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Three Part Question

In a [preterm neonate, with a central venous catheter in situ, who is bacteremic with coagulase negative staphylococcus] can [catheter sterilisation] be achieved without [increased morbidity or mortality]?

Clinical Scenario

A 10 day old neonate (corrected gestation 29 weeks, birthweight 960g) has been slow to establish feeds. Intravenous access is difficult and he is receiving parenteral nutrition through a CVC. He develops temperature instability and hyperglycaemia. You decide to start empirical intravenous antibiotics but keep the CVC in situ as the infant is relatively stable. Peripherally taken blood cultures grow CoNS. Should the CVC be removed, knowing that a future replacement may be very difficult?

Search Strategy

Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, Database of Abstracts of Reviews of Effectiveness. Pubmed.
"Catheterization, Central Venous"[MESH] AND “Staphylococcus”[MESH], limit (newborn: birth - 1 month). There were 22 hits –one relevant study found5 “Central venous catheter” AND “neonate” and “CONS” [all textwords].

Search Outcome

Cochrane, CCTR and DARE - none found. Pubmed - There were 7 hits – two relevant studies, one previously found

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Benjamin DK Jr et al, 2001	NICU inpatients with central venous catheter and CoNS bacteremia (single positive culture)	Retrospective case notes review (level 4)	Prevalence of end organ damage (meningitis, osteomyelitis, abscess, death)	Sterilisation of catheter was attempted in 72 of 84 neonates with CoNS bacteremia with salvage achieved in 51% without complications
			Complicated bacteremia = end organ damage or >2 positive cultures	Attempt at sterilisation did not significantly increase complicated bacteremia ; Odds Ratio (OR) 7.9 (95% CI 0.97 – 64.5) Significant increased risk of end organ damage after 4 positive blood cultures vs 3 or less; OR 29.6 (95% CI 4.7-186.1)
Karlowicz MG et al, 2002	NICU admission with CVC and CoNS bacteremia (2 +ve culture-same organism)	Observational cohort (level 4)	Persistent bacteremia (>3days)	63 of 119 infants had attempted sterilisation of CVC with salvage in 46% But a 30% absolute increase in persistent bacteremia, NNH 3.3 (95%CI 2.2-6.8).
			Death	No increase in death or recurrent bacteremia. None of 19 patients with bacteremia > 4 days achieved catheter salvage.

Comment(s)

Catheter related sepsis in preterm infants is a common neonatal problem - up to 15.3 infections per 1000 catheter days (2). Inspite of this there is no good quality data informing the decision to remove central catheters in bacteremic neonates. Both papers cited are retrospective case notes reviews. As a result the criteria for removal of catheters was not standardised and the management and follow up of the two groups (catheter retained vs removed) may have differed. Benjamin et al did not distinguish between contaminated blood cultures, catheters colonized with CoNS and true catheter related CoNS sepsis. This is a practical problem for clinicians and researchers alike and has been recently reviewed (3). Karlowicz et al used 2 positive peripheral cultures of the same organism within 3 days as their definition of CONS bacteremia consistent with US Centre for Disease Control guidelines (1). Karlowicz found that attempting CVC sterilisation did increase the risk of prolonged bacteria but the numbers were too small to detect a difference in end organ infection and mortality. The concern that bacteremia may ultimately seed to end organs appears to be supported by Benjamin et al. If the CVC was not removed after four positive cultures there was a significant increase in end organ damage. As the number of positive cultures or the duration of bacteremia increased, CVCs were less likely to be successfully salvaged (4,5). These studies suggest that catheters should be removed in infants who remain bacteremic on treatment as the morbidity increases and the chances of line salvage diminishes with time. It is still unclear exactly how long clinicians should wait before abandoning sterilisation attempts and actually removing the catheter.

Clinical Bottom Line

CVCs infected with coagulase negative staphylococcus can be successfully salvaged in ~50% of cases. Attempting sterilisation of infected lines increases the risk of persistent bacteremia, NNH =3. End organ damage may be increased if the CVC is retained inspite of repeated positive cultures. Prospective randomised studies are required to convincing address the risks vs benefits of treating infected CVCs in situ.

References

1. Benjamin DK Jr, Miller W, Garges H, et al. Bacteremia, central catheters, and neonates: when to pull the line. Pediatrics 2001;107(6):1272-6.
2. Karlowicz MG, Furigay PJ, et al. Central venous catheter removal versus in situ treatment in neonates with coagulase-negative staphylococcal bacteremia. Pediatr Infect Dis J 2002;21(1):22-7.
3. Trotter CW. Percutaneous central venous catheter- related sepsis in the neonate: an analysis of the literature from 1990 – 1994 Neonatal network – Journal of Neonatal Nursing 1996;15(3):15-28.
4. Hodge D, Puntis JWL. Diagnosis, prevention and the management of catheter related bloodstream infection during long term parental nutrition. Arch Dis Child Fetal Neonatal Ed 2002;87:F21-F24.
5. Hospital Infection Control Advisory Committee. Recommendations for preventing the spread of vacomycin resistance. Infect Control Hosp Epidemiol 1995;16:105-133.