Toxic shock syndrome is caused by staphylococcal or streptococcal exotoxins. Manifestations include high fever, hypotension, diffuse erythematous rash, and multiple organ dysfunction, which may rapidly progress to severe and intractable shock. Diagnosis is made clinically and by isolating the organism. Treatment includes antibiotics, intensive support, and IV immune globulin.
Toxic shock syndrome (TSS) is caused by exotoxin-producing cocci. Strains of phage-group 1 Staphylococcus aureus elaborate the TSS toxin-1 (TSST-1) or related exotoxins; certain strains of Streptococcus pyogenes produce at least 2 exotoxins.
Staphylococcal toxic shock
People at highest risk of staphylococcal TSS are
Women who have preexisting staphylococcal colonization of the vagina and who leave tampons or other devices (eg, menstrual cups, cervical caps, intrauterine devices, contraceptive sponges, diaphragms, pessaries) in the vagina
Mechanical or chemical factors related to tampon use probably enhance production of the exotoxin or facilitate its entry into the bloodstream through a mucosal break or via the uterus. Estimates suggest about 3 cases/100,000 menstruating women still occur, and cases are still reported in women who do not use tampons and in women who have infection after childbirth, abortion, or surgery. About 15% of cases occur postpartum or as a complication of postoperative staphylococcal wound infections that appear insignificant.
Staphylococcal TSS has also been reported in both men and women with any type of S. aureus infection.
Recurrences are common among women who continue to use tampons and other devices during the first 4 months after an episode (1).
Mortality resulting from staphylococcal TSS is < 3%.
Streptococcal toxic shock
Streptococcal TSS is similar to that caused by Staphylococcus aureus, but mortality is higher (20 to 60%) despite aggressive therapy. In addition, about 50% of patients have Streptococcus pyogenes bacteremia, and 50% have necrotizing fasciitis (neither is common with staphylococcal TSS). Patients are usually otherwise healthy children or adults.
Primary infections in skin and soft tissue are more common than in other sites. In contrast to staphylococcal TSS, streptococcal TSS is more likely to cause acute respiratory distress syndrome (ARDS) and less likely to cause a typical cutaneous reaction.
S. pyogenes TSS is defined as any group A beta-hemolytic streptococci (GABHS) infection associated with shock and organ failure.
Risk factors for GABHS TSS include
Minor trauma
Surgical procedures
Viral infections (eg, varicella)
Use of nonsteroidal anti-inflammatory drugs (NSAIDs)
Diabetes
Alcohol use disorder
Reference
1. Schlievert PM, Davis CC: Device-associated menstrual toxic shock syndrome. Clin Microbiol Rev 33(3):e00032-19, 2020. doi: 10.1128/CMR.00032-19
Symptoms and Signs of Toxic Shock Syndrome
Onset of toxic shock syndrome is sudden, with
Fever (39 to 40.5° C, which remains elevated)
Hypotension (which can be refractory)
A diffuse macular erythroderma
Involvement of at least 2 other organ systems
Staphylococcal TSS is likely to cause vomiting, diarrhea, myalgia, elevated creatine kinase, mucositis, hepatic damage, thrombocytopenia, and confusion. The staphylococcal TSS rash is more likely to desquamate, particularly on the palms and soles, between 3 and 7 days after onset.
Streptococcal TSS commonly causes acute respiratory distress syndrome (in about 55% of patients), coagulopathy, and hepatic damage and is more likely to cause high fever, malaise, tachycardia, tachypnea, and, at the site of a soft-tissue infection, severe pain.
Renal impairment is frequent and common in both types of TSS.
TSS may progress within 48 hours to syncope, tissue necrosis, shock, disseminated coagulation, multisystem organ failure, and death. Less severe cases of staphylococcal TSS are fairly common.
Diagnosis of Toxic Shock Syndrome
Clinical evaluation
Cultures
Diagnosis of toxic shock syndrome (TSS) is made clinically and by isolating the organism from blood cultures (for Streptococcus) or from the local site.
Specimens for culture should be taken from any lesions, the nose (for staphylococci), throat (for streptococci), vagina (for both), and blood.
MRI or CT of soft tissue is helpful in localizing sites of infection.
Continuous monitoring of renal, hepatic, bone marrow, and cardiopulmonary function is necessary.
Differential diagnosis
TSS resembles Kawasaki disease, but Kawasaki disease usually occurs in children < 5 years of age and does not cause shock, azotemia, or thrombocytopenia; the rash is maculopapular.
Other disorders to be considered are scarlet fever, Reye syndrome, staphylococcal scalded skin syndrome, meningococcemia, Rocky Mountain spotted fever, leptospirosis, and viral exanthematous diseases. These disorders are ruled out by specific clinical differences, cultures, and serologic tests.
Treatment of Toxic Shock Syndrome
Local measures (eg, decontamination, debridement)
Fluid resuscitation and circulatory support
Empiric antibiotic therapy (eg, clindamycin or linezolid plus vancomycin, daptomycin, linezolid, or ceftaroline) pending culture results
Patients suspected of having TSS should be hospitalized immediately and treated intensively. Tampons, diaphragms, and other foreign bodies should be removed at once.
Suspected primary sites should be decontaminated thoroughly. Decontamination includes
Reinspection and irrigation of surgical wounds, even if they appear healthy
Repeated debridement of devitalized tissues
Irrigation of potential naturally colonized sites (sinuses, vagina)
Fluids and electrolytes are replaced to prevent or treat hypovolemia, hypotension, and shock. Because fluid loss into tissues can occur throughout the body (because of systemic capillary leak syndrome and hypoalbuminemia), shock may be profound and resistant. Aggressive fluid resuscitation and circulatory, ventilatory, and/or hemodialysis support are sometimes required.
Obvious infections should be treated with antibiotics (for indications and doses, see table Antibiotic Treatment of Staphylococcal Infections in Adultslinezolid
For methicillin-susceptible S. aureus
For methicillin-resistant Staphylococcus aureus
Antibiotics given during the acute illness may eradicate pathogen foci and prevent recurrences. Passive immunization to TSS toxins with IV immune globulin (2 g/kg, followed by 0.4 g/kg daily for up to 5 days) has been helpful in severe cases of both types of TSS and lasts for weeks, but the disease may not induce active immunity, so recurrences are possible.
If a test for seroconversion of the serum antibody responses to TSST-1 in acute- and convalescent-phase paired sera is negative, women who have had staphylococcal TSS should probably refrain from using tampons and menstrual cups, cervical caps, contraceptive sponges, intrauterine devices, diaphragms, and pessaries. Advising all women, regardless of TSST-1 antibody status, to change tampons frequently or use napkins instead and to avoid hyperabsorbent tampons seems prudent.
Key Points
Toxic shock syndrome (TSS) is caused by exotoxin-producing strains of Staphylococcus aureus and Streptococcus pyogenes.
Although classically described as occurring with tampon use, TSS may occur after many staphylococcal or streptococcal soft-tissue infections.
Onset of symptoms is sudden; symptoms include high fever, hypotension (which can be refractory), diffuse erythematous rash, and multiple organ dysfunction.
Provide aggressive supportive care, and decontaminate and/or debride the source site.
linezolid
Give IV immune globulin if TSS is severe.
