The authors have declared that no competing interests exist.
Conceived and designed the experiments: KHP YSK. Performed the experiments: TK SMM JYJ. Analyzed the data: KHP YPC. Contributed reagents/materials/analysis tools: YML HLH TK HJP SYP SHK SOL SHC MNK JHW. Wrote the paper: KHP YSK.
Catheter-related
Consecutive patients with CRSAB were prospectively included from over a 41-month period. We compared the clinical features, 40 bacterial virulence genes, and outcomes between patients with persistent CRSAB (i.e., bacteremia for >3 days after catheter removal and initiation of appropriate antimicrobial therapy) and non-persistent CRSAB.
Among the 220 episodes of CRSAB, the catheter was kept in place in 17 (6%) and removed in 203 (94%) cases. In 43 (21%) of the 203 episodes, bacteremia persisted for >3 days after catheter removal and initiation of antimicrobial therapy. Methicillin resistance (Odds ratio [OR], 9.01; 95% confidence interval [CI], 3.05–26.61;
In patients with CRSAB, bacteremia persisted in 21% of cases despite catheter removal and initiation of antimicrobial therapy. Methicillin resistance, renal failure, and non-catheter prosthetic devices were independent risk factors for persistent CRSAB, which was associated with a higher rate of complications.
In practice, however, CRSAB occasionally persists despite catheter removal and initiation of appropriate antimicrobial therapy. There is limited literature evaluating the clinical characteristics and outcomes of patients with persistent CRSAB despite initiation of appropriate therapy. A previous study of 37 patients with CRSAB showed that fever and/or bacteremia that persisted for >3 days after catheter removal and/or initiation of antimicrobial therapy was associated with development of early complications
Informed consent was waived given that no interventions were planned and collected data were stored anonymously. The Asan Medical Center Institutional Review Board approved the study and waiver of informed consent (IRB number: 2008-0274).
From August 2008 to December 2011, data were collected as part of a prospective cohort study of
CRSAB was classified as definite or probable according to current IDSA criteria guidelines
CRSAB was considered “persistent” if bacteremia persisted for >3 days after initiation of appropriate therapy. Appropriate therapy was considered to have been initiated if the catheter was removed and if at least one intravenous antibiotic to which the isolate was susceptible was started. CRSAB was considered “non-persistent (1) if bacteremia cleared within 3 days after initiation of appropriate therapy or (2) if follow-up blood cultures were not performed because of resolution of signs and symptoms of the catheter infection after initiation of appropriate therapy.
All surviving patients were followed up 12 weeks after the onset of SAB. Complicated SAB was defined as the presence of (1) attributable mortality, (2) complicated infection present at the time of the initial hospitalization, or (3) late complication. Death was attributable to SAB if blood cultures were positive for
All blood cultures were analyzed using by the BACTEC 9240 (Becton Dickinson, Spark, MD, USA) and all
Results were analyzed using a commercially available software package (SPSS software, version 14.0 K for Windows; SPSS, Inc., Chicago, IL). Categorical variables were evaluated using the chi-square or Fisher exact test. Continuous variables were compared using the Student
During the 41-month study period, 239 episodes of CRSAB occurred in 237 adult patients. Two patients had two episodes of CRSAB; only the first episode was included in the analysis. Twelve patients with polymicrobial bacteremia excluded and five patients were lost to follow-up. As a result, 220 patients were included in the analysis. Among them, 135 (61%) were found to have definite CRSAB, and the other 85 (39%) had probable CRSAB.
The source of bacteremia was presumed to be a temporary central venous catheter in 117 (53%), a tunneled cuffed intravascular catheter (e.g., Permcath or Hickman catheter) in 49 (23%), a peripheral vascular catheter in 42 (19%), a peripheral inserted central venous catheter in 5 (2%), a subcutaneous port catheter in 5 (2%), and an arterial catheter in 2 (1%). One hundred and sixty-one patients (73%) had an echocardiogram during the course of therapy; 143 patients (89%) had only transthoracic echocardiogram, and 18 patients (11%) had both transthoracic and transesophageal echocardiogram.
Of the 220 episodes of CRSAB, the catheter was removed from 203 patients (94%), and kept in place in 17 patients (6%). Among the latter 17 patients, 9 recovered, 7 died of SAB, and 1 recovered from SAB but died due to progression of malignancy. Catheter retention group was more likely to have underlying malignancy and long-term intravascular catheters, and to have been received chemotherapy than catheter removal group. Catheter removal group was more likely to be old and to have diabetes mellitus. The complication rate was significantly higher in catheter retained group than catheter removal group (53% [9/17] vs. 27% [55/203],
Variable | Catheter retained (n = 17) | Catheter removed (n = 203) | |
Age, median (IQR) | 50 (46–61) | 62 (50–70) | 0.02 |
Male sex | 11 (65) | 128 (63) | 0.89 |
Community-onset of infection | 0 (0) | 27 (13) | 0.24 |
Methicillin resistance | 9 (53) | 122 (60) | 0.56 |
Comorbidity | |||
Underlying malignancy | 14 (82) | 108 (53) | 0.02 |
Renal failure | 3 (18) | 56 (28) | 0.57 |
Diabetes mellitus | 0 (0) | 56 (28) | 0.008 |
Liver cirrhosis | 2 (12) | 34 (17) | 0.75 |
Type of catheter | |||
Central venous catheter | 16 (94) | 160 (79) | 0.21 |
Long-term intravascular catheters |
12 (71) | 42 (21) | <0.001 |
External signs of catheter infection | 2 (13) | 40 (20) | 0.74 |
Presence of non-catheter prosthetic devices |
1 (6) | 17 (8) | >0.99 |
APACHE II score, median (IQR) | 18 (15–23) | 17 (12–21) | 0.38 |
Pitt bacteremia score, median (IQR) | 1 (1–3) | 1 (0–3) | 0.48 |
Intensive care unit stay | 3 (18) | 59 (29) | 0.41 |
Mechanical ventilation | 1 (6) | 36 (18) | 0.32 |
Prescription of immunosuppressive therapy |
5 (29) | 43 (21) | 0.54 |
Prescription of cancer chemotherapy |
8 (47) | 33 (16) | 0.005 |
Recent surgery |
2 (12) | 57 (28) | 0.25 |
Outcome | |||
Complicated |
9 (53) | 55 (27) | 0.047 |
Complicated infection | 5 (29) | 34 (17) | 0.19 |
Septic thrombophlebitis | 1 (6) | 19 (9) | >0.99 |
Infective endocarditis | 2 (12) | 6 (3) | 0.12 |
Septic emboli to lungs | 2 (12) | 8 (4) | 0.18 |
Deep tissue abscess | 1 (6) | 6 (3) | 0.44 |
Septic arthritis | 0 (0) | 1 (1) | >0.99 |
Osteomyelitis | 0 (0) | 1 (1) | >0.99 |
Attributable mortality | 7 (41) | 23 (11) | 0.003 |
Late complication | 1 (6) | 6 (3) | 0.44 |
No complication due to |
8 (47) | 148 (73) | 0.047 |
Uncomplicated |
7 (41) | 123 (61) | 0.12 |
Death not-related |
1 (6) | 25 (12) | 0.70 |
NOTE: Data are no. (%) of patients, unless otherwise indicated. IQR, interquartile range; APACHE II, Acute Physiology and Chronic Health Evaluation II.
Includes perm catheter (n = 31), Hickman catheter (n = 18), and subcutaneous port catheters (n = 5).
Includes prosthetic valve (n = 7), synthetic vascular graft (n = 6), and orthopedic device (n = 5).
Within previous one month.
Of the 203 episodes of CRSAB in which the catheters were removed, bacteremia persisted for >3 days after catheter removal and initiation of appropriate antimicrobial therapy in 43 patients (21%). Clinical characteristics of 203 patients with persistent and non-persistent CRSAB are shown in
Variable | Non-persistentCRSAB(n = 160) | PersistentCRSAB(n = 43) | Univariate analysis | Multivariate analysis | ||
OR (95% CI) | OR (95% CI) | |||||
Age, median (IQR) | 62 (49–70) | 64 (53–72) | 0.16 | |||
Male sex | 101 (63) | 27 (63) | 0.97 | |||
Community-onset of infection | 20 (13) | 7 (16) | 0.52 | |||
Methicillin resistance | 84 (53) | 38 (88) | <0.001 | 6.88(2.57–18.37) | <0.001 | 9.01(3.05–26.61) |
Comorbidity | ||||||
Underlying malignancy | 86 (54) | 22 (51) | 0.76 | |||
Renal failure | 35 (22) | 21 (49) | <0.001 | 3.41(1.68–6.90) | 0.003 | 3.23(1.48–7.08) |
Diabetes mellitus | 46 (29) | 10 (23) | 0.47 | |||
Liver cirrhosis | 29 (18) | 5 (12) | 0.31 | |||
Type of catheter | ||||||
Central venous catheter | 120 (75) | 40 (93) | 0.01 | 4.44(1.30–15.15) | ||
Long-term intravascular catheters |
31 (19) | 11 (26) | 0.37 | |||
External signs of catheter infection | 32 (20) | 8 (19) | 0.84 | |||
Presence of non-catheter prosthetic devices |
8 (5) | 9 (21) | 0.003 | 5.03(1.81–13.98) | 0.006 | 5.37(1.62–17.80) |
APACHE II score, median (IQR) | 17 (12–21) | 19 (13–23) | 0.13 | |||
Pitt bacteremia score, median (IQR) | 1 (0–3) | 1 (0–3) | 0.76 | |||
Intensive care unit stay | 44 (28) | 15 (35) | 0.34 | |||
Mechanical ventilation | 29 (18) | 7 (16) | 0.78 | |||
Prescription of immunosuppressive therapy |
36 (23) | 7 (16) | 0.38 | |||
Prescription of cancer chemotherapy |
28 (18) | 5 (12) | 0.35 | |||
Recent surgery |
45 (28) | 12 (28) | 0.98 | |||
Clinical management | ||||||
Catheter removal within 48 hrs | 120 (75) | 38 (88) | 0.06 | |||
Initiation of appropriate antibiotics within 48 hrs | 141 (88) | 37 (86) | 0.71 | |||
Initial vancomycin use (to MSSA isolates) | 31/76 (41) | 5/5 (100) | 0.02 | |||
Duration of antibiotic therapy | 15 (11–21) | 27 (20–47) | <0.001 | |||
Outcome | ||||||
Complicated |
24 (15) | 31 (72) | <0.001 | |||
Complicated infection | 7 (4) | 27 (63) | <0.001 | |||
Septic thrombophlebitis | 6 (4) | 13 (30) | <0.001 | |||
Infective endocarditis | 0 (0) | 6 (14) | <0.001 | |||
Other metastatic seeding of infection |
1 (1) | 15 (35) | <0.001 | |||
Attributable mortality | 13 (8) | 10 (23) | 0.01 | |||
Late complication | 4 (3) | 2 (5) | 0.61 | |||
No complications due to |
136 (85) | 12 (28) | <0.001 | |||
Uncomplicated |
113 (71) | 10 (23) | <0.001 | |||
Death not-related |
23 (14) | 2 (5) | 0.09 |
NOTE: Data are no. (%) of patients, unless otherwise indicated. CRSAB, catheter-related
Includes perm catheter (n = 30), Hickman catheter (n = 10), and subcutaneous port catheters (n = 2).
Includes prosthetic valve (n = 7), synthetic vascular graft (n = 5), and orthopedic device (n = 5).
Within previous one month.
Includes septic emboli to lungs (n = 8), deep tissue abscess (n = 6), septic arthritis (n = 1), and osteomyelitis (n = 1).
Catheter was removed within 48 hrs in 120 patients (75%) with non-persistent CRSAB and in 38 patients (88%) with persistent CRSAB (
Complications occurred in 31 patients (72%) with persistent CRSAB and in 24 patients (15%) with non-persistent CRSAB (
Complications were more common in patients who had persistent bacteremia for >3 days after catheter removal and initiation of appropriate antimicrobial therapy than in those who did not have persistent bacteremia (log-rank test,
Variable | No SAB-related complication (n = 148) | SAB-related complication (n = 55) | Univariate analysis | Multivariate analysis | ||
OR (95% CI) | OR (95% CI) | |||||
Age, median (IQR) | 61 (49–70) | 64 (54–71) | 0.29 | 1.01 (0.99–1.04) | ||
Male sex | 91 (62) | 37 (67) | 0.45 | 1.29 (0.67–2.48) | ||
Community-onset of infection | 18 (12) | 9 (16) | 0.43 | 1.41 (0.59–3.37) | ||
Methicillin resistance | 81 (55) | 41 (75) | 0.01 | 2.42 (1.22–4.82) | ||
Underlying malignancy | 74 (50) | 34 (62) | 0.13 | 1.62 (0.86–3.05) | ||
Renal failure | 31 (21) | 25 (46) | 0.001 | 3.15 (1.62–6.10) | ||
Diabetes mellitus | 42 (28) | 14 (26) | 0.68 | 0.86 (0.43–1.74) | ||
Liver cirrhosis | 27 (18) | 7 (13) | 0.35 | 0.65 (0.27–1.60) | ||
Central venous catheter | 112 (76) | 48 (87) | 0.07 | 2.20 (0.92–5.30) | ||
Long-term intravascular catheters | 28 (19) | 14 (26) | 0.31 | 1.46 (0.70–3.05) | ||
External signs of catheter infection | 27 (18) | 13 (24) | 0.39 | 1.39 (0.66–2.93) | ||
Presence of non-catheter prosthetic device | 6 (4) | 11 (20) | 0.001 | 5.92 (2.07–16.92) | 0.052 | 3.50 (0.99–12.40) |
APACHE II score, median (IQR) | 16 (11–21) | 20 (15–24) | 0.001 | 1.06 (1.02–1.11) | <0.001 | 1.07 (1.02–1.12) |
Pitt bacteremia score, median (IQR) | 1 (0–3) | 1 (0–4) | 0.48 | 1.03 (0.91–1.18) | ||
Intensive care unit stay | 44 (30) | 15 (27) | 0.73 | 0.89 (0.44–1.79) | ||
Mechanical ventilation | 28 (19) | 8 (15) | 0.47 | 0.73 (0.31–1.72) | ||
Prescription of immunosuppressive therapy |
29 (20) | 14 (26) | 0.36 | 1.40 (0.68–2.91) | ||
Prescription of cancer chemotherapy |
24 (16) | 9 (16) | 0.98 | 1.01 (0.45–2.34) | ||
Recent surgery |
41 (28) | 16 (29) | 0.85 | 1.07 (0.54–2.12) | ||
Persistent CRSAB | 12 (8) | 31 (56) | <0.001 | 14.64 (6.61–32.42) | <0.001 | 13.84 (5.98–32.06) |
Catheter removal >48 hrs after onset of bacteremia | 115 (78) | 43 (78) | 0.94 | 1.03 (0.49–2.17) | ||
Inappropriate antibiotic therapy within 48 hrs | 14 (10) | 11 (20) | 0.04 | 2.39 (1.01–5.66) | 0.03 | 3.04 (1.09–8.45) |
Vancomycin MIC by Etest |
(n = 81) | (n = 41) | ||||
≤1.0 mg/L | 25 (31) | 15 (37) | NA | reference | ||
1.5 mg/L | 38 (47) | 19 (46) | 0.67 | 0.83 (0.36–1.94) | ||
≥2.0 mg/L |
18 (22) | 7 (17) | 0.43 | 0.65 (0.22–1.91) | ||
hVISA |
27 (33) | 18 (44) | 0.25 | 1.57 (0.72–3.38) |
NOTE: Data are no. (%) of patients, unless otherwise indicated. SAB,
Within previous one month.
Analysis was restricted to 122 MRSA cases.
Two isolates had vancomycin MICs of 3 mg/L.
Because most episodes (88%) of persistent CRSAB were caused by MRSA, we further evaluated the microbiological and genotypic characteristics of 122 MRSA isolates associated with persistent and non-persistent CRSAB. There were no significant differences in the distribution of vancomycin MIC and frequency of hVISA phenotype. Accessory gene regulator (
Characteristic | Non-persistent CRSAB (n = 84) | Persistent CRSAB (n = 38) | |
Vancomycin MIC by Etest | 0.16 | ||
≤1.0 mg/L | 23 (27) | 17 (45) | |
1.5 mg/L | 43 (51) | 14 (37) | |
≥2.0 mg/L |
18 (22) | 7 (18) | |
hVISA | 29 (35) | 16 (42) | 0.42 |
Adhesin genes | |||
|
84 (100) | 38 (100) | NA |
|
84 (100) | 38 (100) | NA |
|
0 (0) | 0 (0) | NA |
|
82 (98) | 36 (95) | 0.59 |
|
84(100) | 38 (100) | NA |
|
82 (98) | 38 (100) | >0.99 |
|
3 (4) | 2 (5) | 0.65 |
|
72 (86) | 30 (79) | 0.35 |
|
77 (92) | 36 (95) | 0.72 |
|
81 (96) | 36 (95) | 0.65 |
Toxin genes | |||
|
0 (0) | 0 (0) | NA |
|
0 (0) | 0 (0) | NA |
|
0 (0) | 0 (0) | NA |
|
82 (98) | 35 (92) | 0.17 |
|
51 (61) | 25 (66) | 0.59 |
|
80 (95) | 37 (97) | >0.99 |
|
0 (0) | 0 (0) | NA |
|
81 (96) | 38 (100) | 0.55 |
|
81 (96) | 38 (100) | 0.55 |
|
0 (0) | 0 (0) | NA |
|
0 (0) | 0 (0) | NA |
|
7 (8) | 1 (3) | 0.43 |
|
0 (0) | 0 (0) | NA |
|
56 (67) | 31 (82) | 0.09 |
|
0 (0) | 0 (0) | NA |
|
0 (0) | 0 (0) | NA |
|
75 (89) | 37 (97) | 0.17 |
|
0 (0) | 0 (0) | NA |
|
76 (91) | 36 (95) | 0.72 |
|
0 (0) | 0 (0) | NA |
|
5 (6) | 1 (3) | 0.66 |
|
66 (79) | 34 (90) | 0.15 |
|
74 (88) | 35 (92) | 0.75 |
|
75 (89) | 36 (95) | 0.50 |
|
75 (89) | 37 (97) | 0.17 |
|
2 (2) | 0 (0) | >0.99 |
|
5 (6) | 1 (3) | 0.66 |
|
61 (73) | 32 (84) | 0.16 |
Other virulence genes | |||
|
84 (100) | 38 (100) | NA |
21 (26) | 4 (10) | 0.06 | |
60 (73) | 34 (90) | 0.04 | |
1 (1) | 0 (0) | >0.99 | |
SCCmec type |
|||
63 (76) | 34 (89) | 0.08 | |
6 (7) | 1 (3) | 0.43 | |
14 (17) | 3 (8) | 0.19 |
NOTE: Data are no. (%) of isolates, unless otherwise indicated. CRSAB, catheter-related
Two isolates had vancomycin MICs of 3 mg/L.
Includes 120 isolates: 2 isolates was nontypeable.
Includes 121 isolates: 1 isolate was nontypeable.
Optimal management of CRSAB includes early catheter removal and initiation of appropriate antimicrobial therapy
Persistent bacteremia was more common in episodes caused by MRSA (31% [38/122]) than in those caused by MSSA (6% [5/81]). These results are in line with a prior report documenting the significant association between methicillin resistance and hematogenous complications of CRSAB
Because most episodes (88%) with persistent CRSAB were caused by MRSA, we evaluated the microbiological and genotypic characteristics of MRSA isolates associated with persistent CRSAB. Our investigation also showed that
The presence of non-catheter prosthetic devices was an independent risk factor for persistent CRSAB in this study. This observation is consistent with prior reports documenting high rates of seeding by
Persistent bacteremia after catheter removal and initiation of appropriate antimicrobial therapy usually reflects serious complications of CRSAB, such as septic thrombophlebitis, endocarditis, or metastatic foci of infection
The current study has several limitations. First, it was conducted in a single tertiary care institution and referral center. This may have caused a selection bias towards more severe or complicated cases, resulting in limitations on the generation of the results. Second, clearance of bacteremia was not documented for some patients with non-persistent CRSAB in whom clinical symptoms and signs of CRSAB frequently resolved after catheter removal and initiation of appropriate antimicrobial therapy. However, similar observations were made after analysis was restricted to patients in whom clearance of bacteremia was documented (data not shown). Third, we did not use PFGE to type MRSA blood isolates, and we thus could not evaluate the possibility that clonal relationships may exist among some isolates.
Bacteremia persisted for >3 days after catheter removal and initiation of appropriate antimicrobial therapy in 21% of our CRSAB cases. Baseline risk factors for persistent CRSAB were methicillin resistance, presence of non-catheter prosthetic devices, and renal failure. Persistent CRSAB was associated with high rates of acute complications and infection-related mortality, and its optimal management remains challenging for clinicians.