Among the 91 patients with MSSA bacteremia identified over the 3-year study period, two patients who did not receive antibiotic treatment, two patients who received initial vancomycin treatment, and three patients who were aged < 18 years were excluded. Among the 84 adult patients included in the study, 28 (33.3%) received initial teicoplanin treatment and 56 (66.7%) initial β-lactam treatment. Subsequently, we stratified these two groups based on propensity score matching according to the outcome analysis using the logistic regression model (Fig. 1).
Comparisons of the demographics, comorbidities, severity of blood stream infection at onset, source of bacteremia, rate of adequate infection source control, infection by strains with teicoplanin MICs ≥ 1.5 mg/L, and clinical outcomes between the two groups before and after propensity score matching are presented in Table 1. Before propensity score matching, no statistically significant differences were observed in terms of sex, age, length of hospital stay, and the proportion of S, aureus strains with teicoplanin MICs ≥ 1.5 mg/L between the groups. A significantly higher prevalence of coronary artery disease (42.9% versus 8.9%, p < 0.01) and congestive heart failure (39.3% versus 7.1%, p < 0.01) was observed in the initial teicoplanin treatment group. There was no statistically significant difference in disease severity (Pittsburgh bacteremia score ≥ 4) between the groups or infection sources of bacteremia. The adequate infection source control rate was higher in the initial teicoplanin treatment group than in the β-lactam treatment group (78.9% versus 41.7%, p = 0.01). We did not find statistically significant differences in short-term favorable outcome, favorable outcome at the time of completion of teicoplanin or β-lactam therapy, and the 30-day overall mortality rate between the two groups (Table 1).
Table 1
Comparisons of demographic and clinical features of patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia who received initial teicoplanin treatment (n = 28) and those who received ß-lactam antibiotic treatment (n = 56)
Variables
|
Initial teicoplanin treatment
n = 28
|
Initial ß-lactam treatment
n = 56
|
P
|
Initial teicoplanin treatment
n = 28
|
Initial ß-lactam treatment
n = 28
|
P*
|
Demographics
|
Male gender, n (%)
|
17 (60.7)
|
37 (66.1)
|
0.64
|
17 (60.7)
|
17 (60.7)
|
> 0.99
|
Age, mean (range), years
|
75 (62–81)
|
67 (55–76)
|
0.06
|
75 (62–81)
|
75 (65–84)
|
NA
|
Length of hospital stay, mean (range), days
|
26 (15-30)
|
21 (12-31)
|
0.29
|
26 (15-30)
|
16 (9-33)
|
0.31
|
MIC of teicoplanin ≥ 1.5 mg/L, n (%)
|
6 (21.4)
|
23 (41.1)
|
0.09
|
6 (21.4)
|
9 (32.1)
|
0.33
|
Comorbidities, n (%)
|
Coronary artery disease
|
12 (42.9)
|
5 (8.9)
|
< 0.01
|
12 (42.9)
|
3 (10.7)
|
0.03
|
Diabetes mellitus
|
12 (42.9)
|
22 (39.3)
|
0.82
|
12 (42.9)
|
8 (28.6)
|
0.26
|
Hypertension
|
18 (64.3)
|
25 (44.6)
|
0.11
|
18 (64.3)
|
11 (39.3)
|
0.08
|
Solid tumor
|
10 (35.7)
|
9 (16.1)
|
0.06
|
14 (50.0)
|
4 (14.3)
|
0.08
|
Hematology malignancy
|
0
|
1 (1.8)
|
> 0.99
|
0
|
1 (3.6)
|
0.61
|
Liver cirrhosis
|
1 (3.6)
|
6 (10.7)
|
0.42
|
1 (3.6)
|
3 (10.7)
|
0.34
|
Chronic obstructive pulmonary disease
|
3 (10.7)
|
4 (7.1)
|
0.68
|
3 (10.7)
|
2 (71.4)
|
0.66
|
IV drug abuser
|
0
|
4 (7.1)
|
0.30
|
0
|
2 (71.4)
|
0.47
|
Congestive heart failure
|
11 (39.3)
|
4 (7.1)
|
< 0.01
|
11 (39.3)
|
3 (10.7)
|
0.04
|
End-stage renal disease
|
7 (25.0)
|
13 (23.2)
|
> 0.99
|
7 (25.0)
|
7 (25.0)
|
> 0.99
|
Cerebral vascular accident
|
7 (25.0)
|
16 (28.6)
|
0.80
|
7 (25.0)
|
8 (28.6)
|
0.76
|
Prosthetic device implantation
|
15 (53.6)
|
17 (30.4)
|
0.06
|
15 (53.6)
|
7(25.0)
|
0.05
|
Pittsburgh bacteremia score ≥ 4a
|
14 (50.0)
|
16 (28.6)
|
0.09
|
14 (50.0)
|
14 (50.0)
|
NA
|
Source of bacteremiab, n (%)
|
Catheter-related bacteremia
|
10 (35.7)
|
7 (12.5)
|
0.02
|
10 (35.7)
|
4 (14.3)
|
0.10
|
Bone and joint infection
|
5 (17.9)
|
16 (28.6)
|
0.42
|
5 (17.9)
|
6 (21.4)
|
0.74
|
Infective endocarditis
|
0
|
6 (10.7)
|
0.17
|
0
|
4 (14.3)
|
0.31
|
Skin and soft infection
|
4 (14.3)
|
13 (23.2)
|
0.40
|
4 (14.3)
|
6 (21.4)
|
0.53
|
Intra-abdominal infection
|
0
|
1 (1.8)
|
> 0.99
|
0
|
1 (3.6)
|
0.61
|
Urinary tract infection
|
0
|
1 (1.8)
|
> 0.99
|
0
|
1 (3.6)
|
0.61
|
Pneumonia
|
3 (10.7)
|
5 (8.9)
|
> 0.99
|
3 (10.7)
|
2 (28.6)
|
0.57
|
Primary bacteremia
|
4 (14.3)
|
5 (8.9)
|
0.47
|
6 (21.4)
|
2 (28.6)
|
0.18
|
Adequate infection source control rate+n/N
|
15/19 (78.9)
|
15/36 (41.7)
|
0.01
|
15/19 (78.9)
|
14/16 (87.5)
|
0.67
|
Clinical outcome, n (%)
|
Short-term favorable outcomec
|
11 (39.3)
|
34 (60.7)
|
0.10
|
11 (39.3)
|
11 (39.3)
|
> 0.99
|
Favorable outcomed
|
24 (85.7)
|
43 (76.8)
|
0.40
|
24 (85.7)
|
18 (64.3)
|
0.07
|
30-day overall mortality
|
4 (14.3)
|
13 (23.2)
|
0.40
|
4 (14.3)
|
10 (35.7)
|
0.07
|
*Propensity score matching (1:1) for age and Pittsburgh bacteremia score ≥ 4 was performed for the initial teicoplanin treatment group (n = 28) versus the initial ß-lactam treatment group (n = 28). Standardized mean difference (SMD) post-propensity score matching: age (-2.78%), Pittsburgh bacteremia score ≥ 4 (0%) |
NA: not applicable |
+Surgical intervention, drainage, central venous catheter removal, and urinary catheter removal were performed for source control. Patients with pneumonia or primary bacteremia were excluded. n: adequate and timely removal or debridement of the source of bacteremia, N: the source of bacteremia needed to be removed or debrided. |
aAt the time of blood sampling for culture. |
bPatients may have had more than one source of bacteremia. |
cAssessment on day 7 after starting the initial teicoplanin or ß-lactam antibiotic therapy. |
dEvaluation at the time of completion of the initial teicoplanin or ß-lactam antibiotic therapy. |
The risk factors for unfavorable clinical response at the completion of teicoplanin or β-lactam therapy in the unadjusted univariate analysis included higher disease severity (Pittsburgh bacteremia score ≥ 4 (94.1% versus 20.9%, p < 0.01) and infective endocarditis as the source of bacteremia (23.5% versus 3.0%, p = 0.01) (Table 2). After adjustments were made in the multivariate analysis, we observed that the Pittsburgh bacteremia score ≥ 4 (odds ratio, 60.6; 95% CI, 7.4–496.8) was independently associated with unfavorable outcome at the time of completion of teicoplanin or β-lactam therapy (Table 2). There was no significant evidence of lack of fit in any of the final models, as the p-values were > 0.05 in the Hosmer-Lemeshow goodness-of-fit tests.
Table 2
Comparisons of demographic and clinical features between patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia with favorable and unfavorable final clinical responses
Outcome at the end of the initial treatment
|
Favorable outcome
n = 67
|
Unfavorable outcome
n = 17
|
P
|
Demographics
|
Male gender, n (%)
|
43 (64.2)
|
11 (64.7)
|
> 0.99
|
Age, mean (range), years
|
68 (59–77)
|
72 (48–85)
|
0.82
|
MIC of teicoplanin ≥ 1.5 mg/L, n (%)
|
22 (32.8)
|
7 (41.2)
|
0.57
|
Co-morbidities, n (%)
|
Coronary artery disease
|
14 (20.9)
|
3 (17.6)
|
> 0.99
|
Diabetes mellitus
|
30 (44.8)
|
4 (23.5)
|
0.17
|
Hypertension
|
38 (56.7)
|
5 (29.4)
|
0.06
|
Solid tumor
|
14 (20.9)
|
5 (29.4)
|
0.52
|
Hematology malignancy
|
1 (1.5)
|
0
|
> 0.99
|
Liver cirrhosis
|
4 (6.0)
|
3 (17.6)
|
0.14
|
Chronic obstructive pulmonary disease
|
5 (7.5)
|
2 (11.8)
|
0.63
|
IV drug abuser
|
2 (3.0)
|
2 (11.8)
|
0.18
|
Congestive heart failure
|
13 (19.4)
|
2 (11.8)
|
0.73
|
End-stage renal disease
|
17 (25.4)
|
3 (17.6)
|
0.75
|
Cerebral vascular accident
|
21 (31.3)
|
2 (11.8)
|
0.14
|
Prosthetic device implantation
|
27 (40.3)
|
5 (29.4)
|
0.58
|
Pittsburgh bacteremia score ≥ 4a
|
14 (20.9)
|
16 (94.1)
|
< 0.01*
|
Source of bacteremiab, n (%)
|
Catheter-related bacteremia
|
15 (22.4)
|
2 (11.8)
|
0.50
|
Bone and joint infection
|
20 (29.9)
|
1 (5.9)
|
0.06
|
Infective endocarditis
|
2 (3.0)
|
4 (23.5)
|
0.01
|
Skin and soft infection
|
16 (23.9)
|
1 (5.9)
|
0.17
|
Intra-abdominal infection
|
0
|
1 (5.9)
|
0.20
|
Urinary tract infection
|
1 (1.5)
|
0
|
> 0.99
|
Pneumonia
|
5 (7.5)
|
3 (17.6)
|
0.35
|
Primary bacteremia
|
6 (9.0)
|
3 (17.6)
|
0.38
|
Adequate infection source control rate+ n/N
|
28/51 (54.9)
|
2/4 (50.0)
|
> 0.99
|
Initial treatment group, n (%)
|
Initial teicoplanin treatment group
|
24 (35.8)
|
4 (23.5)
|
0.40
|
Initial ß-lactam treatment group
|
43 (64.2)
|
13 (76.5)
|
0.40
|
+Surgical intervention, drainage, central venous catheter removal, and urinary catheter removal were performed for source control. Patients with pneumonia or primary bacteremia were excluded. n: adequate and timely removal or debridement of the source of bacteremia, N: the source of bacteremia needed to be removed or debrided. |
aAt the time of blood sampling for culture. |
bPatients may have had more than one source of bacteremia. |
*Multivariate analysis of the risk factors for an unfavorable clinical outcome in patients with MSSA bacteremia treated initially with teicoplanin or ß-lactam antibiotics showed that a Pittsburgh bacteremia score ≥ 4 (odd ratio, 60.6 [95% confidence interval, 7.4–496.8], p < 0.01) was an independent risk factor for an unfavorable outcome. |
All patients included in the study were divided into the initial teicoplanin treatment (n = 28) and β-lactam treatment (n = 28) groups after 1:1 propensity score matching with Pittsburgh bacteremia score ≥ 4 (the independent risk factor for unfavorable outcome) and age. After matching, there were no statistically significant differences in terms of sex, length of hospital stay, and the proportion of S. aureus strains with teicoplanin MICs ≥ 1.5 mg/L between the groups. The incidence of coronary artery disease and congestive heart failure was higher (42.9% versus 10.7%, p = 0.03 and 39.3% versus 10.7%, p = 0.04, respectively) among patients receiving initial teicoplanin treatment than in those receiving β-lactam treatment even after propensity score matching. No statistically significant differences were observed in the source of bacteremia and the rate of adequate infection source control between the two groups after matching. We did not find statistically significant differences in short-term favorable outcome, favorable outcome at the time of completion of teicoplanin or β-lactam therapy, and 30-day overall mortality rate between the groups after propensity score matching.
Among the patients in the initial teicoplanin treatment group, 21 (75.0%) switched to β-lactam treatment and three (14.3%) died within 30 days of hospitalization after the onset of MSSA bacteremia. Altogether, 71.5% (15/21) of the patients switched to β-lactam treatment within 4 days after the onset of bacteremia, which was consistent with the time of availability of final susceptibility test results (Supplementary Figure). On the other hand, the 30-day mortality rate was 14.3% in patients with initial teicoplanin treatment without a switch to β-lactam treatment for MSSA bacteremia (Table 1). The clinical data of seven patients with MSSA bacteremia who received continuous teicoplanin treatment are shown in Supplementary Table. The MIC distributions of teicoplanin in the MSSA strains isolated from patients in the initial teicoplanin treatment group (n = 28) and the β-lactam treatment group (n = 56) are shown in Fig. 2. We observed that 78.6% (22/28) of the MSSA strains in the initial teicoplanin treatment group exhibited teicoplanin MICs < 1.5 mg/L, while 60.7% (34/56) of the MSSA strains in the initial β-lactam treatment group exhibited teicoplanin MICs < 1.5 mg/L.
The Kaplan-Meier curves for 30-day survival in patients with MSSA bacteremia are presented in Fig. 3. The cases were grouped according to the initial treatment (teicoplanin or β-lactam) before propensity score matching (Fig. 3(i)) and were further stratified as the initial teicoplanin treatment group or the β-lactam treatment group after propensity score matching (Fig. 3(ii)). The 30-day survival was not significantly different between the two groups before propensity score matching (hazard ratio, 1.84; 95% CI, 0.60–5.64, p = 0.29) as well as after propensity score matching (hazard ratio, 3.12; 95% CI, 0.98–9.99, p = 0.06).