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Letter
Clostridium tertium
in Necrotizing Fasciitis and Gangrene
Pallab Ray,* Anindita Das,*Kundan Singh,*Anil Bhansali,* and T.D.
Yadav*
*Postgraduate Institute of Medical Education and Research, Chandigarh,
India
Suggested citation
for this article:
Ray P, Das A, Singh K, Bhansali A, Yadav TD. Clostridium tertium
in necrotizing fasciitis and gangrene. Emerg Infect Dis [serial online]
2003 Oct [date cited]. Available from: URL: http://www.cdc.gov/ncidod/EID/vol9no10/03-0287.htm
To the Editor: Bacterial species of the genus Clostridium
are anaerobic or aerotolerant, gram-positive, endospore-forming bacilli
found in the soil and gut of humans and other animals. These species cause
botulism, tetanus, gas gangrene, antibiotic-associated diarrhea, pseudomembranous
colitis, foodborne diarrhea, and necrotic enteritis in humans and infections
in other animals. Clostridium tertium, a non–exotoxin-producing,
aerotolerant species, is an uncommon human pathogen. First isolated by
Henry from war wounds in 1917 (1), C. tertium
was recognized as a human pathogen when cases of bacteremia were reported
in 1963 (2). The organism has been implicated in bacteremia
(3,4), meningitis (5), septic arthritis
(6), enterocolitis (7), spontaneous
bacterial peritonitis (8), posttraumatic brain abscess
(9), and pneumonia (4). Miller and colleagues,
in a recent review of 32 cases, highlighted the role of neutropenia, intestinal
mucosal injury, and exposure to ß-lactam antibiotics predisposing
to C. tertium bacteremia (3). C. tertium
as the sole pathogen causing necrotizing fasciitis and gangrene has not
been reported. We report the first two cases of necrotizing fasciitis
and gangrene caused by C. tertium.
A 58-year-old man was seen at the Postgraduate Institute of Medical Education
and Research, Chandigarh, India, on August 17, 2001, with two nonhealing,
punched-out ulcers near the right lateral malleolus. The ulcers were approximately
2 cm x 2.5 cm in size, with necrotic margins, purulent exudate, and a
foul odor. On the second day, temperature of 39.4°C and gangrene of the
right leg developed. The patient also had alcoholic liver disease and
non-Hodgkin lymphoma, for which he had been receiving chemotherapy for
last 6 months, and he had had a 6 months’ course of antitubercular combination
therapy for pulmonary tuberculosis 2 years earlier.
Peripheral blood showed a leukocyte count of 10,000/mm3 with
80% neutrophils, 11% lymphocytes, and 9% monocytes. The fasting blood
glucose level was 400 mg/dL with normal electrolytes and renal function
test results. Liver function tests showed a serum glutamic oxalacetic
transaminase level of 80 IU/L and a serum glutamic pyruvic transaminase
level of 75 IU/L. Sputum microscopy showed no acid-fast bacilli. Microscopy
of necrotic tissue showed gram-positive bacilli (1–1.5 µm x 5–6
µm) with frequent oval terminal spores. Aerobic blood culture was
sterile. Insulin was given to control his blood glucose level. Antimicrobial
therapy included intravenous metronidazole, vancomycin, and imipenem.
Skin and subcutaneous tissue debridement and fasciotomy were also undertaken.
A 40-year-old man was seen at the Postgraduate Institute on October 17,
2001, with multiple injuries of lower extremities and abdomen following
a motor vehicle accident. After 24 h, the patient’s left leg and thigh
turned gangrenous, and a high-grade fever (38.6°C) and an elevated leukocyte
count of 14,000/mm3 (70% neutrophils, 20% lymphocytes, 10%
monocytes) developed. Microscopy of necrotic tissue showed gram-positive
rods (1 µm x 5 µm) with oval, terminal spores. Aerobic blood
culture was sterile. Skin and subcutaneous tissue were extensively debrided.
Antibiotic therapy with intravenous penicillin, metronidazole, and amikacin
was instituted.
Necrotic tissues from both cases were cultured on Columbia sheep blood
agar plates incubated aerobically and anaerobically (ANOXOMAT system,
MART Microbiology BV, Lictenvoorde, the Netherlands) at 37°C for 24 h
and 48 h, respectively. Overnight aerobic culture grew small gray colonies
(<1 mm in diameter) of non–spore-forming gram-variable bacilli (1 µm
x 5 µm), which, on subculture anaerobically grew gram-positive rods
with oval, terminal spores. Anaerobic culture directly from specimen yielded
similar spore-forming, gram-positive bacilli. The isolates were presumptively
identified as Clostridium species by colony characteristics, Gram-stain
morphology, and negative catalase test results; they were confirmed as
C. tertium based on aerotolerance; shape and location of endospores;
fermentation of glucose, lactose, maltose, and sucrose; nitrate reduction;
and absence of proteolysis. Both isolates of C. tertium were susceptible
in vitro to penicillin, ampicillin, vancomycin, and metronidazole.
C. tertium has been traditionally considered nonpathogenic. The
organism was earlier isolated along with pathogens such as C. perfringens,
C. septicum, and C. sordellii from war wounds and cases
of gangrene (1). C. tertium is being increasingly
reported as a human pathogen (3–9), and the strongest
association has been with septicemia in patients with neutropenia and
hematologic malignancies (3,4). Predisposing factors
for C. tertium bacteremia include intestinal mucosal injury, neutropenia,
ß-lactam antibiotics (third-generation cephalosporins), cytotoxic
chemotherapy, and severe liver disease, as reviewed by Miller and co-workers
(3). Necrotizing fasciitis and gas gangrene caused by
C. tertium as the sole pathogen have not been reported, although
Miller reported necrotizing fasciitis in a patient with acute lymphocytic
leukemia with C. tertium and C. septicum isolated from blood
(3). The importance of isolation of C. tertium,
particularly in polymicrobial cultures, is not well-established. In our
report, the first patient suffered from alcoholic liver disease, had very
high blood glucose levels, and was on cytotoxic chemotherapy for previous
6 months. The risk for intestinal injury is high in severe liver disease
and cytotoxic chemotherapy. Intestinal mucosal compromise may potentiate
translocation of C. tertium to systemic circulation and metastatic
foci. The second patient had no predisposing medical history before the
present episode that might have resulted in acquisition of C. tertium
from the soil. Both patients had pyrexia, necrotizing fasciitis, and gangrene
of a lower limb with C. tertium as the sole bacterial isolate.
Neither patient had neutropenia when they were first seen. This contrasts
with earlier reports of C. tertium infections (predominantly bacteremia),
which usually occurred in patients with preexisting neutropenia (3).
Both patients improved with penicillin or vancomycin and metronidazole,
and both isolates were susceptible to these three antibiotics in vitro.
Therefore, we consider both isolates to be clinically important. The pathogenesis
of infection caused by C. tertium is not well understood, since
the organism does not produce exotoxins. No evidence exists to correlate
oxygen sensitivity with bacterial enzyme production and pathogenicity
in aerotolerant clostridia. Our report adds to the list of recently emerging
diseases caused by C. tertium. The growing acceptance of this organism
as a human pathogen will lead to better delineation and understanding
of its pathogenic potential.
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