Toxic Shock Syndrome

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A 36-year-old man presents to the emergency department (ED) with altered mental status. Family reveals no significant medical history outside of recurrent epistaxis and a progressive flu-like illness for the past week. Vital signs are: temperature 39.4 degrees Celsius, heart rate 128, blood pressure 88/56, respiratory rate 24 breaths per minute, and oxygen saturation 98% on room air.

Physical exam reveals an obtunded patient responsive only to painful stimuli. Desquamation of the palms is noted, as well as diffuse macular erythroderma. Unilateral nasal packing is found on inspection of the right nasal cavity. Lab studies are remarkable for white blood cell count of 42,000 cells/µL, creatinine of 3.4 mg/dL, total bilirubin of 4.3 mg/dL, and lactate of 5.4 mmol/L. The clinician suspects toxic shock syndrome and begins aggressive fluid resuscitation.

Pathogenesis

Toxic shock syndrome (TSS) refers to an infection with Staphylococcus aureus or Streptococcus pyogenes that results in the release of bacterial toxins. Toxic Shock Syndrome Toxin-1 (TSST-1) was the first toxin identified, but many others (eg, enterotoxins B, C, D, and E) also have been observed to produce TSS. As infection develops, these toxins are released hematogenously and act as superantigens eliciting an exuberant immune response. Large numbers of activated T-cells result in a massive cytokine release, thus producing a shock state.1

Epidemiology

TSS was first described in 1978.2 Reports increased in the 1980s as TSS became associated with the use of super-absorbent tampons. The last population-based assessment of TSS from 1986 revealed an annual incidence of 0.53 cases per 100,000 persons in the U.S.3 While TSS has become synonymous with tampon use, current literature shows roughly half of reported cases are not related to menstruation.4

Nonmenstrual cases1,5 have been reported in patients with surgical wounds, postpartum infections, focal cutaneous and subcutaneous lesions, adenitis, bursitis, deep abscesses, respiratory infections following flu, burns, and osteomyelitis.

Overall mortality attributed to TSS has decreased from 5.5 to 1.8%; however, nonmenstrual TSS still has a mortality rate of 6%6,7 — likely secondary to decreased provider recognition.

Diagnosis

TSS should be considered in all patients with fever, rash, hypotension, and evidence of organ dysfunction. Evaluation should include a thorough physical exam and targeted imaging to identify foreign bodies or other brewing sources of infection. Lab studies should include complete blood count, basic metabolic and hepatic function panels, blood cultures, and a lactate level.

Clinicians should carefully consider other life-threatening diagnoses, such as meningitis/encephalitis, septic shock, Steven’s Johnson Syndrome/Toxic Epidermal Necrolysis, Staphylococcal Scalded Skin Syndrome, and necrotizing soft tissue infection. Because no specific diagnostic test exists for TSS, the CDC clinical criteria are used for diagnosis (Table 1).5 Cases are confirmed if patients meet all 5 of the CDC-defined clinical criteria and 1 lab-based criterion. Clinical criteria include fever, rash, desquamation, hypotension, and multisystem involvement. Lab-based criteria include blood or CSF cultures positive for Staphylococcus aureus and negative studies suggesting alternative etiologies.

Table 1. Staphyloccocal toxic shock syndrome (TSS) 2011 Case Definition 

Clinical Criteria (must meet all 5 criteria)
Fever: temperature greater than or equal to 102.0°F (greater than or equal to 38.9°C)
Rash: diffuse macular erythroderma
Desquamation: 1-2 weeks after onset of illness, particularly on the palms and soles
Hypotension: systolic blood pressure less than or equal to 90 mm Hg for adults or less than fifth percentile by age for children aged less than 16 years; orthostatic drop in diastolic blood pressure greater than or equal to 15 mm Hg from lying to sitting, orthostatic syncope, or orthostatic dizziness
Multisystem involvement (three or more of the following)

· Gastrointestinal: vomiting or diarrhea at onset of illness
· Muscular: severe myalgia or creatine phosphokinase level at least twice the upper limit of normal
· Mucous membrane: vaginal, oropharyngeal, or conjunctival hyperemia
· Renal: blood urea nitrogen or creatinine at least twice the upper limit of normal for laboratory or urinary sediment with pyuria (greater than or equal to 5 leukocytes per high-power field) in the absence of urinary tract infection
· Hepatic: total bilirubin, alanine aminotransferase enzyme, or asparate aminotransferase enzyme levels at least twice the upper limit of normal for laboratory
· Hematologic: platelets less than 100,000/mm3
· Central nervous system: disorientation or alterations in consciousness without focal neurologic signs when fever and hypotension are absent

Laboratory Criteria
·   Blood or cerebrospinal fluid cultures blood culture may be positive for Staphylococcus aureus
·   Must have negative serologies for Rocky Mountain spotted fever, leptospirosis, or measles, if obtained.

It is important to note that group A Streptococcus can cause Streptococcus toxic shock syndrome (STSS), which presents in similarly to staphylococcal toxic shock syndrome and is diagnosed based on isolation of group A Streptococcus from a normally sterile site (eg, blood, CSF, joint, or pleural fluid) in combination with hypotension and involvement of 2 or more organ systems. STSS most often occurs in association with infection of a cutaneous lesion; however, it may occur with infection at any site.8


Table 2. Suggested Empiric Antimicrobial Regimens for TSS

  • Penicillin G 24 million units/day IV in divided doses (Streptococcal TSS) OR
  • Nafcillin2 gm IV q4h or Oxacillin 2 gm IV q4h (Staphylococcal TSS) AND
  • Clindamycin900 mg IV every 8 hours (suppress toxin production)

Consider:

  • Vancomycin15-20 mg/kg gm IV every 12 hours (if MRSA suspected or penicillin allergy)
  • Piperacillin-tazobactam 4.5 gm IV q8h (if gram negative infection suspected)
  • IVIG 1 gm/kg on day 1, then 0.5 gm/kg on days 2 and 3 for refractory hypotension

*Antimicrobial regimes vary institutionally and local hospital protocols should be evaluated.
**Duration of therapy is individualized; minimum of 14 days if associated bacteremia


Treatment

Initial treatment for patients with TSS includes aggressive fluid resuscitation and vasopressor therapy  with the goal of restoring end-organ perfusion. Broad antimicrobial therapy must be initiated early and should include agents with activity against both S. aureus and S. pyogenes (Table 2).9 Removal of indwelling foreign bodies, surgical debridement, or drainage of infection may be necessary to achieve source control. These patients require admission to the intensive care unit, and clinicians may need to consult with general surgery and/or dermatology. Cases refractory to initial resuscitation may benefit from intravenous immunoglobulin. It is suspected to assist patients who are immunosuppressed or who are otherwise unable to produce an adequate antibody response to the toxins.10

References

  1. Low DE. Toxic shock syndrome: major advances in pathogenesis, but not treatment. Critical Care Clinics.2013;29(3):651-675.
  2. Todd J, et al. Toxic-shock syndrome associated with phage-group-I staphylococci.  Lancet.1978 Nov 25;2(8100):1116-1118.
  3. Gaventa S, et al. Active surveillance for toxic shock syndrome in the United States, 1986. Review of Infectious Diseases11.Supplement 1 (1989): S28-S34.
  4. DeVries AS, et al. Staphylococcal toxic shock syndrome 2000–2006: epidemiology, clinical features, and molecular characteristics.PLoS One.2011;6(8):e22997.
  5. Toxic Shock Syndrome (other than Streptococcal) (TSS). Centers for Disease Control. N.p., Aug. 2011. Accessed July 2, 2015. http://wwwn.cdc.gov/nndss/conditions/toxic-shock-syndrome-other-than-streptococcal/case-definition/2011.
  6. Hajjeh RA, Reingold A, Weil A, et al. Toxic shock syndrome in the United States: surveillance update, 1979 1996. Emerg Infect Dis. 1999;5:807.
  7. Broome CV. Epidemiology of toxic shock syndrome in the United States: overview. Rev Infect Dis. 1989;11 Suppl 1:S14.
  8. Streptococcal toxic-shock syndrome (STSS) (Streptococcal Pyogenes) 2010 Case Definition. Centers for Disease Control. N.p. 2010. Accessed July 30, 2015. http://wwwn.cdc.gov/nndss/conditions/streptococcal-toxic-shock-syndrome/case-definition/2010
  9. Gilbert DN, Eliopoulos GM, Chambers HF, Saag MS. The Sanford Guide to Antimicrobial Therapy. 2015.
  10. Barry W, et al. Intravenous immunoglobulin therapy for toxic shock syndrome. JAMA. 1992;267(24):3315-3316.
Nathan VanderVinne, MSIII

Nathan VanderVinne, MSIII

EMRA MSC Legislative Coordinator, Edward Via College of Osteopathic Medicine, Blacksburg, VA
Nathan VanderVinne, MSIII

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Nicholas Johnson, MD

Nicholas Johnson, MD

Fellow, Critical Care Medicine, Division of Pulmonary & Critical Care Medicine, University of Washington, Seattle, WA
Nicholas Johnson, MD

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