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Patients with necrotizing fasciitis of extremities in ICU

Hong, Kam-fai;

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2011

http://hdl.handle.net/10722/173741

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PatientswithNecrotizingFasciitisofExtremitiesinICU

By

Dr.HongKamFai,Jeffrey

Thisworkissubmittedto
FacultyofMedicineofTheUniversityofHongKong
Inpartialfulfillmentoftherequirementsfor
ThePostgraduateDiplomainInfectiousDiseases,PDipID(HK)

Date:25/2/2011

Supervisor:ProfessorPatrickWoo
Declaration

I,HongKamFai,Jeffreydeclarethatthisdissertationrepresentsmyownworkandthatithas
notbeensubmittedtothisorotherinstitutioninapplicationforadegree,diplomaoranyother
qualifications.

I, Hong Kam Fai, Jeffrey 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:

HongKamFai,Jeffrey

Signature:

Date:

ACKNOWLEDGEMENT

I wish to express my sincere gratitude to Dr. Lai KY, COS, Department of Intensive Care,
Queen Elizabeth Hospital for providing me an opportunity to do my project on Patients with
Necrotizing Fasciitis of Extremities in ICU. I sincerely thank to my project guide Professor
Patrick Woo, Department of Microbiology, University of Hong Kong for guidance and
encouragement in carrying out this project work. I also wish to express my gratitude to Miss
Katherine Chan, Statistic Officer, Queen Elizabeth Hosptial, who rendered her help in statistical
analysis during the period of my project work.

Abstract
Title: Patients with Necrotizing Fasciitis of Extremities in ICU

Study objective:
To evaluate the relationship between the adequacies of effective empirical antimicrobial
therapy for severe necrotizing fasciitis involve extremities and clinical outcome among
patients required ICU admission.

Design: Retrospective Study

Setting: A medical and surgical ICU (18beds) from a government tertiary referral
hospital

Results:
Between 1 Jan 2006 to 31 December 2010, 32 patients were admitted consecutively to
intensive care unit and diagnosed suffering from necrotizing fasciitis of their
extremities. . The mean age was 63 + 11.96 year old. Most patients had documented
preexisting medical conditions(75%); the most common was diabetes mellitus in 12
patients (37.5%). 26 patients (81.25%) admitted to our unit for post operative care, while
the rest were admitted for treatment of acute organs failure. A single causative organism
was identified in 27 patients (84.4%). The most common organisms isolated were
Streptococcus Pyogenes, Vibrio Vulnificus and Aeromonas species. 75% of patients

suffered from Vibrio species and 50% of Aeromonas species associated necrotizing
fasciitis had contact history with contaminated seawater/fresh water. Ten patients
(31.25%) patients in this study received ineffective empirical antimicrobial therapy. The
prolong duration between admissions to administration of effective antibiotic (hrs)
associated with amputation of their extremities (15.79 + 17.30 hrs verses 4.93 +/-11.99
hrs; with P value = 0.005). Patients received amputation also had significantly lower
hemoglobin level (9.03 gm/dl +1.72 versus 10.46gm/dl +1.77; P value = 0.036) and
received less operations (2.0 +1.03 verses 3.25 +1.95; P value =0.026). ICU mortality
was 37.5%. ICU nonsurvivors had statistically lower hemoglobin level, received less
operation, and had higher APACHE II scores. The crude mortality rate was 43.75%. Pre
existing diabetes mellitus, acute renal failure that required renal replacement therapy,
high APACHE II scores were factors associated with increase in hospital mortality.

Conclusion:
Prompt diagnosis and early administration of effective antibiotic, reduced morbidity.
Base on the bacteriologic findings, early use of board spectrum empirical antibiotics to
cover Streptococcus, Enterobacteriaceae; Vibrio and Aeromonas species in patients with
history of seafood and fresh/seawater contacted is recommended.

Patients with Necrotizing Fasciitis of Extremities in ICU

Introduction
Necrotizing fasciitis was once thought to be the disease of the old day and associated with high
mortality and morbidity. It was first described by Hippocrates in Fifth century BC (1). However
despite vast amount of public interest and advance in medical care, we were still seeing a
significant numbers of cases in the world. The incidence of necrotizing fasciitis was 0.04/1000
person-years in the United States (4).
This group of patients consumed large amount of health resources and yet the mortality and
morbidity remain high. The mean hospital length of stay was 36 days and the mean cost of
treating a patient with necrotizing fasciitis was $64517 in Australia (8). In another study from
Taiwan, the average hospital length of stay for patients suffered from necrotizing fasciitis were
28 days (6). The overall mortality of necrotizing fasciitis was reported to be 15% to 35% (5, 6,
7). The crude death rate due to fasciitis increased from 0.1 in 2001 to 0.4 in 2006 in Hong Kong
(3). Clinical diagnosis of necrotizing fasciitis is often difficult and easily missed (2, 9). High
clinical suspicious and close observation of these groups of patients may facilitate early clinical
diagnosis. Diagnosis is often made clinically, and confirmed at the operation theater with
demonstration of foul smelling dishwater pus and lack of resistance of superficial fascia to
blunt dissection (9).
Multiple risk factors liked diabetic mellitus; chronic steroid treatment, intravenous addict and
liver cirrhosis, renal failure, myelodysplastic syndrome, malignancy, congestive heart disease
and chronic pulmonary disease had been identified as risk factor for necrotizing fasciitis (2, 6, 20,
12, 23, 24). As suggested by previous journals, early detection of the disease with aggressive
debridement will significantly reduce the mortality and morbidity (10,11 )

Recent studies suggested that early administration of appropriate antimicrobial therapy was
paramount in the treatment of septicemia and improved hospital mortality (14, 15, 16). In this
retrospective study, I postulate that early effective empirical antibiotic treatment will result in
significant lower morbidity and mortality in patient with severe necrotizing fasciitis that required
intensive care management.

Setting:
Retrospective study conducted in a tertiary government referral hospital with 1800 beds and 18
ICU beds. From 1 Jan 2006 to 31 December 2010; all patients admitted consecutively to
intensive care unit and diagnosed suffering from necrotizing fasciitis of their extremities were
included. Our ICU is a close unit model, with 24 hour ICU Specialists on site provide patient
assessment and management. Orthopedic team provides daily assessment and urgent assessment
on consultation basis. In our ICU unit, we use strict glucose control protocol to control glucose
level in septic patients. We also give physiological dose of steroid in septic shock patients

Method
Hospital records, microbiology results and drug administration charts were reviewed. Variables
that were examined in the study included age, gender, history of recent injury and laboratory
findings on ICU admission were collected. A total of ten kinds of comorbidity were recorded,
including diabetes mellitus, liver cirrhosis, congestive heart failure, gout, renal insufficiency,
peripheral vascular disease, chronic pulmonary disease, myelodysplastic syndrome, peripheral
vascular disease, and chronic steroid therapy. The time from onset of pain to hospital admission,
the time from admission to first operation, the number of operations undergone, limb amputation,
the ICU length of stay, the duration of hospitalization, and the mortality rate were also studied.
Histopathology examinations of surgical specimens obtained from first surgical debridement
were used to confirm the diagnosis in each case.
I defined empirical antibiotic treatment as effective if the infecting microorganism was
subsequently found to be susceptible in vitro to the antimicrobial administered. The drug
administration charts of all patients were reviewed and the time from admission to effective
antibiotic therapy administration was analyzed. After adequate fluid resuscitation, inotropic
agents were used to maintain a mean arterial blood pressure > 65mmHg. ICU data included the
used of inotropic agents, dialysis support for renal failure, and number of patients received
mechanical ventilator care > 96 hours were also analyzed. APACHE II point score was
calculated from 12 routinely from physiological measurements during the first 24 hours after
ICU admission.
Statistical analyses were performed using SPSS 15.0 (Statistical Package for the Social
Sciences). Continuous values are expressed as mean + standard deviation (SD) and were
compared using the Mann-Whitney test. Categorical values were compared using the Chi-square
test. A p value of <0.05 was considered significant.

ResultTotal of 32 patients suffered from necrotizing fasciitis involved their distal extremities
were admitted to our unit during study period. The mean age was 63 + 11.96 year old. There
were 22 men and 10 women. Most patients had documented comorbidity (75%); the most
common was diabetes mellitus in 12 patients (37.5%). 26 patients (81.25%) admitted to our unit
for post operative care, while the rest were admitted for treatment of acute organs failure
(Table1).

Microorganism
A single causative organism was identified in 27 patients (84.4%). Among these patients, gram
positive bacteria were isolated in 11 patients (34.4%), and gram negative bacteria in 16 patients
(50%). Polymicrobial was identified in 2 patients (Table 3). No causative organism was
indentified in three patients (Table 2). The most common organisms isolated were Streptococcus
Pyogenes (4 cases), Vibrio Vulnificus (4 cases) and Aeromonas species (4 cases). Three out of
the four patients suffered from necrotizing fasciitis due to Vibrio Vulnificus had history of
contact with raw seafood or injury at the wet market. Three out of the four patients (75%) with
necrotizing fasciitis caused by Aeromonas species had history of injury and two of them also had
contact history with contaminated water.

Three of the four patients with Aeromonas died in intensive care and the fourth died at general
ward after intensive care discharge. All four patients had one or multiple pre existing medical
conditions. Their mean age was 63. Three patients suffered from both diabetes mellitus and
among those two also suffered from cirrhosis. Three patients had history of injury on admission.
Only one patient received effective empirical antimicrobial therapy. Three cases developed acute
renal failure and required renal replacement therapy.

Antibiotic Treatment
Most patients received penicillin base antibiotic on admission (84.4%), mainly
penicillin/ampicillin, augmentin, cloxacillin and tazocin. Ten patients (31.25%) received
treatment with ampicillin/penicillin with cloxacillin as combination therapy (Table 3) alone. Five
patients (50%) out of ten, suffered from necrotizing fasciitis caused by organisms resistance to
both ampicillin/penicillin with cloxacillin.

Ten patients (31.25%) patients in this study received ineffective empirical antimicrobial therapy
(Table 3). All of them suffered from necrotizing fasciitis caused by gram negative organisms and
received penicillin base antibiotic (penicillin, augmentin, and cloxacillin) alone or in
combination with Clindamycin at the general ward. Only four patients were diagnosed suffering
from necrotizing fasciitis at the time of antimicrobial administration. These four patients
suffered from necrotizing fasciitis caused by Vibrio Vulnificus (two cases) andAeromonas
Hydrophilia (two cases) irrespectively. The other six patients were diagnosed suffering from
cellulitis and septicemia on admission. One patient suffered from necrotizing fasciitis caused by
polymicrobial with Proteus Mirabilis and Klebsiella species. The five other cases suffered from
necrotizing fasciitis caused by monomicrobial with Pseudomonas Aeruginosa, Acintobacter,
Serratia Marcescens, Aeromonas Hydrophilia and Coliform with ESBL. All patients
subsequently received effective antimicrobial therapy after admission to ICU, except the patient
who suffered from infection caused by extended-spectrum beta-lactamase producing Coliform,
who died shortly after ICU admission. Nine patients (90%) out of ten in this group had one or
multiple medical co morbidities.

Eleven patients (34.38%) were diagnosed suffering from necrotizing fasciitis at the time of
empirical antibiotic administration. Five out of these eleven patients (45.5%) were given
empirical antimicrobial therapy with inadequate cover for the gram negative organisms. Among
those patients, four received penicillin and clindamycin as combine therapy and the last one
received augmentin and metronidazole (Table 3).

The mean time to delivery of effective antimicrobial therapy after hospital admission was 10.17
+ 15.54 hours. One patient suffered from necrotizing fasciitis caused by extended-spectrum betalactamase producing Coliform and did not receive any effective antibiotic treatment during his
hospital stay. He received urgent debridement of his limb and admitted to our unit for post
operative care. He died within 1 day of ICU admission (day 2 hospital admission) due to
refractory shock and multiple organs failure. His data for effective antibiotic administration time
was regarded as missing during statistic analysis. Three patients had no positive microbiology
culture (both tissue and blood) and also considered to have missing data for the time from
admission to effective antibiotic administration. The average time to delivery of effective
antimicrobial therapy after hospital admission was shorter in both ICU and hospital survivors
than the non-survivors; however the p value was not statistically significant. Patients did not
require amputation of their extremities to control infection received effective antimicrobial
earlier than those who required amputation (P<0.005).

ICU Mortality
Most patients admitted to our Intensive Care Unit for post operative care (81.25%)(Table1).
Twenty five patients (78.13%) were in the state of shock on admission to our unit and required
inotropic support. Eleven patients received dialysis support at our Intensive Care Unit for renal
failure. One patient had end stage renal failure, while the other ten patients (31.25%) developed
acute renal failure and required emergency dialysis support (Table 4).

The mean intensive care length of stay was 6.58 days for nonsurvivors (with range from 1 to 16
days, and medium 4 days) and shorter than the survivors (9.50+6.07), however it was not
statistically significant (P= 0.093).

Twelve patients (37.5%) died at intensive care unit. ICU nonsurvivors had statistically lower
hemoglobin level, received less operation, and had higher APACHE II scores as compared with
survivors. (Table4).

Hospital Mortality
Fourteen patients died in the hospital. The overall mortality rate in this cohort was 43.75%.
Twelve patients died in ICU and two died in general ward after ICU discharge. The two patients
who died at general ward suffered from acute renal failure on ICU admission. They developed
nosocomial infection with multi organs failure and opted for conservative treatment at the
general ward. Hospital survivors had significantly less renal failure and required renal dialysis
therapy (16.7%verse57.1%;P value <0.017) (Table5).

More nonsurvivors suffered from diabetes mellitus died with necrotizing fasciitis (8 verse 4; P
value = 0.043). The APACHE II score was statistically lower in the hospital survivors than the
non survivors (23.39+5.81verse31.07+6.91;P = 0.001). The hospital survivors received
significantly more operations than the non survivors (3.56 verse 1.43; P < 0.001) (Table5).

The average length of stay for this group of patients was 35.06 days. The survivors had
statistically longer length of stay than the non survivor (46.50 + 35.35 vs. 20.36 + 36.29; P
=0.002)(Table5).

Amputation
Sixteen patients (50%) required amputation of their extremities to control the spread of their
infection. The duration between hospital admissions to administration of effective antibiotic (hrs)
was significantly longer in patients who received amputation of their extremities (15.79 +/17.30 hrs verses 4.93 +/-11.99 hrs; P value = 0.005). Also patients received amputation had
statistically lower hemoglobin level (9.03 gm/dl +1.72 versus 10.46gm/dl +1.77; P value = 0.036)
and received less operations (2.0 +1.03 verses 3.25 +1.95; P value =0.026) than the patients who
did not received amputation of their extremities (Table 6).

Discussion
I conducted this study on necrotizing fasciitis of extremities on intensive care prospective. It was
difference from previous studies which base on Orthopedic or infection point of view. I did not
include the full spectrum of disease; rather I selected patients with more severe disease in this
study. Centre of Heath Protection (Hong Kong) reported that only 61% of patients suffered from
necrotizing fasciitis associated Vibrio Vulnificus required intensive care admission. I believed
this group of patients with organ failure and required ICU for organ support, consumed most of
the hospital resources and yet had a relative high mortality.

APACHE II score
APACHE II score was recorded routinely in our unit. Other studies also used APACHE II score
to assess the severity of their patients, however most of them base on the measurement within
the first 24 to 48 hours on hospital admission. A time gap in the APACHE II assessment
properly exists between my cohort and other studies. Furthermore the APACHE II score was
collected routinely in our study group on ICU admission, which would provide better assessment
and less bias as compared to other retrospective studies. My patients had higher mean APACHE
II score than other studies, which properly reflected the selection bias in my study. A significant
higher APACHE II scores in our cohort were found in both ICU and hospital nonsurvivors.
APACHE II score on ICU admission is likely to be an accurate predictor for mortality.

Mortality
Fourteen patients died in the hospital. The hospital mortality rate was 43.75%. Among that
twelve patients succumbed at our intensive care unit. A relative high mortality was observed in
our study group. The report mortality of necrotizing fasciitis of limbs in previous paper was
16.9% to 33.3% (5, 13). The high hospital mortality in our group may due to high incidence of
multiple organ failure, which was reflected by high average APACHE II score due to selection
bias. Secondary the mean age in my cohort was 63 + 11.96, although analysis did not show the
age difference between survivor and nonsurvivors to be statistically significant. Liu and his
colleagues reported that age of more than 60 were an independent factors associated with
mortality. (20)

Renalfailure&DiabetesMellitus
Total of eleven patients (34.4%) received renal replacement therapy. Ten patients (31.25%)
developed acute renal failure and required acute renal replacement therapy. Eight out of ten
patients died in the hospital. The patient with end stage renal failure survived and discharged
from hospital. Less hospital survivors developed acute renal failure and required renal
replacement therapy when compared to the nonsurvivors (16.7% verse 57.1%; P value =0.017).
As described in previous studies, acute renal failure in intensive care patients associated with
significantly higher hospital mortality (17, 18). The data from Clermont et al suggested that the
ICU mortality was 4 times higher in the patients with acute renal failure as compared to those
who did not suffer from acute renal failure (18).

More hospital nonsurvivors suffered from diabetes than the survivor. Diabetic patients had
higher incidence of necrotizing fasciitis than the rest of the population (6, 20, 34,35). Diabetic
mellitus also identified as factor associated with mortality (35).

Microbiology
The diagnosis of necrotizing fasciitis was missed on hospital admission in most patients. Only
eleven patients (34.38%) were diagnosed suffering from necrotizing fasciitis at the time of
empirical antibiotic administration. Most patients were diagnosed suffering from cellulitis or
abscess and given ampicillin/penicillin with cloxacillin (31.25%) as empirical antimicrobial
treatment at on hospital admission.

In this study, 50% of cases suffered from infection caused by gram negative organism. 25 % of
necrotizing fasciitis in the study population caused by Aeromonas species and Vibrio Vulnificus.
Four patients suffered from necrotizing fasciitis associated Aeromonas species (three cases died
in ICU and the other one died in general ward after ICU discharge). Two patients (50%) suffered
from necrotizing fasciitis associated Vibrio Vulnificus died in ICU. Vibrio Vulnificus and
Aeromonas species caused severe necrotizing fasciitis and sepsis in patients with hepatic
diseases, diabetes mellitus, trauma and immunocompromised individual. (21, 22, 23, 24)
The report mortality ranges of Aeromonas necrotizing fasciitis and bacteriaemia varies from
26% to 100% in study reports. [20, 21, 22, 23]. Most patients had contact with contaminated
water. In some studies, 70% of cases had recent exposure to contaminate water.
Vibrio species are halophilic, lactose fermenting bacillus found in coastal waters in subtropical
region. It has been found in many different types of coastal fishes as well as filter feeders such as
oysters, crabs, clams, and mussels (28). Similar to many coastal cities around the world, severe
soft tissue infection caused by Vibrio species is an occupation hazardous to fishermen,
fishmongers and chef. (25) The highest densities of Vibrio species in Hong Kong were detected
in water samples from the Aberdeen shelter and the Jordan ferry pier (21). The wound infection
is mostly caused by exposure of open wounds to sea water or seafood products, or by trauma

during preparation of seafood, and may develop into secondary sepsis with a mortality rate of
82% (30).

Recently Centre of Health Protection in Hong Kong reported 44 patients suffered from
necrotizing fasciitis caused by Vibrio Vulnificus from January 2007 to June 2010(24). 84% of
the patients had underlying chronic medical illness and 73% of the patients had history of raw
sea food contact. The morality rate of in the case report was 30%.

Antibiotic Therapy
Ten patients (31.25%) patients in this study received ineffective empirical antimicrobial therapy.
Six patients did not received effective empirical antibiotic cover due to wrong diagnosis on
admission. Four patients were diagnosed suffering from necrotizing fasciitis while received
ineffective empirical antibiotic treatment.
Ineffective empirical antibiotic treatment was not associated with statistically significant
increase in ICU or hospital mortality. Elliott and his colleagues reported 8.1% of their patients
with necrotizing fasciitis had received inadequate antimicrobial therapy; however that effect on
mortality and morbidity were not evaluated (12).
The possible reasons to account for the lack of statistic significant of effective antibiotic relate to
mortality include the relative small number of patients in the study; and possible usage of board
spectrum antibiotic given prior to patient hospital admission. It was believe that board spectrum
antibiotic were frequently prescript at general practice and that might account for the high
incidence of ESBL in the Hong Kong community (19). The history of board spectrum antibiotic
administration prior to hospital admission was not mention in the clinical notes of all patients.
Thirdly the high mean APACHE II score in my cohort on ICU admission reflected that many
patients suffered from multiple organs failure. The hospital nonsurvivors had a mean APACHE
II score 31.07 + 6.91. Mostly nonsurvivors died within the first few daysafter intensive care
admission (with range from 1 to 16 days, and medium 4 days). While these patients had severe
multiple organ failure, surgery and effective antibiotic would not alter their fatal course. Lastly
even in patients who received effective antibiotic while diagnosed suffering other condition
(such as cellulitis), the dosage of the antibiotic administered often suboptimal for necrotizing
fasciitis, that element was not fully account in this study.

The duration between admissions to administration of effective antibiotic (hrs) was significantly
longer in patients who received amputation of their extremities (15.79 + 17.30 hrs verses 4.93
+11.99 hrs; with P value = 0.005). This was not reported on other studies. The spread of
infection along the tissue plane apparently controlled by the antimicrobial therapy administrated
and thus reduced the need of amputation to control the infection.

The initial intravenous empirical antimicrobial should be board enough to cover diverse
causative agents. Historically, gram positive and anaerobic organisms were covered with high
dose penicillin (18-24 million units per day) and clindamycin, while a third agent was used to
provide additional cover of gram negative organisms. A third or fourth generation cephalosporin,
a fluoroquinolone, aminoglycoside or carbapenem will provide reasonable cover for the gram
negative organisms. Some authority suggests alternative antimicrobial therapy with piperacillintazobactam or ticarcillin-clavulanate to replace penicillin, and therefore also provides cover
including gram negative coverage (31). Patients with history of injury associated with seafood or
aqua origin, should receive antibiotic cover for Vibrio and Aeromonas. Histological antibiotic
therapy for Vibrio Vulnificus necrotizing fasciitis includes combination of ceftazidime and
doxycycline (32). While in Hong Kong, local authority recommended fluoroquinolone and
amoxicillin-clavulanate as the empirical treatment (33).

Five out of these eleven patients (45.5%) were given empirical antimicrobial therapy with
inadequate cover for the gram negative organisms, even though they were diagnosed suffering
from necrotizing fasciitis at the time of antimicrobial administration. The most common
combination antibiotic prescribed was clindamycin and penicillin; which was effective in
treating streptococcus and anaerobic organisms. As mention above, 50% of the cases in the study

suffered from disease caused by gram negative organism with high proportion of cases caused
by Vibrio species and Aeromonas spices. Similar microbiology finding was reported in other
local studies (26, 27, 12). This finding suggests frontline medical staffs lack knowledge in
microbiological causes and the appropriate use of empirical antibiotic treatment in treating
necrotizing fasciitis.

Hospital Length of stay & Operations

The mean hospital length in the cohort is 35 days. Audi report a similar finding in his study (8).
Similar to other studies, survivors had more operation than the nonsurvivors. After initial
debridement or amputation for infection control, survivors received further grafting and
reconstruction operation for their limbs, and result in more numbers of operation than the
nonsurvivors.

Conclusion
Necrotizing fasciitis is a rare severe surgical illness. Prompt diagnosis and early administration
of effective antibiotic, reduced morbidity. Base on the bacteriologic findings, early use of board
spectrum empirical antibiotics to cover Streptococcus, Enterobacteriaceae; Vibrio and
Aeromonas species in patients with history of seafood and fresh/seawater contacted is
recommended.

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Tables

Patient Total

(n =32)

Percentage (%)

Sex: Male (%)

22

68.75%

Admission Age

63 +/- 11.96

History of Injury

17

53.12%

Comorbidity

24

75%

Diabetes

12

37.5%

Autoimmune disease

6.25%

Chronic venous ulcer

6.25%

Cirrhosis

15.63%

Gout

9.38%

Intravenous drug abuse

6.25%

Myodysplastic Syndrome

6.25%

ESRF

3.13%

COPD

6.25%

CHF

6.25%

Amputation

16

50%

Post Operative Care

26

81.25%

Time from symptom to presentation

(days)

2.63(mean)

Time after admission to

administration of sensitive antibiotic
(hrs)

9.78 (mean)

Time from admission to OT (hrs)

23.94 (mean)

APACHE II score

26.79 (mean)

ICU length of stay

8.40 (mean)

Hospital length of stay

35.06 (mean)

Table 1 Demographic data of patients with necrotizing fasciitis of their limbs

Microorganisms

Monomicrobial

Polymicrobial

Total

Gram-positive

11

14

Streptococcus pyogenes

Methicillin-sensitive Staphylococcus
aureus

Enterococcus

Staphylococcus epidermidis

Group G Beta-haemolytic streptococcus

Streptococcus dysgalactiae
subsp.equisimilis

Peptostreptococcus

Clostridium spp

Gram-negative

16

19

E Coli

Proteus Mirabilis

Klebsiella species

Coliform

Pseudomonas aeruginosa

Arcanobacterium haemolyticum

Serratia Marcescens

Actinobacter baumannii

Vibrio vulnificus

Aeromonas hydrophilia

Bacterodies spp

Unknown

Table 2. Microbiologic findings in patients with necrotizing fasciitis

Adequacy of
empirical
Case
Causative
organism

Antibiotic disc
sensitivities
of cultured bacteria

empirical
antibiotic given on
antibiotic given Right diagnosis hospital admission
on hospital
on admission
admission
(Y/N)

cloxacillin,
gentamicin,
erythromycin,

N
Staphylococcus
Aureus

clindamycin,
fusidic acid

Effective

ampicillin
cloxacillin

Ampicillin

Streptococcus
Pyogenes

penicillin,
cotrimoxazole,
erythromycin,
clindamycin

Effective
ampicillin
cloxacillin

Streptococcus
Pyogenes

ampicillin, penicillin,
cotrimoxazole,
erythromycin,
clindamycin

cefuroxime,
metronidazole,
gentamicin

Effective
N

Enterocococcus
species,

Bacteroides
species,
Peptostreptococcu
s species,
Clostridium
species

Effective

Ampicillin,
penicillin,
erythromycin,
metronidazole

erythromycin,
clindamycin,
flagyl, gentamicin

Proteus Mirabilis
and Klebsiella
species

gentamicin,
cefuroxime,
ciprofloxacin,

ampicillin,
cloxacillin

Ineffective

Effective

Effective

Ineffective

augmentin,
cloxacillin

Effective

ampicillin, penicillin,
cotrimoxazole

ampicillin
cloxacillin

Effective

gentamicin,
ciprofloxain,
ceftazidime, imipenem,
cefoperoazone(I)

penicillin,
cloxacillin,

Unknown

Levofloxacin
clindamycin

augmentin,
cotrimoxazole
(S to klebsiella only)

Streptococcus
Pyogenes

ampicillin, penicillin,
cotrimoxazole,
erythromycin,
clindamycin

Rocephin,
clindamycin,
penicillin,
gentamicin

Clostridium
Perfringens

metronidazole

augmentin
metronidazole

gentamicin,
Coliform (ESBL) levofloxacin, amikacin, Augmentin, flagyl
tazocin, meropenm
cloxacillin,

Staphylococcus
Epidermidis

gentamicin,
erythromycin,
clindamycin,
fusidic acid

10
Strept Pyrogenous

11

12

Pseudomonas
Aeruginosa

Unknown

Ineffective
N

Unknown
Y

13

Unknown

Unknown

rocephin;
cloxacillin,
clindamycin,

Unknown

14

Unknown

Unknown

penicillin

amikacin,
cloxacillin,
tazocin

Unknown

Levofloxacin
erythromycin

Effective

ampicillin
cloxacillin

Ineffective

Ineffective

ampicillin
15

Beta-Haemolytic
Strept. Group G

16

Aeromonas
Hydrophilia

penicillin,
cotrimoxazole
ciprofloxacin,
amikacin,
sulperazon

17

Aeromonas
Hydrophilia

gentamicin,
cefuroxime,
cipofloxacin,
cotrimoxazole

penicillin
clinidamycin

18

Serratia
Marcescens

gentamicin,
levofloxacin, timentin,
amikacin, netilmicin

ampicillin
cloxacillin

unasyn, gentamicin,
ciprofloxacin,
sulperazon, amikacin

ampicillin
cloxacillin

19

Actinobacter
Baumannii

Ineffective

Ineffective
N

20

Aeromonas
hydrophilia

gentamicin,
cefuroxime,
levofloxacin, timentin,
Tazocin

21

Beta-Haemolytic
Strept. Group G

ampicillin, penicillin,
cotrimoxazole,
erythromycin,
clindamycin

penicillin
clindamycin

Augmentin

Ineffective

Effective

22

23

Klebsiella
Pneumonia

gentamicin,
cefuroxime,
levofloxacin, timentin,
Augmentin

ampicillin, gentamicin,
cefuroxime,
Vibrio Vulnificus
ciprofloxacin,
cotrimoxazole,
augmentin
ampicillin,
erythromycin,
penicillin,
cotrimoxazole,
tetracycline

24

Arcanobacterim
Haemolyticum

25

cloxacillin, gentamicin,
Staphylococcus
erythromycin,
Aureus
clindamycin, fusidic
acid

26

27

28

29

E Coli

ampicillin, gentamicin,
cefuroxime,
Vibrio vulnificus
levofloxacin, timentin,
augmentin
ampicillin, gentamicin,
cefuroxime,
levofloxacin, timentin,
augmentin

N
Effective

penicillin
clinidamycin

Y
Ineffective

augmentin,
clindamycin,
gentamicin

Effective

penicillin
cloxacillin

Effective

Effective

ampicillin, gentamicin,
cefuroxime,
ciprofloxacin,
rocephin, klacid
cotrimoxazole,
augmentin

ampicillin, gentamicin,
cefuroxime,
Vibrio Vulnificus
levofloxacin, timentin,
augmentin

E Coli

Augmentin

ampicillin
cloxacillin
levofloxacin

Effective
Y

clindamycin,
penicillin,
Y

Ineffective

Effective

ampicillin
cloxacillin

30

31

ampicillin, gentamicin,
cefuroxime,
Vibrio Vulnificus
Tazocin, amikacin
levofloxacin, timentin,
augmentin

Aeromonas
Caviae

gentamicin,
cefuroxime,
ciprofloxacin,
cotrimoxazole

Penicillin,
Tazocin

Effective

Effective
N

32

Streptococcus
Dysgalactiae

ampicillin, penicillin,
cotrimoxazole,
erythromycin,
clindamycin

Augmentin

Effective
N

Table 3. Microbiology, in vitro antibiotic sensitivity and empirical antimicrobial therapy in

patients with necrotizing fasciitis

ICU Survivor (20)

ICU Nonsurvivor (12)

P-value

15 (75%)

7 (75%)

0.325

Admission Age

61.96 +11.81

64.75 +12.53

0.533

History of Injury

11 (55%)

6 (50%)

0.784

Diabetes

6 (30%)

6 (50%)

0.258

Autoimmune disease

0 (0%)

2 (10%)

0.258

Chronic venous ulcer

0 (0%)

2 (16.7%)

0.06

Cirrhosis

2 (10%)

3 (25%)

0.258

Gout

3 (15%)

0 (0%)

0.159

Intravenous drug abuse

1 (5.0%)

1 (8.3%)

0.706

Myodysplastic Syndrome

1 (5.0%)

1 (8.3%)

0.706

ESRF

1 (5%)

0 (0%)

0.431

COPD

0 (0%)

2 (16.7%)

0.06

CHF

0 (0%)

2 (16.7%)

0.06

History of recent injury

11 (55%)

6 50%)

0.784

Time from symptom to

presentation (days)

2.45 +/-2.45

2.92 +/-2.35

0.465

Time after admission to

administration of sensitive
antibiotic (hrs)

6.65 +/-9.79

15.17 +/-20.70

0.144

Time from admission to OT

(hrs)

24 +/-24.48

23.83 +/-21.61

0.984

10.22 +/-1.83

8.94 +/-1.70

0.050

153.83 +/-104.51

121.25 +/-117.20

0.186

Sex: Male (%)

Comorbidity

Laboratory Result on ICU

admission
Hemoglobin (mg/dL)
Platelet

x 109/l

WBC

x109 /L

Urea

mol/l

Creatinine

mol/l

11.96 +/-7.65

0.094

19.15 +/-14.26

0.938

245.27 +/-316.83

193 +/-171.97

0.815

Bicarbonate mmol/l

17.87 +/-4.04

17.67 +/-3.7

0.681

Albumin

gm/l

23.35 +/-6.77

25.42 +/-8.18

0.626

Bilirubin

mol/L

29.10 +/-40.97

44.33 +/-45.23

0.311

IU/L

34.80 +/-19.76

66.08 +/-138.42

0.559

Inotropic Agent

14 (70%)

11 (91.7%)

0.151

Dialysis

5 (25%)

6 (50%)

0.149

Ventilator Care > 96hrs

12 (60%)

4 (33.3%)

0.144

3.3 +/-1.69

1.5 +/-0.8

0.001

9(45%)

7(58.3%)

0.465

APACHE II score

24.65 +/-7.47

30.25 +/-5.75

0.005

ICU length of stay (days)

9.50 +/-6.07

6.58 +/-6.36

0.093

ALT

Total Number of Operation

Amputation

24.17 +/-32.91
23.03 +/-28.92

Table 4. Comparison between ICU survivor and nonsurvivors

Survivor(n=18)

NonSurvivor(n=14)

Pvalue

13(72.2%)

9(64.3%)

0.631

AdmissionAge

60.83+/11.70

65.79+/12.14

0.231

HistoryofInjury

10(55.6%)

7(50%)

0.755

Sex:Male(%)

Comorbidity

Diabetes

4(22.2%)

8(57.1%)

0.043

Autoimmunedisease

2(11.1%)

0(0%)

0.198

Chronicvenousulcer

0(0%)

2(14.3%)

0.098

Cirrhosis

2(11.1%)

3(21.4%)

0.425

Gout

3(16.7%)

0(0%)

0.109

Intravenousdrugabuse

1(5.6%)

1(7.1%)

0.854

MyodysplasticSyndrome

1(5.6%)

1(7.1%)

0.854

ESRF

1(5.6%)

0(0%)

0.370

COPD

0(0%)

2(14.3%)

0.098

CHF

0(0%)

2(14.3%)

0.098

10(55.6%)

7(50.0%)

0.755

Timefromsymptomtopresentation
(days)

2.53+/2.55

2.75+/2.26

0.644

Timeafteradmissionto
administrationofsensitiveantibiotic
(hrs)

6.0+/9.49

14.64+/19.53

0.150

23.67+/25.67

24.29+/20.33

0.690

10.20+/1.90

9.15+/1.70

0.124

144.69+/102.24

137.64+/120.41

0.518

Historyofrecentinjury

TimefromadmissiontoOT(hr)
LaboratoryResultonICUadmission
Haemoglobin (mg/dL)
Platelet

x109 /L

WBC

x109 /L

23.67+/34.55

14.35+/10.25

0.382

Urea

mol/l

21.38+/29.29

21.80+/16.76

0.543

Creatinine

mol/l

199.46+/265.59

259.36+/280.89

0.287

Bicarbonate mmol/l

18.02+/4.24

17.50+/3.44

0.457

Albumin

gm/l

23.67+/7.06

24.71+/7.76

0.954

Bilirubin

mol/l

29.83+/43.22

41.21+/42.39

0.209

IU/L

35.50+/20.51

60.71+/128.11

0.482

InotropicAgent

12(66.7%)

13(92.29%)

0.075

Dialysis

3(16.7%)

8(57.1%)

0.017

VentilatorCare>96hrs

10(55.6%)

6(42.9%)

0.476

3.56+/1.58

1.43+/0.76

0.000

7(38.9%)

9(64.3%)

0.154

APACHEIIscore

23.39+/5.81

31.07+/6.91

0.001

ICUlengthofstay(days)

8.83+/5.08

7.86+/7.65

0.278

46.50+/35.35

20.36+/36.29

0.002

ALT

TotalNumberofOperation
Amputation

Hospitallengthofstay

Table 5. Comparison between Hospital survivor and nonsurvivors

WithoutAmputation
(n=16)

Amputation(n=16)

PValue

Sex: Male (%)

12 (75%)

10 (62.5%)

0.446

Admission Age

60.31 +/-12.41

65.69 +/-11.24

0.181

History of Injury

8 (50%)

9 (56.3%)

0.723

5 (31.3%)

7 (43.8%)

0.465

Autoimmune disease

0 (0%)

2 (12.5%)

0.144

Chronic venous ulcer

1 (6.3%)

1 (6.3%)

1.0

Cirrhosis

1 (6.3%)

4 (25%)

0.144

Gout

2 (12.5%)

1 (6.3%)

0.544

Intravenous drug abuse

1 (6.3%)

1 (6.3%)

1.0

Myodysplastic Syndrome

0 (0%)

2 (12.5%)

0.144

ESRF

0 (0%)

1 (6.3%)

0.310

COPD

1 (6.3%)

1 (6.3%)

1.0

CHF

1 (6.3%)

1 (6.3%)

1.0

History of recent injury

8 (50%)

9 (56.3%)

0.723

Time from symptom to

presentation (days)

2.81 +/-2.59

2.44 +/-2.24

0.579

Time after admission to

administration of sensitive
antibiotic (hrs)

4.93 +/-11.99

15.79 +/-17.30

0.005

Time from admission to OT (hrs)

20.31+/-14.68

27.56+/-29.29

0.925

10.46 +/-1.77

9.03 +/-1.72

0.036

Comorbidity
Diabetes

Laboratory Result on ICU

admission
Haemoglobin (mg/dL)

Platelet

x109 /L

153.69 +/-114.66

129.53 +/-104.78

0.366

WBC

x109 /L

16.88 +/-9.96

22.31 +/-37.07

0.498

Urea

mol/l

22.88 +/-31.06

20.25 +/-15.74

0.777

Creatinine

mol/l

157.71 +/-167.16

293.63 +/-335.28

0.258

Bicarbonate

mmol/l

16.59 +/-4.43

19.00 +/-2.83

0.096

Albumin

gm/l

23.25 +/-7.10

25.00 +/-7.56

0.509

Bilirubin

mol/l

34.50 +/-42.17

35.13 +/-44.22

0.792

ALT

IU/L

57.75 +/-119.57

35.31 +/-21.66

0.611

Inotropic Agent

4 (25%)

3 (18.8%)

0.669

Dialysis

4 (25%)

7 (43.8%)

0.264

6 (37.5%)

10 (62.5%)

0.157

Total Number of Operation

3.25 +/-1.95

2.0 +/-1.03

0.026

APACHE II score

27.19 +/-6.02

26.31 +/-8.60

0.637

ICU length of stay (days)

7.13 +/-5.57

9.69 +/-6.78

0.281

40.63 +/-40.09

29.50 +/-35.26

0.386

Ventilator Care > 96hrs

Hospital length of stay (days)

Table 6. Comparison between patients with amputation and those without amputation