AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Toxic shock syndrome (TSS) is an inflammatory response syndrome characterized by fever, rash, hypotension, constitutional symptoms, and multiorgan involvement. Todd first described it in 1978 in 7 children, aged 8-17 years, with Staphylococcus aureus infection. However, after an epidemic in 1981, TSS has been typically associated with tampon use in healthy menstruating women. The disease is now known to also exist in men, neonates, and nonmenstruating women. TSS has been linked to many bacterial infections, including pneumonia, osteomyelitis, sinusitis, and skin and gynecologic infections.

Pathophysiology

TSS is a toxin-mediated disease. Exotoxin toxic shock syndrome toxin-1 (TSST-1) is the major toxin produced by strains of S aureus that are responsible for causing TSS. Streptococcus pyogenes exotoxin A (SPEA) and S pyogenes exotoxin B (SPEB) are the major toxins produced by group A beta-hemolytic streptococci. The toxins activate production of superantigens, such as tumor necrosis factor, interleukin-1, M protein, and gamma-interferon.

Almost every organ system can be involved, including the cardiovascular, renal, skin, mucosa, GI, musculoskeletal, hepatic, hematologic, and central nervous systems.

Frequency

United States

With staphylococcal TSS, the highest incidence occurred in 1980; rates ranged from 2.4-16 cases per 100,000 population. Since then, the rate of menstrual-related TSS has persistently declined, largely because of a decrease in the use of superabsorbent tampons and consumer education. With streptococcal TSS, the prevalence is not well known, but it is estimated to be 10-20 cases per 100,000 population. A similar decline has not been demonstrated in nonmenstrual cases of TSS. The proportion of postsurgical TSS cases has been increasing.

Mortality/Morbidity

Mortality varies with the bacteria involved.

• With staphylococcal TSS, the mortality rate is less than 3%.
• With streptococcal TSS, the mortality rate is 30-70%.
• Recurrences have been reported in 30-40% of cases.

Race

No race predilection exists in TSS.

Sex

• With staphylococcal TSS, the incidence is higher in women than in men.
• With streptococcal TSS, either sex can be affected.

Age

TSS predominantly occurs in young, healthy individuals.

• With staphylococcal TSS, patients primarily are aged 15-35 years.
• With streptococcal TSS, patients primarily are aged 20-50 years.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Symptoms are similar for streptococcal TSS and staphylococcal TSS. The major difference is that a source of infection usually is identified with streptococcal TSS. Symptoms may include the following:

• Prodromal period of 2-3 days
• Fever and/or chills
• Nausea and/or vomiting
• Profuse watery diarrhea with abdominal pain
• Lightheadedness and/or syncope
• Myalgias and/or arthralgias
• Pharyngitis and/or headache
• Confusion (more common with staphylococcal TSS than with streptococcal TSS)
• Pain at site of infection (most common symptom of streptococcal TSS)

Physical

At physical examination, findings may include the following:

• Fever higher than 102°F
• Hypotension - Systolic BP less than 90 mm Hg or orthostatic decrease in systolic BP of 15 mm Hg
• Skin findings
• • Diffuse rash, occasionally patchy and erythematous, with desquamation occurring approximately 1-2 weeks later

  • Rash initially appearing on trunk, spreading to arms and legs, and involving palms and soles

• Signs of multiorgan involvement
• • Physical findings associated with ventricular arrhythmias, renal failure, or hepatic failure

  • Disseminated intravascular coagulation (DIC)

  • Acute respiratory distress syndrome

  • Necrotizing fasciitis and/or myositis

  • Altered consciousness (CNS involvement)

  • Mucosal inflammation (eg, vaginitis, conjunctivitis, pharyngitis)

• The Centers for Disease Control and Prevention (CDC) criteria for the diagnosis of staphylococcal TSS are as follows:
• • Fever, hypotension, and rash (as defined above)

  • Involvement of 3 or more organ systems

  • Absence of serologic evidence of Rocky Mountain spotted fever, leptospirosis, measles, hepatitis B, antinuclear antibody, positive Venereal Disease Research Laboratory (VDRL) test results, and antibodies at Monospot testing

• The CDC criteria for streptococcal TSS are as follows:
• • Isolation of group A streptococcus from a normally sterile site (eg, blood, cerebrospinal fluid [CSF], surgical wounds) or a nonsterile site (eg, throat)

  • Hypotension (as defined above)

  • Involvement of 2 or more organ systems

Causes

An absence of protective immunity is postulated to be a major risk factor for acquisition and recurrence of TSS.

• TSS is caused by coagulase-positive staphylococci (S aureus) and group A beta-hemolytic streptococci (S pyogenes).
• Risk factors include the following:
• • Use of superabsorbent tampons

  • Postoperative wound infection

  • Postpartum toxic shock

  • Nasal packing

  • Common bacterial infections

  • Viral infection with influenza A or varicella

  • Diabetes mellitus

  • Infection with HIV

  • Chronic cardiac and/or pulmonary disease

• An association of TSS with prior use of nonsteroidal anti-inflammatory drugs has been suggested, but a causal relationship has not been established.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Meningococcemia
Pneumococcal sepsis

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• The CBC may reveal leukocytosis (77% of cases) with bandemia, mild anemia with abnormal cells on smears, and/or thrombocytopenia.
• Electrolyte levels may indicate hyponatremia, hypokalemia, hypocalcemia out of proportion to hypoalbuminemia, hypophosphatemia, and hypomagnesemia.
• Liver function test results (at least 2 times normal levels) may reveal hyperbilirubinemia (76% of cases), an elevated aspartate aminotransferase (SGOT) level (75% of cases), and an elevated alanine aminotransferase (SGPT) level (50% of cases).
• Coagulation studies may reveal an elevated activated partial thromboplastin time (aPTT) (46% of cases) and fibrin split products. Fibrinogen levels and prothrombin times (PTs) usually are normal.
• Azotemia and/or acute tubular necrosis may be present.
• Urinalysis may reveal sterile pyuria, myoglobinuria, and red cell casts.
• Creatine kinase levels may indicate rhabdomyolysis (63% of cases).
• ABG findings may indicate metabolic acidosis secondary to hypotension and/or hypoxia.
• Culture all potentially infected sites (including blood). More than 50% of patients with streptococcal TSS have a positive blood culture result. Recent studies have suggested that early and definitive diagnosis can be made by observing the expansion of TSS-1 reactive V beta2-positive T-cell receptors in peripheral blood mononuclear cells.

Imaging Studies

• A chest radiograph may show evidence of acute respiratory distress syndrome or pulmonary edema.
• Radiographs of the infected site may show soft-tissue swelling.
• An echocardiogram may show wall-motion abnormality suggestive of toxic cardiomyopathy.
• A CT scan should be obtained if the diagnosis is in question. Findings should be normal in TSS.

Other Tests

• The ECG may show the following:
• • Ventricular arrhythmias

  • Bundle branch blocks

  • First-degree heart block

  • ST-T–wave changes, with ischemia

• Serologic tests should be performed to assess Rocky Mountain spotted fever, leptospirosis, measles, hepatitis B surface antigen, and antinuclear antibody. The VDRL test and the Monospot antibody test also should be performed.
• The rapid streptococcal test can be performed in 10-15 minutes. The test has a sensitivity of 87-95%.

Procedures

• Lumbar puncture should be performed if the diagnosis is in question. Findings should be normal in TSS.
• Swan-Ganz catheterization should be performed to enable monitoring of fluid resuscitation, pulmonary capillary wedge pressure, systemic vascular resistance, and cardiac output.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Prehospital Care

• Aggressive fluid resuscitation should begin in the field, especially for the severely hypotensive patient.
• Oxygen should be administered.

Emergency Department Care

Aggressive fluid resuscitation should continue in the ED. Administer oxygen therapy. Continuously monitor heart rate, respiratory rate, and BP.

The use of intravenous immunoglobulin G (IVIG) has been shown to be effective in neutralizing the TSS toxin and therefore aids in recovery.

• Fluid resuscitation
• • Crystalloids may be administered. As much as 10-20 L/d often is necessary.

  • Some authors suggest that colloids may decrease the risk of pulmonary edema.

• Oxygen therapy
• • Administer supplemental oxygen therapy to maximize tissue oxygenation and to correct hypoxia and/or acidosis.

  • Assisted ventilation may be required if acute respiratory distress syndrome develops.

  • Hyperbaric oxygen therapy has been used in necrotizing soft-tissue infections, but the benefit of this intervention has not been proven.

• Cardiac monitoring should be performed, with treatment of high-grade arrhythmias.
• A Foley catheter should be placed to monitor urine output (assess adequacy of resuscitation).
• Tampons and packing materials, if present, should be removed.

• For patients with menstruation-related TSS, irrigation of vagina with isotonic sodium chloride solution or povidone-iodine solution has been advocated.

Consultations

• Prompt consultation with a surgeon may be necessary for drainage, débridement, fasciotomy, or amputation of a clearly infected site.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Antibiotics are important in the treatment of TSS. Because of the similarity in the clinical appearances of TSS and STSS, adequate antibiotic coverage for both staphylococci and streptococci should be initiated until a definitive diagnosis is made. Once a diagnosis is made, TSS requires penicillinase-resistant antibiotics. Because of the increasing resistance of streptococci to penicillin G, clindamycin often is considered the drug of first choice for invasive group A streptococcal infections such as STSS.

Drug Category: Antibiotics

Therapy must be comprehensive and cover all likely pathogens in the context of the clinical setting.

Drug Name	Clindamycin (Cleocin)
Description	DOC for invasive group A streptococcal infections (eg, STSS). Lincosamide for treatment of serious skin and soft-tissue staphylococcal infections. Also effective against aerobic and anaerobic streptococci (except enterococci). Inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest.
Adult Dose	600-900 mg IV q8h
Pediatric Dose	20-40 mg/kg/d IV divided q6-8h
Contraindications	Documented hypersensitivity; regional enteritis, ulcerative colitis, hepatic impairment, antibiotic-associated colitis
Interactions	Increases duration of neuromuscular blockade induced by tubocurarine and pancuronium; erythromycin may antagonize effects; antidiarrheals may delay absorption
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in severe hepatic dysfunction; no adjustment necessary in renal insufficiency; associated with severe and possibly fatal colitis

Drug Name	Erythromycin (E.E.S., E-Mycin, Ery-Tab)
Description	Inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest. For treatment of staphylococcal and streptococcal infections.
Adult Dose	1 g IV q6h
Pediatric Dose	30-50 mg/kg/d IV divided qid; age, weight, and severity of infection determine proper dosage; for bid dosing, half of the total daily dose may be given q12h; for more severe infections, double the dose
Contraindications	Documented hypersensitivity; hepatic impairment
Interactions	Coadministration may increase toxicity of theophylline, digoxin, carbamazepine, and cyclosporine; may potentiate anticoagulant effects of warfarin; coadministration with lovastatin and simvastatin, increases risk of rhabdomyolysis
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Caution in liver disease; estolate formulation may cause cholestatic jaundice; GI adverse effects are common (give doses pc); discontinue use if nausea, vomiting, malaise, abdominal colic, or fever occur

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Admit the patient to the ICU for further hemodynamic monitoring and/or ventilatory support.
• Perinatal antibiotic therapy should be administered for 7 days, followed by 7 days of oral therapy.
• Some patients may require dialysis.

Further Outpatient Care

• Close follow-up is recommended, because some patients can have sequelae.

Complications

• Reversible loss of hair and nails
• Prolonged neuromuscular abnormalities
• Late onset rash
• Gangrene and/or cyanotic extremities
• Memory and/or concentration difficulties
• Recurrence of TSS

Prognosis

• The prognosis generally is poor for streptococcal TSS, with mortality rate as high as 70%.
• Recurrences may result in 40-50% of patients
• • Most recurrences occur sooner than 2 months after the initial episode.

  • Recurrences generally are less severe than the initial episode, but deaths have been reported.

Patient Education

• For excellent patient education resources, visit eMedicine's Women's Health Center. Also, see eMedicine's patient education article Toxic Shock Syndrome.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Lack of early surgical control of the infection

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Ault MJ, Geiderman J, Sokolov R. Rapid identification of group A streptococcus as the cause of necrotizing fasciitis. Ann Emerg Med. Aug 1996;28(2):227-30. [Medline].
• Bernaldo de Quiros JC, Moreno S, Cercenado E, et al. Group A streptococcal bacteremia. A 10-year prospective study. Medicine (Baltimore). Jul 1997;76(4):238-48. [Medline].
• Davis D, Gash-Kim TL, Heffernan EJ. Toxic shock syndrome: case report of a postpartum female and a literature review. J Emerg Med. Jul-Aug 1998;16(4):607-14. [Medline].
• Hajjeh RA, Reingold A, Weil A, et al. Toxic shock syndrome in the United States: surveillance update, 1979 1996. Emerg Infect Dis. Nov-Dec 1999;5(6):807-10. [Medline].
• Hill MK, Sanders CV. Skin and soft tissue infections in critical care. Crit Care Clin. Apr 1998;14(2):251-62. [Medline].
• Lefering R, Neugebauer EA. Steroid controversy in sepsis and septic shock: a meta-analysis. ALYSIS. Jul 1995;23(7):1294-303. [Medline].
• Manders SM. Toxin-mediated streptococcal and staphylococcal disease. J Am Acad Dermatol. Sep 1998;39(3):383-98; quiz 399-400. [Medline].
• Matsuda Y, Kato H, Yamada R, et al. Early and definitive diagnosis of toxic shock syndrome by detection of marked expansion of T-cell-receptor VBeta2-positive T cells. Emerg Infect Dis. Mar 2003;9(3):387-9. [Medline].
• Murthy BV, Nelson RA, Mannion PT. Immunoglobulin therapy in non-menstrual streptococcal toxic shock syndrome. Anaesth Intensive Care. Jun 2003;31(3):320-3. [Medline].
• Nakae T, Hirayama F, Hashimoto M. [Neutralizing activity of human immunoglobulin preparation against toxic shock syndrome toxin-1]. Kansenshogaku Zasshi. Mar 2002;76(3):195-202. [Medline].
• Pichichero ME. Group A beta-hemolytic streptococcal infections. Pediatr Rev. Sep 1998;19(9):291-302. [Medline].
• Reese RE, Betts RF, eds. Septic shock. In: Practical Approach to Infectious Diseases. 4th ed. Little Brown;1996:36-40.
• Stevens DL. The toxic shock syndromes. Infect Dis Clin North Am. Dec 1996;10(4):727-46. [Medline].
• Tintinalli JE. Toxic shock syndrome and toxic shock-like syndrome. In: Emergency Medicine: A Comprehensive Study Guide. 4th ed. McGraw-Hill;1995:697-701.
• Wiles CE III, Reynolds HN, Bar-Lavie Y. Flush resuscitation for group A streptococcus toxic shock: a possible role for continuous renal replacement therapy and plasmapheresis. Md Med J. Aug 1998;47(4):188-90. [Medline].

Article Last Updated: Dec 5, 2005