Critical Care Medicine-Infections and Immunologic Disease>>>>>Immunological Effects of Infections
Question 2#

A 68-year-old diabetic man, who had open sigmoidectomy 10 days ago for diverticulitis, is brought to emergency department (ED) after his son found him altered at home. Initial vitals are notable for:

His blood glucose is normal. Blood cultures, chest x-ray, urinalysis, and urine culture are obtained. He is given vancomycin, cefepime, metronidazole, and 2 L of lactated Ringer’s and is subsequently intubated for airway protection. CT scans of the head, chest, abdomen, and pelvis, obtained before the ICU admission, are unremarkable.

On ICU arrival, detailed physical examination reveals diffuse erythematous blanching rash and hyperemic mucus membranes of the mouth and conjunctiva. His abdominal incision is slightly erythematous but without frank purulence

Subsequent management should include which of the following?

A. Intravenous (IV) piperacillin-tazobactam monotherapy
B. Continuation of IV vancomycin, cefepime, metronidazole, and addition of IV clindamycin
C. Discontinuation of vancomycin because of skin reaction
D. IV diphenhydramine and hydrocortisone

Correct Answer is B


Correct Answer: B

Toxic shock syndrome (TSS) is a life-threatening condition because of Staphylococcus aureus or group A Streptococcus toxin. Patients with surgical and postpartum wounds and, classically, menstruating women are at increased risk. Diagnostic criteria for TSS include fever greater than 38°C, multisystem organ dysfunction including vomiting or diarrhea (often watery), muscular symptoms (myalgias/creatine phosphokinase levels >2× upper limit of normal), mucus membrane involvement, renal dysfunction or pyuria in the absence of urinary tract infection, hepatic dysfunction (elevated bilirubin and aminotransferases), thrombocytopenia, and altered mental status without focal neurologic findings. 

The pathophysiology of TSS involves super antigens that cause overwhelming T-cell activation leading to a state of cytokine storm with high levels of IL-1, IL-2, and TNF-alpha and beta, as well as interferon gamma. Super antigens involved in the pathophysiology of TSS include TSST-1 and staphylococcal enterotoxins (A-D).

The best empiric antibiotic management while awaiting culture data is IV clindamycin (to halt toxin synthesis) and vancomycin (methicillinresistant Staphylococcus aureus coverage). Piperacillin-tazobactam is not an optimal antibiotic regimen as it does not have appropriate methicillinresistant Staphylococcus aureus coverage and will not decrease toxin production.

There is currently clinical equipoise regarding the use of intravenous immunoglobulin (IVIg), although observational comparative studies have demonstrated that IVIg is associated with significantly lower mortality at 28 days. The mechanism is thought to include neutralization of the super antigens. This treatment is not ubiquitously used at all institutions. 


  1. CDC Notifiable Disease Surveillance System. Toxic Shock Syndrome (Other Than Streptococcal) (TSS) 2011 Case Definition. Available at
  2. Schliever PM. Use of intravenous immunoglobulin in the treatment of staphylococcal and streptococcal toxic shock syndromes and related illnesses. J Allergy Clin Immunol. 2001;108(4):S107-S110.
  3. Sivagnanam S, Deleu D. Red man syndrome. Crit Care. 2003;7(2):119-120.
  4. Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014, update by the infectious diseases society of America. Clin Infect Dis. 2014:59(2):e10-e52.