Non-purulent skin and soft tissue infections: predictive power of a severity score and the appropriateness of treatment in a prospective cohort

Figures & data

Figure 1. The modified Dundee classification. ^aqSOFA: quick Sequential Organ Failure Assessment score. ^bNEWS2: National Early Warning Score 2. Total NEWS ≥5 or 3 points in one variable. ^cNSTI: Necrotising Soft Tissue Infection. ^dSIRS: Systemic Inflammatory Response Syndrome. ^eSignificant co-morbid conditions: Peripheral vascular disease, chronic venous insufficiency, morbid obesity (BMI ≥40).

Table 1. Local antimicrobial treatment recommendations for non-purulent SSTIs.

Class I
Appropriate	Oral penicillin or penicillinase-resistant penicillin. If allergic to penicillin: Oral clindamycin, macrolides or 1st gen. cephalosporin (non-immediate penicillin allergy).
Over-treatment	Any intravenous antibiotics or an oral antibiotic with unnecessary broad spectrum, which includes the following: Clindamycin^a, macrolides, any cephalosporins, amoxicillin/clavulanate, any fluoroquinolone, linezolid, tedizolid, any tetracycline.
Under-treatment	Oral or intravenous therapy with insufficient activity against β-haemolytic Streptococci (BHS), including ciprofloxacin.
Class II and class III
Appropriate	I.v. penicillin or penicillinase-resistant penicillin. If allergic to penicillin: Clindamycin or macrolide or 1st gen. cephalosporin (non-immediate penicillin allergy).
Over-treatment	Intravenous therapy with unnecessary broad-spectrum coverage, including clindamycin^a piperacillin/tazobactam, any carbapenems, vancomycin, teicoplanin, tigecycline, linezolid, tedizolid, daptomycin, quinupristin/dalfopristin, second or higher generation of cephalosporines. Any fluoroquinolone. Oral linezolid or tedizolid.
Under-treatment	Any oral antibiotic or intravenous therapy with inadequate coverage against BHS, except for linezolid or tedizolid which would be deemed over treatment.
Class IV
Appropriate	Intravenous therapy against S. aureus and S. pyogenes/BHS, anaerobes and Gram-negative bacteria, which includes carbapenems and piperacillin/tazobactam. Should include a protein synthesis-inhibitor (clindamycin or linezolid) if S. pyogenes/BHS or Clostridium spp. are suspected^b.
Under-treatment	Any oral antibiotics, or intravenous therapy with inadequate coverage against potential pathogens and their toxins.

^a If no known penicillin allergy registered.

^b Any of the following: Suspected streptococcal infections: Shock/hypotension; toxaemic appearance; streptococcal infections in household contacts; extremity location. Suspected clostridial myonecrosis: Posttraumatic or postsurgical infections with severe pain and gas in soft tissue (crepitus or on radiology) and systemic toxicity. In head/neck, abdominal or genital location a protein synthesis-inhibitor is not necessary for fulfilling appropriateness.

Table 2. Demographics and clinical characteristics by severity class^a.

Characteristics	All cases	Severity class
		I	II	III	IV
	n = 219 (%)	69 (32)	34 (15)	62 (28)	54 (25)
Demographics
Age (years), median (range)	55.3 (18.7–94.1)	49.0 (18.7–89.5)	61.4 (24.1–90.8)	54.8 (19.7–94.1)	62.0 (26.4–88.3)
Male gender	128 (58.4)	43 (62.3)	16 (47.1)	38 (55.1)	31 (57.4)
Weight in kg, median (range)	86.0 (54–187)	85.0 (55–140)	90.0 (54–187)	85.0 (54–172)	88.0 (58–165)
Underlying condition
Cardiovascular disease	83 (37.9)	14 (20.3)	19 (55.9)	25 (40.3)	25 (46.3)
Chronic oedema	75/214 (35.0)	0/68 (0.0)	29 (85.3)	23/61 (37.7)	23/51 (45.1)
Diabetes	27 (12.3)	4 (5.8)	4 (11.8)	10 (16.1)	9 (16.7)
Immunocompromised^b	21 (9.6)	6 (8.7)	2 (5.9)	5 (8.1)	8 (14.8)
Comorbidity in total^c	145 (66.2)	26 (37.7)	34 (100.0)	43 (69.4)	42 (77.8)
IDU	14/218 (6.4)	7 (10.1)	0/33 (0.0)	2 (3.2)	5 (9.3)
Alcohol abuse	10/217 (4.6)	2 (2.9)	2 (5.9)	4 (6.5)	2/52 (3.8)
Final diagnosis
Cellulitis	200 (91.3)	69 (100)	33 (97.1)	62 (100)	36 (66.7)
NSTI^d	19 (8.7)	0 (0.0)	1 (2.9)	0 (0.0)	18 (33.3)
Localisation
Head/neck	48 (21.9)	27 (39.1)	0 (0.0)	16 (25.8)	5(9.3)
Upper extremities	38 (17.3)	14 (20.3)	4 (11.8)	9 (14.5)	11 (20.4)
Lower extremities	123 (56.2)	28 (40.6)	29 (85.3)	34 (54.9)	32 (59.2)
Other	10 (4.6)	0 (0.0)	1 (2.9)	3 (4.8)	6 (11.1)
β-haemolytic Streptococci+^e	175 (79.9)	54 (78.3)	31 (91.2)	55 (88.7)	35 (64.8)
Blood cultures (positive)^f	12/207 (5.8)	0/61 (0.0)	0/33 (0.0)	2/60 (3.3)	10/53 (18.9)
Other characteristics
TBSA%, median (IQR)^g	3 (1–5)	2 (1–3.5)	5 (3–6.25)	3 (2–5)	3 (1.75–5)
NRS, median (IQR)^h	2 (1–6)	2 (1–5)	2 (1–5)	2 (1–5)	6 (2–8)
Leucocytes, median (IQR)^i	12.0 (9.1–15.3)	10.1 (8.4–12.3)	10.5 (8.9–13.4)	13.7 (11.0–16.8)	13.1 (10.1–17.0)
CRP, median (IQR)^j	99 (45–193)	91 (48–170)	113 (58–224)	100 (40–198)	123 (41–231)
PCT, median (IQR)^k	0.26 (0.11–1.20)	0.13 (0.1–0.25)	0.31 (0.12–1.31)	0.31 (0.10–5.44)	0.92 (0.25–6.85)

^a The data are presented as numbers or numbers/evaluable cases. Percentages in parentheses, if not otherwise specified.

^b Immunodeficiency (e.g. hypogammaglobulinaemia, HIV) or immunosuppressive treatment, including cytostatic treatment within the last 6 months, or steroids the last month.

^c Diabetes mellitus, malignancy, immunosuppression, rheumatic disease or chronic disease of the cardiovascular system, lungs, gastrointestinal tract, liver, pancreas, kidney or nervous system.

^d NSTI: Necrotising soft tissue infection.

^e β-haemolytic Streptococci+: Evidence of β-haemolytic streptococcal aetiology (growth in blood culture, sterile tissue, swab from affected site, positive streptococcal antibodies or successful penicillin monotherapy).

^f The microbes cultured were; Streptococcus pyogenes (5), S. dysgalactiae subsp. equisimilis (4), S. agalactiae (1), Staphylococcus aureus (1). In one case Klebsiella oxytoca and Enterobacter spp. were found in co-culture.

^g Total body surface area in per cent.

^h Numerical Rating Scale: An analogue verbal scale for pain measurement. Scale 0–10. Ten being the most severe pain.

ⁱ Unit: 10⁹/L.

^j C-reactive protein (mg/L).

^k Procalcitonin (µg/L).

Table 3. Treatment and outcome by severity class^a.

Characteristics	All cases	Severity class
		I	II	III	IV
	n = 219 (%)	69 (32)	34 (15)	62 (28)	54 (25)
ICU stay^b	52 (23.7)	1 (1.4)	4 (11.8)	12 (19.4)	35 (64.8)
Vasopressor	13 (5.9)	0 (.00)	1 (2.9)	1 (1.6)	11 (20.4)
Surgery during stay	31 (14.2)	3 (4.3)	4 (11.8)	1 (1.6)	23 (42.6)
Length of stay, median (range)	3.0 (1–40)	2.0 (1–14)	4.0 (1–33)	3.5 (1–21)	7.0 (1–40)
Duration of iv AB^c, median (range)	3.0 (1–42)	2.0 (1–11)	4.0 (1–42)	4.0 (1–21)	7.0 (1–33)
Total duration of AB^c, median (range)	12 (1–104^d)	10.0 (6–19)	12.0 (8–42)	13.0 (8–36)	15.5 (1–104^d)
Broad-spectrum AB^c, during stay^e	58 (26.5)	6 (8.7)	4 (11.8)	15 (24.2)	33 (61.1)
Treatment escalation during stay^f	48 (21.9)	13 (18.8)	6 (17.6)	14 (22.6)	15 (27.8)
Treatment de-escalation during stay^f	46 (21.0)	7 (10.1)	5 (14.7)	11 (17.7)	23 (42.6)
Toxin-inhibitors (protein synthesis inhibitors)^g	124 (56.6)	28 (40.6)	13 (38.2)	36 (58.1)	47 (87.0)
Diarrhoea (during or after stay)	39/192 (20.3)	11/64 (17.2)	10/31 (32.3)	10/57 (17.5)	8/40 (20.0)
Complicated course^h	60 (27.4)	3 (4.3)	7 (20.6)	13 (21.0)	37 (68.5)
Nosocomial infections	12/214 (5.6)	0 (0.0)	1 (2.9)	3/61 (4.9)	8/50 (16.0)
Rash/allergic reactions	5/218 (2.3)	1 (1.4)	0 (0.0)	2 (3.2)	4/53 (7.5)
Relapse	24/204 (11.8)	7/65 (10.8)	5/33 (15.2)	10/59 (16.9)	2/47 (4.3)
Mortality	3 (1.4)	0 (0.0)	0 (0.0)	0 (0.0)	3 (5.6)

^a The data are presented as numbers or numbers/evaluable cases. Percentages in parentheses, if not otherwise specified.

^b Stay in intensive care unit or high dependency unit.

^c AB: Antibiotic treatment.

^d Very skewed because one patient was treated for a prolonged period after surgery (class IV, NSTI).

^e Defined as gram-negative coverage for at least 24 h.

^f Antibiotic treatment escalation defined as addition of an antimicrobial agent or other change resulting in broader antimicrobial spectrum. De-escalation defined as discontinuation of an antimicrobial agent or alteration to regimen with narrower antimicrobial spectrum.

^g Includes only clindamycin and linezolid.

^h Presence of bacteraemia, surgical escalation (the first surgery was performed >24 h after start of treatment, or a later surgery was more extensive than the preceding), admission to ICU or high dependency unit, or death within 30 days.

Figure 2. Treatment appropriateness according to severity class. (a) Treatment appropriateness according to local treatment recommendations. (b) Treatment appropriateness according to IDSA guidelines. (c) Treatment appropriateness according to CREST guidelines.