Low serum citrulline concentration correlates with catheter-related bloodstream infections in children with intestinal failure

Abstract

Background: Serum citrulline concentration is used as a biomarker of enterocyte mass and enteral tolerance, and low serum concentrations are correlated with bacteremia in immunosuppressed adults undergoing hematopoietic stem cell transplant. The authors sought to determine if citrulline was associated with the development of catheter-related bloodstream infections (CRBSIs) in children with intestinal failure.

Methods: Data were reviewed from 66 children treated in a multidisciplinary intestinal rehabilitation program, who had serum concentration citrulline measured between January 2007 and August 2009. All patients had a diagnosis of intestinal failure requiring parenteral nutrition (PN) support. Exclusion criteria included central venous catheter in situ <30 days, creatinine clearance <20 mL/minute, or a history of organ transplant/immunosuppression.

Results: A total of 15 patients were excluded because of the above criteria. In this cohort of 51 patients, 26 (51%) developed CRBSIs. Both groups were similar in terms of gestational age, diagnosis, nutrition status, and biochemical liver function tests. The mean (± standard deviation [SD]) minimum serum citrulline concentration was significantly lower in patients who developed CRBSIs (6.7 ± 4.6 µmol/L) than in those who did not (11.3 ± 6.4 µmol/L, P = .004). Multivariate logistic regression analysis identified lower minimum serum citrulline concentration and longer central venous catheter duration as independently associated with CRBSI (P = .003 and P = .038, respectively).

Conclusions: Low serum citrulline concentration and longer central venous catheter time are independently associated with CRBSI in children with intestinal failure. Serum citrulline concentration may be a useful biomarker to identify patients with intestinal failure who are at high risk of developing a CRBSI.

Figures

Figure 1

Minimum serum citrulline in patients with and without catheter-related bloodstream infections (CRBSI). Individual data points (triangles) and group means (horizontal lines) are shown. Citrulline was lower in patients with CRBSI (6.7 ± 4.6 μmol/L) than in those without (11.3 ± 6.4 μmol/L) (P = .004).

Figure 2

Minimum preinfection serum citrulline in patients with and without catheter-related bloodstream infections (CRBSIs). Individual data points (triangles) and group means (horizontal lines) are shown. Citrulline was lower in patients with CRBSI (6.6 ± 4.1 μmol/L) than in those without (11.3 ± 6.4 μmol/L) (P = .009).

Figure 3

Histogram comparing minimum serum citrulline in patients with and without catheter-related bloodstream infections (CRBSIs), with superimposed theoretical probability curve from logistic regression. Patients who developed CRBSI (gray bars) had lower citrulline than those who did not (white bars). Probability of CRBSI (black curve) decreases with increasing citrulline (P = .003).

Figure 4

Probability of catheter-related bloodstream infections (CRBSI) based on catheter duration and minimum serum citrulline (Cit). Probability of CRBSI increases with increasing catheter duration (P = .038) and decreasing minimum serum citrulline (P = .003). Multivariate analysis confirmed both variables as significant predictors of CRBSI.