Basics
Description
- Toxic shock syndrome (TSS) is a severe, acute life-threatening illness
- Etiologic organisms:
- Staphylococcus aureus, more common (TSS)
- Group A streptococcus or GAS, less common (Streptococcal TSS or STSS)
- S. aureus produce structurally similar toxins:
- Toxic shock syndrome toxin (TSST-1)
- Enterotoxin B (SEB)
- Enterotoxin C (SEC)
- GAS pyrogenic exotoxins:
- Exotoxin A (SPEA)
- Exotoxin B (SPEB)
- Exotoxins act as superantigens causing overwhelming immune response:
- Massive cytokine production
- Induce fever directly at the hypothalamus or indirectly via interleukin-1 (IL-1) and tumor necrosis factor (TNF) production
- Enhance delayed hypersensitivity
- Suppress neutrophil migration and immunoglobulin
- Enhance host susceptibility to endotoxins
- Massive vasodilation occurs
- Serum protein and fluid shifts leading to hypotension
Etiology
- Initial cases described in young healthy menstruating females due to highly absorbent tampons
- Changes made in tampon composition to decrease incidence
- Approximately one-half of reported TSS cases are nonmenstrual:
- Surgical wounds
- Postpartum wound infections
- Mastitis
- Septorhinoplasty
- Sinusitis
- Osteomyelitis
- Arthritis
- Burns
- Nasal packing (nasal tampons)
- Cutaneous and subcutaneous lesions
- Nonmenstrual cases predominantly due to SEB and SEC producing S. aureus
- 30 " “50% of healthy adults and children carry S. aureus in the nasal vestibule, vagina, rectum and/or on the skin
- GAS infections often begin within 24 " “72 hr at the site of minor trauma, often without a visible in skin
- Despite increased incidence of Methicillin-resistant S. aureus (MRSA) infections, a recent study reported MRSA only accounting for 7% of cases
Diagnosis
Signs and Symptoms
TSS Criteria for Diagnosis
- CDC case definition:
- Fever >38.9 ‚ °C (102 ‚ °F)
- Hypotension (systolic BP <90 mm Hg) or shock
- Diffuse, blanching nonpruritic macular erythroderma rash
- Subsequent desquamation 1 " “2 wk after the onset of illness (particularly involving palms and soles)
- Multisystem involvement " ”at least 3 of the following should be present:
- GI: Profuse diarrhea or vomiting at onset of illness
- Musculoskeletal: Severe myalgias or greater than a 2-fold increase in creatine phosphokinase (CPK)
- Mucosal inflammation: Conjunctival, vaginal, or pharyngeal hyperemia
- Renal: Increase in BUN or creatinine >2 times normal upper limit or sterile pyuria without evidence of infection
- Hepatic: Total bilirubin or transaminases >2 times normal upper limit
- Hematologic: Thrombocytopenia <100,000/mm3
- CNS: Disorientation, confusion, or hallucinations
- Negative results on the following tests, if obtained: Throat, or CSF cultures, rise in titer to Rocky Mountain spotted fever (RMSF), leptospirosis, or rubeola
Streptococcal TSS (STSS) Criteria for Diagnosis
- CDC case definition:
- Isolation of GAS from a normally sterile site
- Hypotension
- Plus 2 or more of the following:
- Renal impairment (creatinine >2)
- Coagulopathy
- Liver involvement (>2 times the upper limit of normal for transaminases or bilirubin)
- ARDS
- Erythematous macular rash, may desquamate
- Soft tissue necrosis
Other
- Tachycardia frequently present
- Can rapidly progress to multisystem dysfunction (ARDS or DIC)
- STSS often presents with diffuse or localized pain " ”abrupt in onset and severe
- Pain precedes physical findings
- Nearly 80% of patients with STSS have clinical signs of soft tissue infection
Essential Workup
- Clinical diagnosis using diagnostic criteria in the absence of other attributable illness
- Thorough history and physical exam
Diagnosis Tests & Interpretation
Lab
- CBC:
- Leukocytosis or leukopenia, marked bandemia common
- Electrolytes, BUN, creatinine, glucose:
- Elevated BUN and creatinine common
- Calcium, magnesium:
- Hypocalcemia/hypomagnesemia often present
- Urinalysis:
- Normal or sterile pyuria without evidence of infection
- CPK:
- Hepatic function:
- Elevated total bilirubin, AST, ALT
- Prothrombin time (PT), partial thromboplastin time (PTT), platelets:
- Thrombocytopenia <100,000 platelets/mm3
- Culture the site of injury/infection if possible
- Blood, urine, throat, and CSF cultures as indicated:
- The case definition does not require a positive blood culture for S. aureus, but does for Streptococcus organisms.
- Serology for RMSF, rubeola, and leptospirosis
- Hepatitis B surface antigen
Imaging
- Chest x-ray " “ to rule out other sources of systemic illness
- Consider x-ray or CT scan if localized pain is concerning for abscess or necrotizing infection
Differential Diagnosis
- Staphylococcal scalded skin syndrome:
- In children <5 yr of age
- Initial macular rash followed by the formation of ill-defined bullae that can be rubbed off revealing a shiny, moist epidermis (positive Nikolsky sign)
- Scarlet fever:
- Preceding streptococcal pharyngitis
- Rash begins on the upper chest, neck, and back spreading to the remainder of the trunk, sparing the palms and soles
- Hypotension absent
- Kawasaki disease:
- Fever, conjunctival hyperemia, and erythema of the mucous membranes
- Not associated with renal failure, hypotension, or thrombocytopenia
- Stevens " “Johnson syndrome:
- Severe multisystem involvement
- Mucosal involvement of the mouth, conjunctivae, vagina, anus, and urethral meatus
- Leptospirosis:
- Transmitted through contact with infected animals
- Fever, headache, severe myalgias, and conjunctival suffusion
- Truncal rash that only desquamates in children
- RMSF:
- Rash is pink and macular, beginning on the wrists, palms, ankles, and soles spreading to the trunk and face
- Petechiae appear after 4 days
- Meningococcemia:
- Meningismus present
- Rash is petechial
Treatment
Pre-Hospital
- ABCs
- IV access
- IV fluids for hypotension
Initial Stabilization
- Again, ABCs
- Aggressive management of circulatory shock
Ed Treatment/Procedures
Hypotension
- Aggressive fluid replacement
- The 1st 24 hr may require 4 " “20 L of crystalloid and/or fresh frozen plasma (colloid)
- Caution: Large amounts of IV fluids and pressors used to treat refractory hypotension can result in rapid onset pulmonary edema
- Pressors (dopamine/norepinephrine) if fluid correction fails to restore normal arterial pressure
Infection Management
- Search for and treat the focus of infection
- Remove the source of infection (e.g., tampon, nasal or wound packing)
- Early surgical/gynecologic consultation if drainage or debridement of infectious sites necessary
- Antibiotics
- Recommended to reduce recurrence, but have not been shown to alter the course of the initial infection
- Clindamycin and linezolid are potent suppressers of bacterial toxin synthesis
- Clindamycin or linezolid+vancomycin for TSS
- Linezolid+vancomycin for TSS with extensive infection
- If TSS due to known methicillin-susceptible S. aureus then clindamycin +oxacillin or nafcillin
- Clindamycin + imipenem or meropenem or ticarcillin " “clavulanate or piperacillin " “tazobactam for STSS
- IV immunoglobulin (IVIG) treatment:
- May be efficacious in streptococcal toxic shock, but no controlled trials have proven efficacy in staphylococcal TSS.
- May initiate if no response to fluids, pressors, and antibiotics in patients with pulmonary edema and hypotension
Medication
- Clindamycin: 600 " “900 mg (peds: 20 " “40 mg/kg/24 h) IV q6 " “8h
- Dopamine: 2 " “20 Ž ¼g/kg/min IV, titrate to BP
- Linezolid: 600 mg (peds: 10 mg/kg/12 h) IV q12h
- Meropenem: 1 g IV q8h
- Nafcillin: 1.5 g (peds: 100 mg/kg/24 h) IV q4h
- Norepinephrine: 0.01 " “3 mcg/kg/min IV, titrate to BP
- Oxacillin: 1 " “2 g (peds: 50 " “100 mg/kg/24 h) IV q4h
- Piperacillin " “tazobactam: 4.5 g q6h
- Ticarcillin " “clavulanate: 3.1 g q4h
- Vancomycin: 30 mg/kg QD IV div. in 2 doses (peds: 40 mg/kg QD IV div. in 4 doses)
- Staphylococcal TSS: IVIG, 400 mg/kg over several hours
- Streptococcal TSS: IVIG 1 g/kg on day 1 then 0.5 g/kg on days 2 and 3
Follow-Up
Disposition
Admission Criteria
- Cases necessitateadmission
- ICU admission for critically ill or those in shock
Discharge Criteria
None ‚
Issues for Referral
Early surgical/gynecologic consultation if drainage or debridement is needed ‚
Follow-Up
Follow-Up Recommendations
- Patients who are bacteremic are treated for a minimum of 14 days:
- Depending on the clinical course
- Continue treatment for 14 days from the last positive culture.
- Screening for S. aureus nasal carriage in patient with S. aureus TSS and eradication of the carrier state with mupirocin
Pearls and Pitfalls
- Consider the diagnoses of staphylococcal TSS and GAS TSS
- Ensure adequate supportive care for hypotension in TSS
- Prompt and aggressive exploration and debridement of suspected deep-seated infection
- Empiric broad-spectrum antibiotics including clindamycin or linezolid is recommended
Additional Reading
- DeVries ‚ AS, Lesher ‚ L, Schlievert ‚ PM, et al. Staphylococcal toxic shock syndrome 2000 " “2006: Epidemiology, clinical features, and molecular characteristics. PLoS One. 2011;6(8):e22997.
- Darenberg ‚ J, Ihendyane ‚ N, Sj ƒ ¶lin ‚ J, et al. Intravenous immunoglobulin G therapy in streptococcal toxic shock syndrome: A European randomized, double-blind, placebo-controlled trial. Clin Infect Dis. 2003;37:333 " “340.
- Lappin ‚ E, Ferguson ‚ AJ: Gram-positive toxic shock syndromes. Lancet Infect Dis. 2009;281 " “290.
- O 'Brien ‚ KL, Beall ‚ B, Barrett ‚ NL, et al. Epidemiology of invasive group A streptococcus disease in the United States, 1995 " “1999. Clin Infect Dis. 2002;35:268 " “276.
- Stevens ‚ DL, Wallace ‚ RJ, Hamilton ‚ SM, et al. Successful treatment of staphylococcal toxic shock syndrome with linezolid: A case report and in vitro evaluation of the production of toxic shock syndrome toxin type 1 in the presence of antibiotics. Clin Infect Dis. 2006;42:729 " “730.
See Also (Topic, Algorithm, Electronic Media Element)
- Streptococcal Infections
- Kawasaki Disease
- Meningococcemia
- Leptospirosis
Codes
ICD9
040.82 Toxic shock syndrome ‚
ICD10
A48.3 Toxic shock syndrome ‚
SNOMED
- 18504008 Toxic shock syndrome (disorder)
- 240450004 Staphylococcal toxic shock syndrome (disorder)
- 240451000 Streptococcal toxic shock syndrome (disorder)