We reviewed the records of thirty-two patients with necrotizing soft-tissue
infections and sepsis caused by Vibrio vulnificus and Aeromonas who
were admitted to our hospital between June 2002 and November 2005. The
principal symptoms on presentation were pain and swelling of the involved
limbs with patchy, edematous, erythematous, and bullous skin lesions at the
time of consultation in the emergency room or on the hospital ward.
Broad-spectrum antibiotic therapy with ceftriaxone or ceftazidime combined
with doxycycline or gentamicin was administered to all patients when Vibrio or
Aeromonas infection was suspected.
Culture findings by the microbiology laboratory confirmed Vibrio
vulnificus in seventeen patients and Aeromonas species in fifteen
patients. The patients in whom Aeromonas species were present in a mixed
culture were included in this study only when the Aeromonas growth was heavy
and predominant. A culture for Aeromonas hydrophila, the species most
frequently identified in the Aeromonas group, was positive in ten patients,
Aeromonas sobria grew on wound culture specimens from four patients,
and Aeromonas caviae grew on wound culture specimens from one
patient. In one patient (Case 9), Aeromonas sobria grew on a wound
culture sample and a blood sample was positive for Aeromonas caviae
(see Appendix). Culture findings demonstrated polymicrobial infection in seven
patients. Additional pathogens identified were Enterococcus, Escherichia
coli, Enterobacter cloacae, Pseudomonas aeruginosa, Klebsiella oxytoca,
Clostridium, and Serratia marcescens.
The Vibrio vulnificus group included twelve men and five women who
had a mean age of sixty years (range, thirty-six to seventy-seven years). All
patients had a history of contact with raw seafood or exposure to warm
seawater, and most infections had occurred in the summer months (May to
September). Eight patients had a history of hepatic disease, including liver
cirrhosis and diabetes mellitus in three patients, liver cirrhosis and
diabetes mellitus with hepatitis in two patients, and liver cirrhosis in one
patient, hepatitis B and C in one patient, and hepatitis C with diabetes
mellitus in one patient. Four patients had diabetes mellitus without hepatic
disease, two patients had chronic renal insufficiency, and one patient had
rheumatoid arthritis. One patient (Case 13) was in good health, and another
(Case 14) had a history of drug abuse (see Appendix).
The Aeromonas group included twelve men and three women who had a mean age
of sixty-two years (range, twenty-two to seventy-nine years). Twelve patients
were farmers. Of the fifteen patients with Aeromonas infections, five had
acquired wounds while working, one patient had handled fish, four patients
fell into a ditch during a motor vehicle accident, and four patients did not
recall any injury. The remaining patient (Case 3) had hepatocellular
carcinoma, diabetes mellitus, and liver cirrhosis and had undergone
transhepatic arterial chemoembolization four days prior to the onset of
necrotizing fasciitis. Two patients were healthy before the infection
occurred. Six patients had diabetes mellitus, two patients had alcoholic liver
disease, one patient had chronic renal insufficiency, one had gout, one had a
history of steroid intake, and one had both diabetes mellitus and gout.
The demographic data, underlying diseases, laboratory results, interval
between injury and admission, interval between the diagnosis of necrotizing
fasciitis and surgery, and clinical outcomes were analyzed for each patient.
The Wilcoxon rank-sum test and Fisher exact test were applied to test for
significant relationships between these factors for the Vibrio
vulnificus and Aeromonas groups. A p value of <0.05 was considered
significant.
Surgical débridement or immediate limb amputation was initially
performed in all patients with necrotizing soft-tissue infections. Ten
patients died, resulting in a mortality rate of 31%. The patients who died had
significantly lower serum albumin levels than the patients who survived (p
< 0.05). Patients with hepatic dysfunction and diabetes mellitus had higher
mortality rates than those with hepatic disease or diabetes mellitus alone (p
< 0.05) (Table I).
The clinical characteristics and laboratory data of the seventeen patients
with Vibrio vulnificus infection are summarized in tables in the
Appendix. Ten patients had skin lesions on their lower limbs, and seven had
them on their upper limbs (Fig.
1). Sixteen patients initially underwent fasciotomy and
débridement. Progressive sepsis after fasciotomy resulted in amputation
in four patients. Two patients had above-the-elbow amputations, and two had
above-the-knee amputations. One patient immediately underwent an
above-the-knee amputation because of severe skin lesions and sepsis at the
time of presentation in the emergency room. Three of the seventeen patients
had a fever (a temperature of >38.5°C or 101.3°F). Twelve patients
were hypotensive with a systolic blood pressure of =90 mm Hg. Five patients
died within two to twelve days after admission, and one patient (Case 6) died
two months after surgery because of the complications of pneumonia, persistent
sepsis, and respiratory failure. The mortality rate for the Vibrio
vulnificus group was 35%.
The clinical characteristics and laboratory data for the fifteen patients
with Aeromonas infection are summarized in tables in the Appendix. Thirteen
patients had lower-limb involvement, and two patients had upper-limb
involvement. Eleven patients initially underwent fasciotomy and
débridement. Fasciotomy was followed by amputation in three patients,
two of whom had an above-the-knee amputation and one who had a below-the-knee
amputation. Two patients immediately underwent an above-the-knee amputation to
treat severe necrotizing fasciitis and sepsis. Two patients (Cases 6 and 15)
had fallen into dirty ditches and had open bimalleolar fractures. The
fractures first were treated with débridement and screw fixation, and
the wounds were left open. However, progressive infection with patchy
erythematous skin lesions and muscle necrosis developed a few days later, and
below-the-knee amputations were performed. None of the fifteen patients had a
fever. Three patients had a systolic blood pressure of =90 mm Hg. Four
patients died within two to eleven days after admission, and eleven patients
survived, resulting in a mortality rate of 27%.
The Vibrio vulnificus and Aeromonas groups were not significantly
different with respect to the age of the patient, presence of a fever,
interval between injury and admission, white blood-cell count, platelet count,
and serum albumin level. However, the difference between the groups with
regard to the number of patients with a systolic blood pressure of =90 mm
Hg was significant (p = 0.006) (Table
II).
The data on the patients who died in each group were compared. The patients
in the Aeromonas group who died had significantly decreased white
blood-cell counts (p = 0.03) and segmented white blood-cell counts (p = 0.01)
than those who died in the Vibrio group. A significantly greater number of
patients who died in the Vibrio vulnificus group had a systolic blood
pressure of =90 mm Hg in the emergency room compared with those who died in
the Aeromonas group (p = 0.03).
Vibrio vulnificus and Aeromonas species, members of the
Vibrionaceae family, are gram-negative bacteria with positive oxidase activity
and glucose
fermentation1,4.
Vibriovulnificus is arginine dehydrogenase negative, lysine
decarboxylase positive, and ornithine decarboxylase positive. These
characteristics of Vibrio vulnificus can be differentiated from
Aeromonas species, which are arginine dehydrogenase positive and sensitive to
vibriostatic agent
O1294.
Human illnesses typically caused by Vibrio and Aeromonas are acute
gastroenteritis, wound infection, and primary septicemia. Necrotizing
fasciitis is a rare disease in healthy individuals. Chronic illnesses, such as
cirrhosis of the liver, alcoholic liver disease, malignant tumors, gouty
arthritis, chronic renal failure, diabetes mellitus, or chronic steroid use
have been associated with Vibrio vulnificus and Aeromonas
infections1-3,6,9,17.
The reported mortality rates for Vibrio infection have ranged from 25% to 33%
among patients with chronic illnesses who underwent débridement to 66%
to 100% among those who did not undergo
débridement2,3,14,15.
The fatality rate associated with Aeromonas soft-tissue infections and
bacteremia has been reported to be as high as 28% to
73%1,5,6,8,18.
Wound infections in both groups typically occur one day after injury and
are characterized by pain, swelling, hemorrhagic bullae, subcutaneous
bleeding, purpura, necrosis, and gangrene, all of which are difficult to
differentiate at the time of presentation. In our hospital, the treatment
protocol for patients suspected of having Vibrio necrotizing fasciitis and who
have a recent history of exposure to seawater or seafood is emergency
fasciotomy or amputation, broad-spectrum antibiotic therapy, and admission to
the intensive care unit when the infection is
severe2. However,
the mortality rate remained high, with a rate of 35% for the Vibrio
vulnificus group and 27% for the Aeromonas group.
Vibrio vulnificus and Aeromonas species can release factors into
the circulation to cause a fulminant course of sepsis. Vibrio
vulnificus hemolysin frequently disrupts various eukaryotic erythrocytes
and mast cells. The Vibrio vulnificus protease also enhances vascular
permeability that can result in a hemorrhagic lesion that finally provokes
severe skin necrosis. Thus, the protease can facilitate edema formation and
bacterial
invasion19.
Aeromonas species have potent exotoxins, which are probably responsible for
the extensive muscular necrosis that is common in patients with necrotizing
fasciitis1,8,20-22.
Aeromonas soft-tissue infections, such as Aeromonas hydrophila and
Aeromonas sobria, can be severe with myonecrosis and gas production,
resembling those caused by
clostridia1,23-27.
Itoh et al. reported that autopsy findings in a patient with alcoholic liver
cirrhosis and Aeromonas sobria soft-tissue infection showed extensive
cellulitis, rhabdomyolysis, and epidermolysis with some bacterial
colonies28. In our
patients, we found that the lesions in the Aeromonas group had considerably
more muscle involvement and foul odor than those in the Vibrio
vulnificus group.
Aeromonas hydrophila is frequently isolated in polymicrobial
infections and can result in synergistic necrotizing fasciitis with
gram-negative bacilli and Clostridium species; however, Vibrio
vulnificus seldom is found in a polymicrobial
infection1,20,29.
Gold and Salit reported that nine of eleven patients with an Aeromonas
infection had a polymicrobial infection by wound culture, but none
died1. On the other
hand, Ko and Chuang reported that nine of nineteen patients with polymicrobial
infections and bacteremia
died5. Seven of our
fifteen patients with Aeromonas infection had polymicrobial infections;
however, the mortality rate was four of fifteen patients and did not appear to
be related to polymicrobial infection.
Many studies have proposed that fever and hypotension are the most common
manifestations associated with Vibrio vulnificus and Aeromonas
sepsis1,5,13,30.
In this study, no patient with an Aeromonas infection had a fever and only
three patients in the Vibrio vulnificus group had a temperature of
>38.5°C. The number of patients with a systolic blood pressure of
=90 mm Hg in the Vibrio vulnificus group (twelve of seventeen) was
significantly higher than that in the Aeromonas group (p = 0.006).
Because of the high mortality rates associated with Vibrio
vulnificus and Aeromonas infections, early diagnosis and prompt
aggressive débridement are essential in order to save the patient's
life. In fact, the clinical symptoms and signs of necrotizing soft-tissue
infections and sepsis caused by these organisms are characteristically similar
and indistinguishable at the time of presentation. This study identified
differences between Vibrio vulnificus and Aeromonas infections.
First, the contact mechanisms for the two infections differ. Most patients who
had a Vibrio vulnificus infection lived on the seacoast and had a
history of contact with seawater through their occupation, which involved
catching and raising oysters, fish, or other seafood. Most patients with
Aeromonas infections were farmers and had a history of contact with soil,
wood, brackish water, or dirty ditches. Second, although the soft-tissue
infections in both groups had similar hemorrhagic bullae, subcutaneous
bleeding, purpura, necrosis, and gangrene, the Aeromonas infections had
markedly more myonecrosis and often had a distinctive foul odor following
fasciotomy. Finally, the overall clinical course of the Vibrio
vulnificus group was more fulminant than that of the Aeromonas group,
especially in patients with low systolic blood pressure and high band forms of
white blood cells. For both infections, necrotizing soft-tissue lesions in
patients with both hepatic dysfunction and diabetes mellitus were associated
with a higher mortality rate than were lesions in patients with hepatic
disease or diabetes mellitus alone. We also found that the patients who died
had significantly lower serum albumin levels at the time of presentation than
did the patients who survived (p = 0.018).
In conclusion, necrotizing soft-tissue infections and sepsis caused by
Vibrio vulnificus and Aeromonas species are surgical emergencies.
Early fasciotomy should be performed, and culture-directed antimicrobial
therapy should be given to patients with hypotensive shock, leukopenia, severe
hypoalbuminemia, and underlying chronic illness, particularly a combination of
hepatic dysfunction and diabetes mellitus. The contact history of patients
with the rapid onset of cellulitis can alert clinicians to an early
differential diagnosis of soft-tissue infection with Vibrio
vulnificus (contact with seawater or raw seafood) or Aeromonas species
(contact with fresh or brackish water, soil, or wood).
Tables showing the detailed clinical and laboratory findings for both
groups are available with the electronic versions of this article, on our web
site at
(go to the article citation and click on "Supplementary Material")
and on our quarterly CD-ROM (call our subscription department, at
781-449-9780, to order the CD-ROM). ?