Clinical predictors for severe sepsis in patients with necrotizing fasciitis: an observational cohort study in northern Thailand

Figures & data

Figure 1 Study flow.

Abbreviation: NF, necrotizing fasciitis.

Table 1 Organ dysfunction in patients with necrotizing fasciitis and severe sepsis

Organ involved	n (%)
Acute renal failure	136 (57.4)
Respiratory failure	195 (82.3)
Heart failure	8 (3.4)
CNS (delirium)	11 (4.6)

Notes: The data reflect 237 patients and 350 organs. Values are expressed as n (%).

Abbreviation: CNS, central nervous system.

Table 2 Microorganisms in blood and wound cultures of patients with necrotizing fasciitis

Organism	Severe sepsis		Without severe sepsis
	Blood	Wound	Blood	Wound
Gram-positive
Staphylococcus aureus	3 (2.2)	13 (9.7)	2 (0.8)	76 (13.3)
MRSA	2 (1.4)	2 (1.5)	0 (0.0)	7 (1.2)
Coagulase negative staphylococcus	8 (5.7)	14 (10.7)	13 (5.1)	31 (5.4)
Streptococcus pyogenes	4 (2.9)	32 (24.1)	5 (2.0)	84 (14.7)
Other gram-positive	5 (3.6)	4 (3.1)	5 (2.0)	22 (3.9)
Gram-negative
Acinetobacter spp.	2 (1.5)	9 (6.7)	1 (0.4)	27 (4.7)
MDR Acinetobacter spp.	0 (0.0)	2 (1.5)	0 (0.0)	2 (0.4)
Citrobacter spp.	1 (0.7)	2 (1.5)	1 (0.4)	16 (2.8)
Escherichia coli	3 (2.2)	15 (11.3)	1 (0.4)	33 (5.8)
E. coli (ESBLs)	1 (0.7)	2 (1.5)	1 (0.4)	8 (1.4)
Klebsiella pneumoniae	3 (2.2)	2 (1.5)	1 (0.4)	31 (5.5)
K. pneumoniae (ESBLs)	1 (0.7)	1 (0.8)	0 (0.0)	4 (0.7)
Pseudomonas aeruginosa	5 (3.6)	18 (13.4)	3 (1.2)	33 (5.8)
Aeromonas hydrophila	0 (0.0)	0 (0.0)	0 (0.0)	4 (0.7)
Other gram-negative	0 (0.0)	4 (3.0)	0 (0.0)	27 (4.7)

Notes: Of 1,452 patients, the blood culture was not done in 1,052 (72.5%). Positive isolates were found in 69 patients (4.8%), and no bacterium was found in 330 patients (22.7%). Wound culture was carried out with 714 patients (49.2%), and 460 patients showed positive isolated specimens (31.7%); 254 patients (17.5%) had negative wound culture. Values are expressed as n (%).

Abbreviations: ESBL, extended spectrum β lactamase; MDR, multidrug resistant; MRSA, methicillin-resistant Staphylococcus aureus.

Table 3 Demographic characteristics and clinical manifestations in patients with necrotizing fasciitis, with severe sepsis and without severe sepsis (n=1,452)*

Characteristics	Severe sepsis (n = 237)	Without severe sepsis (n = 1,215)	P-value
Sex			0.027
Male	118 (49.8)	700 (57.7)
Female	119 (50.2)	514 (42.3)
Age (years)			<0.001
<60	77 (32.9)	594 (49.3)
≥60	157 (67.1)	611 (50.7)
BMI			0.668
≤18.50	27 (13.1)	162 (14.9)
18.51–29.99	161 (78.2)	844 (77.6)
≥30.00	18 (8.7)	81 (7.5)
Education			<0.001
No education	135 (57.2)	483 (39.8)
Primary education	97 (41.1)	648 (53.4)
Secondary education	4 (1.7)	56 (4.6)
Bachelor’s degree and more	0 (0.0)	26 (2.2)
Occupation			0.010
Elderly who stays at home	129 (54.4)	537 (44.2)
Farmers/laborers	101 (42.6)	612 (50.4)
Officials	7 (3.0)	65 (5.4)
Underlying disease
Diabetes	70 (29.5)	308 (25.4)	0.195
Heart disease	29 (12.3)	61 (5.0)	<0.001
Renal disease	13 (5.5)	30 (2.5)	0.019
Cirrhosis	14 (5.9)	42 (3.5)	0.094
Hypertension	107 (45.2)	406 (33.4)	0.001
Gout	39 (16.5)	100 (8.3)	<0.001
Chronic alcoholism	40 (16.9)	185 (15.2)	0.556
Wound appearance
Soft tissue swell	193 (81.4)	1,018 (83.8)	0.390
Erythema	154 (65.0)	587 (48.3)	<0.001
Bleb	133 (56.1)	489 (40.3)	<0.001
Necrosis	73 (30.8)	317 (26.1)	0.149
Gangrene	8 (3.4)	29 (2.4)	0.368
Severe pain	222 (93.7)	1,045 (86.1)	0.001
Site of wound			0.384
Head and neck	1 (0.4)	5 (0.4)
Trunk	7 (3.0)	19 (1.6)
Upper limb	47 (19.8)	213 (17.5)
Lower limb	175 (73.9)	952 (78.3)
Fournier’s gangrene	6 (2.5)	23 (1.9)
Multiple sites	1 (0.4)	3 (0.3)
Hospital			0.718
Chiang Rai	121 (51.1)	654 (53.8)
Kamphaeng Phet	95 (40.1)	455 (37.5)
Phayao	21 (8.8)	106 (8.7)

Notes: values are n (%).

* Some variables have missing data, therefore, the total number of patients in each group maybe different from the number that shown in the title.

Abbreviation: BMI, body mass index.

Table 4 Laboratory findings, vital sign measurements, and outcomes in patients with necrotizing fasciitis, with severe sepsis and without severe sepsis (n=1,452)

Characteristics	Severe sepsis (n=237)	Without severe sepsis(n=1,215)	P-value
Laboratory on admission
WBC (/mm^3)	17,755.7±10,808.7	16,897.8±8,782.5	0.609
PMN (%)	85.5±10.2	81.5±11.9	<0.001
Creatinine (mg/dL)	2.9±1.7	1.7±1.3	<0.001
Bicarbonate (mmol/L)	17.2±5.4	22.7±4.6	<0.001
Total protein (g/dL)	5.7±1.0	6.6±1.0	<0.001
Laboratory 48–72 hours
WBC (/mm^3)	16,462.0±8,182.7	13,509.9±7,700.0	<0.001
PMN (%)	84.5±12.8	76.2±14.5	<0.001
Creatinine (mg/dL)	2.8±1.9	1.9±1.6	<0.001
Bicarbonate (mmol/L)	23.4±28.6	22.4±5.1	0.002
Total protein (g/dL)	5.2±1.2	6.2±1.0	<0.001
Vital sign on admission
Body temp (°C)	37.2±1.0	37.3±0.9	0.183
Pulse (/minute)	96.6±17.2	89.6±14.6	<0.001
Respiratory rate (/minute)	21.5±5.1	20.3±1.7	<0.001
Systolic blood pressure (mmHg)	103.5±26.2	120.6±22.5	<0.001
Diastolic blood pressure (mmHg)	62.2±15.8	72.2±13.5	<0.001
Vital sign 48–72 hours
Body temp (°C)	37.5±1.1	37.2±0.7	<0.001
Pulse (/minute)	96.0±19.6	86.1±12.3	<0.001
Respiratory (/minute)	17.9±8.0	19.9±2.6	<0.001
Systolic blood pressure (mmHg)	117.1±21.4	121.3±16.7	0.002
Diastolic blood pressure (mmHg)	69.0±14.6	73.8±10.5	<0.001
Treatment and outcome
I&D	6 (2.5)	38 (3.1)	0.836
Debridement	152 (64.1)	796 (65.5)	0.709
Fasciotomy	95 (40.1)	525 (43.3)	0.389
Amputation	32 (13.5)	95 (7.8)	0.008
Antibiotic use in admission date			0.052
Cephalosporin + clindamycin	81 (34.2)	409 (33.7)
Cefazolin + cloxacillin + clindamycin	21 (8.9)	54 (4.5)
Cephalosporin + cloxacillin	16 (6.8)	46 (3.8)
Cloxacillin + clindamycin	25 (10.6)	189 (15.6)
Augmentin	16 (6.8)	164 (13.5)
Cloxacillin	12 (5.1)	142 (11.7)
Clindamycin	9 (3.8)	38 (3.1)
Other	57 (24.1)	171 (14.1)
Activity
Broad-spectrum antibiotic	126 (53.2)	539 (44.4)	0.015
In-hospital mortality rate	165 (69.6)	66 (5.5)	<0.001
Entire 28 days mortality rate	18 (7.6)	2 (0.2)
Length of hospitals stay (days) Median (IQR)	9 (3–17)	8 (5–14)	0.805

Note: Values are mean ± standard deviation or n (%).

Abbreviations: I&D, incision and drainage; PMN, polymorphonuclear neutrophils; WBC, white blood cell count; IQR, interquartile range.

Table 5 Subgroup analysis of age and underlying between male and female in patients with necrotizing fasciitis (n=1,438–1,451)

Characteristics	Male	Female	P-value
Age (year)			0.005
≥60	406 (50.1)	361 (57.6)
<60	405 (49.9)	266 (42.4)
Underlying			<0.001
Diabetes
Yes	182 (22.3)	195 (30.9)
No	636 (77.7)	437 (69.1)
Heart disease			0.011
Yes	39 (4.8)	51 (8.1)
No	778 (95.2)	580 (91.9)
Renal disease			0.086
Yes	30 (3.7)	13 (2.1)
No	787 (96.3)	620 (97.9)
Cirrhosis			<0.001
Yes	45 (5.5)	11 (1.7)
No	773 (94.5)	622 (98.3)
Hypertension			<0.001
Yes	243 (29.7)	269 (42.5)
No	575 (70.3)	364 (57.5)
Gout			<0.001
Yes	113 (13.8)	26 (4.1)
No	705 (86.2)	607 (95.9)

Table 6 Data shown univariable risk regression analysis of severe sepsis demonstrated by risk ratio, 95% confidence interval and P-value

Risk factors	RR	95% CI	P–value
Female	1.30	0.86–1.98	0.213
Age ≥60	1.78	1.42–2.24	<0.001
BMI ≤18.50	0.89	0.61–1.31	0.556
BMI ≥30.00	1.13	0.59–2.17	0.720
Primary education	0.66	0.58–0.75	<0.001
Secondary education	0.40	0.14–1.10	0.075
Bachelor’s degree and more	1.11	2.31–5.33	<0.001
Elderly who stay at home	1.40	1.21–1.64	<0.001
Famers/labors	0.77	0.68–0.87	<0.001
Official	0.58	0.35–0.96	0.033
Diabetes	1.19	0.79–1.78	0.401
Heart disease	2.12	1.83–2.44	<0.001
Renal disease	1.90	0.97–3.73	0.062
Cirrhosis	1.57	0.81–3.01	0.180
Hypertension	1.51	1.31–1.74	<0.001
Gout	1.86	1.72–2.21	<0.001
Chronic alcoholism	1.11	0.85–1.45	0.458
Swell	0.87	0.59–1.29	0.494
Erythema	1.78	1.17–2.70	0.007
Bleb	1.71	1.40–2.09	<0.001
Skin necrosis	1.21	1.06–1.38	0.005
Gangrene	1.34	0.95–1.88	0.099
Severe pain	2.15	1.74–2.65	<0.001
Head and neck	1.02	0.14–7.36	0.983
Trunk	1.67	1.32–2.12	<0.001
Upper limb	1.13	0.89–1.14	0.305
Lower limb	0.81	0.77–0.86	<0.001
Fournier’s gangrene	1.27	0.87–1.87	0.213
Multiple site	1.53	0.71–3.34	0.280
Total protein <6 (g/dL)	2.97	2.09–4.21	<0.001
Broad-spectrum antibiotic	1.33	1.08–1.65	0.007

Abbreviations: BP, blood pressure; BMI, body mass index; CI, confidence interval; nd, not defined; PMN, polymorphonuclear neutrophils; RR, relative risk ratio; WBC, white blood cell.

Table 7 Summarized independent predictors of severe sepsis in patients with necrotizing fasciitis using multivariable analysis generalized linear model with step backward method (n=1,452)

Risk factors	RR	95% CI	P–value
Female	1.51	1.04–2.20	0.032
Age >60 years	1.25	0.98–1.61	0.076
Diabetes	1.40	1.25–1.58	<0.001
Heart disease	1.31	1.15–1.49	<0.001
Bleb	1.47	1.32–1.63	<0.001
Necrosis	1.45	1.34–1.57	<0.001
Total protein <6 g/dL	2.67	1.60–4.47	<0.001

Abbreviations: CI, confidence interval; RR, relative risk ratio.