Title

Author(s)

A retrospective review of necrotizing fasciitis in a regional

hospital in Hong Kong

Sinn, Ting-ting, Maria;

Citation

Issued Date

URL

Rights

2012

http://hdl.handle.net/10722/173742

Creative Commons: Attribution 3.0 Hong Kong License

A Retrospective Review of Necrotizing Fasciitis

in a regional Hospital in Hong Kong

By

Sinn Ting Ting , Maria

This work is submitted to

Faculty of Medicine of the University of Hong Kong
In partial fulfillment of the requirements for
The Postgraduate Diploma in Infectious Diseases, PDipID (HK)

Date: 27 June 2012

Supervisor: Professor Patrick CY Woo

Declaration

I, Sinn Ting Ting, Maria , declare that this dissertation represents my own work and
that it has not been submitted to this or other institution in application for a degree,
diploma or any other qualifications.
I, Sinn Ting Ting , Maria also declare that I have read and understand the guideline
on What is plagiarism? published by The University of Hong Kong (available at
http://www.hku.hk/plagiarism/) and that all parts of this work complies with the
guideline.

Candidate: Sinn Ting Ting, Maria

Signature:
27 June 2012
Date:

Table of Contents

Page

1. Abstract

2. Introduction

3. Materials and methods

4. Results

10

5. Discussion

21

6. Conclusion

31

7. Appendix

32

8. References

33

A retrospective review of necrotizing fasciitis in a regional

hospital in Hong Kong.

Abstract
Background
Necrotizing fasciitis(NF) is a severe form of soft tissue infection that primarily
involves the superficial fascia. The purpose of this study is, by reviewing all the NF
cases in our hospital, to see if any areas that can be done to optimize the outcome of
this group of patients.

Objective
To study the clinical features, risk factors, spectrum of organisms, treatment and
outcomes of necrotizing fasciitis cases which were admitted to Tseung Kwan O
Hospital.

Methodology
A retrospective study including 28 patients who were discharged with the diagnosis of
Necrotizing Fasciitis (NF) or Fourniers Gangrene (FG) in Tseung Kwan O
Hospital from June 2010 to May 2012 were recruited. Data regarding co-morbidities,
laboratory variables, micro-organisms and surgical treatment were collected. Fishers
exact test and Mann-Witney U test were utilized for comparing variables.

Results
A total of 27 patients but 28 episodes were included in this study. The mean age of
hospital survivors was 56.6 years(17.9 years), while for the non-survivors was 60.6
years(20.6 years). Diabetes mellitus (35.7%) and hypertension (46.4%) were the
most frequent co-mobidities. Most (16, 57.1%) of them were in stage 1 NF, five
(17.9%) in stage 2 and seven (25%) in stage 3. Less than half (39.3%) were febrile on
admission. Fifty percent had one lower limb involvement on presentation, 32.1% had
upper limb involvement and the rest (17.9%) were central NF, ie Fourniers gangrene
(FG), primarily involve the perineum on admission. Among the 23 NF cases, 39.1 %
grew vibrio vulnificus, 21.7% grew streptococcus pyogenes ( in which one of them
grew mixed streptococcus pyogenes and E.coli), 17.4% grew mixed flora. Among the
5 FG cases, all but one grew mixed flora. Of the 22 extremities NF cases who
underwent operation, 10(45.5%) had amputation done. Mean number of operation was
4.1( range 1-16). The mean length of hospital stay for survivors were significantly
longer than that of non-survivors (54.15 days [SD 49.66] vs 4.11 days[SD 4.11] ,
p <0.001). The overall hospital mortality was 32.1%. The presence of septic shock,
disseminated intravascular coagulation and acute kidney injury were significantly
associated with mortality.

Conclusion
Necrotizing fasciitis runs a rapid deteriorating course and is associated with high
morbidity and mortality. The success in management requires prompt diagnosis, early
and aggressive surgical debridement, as well as appropriate antibiotics.

A retrospective review of necrotizing fasciitis in a regional

hospital in Hong Kong

Background

Necrotizing fasciitis(NF) is a severe form of soft tissue infection that primarily

involves the superficial fascia. The incidence in adults is 0.4 cases per 100,000
population and in children, 0.08 cases per 100,000 population. In general, the
mortality is 25%, but when sepsis and renal failure set in, the mortality can go up to
70% (1).
NF places a great burden on the medical resources. In an Australian study, the mean
hospital length of stay for NF survivors was 36 days and the average ICU length of
stay was 11 days. The mean cost per patient was $64 517 (2).
The purpose of this study is, by reviewing all the NF cases in our hospital, to see if
any areas that can be done to optimize the outcome of this group of patients.

Objective:
To study the clinical features, risk factors, spectrum of organisms, treatment and
outcomes of necrotizing fasciitis cases which were admitted to Tseung Kwan O
Hospital.

Design:
This is a retrospective study.

Methods:
A computer-based search in the Computer Management System was utilized to
identify patients who were discharged with the diagnosis of Necrotizing Fasciitis
(NF) or Fourniers Gangrene (FG) in Tseung Kwan O Hospital from June 2010 to
May 2012.

Diagnosis was defined by either specific physical signs( for example, rapidly
progressive soft tissue inflammation with necrosis, bullae or gas formation in the deep
tissue) , or clinical suspicion( such as rapidly progressive tissue inflammation but
without necrosis, bullae or gas) further confirmed during operation or by biopsy
findings. Characteristic CT findings were accepted if operation was not done.

Demographic data collected were their sex, age, social habits (smoking ,drinking, and
intravenous drug abuse ) . Comorbidities in particular history of diabetes mellitus
hypertension and other cardiovascular diseases, liver and renal diseases, malignancies,
gout, as well as the use of steroids or immunosuppressants were recorded. Etiology,
site of infection on admission and the subsequent area involved were recorded. The
presentation on admission, including temperature (fever is defined by temperature
38.3 OC, hypothermia < 36 OC , normothermia is the temperature in between) ,
presence or absence of shock (systolic blood pressure < 90 mm Hg) , the presence of
pain, the condition of the lesions( presence of erythema, swelling, tenderness, warmth,
crepitus, blister/ bullae, haemorrhagic bullae, skin anesthesia, gangrenous changes,
ulcer or purulent/serous discharge ) as well as the stage of disease were recorded. The
definitions of hypotension, fever and hypothermia were classified according to the
2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference.

(3)Whereas, the stage of disease is defined according to the scheme adopted by Wong
and Wang (4): table 1

Table 1: Clinical stages of necrotizing fasciitis

Stage 1 (Early)
Tenderness (extending
beyond the apparent area of
skin involvement)
Erythema
Swelling
Warm skin

Stage 2 (Intermediate)
Blister or bullae (serous
fluid)
Skin fluctuance
Skin induration

Stage 3 (Late)
Hemorrhagic bullae
Skin anesthesia
Tissue crepitus
Skin necrosis with dusky
discoloration progressing
to frank gangrene

The time from onset of symptoms to admission was recorded. The time of operation
was defined by the duration between admission and the time of operation. The time of
diagnosis was defined as the duration between admission and the time when diagnosis
of NF was highly suspected, for example when the surgeon was consulted for
suspected NF, or the operation was arranged for NF. The initial admission diagnosis
was also recorded.
The month of admission and the initial specialty on admission were recorded.
Concerning the investigations, laboratory data like complete blood picture, renal and
liver function, clotting, C-reactive protein, glucose level were collected. Any presence
of gas in XR was recorded. The need of CT scanning to make the diagnosis or
delineate the extent of involvement was also recorded.
Concerning the treatment of NF, the type of empirical antibiotics used prior to the
diagnosis NF and the definitive antibiotics for NF were recorded. The number of
operations and any amputation done were recorded.
Microbiological cultures of tissue were obtained at the time of operation. The
microbiological and blood culture results were recorded.

Data of critical care support included time of ICU admission, length of ICU stay, the
need of inotropes, mechanical ventilation and dialysis were recorded.

Complication data included septic shock, disseminated intravascular coagulopathy

(DIC), acute myocardial infarction(AMI), acute kidney injury(AKI), compartment
syndrome, gastrointestinal bleeding(GIB), pneumonia and acute respiratory distress
syndrome(ARDS). The definitions of septic shock and DIC were classified according
to the 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions
Conference (3). Acute kidney injury was defined according to the RIFLE criteria
established by the Acute Dialysis Quality Initiative Group (5) .
Outcome data like hospital mortality, length of hospital stay and destination of
discharge were also recorded.

Statistical Analyses
Statistical analyses were performed using Statistical Package for the Social Sciences
software(SPSS), version 16.0. Continuous variables were expressed as mean with
standard deviation ( SD), and they were compared using the Mann-Witney U test.
Fishers exact test was utilized for comparing categorical variables. Tests were twotailed with a significance level of 0.05.

Results:

Demographics of the study population:

Actually, a total of 27 patients but 28 episodes were included in this study. As one of
these patients had experienced two separate episodes of necrotizing fasciitis (NF), it
would be described as two patients in the subsequent paragraphs to ease
communication. Of these, 23 episodes were diagnosed to have NF and the remaining
5 were fourniers gangrene(FG).
There were altogether 19 males (68%) and 9 females (32%) in this cohort. The mean
age of hospital survivors was 56.6 years(17.9 years), while for the non-survivors was
60.6 years(20.6 years). Table 1
Five (20.8%) of them were smokers and 4 (16.7%) of them were drinkers. None of
them were drug addicts.
Diabetes mellitus and hypertension were the most frequent co-mobidities in this
cohort. Ten patients got diabetes (35.7%) and 13 (46.4%) had hypertension. Seven
(25%) got liver diseases: 2 of them got alcoholic liver disease, one fatty liver, three
hepatitis B carrier while one hepatitis B -related liver cirrhosis. Three (10.7%) of them
had malignancies: two of them had active carcinoma of rectum and one of them had
history of papillary carcinoma of thyroid with thyroidectomy done. Two (7.1%) got
renal diseases: one of them with end- stage renal failure and was on long term dialysis,
while the other one had renal failure and renal transplant done and was therefore on
long term immunosuppressants. Only 3 patients (10.7%) in this cohort enjoyed good
past health. Table 2

Table 1: Ages

All
Patients
Parameter

AGE

28

Nonsurvivors
Mean(SD)
57.85(18.49)

Survivors

Mean(SD)

Mean(SD)

p Value

60.55(20.6)

19

56.57(17.86)

0.69

Table 2
No. of patients

Nonsurvival

N (%)

60.55(20.6)

0.69

Male

19

6(31.5)

>0.09

Female

3(33.3)

Yes

2(40)

No

13

1(7.6)

Yes

2(50)

No

15

3(20)

Yes

10

4(40)

No

18

5(27.7)

Yes

3(42.8)

No

20

6(30)

Yes

0(0)

No

26

9(34.6)

Yes

13

5(38.4)

No

15

4(26.6)

Yes

1(33.3)

No

25

8(32)

Yes

0(0)

No

27

9(33.3)

Yes

0(0)

No

27

9(33.3)

Yes

0(0)

No

26

9(34.6)

Yes

14

3(21.4)

No

14

6(42.8)

Age
Sex
Smoker
Drinker
DM
Liver diseases
Renal diseases
HT
Malignancies
Gout
Use of steroid
Immunosuppressants
Predisposing
wound/injury

p Value

0.172
0.272
0.677
0.653
>0.09
0.689
>0.09
>0.09
>0.09
>0.09

0.42

Initial clinical parameters, laboratory data and imaging

On admission, less than half got fever (11, 39.3%), 12 (42.9%) of them were
normothermic and 5 (17.9%) even hypothermic. All but one (96.4%) complained of
pain because the latter was already confused with hypotension on presentation.

Most (16, 57.1%) of them were in stage 1 NF, five (17.9%) in stage 2 and seven(25%)
in stage 3. The most consistent physical finding was swelling (25, 92.6%, n=27).
Erythema was present in 20 patients( 87.0%, n= 23). Blisters/ bullae were uncommon
(6 patients, 21.4%), so as gangrenous changes (6 patients, 21.4%), tissue crepitus(1
patient, 3.6%) and haemorrhagic bullae formation(3 patients, 10.7%).
Hypotension was present in 7 (25%) patients upon admission, but 9 more patients
(total 16, 57.1%) developed shock during the subsequent hospital course. Table 3

Table 3: Initial physical findings

No. of patients

Percentage %

Erythema (n=23)

20

87

Swelling (n=27)

26

96.2

Ulcer (n=28)

21.4

p/S discharge (n=28)

10

35.7

Tenderness (n=21)

21

100

Warmth (n=12)

58.3

Crepitus (n=28)

14.2

blisters/bullae (n=28)

21.4

hemorrhagic bullae (n=28)

14.2

Anesthesia (n=28)

3.6

gangrenous changes (n=28)

17.8

stage of disease: 1

16

57.1

17.9

25

Temp : Hypothermia

17.9

Normothermia

12

42.9

Hyperthermia
Hypotension on admission
(n=28)

11

39.2

25.0

p/s discharge : purulent /serous discharge; n might not equal to 28 because the
signs/symptoms were not documented in case notes.

The initial diagnoses were mostly cellulitis(11 patients, 39.3% , n= 28).Table 4 The
diagnosis of NF was already suspected on admission in 4 patients (17.4%, n= 23),
whereas that of fourniers gangrene in 2 (40%, n=5). The other common diagnosis
was abscess (4 patients, 14.3%). One patient had recurrent carcinoma(CA) of rectum
and presented with buttock pain. The admission diagnosis was bone pain secondary to
the carcinoma. It was only when the patient developed fever and shock, the lower
limb already progressed to stage 3 NF with haemorrhagic bullae, crepitus, gangrenous
change on the 4th day of admission, a CT was done and the diagnosis of NF was
confirmed.
Out of the 23 NF cases, 14 (60.9%) were admitted to orthopaedics, 7 (30.4%)to
medical, 1 (4.3%)to surgical and 1(4.3%) to paediatrics. All of the 5 FG cases were
admitted to surgical ward. Or put it in another way, out of the 7 stage 3 NF, 6 were
admitted to the orthopaedic ward, only 1 was admitted to the medical ward. Of the 4
stage 2 NF cases, all were admitted to the orthopaedic ward.

Table 4 Initial diagnoses on admission

Stage of disease
Initial diagnosis
1
Ulcer
Cellulites
Abscess
NF
FG
DVT
Bone pain
2
Cellulites
Abscess
Burn
3
Pemphigus/pemphigoid
NF
cellulitis

n
2
7
2
1
2
2
1
2
2
1
1
3
2

White blood cell count was normal in 8 (28.6%) cases and low in 1 (3.6%) case, while
the rest showed raised count. Table 5

Table 5 : Laboratory parameters on admission

All

Non-Survival

Survival

Mean(SD)

Mean(SD)

Mean(SD)

p-value

WBC (cells/mm )

28

15.18(7.96)

11.45(6.48)

19

16.94(8.13)

0.09

Hb (dL)

28

12.13(2.97)

12.62(2.26)

19

11.91(3.29)

0.68

28 203.17(111.98)

178.55(140.98)

19

214.84(97.61)

0.24

CRP (mg/L)

106.51(89.99)

101.93(97.69)

0.62

Cr (umol/L)

28 189.25(223.44)

177.88(88.76)

19

194.63(267.01)

0.23

Na (mmol/L)

28

134.21(4.96)

133(3.9)

19

134.78(5.4)

0.39

Albumin (g/dL)

27

33.85(9.07)

30.62(7.32)

19

35.21(9.56)

0.28

Plt (10 /L)

Table 6: Clinical parameters

All

Non-Survival

Survival

Mean(SD)

Mean(SD)

Mean(SD)

p-value

Onset of Symptoms
to admission (day)

28

3.53(5.03)

3.25(4.43)

19

3.66(5.4)

0.74

Hrs to OT from
admission(hr)

27

27.11(46.55)

16.93(10.12)

19

31.39(55)

0.30

Hrs to ICU (hr)

15

53.03(158.3)

16.56(10.58)

94.71(233.54)

0.16

Hrs to Diagnosis
of NF (hr)

27

67.44(135.57)

19.06(23.03)

19

87.81(157.68)

0.54

Length of ICU stay

(day)

28

5.43(10.8)

3.02(4.72)

19

6.57(12.68)

0.22

Length of hospital
stay(day)

28

38.07(47.09)

4.11(4.7)

19

54.15(49.66)

<0.001

X-ray findings were helpful only in one case (3.6%) by showing subcutaneous gas
formation. In fact, tissue crepitation can be elicited clinically in that case. CT scan
imaging was done in 8 patients (28.6%) to make the diagnosis or to delineate the
extent of involvement.

Anatomical site of infection

Most (14, 50%) of them had one lower limb involvement on presentation, of which
one of them had already spread to involve the groin and abdomen on admission. Nine
(32.1%) of them had upper limb involvement, of which 8 of them were unilateral. The
rest (5, 17.9%) were central NF, primarily involve the perineum on admission. Table
7

Microbiological findings
Blood culture was done in 24 cases and of which, only six (25%) had positive growth.
In contrast, tissue cultures had a much higher yield. All 26 cases sent had positive
growth. Among the 23 NF cases, 9 grew vibrio vulnificus(39.1%), 5(21.7%) grew
streptococcus pyogenes ( in which one of them grew mixed streptococcus pyogenes
and E.coli), 4(17.4%) grew mixed flora, and one (4.3%) grew photobacterium
damsela. Among the 5 FG cases, all but one grew mixed flora, the remaining one
grew E.coli. Table 7
Among the 9 vibrio cases, one occurred in July and August respectively, three in
September, two in October and November respectively. Five (55.6%) of them
involved the upper limb and the remaining the lower limb. Only five (55.6%) of them
recalled history of injury: 3 were injured by fish, 1 by crab, one had lower limb injury
after a fall from stairs.

Table 7 Co-mobidities, site of infection, microbiology, use of antibiotics in relation to

mortality
Patient Sex/
no.
Age

Comorbidities

M/71 DM, IHD

Initial
site
Injury/
Extent
involve
wound
d
L arm,
chest ,
L hand
lower
/
jaw,RU
L

Organisms

photobacterium
damsela

Initial antibiotics

flagyl, ampicillin ,
cloxacillin

Definitive
antibiotics

Death

clindamycin,g
entamicin,cirp
ofloxacin,
vancomycin

Yes

L thigh food ulcer

E.coli, Klebsiella,
enterococcus,
bacteriodes fragilus,
corynebacterium

L hand

forearm crab

vibrio vulnificus

L ankle

L leg

vibrio vulnificus

L calf

vibrio vulnificus

L thigh
and
/
groin,
abdomen

GAS

zinacef, flagyl

pen G and
clindamycin

Yes

augmentin,
flagyl

Yes

rocephin,
ciprofloxacin,
minocycline

augmentin

ciprofloxacin,
cloxacillin

DM, anaemia of
L foot
chronic disease

M/47

DM, faty liver,

parosysmal
M/51 nocturnal
haematuria,
psoriasis

F/88 DM

M/73

DM, HT, old

CVA

flagyl,
rocephin, ampicillin , timentin,
cloxacillin, flagyl
ciprofloxacin,
clindamycin
ampicillin, cloxacillin,
flagyl, clindamycin, rocephin,
rocephin,
ciprofloxacin
ciprofloxacin,
and doxycline
doxycycline
rocephin,
ampicllin,
ciprofloxacin
cloxacillin,flagyl,
and
levofloxacin
minoxycline
rocephin,
ampicllin, cloxacillin,
levofloxacin
pen G
and doxycline

F/29 /

M/39

recurrent CA
rectum for
conservative
management

R calf
R buttock and
thigh

F/42

hepatitis B
carrier

L hand

fish fin

vibrio vulnificus

M/84 HT

L leg

L foot

contusion

GAS and E.coli

10

M/58 HT

L foot
and leg

pseudomonas
aeruginosa and
serratia species

11

F/66 anaemia

L hand

L
fish
forearm

vibrio vulnificus

L
fish bone
forearm

vibrio vulnificus

GAS

ampicillin, cloxacillin

ampicillin, cloxacillin ertapenem

12

13

CHF,AF,post
F/84 RAI
L hand
hypothyroidism
ESRF with renal
M/44 transplant done, R leg
HT, gout

rocephin,
ciprofloxacin,
minocycline, flagyl
ampicillin, cloxacillin,
flagyl
zinacef,cloxacillin

rocephin,
ampicillin, cloxacillin,
ciprofloxacin,
flagyl
minocycline
rocephin,
ampicillin, cloxacillin ciprofloxacin,
minocycline

14

M/59

HT, hepatitis B
L thigh
carrier

L
/
buttock

streptococcus
pneumoniae, ESBL
E.coli

15

M/57

HT, alcoholic
liver disease

L leg

contusion

vibrio vulnificus

16

M/36 /

R hand

abrasion

erysipelothrix
rhusiopathiae

17

F/52 HT

bilateral
feet

scald

GAS

18

M/49

L calf

L thigh /

vibrio vulnificus

augmentin,
klebsiella pneumoniae clindamycin,
ciprofloxacin

alcoholic liver
disease

19

M/75 DM

L thigh

L
buttock,
/
liver
abscess

20

HT,
F/68 hyperlipidaemia, L hand
obesiy

L
/
forearm

vibrio vulnificus

20

F/8

GAS

R thigh

insect bite

pen G and
clindamycin

claforan,
ampicillin, cloxacillin,
ciprofloxacin,
gentamicin, flagyl
minocycline
augmentin ,
zinacef, flagyl,
flagyl,
gentamicin
gentamicin
pen G,
augmentin,
pipercillin,
clindamycin,
amikan,
cloxacillin
vancomycin
cloxacillin

Yes

Yes

Yes

Yes

cloxacillin

Yes

rocephin

rocephin, clinamycin, rocephin,

minocycline,
ciprofloxacin,
ciprofloxacin
minocycline
pen G,
ampicillin, cloxacillin clindamycin,
flagyl

R hand
HT, hepatitis B
and
carrier
forearm

20

M/59

20

HT,
F/73 hyperlipidaemia, R foot
pseudogout

20

20

20

20

20

M/47 DM

R
perianal

DM,HT, IHD,
ESRF on HD,
R
M/56
CA thyroid with scrotum
OT done, gout
R groin,
M/56 DM
L chest
wall
perianal
CA rectum, post
M/62
and
chemotherapy
scrotum
DM,
perianal
HT,hepatitis B
M/87
and
liver cirrhosis,
scrotum
beta-thal trait

R leg

abrasion

bilateral
posterior
/
thigh,
back
perineu
/
m

R thigh /
upper
thigh

cloxacillin,
clindamycin

rocephin,
flagyl ,
levofloxacin

tienam

strep.anginosus/milleri
, bacteroides fragilis, meropenem
E.coli

meropenem

strep.anginosus/milleri
, bacteroides fragilis, augmentin
klebsiella
strep.anginosus/milleri
, bacteroides fragilis, augmentin
E.coli

augmentin,
clindamycin,
amikan
augmentin,
cloxacillin ,
flagyl

E.coli

augmentin,
flagyl,
levofloxacin

stap. Aureus

ampicillin, cloxacillin

proteus,
strep.anginosus/milleri rocephin, clinamycin,
, bacteroides fragilis, levofloxacin
enterococcus
streptococcus
anginosus, ESBL
zinacef, flagyl
E.coli,
peptostreptococcus

augmentin, flagyl

Surgical treatment
Apart from the afore-mentioned case of recurrent CA rectum, all patients (96.4%)
underwent operation. None of the FG or central NF cases received amputation. Of the
22 NF cases who underwent operation, 10(45.5%)had amputation done. Mean number
of operation was 4.1( range 1-16).
Critical care support and complications
ICU admission was necessary in 15 (53.6%) patients. Inotropes were required in 18
(64.3%) patients. Fifteen(53.6%) patients required mechanical ventilation. Thirteen
(46.4%) of them had DIC and 14 (50%) had acute kidney injury. Eight (28.6%) of
them undergone dialysis. The presence of septic shock, DIC and AKI were
significantly associated with mortality. Table 8

Table 8: Complications

Septic shock
DIC
AKI
Compartment syndrome

No. of patients
n
16
13
14
1

Nonsurvival
n (%)
9(56.2)
9(69.2)
9(64.2)
1(100)

p Value
0.002
<0.01
0.001
0.321

Yes

GIB
pneumonia
ARDS

4
2
2

1(25)
0(0)
2(100)

>0.09
>0.09
0.087

Outcome
The overall hospital mortality was 32.1%( n=9). Among the 23 NF cases, hospital
mortality was 34.8% (n=8) . Among the remaining 5 FG cases, hospital mortality was
20%(n= 1). Among the 19 survivors, 4 were transferred to other hospitals ( 3 to
rehabilitation hospitals, 1 to renal unit of the hospital patient used to attend), the
remaining were discharged home. Six of them were discharged with limb loss.

Discussion
Necrotizing fasciitis is a surgical emergency. Even for virulent organism as vibrio
vulvificus, mortality rate decreases from 23.0 % to 4.9% if surgical debridement and
fasciotomy are done within 24 hours of onset of symptoms (6). Therefore, early
diagnosis, early and aggressive debridement or amputation, coupled with appropriate
antibiotics is essential for survival. However, the diagnosis of NF is notoriously
difficult to make. The main differential is cellulitis of which the infection begins at the
junction between the dermis and superficial fascia. Whereas the primary pathology of
NF is at the superficial fascia. Proliferation of bacteria results in angio-thrombotic
microbial invasion and liquefactive necrosis of the superficial fascia. Later, occlusion
of the perforating vessels to skin caused skin ischemia and subsequent necrosis of
subcutaneous fat, dermis and epidermis, resulting in bullae formation, ulceration and
gangrenous changes. Clinically the skin changes can be categorized into stages as
proposed by Wong and Wang(see Table 1 )(4). It is hard to differentiate stage 1 NF
with cellulitis when there is only erythema, swelling and tenderness. However, in NF,
the margins of tissue involvement are often poorly defined and tenderness often
extend beyond the apparent area of involvement. In other words, pain is often out of

proportion to the clinical appearance. Also, lymphangitis is rarely seen in NF. In stage
2, blister or bulla formation already signifies the onset of critical skin ischemia. It is
rarely seen in cellulitis and its presence should ring the bell for the diagnosis of NF. In
stage 3, the presence of tissue necrosis is manifested by the appearance of
hemorrhagic bullae, skin anesthesia and gangrene. In our cohort, 3 and 2 of the
patients with stage 3 and stage 2 diseases respectively were diagnosed to have
cellulitis on admission. The use of this clinical staging can heighten our alertness
towards the diagnoses of more serious soft tissue infection rather than just cellulitis,
and thereby arrange surgical debridement earlier. For those with stage 1 disease, if
serial clinical monitoring reveals progression towards higher stage despite the use of
antibiotics, early surgical exploration is warranted. Luckily in our cohort , all but one
of the stage 2 and 3 NF cases were triage under the specialty of orthopaedic, thereby
preventing further delay in surgical treatment.
Besides clinical appearance, a bedside procedure finger test can be performed that
aids diagnosis. A 2-cm incision down to the deep fascia is made under local
anaesthesia. Then the level of superficial fascia is probed with a gloved finger. Lack
of bleeding, foul-smelling dishwater pus and minimal tissue resistance to finger
dissection represent a positive finger test and are diagnostic of NF (7). However, this
procedure is seldom performed in our hospital.
Most of the patients with NF had some chronic illnesses such as diabetes mellitus,
alcohol abuse, or renal impairment. Among these, the presence of diabetes and
immunocompromised state were associated with mortality (8,9). Diabetes was present
in 35.7 % in our cohort and only 10 % enjoyed good past health. However, our study
was underpowered to detect any association between co-morbidities and death.

Fever was present in only 39.3 % of this cohort, therefore it per sc is not a sensitive
marker for NF. Hypotension on admission was present in 25 % of them. The result
was consistent with the review by Wong et al of 89 consecutive patients, with fever
only present in 53 % and hypotension in 18 % at presentation, especially in
immunocompromised patients such as those diabetics (10). Therefore these patients
might appear systemically quite well at least on presentation.
Concerning the laboratory data, raised white cell count (raised in 67.9% of patients)
was not a sensitive marker for NF.
Though a low admission serum sodium level( < 135 mEq/L) was not associated with
hospital mortality in this study, it was not so in studies like that of Arezou et al (11).
There are some possible mechanisms. Firstly, sepsis leads to increase muscle glucose
uptake, increase in ratio of muscle membrane permeabilities to Na+ and K+ and
increase intracellular Na+ concentration, mediated by complement activation.
Secondly, sepsis is associated with an increase in antidiuretic hormone and with
adrenal insufficiency. Thirdly, severe sepsis can induce marked third spacing of fluids,
which may be replaced by free water. All these can give rise to hyponatremia. In fact,
hyponatremia was one of variables in the LRINEC( Laboratory Risk Indicator for
Necrotizing fasciitis) score developed by Wong et al to discriminate between
necrotizing soft tissue infection from its non-necrotizing counterpart (12) [Appendix
1] . A score of 6 has a positive predictive value of 92.0% and negative predictive
value of 96.0% for the diagnosis of NF. However, the turnaround time of C-reactive
protein (CRP) was too long in our hospital to render it useful in making the diagnosis.
In fact, only 7 of our patients had their CRP checked on admission. The LRINEC
score can only be calculated in 5 of them because of missing data( no admission

glucose) and the scores are 0,0, 3,6 and 8. Therefore, the sensitivity for the diagnosis
of NF was only 33.3%.

In this cohort, Vibrio vulnificus was the most common culprit (32.1%). Vibrio species
are natural inhabitants of brackish water and salt water worldwhile. For vibrio
vulnificus, a water salinity of 0.7% to 1.6% and warm temperatures(>20 OC) facilitate
its growth (13). As these organisms are ubiquitous in the coastal waters at the
temperate zones, they tend to cause illness in the warmer months of the year when
their concentrations become high enough. Since the mean sea surface temperature is
26 OC during the summer months in Hong Kong, the disease should be more prevalent
in summer (14). The bacterium is frequently found in oysters, crustaceans and
shellfish. Up to 50% of oysters and 11 % of crabs were cultured positive for vibrio
vulnificus during summer months (15) . Human infection can be acquired through
contamination of wound by these marine organisms or through consumption of
contaminated raw or undercooked seafood. In our cohort, patients were infected
between July to November, in fact most of them occurred between September to
November which was not quite summer already. This might reflect global
rewarming resulting in lengthening of the summer months. Four out of 5 of the upper
extremities NF cases had contact history of crab/ fish, whereas one of the 4 lower
extremities NF cases had history of seafood contact.
Most patients with vibrio vulnificus infections are immunocompromised and they
mostly suffer from chronic liver disease, diabetes, adrenal insufficiency, malignancies,
haemochromatosis, thalassaemia ,chronic renal insufficiency or alcoholism (14). In
our cohort, 3 out of the 9 patients got diabetes, one got alcoholic liver disease and one
was a hepatitis B carrier. As v. vulnificus is endemic in this locality, wearing globes is

advisable when handling seafood and especially for those immunocompromised

patients, seafood should be thoroughly cooked before consumption.
Mortality for these 9 vibrio cases were high(4 patients, 44.4%) . The reported
mortality rate varied from 0 % to 17 % in most series (6,16,17,18).

There is one case of NF caused by Photobacterium damsela(Vibrio damsela) . In fact

this organism, together with other vibrio species like v. vulnificus and v.
parahaemolyticus, are notable for causing hyperacute NF, which run an extremely
fulminant course with extensive undermining of surrounding tissue, severe
septicaemia and multiple organ failure within 24 hours of the inciting event. Mortality
reaches 100 % unless diagnoses and definitive surgical treatment are offered early
(19). In our patient, he presented with left hand pain and discoloration of left arm. No
predisposing wound or injury was noted. On examination, there was already stage 3
NF and above elbow amputation was done about 15 hours after first onset of pain.
Despite these, the necrosis spread to involve the chest wall, the left neck and lower
jaw, the right upper limb a few hours after operation. He finally sucummbed 29 hours
after the onset of pain.

In this cohort, the second most prevalent organism was streptococcus pyogenes. Four
patients were lower limb NF and the remaining one involved the hand. Three( 60%)
had history of injury and the mortality was 40%. In the report by Brown et al, almost
40 % of those with invasive group A streptococcal (GAS)infection had no
predisposing illnesses or risk factors and in up to 45 % of cases there is no direct
injury (20). The most prevalent types of GAS in Hong Kong were M1(15%) and
M12(21%) (21). They were usually found in skin and throat isolates and commonly

associated with invasive disease (64 % of cases). The virulence of M1 type may be
related to its ability to enhance adhesion of streptococci to tissues and thus preventing
phagocytosis by neutrophils. Moreover, patients with invasive GAS disease had lower
level of antibodies against M-protein and superantigens than those with noninvasive
disease, implying poor humoral immunity against GAS virulence factors (22). The
mortality of GAS induced NF was around 20% (23).

All but one of the patients underwent operation and 19 (70.4%) were done within 24
hours after admission. In the study by Wong et al, a delay in surgery of greater than
24 hours was associated with an increase risk of death (relative risk = 9.4, p<0.05)
(10). In fact, multiple studies have shown the single most common factor associated
with increased mortality was delay to operative debridement (24,25,26,27). Other
parameters that have been associated with increase mortality include age > 50 years,
extent of infection, lactic acidosis, degree of organ dysfunction at admission,
hypotension, immune compromise, and a white cell count > 30,000/mm3
(11,24,25,26,27,28). In this study, the presence of septic shock, AKI and DIC were
significantly associated with mortality. However, the mean time to operation was
paradoxically longer in those survivors (31.39 hr vs 16.93 hrs in non-survivors),
though the difference was not statistically significant. The reason was that some
patients with less virulent organisms had a much longer time to operation but better
survival.

Concerning the antibiotics therapy, it is best to start with a combination of broadspectrum antibiotics in those with necrotizing soft-tissue infections. It is refined later
based on culture results and clinical response. According to the IMPACT guideline

(29), combination of iv penicillin and iv clindamycin is recommended for those with

GAS infection. Clindamycin has been found to have unique property of suppressing
toxin production by staphalococcus aureus, hemolytic streptococcus and clostridia and
so should be included when these organisms are present or suspected (30).
Clindamycin can also facilitate phagocytosis of GAS by inhibiting M protein
synthesis. It has been shown that using cell wall-inhibiting agent alone was associated
with a 68% failure rate, and addition of clindamycin had a more favourable
outcome(83% vs 14%, p=0.006) in these deep infections (31) . While for those with
vibrio vulnificus, combination of iv fluoroquinolones and iv amoxicillin-clavulanate
is recommended. For those polymicrobial type I NF, which is most often caused by
enterobacteriaceae, streptococci and anaerobes, as in our patients, a combination of iv
fluroquinolones and iv amoxicillin-clavulanate or imipenem/meropenem is
recommended (29). In this cohort, the initial choices of antibiotics were often
ampicillin and cloxacillin which were suboptimal in such severe soft -tissue infection.
If the patient has a known injury caused by seafood and presented with severe soft
tissue infection, it is wise to treat as NF with a combination of fluoroquinolone and
amoxicillin-clavulanate especially in our hospital where the prevalence of v.vulnificus
is so high.

The usefulness of hyperbaric oxygen (HBO) therapy has been conflicting (32). None
of our patients has been sent to the Recompression Treatment Centre on Stonecutters
Island, where the location rendered it too risky to send our most haemodynamically ill
patients for this therapy.

In our cohort, 53.6% of the patients required ICU care. The rate was much lower than
that from another local study which was 93% (7). However, the amputation rate was
similar, ours was 45.5% and theirs was 46%.
It has been found that an average of 3 debridements, spaced 12 to 36 hours apart, is
needed to control gross infection (10,25,33). In this study, the mean number of
operation was 4.1 ( range 1-16).

The mortality of necrotizing soft tissue infection was reported to be 33 % to 40% in

the past. A review of over 3000 patients has shown that mortality has dropped from
23.5 % between 1980 and 2008, to less than 22 % since 1999 (34). The recent
National Surgical Quality Improvement Program reported a mortality of only 12%
(35). From the statistics of NF cases reported to the Centre for Health Protection in
Hong Kong, four out of 30 patients succumbed between 2005 and July 2008 (7). Our
overall hospital mortality was 32.1%. There are several areas that can be done to
improve the survival. Firstly, only half (15 patients, 53.6%) of the cases were
presented 24 hours after the onset of symptoms. Public awareness of this dreadful
disease should be heightened. Secondly, early aggressive surgical debridement for
those presented clinically with stage 2 and 3 necrotizing soft tissue infection. For
those indeterminate stage 1 diseases, close monitoring to look for clinical deterioation
and proceed to surgical debridement should clinical suspicion of NF arise. In doubtful
cases, a bedside finger test can be performed to aid diagnosis. Lastly, the spectrum
of empirical antibiotics can be broadened accordingly especially when an
immunocompromised patient with typical injury or post surgery presents with severe
soft-tissue infection.

Conclusion

Necrotizing fasciitis runs a rapid deteriorating course and is associated with high
morbidity and mortality. The success in management requires prompt diagnosis, early
and aggressive surgical debridement, as well as appropriate antibiotics. Preventive
measures include use of gloves in handling seafood especially in
immunocompromised patients. The public awareness of this condition should be
heightened and seeking medical advice early can certainly improve the outcome.

Appendix 1 : Laboratory Risk Indicator for Necrotizing fasciitis Score (LRINEC)

Variable, Units
C-reactive protein, mg/L
<150
150
Total white cell count, per mm3
<15
15-25
>25
Hemoglobin, g/dL
>13.5
11-13.5
<11
Sodium, mmol/L
135
<135
Creatinine, umol/L
141
>141
Glucose,mmol/L
10
>10

Score
0
4
0
1
2
0
1
2
0
2
0
2
0
1

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