1. Supplementary Table 1 C min of Teicoplanin at 1 st and 2 nd TDM in patients with administration of additional loading dose on the 4 th day Teicoplanin C min Conventional loading regimen (n=25) Enhanced loading regimen (n=16) C min at initial TDM Median (IQR, Range) (µg/mL)9.7 (7.9-11.4, 6.4-14.0)12.3 (11.3-13.0, 9.4-14.8) No. of patients with < 10 µg/mL (rate)13 (52.0%)2 (12.5%) No. of patients with 10-15 µg/mL (rate)12 (48.0%)14 (87.5%) No. of patients with 15-30 µg/mL (rate)0 (0.0%) No. of patients with >30 µg/mL (rate)0 (0.0%) C min at secondary TDM Median (IQR, Range) (µg/mL)14.9 (13.1-23.7, 7.9-26.2)18.8 (16.1-19.8, 10.1-25.4) No. of patients with < 10 µg/mL (rate)2 (8.0%)0 (0.0%) No. of patients with 10-15 µg/mL (rate)11 (44.0%)2 (12.5%) No. of patients with 15-30 µg/mL (rate)12 (48.0%)14 (87.5%) No. of patients with >30 µg/mL (rate)0 (0.0%) C min : trough concentration, TDM: therapeutic drug monitoring, IQR: Interquartile range

2. Supplementary Table 2 Fulfillment of the criteria of each factor included in the definition of clinical success Factors for definitionNo of patients who met the definition of clinical success at the end of therapy (rate) Each factorClinical success Inflammatory biomarker (CRP/PCT) 75 * /106 (70.8%) 68 (64.2%) Peripheral white blood cell count 85/106 (80.2%) Body temperature 84/106 (79.2%) Clinical features 75/106 (70.8%) X-ray 38/58 ** (67.9%) CRP: C-reactive protein, PCT: procalcitonin, * : Fulfillment of criteria in PCT was observed in 15 patients who failed to meet the criteria of CRP ** : Patients with respiratory tract infections, intraabdominal infections, and mediastinitis

3. Supplementary Table 3 Fulfillment of the criteria of each factor included in the definition of clinical improvement on the 4 th day of therapy Factors for definition No of patients who met the definition of clinical improvement on the 4 th day (rate) Each factorClinical improvement Inflammatory biomarker (CRP/PCT) 76 * /106 (71.7%) 83/106 (78.3%) 67/106 (63.2%) Peripheral white blood cell count 33/106 (31.1%) Body temperature 68/90 ** (75.6%) Clinical features 77/106 (72.6%) * : Fulfillment of criteria in PCT was observed in 2 patients who failed to meet the criteria of CRP, ** : Sixteen patients were afebrile at the start of therapy

4. Supplementary Table 4. Clinical success rate in patients who achieved initial and maximal C min of >15 µg/mL and in those that did not in conventional and enhanced loading regimens regimen No of patients with clinical success (rate) initial C min Maximal C min >15 µg/mL<15 µg/mLP-value>15 µg/mL<15 µg/mLP-value Conventional regimen6/6 (100%)17/32 (53.1%)0.06313/16 (81.3%)10/22 (45.5%)0.026 Enhanced loading regimen39/54 (72.2%)6/14 (42.9%)0.05742/59 (71.2%)3/9 (33.3%)0.052 C min : trough concentration

5. Factors No of patients with clinical success at the end of therapy (%) P-value Crude odds ratio (95%CI) Adjusted odds ratio (95%CI) Patients with factorPatients without factor Sex (male)48/75 (64.0%)20/31 (64.5%)0.9600.98 (0.41-2.34)- Age (>65 years)48/74 (64.9%)20/32 (62.5%)0.8161.11 (0.47-2.62)- eGFR<40mL/min/1.73m230/47 (63.8%)38/59 (64.4%)0.9510.98 (0.44-2.17)- Heart disease26/42 (61.9%)42/64 (65.6%)0.6960.85 (0.38-1.91)- Chronic renal failure18/28 (64.3%)50/78 (64.1%)0.9861.01 (0.41-2.48)- Diabetes mellitus23/35 (65.7%)45/71 (63.4%)0.8141.11 (0.47-2.59)- Collagen disease6/11 (54.5%)62/95 (65.3%)0.5180.64 (0.18-2.25)- Chronic respiratory disease4/8 (50.0%)64/98 (65.3%)0.4530.53 (0.12-2.26)- Inflammatory bowel disease5/7 (71.4%)63/99 (63.6%)0.6781.43 (0.26-7.74)- Intensive care unit stay (>3 days)10/19 (52.6%)58/87 (66.7%)0.2480.56 (0.20-1.52)- Immunosuppressive therapy2/4 (50.0%)66/102 (64.7%)0.6170.55 (0.07-4.04)- Liver cirrhosis/chronic hepatic dysfunction14/27 (51.9%)54/79 (68.4%)0.1230.50 (0.20-1.22)- Malignant tumor25/48 (52.1%)43/58 (74.1%)0.0180.38 (0.17-0.86)0.18 (0.05-0.62) Malnutrition31/54 (57.4%)37/52 (71.2%)0.1400.55 (0.24-1.22)- Total parenteral nutrition15/31 (48.4%)53/75 (70.7%)0.0300.39 (0.16-0.92)- Ventilator use6/16 (37.5%)62/90 (68.9%)0.0160.28 (0.10-0.82)0.26 (0.06-1.15) APACHE II score > 11 (median)25/55 (45.5%)43/51 (84.3%)<0.0010.16 (0.06-0.39)0.12 (0.03-0.43) Surgery within 28 days33/46 (71.7%)35/60 (58.3%)0.1541.81 (0.80-4.12)- Steroid use12/23 (52.2%)56/83 (67.5%)0.1760.53 (0.21-1.34) 0.34 （ 0.09-1.24) Anticancer therapy5/17 (29.4%)63/89 (70.8%)0.0010.17 (0.06-0.54)- Blood infections13/26 (50.0%)55/80 (68.8%)0.0830.45 (0.18-1.12)- Skin & soft tissue infections18/22 (81.8%)50/84 (59.5%)0.0523.06 (0.95-9.84)- Osteomyelitis and arthritis2/7 (28.6%)66/99 (66.7%)0.0950.20 (0.04-1.09) 0.01 （ 0.01-0.14) Urinary tract infection5/2 (100%)63/101 (62.4%)0.157-- Other typr of infections0/2 (0%)68/104 (65.4%)0.126-- Respiratory infection24/40 (60.0%)44/66 (66.7%)0.4880.75 (0.33-1.69)- Intra-abdominal infection11/16 (68.8%)57/90 (63.3%)0.6771.27 (0.41-3.99)- Mixed infection with Gram-negative organisms38/64 (59.4%)30/42 (71.4%)0.2060.58 (0.25-1.35)- Therapy for definitive or presumed fungal infections7/13 (53.8%)61/93 (65.6%)0.5380.61 (0.19-1.97)- Enhanced loading regimen45/68 (66.2%)23/38 (60.5%)0.5611.28 (0.56-2.90)- Teicoplanin initial C min ≥15 μg/mL45/60 (75.0%)23/46 (50.0%)0.0083.00 (1.32-6.82)4.20 (1.34-13.15) Teicoplanin maximal C min ≥15 μg/mL55/75 (73.3%)13/31 (41.9%)0.0023.81 (1.58-9.16)2.88 (0.96-8.62) Supplementary Table 5. Variable associated with clinical success at the completion of teicoplanin therapy: univariate and multivariate analysis. eGFR: estimated glomerular filtration rate, APACHE II : Acute physiology and chronic health evaluation II score