You are in: eMedicine Specialties > Dermatology > BACTERIAL INFECTIONS Toxic Shock SyndromeArticle Last Updated: Jul 15, 2008AUTHOR AND EDITOR INFORMATIONSection 1 of 11
  Author: Steven M Manders, MD, Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania; Associate Professor, Department of Internal Medicine, Division of Dermatology, University of Medicine and Dentistry of New Jersey Steven M Manders is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, and American Medical Association Coauthor(s): Clara-Dina Cokonis, MD, Staff Physician, Department of Medicine, Division of Dermatology, Cooper Hospital University Medical Center Editors: Franklin Flowers, MD, Chief, Division of Dermatology, Professor, Department of Medicine and Otolaryngology, University of Florida College of Medicine; Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University School of Medicine; Consulting Staff, Mountain View Dermatology, PA; Paul Krusinski, MD, Director of Dermatology, Professor, Department of Internal Medicine, Fletcher Allen Health Care, University of Vermont; Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University; Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center Author and Editor Disclosure Synonyms and related keywords: shock, TSS, STSS, toxic strep, streptococcal toxic shock-like syndrome, streptococcal TSS, Staphylococcus aureus, S aureus INTRODUCTIONSection 2 of 11
  BackgroundToxic shock syndrome (TSS) is an acute febrile illness characterized by a generalized erythematous eruption accompanied by systemic involvement. It is due to toxin-producing strains of Staphylococcus aureus, both methicillin-sensitive S aureus (MSSA) and methicillin-resistant S aureus (MRSA). Originally described in 1978 and soon thereafter associated with tampon use,1 TSS is now recognized to occur in both menstrual and nonmenstrual forms. In the late 1980s, a disease similar in appearance to TSS, but caused by invasive streptococci, was recognized. Also known as toxic strep or streptococcal toxic shocklike syndrome, streptococcal TSS (STSS) was found to share many clinical features with TSS. PathophysiologyMassive cytokine release as a result of toxin/superantigen activity is postulated to be the mediator of the clinical signs of TSS.2 Both menstrual and nonmenstrual forms of TSS have been linked to toxin-producing strains of S aureus. More than 90% of menstrual TSS is mediated by TSS toxin-1 (TSST-1) production, which is associated with massive release of tumor necrosis factor-alpha (TNF-a) and interleukin (IL)–1. These cytokines have been demonstrated to produce fever, rash, hypotension, tissue injury, and shock. The absence of an antibody to TSST-1 has been shown to be a major risk factor for acquisition of TSS; failure to generate anti-TSST-1 antibody after an episode of TSS predisposes patients to recurrent episodes. Isolates of S aureus from nonmenstrual TSS produce TSST-1 in approximately 50% of cases, whereas the remainder produces staphylococcal enterotoxin B (SEB) and staphylococcal enterotoxin C (SEC). Staphylococcal enterotoxins have been shown to be potent mediators of cytokine production and release in a similar fashion to TSST-1, thereby producing clinically similar diseases. In most cases of STSS, toxin-producing group A streptococci have been isolated, with streptococcal pyrogenic exotoxin-A (SPE-A) production being most closely linked with invasive disease. However, group A streptococci producing streptococcal pyrogenic exotoxin-B (SPE-B), streptococcal pyrogenic exotoxin-C (SPE-C), streptococcal superantigen and mitogenic factor, as well as non–group-A streptococci, have been found to be causative in individual cases of STSS. In a similar manner to classic TSS, it is postulated that massive cytokine release (primarily TNF-a, IL-1beta, and IL-6), as a result of toxin/superantigen activity, mediates the clinical signs of STSS. In addition, streptolysin O, produced by 100% of streptococcal strains associated with STSS, has also been shown to cause TNF-a, and IL-1beta production and has been demonstrated to act synergistically with SPE-A. An absence of protective immunity is postulated as a potential risk factor in this population as well. FrequencyUnited StatesBoth TSS and STSS are relatively rare; the incidence of nonmenstrual TSS exceeds that of menstrual TSS. Mortality/Morbidity
SexYoung adult women are affected more often than men. AgeThe majority of cases of TSS and STSS have occurred in young, otherwise healthy persons aged 20-50 years, despite the fact that very young, elderly, diabetic, or immunocompromised persons are more susceptible to the acquisition of invasive staphylococcal and streptococcal infections. CLINICALSection 3 of 11
HistoryClinically, menstrual TSS, nonmenstrual TSS, and STSS have similar features. Fever, rash, hypotension, and multiple organ involvement are the hallmarks of TSS. Desquamation of the palms and soles, as seen in many bacterial toxin-mediated disorders, usually follows the onset of the illness by 1-2 weeks. Physical
Causes
DIFFERENTIALSSection 4 of 11
Acanthosis Nigricans Kawasaki Disease Scarlet Fever Staphylococcal Scalded Skin Syndrome
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| Drug Name | Nafcillin (Nafcil, Unipen, Nallpen) |
|---|---|
| Description | Initial therapy for suspected penicillin G-resistant streptococcal or staphylococcal infections. Use parenteral therapy initially in severe infections. Change to oral therapy as condition warrants. Due to thrombophlebitis, particularly in the elderly, administer parenterally only for short term (1-2 d); change to oral route as clinically indicated. |
| Adult Dose | 1-2 g IV q4h |
| Pediatric Dose | 50-200 mg/kg/d IV divided q4-6h |
| Contraindications | Documented hypersensitivity |
| Interactions | Associated with warfarin resistance when administered concurrently; effects may decrease with bacteriostatic action of tetracycline derivatives |
| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals |
| Precautions | To optimize therapy, determine causative organisms and susceptibility; treat for >10 d to eliminate infection and prevent sequelae (eg, endocarditis, rheumatic fever); take cultures after treatment to confirm that infection is eradicated |
| Drug Name | Clindamycin (Cleocin) |
|---|---|
| Description | Drug of choice in 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, antibiotic-associated colitis |
| Interactions | Increases duration of neuromuscular blockade induced by tubocurarine and pancuronium; erythromycin may antagonize effects of clindamycin; antidiarrheals may delay absorption of clindamycin |
| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals |
| Precautions | Adjust dose in severe hepatic dysfunction; no adjustment necessary in renal insufficiency; associated with severe and possibly fatal colitis |
| Drug Name | Cefazolin (Ancef) |
|---|---|
| Description | Semisynthetic first-generation cephalosporin that exhibits bactericidal activity by inhibiting cell wall synthesis. Active against penicillinase producing S aureus; however, MRSA and GAS are resistant. |
| Adult Dose | 0.5-1.5 g IM/IV q6-8h |
| Pediatric Dose | 25-100 mg/kg IM/IV qd divided q6-8h |
| Contraindications | Documented hypersensitivity to the cephalosporin group of antibiotics |
| Interactions | Probenecid may decrease excretion; may increase INR when used with warfarin |
| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals |
| Precautions | Adjust dosage in renal insufficiency or failure; seizures may occur in patients with renal impairment administered high doses; caution in patients with a penicillin or beta-lactam allergy; may cause pseudomembranous colitis; may increase prothrombin time |
| Drug Name | Vancomycin (Vancocin) |
|---|---|
| Description | Tricyclic glycopeptide antibiotic that exhibits bactericidal effects by inhibiting cell wall and RNA synthesis and by altering bacterial cell membrane permeability; ideally used when MRSA is suspected |
| Adult Dose | 1 gram IV q12h |
| Pediatric Dose | 10 mg/kg IV q6h |
| Contraindications | Documented hypersensitivity; cidofovir combined with vancomycin may increase risk of nephrotoxicity |
| Interactions | Cidofovir is contraindicated; clofarabine, gallium, aminoglycosides and other nephrotoxic drugs may increase nephrotoxicity |
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus |
| Precautions | Adjust dosage in renal insufficiency or failure; may cause nephrotoxicity, ototoxicity, reversible neutropenia, and, rarely thrombocytopenia; red man syndrome erythroderma may occur; oral formulations of vancomycin are not systemically absorbed and should not be used for systemic infections |
| Drug Name | Linezolid (Zyvox) |
|---|---|
| Description | Prevents formation of functional 70S initiation complex, which is essential for bacterial translation process. Bacteriostatic against enterococci and staphylococci and bactericidal against most strains of streptococci. Used as alternative in patients allergic to vancomycin and for treatment of vancomycin-resistant enterococci. |
| Adult Dose | 600 mg PO/IV q12h for 10-14 d |
| Pediatric Dose | Preterm neonate <7 days: 10 mg/kg PO/IV q12h; in cases of suboptimal response, may use 10 mg/kg PO/IV q8h Term neonates to 12 years: 10 mg/kg PO/IV q8h for 10-14 d >12 years: Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | May cause hypertension when used concomitantly with adrenergic agents including pseudoephedrine, sympathomimetic agents, vasopressor or dopaminergic agents (reduce dose of dopamine or epinephrine if concurrent use required); serotonin syndrome may occur if used concomitantly with serotonergic agents including tricyclic antidepressants, meperidine, dextromethorphan, trazodone, venlafaxine, and selective serotonin reuptake inhibitors; may cause myelosuppression or pseudomembranous colitis inhibitors |
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus |
| Precautions | Has mild MAOI properties and has potential to have same interactions as other MAOIs; caution in uncontrolled hypertension, pheochromocytoma, carcinoid syndrome, or untreated hyperthyroidism, and patients who are at increased risk for bleeding, have preexisting thrombocytopenia, receive concomitant medications that may decrease platelet count or function, or who may require >2 wk of therapy (monitor platelet counts); unnecessary use may lead to development of resistance to drug; may cause peripheral or optic neuropathy |
Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.
The authors and editors of eMedicine gratefully acknowledge the contributions of previous Chief Editor, William D. James, MD, to the development and writing of this article.
Article Last Updated: Jul 15, 2008
