BACKGROUND

Guidelines for treatment of central line–associated bloodstream infection (CLABSI) recommend removing central venous catheters (CVCs) in many cases. Clinicians must balance these recommendations with the difficulty of obtaining alternate access and subjecting patients to additional procedures. In this study, we evaluated CVC salvage in pediatric patients with ambulatory CLABSI and associated risk factors for treatment failure.

METHODS

This study was a secondary analysis of 466 ambulatory CLABSIs in patients <22 years old who presented to 5 pediatric medical centers from 2010 to 2015. We defined attempted CVC salvage as a CVC left in place ≥3 days after a positive blood culture result. Salvage failure was removal of the CVC ≥3 days after CLABSI. Successful salvage was treatment of CLABSI without removal of the CVC. Bivariate and multivariable logistic regression analyses were used to test associations between risk factors and attempted and successful salvage.

RESULTS

A total of 460 ambulatory CLABSIs were included in our analysis. CVC salvage was attempted in 379 (82.3%) cases. Underlying diagnosis, CVC type, number of lumens, and absence of candidemia were associated with attempted salvage. Salvage was successful in 287 (75.7%) attempted cases. Underlying diagnosis, CVC type, number of lumens, and absence of candidemia were associated with successful salvage. In patients with malignancy, neutropenia within 30 days before CLABSI was significantly associated with both attempted salvage and successful salvage.

CONCLUSIONS

CVC salvage was often attempted and was frequently successful in ambulatory pediatric patients presenting with CLABSI.

What’s Known on This Subject:

Many pediatric patients need long-term central venous access, placing them at risk for ambulatory central line–associated bloodstream infections (CLABSIs). Salvage therapy is frequently attempted in pediatric inpatient CLABSIs.

What This Study Adds:

In a multicenter study of pediatric ambulatory CLABSIs, salvage therapy was attempted in 82.3% of cases and successful in 75.5% of attempted cases. Characteristics of patients, central venous catheters, and infections may guide clinical decision-making to maximize likelihood of successful central venous catheter salvage.

Central line–associated bloodstream infections (CLABSIs) are common complications of central venous catheter (CVC) use and are associated with significant morbidity and mortality.1,2  The incidence of CLABSI among pediatric patients varies on the basis of device type and underlying diagnosis, and previous studies have found CLABSI rates in pediatric patients ranging from 0.2 to 11.3 infections per 1000 line-days.1,2  Incidence rates for ambulatory CLABSIs in pediatric patients with CVCs are less well understood but may occur at comparable rates to inpatient CLABSIs.3,4 

Children with malignancy or intestinal failure (IF), among other conditions, require long-term venous access, leaving them particularly at risk for ambulatory CLABSIs.2,3,5,6  The Infectious Disease Society of America (IDSA) recommends that CVCs be removed in cases of CLABSI with persistent bacteremia, severe illness, or causative organisms that are difficult to eradicate, such as Staphylococcus aureus, Pseudomonas aeruginosa, or Candida species.6  However, difficulties in finding alternative access sites and desire on the part of clinicians to avoid unnecessary procedures and anesthetics in pediatric patients may lead clinicians to avoid removing or replacing CVCs in in cases of pediatric CLABSI.7  Accordingly, IDSA guidelines permit clinicians to attempt salvaging the CVC in pediatric patients with CLABSIs in cases of “unusual extenuating circumstances.”6 

In few studies, researchers have investigated rates of CVC salvage in pediatric patients with long-term CVCs. Previous studies of pediatric patients with S aureus CLABSIs found that CVC salvage was successful in 68% to 79% of cases.8,9  In one study, CVC salvage failure was significantly associated with polymicrobial infection, inadequate serum concentration of vancomycin, and inadequate empirical treatment of CLABSIs.8  However, to our knowledge there have been no studies of salvage therapy for patients presenting with an ambulatory CLABSI. Because up to 3 times as many CLABSIs occur in ambulatory patients than in hospitalized patients, there is a need to better understand outcomes associated with ambulatory CLABSIs in children.3  In this study, we aimed to understand the epidemiology of CVC salvage in patients with pediatric ambulatory CLABSIs and to examine risk factors associated with salvage failure and outcomes associated with attempted CVC salvage.

This retrospective observational study was conducted at 5 urban, academic, pediatric tertiary care medical centers and was approved by the Biomedical Research Alliance of New York and site-specific institutional review boards. This study was a secondary analysis of data collected to investigate incidence, risk factors, outcomes, and cost of all pediatric ambulatory CLABSIs.10  All pediatric patients from birth to 21 years of age, inclusive, who had an ambulatory visit at 1 of the 5 study sites from October 1, 2010, to September 30, 2015, were eligible for inclusion. The upper age limit of 21 years was chosen on the basis of contemporary pediatric practice of seeing patients through this age and its identification by national pediatric associations.11  To obtain complete event capture from this population, patients who might have been at risk for ambulatory CLABSI were identified with 3 broad queries of electronic medical records, which have been described previously.10  Briefly, the first query included all patients with International Classification of Disease, Ninth Revision (ICD-9) codes for CLABSI or other infection or complication due to CVC or other indwelling devices. The second query included all patients with positive blood culture results and one of the following: ICD-9 diagnosis for a condition with high risk for CVC use, antibiotic lock use, infectious disease clinic visit, and ICD-9 or Current Procedural Terminology codes for CVC insertion, removal, or access. The third query included all patients with an ICD-9 or Current Procedural Terminology code for CVC insertion, removal, or access.

All patients identified by any of the 3 electronic queries received manual chart review to screen for ambulatory CVC presence and ambulatory CLABSI. Chart review was completed by 3 abstractors (W.J.H.F., E.K., and O.O.-B.), who were trained to adjudicate ambulatory CLABSIs by a pediatric hospital epidemiologist (L.S.). Abstractors frequently shared adjudication questions with each other, the lead investigator (M.L.R.), and the hospital epidemiologist. Risk factors and outcomes data for patients with CLABSIs were entered into a REDCap database.12 

The 2015 National Healthcare Safety Network (NHSN) definitions for CLABSI were modified for use in the ambulatory context.13  CLABSI was defined as a known pathogen identified on ≥1 blood culture in a patient with an eligible CVC or as an NHSN-defined common commensal organism identified on ≥2 blood cultures drawn on separate occasions in a patient with an eligible CVC with at least 1 systemic sign or symptom of fever (>38.0°C, chills, or hypotension) or hypothermia (<36.0°C, apnea, or bradycardia in a patient ≤1 year of age). An eligible CVC was any CVC in place for ≥2 days at the time of the positive blood culture result. The NHSN definition of inpatient CLABSI includes infections with positive results on blood cultures drawn ≥48 hours after hospital admission or <48 hours after discharge. In this study, infections were considered ambulatory if the positive blood culture result used to identify the CLABSI was drawn within ≤48 hours of hospital admission or >48 hours after discharge.

Patients with an ambulatory CLABSI were determined to have 1 of 3 possible outcomes: salvage not attempted, salvage attempted and failed, and salvage successful (Fig 1). Similar to previous studies of CVC salvage in S aureus CLABSI, attempted catheter salvage was defined as the CVC left in place ≥3 days after the date that the blood culture used to diagnose ambulatory CLABSI was drawn.8,9  If the CVC was removed <3 days after CLABSI, salvage was considered not to have been attempted. Failed salvage was defined as removal of the CVC ≥3 days after a CLABSI for any reason. Successful salvage was defined as treatment of a CLABSI without removal of the affected CVC. The NHSN defines the repeat-infection time frame as 14 days after CLABSI, with the date of the positive blood culture result as day 1.13  During this time frame, “additional pathogens recovered…from the same type of infection are added to the event.”13  For this reason, instances of positive blood culture results >14 days after a CLABSI in which CVC salvage was attempted were treated as a separate infection and not as failed salvage. Cases in which a new CVC was explicitly placed to treat the CLABSI but it was not clear whether the new CVC was used to treat the patient’s underlying diagnosis were excluded from our analysis because we were unable to determine if salvage had been attempted.

FIGURE 1

Flow diagram of pediatric ambulatory CLABSI included in analysis. Attempted salvage was defined as the CVC in place ≥3 days after the blood culture date. Failed salvage was defined as removal of the CVC ≥3 days after a CLABSI and placement of a new CVC to treat underlying diagnosis. Successful salvage was defined as treatment of a CLABSI without removal of the affected CVC.

FIGURE 1

Flow diagram of pediatric ambulatory CLABSI included in analysis. Attempted salvage was defined as the CVC in place ≥3 days after the blood culture date. Failed salvage was defined as removal of the CVC ≥3 days after a CLABSI and placement of a new CVC to treat underlying diagnosis. Successful salvage was defined as treatment of a CLABSI without removal of the affected CVC.

Close modal

In this study’s primary analysis, we identified associations of patient demographic and clinical factors with the outcomes of (1) attempted CVC salvage and (2) successful CVC salvage in patients with pediatric ambulatory CLABSI. χ2 and Fisher’s exact tests for independence were used to compare categorical data, as appropriate. Mann–Whitney U tests were used to compare continuous data. Data analyses were performed by using SAS version 9.4 (SAS Institute, Inc, Cary, NC), and Prism version 9.0.1 (GraphPad Software, LLC, San Diego, CA). Unadjusted odds ratios (ORs) and adjusted odds ratios (aORs) were estimated from bivariate and multivariable logistic regression models, respectively. The multivariable logistic models included all variables with significant ORs in the bivariate analysis. The 2-tailed threshold for significance was set at P < .05 for all tests.

During a 5-year study period, 247 unique patients experienced a total of 466 ambulatory CLABSIs (Fig 1). Of these, 3 cases resulted in placement of a new CVC that was unrelated to the underlying diagnosis and were excluded from further analysis; a further 3 cases had data entry errors, with removal dates recorded before the date of the blood culture draw, and were excluded from analysis because the correct CVC removal date could not be verified. The remaining 460 ambulatory CLABSIs, experienced by 244 unique patients, were included in analysis.

Of 460 ambulatory CLABSIs, CVC salvage was attempted in 379 (82.3%) cases (Table 1). In the bivariate logistic regression analyses, by using all 460 CLABSIs, 8 risk factors were associated with attempted salvage (Table 1). Of these risk factors, neutropenia, defined as an absolute neutrophil count of <500 cells per μL measured ≤30 days leading up to CLABSI, was only included in the bivariate analysis because this variable was only defined for patients with a primary diagnosis of malignancy. In a multivariable model that included the remaining 7 variables, patients with a CVC type of tunneled external catheter (TEC) (aOR 2.11 [95% confidence interval [CI] 1.02–4.38]) or port (aOR 3.24 [95% CI 1.15–9.17]) had increased odds of receiving salvage therapy compared with patients with peripherally inserted central catheters (PICCs). Patients with single-lumen CVCs had higher odds of receiving salvage therapy compared with patients with multilumen CVCs (aOR 2.00 [95% CI 1.00–3.99]). Patients with a primary diagnosis other than IF or malignancy (aOR 0.40 [95% CI 0.17–0.91]) and patients with candidemia (aOR 0.11 [95% CI 0.04–0.29]) had lower odds of receiving salvage therapy compared with patients with IF and patients without candidemia, respectively.

TABLE 1

Patient Demographics and Characteristics Associated With Attempted Salvage

All, N = 460Salvage Not Attempted (n = 81; 17.8%)Salvage Attempted (n = 379; 82.3%)P (Bivariate Analysis)Unadjusted OR (95% CI)Adjusted ORa (95% CI)
Patient demographics       
 Age, y 5.1 (1.9–10.6) 5.5 (3.1–15.1) 4.6 (1.7–10.3) .01 0.95 (0.91–0.99) 1.0 (0.96–1.05) 
 Sex    .84   
  Female 209 36 (17.2%) 173 (82.8%)  Reference — 
  Male 251 45 (17.9%) 194 (82.1%)  0.95 (0.60–1.54) — 
Primary diagnosis    .001   
 IF 219 24 (11.0%) 195 (89.0%)  Reference Reference 
 Malignancy 143 32 (22.4%) 111 (77.6%)  0.43 (0.24–0.76) 0.50 (0.21–1.17) 
 Other 98 25 (25.5%) 73 (74.5%)  0.36 (0.19–0.67) 0.40 (0.17–0.91) 
CVC type (excludes 20 missing)    <.001   
 TEC 323 47 (14.6%) 276 (85.5%)  3.41 (1.77–6.58) 2.11 (1.02–4.38) 
 Port 68 9 (13.2%) 59 (86.8%)  3.81(1.53–9.46) 3.24 (1.15–9.17) 
 PICC 49 18 (36.7%) 31 (63.3%)  Reference Reference 
No. lumens (excludes 20 missing)    <.001   
 1 332 41 (12.4%) 291 (87.7%)  3.12 (1.85–5.27) 2.00 (1.00–3.99) 
 >1 108 33 (30.6%) 75 (69.4%)  Reference Reference 
Polymicrobial infection    .12   
 Yes 96 22 (22.9%) 74 (77.1%)  0.65 (0.38–1.13) — 
 No 364 59 (16.2%) 305 (83.8%)  Reference — 
Causative organism       
S aureus    .93   
  Infected 81 14 (17.3%) 67 (82.7%)  1.03 (0.55–1.94) — 
  Not infected 379 67 (17.8%) 312 (82.3%)  Reference — 
 Coagulase-negative Staphylococcus    .71   
  Infected 46 9 (19.6%) 37 (80.4%)  0.87 (0.40–1.87) — 
  Not infected 414 72 (17.4%) 342 (82.6%)  Reference — 
Enterobacteriaceae    .02   
  Infected 202 26 (12.9%) 176 (87.1%)  1.83 (1.10–3.05) 1.45 (0.80–2.60) 
  Not infected 258 55 (21.3%) 203 (78.7%)  Reference — 
P aeruginosa    .12   
  Infected 19 6 (31.6%) 13 (68.4%)  0.44 (0.16–1.21) — 
  Not infected 441 75 (17.0%) 336 (83.0%)  Reference — 
Candida spp    <.001   
  Infected 22 13 (59.1%) 9 (40.9%)  0.13 (0.05–0.31) 0.11 (0.04–0.29) 
  Not infected 438 68 (15.5%) 370 (84.5%)  Reference Reference 
Previous CLABSI    .04   
 Yes 242 34 (14.1%) 208 (86.0%)  1.68 (1.04–2.71) 1.03 (0.56–1.88) 
 No 218 47 (21.6%) 171 (78.4%)  Reference Reference 
Bone marrow transplant ≤100 d before CLABSI (excludes 5 missing)    .79   
 Yes 25 5 (20.0%) 20 (80.0%)  0.85 (0.32–2.12) — 
 No 430 75 (17.4%) 355 (82.6%)  Reference — 
Insurance type (excludes 2 missing)    .70   
 Private 150 28 (18.7%) 122 (81.3%)  0.91 (0.54–1.49) — 
 Other 308 53 (17.2%) 255 (82.8%)  Reference — 
Primary immunodeficiency (excludes 2 missing)    .48   
 Yes 14 1 (7.1%) 13 (92.9%)  2.81 (0.36–21.80) — 
 No 444 79 (17.8%) 365 (82.2%)  Reference — 
Neutropenia ≤30 d before CLABSI (of 143 cases in which malignancy was primary diagnosis; excludes 2 missing)    .02   
 Yes 40 4 (10%) 36 (90%)  3.45 (1.13–10.59) b 
 No 101 28 (28%) 73 (72%)  Reference — 
Antibiotic locks ≤7 d before CLABSI (excludes 2 missing)    N/A   
 Yes 0 (0.0%) 2 (100.0%)  — — 
 No 456 80 (17.5%) 376 (82.5%)  — — 
Ethanol locks ≤7 d before CLABSI (excludes 3 missing)    .23   
 Yes 11 0 (0.0%) 11 (100.0%)  — — 
 No 446 80 (17.9%) 366 (82.1%)  — — 
All, N = 460Salvage Not Attempted (n = 81; 17.8%)Salvage Attempted (n = 379; 82.3%)P (Bivariate Analysis)Unadjusted OR (95% CI)Adjusted ORa (95% CI)
Patient demographics       
 Age, y 5.1 (1.9–10.6) 5.5 (3.1–15.1) 4.6 (1.7–10.3) .01 0.95 (0.91–0.99) 1.0 (0.96–1.05) 
 Sex    .84   
  Female 209 36 (17.2%) 173 (82.8%)  Reference — 
  Male 251 45 (17.9%) 194 (82.1%)  0.95 (0.60–1.54) — 
Primary diagnosis    .001   
 IF 219 24 (11.0%) 195 (89.0%)  Reference Reference 
 Malignancy 143 32 (22.4%) 111 (77.6%)  0.43 (0.24–0.76) 0.50 (0.21–1.17) 
 Other 98 25 (25.5%) 73 (74.5%)  0.36 (0.19–0.67) 0.40 (0.17–0.91) 
CVC type (excludes 20 missing)    <.001   
 TEC 323 47 (14.6%) 276 (85.5%)  3.41 (1.77–6.58) 2.11 (1.02–4.38) 
 Port 68 9 (13.2%) 59 (86.8%)  3.81(1.53–9.46) 3.24 (1.15–9.17) 
 PICC 49 18 (36.7%) 31 (63.3%)  Reference Reference 
No. lumens (excludes 20 missing)    <.001   
 1 332 41 (12.4%) 291 (87.7%)  3.12 (1.85–5.27) 2.00 (1.00–3.99) 
 >1 108 33 (30.6%) 75 (69.4%)  Reference Reference 
Polymicrobial infection    .12   
 Yes 96 22 (22.9%) 74 (77.1%)  0.65 (0.38–1.13) — 
 No 364 59 (16.2%) 305 (83.8%)  Reference — 
Causative organism       
S aureus    .93   
  Infected 81 14 (17.3%) 67 (82.7%)  1.03 (0.55–1.94) — 
  Not infected 379 67 (17.8%) 312 (82.3%)  Reference — 
 Coagulase-negative Staphylococcus    .71   
  Infected 46 9 (19.6%) 37 (80.4%)  0.87 (0.40–1.87) — 
  Not infected 414 72 (17.4%) 342 (82.6%)  Reference — 
Enterobacteriaceae    .02   
  Infected 202 26 (12.9%) 176 (87.1%)  1.83 (1.10–3.05) 1.45 (0.80–2.60) 
  Not infected 258 55 (21.3%) 203 (78.7%)  Reference — 
P aeruginosa    .12   
  Infected 19 6 (31.6%) 13 (68.4%)  0.44 (0.16–1.21) — 
  Not infected 441 75 (17.0%) 336 (83.0%)  Reference — 
Candida spp    <.001   
  Infected 22 13 (59.1%) 9 (40.9%)  0.13 (0.05–0.31) 0.11 (0.04–0.29) 
  Not infected 438 68 (15.5%) 370 (84.5%)  Reference Reference 
Previous CLABSI    .04   
 Yes 242 34 (14.1%) 208 (86.0%)  1.68 (1.04–2.71) 1.03 (0.56–1.88) 
 No 218 47 (21.6%) 171 (78.4%)  Reference Reference 
Bone marrow transplant ≤100 d before CLABSI (excludes 5 missing)    .79   
 Yes 25 5 (20.0%) 20 (80.0%)  0.85 (0.32–2.12) — 
 No 430 75 (17.4%) 355 (82.6%)  Reference — 
Insurance type (excludes 2 missing)    .70   
 Private 150 28 (18.7%) 122 (81.3%)  0.91 (0.54–1.49) — 
 Other 308 53 (17.2%) 255 (82.8%)  Reference — 
Primary immunodeficiency (excludes 2 missing)    .48   
 Yes 14 1 (7.1%) 13 (92.9%)  2.81 (0.36–21.80) — 
 No 444 79 (17.8%) 365 (82.2%)  Reference — 
Neutropenia ≤30 d before CLABSI (of 143 cases in which malignancy was primary diagnosis; excludes 2 missing)    .02   
 Yes 40 4 (10%) 36 (90%)  3.45 (1.13–10.59) b 
 No 101 28 (28%) 73 (72%)  Reference — 
Antibiotic locks ≤7 d before CLABSI (excludes 2 missing)    N/A   
 Yes 0 (0.0%) 2 (100.0%)  — — 
 No 456 80 (17.5%) 376 (82.5%)  — — 
Ethanol locks ≤7 d before CLABSI (excludes 3 missing)    .23   
 Yes 11 0 (0.0%) 11 (100.0%)  — — 
 No 446 80 (17.9%) 366 (82.1%)  — — 

Data for age are median (interquartile range). —, not applicable.

a

Estimated from a multivariable logistic regression that included all variables that were significantly associated with salvage attempt in the bivariate analysis, except neutropenia ≤30 d before CLABSI.

b

Neutropenia ≤30 d before CLABSI was not included in the multivariable model because this variable was defined only for the malignancy diagnosis group.

Of 379 ambulatory CLABSIs in which CVC salvage was attempted, salvage was successful in 287 (75.7%) cases (Table 2). In the bivariate logistic regression analyses, 6 risk factors were associated with successful salvage. Neutropenia within ≤30 days before CLABSI was associated with successful salvage; this variable was again excluded from the multivariable analysis because it was only defined for patients with a primary diagnosis of malignancy. In a multivariable model that included the remaining 5 variables, patients with a CVC type of TEC (aOR 2.83 [95% CI 1.21–6.59]) had increased odds of having successful salvage compared with patients with PICCs. Patients with a primary diagnosis other than IF or malignancy (aOR 0.38 [95% CI 0.17–0.84]) and patients with candidemia (aOR 0.03 [95% CI 0.004–0.29]) had lower odds of successful salvage compared with patients with IF and patients without candidemia, respectively.

TABLE 2

Characteristics Associated With Successful Salvage

All, N = 379Salvage Failed (n = 92; 24.3%)Salvage Successful (n = 287; 75.7%)P (Bivariate Analysis)Unadjusted OR (95% CI)Adjusted ORa (95% CI)
Patient demographics       
 Age, y 4.6 (1.7–10.3) 4.9 (2.0–12.3) 4.6 (1.7–10.2) .17 0.97 (0.93–1.01) — 
 Sex    .06   
  Female 173 34 (19.7%) 139 (80.4%)  Reference — 
  Male 206 58 (28.2%) 148 (71.8%)  0.62 (0.39–1.01) — 
Primary diagnosis    <.001   
 IF 195 30 (15.4%) 165 (84.6%)  Reference Reference 
 Malignancy 111 35 (31.5%) 76 (68.5%)  0.40 (0.22–0.69) 0.51 (0.23–1.15) 
 Other 73 27 (37.0%) 46 (63.0%)  0.31 (0.17–0.57) 0.38 (0.17–0.84) 
CVC type    <.001   
 TEC 276 53 (19.2%) 233 (80.8%)  5.11 (2.37–11.0) 2.83 (1.21–6.59) 
 Port 59 19 (32.2%) 40 (67.8%)  2.56 (1.05–6.25) 1.82 (0.66–5.03) 
 PICC 31 17 (54.8%) 14 (45.2%)  Reference Reference 
No. lumens (excluded 13 missing)    <.001   
 1 291 59 (20.3%) 232 (79.7%)  2.61 (1.50–4.46) 1.61 (0.79–3.27) 
 >1 75 30 (40.0%) 45 (60.0%)  Reference Reference 
Polymicrobial infection    .13   
 Yes 74 23 (31.1%) 51 (68.9%)  0.65 (0.37–1.14) — 
 No 305 69 (22.6%) 236 (77.4%)  Reference — 
Causative organism       
S aureus    .10   
  Infected 67 11 (16.4%) 56 (83.6%)  1.79 (0.89–3.57) — 
  Not infected 312 81 (26.0%) 231 (74.0%)  Reference — 
 Coagulase-negative Staphylococcus    .04   
  Infected 37 4 (10.8%) 33 (89.2%)  2.86 (1.10–9.78) 2.82 (0.94–8.53) 
  Not infected 342 88 (25.7%) 254 (74.3%)  Reference Reference 
Enterobacteriaceae       
  Infected 176 40 (22.7%) 136 (77.3%)  1.17 (0.73–1.88) — 
  Not infected 203 52 (25.6%) 151 (74.4%)  Reference — 
P aeruginosa    .53   
  Infected 3 (37.5%) 5 (62.5%)  0.71 (0.21–2.37) — 
  Not infected 366 88 (24.0%) 278 (76.0%)  Reference — 
Candida spp    <.001   
  Infected 8 (88.9%) 1 (11.1%)  0.04 (0.005–0.30) 0.03 (0.004–0.29) 
  Not infected 370 84 (22.7%) 286 (77.3%)  Reference Reference 
Previous CLABSI    .19   
 Yes 208 45 (21.6%) 163 (78.4%)  1.37 (0.86–2.19) — 
 No 171 47 (27.5%) 124 (72.5%)  Reference — 
Bone marrow transplant ≤100 d before CLABSI (excludes 5 missing)    .11   
 Yes 20 8 (40.0%) 12 (60.0%)  0.46 (0.19–1.15) — 
 No 355 84 (23.7%) 271 (76.3%)  Reference — 
Insurance type (excludes 2 missing)    .90   
 Private 122 29 (23.8%) 93 (76.2%)  1.05 (0.64–1.74) — 
 Other 255 63 (24.7%) 192 (75.3%)  Reference — 
Primary immunodeficiency (excludes 2 missing)    .32   
 Yes 13 5 (38.5%) 8 (61.5%)  0.49 (0.15–1.37) — 
 No 365 86 (23.6%) 279 (76.4%)  Reference — 
Neutropenia ≤30 d before CLABSI (of 111 cases in which malignancy was primary diagnosis; excludes 2 missing)    .008   
 Yes 36 5 (14%) 31 (86%)  4.09 (1.41–11.73) b 
 No 73 29 (40%) 44 (60%)  Reference — 
Antibiotic locks ≤7 d before CLABSI (excludes 2 missing)    N/A   
 Yes 0 (0.00%) 2 (100.0%)  — — 
 No 376 92 (24.5%) 284 (75.5%)  — — 
Ethanol locks ≤7 d before CLABSI    .73   
 Yes 11 3 (27.3%) 8 (72.7%)  0.86 (0.22–3.30) — 
 No 366 89 (24.3%) 277 (75.7%)  Reference — 
All, N = 379Salvage Failed (n = 92; 24.3%)Salvage Successful (n = 287; 75.7%)P (Bivariate Analysis)Unadjusted OR (95% CI)Adjusted ORa (95% CI)
Patient demographics       
 Age, y 4.6 (1.7–10.3) 4.9 (2.0–12.3) 4.6 (1.7–10.2) .17 0.97 (0.93–1.01) — 
 Sex    .06   
  Female 173 34 (19.7%) 139 (80.4%)  Reference — 
  Male 206 58 (28.2%) 148 (71.8%)  0.62 (0.39–1.01) — 
Primary diagnosis    <.001   
 IF 195 30 (15.4%) 165 (84.6%)  Reference Reference 
 Malignancy 111 35 (31.5%) 76 (68.5%)  0.40 (0.22–0.69) 0.51 (0.23–1.15) 
 Other 73 27 (37.0%) 46 (63.0%)  0.31 (0.17–0.57) 0.38 (0.17–0.84) 
CVC type    <.001   
 TEC 276 53 (19.2%) 233 (80.8%)  5.11 (2.37–11.0) 2.83 (1.21–6.59) 
 Port 59 19 (32.2%) 40 (67.8%)  2.56 (1.05–6.25) 1.82 (0.66–5.03) 
 PICC 31 17 (54.8%) 14 (45.2%)  Reference Reference 
No. lumens (excluded 13 missing)    <.001   
 1 291 59 (20.3%) 232 (79.7%)  2.61 (1.50–4.46) 1.61 (0.79–3.27) 
 >1 75 30 (40.0%) 45 (60.0%)  Reference Reference 
Polymicrobial infection    .13   
 Yes 74 23 (31.1%) 51 (68.9%)  0.65 (0.37–1.14) — 
 No 305 69 (22.6%) 236 (77.4%)  Reference — 
Causative organism       
S aureus    .10   
  Infected 67 11 (16.4%) 56 (83.6%)  1.79 (0.89–3.57) — 
  Not infected 312 81 (26.0%) 231 (74.0%)  Reference — 
 Coagulase-negative Staphylococcus    .04   
  Infected 37 4 (10.8%) 33 (89.2%)  2.86 (1.10–9.78) 2.82 (0.94–8.53) 
  Not infected 342 88 (25.7%) 254 (74.3%)  Reference Reference 
Enterobacteriaceae       
  Infected 176 40 (22.7%) 136 (77.3%)  1.17 (0.73–1.88) — 
  Not infected 203 52 (25.6%) 151 (74.4%)  Reference — 
P aeruginosa    .53   
  Infected 3 (37.5%) 5 (62.5%)  0.71 (0.21–2.37) — 
  Not infected 366 88 (24.0%) 278 (76.0%)  Reference — 
Candida spp    <.001   
  Infected 8 (88.9%) 1 (11.1%)  0.04 (0.005–0.30) 0.03 (0.004–0.29) 
  Not infected 370 84 (22.7%) 286 (77.3%)  Reference Reference 
Previous CLABSI    .19   
 Yes 208 45 (21.6%) 163 (78.4%)  1.37 (0.86–2.19) — 
 No 171 47 (27.5%) 124 (72.5%)  Reference — 
Bone marrow transplant ≤100 d before CLABSI (excludes 5 missing)    .11   
 Yes 20 8 (40.0%) 12 (60.0%)  0.46 (0.19–1.15) — 
 No 355 84 (23.7%) 271 (76.3%)  Reference — 
Insurance type (excludes 2 missing)    .90   
 Private 122 29 (23.8%) 93 (76.2%)  1.05 (0.64–1.74) — 
 Other 255 63 (24.7%) 192 (75.3%)  Reference — 
Primary immunodeficiency (excludes 2 missing)    .32   
 Yes 13 5 (38.5%) 8 (61.5%)  0.49 (0.15–1.37) — 
 No 365 86 (23.6%) 279 (76.4%)  Reference — 
Neutropenia ≤30 d before CLABSI (of 111 cases in which malignancy was primary diagnosis; excludes 2 missing)    .008   
 Yes 36 5 (14%) 31 (86%)  4.09 (1.41–11.73) b 
 No 73 29 (40%) 44 (60%)  Reference — 
Antibiotic locks ≤7 d before CLABSI (excludes 2 missing)    N/A   
 Yes 0 (0.00%) 2 (100.0%)  — — 
 No 376 92 (24.5%) 284 (75.5%)  — — 
Ethanol locks ≤7 d before CLABSI    .73   
 Yes 11 3 (27.3%) 8 (72.7%)  0.86 (0.22–3.30) — 
 No 366 89 (24.3%) 277 (75.7%)  Reference — 

Data for age are median (interquartile range). —, not applicable.

a

Estimated from a multivariable logistic regression that included all variables that were significantly associated with salvage attempt in the bivariate analysis, except neutropenia ≤30 d before CLABSI.

b

Neutropenia ≤30 d before CLABSI was not included in the multivariable model because this variable was defined only for the malignancy diagnosis group.

To our knowledge, this is the first study of CVC salvage exclusively in pediatric ambulatory CLABSIs. In a 5-year multisite study, CVC salvage was attempted in 82.3% of cases and was successful in 75.7% of those cases. In previous studies of salvage therapy in pediatric CLABSIs, researchers have studied a narrower range of causative organisms and have mainly limited analysis to inpatient CLABSIs. Our results complement earlier findings that CVC salvage occurs frequently in pediatric inpatients with CLABSI, suggesting the need for further work optimizing CVC salvage success.8,9  Although rates of attempted salvage were comparable with previously published data, the rate of successful CVC salvage among this cohort of patients with ambulatory CLABSIs was higher.8  This may be due to differences in the baseline health status of patients who experience a CLABSI in the outpatient environment and potentially more acutely ill inpatients. Although we did not collect antibiotic susceptibility data for ambulatory CLABSIs, it is conceivable that differing rates of antibiotic resistance between the causative organisms of ambulatory and inpatient CLABSIs may contribute to the higher salvage success rate in this cohort. Additionally, the relatively infrequent usage of antibiotic locks and ethanol locks in this population might have affected the likelihood of successful salvage.

By not using pathogen species as an inclusion or exclusion criteria, our study builds on previous research focused on single species. IDSA guidelines differentiate between causative pathogens when giving recommendations for CVC salvage. In particular, guidelines recommend prompt removal of a long-term CVC in a patient experiencing CLABSI in which the causative pathogen is S aureus, P aeruginosa, Candida, or mycobacteria and only recommend clinicians consider salvage in cases of “unusual extenuating circumstances.”6  However, we found no association between patients with S aureus or P aeruginosa CLABSI and attempted salvage or salvage success. Our results suggest patterns of clinical decision-making by individual practitioners or health systems who may be broadly defining these “unusual circumstances,” with apparent success, in the majority of pediatric patients with outpatient CVCs. This pattern may vary by organism, and therefore conclusions may be affected by the heterogeneity of organisms present in this study. It is also possible more fastidious organisms may be misclassified by this methodology as successful salvage, necessitating prospective research to clarify further. However, our study did reinforce the IDSA recommendation to remove CVCs in cases of CLABSI associated with Candida. In our study population, only 9 CLABSIs due to Candida resulted in attempted salvage, with salvage successful in only 1 case. Although it is difficult to draw broad conclusions given the low number of cases due to Candida, among the highly virulent pathogens named in IDSA guidelines as necessitating removal of long-term CVCs, Candida was unique in that it was the only pathogen significantly negatively associated with both attempted and successful salvage in this study.

A key factor in CVC salvage may be the role that CVC characteristics play in the decision to attempt salvage therapy. CVC salvage was more likely to be attempted in single-lumen CVCs compared with double-lumen CVCs. Salvage was also more likely to be attempted in TECs and ports compared with PICCs, which may reflect attempts to avoid invasive and potentially risky procedures to remove and replace these more sophisticated access devices. The higher rates of attempted salvage in CVCs with fewer lumens may reflect past clinical experience or reasonable suspicion on the part of practitioners that salvage therapy in double- and triple-lumen CVCs is less likely to succeed. Our findings suggest that providers may consider early removal and replacement of double- or triple-lumen CVCs to avoid delays in care due to attempted salvage in cases in which success is unlikely.

Underlying clinical circumstances also appear to play a role in the decision to pursue salvage therapy. Although age was not associated with salvage success, we found that patients in whom salvage was attempted were ∼1 year younger than patients who did not undergo salvage. Clinicians may be acting on the basis of differences in perceived risks and benefits of various therapeutic strategies between these 2 populations. We found that practitioners were more likely to attempt CVC salvage when the indication for CVC use was IF or malignancy compared with other diagnoses. We believe this relative preference for attempting CVC salvage in patients with IF or malignancy reflects a risk/benefit calculation on the part of physicians who need to balance the risk of reinfection with patients’ need for long-term vascular access, potentially over many years in the case of IF.4  Additionally, patients’ previous experience with CLABSI may play a role in the decision to attempt salvage because any previous CLABSI was significantly associated with attempted salvage in the bivariate analysis. We hypothesize that these findings may reflect a complicated decision-making process involving concern on the part of clinicians for preserving future vein patency in patients with need for long-term central access and for reducing patient exposure to repeat procedures and attendant risk of complication, which has been noted in IDSA guidelines.6  Contrary to our hypothesis, recent neutropenia was associated with salvage success in a bivariate analysis of patients with malignancy. We hypothesize that this association could be due to patients with neutropenia receiving broader antibiotics and care more quickly after infection was appreciated because of heightened clinician and caregiver awareness of infection, neutropenia suggesting greater need for central access, or clinician reluctance to subject patients with neutropenia to repeated central-line insertion procedures. More research is needed to clarify this association, however because this variable was not included in the multivariable analysis.

As in any retrospective observational study, this study of CVC salvage has limitations. Our data collection was limited to only what was documented in patients’ medical records, and we were unable to identify the specific indication for CVC removal, including central-line dysfunction, or which factors influenced clinicians to pursue salvage. Further study is required to elucidate the basis for clinical decision-making in cases in which CVC salvage may be attempted. We believe our definition of attempted salvage is in line with that in previous studies of CVC salvage in S aureus CLABSI8,9 ; however, this introduces the potential for misclassification bias with respect to whether CVC salvage failed or was successful. Importantly, we did not take into consideration recurrent infections in our analysis, and apparent reinfection with a highly virulent organism may actually reflect failure to adequately treat the first infection, which could have led to overestimation of the true rate of CVC salvage.

In contrast to previous studies of CVC salvage, we collected data that primarily captured ambulatory risk factors for developing CLABSI.10  As such, we were unable to investigate risk factors that have been previously studied for CVC salvage outcomes among pediatric inpatients with CLABSIs, such as admission to the ICU and inotrope support.9  Nor were we able to analyze risk factors, such as specific antibiotic dosing regimens for antimicrobial susceptibility data, that were not collected for the primary study on which this secondary analysis is based. Quantitative blood cultures may be used to differentiate between CLABSI and catheter-related bloodstream infections.14  Because CLABSI was examined in the primary study for this secondary analysis, we did not collect data on quantitative blood cultures, which introduces the possibility for misclassification bias if some of the infections included in our study were bloodstream infections secondary to a non-CVC source. Because IDSA guidelines for treatment of CLABSI differ on the basis of the causative pathogen, our decision to include all CLABSIs regardless of the causative pathogen may obscure important pathogen-specific risk factors associated with CVC salvage. However, we believe that the ability to make comparisons between different pathogens is a strength of our study.

We are unable to present between-site comparisons in this multisite study because of data-sharing agreements with the participating sites. As a result, we were limited in our ability to elucidate institutional differences that may shed light on additional factors in CVC salvage, although interinstitutional differences in management of pediatric patients with CLABSI could conceivably play a significant role in salvage outcomes.

In a 5-year multisite cohort of pediatric patients experiencing ambulatory CLABSI, CVC salvage was attempted in the vast majority of cases and was successful in four-fifths of attempts. These results may reflect greater concern on the part of physicians for balancing the negative outcomes of CLABSI with an imperative to maintain vascular access, particularly among children with chronic conditions. Future researchers should seek to improve selection criteria to identify patients most likely to benefit from salvage therapy and optimal strategies to maximize likelihood of salvage success while minimizing the adverse effects of salvage failure, such as prolonged hospitalization and potentially increased morbidity.

Mr Ford conceptualized and designed the study, led data collection and data storage efforts, conducted the initial analyses, drafted the initial manuscript, and reviewed and revised the manuscript; Drs Rinke, Bundy, Saiman, Rosenberg, DeLaMora, Zachariah, Mirhaji, and Oyeku and Ms Rabin helped conceptualize and design the study, participated in key decisions, contributed to data analysis, and reviewed and revised the manuscript; Ms Klein, Ms Obaro-Best, Mr Drasher, and Mr Peshansky led data collection and data storage efforts, participated in key decisions, contributed to data analysis, and reviewed and revised the manuscript; Dr Heo helped design the study, contributed to data analysis, and reviewed and revised the manuscript; and all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Deidentified individual participant data will not be made available.

FUNDING: Supported by the Agency for Healthcare Research and Quality (grant R01HS24432). The Agency for Healthcare Research and Quality had no role in the design and conduct of this study. Funded by the National Institutes of Health (NIH).

aOR

adjusted odds ratio

CI

confidence interval

CLABSI

central line–associated bloodstream infection

CVC

central venous catheter

ICD-9

International Classification of Disease Ninth Revision

IDSA

Infectious Disease Society of America

IF

intestinal failure

NHSN

National Healthcare Safety Network

OR

odds ratio

PICC

peripherally inserted central catheter

TEC

tunneled external catheter

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Competing Interests

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.