Staphylococcal Toxic Shock Syndrome

Staphylococcal toxic shock syndrome is an acute multisystem illness with fever, diffuse erythroderma, hypotension, multi-organ dysfunction and later desquamation, caused by superantigen toxins (toxic shock syndrome toxin-1 and staphylococcal enterotoxins B and C) from Staphylococcus aureus.

Epidemiology. It is uncommon, at about 0.5 cases in 100,000 each year in menstruating women and now about equal in non-menstrual disease. Mortality is under 5% in menstrual cases and higher in non-menstrual disease.

Causes and associations. Tampons and menstrual cups, contraceptive diaphragms, nasal packing, surgical site infection (including breast and orthopaedic surgery), burns, postpartum infection, skin and soft tissue infection, sinusitis, and influenza related pneumonia.

Pathophysiology. Superantigens bind major histocompatibility complex class II and T-cell receptors outside the antigen groove, activating up to 20% of T cells. This causes massive release of interleukin-1, interleukin-6 and tumour necrosis factor, vasodilation, capillary leak and shock. Lack of protective antibody to toxin-1 increases risk.

Presentation is high fever (38.9 °C or more), diffuse macular erythroderma (sunburn like), hypotension (systolic under 90 mmHg), confusion, headache, myalgia, vomiting, diarrhoea, hyperaemia of mucous membranes, and desquamation of the palms and soles 1 to 2 weeks later. Three or more organ systems are involved (gastrointestinal, muscular, mucous membranes, renal, hepatic, haematological, neurological).

Red flags.

• Hypotension with rash, fever and retained tampon or packing.
• Renal failure, coagulopathy, confusion or ARDS.
• Wound with minimal local inflammation but systemic toxicity.

Diagnosis is clinical, with case criteria: fever, rash, hypotension, desquamation, and involvement of three or more organs, plus negative tests for other causes. Take cultures of blood, wound, vagina, throat and nose (positive blood cultures are present in under 5%). Measure creatine kinase, liver tests, creatinine, platelets, coagulation, calcium and lactate. Test isolates for toxin gene.

Differential diagnosis. Streptococcal toxic shock syndrome, scarlet fever, Kawasaki disease, drug reaction, meningococcaemia, leptospirosis, Rocky Mountain spotted fever, measles and Stevens-Johnson syndrome.

Remove the source. Remove tampons, packing or foreign bodies, open and drain wounds, and debride infected tissue.

Resuscitation. Aggressive IV balanced crystalloid (commonly 4 to 6 L in the first 24 hours, with attention to capillary leak), noradrenaline 0.05 to 1 microgram/kg/min as needed, and management of organ failure in intensive care.

Antibiotics (give within 1 hour).

• Flucloxacillin 2 g IV every 4 to 6 hours (or cefazolin 2 g IV every 8 hours), adjusted to renal function. Add vancomycin 25 to 30 mg/kg IV loading, then 15 to 20 mg/kg every 8 to 12 hours (levels or area under the curve monitoring), or linezolid 600 mg IV every 12 hours, if methicillin resistance is possible.
• Add clindamycin 900 mg IV every 8 hours for toxin suppression for 3 to 7 days (stop if the isolate is resistant, and monitor for Clostridioides difficile infection).

Immunoglobulin. Intravenous immunoglobulin 1 g/kg on day 1, then 0.5 g/kg on days 2 and 3, for refractory shock or persistent organ failure after 6 hours, though evidence is limited. Check renal function and give slowly.

Duration. Treat for at least 10 to 14 days, longer if there is deep infection.

Corticosteroid. Hydrocortisone 50 mg IV every 6 hours if the shock is refractory.

Supportive care. Replace calcium and phosphate, correct coagulopathy, renal replacement if needed and prevent venous thrombosis.

Prevention of recurrence. Avoid tampons and nasal packing in survivors, and decolonise nasal carriage (mupirocin 2% to each nostril twice daily for 5 days).

Monitoring. Haemodynamics, urine output, creatinine, liver tests, creatine kinase, platelets and coagulation, lactate and skin.

Referral and escalation. Intensive care, infection specialist, and surgical or gynaecological teams for source control.

Special groups. In postpartum disease, drain collections and treat the uterine focus. In children, antibiotic doses are weight based, and burns are an important source.