Diagnosis: Cultures taken of the patient’s throat, stool, cerebrospinal fluid, and blood revealed no organisms. However, a nasopharyngeal swab was positive for Staphylococcus aureus. In addition serologic tests for Rocky Mountain Spotted Fever, leptospirosis, and Ehrlichiosis were negative. The patient was diagnosed with Staphylococcal Toxic Shock Syndrome.

Epidemiology: Toxic Shock Syndrome associated with S. aureus infections (Staph TSS) was described in 1978. The majority of cases involve women with >90% of these cases seen in 15 to 19-year-old white females. The peak of reported cases of Staph TSS was in 1980 and since then there has been a marked and persistent decline. Studies have established that the illness is associated with females during the menstrual cycle and that vaginal colonization and infection plays a major role. Nonmenstrual cases of staphylococcal TSS occur among both sexes, regardless of age, and are associated with surgical procedures such as rhinoplasty and nasal packing. There is also an association between staphylococcal TSS and a variety of primary S. aureus infections including cutaneous, postsurgical, postpartum, focal tissue sites, and pneumonia. Clinically, patients have a prodromal period of 2 to 3 days consisting of malaise, myalgia, and chills. Many patients also develop diarrhea early in the illness. Fever then begins accompanied by symptoms of hypovolemia. It has also been observed that many patients develop an erythematous rash that is usually diffuse but may be patchy in distribution. Desquamation of the skin at sites of previous rash, particularly on the palms and soles, occurs in 7 to 14 days. Mortality for this disease is at about 3% for menstrual cases and is two- to three-fold higher for nonmenstrual cases.

Pathogenesis: Toxic Shock Syndrome Toxin-1 (TSST-1) and staphylococcal enterotoxins are the major virulence factors associated with cases of staphylococcal TSS. TSST-1 was found in more than 90% of S. aureus strains isolated from menstrual cases of staphylococcal TSS. In contrast TSST-1 has been detected in only half of strains isolated from patients with nonmenstrual staphylococcal TSS. Staphylococcal enterotoxin B (SEB) and to a lesser extent enterotoxins A (SEA) and C (SEC) have been found in the remaining strains. TSST-1 and the enterotoxins belong to the family of superantigens which can activate subsets of T lymphocytes to liberate various cytokines, gamma-interferon, and tumor necrosis factors. This leads to major systemic effects including fever, hypotension, skin lesions, shock, multiorgan failure, and death.

Although it was not done in the case presented above, it is important to be aware that the microbiology laboratory can test for pyrogenic exotoxins including Staphylococcal enterotoxins A, B, and C as well as the toxic shock syndrome toxin TSST-1. The test uses an Enzyme-Linked Immunosorbent Assay for the above listed toxins and is performed on the patient’s S. aureus isolates. Sensitivity and specificity for detection of TSST-1 are, respectively, 95% and 100%, for SEA 95.2% and 100%, for SEB 100% and 98.9%, and for SEC 100% and 98.9%.

Treatment: Acute management of a patient with staph TSS requires aggressive fluid replacement and supportive care. Antibiotic treatment based on in vitro susceptibility studies suggest that nafcillin, first or second generation cephalosporins, vancomycin, clindamycin, erythromycin, and fluoroquinolones are reasonable choices. However, antibiotics that suppress the toxin synthesis may be more efficacious than cell wall active antibiotics. Parsonnet et al (Program and Abstracts of the 32^nd Meeting of the IDSA, 1994) recently demonstrated that clindamycin, erythromycin, rifampin, and fluoroquinolones all suppress TSST-1 synthesis by 90%. The use of immunoglobulins against TSST-1 has also been studied and found to be therapeutic in animal models.