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Toxic Shock Syndrome: Treatment & Medication

Author: Sat Sharma, MD, FRCPC, Professor and Head, Division of Pulmonary Medicine, Department of Internal Medicine, University of Manitoba; Site Director, Respiratory Medicine, St. Boniface General Hospital
Contributor Information and Disclosures

Updated: May 1, 2009

Treatment

Medical Care

TSS has a rapid, dramatic, and fulminant onset. Quick recognition of the syndrome is important for enabling appropriate and prompt treatment. S pyogenes continues to be susceptible to beta-lactam antibiotics. Although very effective in treating pharyngitis and other superficial infections, aggressive GAS infections do not respond well to penicillin and continue to be associated with high mortality rates and extensive morbidity.

The principles in the management of septic shock in general must be instituted as soon as possible (see Septic Shock). These include the following components:

1. Early recognition
2. Early and adequate antibiotic therapy
3. Source control
4. Early hemodynamic resuscitation and continued support
5. Corticosteroids (refractory vasopressor-dependent shock)
6. Drotrecogin alpha (Severely ill if APACHE II > 25)
7. Tight glycemic control
8. Proper ventilator management with low tidal volume in patients with acute respiratory distress syndrome (ARDS)

• In experimental models of S pyogenes infection, penicillin proved to be inferior to clindamycin. The physiologic state of the organism attributed to the inoculum effects is suggested as the mechanism of failure.
  • Penicillin and other beta-lactam antibiotics are most efficacious against rapidly growing bacteria; therefore, these antibiotics have the greatest efficacy when organisms are growing rapidly during the early stages of infection or in mild infections. When higher concentrations of GAS accumulate (eg, deep-seeded infections), the effectiveness of beta-lactam antibiotics decreases because the bacterial growth slows (stationary phase).
  • Penicillin mediates its antibacterial action against GAS by interacting with penicillin-binding proteins (PBPs). Experimentally, the binding of penicillin has been shown to decrease in stationary cells, related to cells in the logarithmic growth phase; thus, the loss of certain PBPs during the stationary growth phase may be secondary to the inoculum effect and may account for penicillin failure.
• Clindamycin
  • This drug has multiple effects against GAS infection.
  • The efficacy of clindamycin is not affected by inoculum size or growth stage; furthermore, this agent is a potent suppressor of bacterial toxin synthesis.
  • Clindamycin facilitates phagocytosis of S pyogenes by inhibiting M protein synthesis.
  • Clindamycin suppresses synthesis of PBPs, which also are enzymes involved in cell wall synthesis.
  • Clindamycin has a longer postantibiotic effect than penicillin.
  • Clindamycin causes suppression of lipopolysaccharide-induced monocyte synthesis of TNF.¹⁴
• Recommended antibiotic therapy
  • For patients with GAS infection, the administration of clindamycin (900 mg IV q8h) is recommended. Other clinicians recommend combined therapy, in which penicillin G (4 million U IV q4h) is combined with clindamycin.
  • Because differentiating between STSS and streptococcal TSS on clinical grounds alone is difficult, intravenous penicillin also should be administered in addition to a beta-lactamase resistant antibiotic until a bacteriologic diagnosis is confirmed by culture. Alternatively, a first-generation cephalosporin or vancomycin can be used.
• Staphylococcal toxic shock syndrome
  • Large doses of a beta-lactamase–resistant, antistaphylococcal, antimicrobial agent should be administered intravenously to patients with staphylococcal infections. The usually prescribed antibiotics are nafcillin, oxacillin, and first generation cephalosporin. Nafcillin or oxacillin (2 g q4h) is generally recommended. Vancomycin can used in penicillin-allergic patients.
  • These agents have been known to increase TSST-1 in culture possibly by cell lysis. Therefore, clindamycin may be used in combination for the first few days to reduce synthesis of TSST-1.
  • The antibiotic treatment is continued for 10 to 14 days in absence of a complication.
• Intravenous fluids
  • TSS causes intractable hypotension and diffuse capillary leak; therefore, massive amounts of intravenous fluids (10-15 L/d) often are necessary. Patients in shock may require central venous monitoring or right heart catheterization to guide fluid management.
  • The patient's blood pressure may improve with administration of fluids alone; otherwise, vasopressors (eg, dopamine) or even more potent vasoconstrictors (eg, norepinephrine) are required. Norepinephrine with or without dobutamine may be more effective than high-dose dopamine or epinephrine to preserve splanchnic perfusion.
  • Patients with TSS will require supportive measures, including intubation and mechanical ventilation, dialysis in patients who have developed renal failure, and adequate nutritional support.
• Other treatment measures
  • Intravenous immunoglobulin: Several anecdotal reports, 1 large series of 21 patients and a case control study, reported lower mortality rates for patients with STSS treated with intravenous immunoglobulins.^11,15,16 Intravenous immunoglobulins also have been reported to be beneficial in severe cases of STSS. The recommended initial dosage is 2 g/kg, followed by 0.4 g/kg for as long as 5 days. The mechanism responsible for the efficacy of gamma-globulin therapy may be neutralization of the circulating toxins, inhabitation of TNF-alpha production via nonspecific inhabitation of monocyte or T-cell activation, or inhibition of other streptococcal virulence factors. The contraindications include a history of anaphylaxis from immune globulin in past, immunoglobulin A (IgA) deficiency, and circulating anti-IgA antibodies.A recent case series described 7 patients with severe soft tissue infection caused by GAS and toxic shock syndrome. All were treated with effective antimicrobials and high-dose intravenous immune serum globulin (IVIG). Surgery was either not performed or only limited exploration was carried out. Six of the patients had toxic shock syndrome. The study suggests that the use of a medical regimen including IVIG in patients with severe GAS soft tissue infections may allow a minimally invasive approach. This can limit the need to perform immediate wide debridements and amputations in unstable patients.¹⁷ Another prospective, randomized, controlled study included patients with severe sepsis and septic shock of intra-abdominal origin admitted to the ICU. Polyvalent IgM-enriched immunoglobulin (Ig) (Pentaglobin; IVIG group) at a dosage of 7 mL/kg/day for 5 days or an equal amount of 5% human albumin (control group) was randomized. Fifty-six patients were enrolled. The overall mortality rate was 37.5%. In the intent-to-treat analysis, the mortality rate was reduced from 48.1% in patients treated with antibiotic plus albumin to 27.5% for patients with antibiotic plus IVIG. IVIG administration in combination with adequate antibiotics improved the survival of surgical ICU patients with intra-abdominal sepsis.¹⁸
  • Hyperbaric oxygen has been used anecdotally in few patients, but whether this treatment is useful is not clear.
  • High-dose corticosteroid therapy has not been shown to be beneficial; if adrenal suppression is suspected, empirical dexamethasone (4 mg IV qid) may be initiated until results of the adrenocorticotropic hormone (ACTH) stimulation test become available.
  • In recent years, research is continuing to develop either monoclonal antibodies against TSST-1 or other peptides to block the ability of bacterial toxins to activate T cells, therefore blocking the toxicity cascade. Most of this research presently is focused on in vitro and animal models of toxic shock.

Surgical Care

Prompt, aggressive exploration and debridement of patients thought to have deep-seeded pyogenic infection constitutes a surgical emergency. Surgical exploration through a small incision with visualization of the muscle and fascia may provide an early and definitive diagnosis of necrotizing fasciitis. Infection often is more extensive than is apparent from external examination. Surgical debridement of infected tissue is extremely important and often requires re-exploration to ensure adequacy of resection.

Consultations

• Consultation with a surgeon should occur early.
• A consultation with an infectious diseases specialist is mandatory, and a consultation with an intensivist also is required for management of these patients in an intensive care unit.

Medication

The goals of pharmacotherapy are to reduce morbidity, prevent complications, and eradicate the infection.

Antibiotics

Antimicrobial therapy must cover all likely pathogens in the context of the clinical setting.

Clindamycin (Cleocin)

Lincosamide for treatment of serious skin and soft tissue staphylococcal infections. Also effective against aerobic and anaerobic streptococci (except enterococci). As much as 20% of group B streptococci may be resistant. Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes causing RNA-dependent protein synthesis to arrest.

Aqueous penicillin G (Pfizerpen)

Interferes with synthesis of cell wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible microorganisms.

Nafcillin (Nafcil, Unipen, Nallpen)

Initial therapy for suspected penicillin G–resistant staphylococcal infections. Use parenteral therapy initially in severe infections.
Due to thrombophlebitis, particularly in elderly patients, administer parenterally only for short term (1-2 d); change to oral route as clinically indicated.

Vancomycin (Lyphocin, Vancocin, Vancoled)

Potent antibiotic directed against gram-positive organisms and active against Enterococcus species. Useful in treatment of patients with septicemia and skin structure infections. Indicated for patients who cannot receive or have failed to respond to penicillins and cephalosporins or who have infections with resistant staphylococci (eg, MRSA). For abdominal penetrating injuries, combine with an agent active against enteric flora and/or anaerobes.
Use creatinine clearance to adjust dose in patients with renal impairment.

Oxacillin (Bactocill, Prostaphlin)

Bactericidal antibiotic that inhibits cell wall synthesis. Used in the treatment of infections caused by penicillinase-producing staphylococci. May be used to initiate therapy when staphylococcal infection is suspected.

• Search for CME/CE on This Topic »

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