risk factors for central line–associated bloodstream infection in pediatric intensive care...

Risk Factors for Central Line–Associated Bloodstream Infection in Pediatric Intensive CareUnits • Author(s): Matthew C. Wylie, MD; Dionne A. Graham, PhD; Gail Potter‐Bynoe, BS, CIC;Monica E. Kleinman, MD; Adrienne G. Randolph, MD; John M. Costello, MD, MPH;Thomas J. Sandora, MD, MPHSource: Infection Control and Hospital Epidemiology, Vol. 31, No. 10 (October 2010), pp. 1049-1056Published by: The University of Chicago Press on behalf of The Society for Healthcare Epidemiologyof AmericaStable URL: http://www.jstor.org/stable/10.1086/656246 .

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infection control and hospital epidemiology october 2010, vol. 31, no. 10

o r i g i n a l a r t i c l e

Risk Factors for Central Line–Associated Bloodstream Infectionin Pediatric Intensive Care Units

Matthew C. Wylie, MD; Dionne A. Graham, PhD; Gail Potter-Bynoe, BS, CIC; Monica E. Kleinman, MD;Adrienne G. Randolph, MD; John M. Costello, MD, MPH; Thomas J. Sandora, MD, MPH

objective. We sought to identify risk factors for central line–associated bloodstream infection (CLABSI) to describe children who mightbenefit from adjunctive interventions.

design. Case-control study of children admitted to the medical-surgical intensive care unit (ICU) or cardiac ICU from January 1, 2004,through December 31, 2007.

setting. Children’s Hospital Boston is a freestanding, 396-bed quaternary care pediatric hospital with a 29-bed medical-surgical ICUand a 24-bed cardiac ICU.

patients. Case patients were patients with CLABSI who were identified by means of prospective surveillance. Control subjects werepatients with a central venous catheter who were matched by ICU admission date.

methods. Multivariate conditional logistic regression models were used to identify independent risk factors for CLABSI and to deriveand to validate a prediction rule.

results. Two hundred three case patients were matched with 406 control subjects. Independent predictors of CLABSI included durationof ICU central access (odds ratio [OR] for 15 or more days, 18.41 [95% confidence interval {CI}, 4.10–82.56]; ), central venousP ! .001catheter placement in the ICU (OR for 2 or more ICU-placed catheters, 8.63 [95% CI, 2.63–28.38]; ), nonoperative cardiovascularP p .001disease (OR, 7.44 [95% CI, 2.13–25.98]; ), presence of gastrostomy tube (OR, 3.48 [95% CI, 1.55–7.79]; ), receipt ofP p .012 P p .003parenteral nutrition (OR, 3.12 [95% CI, 1.55–6.32]; ), and receipt of blood transfusion (OR, 2.55 [95% CI, 1.21–5.36];P p .002 P p

). By use of risk factors known before central venous catheter placement, our model predicted CLABSI with a positive predictive value.014of 54% and a negative predictive value of 79%.

conclusions. Duration of central access, receipt of parenteral nutrition, and receipt of blood transfusion were confirmed as risk factorsfor CLABSI among children in the ICU. Newly identified risk factors include presence of gastrostomy tube, nonoperative cardiovasculardisease, and ICU placement of central venous catheter. Children with these risk factors may be candidates for adjunctive interventions forCLABSI prevention.

Infect Control Hosp Epidemiol 2010; 31(10):1049-1056

From the Division of Critical Care Medicine, Department of Anesthesia (M.C.W., M.E.K., A.G.R.), the Clinical Research Program (D.A.G.), the Departmentof Cardiology (D.A.G., J.M.C.), the Infection Prevention and Control Program (G.P.-B., T.J.S.), the Division of Infectious Diseases (T.J.S.), and the Departmentsof Medicine (T.J.S.) and Laboratory Medicine (T.J.S.), Children’s Hospital Boston, Harvard Medical School, Boston, Massachusetts.

Received February 23, 2010; accepted April 25, 2010; electronically published August 23, 2010.� 2010 by The Society for Healthcare Epidemiology of America. All rights reserved. 0899-823X/2010/3110-0010$15.00. DOI: 10.1086/656246

Morbidity and mortality related to healthcare-associated in-fection have been the subject of unprecedented scrutiny fromhealthcare authorities and the public over the last decade.Bloodstream infection is the most common pediatric noso-comial infection, and it is overwhelmingly associated withintravascular catheter use.1 Nationally reported estimates forcentral line–associated bloodstream infections (CLABSIs)among all age groups range from 80,000 to 400,000 infectionsper year.2,3

Although the majority of research has been conducted inadults, pediatric literature published over the past 30 yearsreveals a high incidence of CLABSI in children.4-7 Pooled data

in 2006 from 211 hospitals nationwide showed that, with theexception of units dedicated to treatment of burns, pediatricintensive care units (ICUs) have the highest mean CLABSIrate of all hospital units, despite device use ratios that aresimilar to those in adult ICUs.7 Furthermore, morbidity andmortality due to CLABSI in a pediatric population may exacta greater toll in terms of productive life-years lost becausethe injury occurs at a younger age,8 and approximately halfof the children admitted to the pediatric ICU are previouslyin good or excellent health.9

In addition to increasing morbidity, nosocomial infectionsmarkedly increase the cost of hospitalization.10-16 A large case-



1050 infection control and hospital epidemiology october 2010, vol. 31, no. 10

control study of adverse events in the pediatric ICU foundinfectious complications to be more important predictors ofcosts than were airway or vascular complications.16 More re-cent studies in pediatric ICU populations have supported thisfinding, consistently demonstrating per patient increases ofapproximately $40,000 attributable to CLABSI after adjustingfor age, severity of illness, and underlying disease.13,14

Comprehensive interventions to improve hand hygiene, touse sterile techniques during line insertion and manipulation,to remove unnecessary central venous catheters (CVCs), andto provide reinforcement of these practices are now consid-ered standard practice and have drastically decreased CLABSIincidence and costs related to infection.16,17 Adjunctive strat-egies to prevent CLABSI are available but are associated withadditional costs. Antibiotic-coated catheters and antiseptic-impregnated sponges have been shown to decrease the in-cidence of CLABSI among critically ill adults in multicenter,randomized trials.18-26 Other adjunctive methods for CLABSIprevention, including antibiotic locks, antibiotic flushes, andchlorhexidine bathing, show merit in more limited trials.27-30

Despite the application of evidence-based “bundles” of tech-niques to prevent CLABSI for all ICU patients, infection ratesremain unacceptably high among critically ill children. Theaim of this study was to find risk factors for CLABSI amongchildren in ICUs and thereby to identify candidates for ad-ditional preventive measures.

methods

We performed a case-control study that was reviewed andwas approved by the Committee on Clinical Investigation atChildren’s Hospital Boston. Case patients were identifiedthrough prospective active surveillance by the Children’s Hos-pital Boston Infection Prevention and Control Program. Casepatients were patients admitted to the medical-surgical ICUor cardiac ICU from January 1, 2004, through December 31,2007, who had a CVC and who developed a CLABSI, asdefined by National Healthcare Safety Network (NHSN) cri-teria.31 CVCs included peripherally inserted central catheters,percutaneous temporary CVCs, hemodialysis catheters, to-tally implanted catheters, and tunneled catheters with or with-out hub, as defined by NHSN criteria. Each patient was se-lected once, although patients who had CLABSI in a previoushospitalization were eligible for inclusion as a control subjectin a subsequent ICU stay without CLABSI. No eligible pa-tients were excluded.

For each case patient, we randomly selected 2 control sub-jects who were admitted within 7 days after the case patientwas admitted and who had a CVC but who did not developCLABSI. Case patients and control subjects were matched byunit of admission. Case patients and control subjects werealso matched by date of admission to ensure that changes inCLABSI prevention strategies over time would not influencethe results. Our current CLABSI prevention strategies were

previously reported in our cardiac ICU population and wereimplemented in the medical-surgical ICU in 2005.32

A list of potential risk factors was developed by literaturereview and expert consensus. Case patients and control sub-jects were screened for these risk factors through retrospectivereview of medical records. Data on variables for patients werecollected until the date of CLABSI for case patients and untilthe removal of the CVC or discharge from the ICU, whichevercame sooner, for control subjects. When the line insertiondate could not be determined, the date of ICU admission wasused as a proxy.

Patient characteristics and hospital outcomes (ie, contin-uous variables) were summarized with mean values and stan-dard deviations as well as median values and ranges; cate-gorical variables were reported as counts and percentages.Comparisons of characteristics between case patients andcontrol subjects were made using the 2-sample t test, theWilcoxon rank sum test, and the x2 test, as appropriate. Uni-variate conditional logistic regression models were created toestimate the strength of the association between potentialpredictors and CLABSI. Multivariate conditional logistic re-gression models were used to identify independent risk factorsfor CLABSI. Two-sided P values of less than .05 were con-sidered to be statistically significant. Analyses were performedusing SAS, version 9.2 (SAS Institute).

In a randomly selected derivation set that comprised two-thirds of our data set, a second multivariate analysis wasperformed, and independent risk factors that were known atthe time of CVC placement were identified. These results werethen used to develop a prediction rule. The score for anindividual patient was determined by assigning integers thatreflected the relative influence for each risk factor present andthen summing the points. The prediction rule’s performancewas then tested in a validation set that comprised the re-maining one-third of our data set. Test characteristics of thescore (sensitivity, specificity, positive predictive value, andnegative predictive value) were calculated. Performance ofthe model in the derivation and validation sets was comparedusing receiver operating characteristic (ROC) curves.

results

A total of 203 unique patients developed CLABSI during thestudy period; they were matched with 406 control subjects.Table 1 displays patient characteristics and selected outcomesfor each group. Case patients had longer unadjusted ICUlengths of stay and higher ICU mortality than did controlsubjects. During the study period, the annual number ofCLABSIs and the annual number of CLABSIs in patients withICU-placed CVCs decreased (Figure 1). Gram-positive or-ganisms were the most frequent cause of CLABSI, identifiedin 138 case patients (68%), with coagulase-negative staphy-lococci causing 99 infections, 49% of the total.

Table 2 displays patient-dependent and patient-indepen-dent characteristics that were assessed in univariate analysis



clabsi in pediatric icus 1051

table 1. Patient Characteristics and Selected Outcomes in Study of Central Line–Associated Bloodstream Infectionin Pediatric Intensive Care Units

CharacteristicCase patients

(n p 203)Control subjects

(n p 406) P

Age at admission, median (range), years 0.7 (0–37.5) 3.0 (0–54.0) !.001Gestational age for patients !1 year old, proportion (%)a .005

x35 weeks 88/113 (77.9) 126/139 (90.6)!35 weeks 25/113 (22.1) 13/139 (9.4)

Weight at admission, median (range), kg 6.7 (1.3–182.0) 13.2 (0.2–109.0) !.001Male sex 109 (53.7) 221 (54.4) .86Hospital unit at admission

Medical-surgical ICU 105 (51.7) 210 (51.7)Cardiac ICU 98 (48.3) 196 (48.3)

ICU length of stay, median (range), days 27 (3–395) 3 (0–59) !.001Died in ICU 42 (20.7) 20 (4.9) !.001

note. Data are no. (%) of patients, unless otherwise indicated. ICU, intensive care unit.a Gestational age was evaluated as a risk factor for patients !1 year old.

figure 1. Bar graph showing trend in central line–associatedbloodstream infection (CLABSI) during study period. ICU, intensivecare unit.

as potential risk factors for CLABSI. Compared with patientswho did not develop a CLABSI, patients who developed aCLABSI were younger, more severely ill, and more likely tobe admitted emergently rather than electively. They also weremore likely to receive parenteral nutrition, blood products,vasoactive medications, and intravenous alteplase. Althoughcase patients were more likely than control subjects to receivesteroids, the use of immunosuppressive medications otherthan steroids during hospitalization or in the 2 weeks beforeadmission was not more prevalent in case patients. Patientswho developed CLABSI were also more likely to have receivedan arterial line, mechanical ventilation, and/or extracorporealmembrane oxygenation during the hospitalization.

Catheter characteristics were significantly different be-tween case and control populations. Patients who devel-oped CLABSI were more likely to have a CVC placed in theICU, emergency department, or at an outside hospital. Theywere less likely to have a CVC placed in the operating roomor in interventional radiology. Receipt of percutaneous cath-eter, peripherally inserted central catheter, tunneled cathe-ter, umbilical venous catheter, or catheter for extracorporealmembrane oxygenation was associated with the developmentof CLABSI, whereas receipt of a totally implantable devicewas protective. The femoral and umbilical sites of CVC place-ment were significantly associated with CLABSI.

There was no association between use of dialysis, diabetes,stem cell transplant, or solid-organ transplant and the de-velopment of CLABSI. Oncologic disease was more prevalentin the control subjects. Patients who had an operation (ex-cluding CVC placement) during hospitalization or in the 24hours before their ICU admission were less likely to be a casepatient. However, patients who had multiple surgeries dur-ing their hospitalization were more likely to develop CLABSI,and the association strengthened with increased number ofoperations.

The risk factors that remained significant in multivariateanalyses are presented in Table 3. These include duration ofcentral venous catheterization in the ICU, nonoperative car-

diovascular disease, receipt of gastrostomy tube, receipt ofparenteral nutrition, central line placement in the ICU, andreceipt of a packed red blood cell transfusion.

We also assessed the association with CLABSI for a subsetof risk factors that were present and known at the time ofline placement to derive and to validate a prediction rule.Among these risk factors, independent predictors of CLABSIin both the derivation and validation sets included a PredictedRisk of Mortality (PRISM) score of at least 16, nonoperativecardiovascular disease, receipt of gastrostomy tube, receipt ofmechanical ventilation, and lack of prior operation duringthis hospitalization. Table 4 displays a scoring system thatuses these risk factors at the time of line placement. Figure2 displays the ROC curves for the derivation and validationsets and the test characteristics for the prediction rule.

discussion

We report the results of what is, to our knowledge, the largestpublished case-control study identifying risk factors associ-ated with CLABSI in a critically ill pediatric population. We




table 2. Univariate Risk Factors for Central Line-Associated Bloodstream Infection in Pediatric Intensive Care Units

Risk factorCase patients


(n p 406) Crude OR (95% CI) P

Demographic characteristicAge !.001

X28 days 54 (26.6) 49 (12.1) 3.52 (1.93–6.41)29–364 days 59 (29.1) 91 (22.4) 1.76 (1.05–2.96)1–11 years 44 (21.7) 158 (38.9) 0.7 (0.43–1.14)x12 years 46 (22.7) 108 (26.6) Reference

Gestational age !35 weeks, proportion (%) 25/113 (22.1) 13/139 (9.4) 1.44 (0.66–3.17) .36Weight !5 kg 80 (39.4) 85 (20.9) 2.82 (1.86–4.26) !.001

HospitalizationElective admission 46 (22.7) 197 (48.5) 0.29 (0.20–0.44) !.001Time of admission

7:00 AM–6:59 PM 149 (73.4) 284 (70.0) 1.19 (0.81–1.73) .377:00 PM–6:59 AM 54 (26.6) 122 (30.0) Reference

Median censored ICU length of stay (range), daysa 11 (2–86) 3 (0–59) 1.12 (1.09–1.16) !.001Characteristics of illness

PRISM III scoreb !.0010–5 62 (30.5) 199 (49.0) Reference6–10 61 (30.0) 127 (31.3) 1.59 (1.05–2.41)11–15 42 (20.7) 57 (14.0) 2.39 (1.45–3.96)x16 38 (18.7) 23 (5.7) 5.28 (2.88–9.68)

CPR before ICU admission 15 (7.4) 7 (1.7) 4.77 (1.84–12.36) .001Medical history

Previous ICU admission 117 (57.6) 208 (51.2) 1.32 (0.93–1.88) .12Cardiovascular disease 127 (62.6) 202 (49.8) 4.97 (2.56–9.63) !.001Oncologic disease 11 (5.4) 55 (13.5) 0.36 (0.18–0.71) .003Bone marrow transplant 5 (2.5) 16 (3.9) 0.63 (0.23–1.71) .36Solid-organ transplant 8 (3.9) 22 (5.4) 0.70 (0.29–1.64) .41Dialysis 12 (5.9) 12 (3.0) 2.00 (0.90–4.45) .09Trauma 3 (1.5) 7 (1.7) 0.84 (0.20–3.49) .81Chromosomal abnormality 21 (10.3) 25 (6.2) 1.78 (0.96–3.29) .07Gastrostomy tube 57 (28.1) 66 (16.3) 2.23 (1.43–3.49) !.001Tracheostomy tube 17 (8.4) 14 (3.4) 2.52 (1.22–5.21) .01

Vital signs and laboratory valuesc

Systolic blood pressure !age-corresponding minimumd 24 (11.8) 18 (4.4) 2.84 (1.50–5.37) .001Glasgow Coma Score !8 2 (1.0) 14 (3.4) 0.29 (0.06–1.26) .10pH level, proportion (%) !.001

!7.00 3/164 (1.8) 2/320 (0.6) 2.80 (0.34–22.56)7.00–7.28 73/164 (44.5) 67/320 (20.9) 3.41 (2.10–5.54)17.28 88/164 (53.7) 251/320 (78.4) Reference

White blood cell countLowest count !5,000 cells/mL 20/179 (11.2) 39/357 (10.9) 1.02 (0.56–1.86) .96Highest count 115,000 cells/mL 63/179 (35.2) 115/357 (32.1) 1.14 (0.77–1.69) .51

Hemoglobin level, proportion (%) .81!7.0 g/dL 2/179 (1.1) 5/357 (1.4) Reference7.0–9.9 g/dL 43/179 (24.0) 98/357 (27.5) 1.14 (0.22–6.05)19.9 g/dL 134/179 (74.9) 254/357 (71.1) 1.31 (0.25–6.83)

Platelets !50,000 cells/mL 11/178 (6.2) 18/357 (5.0) 1.14 (0.52, 2.51) .74Interventions

Glucocorticoids 103 (50.7) 129 (31.8) 2.25 (1.58–3.20) !.001Parenteral nutrition 146 (71.9) 94 (23.2) 10.6 (6.44–17.47) !.001Vasoactive medicine 154 (75.9) 196 (48.3) 3.9 (2.56–5.93) !.001Intravenous alteplase administration 56 (27.6) 40 (9.9) 4.19 (2.50–7.00) !.001Blood product transfusion 166 (81.8) 158 (38.9) 8.94 (5.41–14.77) !.001Arterial catheter 178 (87.7) 311 (76.6) 2.41 (1.44–4.05) !.001Mechanical ventilation 190 (93.6) 296 (72.9) 6.4 (3.34–12.23) !.001Extracorporeal membrane oxygenation 27 (13.3) 9 (2.2) 8.29 (3.41–20.18) !.001Operation during hospitalization 125 (61.6) 292 (71.9) 0.58 (0.39–0.85) .006No. of operations during hospitalization !.001

0 78 (38.4) 114 (28.1) Reference1 80 (39.4) 263 (64.8) 0.40 (0.26–0.62)x2 45 (22.2) 29 (7.1) 1.84 (1.06–3.19)

Cardiac catheterization 20 (9.9) 23 (5.7) 2.05 (1.02–4.11) .04




table 2. (Continued)

Risk factorCase patients


(n p 406) Crude OR (95% CI) P

CVC characteristicsDuration of ICU central venous catheterization

Median days (range) 11 (2–86) 2.5 (0–57) 1.17 (1.13–1.22) !.001No. of days !.001

0–3 12 (5.9) 239 (58.9) Reference4–14 121 (59.6) 137 (33.7) 41.3 (13.0–131.4)x15 70 (34.5) 30 (7.4) 142.2 (39.7–509.6)

Type of CVCTemporary percutaneous 156 (76.8) 274 (67.5) 1.68 (1.12–2.52) .01Peripherally inserted central 67 (33.0) 69 (17.0) 2.45 (1.64–3.67) !.001Tunneled 26 (12.8) 20 (4.9) 2.83 (1.53–5.25) !.001Totally implanted 5 (2.5) 43 (10.6) 0.22 (0.08–0.55) .001Intracardiac 48 (23.6) 116 (28.6) 0.69 (0.43–1.10) .11Umbilical 31 (15.3) 20 (4.9) 3.86 (2.04–7.32) !.001

Placement siteFemoral 86 (42.4) 90 (22.2) 2.59 (1.78–3.77) !.001Jugular 89 (43.8) 162 (39.9) 1.21 (0.84–1.76) .31Subclavian 54 (26.6) 94 (23.2) 1.23 (0.82–1.85) .33

Location of CVC placementIntensive care unit 131 (64.5) 106 (26.1) 5.8 (3.81–8.85) !.001Operating room 124 (61.1) 298 (73.4) 0.53 (0.36–0.78) .001Other institution 35 (17.2) 30 (7.4) 2.55 (1.52–4.29) !.001

note. Data are no. (%) of patients, unless otherwise indicated. CI, confidence interval; CPR, cardiopulmonary resuscitation; CVC, centralvenous catheter; ICU, intensive care unit; OR, odds ratio; PRISM, Predicted Risk of Mortality.a When considered as a risk factor, length of stay was censored on the day that the blood sample that eventually tested positive for infectionwas obtained. Length of stay for control subjects was the entire ICU stay.b PRISM III score was calculated with vital sign and laboratory values recorded in the first 12 hours after hospitalization.c Vital sign and laboratory data from the first 12 hours after hospitalization.d Minimum from PRISM score: systolic blood pressure !40 in neonate, !45 in infant, !55 in child, and !65 in adolescent.

found that several patient-level characteristics and ICU in-terventions were independently associated with the devel-opment of CLABSI. Duration of central venous access in theICU, receipt of blood transfusion, and receipt of parenteralnutrition were confirmed to be significant risk factors in ourstudy. Medical cardiovascular disease, receipt of gastrostomytube, and ICU placement of CVC were newly identified riskfactors in this population. Although admission weight andPRISM III score were significant predictors in univariate anal-ysis, they were not independently associated with CLABSI.

Duration of central access is recognized as a consistent riskfactor for bloodstream infection, and national infection pre-vention strategies have emphasized early removal of CVCs.Long-term central venous access is frequently unavoidablein critically ill children. Given the morbidity and mortalitydue to CLABSI and the availability of additional preventivemeasures, identification of other modifiable risk factors iswarranted.

Transfusion of blood products has been identified as a riskfactor for CLABSI in previous prospective and retrospectivestudies.33-35 In our study, receipt of a packed red blood celltransfusion was strongly associated with the development ofCLABSI. Potential mechanisms proposed to account for therisk of blood product transfusion include immune suppres-sion, increased frequency of CVC access, and promotion ofpathogen proliferation.

Similar mechanisms have been proposed to explain the riskconferred by receipt of parenteral nutrition. It has been sug-gested that lipid contamination, glycemic changes, and break-down of gastrointestinal mucosa related to lack of enteralnutrition also contribute to the risk of CLABSI.36 Early tran-sition to enteral feeding will likely reduce the risk of CLABSI.Given the significant risk posed by receipt of transfusionand/or parenteral nutrition, early markers of the need forthese interventions could be useful. Admission hemoglobinand albumin levels were not associated with CLABSI in ourpopulation.

Several potential predictors related to a patient’s immunityhave proven to be controversial as risk factors for CLABSIin critically ill children. Some previous studies have foundneutropenia,35,37,38 leukopenia,35 and steroid administration35

to be independently associated with CLABSI, although othershave not.39,40 Leukopenia was not associated with CLABSI inour study, and the number of patients with neutropenia wastoo small to provide robust evidence about its associationwith CLABSI. Although steroid treatment was associated withCLABSI in univariate analysis, it did not remain an inde-pendent predictor in multivariate analysis. In contrast to pre-vious work in a subset of our population in which hydro-cortisone use was assessed as a risk factor,35 steroid treatmentin this study included shorter courses for airway indica-tions, potentially masking an association between CLABSI




table 3. Independent Risk Factors for Central Line-Associ-ated Bloodstream Infection in Pediatric Intensive Care Units

Risk factor Adjusted OR (95% CI) P

Receipt of parenteralnutrition

3.12 (1.55–6.32) .002

Receipt of packed redblood cell transfusion

2.55 (1.21–5.36) .014

No. of ICU CVCplacements

.001

0 Reference1 2.44 (1.14–5.22)x2 8.63 (2.63–28.38)

Receipt of gastrostomytube

3.48 (1.55–7.79) .003

Status of surgery and CVDa .012No surgery and no CVD ReferenceSurgery and no CVD 1.19 (0.5–2.86)No surgery and CVD 7.44 (2.13–25.98)Surgery and CVD 2.19 (0.65–7.4)

Duration of ICU CVC !.0010–3 days Reference4–14 days 14.72 (4.21–51.47)x15 days 18.41 (4.10–82.56)

note. CI, confidence interval; CVC, central venous catheter; CVD,cardiovascular disease; ICU, intensive care unit; OR, odds ratio.a The interaction term for surgery and CVD was significant at P p

..037

table 4. Independent Risk Factors for Central Line–Associated Bloodstream Infection (Known at Time of LinePlacement) and the Prediction Rule Scoring System

Risk factor

Derivation set Validation setPrediction

scoreOdds ratio P Odds ratio P

PRISM score .002 .070–10 Reference Reference 011–15 2.2 (1.07–4.52) 1.85 (0.65–5.29) 1x16 4.88 (1.83–13.03) 3.16 (1.15–8.72) 3

Receipt of gastrostomy tube 3.06 (1.49–6.3) .002 3.47 (1.26–9.6) .02 2Receipt of mechanical ventilation 6.25 (2.56–15.28) !.001 6.97 (2.1–23.12) .002 4Status of surgery and CVD !.001 .001

No surgery and no CVD 1.56 (0.44–5.54) 0.56 (0.13–2.37) 0Surgery and no CVD 1.22 (0.34–4.31) 0.50 (0.11–2.36) 0No surgery and CVD 11.19 (4.65–26.91) 5.63 (1.86–17.06) 5Surgery and CVD Reference Reference 0

note. CVD, cardiovascular disease; PRISM, Predicted Risk of Mortality.

and longer steroid courses. Also, it is possible that perceivedor actual immune suppression was associated with antibioticadministration, which might have impacted the developmentof CLABSI in our population.

ICU placement of CVCs has not been previously identifiedas a discrete risk factor for pediatric CLABSI. It is likely relatednot only to severity of illness—incompletely controlled forby the inclusion of PRISM III in our model—but also tourgency around CVC placement and access. We suspect thatpatients who have CVCs placed in the ICU receive moremedications, have more frequent access of their CVCs, andexperience more transitions between locations of care. Un-fortunately, it was not feasible to capture these data in our

study. Regardless of etiology, our data suggest that patientswho have a CVC placed in the ICU may be candidates foradjunctive interventions to prevent CLABSI, particularly ifthe patient is receiving a second ICU-placed line.

Medical cardiovascular disease is another novel risk factorindependently associated with CLABSI. There may be lessantibiotic use in this population if hemodynamic abnormal-ities are attributed to cardiac causes rather than to infection.Also, chronic low cardiac output may make tissues moresusceptible to proliferation of pathogenic bacteria.

It is unclear why the presence of a gastrostomy tube wasa risk factor for CLABSI. We suspect that it may be a markerof chronic comorbid illness or poor nutritional status. It isalso possible that patients with a gastrostomy tube are moresusceptible to the transfer of enteric pathogens to their CVCduring routine care. Vigilant attention to skin and tube sitecare may reduce the influence of this risk factor.

Over the past 5 years, a number of best practices to preventCLABSI have become standard in our institution, includingenhanced emphasis on hand hygiene, the use of maximalsterile barriers during CVC insertion, skin antisepsis withchlorhexidine, and efforts to limit line access and to removelines as soon as feasible. The number of CVCs that are placedin our ICUs has also decreased. These interventions have beenassociated with a decrease in the incidence of CLABSI.

Prediction rules can be a useful way for clinicians to quicklyidentify a subset of patients at low or high risk for a givenoutcome. As expected, the performance of our prediction rulein our validation set was not as robust as in the derivationset. Given the relatively low predictive value, more researchis needed to identify additional risk factors that could im-prove its performance. Specifically, unmeasured but poten-tially important factors include adherence to CVC inser-tion and maintenance bundles, number of CVC accesses pershift, antibiotic administration, and patient-dependent fac-tors that may influence susceptibility to infection, such as ge-netic polymorphisms.

Data from a subset of case patients from our cardiac ICU




figure 2. Receiver operating characteristic (ROC) curves comparing prediction rule performance in derivation and validation sets.AUC, area under curve; NPV, negative predictive value; PPV, positive predictive value.

were previously reported.35 However, the present study in-cludes patients from both medical and cardiac ICUs, newcontrol subjects for each case, and a substantially expandedsample size. The single-center design of our study limits gen-eralization of our findings. Because case patients and controlsubjects were not matched for diagnosis, comorbidities, and/or severity of illness at presentation, our crude mortality andlength of stay data likely overestimate the attributable impactof CLABSI. Although we are not able to determine the prob-ability of CLABSI for an individual patient by means of acase-control study, we have highlighted a group of risk factorsthat can help identify patients who are at higher risk forCLABSI.

In addition to strict adherence to the standard infectionprevention practices for all patients, clinicians should con-sider the use of adjunctive interventions to prevent CLABSI,such as antibiotic-coated catheters, antiseptic dressings, orantibiotic locks, for critically ill children with preexisting car-diovascular disease, gastrostomy tubes, or mechanical ven-tilation or those requiring CVC placement in the ICU. Theseinterventions should also be considered for patients who arelikely to require parenteral nutrition or transfusion of bloodproducts. Furthermore, patients at high risk for CLABSI maybe candidates for clinical trials of novel preventative measures.

acknowledgments

We thank Emily Scheer and Patricia Berry for their assistance with databaseaccess, and we acknowledge the Boston Combined Residency Program for

providing structured time and assistance with study design during the CareerDevelopment Block.

Potential conflicts of interest. All authors report no conflicts of interestrelevant to this article.

Address reprint requests to Matthew C. Wylie, MD, Division of CriticalCare Medicine, Department of Anesthesia, Children’s Hospital Boston, 300Longwood Avenue, Bader 634, Boston, MA 02115 ([email protected]).

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