Toxic Shock Syndrome

Jared Helms D.O.7 March 2007

What Comes To Mind? Tampon use Minor trauma Injuries resulting in hematoma, bruising,

or muscle strain Surgical procedures (eg, suction

lipectomy, hysterectomy, vaginal delivery , bunionectomy, bone pinning, breast reconstruction, cesarean section)

Viral infections (eg, varicella, influenza) Use of nonsteroidal antiinflammatory

drugs

What Comes To Mind?

Cause Staphylococcus aureus (appx 0.8 per

100,000) Group A streptococcus (appx 3.5 per

100,000)

Staphylococcal toxic shock syndrome

Term toxic shock syndrome was coined in 1978

Public attention in 1980 based upon a series of menstrual-associated cases

CDC proposed a revised clinical case definition in 1981

Case definition of toxic shock syndrome from the CDC

Fever T >38.9°C (102.0°F)

Hypotension SBP< 90 mmHg; Orthostatic syncope or dizziness

Rash Diffuse macular erythroderma

Desquamation 1 to 2 weeks after onset of illness, particularly involving palms and soles

Case definition of toxic shock syndrome from the CDC

Multisystem involvement (3 or more of the following organ systems)

GI: Vomiting or diarrhea at onset of illnessMuscular: Severe myalgia or CPK elevation >2 times the normal

upper limitMucous membranes: Vaginal, oropharyngeal, or conjunctival

hyperemiaRenal: BUN or serum creatinine >2 times the normal upper limit, or

pyuria (>5 WBC/hpf)Hepatic: Bilirubin or transaminases >2 times the normal upper limitHematologic: Platelets <100,000/ LCentral nervous system: Disorientation or alterations in

consciousness without focal neurologic signs in the absence of fever and hypotension

Menstrual

Between 1979 and 1996, 5,296 TSS cases were reported 59 percent from 1987 to 1996 number of cases of menstrual TSS to

1 out of 100,000 women since 1986 case-fatality rate was 1.8 percent in

1987 to 1996

Nonmenstrual Approximately one-half of reported

TSS cases are nonmenstrual surgical and postpartum wound infections,

mastitis, septorhinoplasty, sinusitis, osteomyelitis, arthritis, burns, cutaneous and subcutaneous lesions (especially of the extremities, perianal area, and axillae), and respiratory infections following influenza

The proportion of cases following surgical procedures increased from 14 percent in 1979 through 1986 to 27 percent in 1987 through 1996

Menstrual versus nonmenstrual cases Clinical presentations of menstrual

and nonmenstrual TSS are similar Nonmenstrual TSS was associated

with earlier onset of rash and fever Surgical wound sites and

cutaneous infections are frequently benign-appearing without obvious purulence

PATHOGENESIS Toxic shock syndrome toxin-1 —

initial exotoxin isolated from S. aureus isolates implicated in TSS in 1981

Enterotoxins A, C, D, E, and H

PATHOGENESIS S. aureus

exotoxins cause disease because they are superantigens

Activate large numbers of T cells Activated T cells then release

interleukin (IL)-1, IL-2, tumor necrosis factor (TNF)-alpha and TNF-beta, and interferon (IFN)-gamma

Laboratory findings

Leukocytosis may not be present total number of mature and immature

neutrophils usually exceeds 90 percent immature neutrophils accounting for 25 to

50 percent of the total number of neutrophils

Thrombocytopenia and anemia

DIAGNOSIS

Based upon clinical presentation Isolation of S. aureus is not

required for the diagnosis of staphylococcal TSS

Cultures from mucosal and wound sites should be obtained

DIFFERENTIAL DIAGNOSIS

Streptococcal TSS associated with severe pain and tenderness

signifying infection at a site of local trauma

Rocky Mountain spotted fever the rash associated with RMSF typically is

petechial, involves the extremities first

Meningococcemia meningitis is frequently seen in conjunction

with meningococcemia and is rare in TSS

MANAGEMENT

Mainstay of treatment for TSS is supportive may require extensive fluid

replacement (10 to 20 liters per day) to maintain perfusion

vasopressors may also be required Episodes of menstrual TSS can

resolve with supportive care only

MANAGEMENT Examination for the presence of foreign

material in the vaginal canal Drainage of any identified infectious

focus Surgical wounds may not appear to be

infected because of the decreased inflammatory response but should nevertheless be explored and debrided if the patient fulfills the clinical criteria for TSS.

MANAGEMENT

It is not clear whether antibiotics alter the course of acute TSS, however antistaphylococcal antibiotic therapy is needed to eradicate organisms

Antibiotic therapy

All patients with suspected TSS receive empiric treatment with clindamycin (adults: 600 mg IV every eight hours; children: 25 to 40 mg/kg per day in three divided doses) plus vancomycin (adults: 30 mg/kg per day IV in two divided doses; children: 40 mg/kg per day IV in four divided doses)

Typically treat with a 10 to 14 day course

PROGNOSIS Death associated with TSS usually

occurs within the first few days of hospitalization but may occur as late as 15 days after admission

Questions about Staphylococcal toxic shock

syndrome?

Group A streptococcus TSS

Defined as any GAS infection associated with the acute onset of shock and organ failure

Any infection associated with the isolation of GAS from a normally sterile body site aerobic gram-positive coccus that causes

pharyngitis and a spectrum of skin and soft tissue infections such as impetigo, erysipelas, and localized cellulitis

PATHOGENESIS

Group A streptococcal TSS is mediated by toxins that act as superantigens

Cytokines cause capillary leak and tissue damage, leading to shock and multiorgan failure

PATHOGENESIS

Most common portals of entry for streptococcal infections are the skin, vagina, or pharynx

Portal of entry cannot be identified in 45% of cases

CLINICAL PRESENTATION Most common initial symptom is severe pain

abrupt in onset diffuse or localized typically involves an extremity may also mimic peritonitis, pelvic inflammatory

disease, pneumonia, acute myocardial infarction, cholecystitis, or pericarditis

Fever is the most common presenting sign hypothermia may be present in patients with shock

Other manifestations 80 % clinical signs of soft tissue

infection influenza-like syndrome (20%)

fever, chills, myalgia, nausea, vomiting, and diarrhea

50% of patients are normotensive on presentation or admission, but become hypotensive within the subsequent four hours.

Laboratory findings Mild leukocytosis

percentage of immature neutrophils may reach 40 to 50 percent

Serum creatinine is frequently elevated precedes the development of hypotension in

40 to 50 percent of cases Myoglobinuria and hemoglobinuria

can contribute to the development of acute renal failure

Laboratory findings

Increase in the serum creatinine kinase suggests the presence of necrotizing

fasciitis or myositis Positive blood cultures

approximately 60 % of cases (5% in Staph TSS)

DIFFERENTIAL DIAGNOSIS

Staphylococcal toxic shock syndrome Gram-negative sepsis

uncommon in healthy patients outside the hospital setting Rocky Mountain spotted fever

severe headache and rash are present in most patients with RMSF; rash is present in only 10% of patients with GAS TSS

Acute meningococcemia rash is petechial and meningitis is common in

meningococcemia but is infrequent in GAS TSS

DIAGNOSIS Isolation of GAS from a normally sterile site Hypotension (systolic blood pressure 90 mm Hg in

adults )

Plus two or more of the following: Renal impairment Coagulopathy Liver involvement Erythematous macular rash, may desquamate Soft tissue necrosis

Treatment

Hemodynamic support Massive amounts of intravenous fluids

(10 to 20 L/day) are often necessary vasopressors may also be required

Surgical therapy Prompt and aggressive exploration

and debridement of suspected deep-seated infection is mandatory

Treatment

Antibiotic therapy Presumptive therapy should be

initiated pending culture results Clindamycin suppresses the synthesis

of bacterial toxins and suppresses TNF The role of IVIG in GAS TSS remains

to be determined by controlled trials.

Recommended Empiric Therapy

Clindamycin (900 mg IV every eight hours) plus one of the following:

A carbapenem (meropenum 1g every eight hours)

A combination drug containing a penicillin plus beta-lactamase inhibitor (eg, ticaracillin-clavulanate 3.1 g every four hours or piperacillin-tazobactam 4.5 g every six hours)

PROGNOSIS

Overall mortality rate in GAS TSS varies from 30 to 70 percent

Signs of poor prognosis*: Lower white blood cell count (1000 vs

16000) Lower platelet counts (120 vs 170) Higher serum creatinine (3.0 vs 2.0) Lower systolic blood pressure (99 vs 120)

Review

1. Toxic shock syndrome is bad2. Fortunately, it is uncommon3. Treat hypotension with lots of fluids4. Surgical debridement should be

considered early

5. Clindamycin is the drug of choice

A 29 year old man comes to the ER with 1 day history of increasing pain in the upper right thigh. Two days ago, he was cutting rebar with a power saw when he suddenly developed right thigh pain from a splinter thrown by the saw. The pain abated over the next hour, and there was no lesion when he examined the thigh that evening. PMH is unremarkable. On physical exam vitals are 96/68-108-16-101.1. The right thigh is moderately tender. There is no erythema or swelling.

CT scan shows a minute metal fragment in the facial plane beneath the subcutaneous tissue with edema and stranding in adjacent areas.

The patient is hospitalized and begun on empiric vancomycin pending culture results. Three hours after admission, his BP drops to 60/0. IV fluids and vasopressors are started with mild improvement in pressure. Over the next several days the patient develops signs of renal and hepatic insufficiency (gradually returns to normal).

1. Armed with the knowledge of a stellar noon-time lecture you astutely diagnose:

A. CellulitisB. Staphylococcal toxic shock syndrome C. Streptococcal toxic shock syndromeD. Adverse reaction to vancomycin

2. Management of this patient includes:A. Continue vancomycin and increase fluidsB. Switch to clindamycin and nafcillinC. Add clindamycin to the vancomycin and get a

surgical evaluationD. Have him (or DPOAHC) fill out DNR papers

3. When grilled on rounds about the incidence of this infection, you confidently answer:

A. 0.8 cases per 100,000B. 3.5 cases per 100,000C. “It’s actually pretty common”D. Million to one shot doc