Toxic shock syndrome (TSS) is a rare toxin-mediated life-threatening acute condition caused by toxin-producing strains of Streptococcus pyogenes and Staphylococcus aureus. These bacterial strains produce superantigenic exotoxins, which trigger massive cytokine release and cause endothelial cell wall damage; this can lead to capillary leak syndrome and end-organ damage. include prolonged tampon placement, wounds (including surgical wounds), and invasive/aggressive Group A Streptococcus (GAS) infections (e.g., necrotizing fasciitis). TSS initially manifests with flu-like prodromal symptoms followed rapidly by symptoms of a , which may progress to and . Diagnostic studies often demonstrate end-organ dysfunction, and positive cultures can help narrow antibiotic therapy. TSS is a clinical diagnosis and treatment should be initiated as soon as TSS is suspected. Rapid recognition of TSS, followed by fluid resuscitation, appropriate antibiotic selection, reduction/neutralization of the toxin load, and removal of the infection source are essential for the management of TSS. TSS can be fatal if treatment is not initiated promptly; streptococcal TSS has a mortality rate of ∼ 30–80%.
Streptococcus pyogenes and Staphylococcus aureus both cause TSS; however, streptococcal TSS and staphylococcal TSS often differ in their etiologies, clinical presentation, laboratory findings, and mortality rates.
|Overview of toxic shock syndrome (TSS)|
|Streptococcal TSS||Staphylococcal TSS|
|Menstrual TSS||Nonmenstrual TSS|
|Etiology and risk factors|| || |
|Superantigens implicated in TSS |
|Onset|| || || |
|Characteristic clinical features|
|Blood cultures|| || |
|Mortality rates|| || || |
|Risk factors for TSS |
|Streptococcal TSS||Invasive GAS infections |
|Noninvasive GAS infections|| |
|Staphylococcal TSS|| Menstrual factors |
(∼ 50% of cases) 
|Nonmenstrual factors || |
|Both||Underlying medical conditions|
|Recent viral infections |
- Superantigen production: Causative organisms (S. pyogenes and S. aureus) produce (see “ ”)
Superantigen-mediated T-cell activation 
- Superantigens bypass processing and presentation by antigen-presenting cells.
- Superantigens directly connect the MHC class II molecule on antigen-presenting cells to the T-cell receptor on T-cells by forming a bridge outside of the normal binding sites → nonspecific T-cell activation → rapid activation of excessive numbers of T cells → massive cytokine release 
- SIRS: ↑↑↑ Cytokines → generalized endothelial disruption → capillary leak syndrome → generalized edema → intravascular hypovolemia → organ dysfunction and disseminated intravascular coagulation (DIC)
- Streptococcal TSS: variable onset
- Staphylococcal TSS
- Flu-like symptoms: high fever, chills, myalgia, headache, nausea, vomiting, diarrhea
- Dermal rash: more common in menstrual staphylococcal TSS than in nonmenstrual staphylococcal TSS and streptococcal TSS ; 
- Mucosal involvement 
- Evidence of points of entry: superficial cuts or burns; surgical wounds 
- Evidence of underlying GAS infections: deep infections, e.g., cellulitis, myositis, necrotizing fasciitis (may occur following blunt trauma)
Shock and end-organ dysfunction 
- Early: : tachycardia, tachypnea, high fever, altered mental status 
- Suspect TSS in a previously healthy individual presenting with hypotension and rapidly progressive multiorgan dysfunction preceded by fever with or without a rash.
- The presence of any should further raise suspicion of TSS.
- Obtain blood cultures and initiate . as soon as TSS is suspected
- and obtain additional focused cultures based on the suspected site(s) of primary infection.
- Consider and obtain diagnostics as needed.
- Consider imaging to assess for alternate diagnoses, underlying conditions, and complications.
- Consider toxin studies in patients with suspected staphylococcal TSS.
Initiate laboratory studies. as soon as TSS is suspected; do not wait for the results of
Laboratory studies 
Findings are typically nonspecific but may show evidence of infection and end-organ involvement.
- Coagulation screen: ↑ PT, ↑ PTT, ↓ fibrinogen, ↑
- Liver chemistries: ↑ ALT/AST, ↑ total bilirubin, ↓ albumin, ↓ total protein
- Basal metabolic panel 
- VBG/ABG: ↑ lactate; ABG may show signs of respiratory failure
- Inflammatory markers: ↑ ESR, ↑ CRP
- Creatine kinase: may be elevated
- Urinalysis: urinary sediment, ↑ urine leukocytes without UTI (sterile pyuria)
- Blood cultures: Obtain blood cultures in all patients, preferably before administering empiric antibiotics.
- Focused cultures
- CSF culture: Consider to rule out alternative diagnoses (e.g., meningitis, encephalitis) in patients with fever and altered mental status.
- TSST-1 assay of S. aureus culture isolate 
TSST-1 antibody titers 
- Consider in patients with menstrual TSS or recurrent staphylococcal TSS.
- Undetectable or low antibody titers indicate an increased risk of .
Imaging is not needed to make a diagnosis of TSS, but it may be considered if patients have the following symptoms:
- Severe muscle pain: CT or MRI of the affected region to evaluate for myositis, necrotizing fasciitis , or an abscess
- Altered mental status: CT head to rule out an alternate intracranial cause 
- Respiratory symptoms: CXR to evaluate for concurrent pneumonia or the development of ARDS
The symptoms of TSS overlap with many other conditions, including the following:
- See also “Differential diagnoses by associated finding” in “Fever.”
- Hemodynamic resuscitation as needed
- Identify and manage the source of infection; obtain cultures of the suspected primary site(s) of infection.
- Initiate within 1 hour of presentation; consider IVIG as adjunctive therapy in streptococcal TSS.
- Consider measures to prevent recurrent TSS, especially in patients with staphylococcal TSS.
- TSS is a reportable disease in the US; see “Public health surveillance” below for details.
TSS is a life-threatening emergency that requires early diagnosis and a multidisciplinary approach to management.
- Urgent IV fluid resuscitation is indicated for hemodynamically unstable patients.
- Hypotension refractory to fluids: Administer .
- See “Management of sepsis” for further guidance.
Management of source(s) of infection 
- Examine for skin lesions and wounds.
- Remove any foreign bodies (e.g., tampons, nasal packs, surgical packs).
- Drain infected fluid collections (e.g., abscess).
- Urgent surgical consult for suspected necrotizing fasciitis/myositis.
Obtain cultures from any potential site(s) of infection.
Antibiotic therapy 
- Indication: all patients with suspected TSS; preferably initiated within an hour of presentation
- A bactericidal antibiotic that covers both S. pyogenes and S. aureus (i.e., vancomycin, beta-lactam antibiotic)
- PLUS a protein-synthesis inhibitor (e.g., clindamycin, linezolid).
- Tailor antibiotic therapy to the antibiogram once available.
- For patients with penicillin allergy, replace the beta-lactam antibiotic with vancomycin.
- Total duration of antibiotic therapy: not well-defined; 2 weeks minimum
- Treat concurrent or underlying infection: e.g., see “ ”
Protein synthesis-inhibiting antibiotics inhibit toxin production but as they are bacteriostatic, they should be used in combination with a bactericidal antistreptococcal and/or antistaphylococcal antibiotic.
|Empiric antibiotic therapy for TSS |
Causative organism unclear
| Based on suspected pathogen |
(i.e., based on history, clinical features, Gram stain, or cultures)
|Suspected streptococcal TSS |
|Suspected staphylococcal TSS |
Adjunctive therapy 
- Consider IVIG in adults with streptococcal TSS (e.g., those with hypotension refractory to vasopressors). 
Consults and disposition
Acute management checklist for suspected TSS
- Suspect TSS in an otherwise healthy individual presenting with hypotension and rapidly progressive multi-organ dysfunction preceded by fever with/without a rash.
- Assess for signs of sepsis; if present, see also “Acute management checklist for sepsis.”
- In patients with hypotension and signs of shock:
- Initiate 1 hour of presentation. within
- Identify and manage any likely source of infection.
- Urgently consult appropriate surgical services, as needed: ENT, OB/GYN, general surgery, orthopedics.
- Consult critical care/infectious disease to guide management.
- Toxic shock syndrome is a reportable disease; see “Public health surveillance.”
Public health surveillance
- TSS is a reportable disease in the United States. 
- The CDC has described features that are typical of streptococcal TSS and nonstreptococcal TSS for reporting purposes only; these criteria should not be used for diagnosis or to guide treatment.
Reporting criteria for toxic shock syndrome (TSS)
|Streptococcal TSS ||Nonstreptococcal (staphylococcal) TSS |
|Causative pathogen|| |
Use these criteria for reporting only, not diagnosis! Early, aggressive treatment is recommended to prevent dangerous sequelae even if not all criteria have been met.
- Most often occurs with staphylococcal TSS
- Caused by persistent colonization by TSST-1-producing strains of S. aureus in patients with an inadequate antibody response to a previous episode of TSS 
- recurrent TSS. help identify patients at risk of developing
- Arrange a follow-up appointment for patients with staphylococcal TSS after discharge to screen for colonization of TSST-1-producing S. aureus.
- Consider nasal decolonization with mupirocin and/or vaginal decolonization with antistaphylococcal antibiotics. 
- Consider topical decolonization with chlorhexidine washes in patients with recurrent skin and soft tissue staphylococcal infections. 
- Educate patients to avoid the use of tampons, menstrual cups, or sponges if they have a history of menstrual TSS.