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Staphylococcal toxic shock syndrome

Staphylococcal toxic shock syndrome
Author:
Vivian H Chu, MD, MHS
Section Editors:
Sheldon L Kaplan, MD
Franklin D Lowy, MD
Deputy Editor:
Elinor L Baron, MD, DTMH
Literature review current through: Aug 2021. | This topic last updated: Oct 29, 2020.

INTRODUCTION — Staphylococcal toxic shock syndrome (TSS) is a clinical illness characterized by rapid onset of fever, rash, hypotension, and multiorgan system involvement. TSS due to Staphylococcus aureus was initially described in 1978; the disease came to public attention in 1980 with the occurrence of a series of menstrual-associated cases [1,2].

The epidemiology, pathogenesis, clinical manifestations, diagnosis, and treatment of staphylococcal TSS will be reviewed here. Other issues related to staphylococcal infection are discussed separately. (See "Clinical manifestations of Staphylococcus aureus infection in adults" and "Clinical approach to Staphylococcus aureus bacteremia in adults".)

EPIDEMIOLOGY — TSS associated with S. aureus was first described in a series of pediatric cases in 1978 [1,3]. The incidence rose sharply in 1980; more than 800 cases of menses-related TSS occurred, largely among young women [2,4]. Clinical illness arose during menstruation and was associated with use of absorbent tampons [3,5]. The incidence of TSS declined sharply after the withdrawal of some tampon brands.

Subsequently, between 2000 and 2003, the incidence rose slightly; in one report, the incidence increased from 0.8 to 3.4 per 100,000 [6]. These cases occurred among women of menstrual age but included both menstrual and nonmenstrual cases. The observed increase in the number of cases may reflect increased recognition due to active laboratory testing for toxin-producing strains, rather than an overall increase in incidence. One study in Minneapolis between 2000 and 2006 noted a stable incidence of staphylococcal TSS overall, with decreasing annual incidence of menstrual TSS among women >24 years [7]. A review of patients with TSS in Colorado demonstrated no significant change in the incidence of staphylococcal TSS between 1993 and 2006 [8]. A survey of TSS cases in the United Kingdom from 2008 to 2012 noted a stable incidence of nonmenstrual TSS but a decline in menstrual TSS cases; in this study, 59 percent of cases were nonmenstrual [9].

Menstrual cases — Between 1979 and 1996, approximately 5300 cases of staphylococcal TSS were reported [10]. The proportion of cases associated with menstruation decreased significantly between 1979 and 1996 (from 91 percent between 1979 and 1980, to 59 percent between 1987 and 1996).

Between 1980 and 1986, the number of cases of menstrual TSS declined (from 9 in 100,000 to 1 in 100,000 women) [11]. Between 1979 and 1996, the case-fatality rate for menstrual TSS also declined (from 5.5 percent between 1979 and 1980, to 1.8 percent between 1987 and 1996) [10].

The decrease in cases of menstrual TSS may be explained in part by the withdrawal of highly absorbent tampons and polyacrylate rayon-containing products from the market; however, tampon use remains a risk factor for TSS [12]. Women who develop TSS are more likely to have used tampons with high absorbency, used tampons continuously for more days of their cycle, and kept a single tampon in place for a longer period of time [13,14].

Nonmenstrual cases — At least half of reported staphylococcal TSS cases are not related to menstruation [11,15]. Nonmenstrual TSS can occur in a variety of clinical circumstances, including surgical and postpartum wound infections, mastitis, septorhinoplasty, sinusitis, osteomyelitis, arthritis, burns, cutaneous and subcutaneous lesions (especially of the extremities, perianal area, and axillae), respiratory infections following influenza, and enterocolitis [16-24].

In one report including 5300 cases of TSS between 1979 and 1996, the proportion of TSS cases following surgical procedures increased from 14 percent to 27 percent [10]. In this report, 93 percent of cases occurred among women, and 73 percent of nonmenstrual cases occurred among women [10]. The case-fatality rate for nonmenstrual TSS was 5 percent.

In another study including 130 TSS cases, the gender distribution was equal (with exclusion of vaginal and postpartum-associated cases) [25]. A subsequent report including 61 TSS cases between 2000 and 2006 noted nonmenstrual TSS comprised 46 percent of cases; among these, no primary source was identified in 36 percent of cases [7].

Compared with patients with menstrual TSS, patients with nonmenstrual TSS are older (mean age 27 versus 23 years) [15,21,25].

TSS also occurs in children. In the United States between 1979 and 1996, children <2 years accounted for approximately half of pediatric cases; antecedent cutaneous lesions were present in 62 percent of cases [10]. Similarly, in the United Kingdom between 2008 and 2012, children ≤16 years accounted for 39 percent of all cases; 42 percent of pediatric cases occurred in children <2 years [9]. A subsequent report from 2009 to 2014 estimated that among more than 8200 children with septic shock (the median age 14 years; 69 percent female), 9 percent were thought to have staphylococcal TSS [26].

MICROBIOLOGY AND PATHOGENESIS

S. aureus — Most reported cases of TSS have been due to methicillin-susceptible S. aureus (MSSA). However, as rates of infection due to methicillin-resistant S. aureus (MRSA) have increased, cases of TSS due to MRSA have also emerged [27,28]. MRSA strains are capable of producing TSS toxin-1 (TSST-1) and other exotoxins, and patients infected with these strains may develop TSS.

In one series including 30 patients from France and Switzerland with infection due to TSST-1-positive MRSA strains, 5 had TSS, 9 had possible TSS (fever and rash without shock), 2 had neonatal TSS-like exanthematous disease (NTED), 1 had scarlet fever, and the others had other infections [27]. The MRSA strains were community acquired (CA) in approximately 30 percent of cases. NTED has also been reported in neonates in Japan and France who are colonized with TSST-1-producing MRSA [29,30]. (See "Neonatal and infantile erythroderma", section on 'Neonatal toxic shock syndrome-like exanthematous disease'.)

In another series of CA-MRSA isolates derived from a Native American reservation, a high prevalence of superantigens (ie, SEB or SEC) was observed; these isolates were genetically related to nonmenstrual TSS-causing strains from elsewhere in the United States [28]. The potential for CA-MRSA strains to cause TSS was also demonstrated in a series of cases in Japan where TSS was due to CA-MRSA isolates producing TSST-1, SEB, SEC, or other exotoxins [31].

Toxin production — Toxin production plays in important role in the pathogenesis of staphylococcal TSS [32].

TSST-1 was the initial exotoxin isolated from S. aureus isolates implicated in TSS [33,34]. TSST-1 is produced by 90 to 100 percent of S. aureus strains associated with menstrual cases of TSS and by 40 to 60 percent of strains associated with nonmenstrual cases. The reason for the discrepancy in TSST-1 production between menstrual and nonmenstrual cases is not well understood [35].

Other toxins may be more virulent than TSST-1; in one study of 32 S. aureus isolates from nonmenstrual TSS, 50 percent of individuals infected with a TSST-1-negative strain died, compared with 10 percent of TSST-1-positive strains [36].

Other potential toxins include enterotoxins A, B, C, D, E, and H. Several animal studies suggest that enterotoxin A may be a cofactor of TSST-1 [37,38]. Staphylococcal enterotoxin B is produced by 38 to 62 percent of nonmenstrual TSST-1-negative strains [39,40]. In a study of 183 isolates of S. aureus from clinical specimens (but not necessarily TSS cases), 40 percent of the strains produced one or more toxins [41]. TSST-1 was produced by 14 percent of isolates; enterotoxins A, B, C, and D were produced by 20, 8, 6, and 3 percent of isolates, respectively.

Role of superantigens — S. aureus exotoxins are superantigens capable of activating large numbers of T cells, resulting in massive cytokine production [42]. In typical T cell recognition, an antigen is taken up by an antigen-presenting cell, processed, expressed on the cell surface in complex with class II major histocompatibility complex (MHC), and recognized by an antigen-specific T cell receptor. Superantigens do not require processing by antigen-presenting cells; they interact directly with the invariant region of the class II MHC molecule. Two regions of the TSST-1 toxin have been found to be important for MHC class II binding [43]. (See "Major histocompatibility complex (MHC) structure and function".)

Activated T cells release interleukin (IL)-1, IL-2, tumor necrosis factor (TNF)-alpha, TNF-beta, and interferon (IFN)-gamma in large amounts. IL-1 is an endogenous pyrogen and thus causes high fevers. In addition, IL-1 mediates skeletal muscle proteolysis and probably accounts for the myalgia and elevated creatine phosphokinase seen in TSS [44]. (See "Pathophysiology and treatment of fever in adults" and "Fever in infants and children: Pathophysiology and management", section on 'Pathogenesis'.)

TNF production inhibits polymorphonuclear leukocyte (PMN) functions. TSST-1-producing S. aureus do not engender a purulent response, which in part may be explained by PMN inhibition [42]. In addition, data suggest that TSST-1 and enterotoxin B repress production of other S. aureus exoproteins, which may explain the absence of purulence in S. aureus infections associated with TSS [45]. (See 'Dermatologic manifestations' below.)

Host immune response — The host immune response to S. aureus exotoxins plays an important role in the pathogenesis of TSS. Approximately 70 to 80 percent of individuals develop antibody to TSST-1 by early adulthood; by the fourth decade, such antibody is present in 90 to 95 percent of individuals [46,47]. In one study including more than 3000 menstruating women in North America, TSST-1 antibody titers among Black women were lower than among White women (89 versus 98 percent) [47].

The age of six months to two years is a period of vulnerability during which passive immunity is waning but active immunity has not developed. In one study, detectable antibody titers to TSST-1 among infants age 0 to 6 months were observed in 76 percent of cases; among children 7 to 24 months of age, detectable antibodies were observed in 30 percent of cases [48].

Patients with TSS do not develop a sufficient antibody response to TSST-1; in addition, they frequently fail to develop appropriate antibodies in convalescent serum [49]. Reduced titers to other staphylococcal enterotoxins in patients with TSS have also been observed [33]. In one study of burn patients with MRSA infection, TSST-1 antibody level was lower among patients who developed TSS than those who did not [50].

CLINICAL MANIFESTATIONS

Symptoms and signs — Clinical criteria for TSS have been established by the United States Centers for Disease Control and Prevention (table 1). The symptoms and signs of TSS develop rapidly (within 48 hours), frequently in otherwise healthy individuals.

Clinical manifestations of TSS include fever/chills, hypotension (may include orthostasis or syncope), dermatologic manifestations (diffuse macular erythroderma, followed by desquamation one to two weeks later), and multiorgan system involvement [51,52].

Manifestations of multiorgan system involvement include gastrointestinal symptoms (abdominal pain, vomiting, and/or watery diarrhea), myalgias, mucous membrane (vaginal, oropharyngeal, or conjunctival) involvement, renal involvement, hepatic involvement, thrombocytopenia, and neurologic symptoms (headache, somnolence, confusion, irritability, agitation, hallucinations). Other manifestations include cyanosis and edema of the extremities.

The clinical presentations of menstrual and nonmenstrual TSS are similar. In one small study, nonmenstrual TSS was associated with earlier onset of rash and fever, more pronounced renal and central nervous system (CNS) complications, and less musculoskeletal involvement [53]. In menstrual cases, the median interval between the onset of menstruation and TSS is two to three days [54]. In postsurgical infection, the median interval between surgery and TSS is two days; however, onset of TSS has been reported as late as 65 days postoperatively [16,25].

Hypotension — Rapid onset of hypotension (for adults: systolic blood pressure ≤90 mmHg; for children <16 years of age: less than fifth percentile by age) often leads to tissue ischemia and organ failure.

Hypotension is caused by a decrease in systemic vascular resistance and leakage of fluid from the intravascular to the interstitial space [55]. These occur as a consequence of massive cytokine release induced by the toxins.

Hypotension may be unresponsive to large quantities of intravenous fluids and can persist for several days.

Dermatologic manifestations — A variety of skin manifestations are seen in TSS.

The initial erythroderma is characterized by a diffuse, red, macular rash resembling sunburn that also involves the palms and soles (picture 1 and picture 2). This rash can be subtle and fleeting. In postoperative TSS, the erythema may be more intense around the surgical wound site. Surgical wounds (and other cutaneous sites of infection) that harbor toxin-producing S. aureus frequently appear benign, without obvious purulence [25,53].

Mucosal involvement includes conjunctival-scleral hemorrhage (picture 3) and hyperemia of the vaginal and oropharyngeal mucosa [56]. In more severe cases, superficial ulcerations occur on the mucous membranes, and petechiae, vesicles, and bullae develop. Patients also have nonpitting edema due to increases in interstitial fluid.

Late-onset skin manifestations include a pruritic maculopapular rash (may occur one to two weeks after onset of illness) and desquamation of the palms and soles (characteristically begins one to three weeks after onset of illness) (picture 4). In some cases, TSS may not be considered in the differential diagnosis until desquamation is observed; this is particularly true in nonmenstrual disease [57]. Some patients also experience loss of hair and nails one to two months following onset of illness; hair and nails regrow by six months.

Multiorgan system involvement — TSS can involve all organ systems. Many patients report diffuse myalgias and weakness as presenting symptoms, which are usually accompanied by an increase in serum concentrations of creatine phosphokinase (CPK). Gastrointestinal symptoms are also common, particularly profuse diarrhea. Both prerenal and intrinsic renal failure can occur and are often accompanied by other metabolic abnormalities including hyponatremia, hypoalbuminemia, hypocalcemia, and hypophosphatemia [58].

Encephalopathy, manifested by disorientation, confusion, or seizure activity, can be a presenting symptom of TSS [59] and is probably due to cerebral edema [60]. Other CNS findings have been reported in some patients. Persistent neuropsychologic sequelae can develop such as headaches, memory loss, and poor concentration [61]. Other findings include pulmonary edema and pleural effusions, depression of myocardial function [62], hepatic dysfunction, and hematologic abnormalities, such as anemia and thrombocytopenia.

Recurrent illness — Recurrent TSS has been described. Recurrent TSS tends to occur in patients who have not been treated with appropriate antimicrobial therapy and/or who fail to develop an appropriate antibody response to staphylococcal toxins [21,57,63]. Recurrence can occur days to months after the initial episode. In menstrual TSS, recurrent episodes are generally milder than the initial disease [63].

There is also a variant of TSS described in patients with AIDS; this presentation is characterized by a subacute illness with persistent and recalcitrant erythroderma, desquamation, mucosal injection, fever, and hypotension lasting or recurring over a period of weeks [64].

Laboratory findings — Laboratory abnormalities reflect shock and organ failure: elevated blood urea nitrogen and creatinine, elevated liver function tests, and an elevated CPK (table 1) [58,65,66].

Leukocytosis may be absent, but the total number of mature and immature neutrophils usually exceeds 90 percent (with immature neutrophils accounting for 25 to 50 percent of the total number of neutrophils). Thrombocytopenia and anemia are present during the first few days, frequently accompanied by prolonged prothrombin and partial thromboplastin times. Disseminated intravascular coagulation may be present.

Most laboratory tests normalize 7 to 10 days after onset of illness.

DIAGNOSIS — Staphylococcal TSS should be suspected in otherwise healthy individuals with rapid onset of fever, rash, hypotension, and multiorgan system involvement; relevant risk factors include recent tampon use, recent surgery, and recent infection (involving skin or soft tissue or other site).

The diagnosis of staphylococcal TSS is established based on clinical and laboratory criteria (table 1) [52,67].

Cultures (including blood cultures, cultures from mucosal sites [including the vaginal canal in cases of suspected menstrual TSS], cultures from wound sites, and cultures from nares) should be obtained. Any foreign material in the vaginal canal (such as a tampon, contraceptive sponge, or intrauterine device) should be removed if present.

Detection of S. aureus in culture is not required for the diagnosis of staphylococcal TSS. S. aureus is recovered from blood cultures in approximately 5 percent of cases [25]; it is recovered from wound or mucosal sites in 80 to 90 percent of cases [63].

According to the United States Centers for Disease Control and Prevention (CDC), a confirmed case is a case that meets the following clinical criteria: fever, hypotension, diffuse erythroderma, desquamation (unless the patient dies before desquamation can occur), and involvement of at least three organ systems, with cultures negative for alternative pathogens and serologic tests negative for other conditions (if obtained). A patient who is missing one of the above clinical criteria may be considered a probable case.

The CDC criteria were established for epidemiologic surveillance and should be not be used to exclude a case that is highly suspicious for TSS, even if all criteria are not met.

In settings where further laboratory investigation is feasible, additional tests can be helpful in making a retrospective diagnosis of TSS. S. aureus isolates can be tested for toxin production in research laboratories. In addition, acute and convalescent serum can be analyzed for antibody responses to various S. aureus exotoxins. The presence of a strain of S. aureus that produces toxin in a patient who does not have acute-phase antibody to the toxin is highly suggestive of TSS.

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of staphylococcal TSS includes:

Streptococcal TSS – Streptococcal TSS typically presents with pain that precedes physical findings of infection. At the site of minor trauma (such as a bruise, strained muscle, or sprained ankle), patients may develop deep infection such as necrotizing fasciitis or myonecrosis, often with no visible break in the skin. The diagnosis of streptococcal TSS consists of hypotension and isolation of streptococci from a normally sterile site, together with two or more findings including renal dysfunction, coagulopathy liver dysfunction, acute respiratory distress syndrome, rash, and/or soft tissue necrosis. (See "Invasive group A streptococcal infection and toxic shock syndrome: Epidemiology, clinical manifestations, and diagnosis".)

Sepsis or septic shock due to other pathogens – Other causes of sepsis include gram-negative and fungal pathogens; in some cases, no organism is identified. Sepsis due to other causes is not classically associated with dermatologic manifestations. The diagnosis is often made empirically at the bedside upon presentation. (See "Sepsis syndromes in adults: Epidemiology, definitions, clinical presentation, diagnosis, and prognosis" and "Evaluation and management of suspected sepsis and septic shock in adults".)

Drug reaction – Drug reactions may be associated with fever, systemic symptoms, dermatologic involvement, and neutropenia. The diagnosis should be suspected in a patient presenting with these findings who received a new drug in the previous two to six weeks. The diagnosis is based on history and clinical manifestations. Eosinophilia can further support the diagnosis of a drug reaction. (See "Drug reaction with eosinophilia and systemic symptoms (DRESS)".)

Kawasaki disease – Kawasaki is a vasculitis that occurs in children, characterized by systemic inflammation manifested by fever and mucocutaneous involvement. The diagnosis is established based on clinical history and supported by laboratory findings. (See "Kawasaki disease: Clinical features and diagnosis".)

COVID-19 multisystem inflammatory syndrome – There have been reports of multisystem inflammatory syndrome possibly associated with COVID-19 with clinical features similar to those of TSS, Kawasaki disease shock syndrome, and/or Kawasaki disease (eg, abdominal pain, gastrointestinal symptoms, myocarditis), and laboratory findings associated with increased inflammation (eg, elevated C-reactive protein, erythrocyte sedimentation rate, and ferritin). Some, though not all, of these patients have tested positive for SARS-CoV-2. (See "COVID-19: Multisystem inflammatory syndrome in children (MIS-C) clinical features, evaluation, and diagnosis".)

Meningococcal infection – Meningococcal infection is characterized by acute onset of fever, nausea, vomiting, headache, confusion, and myalgia. Nonblanching purpuric rash may be observed. The infection is transmitted by person-to-person contact and occurs worldwide. The incubation period is 2 to 10 days, and the diagnosis is established via culture of blood or spinal fluid, agglutination tests, or polymerase chain reaction. (See "Clinical manifestations of meningococcal infection".)

Rocky Mountain spotted fever (RMSF) – RMSF is a tick-borne illness; manifestations include fever, headache, and rash. Typically the rash is petechial, involves the extremities first, and occurs an average of three days after the development of fever. The diagnosis of RMSF can rarely be confirmed or disproved in its early phase. In later illness, the diagnosis can be made by skin biopsy and confirmed serologically. (See "Clinical manifestations and diagnosis of Rocky Mountain spotted fever".)

Leptospirosis – Leptospirosis is characterized by fever, rigors, myalgia, conjunctival suffusion, and headache; respiratory involvement can develop as a complication. Less common symptoms and signs include cough, nausea, vomiting, diarrhea, abdominal pain, and jaundice. It is transmitted via exposure to animal urine, contaminated water or soil, or infected animal tissue; outbreaks in endemic areas are associated with increased rainfall or flooding. The incubation is 2 to 29 days. The diagnosis is established via serology or culture of blood or urine (See "Leptospirosis: Epidemiology, microbiology, clinical manifestations, and diagnosis".)

Dengue fever – The cardinal features of dengue fever include fever, increased vascular permeability, hemorrhagic manifestations, and marked thrombocytopenia (≤100,000 cells/mm3). The virus is transmitted by Aedes aegypti mosquitoes, which have broad epidemiologic distribution; the incubation period is 4 to 7 days (range 3 to 10 days). The diagnosis is established via serologic testing. (See "Dengue virus infection: Clinical manifestations and diagnosis".)

Enteric fever – Enteric fever refers to both typhoid fever (caused by Salmonella enterica serotype Typhi [formerly Salmonella typhi]) and paratyphoid fever (caused by S. enterica serotype Paratyphi A, B, and C worldwide; predominantly Paratyphi B in South America). Enteric fever is characterized by abdominal pain, fever, and chills. Classic manifestations include relative bradycardia, pulse-temperature dissociation, and "rose spots" (faint salmon-colored macules on the trunk and abdomen). Hepatosplenomegaly, intestinal bleeding, and perforation may occur, leading to secondary bacteremia and peritonitis. Transmission is fecal-oral; the incubation period is 6 to 30 days. The diagnosis is established via culture. (See "Epidemiology, microbiology, clinical manifestations, and diagnosis of enteric (typhoid and paratyphoid) fever".)

MANAGEMENT

Overview — Management of staphylococcal TSS includes treatment of shock, surgical debridement (if warranted), and antibiotic therapy. In addition, any foreign material in the vaginal canal (such as a tampon, contraceptive sponge, or intrauterine device) or nasopharynx (such as nasal packing) should be removed if present.

Treatment of shock — Staphylococcal TSS may be associated with intractable hypotension and diffuse capillary leak, requiring extensive fluid replacement to maintain perfusion. Vasopressors may also be required. Issues related to management of shock are discussed separately. (See "Evaluation and management of suspected sepsis and septic shock in adults" and "Initial management of shock in children".)

Surgical debridement — Any focus of infection must be drained. Surgical wounds may not appear to be infected because of diminished inflammatory response; nonetheless, wound exploration (with debridement if warranted) should be pursued for patients with TSS in the setting of recent surgery. Any packing should be removed, if present.

Antibiotic therapy

Antibiotic selection — Antistaphylococcal antibiotic therapy is needed to eradicate organisms and to prevent recurrence [2,63]. No randomized studies have evaluated antibiotic regimens for treatment of TSS; the approach is based on case series and animal studies.

Empiric therapy — For empiric treatment of sepsis of unknown cause that might represent staphylococcal TSS, we favor the following regimen (pending culture results):

Vancomycin (adults: dosing as summarized in the table (table 2); children: 60 mg/kg per day IV in four divided doses)

PLUS

Clindamycin (adults: 900 mg IV every eight hours; children: 25 to 40 mg/kg IV per day in three divided doses)

PLUS one of the following:

A combination drug containing a penicillin plus beta-lactamase inhibitor (adults: piperacillin-tazobactam 4.5 g IV every six hours)

Cefepime (adults: 2 g IV every 8 hours; children: 50 mg/kg/dose every 8 hours up to 2 g per dose)

A carbapenem (adults: meropenem 1 g IV every 8 hours or imipenem 1 g IV every 6 to 8 hours; children: meropenem 25 mg/kg/dose every 8 hours or imipenem 15 to 25 mg/kg/dose every 6 hours [maximum 4 g per day])

Tailored therapy — For treatment of TSS due to methicillin-susceptible S. aureus (MSSA), we favor the following regimen:

Oxacillin or nafcillin (adults: 2 g IV every four hours; children: 150 to 200 mg/kg per 24 hours IV in four divided doses). A first-generation cephalosporin such as cefazolin (2 g IV every eight hours; children: 100 to 150 mg/kg/day in 3 divided doses every 8 hours) is an acceptable alternative in patients with hypersensitivity to the preceding agents.

PLUS

Clindamycin (if susceptible; adults: 900 mg IV every eight hours; children: 25 to 40 mg/kg per day in three divided doses)

For treatment of TSS due to methicillin-resistant S. aureus (MRSA), we favor the following regimen:

Vancomycin (adults: dosing as summarized in the table (table 2); children: 60 mg/kg per day IV in four divided doses). Alternatives for patients unable to tolerate vancomycin include daptomycin (adults: 8 to 10 mg/kg IV every 24 hours; children: age-dependent, as summarized in Lexicomp) or ceftaroline (adults: 600 mg IV every 12 hours; children: 15 mg/kg IV every 8 hours infused over 2 hours). (See "Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Treatment of bacteremia".)

PLUS

Clindamycin (if susceptible; adults: 900 mg IV every eight hours; children: 30 to 40 mg/kg per day in three divided doses)

Inclusion of clindamycin for treatment of staphylococcal TSS is based on the ability of this drug to suppress synthesis of bacterial toxins. This issue is discussed further separately. (See "Invasive group A streptococcal infection and toxic shock syndrome: Treatment and prevention", section on 'General principles'.)

In the event of resistance to clindamycin, linezolid (adults: 600 mg orally or IV every 12 hours; children <12 years old: 10 mg/kg every 8 hours; children >12 years old: 10 mg/kg every 12 hours [not to exceed adult dose]) is a reasonable alternative agent. In such cases, linezolid may be used as monotherapy given its antistaphylococcal and anti-toxin activity.

For patients with deep-seated infections and/or bacteremia, we favor combination therapy with clindamycin and an antistaphylococcal penicillin (eg, oxacillin or nafcillin) or vancomycin, until hemodynamics have stabilized.

Theoretically, clindamycin and linezolid (which suppresses protein synthesis and, therefore, toxin synthesis) may be more efficacious than cell wall-active agents (such as beta-lactams and vancomycin) for treatment of staphylococcal TSS, since S. aureus produces potent toxins and these bacteriostatic drugs suppress toxin production [68]. This approach contrasts with the approach to treatment of bacteremia caused by organisms not associated with toxin production (for which bactericidal antibiotics are preferred over bacteriostatic antibiotics). As an example, in one case report, TSS was treated successfully with linezolid; in vitro analysis of TSST-1 synthesis supported the superior efficacy of protein synthesis inhibitors over cell wall-active agents [69].

Duration of therapy — The duration of therapy for S. aureus infection depends on the underlying etiology. Issues related to duration of therapy in the setting of S. aureus bacteremia are discussed separately. (See "Clinical approach to Staphylococcus aureus bacteremia in adults", section on 'Duration of therapy'.)

There are no clinical studies to inform duration of therapy for staphylococcal TSS. In the absence of bacteremia or a distinct focus of infection, we typically treat for 10 to 14 days. Combination therapy with clindamycin (or linezolid, if used in place of clindamycin) should be continued until patients are clinically and hemodynamically stable for at least 48 to 72 hours; thereafter, monotherapy with an antistaphylococcal agent may be administered.

It is uncertain whether intravenous therapy is required for the entire duration of antibiotic therapy. Following completion of surgical debridement (if needed) and resolution of systemic signs of infection, it may be reasonable to complete the course of antibiotic therapy with an oral regimen.

A reasonable oral regimen for completion of treatment for infection due to MSSA consists of dicloxacillin (adults: 500 mg orally every six hours; children: 100 mg/kg/day divided every six hours [maximum 500 mg per dose]) OR cephalexin (adults: 500 mg orally every six hours; children: 75 to 100 mg/kg/day in three divided doses [maximum 4 g per day]).

A reasonable oral regimen for completion of treatment for infection due to MRSA consists of clindamycin (adults: 300 to 450 mg orally four times daily; children: 10 to 13 mg/kg per dose orally every 8 hours, not to exceed the maximum adult dose) OR linezolid (adults: 600 mg orally every 12 hours; children <12 years old: 10 mg/kg every 8 hours; children >12 years old: 10 mg/kg every 12 hours [not to exceed adult dose]).

Adjunctive therapy

Intravenous immune globulin — In general, we do not favor use of intravenous immune globulin (IVIG) for treatment of staphylococcal TSS, given the lack of substantive clinical data to suggest a benefit with IVIG in staphylococcal TSS and the potential for adverse effects. Use of IVIG may be considered in patients with severe staphylococcal TSS who are unresponsive to other therapeutic measures [70]. (See "Overview of intravenous immune globulin (IVIG) therapy".)

It has been proposed that IVIG may be beneficial for patients with staphylococcal TSS in the setting of diminished antibody production to toxin [71-74]. However, there have been no controlled trials of IVIG therapy in staphylococcal TSS; data are limited to case reports and retrospective reviews:

In one case report of a 39-year-old man with HIV infection and diffuse erythema of the arms and legs, desquamation (of the arms, hands, feet, and eyebrows), pharyngeal erythema, and a lesion that grew a TSST-1-producing S. aureus, IVIG (200 mg/kg per day) was administered for five days after failing antibiotic therapy; symptoms subsequently resolved [64].

In a retrospective study of patients with necrotizing fasciitis and shock associated with group A Streptococcus or S. aureus, adjunctive IVIG has no apparent impact in mortality [75].

PROGNOSIS — Death associated with TSS usually occurs within the first few days of hospitalization but may occur as late as two weeks after admission. Fatalities have been attributed to refractory cardiac arrhythmias, cardiomyopathy, irreversible respiratory failure, and, rarely, bleeding caused by coagulation defects [76,77].

The TSS-related mortality rate in menstrual cases has decreased since the syndrome was first recognized in 1980, from 5.5 to 1.8 percent between 1987 and 1996 [10]. The mortality due to nonmenstrual TSS is higher and has remained essentially unchanged between 1980 and 1996, at approximately 6 percent [10,12]. The mortality due to TSS in children is 3 to 5 percent [78].

PREVENTION — Patients who have had tampon-associated TSS should not resume tampon use.

For patients with staphylococcal TSS and S. aureus nasal carriage, we suggest decolonization as an attempt at prevention; however, the impact of this intervention on the likelihood of a subsequent episode of staphylococcal TSS is uncertain. In addition, decolonization itself may not be effective or durable. (See "Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Prevention and control", section on 'Targeted decolonization'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Skin and soft tissue infections".)

SUMMARY AND RECOMMENDATIONS

Staphylococcal toxic shock syndrome (TSS) is a clinical illness characterized by rapid onset of fever, rash, hypotension, and multiorgan system involvement. The disease came to public attention in 1980 with the occurrence of a series of menstrual-associated cases. However, at least half of reported staphylococcal TSS cases are not related to menstruation. (See 'Introduction' above and 'Epidemiology' above.)

Clinical criteria for TSS have been established by the United States Centers for Disease Control and Prevention (table 1). Clinical manifestations of TSS include fever/chills, hypotension (may include orthostasis or syncope), dermatologic manifestations (diffuse macular erythroderma, followed by desquamation one to two weeks later), and multiorgan system involvement. The symptoms and signs of TSS develop rapidly (within 48 hours), frequently in otherwise healthy individuals. (See 'Clinical manifestations' above.)

Staphylococcal TSS should be suspected in patients with rapid onset of fever, rash, hypotension, and multiorgan system involvement; relevant risk factors include recent tampon use, recent surgery, and recent infection (involving skin or soft tissue or other site). The diagnosis of staphylococcal TSS is established based on clinical and laboratory criteria (table 1). (See 'Diagnosis' above.)

Cultures (including blood cultures, cultures from mucosal sites [including the vaginal canal in cases of suspected menstrual TSS], cultures from wound sites, and cultures from nares) should be obtained. Detection of Staphylococcus aureus in culture is not required for the diagnosis of staphylococcal TSS. S. aureus is recovered from blood cultures in approximately 5 percent of cases; it is recovered from wound or mucosal sites in 80 to 90 percent of cases. (See 'Diagnosis' above.)

Management of staphylococcal TSS includes treatment of shock, surgical debridement (if warranted), and antibiotic therapy. Surgical wounds may not appear to be infected because of diminished inflammatory response; nonetheless, wound exploration (with debridement if warranted) should be pursued for patients with TSS in the setting of recent surgery, and any packing should be removed (if present). In addition, any foreign material in the vaginal canal (such as a tampon, contraceptive sponge, or intrauterine device) should be removed if present. Issues related to management of shock are discussed separately. (See 'Management' above and "Evaluation and management of suspected sepsis and septic shock in adults" and "Initial management of shock in children".)

We suggest that patients with suspected TSS be treated with combination antibiotic therapy including an antistaphylococcal agent and an antibiotic that suppresses protein synthesis such as clindamycin (rather than antistaphylococcal therapy alone) (Grade 2C), given the importance of toxin production in the pathogenesis of staphylococcal TSS. For treatment of staphylococcal TSS, we typically use the following regimens; dosing is summarized above (see 'Toxin production' above and 'Antibiotic selection' above):

For patients with sepsis of unknown cause that might represent staphylococcal TSS, we favor treatment with vancomycin, clindamycin, and either a combination drug containing a penicillin plus beta-lactamase inhibitor or a carbapenem.

For patients with TSS due to methicillin-susceptible S. aureus, we favor treatment with oxacillin or nafcillin plus clindamycin. A first-generation cephalosporin such as cefazolin is an acceptable alternative in patients with hypersensitivity to the preceding agents.

For patients with TSS due to methicillin-resistant S. aureus, we favor treatment with vancomycin plus clindamycin.

For patients with staphylococcal TSS, we suggest not administering intravenous immune globulin (Grade 2C), given the lack of substantive clinical data to suggest a benefit with IVIG in staphylococcal TSS and the potential for adverse effects. Use of IVIG may be considered in patients with severe staphylococcal TSS who are unresponsive to other therapeutic measures. (See 'Intravenous immune globulin' above.)

For patients with staphylococcal TSS, we suggest decolonization as an attempt at prevention (Grade 2C); however, the impact of this intervention on the likelihood of a subsequent episode of staphylococcal TSS is uncertain. (See 'Prevention' above and "Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Prevention and control", section on 'Targeted decolonization'.)

REFERENCES

  1. Todd J, Fishaut M, Kapral F, Welch T. Toxic-shock syndrome associated with phage-group-I Staphylococci. Lancet 1978; 2:1116.
  2. Davis JP, Chesney PJ, Wand PJ, LaVenture M. Toxic-shock syndrome: epidemiologic features, recurrence, risk factors, and prevention. N Engl J Med 1980; 303:1429.
  3. Reingold AL, Hargrett NT, Shands KN, et al. Toxic shock syndrome surveillance in the United States, 1980 to 1981. Ann Intern Med 1982; 96:875.
  4. Centers for Disease Control (CDC). Update: toxic-shock syndrome--United States. MMWR Morb Mortal Wkly Rep 1983; 32:398.
  5. Osterholm MT, Davis JP, Gibson RW, et al. Toxic shock syndrome: relation to catamenial products, personal health and hygiene, and sexual practices. Ann Intern Med 1982; 96:954.
  6. Schlievert PM, Tripp TJ, Peterson ML. Reemergence of staphylococcal toxic shock syndrome in Minneapolis-St. Paul, Minnesota, during the 2000-2003 surveillance period. J Clin Microbiol 2004; 42:2875.
  7. DeVries AS, Lesher L, Schlievert PM, et al. Staphylococcal toxic shock syndrome 2000-2006: epidemiology, clinical features, and molecular characteristics. PLoS One 2011; 6:e22997.
  8. Smit MA, Nyquist AC, Todd JK. Infectious shock and toxic shock syndrome diagnoses in hospitals, Colorado, USA. Emerg Infect Dis 2013; 19:1855.
  9. Sharma H, Smith D, Turner CE, et al. Clinical and Molecular Epidemiology of Staphylococcal Toxic Shock Syndrome in the United Kingdom. Emerg Infect Dis 2018; 24.
  10. 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.
  11. Centers for Disease Control (CDC). Reduced incidence of menstrual toxic-shock syndrome--United States, 1980-1990. MMWR Morb Mortal Wkly Rep 1990; 39:421.
  12. Broome CV. Epidemiology of toxic shock syndrome in the United States: overview. Rev Infect Dis 1989; 11 Suppl 1:S14.
  13. Reingold AL, Broome CV, Gaventa S, Hightower AW. Risk factors for menstrual toxic shock syndrome: results of a multistate case-control study. Rev Infect Dis 1989; 11 Suppl 1:S35.
  14. Billon A, Gustin MP, Tristan A, et al. Association of characteristics of tampon use with menstrual toxic shock syndrome in France. EClinicalMedicine 2020; 21:100308.
  15. Gaventa S, Reingold AL, Hightower AW, et al. Active surveillance for toxic shock syndrome in the United States, 1986. Rev Infect Dis 1989; 11 Suppl 1:S28.
  16. Bartlett P, Reingold AL, Graham DR, et al. Toxic shock syndrome associated with surgical wound infections. JAMA 1982; 247:1448.
  17. Dann EJ, Weinberger M, Gillis S, et al. Bacterial laryngotracheitis associated with toxic shock syndrome in an adult. Clin Infect Dis 1994; 18:437.
  18. Ferguson MA, Todd JK. Toxic shock syndrome associated with Staphylococcus aureus sinusitis in children. J Infect Dis 1990; 161:953.
  19. Morrison VA, Oldfield EC 3rd. Postoperative toxic shock syndrome. Arch Surg 1983; 118:791.
  20. Paterson MP, Hoffman EB, Roux P. Severe disseminated staphylococcal disease associated with osteitis and septic arthritis. J Bone Joint Surg Br 1990; 72:94.
  21. Reingold AL, Hargrett NT, Dan BB, et al. Nonmenstrual toxic shock syndrome: a review of 130 cases. Ann Intern Med 1982; 96:871.
  22. Vuzevski VD, van Joost T, Wagenvoort JH, Dey JJ. Cutaneous pathology in toxic shock syndrome. Int J Dermatol 1989; 28:94.
  23. Kotler DP, Sandkovsky U, Schlievert PM, Sordillo EM. Toxic shock-like syndrome associated with staphylococcal enterocolitis in an HIV-infected man. Clin Infect Dis 2007; 44:e121.
  24. MacDonald KL, Osterholm MT, Hedberg CW, et al. Toxic shock syndrome. A newly recognized complication of influenza and influenzalike illness. JAMA 1987; 257:1053.
  25. Reingold AL, Dan BB, Shands KN, Broome CV. Toxic-shock syndrome not associated with menstruation. A review of 54 cases. Lancet 1982; 1:1.
  26. Gaensbauer JT, Birkholz M, Smit MA, et al. Epidemiology and Clinical Relevance of Toxic Shock Syndrome in US Children. Pediatr Infect Dis J 2018; 37:1223.
  27. Durand G, Bes M, Meugnier H, et al. Detection of new methicillin-resistant Staphylococcus aureus clones containing the toxic shock syndrome toxin 1 gene responsible for hospital- and community-acquired infections in France. J Clin Microbiol 2006; 44:847.
  28. Fey PD, Saïd-Salim B, Rupp ME, et al. Comparative molecular analysis of community- or hospital-acquired methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 2003; 47:196.
  29. Kikuchi K, Takahashi N, Piao C, et al. Molecular epidemiology of methicillin-resistant Staphylococcus aureus strains causing neonatal toxic shock syndrome-like exanthematous disease in neonatal and perinatal wards. J Clin Microbiol 2003; 41:3001.
  30. van der Mee-Marquet N, Lina G, Quentin R, et al. Staphylococcal exanthematous disease in a newborn due to a virulent methicillin-resistant Staphylococcus aureus strain containing the TSST-1 gene in Europe: an alert for neonatologists. J Clin Microbiol 2003; 41:4883.
  31. Sada R, Fukuda S, Ishimaru H. Toxic shock syndrome due to community-acquired methicillin-resistant Staphylococcus aureus infection: Two case reports and a literature review in Japan. IDCases 2017; 8:77.
  32. Spaulding AR, Salgado-Pabón W, Kohler PL, et al. Staphylococcal and streptococcal superantigen exotoxins. Clin Microbiol Rev 2013; 26:422.
  33. Bergdoll MS, Crass BA, Reiser RF, et al. A new staphylococcal enterotoxin, enterotoxin F, associated with toxic-shock-syndrome Staphylococcus aureus isolates. Lancet 1981; 1:1017.
  34. Schlievert PM, Shands KN, Dan BB, et al. Identification and characterization of an exotoxin from Staphylococcus aureus associated with toxic-shock syndrome. J Infect Dis 1981; 143:509.
  35. Schlievert PM, Jablonski LM, Roggiani M, et al. Pyrogenic toxin superantigen site specificity in toxic shock syndrome and food poisoning in animals. Infect Immun 2000; 68:3630.
  36. Garbe PL, Arko RJ, Reingold AL, et al. Staphylococcus aureus isolates from patients with nonmenstrual toxic shock syndrome. Evidence for additional toxins. JAMA 1985; 253:2538.
  37. De Boer ML, Kum WW, Pang LT, Chow AW. Co-production of staphylococcal enterotoxin A with toxic shock syndrome toxin-1 (TSST-1) enhances TSST-1 mediated mortality in a D-galactosamine sensitized mouse model of lethal shock. Microb Pathog 1999; 27:61.
  38. De Boer ML, Kum WW, Chow AW. Staphylococcus aureus isogenic mutant, deficient in toxic shock syndrome toxin-1 but not staphylococcal enterotoxin A production, exhibits attenuated virulence in a tampon-associated vaginal infection model of toxic shock syndrome. Can J Microbiol 1999; 45:250.
  39. Schlievert PM. Staphylococcal enterotoxin B and toxic-shock syndrome toxin-1 are significantly associated with non-menstrual TSS. Lancet 1986; 1:1149.
  40. Lee VT, Chang AH, Chow AW. Detection of staphylococcal enterotoxin B among toxic shock syndrome (TSS)- and non-TSS-associated Staphylococcus aureus isolates. J Infect Dis 1992; 166:911.
  41. Lehn N, Schaller E, Wagner H, Krönke M. Frequency of toxic shock syndrome toxin- and enterotoxin-producing clinical isolates of Staphylococcus aureus. Eur J Clin Microbiol Infect Dis 1995; 14:43.
  42. Schlievert PM. Role of superantigens in human disease. J Infect Dis 1993; 167:997.
  43. Kum WW, Laupland KB, Chow AW. Defining a novel domain of staphylococcal toxic shock syndrome toxin-1 critical for major histocompatibility complex class II binding, superantigenic activity, and lethality. Can J Microbiol 2000; 46:171.
  44. Parsonnet J. Mediators in the pathogenesis of toxic shock syndrome: overview. Rev Infect Dis 1989; 11 Suppl 1:S263.
  45. Vojtov N, Ross HF, Novick RP. Global repression of exotoxin synthesis by staphylococcal superantigens. Proc Natl Acad Sci U S A 2002; 99:10102.
  46. Vergeront JM, Stolz SJ, Crass BA, et al. Prevalence of serum antibody to staphylococcal enterotoxin F among Wisconsin residents: implications for toxic-shock syndrome. J Infect Dis 1983; 148:692.
  47. Parsonnet J, Hansmann MA, Delaney ML, et al. Prevalence of toxic shock syndrome toxin 1-producing Staphylococcus aureus and the presence of antibodies to this superantigen in menstruating women. J Clin Microbiol 2005; 43:4628.
  48. Quan L, Morita R, Kawakami S. Toxic shock syndrome toxin-1 (TSST-1) antibody levels in Japanese children. Burns 2010; 36:716.
  49. Bonventre PF, Linnemann C, Weckbach LS, et al. Antibody responses to toxic-shock-syndrome (TSS) toxin by patients with TSS and by healthy staphylococcal carriers. J Infect Dis 1984; 150:662.
  50. Matsushima A, Kuroki Y, Nakajima S, et al. Low Level of TSST-1 Antibody in Burn Patients With Toxic Shock Syndrome Caused by Methicillin-Resistant Staphylococcus aureus. J Burn Care Res 2015; 36:e120.
  51. Wharton M, Chorba TL, Vogt RL, et al. Case definitions for public health surveillance. MMWR Recomm Rep 1990; 39:1.
  52. Case definitions for infectious conditions under public health surveillance. Centers for Disease Control and Prevention. MMWR Recomm Rep 1997; 46:1.
  53. Kain KC, Schulzer M, Chow AW. Clinical spectrum of nonmenstrual toxic shock syndrome (TSS): comparison with menstrual TSS by multivariate discriminant analyses. Clin Infect Dis 1993; 16:100.
  54. Tofte RW, Williams DN. Toxic shock syndrome. Evidence of a broad clinical spectrum. JAMA 1981; 246:2163.
  55. Chesney PJ. Clinical aspects and spectrum of illness of toxic shock syndrome: overview. Rev Infect Dis 1989; 11 Suppl 1:S1.
  56. Chesney PJ, Davis JP, Purdy WK, et al. Clinical manifestations of toxic shock syndrome. JAMA 1981; 246:741.
  57. Andrews MM, Parent EM, Barry M, Parsonnet J. Recurrent nonmenstrual toxic shock syndrome: clinical manifestations, diagnosis, and treatment. Clin Infect Dis 2001; 32:1470.
  58. Chesney RW, Chesney PJ, Davis JP, Segar WE. Renal manifestations of the staphylococcal toxic-shock syndrome. Am J Med 1981; 71:583.
  59. Barrett JA, Graham DR. Toxic shock syndrome presenting as encephalopathy. J Infect 1986; 12:276.
  60. Smith DB, Gulinson J. Fatal cerebral edema complicating toxic shock syndrome. Neurosurgery 1988; 22:598.
  61. Rosene KA, Copass MK, Kastner LS, et al. Persistent neuropsychological sequelae of toxic shock syndrome. Ann Intern Med 1982; 96:865.
  62. Olson RD, Stevens DL, Melish ME. Direct effects of purified staphylococcal toxic shock syndrome toxin 1 on myocardial function of isolated rabbit atria. Rev Infect Dis 1989; 11 Suppl 1:S313.
  63. Davis JP, Osterholm MT, Helms CM, et al. Tri-state toxic-shock syndrome study. II. Clinical and laboratory findings. J Infect Dis 1982; 145:441.
  64. Cone LA, Woodard DR, Byrd RG, et al. A recalcitrant, erythematous, desquamating disorder associated with toxin-producing staphylococci in patients with AIDS. J Infect Dis 1992; 165:638.
  65. Gourley GR, Chesney PJ, Davis JP, Odell GB. Acute cholestasis in patients with toxic- shock syndrome. Gastroenterology 1981; 81:928.
  66. Ishak KG, Rogers WA. Cryptogenic acute cholangitis--association with toxic shock syndrome. Am J Clin Pathol 1981; 76:619.
  67. Centers for Disease Control (CDC). Repeat injuries in an inner city population--Philadelphia, 1987-1988. MMWR Morb Mortal Wkly Rep 1990; 39:1.
  68. Schlievert PM, Kelly JA. Clindamycin-induced suppression of toxic-shock syndrome--associated exotoxin production. J Infect Dis 1984; 149:471.
  69. Stevens DL, Wallace RJ, Hamilton SM, Bryant AE. Successful treatment of staphylococcal toxic shock syndrome with linezolid: a case report and in vitro evaluation of the production of toxic shock syndrome toxin type 1 in the presence of antibiotics. Clin Infect Dis 2006; 42:729.
  70. American Academy of Pediatrics. Red Book: 2021-2024 Report of the Committee on Infectious Diseases, 32 ed, Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH (Eds), American Academy of Pediatrics, Itasca, IL 2021.
  71. Best GK, Scott DF, Kling JM, et al. Protection of rabbits in an infection model of toxic shock syndrome (TSS) by a TSS toxin-1-specific monoclonal antibody. Infect Immun 1988; 56:998.
  72. Bonventre PF, Thompson MR, Adinolfi LE, et al. Neutralization of toxic shock syndrome toxin-1 by monoclonal antibodies in vitro and in vivo. Infect Immun 1988; 56:135.
  73. Keller MA, Stiehm ER. Passive immunity in prevention and treatment of infectious diseases. Clin Microbiol Rev 2000; 13:602.
  74. Chesney PJ, Davis JP. Toxic shock syndrome. In: Textbook of pediatric infectious diseases, 4th ed, Feigin RD, Cherry JD (Eds), WB Saunders, Philadelphia 1998. p.830.
  75. Kadri SS, Swihart BJ, Bonne SL, et al. Impact of Intravenous Immunoglobulin on Survival in Necrotizing Fasciitis With Vasopressor-Dependent Shock: A Propensity Score-Matched Analysis From 130 US Hospitals. Clin Infect Dis 2017; 64:877.
  76. Larkin SM, Williams DN, Osterholm MT, et al. Toxic shock syndrome: clinical, laboratory, and pathologic findings in nine fatal cases. Ann Intern Med 1982; 96:858.
  77. Paris AL, Herwaldt LA, Blum D, et al. Pathologic findings in twelve fatal cases of toxic shock syndrome. Ann Intern Med 1982; 96:852.
  78. Chuang YY, Huang YC, Lin TY. Toxic shock syndrome in children: epidemiology, pathogenesis, and management. Paediatr Drugs 2005; 7:11.
Topic 3161 Version 26.0

References

1 : Toxic-shock syndrome associated with phage-group-I Staphylococci.

2 : Toxic-shock syndrome: epidemiologic features, recurrence, risk factors, and prevention.

3 : Toxic shock syndrome surveillance in the United States, 1980 to 1981.

4 : Update: toxic-shock syndrome--United States.

5 : Toxic shock syndrome: relation to catamenial products, personal health and hygiene, and sexual practices.

6 : Reemergence of staphylococcal toxic shock syndrome in Minneapolis-St. Paul, Minnesota, during the 2000-2003 surveillance period.

7 : Staphylococcal toxic shock syndrome 2000-2006: epidemiology, clinical features, and molecular characteristics.

8 : Infectious shock and toxic shock syndrome diagnoses in hospitals, Colorado, USA.

9 : Clinical and Molecular Epidemiology of Staphylococcal Toxic Shock Syndrome in the United Kingdom.

10 : Toxic shock syndrome in the United States: surveillance update, 1979 1996.

11 : Reduced incidence of menstrual toxic-shock syndrome--United States, 1980-1990.

12 : Epidemiology of toxic shock syndrome in the United States: overview.

13 : Risk factors for menstrual toxic shock syndrome: results of a multistate case-control study.

14 : Association of characteristics of tampon use with menstrual toxic shock syndrome in France.

15 : Active surveillance for toxic shock syndrome in the United States, 1986.

16 : Toxic shock syndrome associated with surgical wound infections.

17 : Bacterial laryngotracheitis associated with toxic shock syndrome in an adult.

18 : Toxic shock syndrome associated with Staphylococcus aureus sinusitis in children.

19 : Postoperative toxic shock syndrome.

20 : Severe disseminated staphylococcal disease associated with osteitis and septic arthritis.

21 : Nonmenstrual toxic shock syndrome: a review of 130 cases.

22 : Cutaneous pathology in toxic shock syndrome.

23 : Toxic shock-like syndrome associated with staphylococcal enterocolitis in an HIV-infected man.

24 : Toxic shock syndrome. A newly recognized complication of influenza and influenzalike illness.

25 : Toxic-shock syndrome not associated with menstruation. A review of 54 cases.

26 : Epidemiology and Clinical Relevance of Toxic Shock Syndrome in US Children.

27 : Detection of new methicillin-resistant Staphylococcus aureus clones containing the toxic shock syndrome toxin 1 gene responsible for hospital- and community-acquired infections in France.

28 : Comparative molecular analysis of community- or hospital-acquired methicillin-resistant Staphylococcus aureus.

29 : Molecular epidemiology of methicillin-resistant Staphylococcus aureus strains causing neonatal toxic shock syndrome-like exanthematous disease in neonatal and perinatal wards.

30 : Staphylococcal exanthematous disease in a newborn due to a virulent methicillin-resistant Staphylococcus aureus strain containing the TSST-1 gene in Europe: an alert for neonatologists.

31 : Toxic shock syndrome due to community-acquired methicillin-resistant Staphylococcus aureus infection: Two case reports and a literature review in Japan.

32 : Staphylococcal and streptococcal superantigen exotoxins.

33 : A new staphylococcal enterotoxin, enterotoxin F, associated with toxic-shock-syndrome Staphylococcus aureus isolates.

34 : Identification and characterization of an exotoxin from Staphylococcus aureus associated with toxic-shock syndrome.

35 : Pyrogenic toxin superantigen site specificity in toxic shock syndrome and food poisoning in animals.

36 : Staphylococcus aureus isolates from patients with nonmenstrual toxic shock syndrome. Evidence for additional toxins.

37 : Co-production of staphylococcal enterotoxin A with toxic shock syndrome toxin-1 (TSST-1) enhances TSST-1 mediated mortality in a D-galactosamine sensitized mouse model of lethal shock.

38 : Staphylococcus aureus isogenic mutant, deficient in toxic shock syndrome toxin-1 but not staphylococcal enterotoxin A production, exhibits attenuated virulence in a tampon-associated vaginal infection model of toxic shock syndrome.

39 : Staphylococcal enterotoxin B and toxic-shock syndrome toxin-1 are significantly associated with non-menstrual TSS.

40 : Detection of staphylococcal enterotoxin B among toxic shock syndrome (TSS)- and non-TSS-associated Staphylococcus aureus isolates.

41 : Frequency of toxic shock syndrome toxin- and enterotoxin-producing clinical isolates of Staphylococcus aureus.

42 : Role of superantigens in human disease.

43 : Defining a novel domain of staphylococcal toxic shock syndrome toxin-1 critical for major histocompatibility complex class II binding, superantigenic activity, and lethality.

44 : Mediators in the pathogenesis of toxic shock syndrome: overview.

45 : Global repression of exotoxin synthesis by staphylococcal superantigens.

46 : Prevalence of serum antibody to staphylococcal enterotoxin F among Wisconsin residents: implications for toxic-shock syndrome.

47 : Prevalence of toxic shock syndrome toxin 1-producing Staphylococcus aureus and the presence of antibodies to this superantigen in menstruating women.

48 : Toxic shock syndrome toxin-1 (TSST-1) antibody levels in Japanese children.

49 : Antibody responses to toxic-shock-syndrome (TSS) toxin by patients with TSS and by healthy staphylococcal carriers.

50 : Low Level of TSST-1 Antibody in Burn Patients With Toxic Shock Syndrome Caused by Methicillin-Resistant Staphylococcus aureus.

51 : Case definitions for public health surveillance.

52 : Case definitions for infectious conditions under public health surveillance. Centers for Disease Control and Prevention.

53 : Clinical spectrum of nonmenstrual toxic shock syndrome (TSS): comparison with menstrual TSS by multivariate discriminant analyses.

54 : Toxic shock syndrome. Evidence of a broad clinical spectrum.

55 : Clinical aspects and spectrum of illness of toxic shock syndrome: overview.

56 : Clinical manifestations of toxic shock syndrome.

57 : Recurrent nonmenstrual toxic shock syndrome: clinical manifestations, diagnosis, and treatment.

58 : Renal manifestations of the staphylococcal toxic-shock syndrome.

59 : Toxic shock syndrome presenting as encephalopathy.

60 : Fatal cerebral edema complicating toxic shock syndrome.

61 : Persistent neuropsychological sequelae of toxic shock syndrome.

62 : Direct effects of purified staphylococcal toxic shock syndrome toxin 1 on myocardial function of isolated rabbit atria.

63 : Tri-state toxic-shock syndrome study. II. Clinical and laboratory findings.

64 : A recalcitrant, erythematous, desquamating disorder associated with toxin-producing staphylococci in patients with AIDS.

65 : Acute cholestasis in patients with toxic- shock syndrome.

66 : Cryptogenic acute cholangitis--association with toxic shock syndrome.

67 : Repeat injuries in an inner city population--Philadelphia, 1987-1988.

68 : Clindamycin-induced suppression of toxic-shock syndrome--associated exotoxin production.

69 : Successful treatment of staphylococcal toxic shock syndrome with linezolid: a case report and in vitro evaluation of the production of toxic shock syndrome toxin type 1 in the presence of antibiotics.

70 : Successful treatment of staphylococcal toxic shock syndrome with linezolid: a case report and in vitro evaluation of the production of toxic shock syndrome toxin type 1 in the presence of antibiotics.

71 : Protection of rabbits in an infection model of toxic shock syndrome (TSS) by a TSS toxin-1-specific monoclonal antibody.

72 : Neutralization of toxic shock syndrome toxin-1 by monoclonal antibodies in vitro and in vivo.

73 : Passive immunity in prevention and treatment of infectious diseases.

74 : Passive immunity in prevention and treatment of infectious diseases.

75 : Impact of Intravenous Immunoglobulin on Survival in Necrotizing Fasciitis With Vasopressor-Dependent Shock: A Propensity Score-Matched Analysis From 130 US Hospitals.

76 : Toxic shock syndrome: clinical, laboratory, and pathologic findings in nine fatal cases.

77 : Pathologic findings in twelve fatal cases of toxic shock syndrome.

78 : Toxic shock syndrome in children: epidemiology, pathogenesis, and management.