Vibrio necrotizing soft-tissue infection of the upper extremity: Factors predictive of amputation and death

Journal of Infection (2008) 57, 290e297

www.elsevierhealth.com/journals/jinf

Vibrio necrotizing soft-tissue infection of the upper extremity: Factors predictive of amputation and death Kuo-Chin Huang a,c,*, Pang-Hsin Hsieh b, Kuo-Chung Huang d, Yao-Hung Tsai a a

Department of Orthopaedic Surgery, Chang Gung Memorial Hospital at Chiayi, Taiwan, ROC Department of Orthopaedic Surgery, Chang Gung Memorial Hospital at Taoyuan, Taiwan, ROC c Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Taiwan, ROC d Department of Business Administration (Statistics), Chungyu Institute of Technology, Taiwan, ROC b

Accepted 13 July 2008 Available online 27 August 2008

KEYWORDS Vibrio infection; Necrotizing soft-tissue infection

Summary Background: Vibrio necrotizing soft-tissue infection (VNSTI) is characterized by rapidly progressing soft-tissue necrosis and fulminant septicemia in the at-risk host. Despite advancing antibiotic and infection control practices, VNSTI is still a highly lethal and disabling disease. By evaluating prognostic factors for fatality and major amputation in VNSTI patients, this study was intended to improve treatment strategies, reduce mortality and minimize amputations. Methods: We performed a cohort study of patients with VNSTI in the upper extremity at a trauma center which cares for residents in the costal southern Taiwan. Patients were considered for enrollment in this study if they met the following criteria: (1) histopathologically or surgically proven necrotizing soft-tissue infections of the upper extremities and (2) isolation of Vibrio species from soft-tissue lesions and/or blood collected immediately after arrival at emergency department. All patients were treated with a specified combination of parenteral antibiotic therapy (the combination of a third-generation cephalosporin and tetracycline), aggressive resuscitation and prompt de ´bridement. The main outcome measures in this investigation included inpatient mortality and major amputation. Results: Sixteen patients were enrolled in the 5-year study from July 2002 to June, 2007. The overall mortality rate in this case series was 18.6%. Another 25% of surviving patients required major amputations. These subjects were, then, divided into two groups based on treatment outcome: unsatisfactory (death and major amputation) and satisfactory (survival without major amputation). The two patient groups did not differ in demographic data, treatment

* Corresponding author. Department of Orthopaedic Surgery, Chang Gung Memorial Hospital at Chiayi, 6, West Section, Chia-Pu Road, Pu-Tz City, Chia-Yi County 613, Taiwan, ROC. Tel.: þ886 5 3621000x2004; fax: þ886 5 3623005. E-mail address: [email protected] (K.-C. Huang). 0163-4453/$34 ª 2008 The British Infection Society. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jinf.2008.07.009

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protocol, bacteriological findings or APACHE II and LRINEC scores. Patients with unsatisfactory results had a higher incidence of septic shock requiring vasopressor/inotropic support (p Z 0.020), severe hypoalbuminemia with less than 2 g/dL (p Z 0.001) and elevated AST (p Z 0.039) than those with satisfactory results. The former also had longer ICU stay (p Z 0.039) and a higher incidence of comorbidity during hospitalization (p Z 0.024). Conclusion: APACHE II or LRINEC scoring system cannot be used as a reliable tool for early detection of VNSTI. For treating such a highly lethal and disabling disease, clinical acumen remains of paramount importance regardless of the scores. Expanding purpura in these patients is considered an ominous sign and may indicate surgical intervention. A serial survey of ALT/AST or CPK levels can reflect the extent of muscle damage and help determine the optimal time of amputation. Severe hypoalbuminemia also serve as poor prognostic factors implicating a high probability of death or major amputation. ª 2008 The British Infection Society. Published by Elsevier Ltd. All rights reserved.

Introduction Marine Vibrio bacteria are ubiquitous in aquatic environments and are associated with many diseases in humans,1,2 including primary septicemia, wound infections and gastroenteritis in at-risk hosts.2e7 Immunocompromised patients with Vibrio necrotizing soft-tissue infection (VNSTI) and septicemia are at high risk for mortality (30e88%) and usually die within 48 h after decreased blood pressure and hemorrhagic bullae occur.7e15 Rapid diagnosis and aggressive treatment with specific parenteral antibiotics (the combination of a third-generation cephalosporin and tetracycline or its analogue) and early surgical de ´bridement have been urged as the cornerstone of therapy.4,7,12e14 Many authors recommend major amputation in order to facilitate local infection control and increase patient survival.7,12e14 However, from the perspective of patient satisfaction, avoiding such an extreme measure may be next critical to survival.16,17 The objective of this study was to sort out those parameters that are particularly useful as clinical indicators to help determine the extent and timing of surgical intervention. The information from this series may be valuable in improving VNSTI treatment, thereby reducing the mortality rate and the need for amputation.

Materials and methods Participating patients and the treatment protocol The study included all patients diagnosed with VNSTI of an upper extremity and treated by the authors at Chang Gung Memorial Hospital between July, 2002 and June, 2007. Vibrio infection was confirmed by isolating pathogenic bacteria from soft-tissue lesions and/or blood collected immediately after arrival at emergency department. Necrotizing soft-tissue infection was defined by either histopathologic or surgical findings such as the presence of necrosis of skin, subcutaneous fat, superficial fascia, or underlying muscles. All patients received the same treatment protocol based on the in vitro and in vivo experimental evidence reported in the relevant literature.6,7,13,14,18e20 Once these criteria were met, patients were enrolled in this study, and no further inclusion or exclusion criteria were used.

The aggregate number of enrolled patients in this 5-year study was 16. The three main elements of the treatment protocol were specific combination antibiotic therapy, aggressive resuscitation and prompt radical de ´bridement. Combination therapy of a third-generation cephalosporin (e.g., ceftazidime 1e2 g every 8 h or ceftriaxone 1e2 g every 12 h) and tetracycline (e.g., oxytetracycline 250 mg twice daily) was prescribed immediately upon clinical suspicion of Vibrio infection. Intensive care and aggressive resuscitation with/without vasopressor/inotropic support (dopamine 2e10 mg/kg/min, for example) would be added as part of the whole treatment if septic shock occurred. Fluid administration would begin with 2 L of normal saline solution and repeated as the case may be. If the circulation did not respond to the first few boluses of fluid, which was evidenced by refractory low blood pressure and poor urinary output, vasopressor/inotropic agents would then be administered. Orthopaedic surgeons were consulted for prompt de ´bridement upon suspicion of necrotizing soft-tissue infection. Criteria for surgical intervention were the following (1) hemorrhagic bullae with/without necrotic cutaneous lesions and (2) progressive edema and subcutaneous bleeding such as grouped petechia or purpura.

Patient characteristics and classification We summarized the collected data at the time of study enrollment, which included patient age, gender, history, predisposing factors, presenting signs and symptoms, location of infection, laboratory findings, bacteriologic results, length of stay and outcomes such as survival and limb salvage. Appropriate data were used to calculate the LRINEC (laboratory risk indicator for necrotizing fasciitis) score on arrival at emergency department and the highest APACHE (acute physiological, age, and chronic health evaluation) II score within 24 h after hospital admission. Although the mortality rate in this case series (18.6%) was lower than that reported elsewhere (30e88%),7e15 oneforth of the patients required major amputation. From the perspective of patient satisfaction, upper limb salvage may be next critical to survival. Therefore, establishing an effective regimen to maximize patient satisfaction cannot be overemphasized. Based on this rationale, the enrolled patients with upper extremity VNSTI were separated into

292

Table 1

Patient characteristics Sex

Side

Bacterial species

Underlying diseasesa

Occupation

Affection mechanism

Pre-hospital treatmentb

TiOAc (days)

TiOSd (h)

TyOSe

Comorbidityf

ICU days)

Hospital (days)

Clinical resultsg

Group 1 1 71 2 66 3 75 4 67 5 37 6 55 7 65

M F M M M M F

L R R L L R B

V. V. V. V. V. V. V.

Cholera vulnificus vulnificus parahaemo vulnificus vulnificus vulnificus

CRI, LC ESRD SCCL HB, PU, AI LC, Alc, DA RCC HC, DM, AI

Retiree Retiree Fisher Fisher Farmer Retiree Retiree

Fish fin Sea water Sea water Fish fin Unclear Fish fin Unclear

Nil Nil Nil Nil Nil Nil Nil

4 2 3 1 2 1 4

12 2 5 10 1 2 72

F WE Am WE Am Am WE

Seizure Nil PN UGIB PN Nil PN, MOF

2 10 7 28 24 0 85

2 53 32 28 40 11 85

Death Alive (Am) Alive (Am) Death Alive (Am) Alive (Am) Death

Group 2 1 63 2 62 3 58 4 66 5 71 6 59 7 61 8 71 9 63

M M F M M M M M M

R R R R B L R R L

V. V. V. V. V. V. V. V. V.

Cholera vulnificus vulnificus vulnificus vulnificus vulnificus vulnificus Cholera vulnificus

Asthma CRI, PU, AI RA, HTN HB, PU, AI DM LC, DM DM, PU LC, Spl, An HC, DM, HTN

Farmer Retiree Retiree Fisher Retiree Fisher Retiree Retiree Fisher

Insect bite Sea water Crab Unclear Sea water Oyster Unclear Sea water Fish fin

HD Nil Nil HD Nil Nil Nil Nil Nil

1 3 2 2 2 2 3 2 1

1 13 1 60 1 2 4 1 3

F F WE WE WE WE WE WE WE

Nil Nil Nil Nil Nil Nil UGIB Nil Nil

0 0 9 1 7 2 0 3 0

7 16 42 20 42 13 28 29 23

S S S S S S S S S

Patient

Age (years)

a CRI, chronic renal insufficiency; LC, liver cirrhosis; ESRD, end stage renal disease; SCCL, squamous cell carcinoma of the lung; HB, hepatitis B; PU, peptic ulcer; AI, adrenal insufficiency; Alc, alcoholism; DA, drug abuser; RCC, renal cell carcinoma; HC, hepatitis C; DM, diabetes mellitus; RA, rheumatoid arthritis; HTN, hypertension,; Spl, splenomegaly; An, Anemia. b HD, herb dressing. c TiOA, duration of symptoms prior to arrival to the ER. d TiOS, time of the 1st surgery. e TyOS, type of the 1st surgery; F, fasciotomy; WE, wide excision; Am, Amputation. f PN, pneumonia; UGIB, upper gastrointestinal bleeding; MOF, multiple organ failure. g S, satisfactory result.

K.-C. Huang et al.

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293

the following groups for further analyses: patients with unsatisfactory results (group 1: death or major amputation) and patients with satisfactory results (group 2: survival without major amputation).

Statistical analyses Group 1 and group 2 variables were compared by univariate analysis. Wilcoxon rank sum test was used to compare continuous variables, and Fisher exact test was used to compare dichotomous variables. A two-tailed p-value of <0.05 was considered statistically significant.

Results Sixteen patients with upper extremity VNSTI were enrolled in this 5-year-long study. All patients had undergone the above-mentioned treatment protocol (specific combination antibiotic therapy, aggressive resuscitation and prompt radical de ´bridement). Table 1 summarizes demographic and clinical data for all patients. The median patient age was 64 years (range 37e75); 13 (81.25%) were male, and 3 (18.75%) were female. Among the involved lesion limbs, right were predominant (68.75%). Most patients were immunocompromised (93.75%) and had an unequivocal history of recent exposure to sea water (31.25%) or marine life (37.5%). Hepatic dysfunction was the leading (50%) underlying disease rendering these patients immunocompromised. Most cases were reported during the summer and early fall (particularly in September) of each year (Fig. 1).

Table 2

Group comparison of patient characteristics

Variable

Group 1 (n Z 7)

Group 2 (n Z 9)

p-Value

Age Sex Male Female Affection mechanism Clear Unclear TiOAa (days) TiOSb (h) Co-morbidity Positive Negative APACHEc II score ICU stay (days) Hospital stay (days)

66 (37, 75)

63 (58, 71)

0.597 0.338

5 (71.4) 2 (28.6)

8 (88.9) 1 (11.1)

5 2 2 5

(71.4) (28.6) (1, 4) (1, 72)

6 3 2 2

(66.7) (33.3) (1, 3) (1, 60)

5 2 17 10 40

(71.4) (28.6) (9, 22) (0, 85) (2, 85)

1 8 13 1 23

(11.1) (88.9) (7, 20) (0, 9) (7, 42)

0.635

0.560 0.315 0.024d

0.112 0.039d 0.459

Data are presented as median (min, max) or frequency (%). Age, TiOA, TiOS, ICU and hospital days: Wilcoxon rank sum test. Sex, affection mechanism, and co-morbidity: Fisher exact test. a TiOA, duration of symptoms prior to arrival to the ER. b TiOS, time of the first surgical intervention. c APACHE, acute physiological, age, and chronic health evaluation. d The difference is significant (p < 0.05).

Group comparison of signs/symptoms and microbiological findings (Table 3)

Group comparison of patient characteristics (Table 2) Seven (43.75%) patients died or underwent major amputation (group 1) whereas nine (56.25%) survived without major amputation (group 2). Comparison of groups 1 and 2 revealed no significant differences in age, gender, presence of unequivocal affection mechanism, duration of symptoms prior to arrival to the emergency department, time of first surgical intervention or highest APACHE II scores within 24 h after hospital admission. Patients in group 1 had a longer ICU stay (p Z 0.039) and a higher percentage of comorbidity during hospitalization (p Z 0.024) than those in group 2. However, the two groups did not significantly differ in total length of hospital stay.

7

No. of Cases

6 5 4

All patients were taken to the emergency department because of exquisite wound pain with moderate-tosevere swelling and erythema/purpura (100% in both groups). (Fig. 2) Varying stages of hemorrhagic bullae and septic shock (systolic blood pressure < 90 mmHg) were commonly observed (71.4% and 85.7%, respectively, in group 1; 66.7% and 55.6%, respectively, in group 2). Although the two groups did not statistically differ in incidence of the above signs/symptoms, group 1 had a higher rate of vasopressor/inotropic support for shock than group 2 (p Z 0.020). No patients exhibited symptoms of diarrhea or gastroenteritis. Regarding microbiological findings, Vibrio infection was confirmed by positive blood culture (71.4% in group 1, 66.7% in group 2), positive wound culture (85.7% in group 1, 66.7% in group 2) or both (57.1% in group 1, 33.3% in group 2). The most common (75%) pathogenic specie in this case series was Vibrio vulnificus. There were no statistical differences in microbiological findings when comparing between the two groups.

3

Group comparison of laboratory data (Table 4)

2 1 0

Jan

Feb

Mar Apr May Jun

Jul

Aug Sep

Oct

Nov

Dec

Month

Figure 1 Cases of Vibrio necrotizing soft-tissue infection of the upper extremities by month of symptom onset.

The group 1 patients had a higher rate of leucopenia (p Z 0.026) and a lower rate of left shift (p Z 0.007) than those in group 2. The median LRINEC score on arrival at emergency department was 4 in group 1 (range, 1e8) and 3 in group 2 (range, 0e9). In comparison between the two groups, there were no statistical differences in the

294

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Table 3

Group comparisons of signs/symptoms and microbiological findings

Variable Signs and symptoms Fever (>38  C) Pain and tenderness Swelling/ecchymosis Bullous lesions Clear bullae Hemorrhagic bullae Diarrhea Shock (<90 mmHg) Vasopressor/inotropic support Bacteriological findings Positive blood culture Positive wound culture Positive blood and wound culture Wound culture growth Rare or light Moderate or heavy Mixed infection a

Group 1 (n Z 7) (%)

Group 2 (n Z 9) (%)

p-Value

2 (28.6) 7 (100) 7 (100)

5 (55.6) 9 (100) 9 (100)

0.231 1.000 1.000

0 5 0 6 6

0 6 0 5 2

1.000 0.635 1.000 0.231 0.020a

(0) (71.4) (0) (85.7) (85.7)

(0) (66.7) (0) (55.6) (22.2)

5 (71.4) 6 (85.7) 4 (57.1)

6 (66.7) 6 (66.7) 3 (33.3)

3 (50) 3 (50) 1 (14.3)

5 (83.3) 1 (16.7) 0 (0)

0.635 0.392 0.329 0.242

0.438

The difference is significant (p < 0.05).

LRINEC score or its components, including C-reactive protein, total white cell count, hemoglobin, sodium, creatinine and glucose. Alanine aminotransferase (ALT) level did not significantly differ; however, group 1 patients had a higher level of aspartate aminotransferase (AST) than those in group 2 (p Z 0.039). In addition, group 1 patients had a lower albumin level than those in group 2 (p Z 0.004). Severe hypoalbuminemia (albumin level < 2 g/dL) was also significantly higher in group 1 than in group 2 (p Z 0.001).

Discussion For treating patients with VNSTI of the upper extremity, the authors consistently used the specific combination antibiotic therapy with a third-generation cephalosporin and tetracycline as the definite pharmaceutical treatment regimen. In vitro and in vivo studies have clearly demonstrated the superiority of this treatment regimen even though most Vibrio isolates exhibit in vitro susceptibility to a great variety of antibiotics.13,14,18e20 Our satisfactory treatment outcome and an overall mortality rate (18.6%) lower than that reported in the literature (30e88%) further support the efficacy of this specific combination antibiotic therapy.7e15 We, therefore, recommend that the specific combination antibiotic therapy is one of the main treatment points and should be prescribed as soon as possible when clinical suspicion of Vibrio infection. By evaluating prognostic factors for fatality and major amputation in VNSTI patients, our study further revealed that septic shock requiring vasopressor/inotropic support, severe hypoalbuminemia and elevated serum transaminase level are risk factors for unsatisfactory results (fatality and major amputation). Nearly 70% of patients in this case series had low blood pressure on arrival at emergency

department; however, the proportion of those requiring vasopressor/inotropic support differed. All group 1 patients with septic shock required vasopressor/inotropic support in comparison with 40% of group 2 patients. Group 1 patients exhibited increased need for vasopressor/inotropic support for shock (p Z 0.020), a longer period of ICU stay (p Z 0.039) and a higher rate of comorbidity during hospitalization (p Z 0.024) than group 2 patients, which are all indicative of the clinical severity of septicemia. Even though this seems self-evident, i.e. patients with findings suggestive of more severe infection did worse, we recommend that septic shock patients should be continuously monitored in an intensive care unit and ICU personnel should be prepared for expeditious and vigorous resuscitation.21 Hypoalbuminemia, particularly severe forms with a value less than 2 g/dL, was another important predictor of poor outcome examined in this report. The increased likelihood of poor outcome in acutely ill hypoalbuminemic patients is well recognized in the literature.22e25 Vincent et al. performed a meta-analysis evaluating hypoalbuminemia as an outcome predictor and found that each 1 g/dL decline in serum albumin level significantly increased the incidence of fatality by 137%, morbidity by 89% and prolonged ICU and total hospital stay by 28% and 71%, respectively.24 Sung et al. recommended that a serum albumin concentration of <2.6 g/dL at admission is a significant independent predictor of morbidity and mortality in acutely ill patients.25 The present data revealed no group difference in maximum APACHE II score (p Z 0.112) within 24 h after hospital admission; however, group 1 had a significantly higher rate of severe hypoalbuminemia than group 2 (p Z 0.001). Although the hypoalbuminemia is connected with heightened risk of mortality and morbidity, it is unclear whether it is the cause or the effect of the poor physiologic conditions. It is uncertain whether albumin level correction through parenteral supplement would really help to reduce

Vibrio necrotizing soft-tissue infection

Figure 2 Patient 5 in group 2 was a 71-year-old retired man who suffered from progressing painful swelling of both hands secondary to contact with sea water. Massive hemorrhagic bullae with superficial skin necrosis were observed over left (A) and right (B) hands, respectively. Photographs taken after completing the initial de ´bridement (C), before the second look surgery (D) and at the final follow-up (E) revealed the serial change of wound condition.

mortality and morbidity; however, further study about the effect of early nutrition and exogenous albumin administration should be considered in these hypoalbuminemic patients with VNSTI.22e25 It is interesting that patients in group 1 had an increased level of ALT (p Z 0.064) and AST (p Z 0.039) than those in group 2. A possible explanation is that transaminase leakage into the bloodstream due to myofibrillar damage elevates ALT/AST levels in a manner similar to creatine phosphokinase (CPK) leakage.26e28 Although little is known about the relationship between the transaminase level and myositic severity, Edge et al. reported that elevated serum ALT and/or AST correlate strongly with elevated serum CPK in myositic patients.26 Many investigations have also revealed that a high serum CPK level is useful for detecting muscle damage in necrotizing soft-tissue infections.15,26e29 Persistent and irreversible muscle damage due to the inflammation in VNSTI may be the underlying cause of deteriorated condition requiring major amputation in

295 group 1 patients. Therefore, serial survey of ALT/AST or CPK level is recommended in such cases of fulminant soft-tissue infection to enhance surgical decision-making. An increased and continuously high ALT/AST/CPK level or gross myonecrosis may indicate major amputation to facilitate local infection control and increase patient survival. Many investigations have highlighted the importance of early surgical de ´bridement for VNSTI13,14,30e32; however, the timing of surgical intervention and the extent of de ´bridement remain controversial. In VNSTI patients, the predominant skin lesions are edema and subcutaneous hemorrhage while hemorrhagic bullae and superficial skin necrosis are often observed in the late stage.5e7,12e15,33e36 Chuang et al. and Miyoshi et al. both demonstrated the characteristic hemorrhagic reaction in animal models by intradermal injection of Vibrio metalloprotease.33e36 These studies demonstrated that bacterial protease degrades collagen in the vascular basement membrane, enhance vascular permeability and cause hemorrhagic damage.36 Red blood cell leakage into soft tissues may provide pathogens with heme iron sources, which further accelerates bacterial growth.37,38 Bacterial overgrowth and tissue devascularization compromise the effect of antibiotics and can then cause a vicious cycle and a rapidly deteriorating clinical situation.13,14,33e39 The authors have observed that limited and scattered petechia usually respond well to specific combination antibiotic therapy; however, expanding purpura always advance to hemorrhagic bullae formation and superficial skin necrosis. Therefore, the occurrence of progressive edema and subcutaneous bleeding should be included among surgical indications, and the preliminary results in this study appear promising. Wong et al. advocated using LRINEC score to clinically detect early cases of necrotizing soft-tissue infection.40,41 The LRINEC scoring system is based on several routine laboratory investigations, including C-reactive protein, total white cell count, hemoglobin and levels of serum sodium, creatinine and glucose.40,41 The Wong study indicated that LRINEC scores of 8,  6 and 5 indicate high, intermediate and low, respectively, risk of necrotizing soft-tissue infections.40,41 The current data revealed that the LRINEC scoring system may not be applicable in early management of VNSTI patients. Even though most VNSTI patients in this series exhibited suspect skin lesions and septic shock on arrival at emergency department, their median LRINEC score classified them as low risk. As noted by Wong et al., clinical acumen remains of paramount importance regardless of LRINEC score.40 When clinical suspicion of VNSTI is high, the present treatment protocol should be initiated immediately to minimize fatalities and avoid needless amputations. Despite the promising preliminary results of applying the proposed treatment protocol to VNSTI, this investigation has several key limitations, including a small number of cases, a wide diversity of Vibrio species, and lack of a placebo-control group. A prospectively randomized placebo-controlled clinical trail to determine its superiority than others is, theoretically, necessary but practically impossible because of the high lethality of this disease entity.

296 Table 4

K.-C. Huang et al. Group comparison of laboratory data

Variable 3

3

Total WBC count (10 /mm ) Differential count (%) Band Neutrophil Band þ neutrophil Lymphocyte Hemoglobin (g/dL) Platelet (103/mm3) C-reactive protein (mg/dL) Creatinine (mg/dL) Glucose (mg/dL) Sodium (meq/L) LRINEC scorec AST (u/L) ALT (u/L) Albumin (g/dL)a <2 S2

Group 1 (n Z 7)

Group 2 (n Z 9)

p-Value

5.5 (1.6, 16.1)

11.7 (5.6, 17.3)

0.026b

0 87 87 6 12.5 134 47.8 1.4 126 136 3 37 22 2.6 1 8

0.125 0.011b 0.007b 0.002b 0.169 0.315 0.874 0.427 0.525 0.112 0.597 0.039b 0.064 0.004b 0.001b

5 72 79 11 11.1 85 49.5 2.9 125 140 4 78 36 1.7 7 0

(0, 23) (41, 87) (64, 89) (9, 24) (9.1, 13.1) (70, 161) (11.8, 166.1) (1.3, 5.3) (93, 229) (137, 142) (1,8) (40, 372) (22, 152) (1.4, 1.9) (100) (0)

(0, 12) (72, 93) (84, 94) (2, 10) (5.1, 14.6) (63, 219) (17, 354.4) (0.8, 4.4) (107, 251) (133, 143) (0, 9) (19, 168) (13, 138) (1.7, 3.8) (11.1) (88.9)

Data are presented as median (min, max) and calculated by Wilcoxon rank sum test. a Data are presented as median (min, max) or frequency (%) and calculated by Wilcoxon rank sum test or Fisher exact test. b The difference is significant (p < 0.05). c LRINEC, laboratory risk indicator for necrotizing fasciitis.

Conclusion For treating such a highly lethal and disabling disease like VNSTI, clinical acumen remains of paramount importance regardless of the APACHE II and LRINEC scores. Expanding purpura in these patients is an ominous sign and may indicate surgical intervention. A serial survey of ALT/AST or CPK levels can clarify the extent of muscle damage and help determine the optimal time of amputation. Severe hypoalbuminemia also serve as poor prognostic factors implicating a high probability of death or major amputation. Further study about the effect of albumin level correction through parenteral supplement on outcome improvement should be considered in these hypoalbuminemic patients with VNSTI.

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Vibrio necrotizing soft-tissue infection

20.

21.

22.

23. 24.

25.

26.

27.

28.

29.

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