Prognostic Effects of Delayed Administration of Appropriate Antimicrobials in Bacteraemic Adults Initially Presenting with Various Body Temperatures

Figures & data

Table 1 The iBT-Related Trends in the Clinical Characteristics of Adults with Community-Onset Bacteraemia*

Variables	Case Numbers (%) in Varied iBT Categories						γ	P values
	< 36.0℃ n=239	36.0–36.9℃ n=127	37.0–37.9℃ n=276	38.0–38.9℃ n=1187	39.0–39.9℃ n=943	≥ 40.0℃ n=399
The elderly, ≥ 65 year	158 (66.1)	92 (72.4)	190 (68.8)	729 (61.4)	554 (58.7)	208 (52.1)	−0.860	0.03
Gender, male	149 (62.3)	76 (59.8)	156 (56.5)	606 (51.1)	455 (48.3)	167 (41.9)	−0.990	<0.001
Delayed AAT, hours, median (interquartile range)	2 (4–44)	2 (1–21)	3 (1–16)	2 (1–7.4)	2 (1–5.5)	2 (1–5)	−0.131	0.81
Recipients of IEAT (delayed AAT > 24 hours)	78 (32.6)	31 (24.4)	62 (22.1)	222 (18.7)	151 (16.0)	45 (11.3)	−0.956	0.003
Inadequate source control during antimicrobial therapy	8 (3.3)	4 (3.1)	11 (4.0)	37 (3.1)	26 (2.8)	12 (3.0)	−0.423	0.40
Syndrome in the ED
Sepsis	184 (77.0)	83 (65.4)	103 (37.3)	332 (28.0)	373 (39.6)	393 (98.5)	0.41	0.94
Septic shock	116 (48.5)	56 (44.1)	52 (18.8)	161 (13.6)	159 (16.9)	83 (20.8)	−0.797	0.06
Nursing-home residents	27 (11.3)	23 (18.1)	19 (6.9)	58 (4.9)	34 (3.6)	13 (3.3)	−0.795	0.06
Major comorbidities
Cardiovascular diseases	138 (57.7)	69 (54.3)	156 (56.5)	663 (55.9)	487 (51.6)	188 (47.1)	−0.841	0.04
Diabetes mellitus	93 (38.9)	49 (38.6)	98 (35.5)	454 (38.2)	343 (36.4)	142 (35.6)	−0.706	0.12
Neurological diseases	78 (32.6)	42 (33.1)	79 (28.6)	293 (24.7)	171 (18.1)	61 (15.3)	−0.975	0.001
Malignancies	77 (32.2)	54 (42.5)	82 (29.7)	334 (28.1)	288 (30.5)	113 (28.3)	−0.564	0.24
Chronic kidney diseases	50 (20.9)	21 (16.5)	69 (25.0)	245 (20.6)	149 (15.8)	47 (11.8)	−0.596	0.21
Liver cirrhosis	35 (14.6)	17 (13.4)	37 (13.4)	152 (12.8)	108 (11.5)	48 (12.0)	−0.930	0.007
Polymicrobial bacteraemia	41 (17.2)	23 (18.1)	27 (9.8)	105 (8.8)	75 (8.0)	31 (7.8)	−0.884	0.02
Major causative microorganisms
Escherichia coli	75 (31.4)	42 (33.1)	77 (27.9)	478 (40.3)	443 (47.0)	200 (50.1)	0.88	0.02
Streptococcus species	37 (15.5)	16 (12.6)	34 (12.3)	139 (11.7)	117 (12.4)	41 (10.3)	−0.853	0.03
Klebsiella pneumoniae	34 (14.2)	19 (15.0)	37 (13.4)	184 (15.5)	136 (14.4)	63 (15.8)	0.498	0.32
Staphylococcus aureus	42 (17.6)	20 (15.7)	62 (22.5)	163 (13.7)	92 (9.8)	32 (8.0)	−0.753	0.08
Pseudomonas species	11 (4.6)	5 (3.9)	10 (3.6)	44 (3.7)	46 (4.9)	12 (3.0)	−0.377	0.46
Major bacteraemia sources
Pneumonia	55 (23.0)	39 (30.7)	67 (24.3)	180 (15.2)	87 (9.2)	37 (9.3)	−0.866	0.03
Intra-abdominal	37 (15.5)	9 (7.1)	38 (13.8)	166 (14.0)	100 (10.6)	33 (8.3)	−0.397	0.44
Skin and soft-tissue	23 (9.6)	19 (15.0)	31 (11.2)	121 (10.2)	80 (8.5)	31 (7.8)	−0.615	0.19
Urinary tracts	42 (17.6)	22 (17.3)	57 (20.7)	364 (30.7)	365 (38.7)	177 (44.4)	0.964	0.002
Biliary tracts	16 (6.7)	14 (11.0)	21 (7.6)	99 (8.3)	85 (10.1)	26 (6.5)	−0.087	0.87

Note: *Boldface indicates statistical significance (ie, P < 0.05).

Abbreviations: ED, emergency department; iBT, initial body temperature; IEAT, inappropriate empirical antimicrobial therapy.

Figure 1 The iBT-related trends in the patient proportion of the critical illness and fatal comorbidities (McCabe classifications) as well as 15- and 30-day crude mortality rates.

Abbreviations: AAT, appropriate antimicrobial therapy; iBT, initial body temperature; MEDS, Mortality in Emergency Department Sepsis.

Table 2 Predictors of 30-Day Crude Mortality in Overall 3171 Patients with Community-Onset Bacteraemia*

Variables	Patient Numbers (%)^#		Univariable Analysis		Multivariable Analysis
	Fatal Patients n = 469	Survivors n = 2702	OR (95% CI)	P values	Adjusted OR (95% CI)	P values
Delayed AAT, hours, median (IQR)	2.0 (1.1–12.0)	2.0 (0.9–7.0)	–	–	1.003 (1.002–1.004)	< 0.001
Inadequate source control during antimicrobial therapy	25 (5.3)	73. (2.7)	2.03 (1.27–3.23)	0.002	2.33 (1.25–4.34)	0.008
Male patients	281 (59.9)	1328 (49.1)	1.55 (1.27–1.89)	<0.001	NS	NS
Comorbidities
Cardiovascular diseases	235 (50.1)	1466 (54.3)	0.85 (0.70–1.03)	0.10	NS	NS
Malignancies	227 (48.4)	721 (26.7)	2.58 (2.11–3.15)	<0.001	1.68 (1.31–2.14)	<0.001
Diabetes mellitus	156 (33.3)	1023 (37.9)	0.82 (0.67–1.01)	0.06	NS	NS
Neurological diseases	129 (27.5)	595 (22.0)	1.34 (1.08–1.68)	0.009	NS	NS
Liver cirrhosis	90 (19.2)	307 (11.4)	1.85 (1.43–2.40)	<0.001	NS	NS
Urological diseases	28 (6.0)	218 (8.1)	0.72 (0.48–1.09)	0.12	NS	NS
Autoimmune diseases	16 (3.4)	62 (2.3)	1.50 (0.86–2.63)	0.15	NS	NS
Polymicrobial bacteraemia	79 (16.8)	223 (8.3)	2.25 (1.71–2.97)	<0.001	1.55 (1.07–2.34)	0.02
Causative microorganisms
Escherichia coli	116 (24.7)	1199 (44.4)	0.41 (0.33–0.52)	<0.001	NS	NS
Klebsiella pneumoniae	105 (22.4)	368 (13.6)	1.83 (1.43–2.33)	<0.001	1.33 (0.96–1.85)	0.09
Staphylococcus aureus	80 (17.1)	331 (12.3)	1.47 (1.13–1.92)	0.004	1.44 (1.02–2.03)	0.04
Pseudomonas species	39 (8.3)	89 (3.3)	2.66 (1.80–3.93)	<0.001	1.86 (1.11–3.10)	0.02
Anaerobes	27 (5.8)	88 (3.3)	1.82 (1.17–2.83)	0.008	NS	NS
Proteus species	25 (5.3)	62 (2.3)	2.40 (1.49–3.86)	<0.001	NS	NS
Acinetobacter species	12 (2.6)	32 (1.2)	2.19 (1.12–4.29)	0.02	2.39 (1.03–5.54)	0.04
Vibrio species	9 (1.9)	19 (0.7)	2.76 (1.24–6.14)	0.02	NS	NS
Critical illness (MEDS ≥ 13) in EDs	334 (71.2)	329 (12.2)	17.9 (14.2–22.5)	<0.001	13.52 (10.57–17.28)	<0.001
Bacteraemia sources
Urinary tracts	51 (10.9)	976 (36.1)	0.22 (0.16–0.29)	<0.001	0.29 (0.19–0.84)	0.008
Biliary tracts	22 (4.7)	249 (9.2)	0.49 (0.31–0.76)	0.001	NS	NS
Bone and joints	9 (1.9)	108 (4.0)	0.47 (0.24–0.93)	0.03	0.48 (0.22–1.05)	0.06
Liver abscesses	7 (1.5)	94 (3.5)	0.42 (0.19–0.91)	0.02	0.28 (0.12–0.65)	0.003
Mycotic aneurysm	6 (1.3)	11 (0.4)	3.17 (0.17–8.61)	0.03	2.98 (0.88–10.08)	0.08
Central-nerve-system infections	4 (0.9)	10 (0.4)	2.32 (0.72–7.41)	0.14	NS	NS

Notes: *The variables yielding a P value of <0.2 in the univariable analysis and not belonged to the MEDS assessment are only enrolled. Boldface indicates statistical significance in the multivariable regression model (P < 0.05). ^#Data are expressed as numbers (%), unless indicated specifically.

Abbreviations: AAT, appropriate antimicrobial therapy; CI, confidence interval; ED, emergency department; IQR, interquartile range; MEDS, Mortality in Emergency Department Sepsis; NS, no significance (after processing the stepwise and backward multivariable regression).

Figure 2 Prognostic effects of each hourly AAT delay in different iBT groups*.

Abbreviations: AAT, appropriate antimicrobial therapy; iBT, initial body temperature.

Table 3 Prognostic Effects of Elevated iBTs in Patients Who Received IEAT (ie, Delayed AAT ≥ 24 Hours)*

Variables	Patient Number (%)^#		Univariable Analysis		Multivariable Analysis
	Fatal n=115	Survival n=474	OR (95% CI)	P value	Adjusted OR (95% CI)	P value
The iBT gap from 34.0℃ (degree)	2.4 (1.3–4.4)	1.4 (0.8–1.9)	–	<0.001	1.42 (1.21–1.77)	<0.001
Gender, male	69 (60.0)	248 (52.3)	1.37 (0.90–2.07)	0.14	NS	NS
Causative microorganisms
Escherichia coli	24 (20.9)	172 (36.3)	0.46 (0.28–0.75)	0.002	NS	NS
Klebsiella pneumoniae	15 (13.0)	34 (7.2)	1.94 (1.02–3.70)	0.04	NS	NS
Pseudomonas species	14 (12.2)	39 (8.2)	1.55 (0.81–2.96)	0.19	8.56 (2.28–28.91)	0.001
Acinetobacter species	9 (7.8)	178 (3.6)	2.28 (0.99–5.26)	0.07	2.26 (0.89–8.16)	0.06
Proteus species	7 (6.1)	12 (2.5)	2.50 (0.96–6.49)	0.07	NS	NS
Critical illness (MEDS ≥ 13) in EDs	72 (62.6)	40 (8.4)	18.17 (11.05–29.88)	<0.001	15.01 (8.65–26.05)	<0.001
Bacteraemia sources
Urinary tracts	15 (13.0)	164 (34.6)	0.28 (0.16–0.50)	<0.001	NS	NS
Biliary tracts	7 (6.1)	55 (11.6)	0.49 (0.22–1.12)	0.08	NS	NS
Skin and soft-tissue	6 (5.2)	44 (9.3)	0.54 (0.22–1.30)	0.16	NS	NS
Bone and joints	2 (1.7)	23 (4.9)	0.35 (0.08–1.49)	0.19	NS	NS
Comorbidities
Cardiovascular diseases	61 (53.0)	287 (60.5)	0.74 (0.49–1.11)	0.14	NS	NS
Malignancies	50 (43.5)	125 (26.4)	2.15 (1.41–3.27)	<0.001	3.77 (1.45–8.31)	0.001
Liver cirrhosis	23 (20.0)	47 (9.9)	2.27 (1.31–3.93)	0.03	NS	NS
Chronic obstructive pulmonary diseases	11 (9.6)	20 (4.2)	2.40 (1.12–5.17)	0.02	NS	NS

Notes: *The variables yielding a P value of <0.2 in the univariable analysis and not belonged to the MEDS assessment are only enrolled. Boldface indicates statistical significance in the multivariable regression (ie, P < 0.05). ^#Data are expressed as numbers (%), unless indicated specifically.

Abbreviations: CI, confidence interval; ED, emergency department; iBT, initial body temperature; IEAT, inappropriate empirical antimicrobial therapy; MEDS, Mortality in Emergency Department Sepsis; NS, no significance (after processing the stepwise and backward multivariable regression).