The Expanding Syndrome of Necrotizing Fasciitis

Abstract & Commentary

By Joseph F. John, MD, FACP, FIDSA, FSHEA, Associate Chief of Staff for Education, Ralph H. Johnson Veterans Administration Medical Center; Professor of Medicine, Medical University of South Carolina, Charleston, is Associate Editor for Infectious Disease Alert.

Dr. John is a consultant for Cubist, Genzyme, and bioMerieux, and is on the speaker's bureau for Cubist, GSK, Merck, Bayer, and Wyeth.

Synopsis: Most clinicians associate the hemolytic streptococci as the major cause of necrotizing fasciitis (NF), an association that is usually the case. There are, however, other emerging causes of the syndrome and, in fact, NF is often a polymicrobial synergistic infection, particularly after surgical procedures. Other risk factors include blunt trauma, cuts, burns, varicella infection, and even muscle strains. With this patient, radiotherapy joins the group of risk factors.

Source: Kelesidis T, Tsiodras S. Postirradiation Klebsiella pneumoniae-associated necrotizing fasciitis in the Western Hemisphere: A rare but life-threatening clinical entity. Amer J Med Sci. 2009;338:217-224

A new report and review of the literature comes from Caritas St. Elizabeth's Medical Center in Boston of a 77-year-old Native American with follicular thyroid cancer post-radiation that spread to his hip, resulting in metastatic disease. He developed septic shock and necrotizing fasciitis of both thighs. Wide debridement was performed on both thighs, which grew only Klebsiella pneumoniae; this organism was also present in blood and urine. The patient eventually died.

This patient joins 37 other patients with K. pneumoniae-caused NF that the authors gleaned from the literature, together with one case with K. oxytoca and one case with K. aeruginosa. Several important points differentiate these patients from those with Gram-positive-related NF. Most of the cases occurred in Asian countries: 37% in China, 21% in Taiwan, 13% in Turkey, and four cases in Singapore. Only one case, thus far, has been reported in the United States. The authors go on to describe 15 cases of monomicrobial NF caused by K. pneumoniae.

These patients had significant comorbidities: diabetes in 80%, cirrhosis in 20%, and one each with chronic renal failure and malignancy, respectively. Many of the previously reported cases had liver abscesses. In 10 cases, at least one other organ was involved. Bacteremia was present in 10 of the 15 patients. In 13 of the patients where mortality was reviewed, 31% of the patients died. There was a suggestion in these NF patients of hematogenous spread from multiple foci, so the concept advanced is that invasive K. pneumoniae infection often spreads to multiple organs from where the organism emerges to cause NF.

Therapy with surgical debridement and fasciotomy was the keystone of treatment with the addition of active antimicrobials. In this series only, one isolate was associated with a multiresistant K. pneumoniae. Thus, third-generation cephalosporins were the medical treatment of choice.

Comment

The spectrum of microbial agents capable of causing NF continues to expand. Almost 40 cases have been described related to Klebsiella infection. This genus is notorious over the last half century for causing healthcare-related infection, probably due to its propensity to colonize early in the hospitalized patient and to elaborate certain virulence factors, including capsular material and antibiotic resistance, which obfuscate antimicrobial therapy. The presence of exceptionally mucoid K. pneumoniae has also recently been associated with severe infection and rapid spread. Klebsiella also have, for years, been notorious for having transmissible plasmids that can carry virulence factors like mucoid along with antimicrobial-resistant determinants.

This present study did not address the possibility that intrinsic or acquired toxins may be part of the infectious arsenal of K. pneumoniae, and more work needs to focus on that aspect. Indeed, NF seems to be a response to toxigenic factors in bacteria, classically the streptococcal and staphylococcal toxins. The spectre of Gram-negative toxins hangs over this new review of a classic Gram-negative pathogen, K. pneumoniae, as a capable cause, even in monomicrobial settings, of NF.