock Syndrome

1. Streptococcal Toxic Shock Syndrome Ellen Collett, M.D. AIM Presentation March 27, 2002

2. Case: M.B. is a 73 yo white female admitted from an outside hospital to the Plastic Surgery Service for I+D of her right thumb. The patient reported a cut to her hand about 2 days prior to presenting to the outside hospital. She was working in the yard, but she does not remember specifically how she cut her thumb. At home she began experiencing nausea, vomiting, diarrhea, chills, ? fevers, and pain in her thumb. At the outside hospital she underwent I+D of her thumb and was placed on Levaquin. Her thumb worsened and three days later she was transferred to NCBH. On admission she underwent I+D of right thumb and she was started on Unasyn. The following evening the patient become hypoxic with sats 88-93% on 2 L NC. She became progressively worse with sats at 90% on 3L. Internal Medicine was consulted the following day. The patient had sats of 89% on 3 L. She did not complain of SOB or chest pain. She reported a slight occasional cough. She had not experienced N/V/D since her admission at the outside hospital. Overall she feels improved since her admission.

3. PMH: hypertension, hypothyroid, single kidney (congenital), h/o pneumonia MEDS: Norvasc 5 mg qd, Atenolol 25 mg qd, Celebrex 200 mg qd, Premarin 0.625 mg qd, Lasix 20 mg qd, Synthroid .75 mg qd, Zoloft 100 mg qd, Depakene 350 mg bid, Unasyn 3000 mg q 6h, Heparin 5000 u SC bid All: Codeine FH: son with DM SH: no tobacco use and no history of tobacco use, no alcohol or drug use. Homemaker in Bluefield, WV. PE: T 97.8 Tmax 100, BP 102/54, 89% 3 L NC, pulse 70’s, RR 20 elderly female in NAD PERRL, EOMI, OP clear neck supple, no LAD S1, S2 regular, no M/R/G lungs with crackles bilaterally abd soft, NT, ND, BS + extremities without edema, right thumb with dressing skin without rashes

4. EKG NSR at 70 Echo: EF 55%, no segmental wall abnormalities CXR 3/13 Bilateral airspace disease CXR 3/15 interval improvement but findings c/w pulm edema. Superimposed infection can not be ruled out Labs:on admission: wbc 13.6, hgb 12.3, plt 216, 74% segs, 2% bands, 13% lymphs, Na 140, K 3.5, Cl 103, CO2 26, BUN 13, Cr 1.1 Gluc 108, Ca 8.6. PT 10.7, PTT 28.4, INR 0.78 Wound culture: 4+ beta hemolytic GAS day of consult wbc 10.2 hgb 11.9, plt 308. Na 135, K 3.4, Cl 95, CO2 26, BUN 16 Cr 1.2, Gluc 115, Ca 7.7, Prot 6, Alb 3, Tbili 0.9, Alk Phos 142, AST 36, ALT 37, CK 37, Tn <0.1 ABG 7.4/43.5/64/28/93% on 3L

5. The patient became progressively more hypoxic. She was placed on Azithromycin and Doxycycline. She remained afebrile and her blood pressures remained stable. She continued to deny SOB or chest pain. Her CXR showed no improvement. Six days after the I+D, she underwent amputation of the distal right thumb. Her chest CT done the same day showed bilateral upper lobe ground glass attenuation with areas of consolidation c/w pneumonia with some similar appearing but less extensive areas within right middle lobe and bilateral lower lobes, small bilateral pleural effusions The following day she required 80% FS with sats in the low 90’s. labs wbc 12.2, hgb 10.1, plt 634 65% segs, 1% bands, 27% lymphs Na 131, K 4.1, Cl 93, CO2 27, BUN 17, Cr 1.2, Gluc 94, Ca 7.7 ABG 7.47/36/56/26/91% on 6 L She was transferred to Gen Med and placed on Vanc, Gent, and Penicillin. The following day she improved, requiring 6L NC. Her supplemental oxygen needs decreased and one week later she was on RA. Blood and urine cultures were negative.

6. Streptococcal Toxic Shock Syndrome • Early symptoms (24-48 hrs) may be flu-like, with fever, sore throat, swollen lymph nodes, vomiting, diarrhea, and rash. Localized pain out of proportion to the injury is a hallmark • Pain is severe and acute in onset. Most commonly involves extremity but may be similar to peritonitis, PID, acute MI, pericarditis • Tachycardia, tachypnea, persistent fever and increasing pain at site of infection occur • Fever is persistent and hypotension and shock develop. Multi organ failure, tachycardia, fasciitis and myositis may occur. • In a 1992 study fever was the most common presenting sign in STSS. Confusion was found in 55%, tachycardia in 80%, SBP<110 n 55%. In those with normal BP, 45% developed hypotension within 4 hours of presentation. Soft tissue infection developed into necrotizing faciitis or myositis in 70%

7. Streptococcal Toxic Shock Syndrome • Superantigen induced cytokine release causes vasodilation, DIC, myocardial suppression, renal failure, ARDS, and multiple organ failure • Capillary leak syndrome characterized by hypotension, hypoalbuminemia, and generalized edema • Occurrence of shock and multiorgan failure early in the course of infection characterizes streptococcal toxic shock syndrome and differentiates it from other types of invasive GAS infection • Streptococcal M types 1 and 3 have been associated with invasive GAS infections and strep TSS. M protein is the major virulence factor of GAS and strains with M protein are resistant to phagocytosis, multiply rapidly in blood and can initiate disease • Streptococcal pyrogenic exotoxins (SPE) A and C have also been associated with severe invasive GAS infections

8. Streptococcal Toxic Shock Syndrome • Portals of entry for strep are the pharynx, skin and vagina in 50% of cases. Surgical procedures also provide portals of entry. Rarely infection occurs secondary to streptococcal pharyngitis • Lack of antibody to superantigens and lack of SPE neutralizing antibodies are associated with development of strep TSS • 60-100% of patients with streptococcal TSS are bacteremic (unlike staph TSS) • Mortality rate is higher than with staph TSS--30-50% with fasciitis and up to 80% with myositis • Development of streptococcal TSS during invasive streptococcal infection correlates with significantly higher mortality •Lab finding s include elevated creatinine, hemoglobinuria, hypoalbuminemia, hypocalcemia, elevated CK with deeper soft tissue infections, mild leukocytosis with left shift, thrombocytopenia and anemia

9. Diagnostic Criteria for Streptococcal TSS • Isolation of GAS from • A sterile site for a definite case • A nonsterile site for a probable case • Hypotension • Two of the following: • Renal dysfunction • Liver involvement • Erythematous macular rash • Coagulapathy • Soft tissue necrosis • ARDS

10. Streptococcal Toxic Shock Syndrome • A dramatic decline in GAS infection from the early 20th century until the 1980’s when invasive GAS reemerged • CDC estimates rate of invasive GAS infections in U.S. about 1/100,000 • Patients between the ages of 20 and 50 years old most commonly afflicted with streptococcal TSS • Risk factors for invasive GAS infections and strep TSS include wounds, chickenpox in children, NSAID use, pregnancy and other underlying illnesses • Outbreaks of invasive GAS infections have occurred in closed environments such as nursing homes and hospitals

11. Streptococcal Toxic Shock Syndrome • A study examined invasive GAS infections in Atlanta from 1994-1995 • 183 cases of invasive GAS identified (annual incidence 5.3 cases/100,000) • 14% of invasive GAS were STSS (annual incidence 0.71 cases/100,000) • 64% were males • Average age 44.7 years • 12% were <10 years old, 72% 10-65 years old, 16% >65 years old • Mortality was 48% • Focus of infection: 40% skin/soft tissue, 24% pneumonia, and 20% without identified focus of infection • 60% required MV, 52% required pressors • 80% had underlying conditions • 32% acute/chronic skin condition, 20% DM, 12% Alcohol abuse, 8% chronic lung disease, 8% malignancy, 8% AIDS

12. Severe Group A streptococcal infections associated with a toxic shock-like syndrome and scarlet fever toxin AStevens D, Tanner M, et alNew England Journal of Medicine, 1989 • Group of 20 patients between 1986 and 1988 with GAS soft tissue infection associated with increased morbidity and mortality • Median age was 36 years old • 55% had necrotizing faciitis, 95% had shock, 80% had renal impairment, 55% had ARDS • Mortality rate was 30% despite antibiotics, supportive care and surgical intervention when necessary • 19 had positive tissue cultures and 12 had positive blood cultures • 80% of the patients were less than 50 years old and most did not have an underlying disease, none were immunocompromised and most did not have obvious portals of entry

13. •Most of the patients had soft tissue infection but deeper infections were also seen • M serotype 1 and 3 most common and 80% of the isolates produced pyrogenic exotoxin A • The prevalence of shock, renal failure and mortality was not significantly different in patients with or without bacteremia

14. Invasive Group A streptococcal infections in North Carolina: Epidemiology, clinical features and genetic and serotype analysis of causative organismsKiska D, Thiede B, et al. Journal of Infectious Diseases, 1997 • In a study at UNC, patients in central NC with invasive GAS in 1994 and 1995 were compared with patients from 1987-1993. • At UNC, only 2 to 10 cases of invasive GAS infection/year from 1987 to 1993. In 1994, 34 invasive infections occurred and in 1995 there were 19. • GAS recovered from blood and other sterile body fluids, abscesses and soft tissue. Samples also included if GAS in predominant numbers from cultures of nonsterile sites (pharyngeal abscesses, tracheal aspirates and urine) • Total of 96 patients from December 1993-December 1995 and 35 patients from 1987-1993

15. In the 1993-1995 group median age was 27 years old with 39% of the group less than 18 years old. Clinical site of infection identified in 88% of the patients with the most common site being soft tissue (67%). Trauma or surgery was the most common predisposing condition (49%). • In the 1987-1993 group median age was 20 years with 43% less than 18 years old. A clinical site of infection was identified in 77% of the patients. 30% had decreased host defenses as a predisposing condition • Only 1 case of TSS and no necrotizing faciitis in 1987-1993. In the 1993-1995 group 13% developed necrotizing faciitis and 21% developed TSS • Overall case fatality rate of 3% from 1987-1993 and 11% from 1993-1995.

16. Streptococcal TSS was associated with high mortality rates (71%) in those >60 years old and patients 21-40 years old. The majority of the elderly patients had compromised host defenses. The younger patients typically had no underlying predisposition for infection • TSS accounted for all 11 deaths. Only 5 pediatric patients developed necrotizing faciitis or TSS but there were no deaths • M1 and M3 serotypes predominated in invasive infections and increased with the rise in necrotizing fasciitis and TSS • May be from inherent virulence factors or decreased herd immunity from infrequent exposure over past 50-60 years

17. Treatment • Early surgical intervention with drainage, debridement, fasciotomy or amputation to prevent spread of infection • Supportive care with fluids, pressors, vent support • Antibiotics: penicillin, erythromycin, clindamycin (ceftriaxone) • Antibiotic therapy may be insufficient once severe symptoms develop due to poor circulation and thrombosis of the blood vessels of the infected tissue