Streptococcal Toxic Shock Syndrome

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Streptococcal Toxic Shock Syndrome

• Ellen Collett, M.D.
• AIM Presentation
• March 27, 2002

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Case
M.B. is a 73 yo white female admitted from an
outside hospital to the Plastic Surgery Service
for ID 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 ID of her thumb
and was placed on Levaquin. Her thumb worsened
and three days later she was transferred to NCBH.
On admission she underwent ID 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.
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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 70s, 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
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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 on 3L
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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 ID, 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 90s.
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.
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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, SBPwith normal BP, 45 developed hypotension within
  4 hours of presentation. Soft tissue infection
  developed into necrotizing faciitis or myositis
  in 70

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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

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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
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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

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Streptococcal Toxic Shock Syndrome

• A dramatic decline in GAS infection from the
  early 20th century until the 1980s 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

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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 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

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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

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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
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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

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• 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.

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• 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

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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