Case of the Month

January 2016

Jade Mogambery1, Sumayya Haffejee2, Halima Dawood1

1Grey’s Hospital, Department of Internal Medicine, Infectious Diseases Unit and University of KwaZulu Natal. 2 Department of Microbiology, Northdale Pathology Laboratory, NHLS, Pietermaritzburg and University of KwaZulu Natal

A 28-year old HIV-seronegative woman was referred to the Obstetrics department of a tertiary care hospital from a district health facility. She presented with a swollen knee, hypotension and fever a week after delivering a healthy baby by normal vaginal delivery. She required an episiotomy in order to facilitate the delivery process.
Blood cultures where taken at the district health facility and she was referred for further management to the intensive care unit after a diagnosis of septic shock was made. Puerperal sepsis was considered but following a gynecological examination and imaging this was excluded.
She developed renal impairment with a creatinine of 251 umol/L (50 - 90 umol/L). The international normalized ratio was elevated and the platelet count was less than 100,000/mm3. There was evidence of liver dysfunction with a bilirubin level that had increased to 123 umol/L (<26 umol />L) and transaminases that were more than two times the upper limit of normal.
Following clinical deterioration she required both ventilatory and inotropic support for hypoxia and hypotension respectively. Twenty four hours after admission to the intensive care unit, purpuric lesions developed on the lower limbs and a clinical diagnosis of necrotizing fasciitis was made.
The blood culture, taken at the district health facility, grew a Group A Streptococcus (Streptococcus pyogenes) that was sensitive to penicillin and clindamycin. She was commenced on these antibiotics and was taken to theatre for debridement of the soft Streptococcus tissue. She subsequently required a skin graft and recovered without any further complications.

Question 1: What complication of Group A Streptococcus infection did this patient develop and what are the diagnostic criteria?

Answer to Q1:

This patient developed Streptococcal Toxic Shock Syndrome (TSS).

Diagnostic criteria (CDC 2010)
  • Clinical Criteria
  • An illness with the following clinical manifestations*: Hypotension defined by a systolic blood pressure less than or equal to 90 mm Hg for adults or less than the fifth percentile by age for children aged less than 16 years.
  • Multi-organ involvement characterized by two or more of the following:
    • Renal impairment: Creatinine ≥2 mg/dL (≥177 µmol/L) for adults or greater than or equal to twice the upper limit of normal for age. In patients with preexisting renal disease, a greater than twofold elevation over the baseline level.
    • Coagulopathy: Platelets ≤100,000/mm3 (≤100 x 106/L) or disseminated intravascular coagulation, defined by prolonged clotting times, low fibrinogen level, and the presence of fibrin degradation products.
    • Liver involvement: Alanine aminotransferase, aspartate aminotransferase, or total bilirubin levels greater than or equal to twice the upper limit of normal for the patient's age. In patients with preexisting liver disease, a greater than twofold increase over the baseline level.
    • Acute respiratory distress syndrome: defined by acute onset of diffuse pulmonary infiltrates and hypoxemia in the absence of cardiac failure or by evidence of diffuse capillary leak manifested by acute onset of generalized edema, or pleural or peritoneal effusions with hypoalbuminemia.
    • A generalized erythematous macular rash that may desquamate.
    • Soft-tissue necrosis, including necrotizing fasciitis or myositis, or gangrene.
  • * Clinical manifestations do not need to be detected within the first 48 hours of hospitalization or illness, as specified in the 1996 case definition. The specification of the 48 hour time constraint was for purposes of assessing whether the case was considered nosocomial, not whether it was a case or not.
  • Laboratory Criteria for Diagnosis
  • Isolation of group A Streptococcus.
  • Case Classification
  • Probable
  • A case that meets the clinical case definition in the absence of another identified etiology for the illness and with isolation of group A Streptococcus from a non-sterile site.
  • Confirmed
  • A case that meets the clinical case definition and with isolation of group A Streptococcus from a normally sterile site (e.g., blood or cerebrospinal fluid or, less commonly, joint, pleural, or pericardial fluid).
Our patient had hypotension, as well as indicators of clinical severity namely; renal impairment, coagulopathy, liver involvement and necrotizing fasciitis. In addition, Group A Streptococcus was isolated on blood culture. This patient met the CDC 2010 diagnostic criteria for streptococcal toxic shock syndrome

Question 2: Describe the microbiology of Streptococcus pyogenes and how Group A Streptococci are acquired
Question 3: Describe the epidemiology of streptococcal TSS, the associated virulence factors, and
Answer to Q2

Streptococcus pyogenes is a ß-haemolytic Gram-positive coccus that belongs to Lancefield’s group A. It inhabits the skin and upper respiratory tract and its presence in a specimen is always considered clinically significant. The organism may be cultured on standard laboratory media e.g. 5% blood and chocolate agar. Serological tests remain positive up to 2 months after infection. The serological tests are based on the detection of antibodies that develop in response to antigens of Streptococcus pyogenes namely Streptolysin O and DNase B. Antistreptolysin O titres (ASO T) and anti-DNase B are commercially available.

Means of acquisition of invasive Group A Streptococcus?
  • Suction lipectomy, hysterectomy, normal vaginal delivery and orthopaedic surgery are itratrogenic routes of acquisition.
  • Minor penetrating or non-penetrating trauma
  • Viral infections like varicella zoster or herpes simplex virus may provide a breach that causes GAS colonization to become invasive disease.
Answer to Q3

US population based data estimates an incidence of 1.5-5.2 cases of invasive Group A streptococcal infection per 100 000 people annually. Eight to fourteen percent of these patients will go on to develop TSS. The mortality rates for streptococcal TSS range between 30 and 70 percent.
The virulence factors implicated in the pathogenesis of Streptococcal Toxic Shock Syndrome are shown in the following table:

There is an increase in TNFα, and increase in IL-1 and IL-6 that result in systemic inflammatory response syndrome. In addition bradykinin results in vasodilation. The bacterium is the stationary part of the growth cycle and release of exotoxin is the major mediator in the pathogenesis of streptococcal TSS.

Question 4: What are the risk factors for the development of streptococcal TSS?

Answer to Q4
  • Neonates and the elderly
  • Diabetes mellitus
  • Alcoholism
  • Surgical procedures
  • Trauma (penetrating or non-penetrating)
  • Varicella zoster infections
  • Limited evidence for NSAID use
Question 5: What is the management of streptococcal TSS, and what are its complications?
Answer to Q5:


Source control:Surgical exploration and debridement
Fluid resuscitation:Crystalloids may be infused to maintain blood pressure
Antibiotics:Streptococcus pyogenes remains sensitive to penicillin however due to the toxin mediated pathogenesis of TSS an antibiotic that inhibits protein synthesis is often a better choice. Clindamycin has been shown to be more effective in the treatment of TSS. It is able to inhibit exotoxin and M protein synthesis. It also has a longer half-life than penicillin.
Supportive care:Intensive care as well as offering ventilation, inotropic support and haemodialysis if necessary.
Immunoglobulin:Intravenous immunoglobulin has been shown to reduce mortality by 40% in a single randomized controlled trial. Other trials have not shown such a dramatic improvement in mortality. The immunoglobulins have a neutralizing effect on the exotoxins. Currently the recommendation is that the immunoglobulin be given early and 2 doses may be more beneficial than a single dose.

Complications of Group A Streptococcus infection?

CDC Streptococcal toxic-shock syndrome (STSS) (Streptococcus pyogenes) 2010 Case Definition
Gerald L Mandell. (2010). Principles and Practice of Infectious Diseases. Philadelphia: Churchhill Livingstone Elsevier.
Jessica Darenberg. (2003). Intravenous immunoglobulin G therapy in Streptococcal Toxic Shock Syndrome: A European randomized double-blind placebo-controlled trial. Clinical infectious diseases, 333-337.
Kaul, R. (1999). Intravenous immunoglobulin therapy for streptococcal toxic shock syndrome--a comparative observational study. The Canadian Streptococcal Study Group. Clinical infectious diseases, 800-807.
Stevens, D. L. (1995). Streptococcal Toxic-Shock Syndrome: specturm of disease, pathogenesis and new concepts in treatment. Emerging infectious diseases, 69-78.

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