New syndrome not previously seen in S. aureus infections detected

May 2005

Researchers have identified five cases of purpura fulminans directly associated with Staphylococcus aureus strains that produce high levels of the superantigen toxic shock syndrome toxin-1 (TSST-1), staphylococcal enterotoxin serotype B (SEB) or staphylococcus enterotoxin serotype C (SEC).

An acute illness usually associated with meningococcemia or invasive streptococcal disease, purpura fulminans is characterized by disseminated intravascular coagulation (DIC) and purpuric skin lesions. Three of the five patients died and two bilateral amputations were performed.

According to the study’s lead researcher, Gary Kravitz, MD, at the St. Paul Infectious Disease Associates in St. Paul, Minn., purpura fulminans associated with S. aureus is a “new and devastating syndrome not previously seen in S. aureus infections.” Clinicians should be aware of this, as it could be an important new syndrome, he added.

From 2000 to 2004, five cases were identified in the Minneapolis-St. Paul metropolitan area. Patients were between the ages of 21 and 46 and four were females. The first patient was a 40-year-old female physician. Cultures of blood tested positive for methicillin-susceptible S. aureus (MSSA), which produced SEC and Panton-Valentine leukocidin (PVL). She was treated with ceftriaxone, levofloxacin and nafcillin. Purpura was noted on her extremities and torso. She underwent bilateral below-knee amputations but died on her twelfth day of hospitalization.

The second patient was a 56-year-old female nurse whose blood culture also tested positive for MSSA; SEB was produced. Purpura was noted on her arms, breasts, chest and neck, and she developed respiratory and renal failure. She was treated with nafcillin, but the lesions on her leg became infected with methicillin-resistant S. aureus (MRSA) and penicillin-susceptible Enterococcus species. Her therapy was changed to vancomycin and she survived.

The third patient was a 34-year-old woman who had a 20-year history of juvenile rheumatoid arthritis. Blood cultures tested positive for MSSA and Escherichia coli, urine cultures and specimens from the left-shoulder and left-knee aspirates tested positive for S. aureus, and fungal blood cultures grew Candida albicans. The S. aureus strains were positive for production of SEC and PVL. Purpura was noted on her extremities and trunk, and a CT of the head showed changes accordant with anoxic encephalopathy. She also died on her twelfth day of hospitalization.

The fourth patient was a 21-year-old male. A sputum culture tested positive for MRSA, which appeared to be a community-acquired strain, and SEC and PVL were produced. Blood cultures were negative. He underwent intubation and received intravenous fluids, azithromycin (Zithromax, Pfizer), cefotaxime, levarterenol and sodium bicarbonate. Necrotizing pneumonia and purpura over his entire body were noted. The patient died within 24 hours of intubation.

The fifth patient, a 43-year-old woman presented with severe shock and cyanosis. She received clindamycin, vancomycin and levarterenol as well as ventilatory support. Sputum culture tested positive for MSSA, which produced TSST-1. She remained pressor dependent and developed acute renal failure. Progressive purpura developed on her fingertips, toes and the soles of her feet. She received activated protein C (drotrecogin).

The clinicians noted that the purpura progressed to skin necrosis of the fingertips, toes and soles of her feet. The patient underwent bilateral below-knee amputations and rehabilitation.

New syndrome?

All of the patients’ cultures yielded S. aureus that produced SEB, SEC or TSST-1, which are superantigens that cause most cases of toxic shock syndrome.

The researchers concluded that the purpuric rash seen could be indicative of a more severe form of the syndrome. The initial clinical diagnosis in two of the cases was fulminant meningococcemia, but the clinical presentations for all five of the patients were identical to cases of fulminant meningococcemia.

The researchers recommended treating patients with antibiotics for Neisseria meningitidis, streptococci and also MRSA when presented with a patient with purpura fulminans.

They also suggested that administering activated protein C (drotrecogin) might minimize purpuric skin injury and down-regulate the inflammatory cascade before tissue injury occurs. The researchers also noted in Clinical Infectious Diseases that intravenous immunoglobulin therapy may be indicated because the therapy contains significant antibodies against the causative exotoxins associated with toxic shock syndrome.

For more information:

• Kravitz GR, Dries DJ, Peterson ML, et al. Purpura fulminans due to Staphylococcus aureus. Clin Infect Diseases. 2005;40:941-947.