Approach

The mainstay of treatment for both streptococcal and staphylococcal TSS is supportive and is focused on specific management of the complications and sequelae associated with severe sepsis and multi-organ failure.

Supportive therapy

Early and immediate treatment should include aggressive fluid resuscitation, empirical antibiotic therapy, vasopressor support for refractory hypotension, haemodynamics optimisation, source control, and surgical debridement. Massive fluid resuscitation is often needed because of the diffuse capillary leak phenomenon and the refractory hypotension. The use of the vasopressor dopamine has been associated with higher mortality and more arrhythmic events compared with noradrenaline administration.[90]​ Intravenous corticosteroids should be administered for patients with ongoing vasopressor requirements or vasopressor-refractory septic shock.[83]

General intensive care preventive measures include stress ulcer prophylaxis with H2 antagonists or proton-pump inhibitors, deep venous thrombosis prophylaxis with heparin or low-molecular weight heparin, compression stockings, and enteral nutrition.[83][91][92]​​​ The American Diabetes Association recommends a general glucose goal of 7.8 to 10.0 mmol/L (140-180 mg/dL) in most critically ill patients with diabetes, preferably by using an insulin infusion protocol; however, more stringent control of blood glucose, in the range of 110-140 mg/dL, may be appropriate in a selected population of critically ill patients (such as critically ill patients undergoing surgery), if that can be achieved without the risk of hypoglycaemia.[93]​​ The Surviving Sepsis Campaign recommends the use of validated insulin infusion protocols targeting a blood glucose level of <10 mmol/L (<180 mg/dL).[83]​​

Patients with evidence of acute respiratory distress syndrome should receive lung-protective ventilation using maximum plateau pressures <30 cm H₂O and permissive hypercapnia to limit pulmonary damage.[94]

The patient should be promptly transferred to an intensive care unit for treatment.

Surgical debridement

Early and immediate surgical debridement should be considered in most patients with streptococcal TSS (i.e., those who present with fever, pain, soft-tissue swelling, and/or vesicle and bullae formation) with an appropriate surgical focus of infection. Aggressive surgical debridement of infected tissue including fascia is imperative and mandatory if a site of potential infection is identified. Repeated and sequential operative and bedside debridements of infected tissue are often needed, particularly if necrotising fasciitis is present in streptococcal disease.[63]

Source control is mandatory, including drainage of any existing abscesses and removal of the tampon, if present.

Delaying surgery until the patient develops systemic toxicity and definitive evidence of necrotising fasciitis or myositis increases mortality. In addition to surgical debridements, fasciotomy or amputation may be needed to halt the progression of the disease.

Antibiotic therapy

Definitive randomised, controlled studies on antibiotic therapy for streptococcal and staphylococcal TSS are not available. However, antibiotics remain a key component of therapy.

Suspected TSS

  • Antibiotics should be initiated empirically before culture reports.

  • Recommended empirical therapy is clindamycin plus 1 of the following: a carbapenem (i.e., imipenem/cilastatin or meropenem); a penicillin with a beta-lactamase inhibitor (e.g., ticarcillin/clavulanate or piperacillin/tazobactam); or vancomycin (in patients with penicillin allergies). In patients with suspected staphylococcal TSS, clindamycin plus vancomycin is recommended.

Confirmed streptococcal TSS

  • On the basis of animal studies, most experts recommend combination therapy with benzylpenicillin and clindamycin.[95][96] Beta-lactam antibiotics are effective at treating group A streptococcal (Streptococcus pyogenes) infection. Vancomycin may be used in place of benzylpenicillin in patients who are allergic to penicillin.

  • Treatment failure with penicillin has been reported, especially when organisms are present in large numbers.[97] Also, more aggressive group A streptococcal infections (i.e., necrotising fasciitis, empyema, burn wound sepsis, subcutaneous gangrene, and myositis) respond less well to penicillin.[41][98]​​[99]

  • Clindamycin as an alternative to penicillin has some advantages, especially because its efficacy is not affected by the size of the inoculum. It also inhibits protein synthesis and the synthesis of both M protein and streptococcal pyrogenic exotoxins. However, clindamycin should not be used alone because some strains of group A streptococcus are clindamycin resistant.[100] Increasing resistance of group A streptococcal infections to clindamycin has been seen in Europe, but resistance in the US has been reported in <1% of cases.[101][102]

Confirmed streptococcal TSS: adjunctive therapy

  • The addition of intravenous immunoglobulin (IVIG) may also be considered, but efficacy data are conflicting. Some observational studies suggest modest benefit. However, one small double-blind placebo-controlled trial (prematurely terminated because of slow patient recruitment) and one large retrospective analysis (of patients with debrided necrotising fasciitis with shock caused by group A streptococcus or Staphylococcus aureus) found that adjunctive IVIG was not associated with improved survival.[103][104][105][106][107]​ One meta-analysis including five studies found a potential mortality reduction with IVIG in those receiving clindamycin, but the results are controversial due to the inclusion of a randomised controlled trial among observational studies.[108]

  • Infectious Diseases Society of America (IDSA) guidelines do not include a recommendation regarding the use of IVIG in patients with necrotising fasciitis with streptococcal toxic shock syndrome, citing the need for additional efficacy studies.[109]

  • Consensus recommendations from the World Society of Emergency Surgery and the Surgical Infection Society Europe advocate consideration of IVIG in patients with necrotising fasciitis caused by group A streptococcus, while recognising that the use of IVIG for treating necrotising soft tissue infections remains controversial.[110][111]

Confirmed staphylococcal TSS

  • Anti-staphylococcal antibiotics are needed to eradicate the organism and to prevent recurrences.[12]

  • If the organism is identified as methicillin-sensitive Staphylococcus aureus, clindamycin plus oxacillin or nafcillin is recommended. Vancomycin may be used in place of oxacillin or nafcillin in patients who are allergic to penicillin.

  • If methicillin-resistant S aureus is identified, combination therapy with clindamycin plus vancomycin or linezolid should be given. There is in vitro evidence to suggest that linezolid can inhibit, and in some cases stimulate, toxin production by organisms involved in streptococcal or staphylococcal toxic shock syndrome. However, more research is needed to establish the clinical relevance of these findings.[112]

  • Treatment with topical mupirocin has been suggested to eradicate a positive nasal culture for Staphylococcus, but there are no data to support this practice.

Patients with clinical TSS without confirmed cultures should receive continued empirical therapy. Additional antibiotics may be needed for treating superinfections that may occur.

Treatment duration should be individualised, especially if there is a deep-seated infection. If bacteraemic, the patient should be treated for 14 days. Usually treatment is for 14 days after the last positive culture is obtained at surgery.

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