Chapter 135. Gas Gangrene and Other Clostridial Infections (Part 5) docx

Chapter 135. Gas Gangrene and Other
Clostridial Infections
(Part 5)

Diagnosis
The diagnosis of clostridial disease, in association with positive cultures,
must be based primarily on clinical findings. Because of the presence of clostridia
in many wounds, their mere isolation from any site, including the blood, does not
necessarily indicate severe disease. Smears of wound exudates, uterine scrapings,
or cervical discharge may show abundant large gram-positive rods as well as other
organisms. Cultures should be placed in selective media and incubated
anaerobically for identification of clostridia. The diagnosis of clostridial
myonecrosis can be established by frozen-section biopsy of muscle.
The urine of patients with severe clostridial sepsis may contain protein and
casts, and some patients may develop severe uremia. Profound alterations of
circulating erythrocytes are seen in severely toxemic patients. Patients have
hemolytic anemia, which develops extremely rapidly, along with hemoglobinemia,
hemoglobinuria, and elevated levels of serum bilirubin. Spherocytosis, increased
osmotic and mechanical red blood cell fragility, erythrophagocytosis, and
methemoglobinemia have been described. DIC may develop in patients with
severe infection. In patients with severe sepsis, Wright's or Gram's staining of a
smear of peripheral blood or buffy coat may demonstrate clostridia.
X-ray examination sometimes provides an important clue to the diagnosis
by revealing gas in muscles, subcutaneous tissue, or the uterus. However, the
finding of gas is not pathognomonic for clostridial infection. Other anaerobic
bacteria, frequently mixed with aerobic organisms, may produce gas.
Clostridial Infections: Treatment
(Table 135-1) Traumatic wounds should be thoroughly cleansed and
debrided. Traditionally, the antibiotic of choice for severe clostridial infection has
been penicillin G (20 million units per day in adults). Penicillin G treatment of gas
gangrene has become more controversial because of increasing resistance to this

drug and data obtained from animal models of infection. In a mouse model of gas
gangrene, antibiotics inhibiting toxin synthesis appeared to be preferable to cell
wall–active drugs; clindamycin treatment enhanced survival more than therapy
with penicillin; and the combination of clindamycin and penicillin was superior to
penicillin alone. For severe clostridial sepsis, clindamycin may be used at a dose
of 600 mg every 6 h in combination with high-dose penicillin (3–4 million units
every 4 h). Although no clinical trials validate this choice, it is gaining acceptance
in the infectious disease community.
Table 135-1 Treatment of Clostridial Infections
a


Condition Antibiotic
Treatment
Penicillin
Allergy
Adjunctiv
e
Treatment/Note

Contaminatio
n
None — —
Gas gangrene

Penicillin,
3–
4 million units
IV q4h, plus
Clindamyci

n, 600 mg IV q6h
Chloramphenico
l, metronidazole,
imipenem, doxycycline
(see text)
b

Surgical
debridement with
wide excision is
essential.
Consider
hyperbaric
oxygen.
Clostridial
sepsis
Penicillin,
3–4 mill
ion units
IV q4h, plus
Clindamyci
n, 600 mg IV q6h
Chloramphenico
l, metronidazole,
imipenem, doxycycline
(see text)
b


Transient

bacteremia may
be clinically
insignificant.
Suppurative
deep-tissue
infections (e.g.,
abdominal wall,
gynecologic)
Penicillin,
3–
4 million units
IV q4h, plus
Gentamicin,
5 mg/kg IV q24h,
or
A third-
generation
cephalosporin
(e.g., ceftriaxone, 2
g IV q12h)
As above, plus
gentamicin or a
quinolone
Empirical
therapy should be
given. Therapy
should be based
on Gram's stain
and culture

results when
available.

a
Treatment recommendations for C. difficile
colitis, tetanus, and botulism
are found in Chaps. 123, 133, and 134, respectively.
b
Perform sensitivity testing; consider desensitization.
In cases of penicillin sensitivity or allergy, other antibiotics should be
considered, but all should be tested for in vitro activity because of the occasional
isolation of resistant strains. Clostridia are frequently, but not universally,
susceptible in vitro to cefoxitin, carbenicillin, chloramphenicol, clindamycin,
metronidazole, doxycycline, imipenem, minocycline, tetracycline, third-generation
cephalosporins, and vancomycin. For severe clostridial infections, sensitivity
testing should be done before an antimicrobial agent with unpredictable activity is
used. Simple contamination of a wound with clostridia should not be treated with
antibiotics. Localized skin and soft tissue infection can be managed by
debridement rather than with systemic antibiotics. Drugs are required when the
process extends into adjacent tissue or when fever and systemic signs of sepsis are
present. Surgery is a mainstay of therapy for gas gangrene. Amputation is often
required for rapidly spreading infection involving a limb, as the process frequently
fails to respond to antibiotics. Hysterectomy is required for uterine myonecrosis.
Abdominal wall myonecrosis usually continues despite initial aggressive surgery
and antibiotic therapy and requires repeated surgical debridement of all involved
muscle.
Suppurative infections should be treated with antibiotics. Frequently,
broad-spectrum antibiotics must be used because of the mixed flora involved in
these infections. Aminoglycosides can be used for the aerobic gram-negative
bacteria involved in mixed infections.

The use of a polyvalent gas gangrene antitoxin is still recommended by
some authorities. At present, no such antitoxin is produced in the United States,
and most centers have discontinued its use in the management of patients with
suspected gas gangrene or clostridial postabortion sepsis because of questionable
efficacy and the substantial risk of hypersensitivity to horse serum, from which the
antitoxin is derived.
The use of hyperbaric oxygen in the treatment of gas gangrene is also
controversial. Studies in humans are not well designed to answer questions on
efficacy, but several knowledgeable authors believe that hyperbaric oxygen
therapy has contributed to dramatic clinical improvement. Such therapy may,
however, be associated with untoward effects due to oxygen toxicity and high
atmospheric pressure. Some centers without hyperbaric chambers have reported
acceptable mortality rates; thus expert surgical and medical management and
control of complications are probably the most important factors in the treatment
of gas gangrene. Fasciotomy should not be delayed for hyperbaric oxygen therapy.
Acknowledgments
The authors acknowledge the contributions of Dori F. Zaleznik, MD, to this
chapter in earlier editions
Further Readings
Borriello SP: Clostridial disease of the gut. Clin Infect Dis 20:S242, 1995
Centers for Disease Control and Prevention: Clostridium sordellii
toxic
shock syndrome after medical abortion with mifepristone and intravaginal
misoprostol—United States and Canada, 2001–2005. MMWR 54:724, 2005
Lorber B: Gas gangrene and other Clostridium-
associated diseases, in
Principles and Practice of Infectious Diseases
, 6th ed, GL Mandell et al (eds).
Philadelphia, Elsevier Churchill Livingstone, 2005, pp 2828–2838
Murray-Lillibridge K et al: Epidemiological finding

s and medical, legal,
and public health challenges of an investigation of severe soft tissue infections and
deaths among injecting drug users—
Ireland, 2000. Epidemiol Infect 134:894,
2006 [PMID: 16316497]
Prinssen HM et al: Clostridium septicum myonecros
is and ovarian cancer:
A case report and review of literature. Gynecol Oncol 72:116, 1999 [PMID:
9889043]
Rood JI: Virulence genes of Clostridium perfringens
. Annu Rev Microbiol
52:333, 1998 [PMID: 9891801]
Stevens DL, Bryant AE: The role of clostridia
l toxins in the pathogenesis of
gas gangrene. Clin Infect Dis 35:S93, 2002
Wang C et al: Hyperbaric oxygen for treating wounds: A systematic review
of the literature. Arch Surg 138:272, 2003 [PMID: 12611573]
Bibliography
Ellemor DM et al: Use of genetically manipulated strains of
Clostridium
perfringens
reveals that both alpha-toxin and theta-
toxin are required for vascular
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[PMID: 10456947]
Schalch B et al: Molecular methods for the analysis of
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Tibbles PM, Edelsberg JS: Medical progress: Hyperbaric-
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