Sequence type 8 as an emerging clone of methicillin-resistant Staphylococcus aureus causing bloodstream infections in Taiwan

Figures & data

Figure 1. The change in the proportion of ST8, ST239, ST59, ST45, and other STs among 281 methicillin-resistant Staphylococcus aureus blood isolates by years (a) and by onset setting (b). Abbreviations are as follows: ST, sequence type; CA, community associated; HACO, healthcare-associated, community onset; HA, hospital acquired.

Table 1. Comparisons of clinical characteristics and outcomes of 281 patients with methicillin-resistant Staphylococcus aureus bacteraemia by sequencing types.

	Total (n = 281)	ST8 (n = 52)	ST239 (n = 87)	ST59 (n = 66)	ST45 (n = 29)	Other STs^a (n = 47)	P-value^b
							Overall	ST8 vs. ST239	ST8 vs. ST59	ST8 vs. ST45	ST8 vs. Other STs
Demographics
Age, y, median (IQR)	68 (58–81)	75 (61.5–83.5)	66 (56–83)	68.5 (60–79)	68 (60–79)	67 (51–77)	0.09
Gender, Male	178 (63.4)	34 (65.4)	61 (70.1)	41 (62.1)	18 (62.1)	24 (51.1)	0.30
Underlying diseases or conditions
Cardiovascular diseases	93 (33.1)	16 (30.8)	24 (27.6)	28 (42.4)	10 (34.5)	16 (31.9)	0.41
Respiratory diseases	57 (20.3)	12 (23.1)	24 (27.6)	11 (16.7)	5 (17.2)	5 (10.6)	0.17
Neurology diseases	51 (18.2)	14 (26.9)	15 (17.2)	6 (9.1)	4 (13.8)	12 (25.5)	0.07
Hepatobiliary diseases	57 (20.3)	9 (17.3)	16 (18.4)	13 (19.7)	5 (17.2)	14 (29.8)	0.51
Chronic renal impairment	91 (32.4)	17 (32.7)	30 (34.5)	20 (30.0)	9 (31.0)	15 (31.9)	0.99
Chronic dialysis	44 (15.7)	8 (15.4)	14 (16.1)	9 (13.6)	5 (17.2)	8 (17.0)	0.99
Rheumatology diseases	21 (7.5)	3 (5.8)	8 (9.2)	5 (7.6)	1 (3.5)	4 (8.5)	0.90
Diabetes mellitus	92 (32.7)	26 (50.0)	23 (26.4)	18 (27.3)	9 (31.0)	16 (34.0)	0.05	0.04	0.09	0.80	0.90
Solid tumour	110 (39.2)	16 (30.8)	30 (34.5)	36 (54.6)	16 (55.2)	12 (25.3)	0.003^h	>0.99	0.08	0.29	>0.99
Hematological malignancy	14 (5.0)	0 (0)	9 (10.3)	3 (4.6)	1 (3.5)	1 (2.1)	0.07
Charlson comorbidity index, median (IQR)	4 (2–6)	4 (2–6)	4 (2–6)	5 (3–7)	4 (2–6)	4 (2–6)	0.32
Long-term care facility	33 (11.7)	13 (25.0)	9 (10.3)	4 (6.1)	4 (13.8)	3 (6.4)	0.02	0.09	0.02	>0.99	0.04
Vascular device at onset^c	137 (48.8)	14 (26.9)	61 (70.1)	30 (45.5)	14 (48.3)	18 (48.8)	<0.001	<0.001	0.38	0.55	>0.99
Severity
Shock	75 (26.7)	15 (28.9)	33 (37.9)	12 (18.2)	6 (20.7)	9 (19.2)	0.04^i	>0.99	>0.99	>0.99	>0.99
Pitt bacteremia score, median (IQR)	1 (0–3)	1 (0–3)	2 (1–5)	1 (0–2)	1 (0–3)	1 (0–3)	0.02^j	0.84	>0.99	>0.99	>0.99
Infection focus
Primary	105 (37.4)	24 (46.2)	25 (28.7)	24 (36.4)	12 (41.4)	20 (42.6)	0.26
Catheter-related	71 (25.3)	5 (9.6)	32 (36.8)	15 (22.7)	10 (34.5)	9 (19.2)	0.003	0.003	0.98	0.12	>0.99
Device-related^d	10 (3.4)	2 (3.9)	1 (1.2)	3 (4.6)	0 (0)	4 (8.5)	0.21
Skin and soft tissue	49 (17.4)	13 (25.0)	12 (13.8)	9 (13.6)	3 (10.3)	12 (25.5)	0.17
Pleuropulmonary^e	39 (13.9)	6 (11.5)	18 (20.7)	6 (9.1)	2 (6.9)	7 (14.9)	0.23
Native osteoarticular	7 (2.5)	1 (1.9)	2 (2.3)	3 (4.6)	1 (3.45)	0 (0)	0.64
Endocarditis	14 (5.0)	4 (7.7)	5 (5.8)	3 (4.6)	1 (3.5)	1 (2.1)	0.82
Septic thrombophlebitis	6 (2.1)	1 (1.9)	2 (2.3)	2 (3.0)	1 (3.5)	0 (0)	0.85
Deep infection^f	10 (3.6)	4 (7.7)	1 (1.2)	4 (6.1)	0 (0)	1 (2.1)	0.17
Management
Effective antibiotics within 48 h after onset	197 (70.1)	35 (67.3)	66 (75.9)	46 (69.7)	22 (75.9)	28 (59.6)	0.34
Glycopeptide as the first agents	248 (88.3)	45 (86.5)	80 (92.0)	60 (90.9)	26 (89.7)	37 (78.7)	0.21
Source control^g	140/176 (79.6)	21/28 (75.0)	56/62 (93.2)	28/42 (66.7)	14/17 (82.4)	21/27 (77.8)	0.05	0.93	>0.99	>0.99	>0.99
Infectious disease consultation	191 (68.0)	30 (57.7)	71 (81.6)	39 (59.1)	19 (65.5)	32 (68.1)	0.01	0.03	>0.99	>0.99	>0.99
Outcomes
Persistent bacteremia > 7 days	34 (12.1)	2 (3.9)	21 (24.1)	4 (6.1)	2 (6.9)	5 (10.6)	0.002	0.03	>0.99	>0.99	>0.99
In-hospital mortality	113 (40.2)	16 (30.8)	49 (56.3)	24 (36.4)	10 (34.5)	14 (29.8)	0.007	0.03	>0.99	>0.99	>0.99

Data are presented as no. (%) unless otherwise indicated.

Abbreviations: ST, sequence type; IQR, interquartile range.

^a 14 STs are identified in 47 isolates and listed as follows: ST30 (n = 14), ST5 (6), ST508 (4), ST338 (3), ST15 (2), ST188 (2), ST398 (2), ST573 (2), ST965 (2), ST3235 (2), ST72 (1), ST89 (1), ST789 (1), ST1232 (1), and non-typable (4).

^b Pairwise comparisons with Bonferroni adjustment was performed if overall comparisons were statistically significant (P<0.05), and only pairwise comparisons among ST8 vs. different STs were reported. The detailed statistics are shown in Supplementary Table 2. Bold type indicates P ≤ 0.05.

^c Vascular devices consisted of any type of central vascular catheters, vascular grafts, peripherally inserted central catheters, and any cardiac devices, including heart valves, implantable pacemakers, automated implantable cardioverter-defibrillators, left ventricular assist devices, and extracorporeal membrane oxygenation.

^d Device-related infections were defined as infections due to any devices other than vascular device, including prosthetic joints, orthostatic implants, biliary stents, urinary stents, draining tubes, percutaneous feeding tubes, intrathecal catheters, peritoneal dialysis catheters, and oesophageal stents.

^e Pleuropulmonary infections included pneumonia, necrotizing pneumonia, lung abscess, and empyema.

^f Deep infections were not related to surgery or prosthesis.

^g Source control included removal of vascular catheters and foreign devices as well as procedures such as drainage of skin, deep or visceral abscesses, debridement of infected tissue, and operative joint irrigation and drainage.

^h Pairwise comparison, P < 0.05: ST59 vs. other STs.

ⁱ No pairwise comparison showed statistical significance (P < 0.05).

^j Pairwise comparison, P < 0.05: ST239 vs. ST59.

Figure 2. Molecular characteristics of 52 ST8 methicillin-resistant Staphylococcus aureus blood isolates. Spa types t121, t574, t2558, and t3081 are variants of t008. Plus symbols indicate detection of a given gene, and black squares indicate resistance to a given antibiotic. Abbreviations are as follows: PFGE, pulsed-field gel electrophoresis; no., number; SCCmec, staphylococcal cassette chromosome mec; PVL, Pantone-Valentine leucocidin-encoding genes; ACME, arginine catabolic mobile element-encoding genes.

Table 2. Comparisons of in vitro susceptibilities of methicillin-resistant Staphylococcus aureus bloodstream isolates among different sequencing types (ST) to key antimicrobial agents tested.

	Total (n = 281)	ST8 (n = 52)	ST239 (n = 87)	ST59 (n = 66)	ST45 (n = 29)	Other STs^a (n = 47)	P-value^b
							Overall	ST8 vs. ST239	ST8 vs. ST59	ST8 vs. ST45	ST8 vs. Other STs
Vancomycin
Range (mg/L)	0.5–2	0.5–1	0.5–2	0.5–1	0.5–1	0.5–1
MIC50/MIC90 (mg/L)	1/1	1/1	1/2	1/1	1/1	1/1
S, n (%)	281 (100.0)	52 (100.0)	87 (100.0)	66 (100.0)	29 (100.0)	47 (100.0)	>0.99
Daptomycin
Range (mg/L)	0.5–4	0.5–0.5	0.5–4	0.5–0.5	0.5–0.5	0.5–0.5
MIC50/MIC90 (mg/L)	0.5/0.5	0.5/0.5	0.5/1	0.5/0.5	0.5/0.5	0.5/0.5
S, n (%)	279 (99.3)	52 (100.0)	85 (97.7)	66 (100.0)	29 (100.0)	47 (100.0)	0.34
Linezolid
Range (mg/L)	1–4	2–2	1–2	2–4	2–4	2–4
MIC50/MIC90 (mg/L)	2/2	2/2	2/2	2/2	2/2	2/2
S, n (%)	281 (100.0)	52 (100.0)	87 (100.0)	66 (100.0)	29 (100.0)	47 (100.0)	>0.99
Gentamicin
Range (mg/L)	2–>16	2–>16	2–>16	2–>16	2–>16	2–>16
MIC50/MIC90 (mg/L)	8/>16	2/2	32/>16	2/>16	2/16	2/>16
S, n (%)	137 (48.8)	50 (96.2)	3 (3.5)	38 (57.6)	16 (55.2)	30 (63.8)	<0.001	<0.001	<0.001	<0.001	<0.001
Rifampin
Range (mg/L)	0.5–>4	0.5–0.5	0.5–>4	0.5–0.5	0.5–0.5	0.5–2
MIC50/MIC90 (mg/L)	0.5/0.5	0.5/0.5	0.5/0.5	0.5/0.5	0.5/0.5	0.5/2
S, n (%)	270 (96.1)	52 (100.0)	82 (94.3)	66 (100.0)	29 (100.0)	41 (87.2)	0.002	0.85	>0.99	>0.99	0.009
TMP/SMX
Range (mg/L)	0.5–>4	0.5–0.5	0.5–>4	0.5–>4	0.5–0.5	0.5–>4
MIC50/MIC90 (mg/L)	0.5/>4	0.5/0.5	>4/>4	0.5/0.5	0.5/0.5	0.5/1
S, n (%)	193 (68.7)	52 (100.0)	4 (4.6)	64 (97.0)	29 (100.0)	44 (93.6)	<0.001	<0.001	>0.99	>0.99	0.73
Tetracycline
Range (mg/L)	2–>16	2–>16	2–>16	2–>16	2–>16	2–>16
MIC50/MIC90 (mg/L)	16/>16	2/2	>16/>16	16/>16	>16/>16	2/>16
S, n (%)	138 (49.1)	51 (98.1)	5 (5.8)	31 (47.0)	13 (44.8)	38 (80.9)	<0.001	<0.001	<0.001	<0.001	0.19
Moxifloxacin
Range (mg/L)	0.25–>4	0.25–>4	0.25–>4	0.25–0.25	0.25–>4	0.25–>4
MIC50/MIC90 (mg/L)	2/4	2/2	4/>4	0.25/0.25	2/2	0.25/4
S, n (%)	118 (42.0)	1 (1.9)	4 (4.6)	66 (100.0)	12 (41.4)	35 (74.5)	<0.001	>0.99	<0.001	<0.001	<0.001
Clindamycin
Range (mg/L)	0.5–>2	0.5–>2	0.5–>2	0.5–>2	0.5–>2	0.5–>2
MIC50/MIC90 (mg/L)	>2/>2	0.5/0.5	>2/>2	>2/>2	0.5/0.5	0.5/>2
S, n (%)^c	97 (34.5)	48 (92.3)	4 (4.6)	5 (7.6)	17 (58.6)	23 (48.9)	<0.001	<0.001	<0.001	<0.001	<0.001
Erythromycin
Range (mg/L)	0.25–>4	0.25–>4	0.5–>4	0.25–>4	0.25–>4	0.25–>4
MIC50/MIC90 (mg/L)	>4/>4	>4/>4	>4/>4	>4/>4	0.5/>4	>4/>4
S, n (%)^c	56 (19.9)	9 (17.3)	4 (4.6)	5 (7.6)	17 (58.6)	21 (44.7)

^a Of 47 isolates, 14 STs were identified and listed as follows: ST30 (n = 14), ST5 (6), ST508 (4), ST338 (3), ST15 (2), ST188 (2), ST398 (2), ST573 (2), ST965 (2), ST3235 (2), ST72 (1), ST89 (1), ST789 (1), ST1232 (1), and non-typable (4).

^b Only pairwise comparisons with Bonferroni adjustment among ST8 vs. different STs were reported if overall comparisons were statistically significant (P<0.05).

^c For isolates that tested erythromycin resistant and clindamycin susceptible or intermediate, testing for inducible clindamycin resistance by broth microdilution was performed to determine susceptibility to clindamycin.

Table 3. Univariable and multivariable logistic regression analyses of predictors for in-hospital mortality of patients with methicillin-resistant Staphylococcus aureus bacteraemia

Predictors^a	Death (n = 113)	Survival (n = 168)	Univariable OR (95% CI)	P	Multivariable^b OR (95% CI)	P
Demographics
Age, y, median (IQR)	67 (58–81)	70 (58–81)	1.00 (0.98–1.01)	0.83
Gender, male	70 (62.0)	108 (64.3)	0.90 (0.55–1.48)	0.69
Onset
Community associated	15 (13.3)	38 (22.6)	as reference
Healthcare-associated, community onset	37 (32.7)	58 (34.5)	1.62 (0.78–3.34)	0.20
Hospital acquired	61 (54.0)	72 (42.9)	2.15 (1.08–4.27)	0.03
Underlying diseases or conditions
Cardiovascular diseases	39 (34.5)	54 (32.1)	1.11 (0.67–1.84)	0.68
Respiratory diseases	25 (22.1)	32 (19.1)	1.21 (0.67–2.17)	0.53
Neurology diseases	24 (21.2)	27 (16.1)	1.40 (0.76–2.59)	0.27
Hepatobiliary diseases	26 (23.0)	31 (18.5)	1.32 (0.73–2.37)	0.35
Chronic renal impairment	33 (29.2)	58 (34.5)	0.78 (0.47–1.31)	0.35
Rheumatology diseases	10 (8.9)	11 (6.6)	1.39 (0.57–3.38)	0.69
Diabetes mellitus	31 (27.4)	61 (36.3)	0.66 (0.39–1.11)	0.12
Solid tumour	48 (42.5)	62 (36.9)	1.26 (0.78–2.06)	0.35
Haematological malignancy	6 (5.3)	8 (4.8)	1.12 (0.38–3.32)	0.84
Charlson comorbidity index, median (IQR)	4 (3–6)	4 (2–6)	1.03 (0.94–1.13)	0.52
Chronic dialysis	13 (11.5)	31 (18.5)	0.57 (0.29–1.15)	0.12
Long-term care facility	13 (11.5)	20 (11.9)	0.96 (0.46–2.02)	0.92
Vascular device at onset	66 (58.4)	71 (42.3)	1.92 (1.18–3.11)	0.008
Severity
Shock	53 (46.9)	22 (13.1)	5.86 (3.28–10.48)	<0.001	3.16 (1.52–6.60)	0.002
Pitt bacteraemia score, median (IQR)	3 (1–5)	1 (0–2)	1.43 (1.27–1.62)	<0.001	1.26 (1.10–1.45)	0.001
Infection focus
Primary	43 (38.1)	62 (36.9)	1.05 (0.64–1.72)	0.85
Catheter-related	29 (25.7)	42 (25.0)	1.04 (0.60–1.79)	0.90
Device-related	3 (2.7)	7 (4.2)	0.63 (0.16–2.48)	0.51
Skin and soft tissue	13 (11.5)	36 (21.4)	0.48 (0.24–0.95)	0.03	0.39 (0.18–0.87)	0.02
Pleuropulmonary	22 (19.5)	17 (10.1)	2.15 (1.08–4.26)	0.03
Native osteoarticular	1 (0.9)	6 (3.6)	0.24 (0.03–2.03)	0.19
Endocarditis	8 (7.1)	6 (3.6)	2.06 (0.69–6.10)	0.19
Septic thrombophlebitis	2 (1.8)	4 (2.4)	0.74 (0.13–4.10)	0.73
Deep abscess	2 (1.8)	8 (4.8)	0.36 (0.08–1.73)	0.20
Management
Effective antibiotics within 48 h after onset	77 (68.1)	120 (71.4)	0.86 (0.51–1.44)	0.56
Glycopeptide as the first agents	96 (85.0)	152 (90.5)	0.59 (0.29–1.23)	0.16
Source control	60 (82.7)	80 (75.5)	1.95 (0.87–4.35)	0.10
ID consultation	82 (72.6)	109 (64.9)	1.43 (0.85–2.40)	0.18
Sequence types
ST8	16 (14.2)	36 (21.4)	as reference
ST239	49 (43.4)	38 (22.6)	2.90 (1.40–5.99)	0.004
ST59	24 (21.2)	42 (25.0)	1.29 (0.59–2.79)	0.52
ST45	10 (8.9)	19 (11.3)	1.18 (0.45–3.11)	0.73
Other STs	14 (12.4)	33 (19.6)	0.95 (0.40–2.25)	0.92
Vancomycin MIC
0.5 mg/L	6 (5.3)	22 (13.1)	As reference
1 mg/L	91 (80.5)	139 (82.7)	2.40 (0.94–6.15)	0.07	2.84 (1.01–7.98)	0.05
2 mg/L	16 (14.2)	7 (4.2)	8.38 (2.36–29.74)	0.001	8.45 (2.08–34.38)	0.003

Data are presented as no. (%) unless otherwise indicated.

Abbreviations: IQR, interquartile range; OR, odds ratios; CI, confidence interval.

^a Mann–Whitney U test was used to compare continuous variables, and χ² or Fisher exact test was used to compare categorical variables.

^b Hosmer and Lemeshow goodness-of-fit test P = 0.2292 > 0.05 (df = 9).