NIHR Signal Central lines coated with antibiotics reduce bloodstream infections in children

Published on 10 May 2016

Children in intensive care had lower rates of infection when using antibiotic coated central lines (also called central venous catheters) compared to standard central lines or those coated with heparin – an anti-clotting agent.

Antibiotic or heparin coated central lines have long been used in adults to reduce catheter-associated bloodstream infections, but evidence for benefits in children was lacking.

This NIHR funded trial provides evidence that use of antibiotic coated central lines could reduce bloodstream infections in paediatric intensive care units. The researchers say cost-effectiveness, based on six-month hospital resource data, will be reported elsewhere. Tis evidence is needed, as are studies that look at the overall costs of any change in practice.

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Why was this study needed?

Bloodstream infections can harm patients and raise healthcare costs.

NICE guidance (Healthcare-associated infections) reported MRSA bloodstream and clostridium difficile infections were recorded as the underlying cause or contributory factor in approximately 9,000 deaths in England in 2007.

Paediatric intensive care units have one of the highest reported rates of hospital-acquired bloodstream infections compared to other specialties, with central lines being a frequent suspected cause. Most children who are admitted to children’s intensive care units have their medicines given to them into their veins using a narrow tube called a central venous catheter or central line. Some hospitals use catheters coated with antibiotics, which might prevent infections by killing bacteria, some use catheters coated with heparin – an anti-clotting medicine, and some use standard catheters.

Antibiotic or heparin coated central lines are used successfully in adults to reduce bloodstream infections but the evidence was lacking for effectiveness in children.

The NIHR funded this trial to help the NHS understand whether antibiotic or heparin coated central lines were better than standard central lines for reducing blood infections in children needing intensive care, and which, if any, of the two coated central line types was best.

What did this study do?

This randomised controlled trial recruited 1,485 children under 16 years admitted to 14 paediatric intensive care units in England between 2010 and 2012.

Children were included only if they were expected to need a central line for three or more days. They were randomised to receive a:

  • a central line coated with antibiotics
  • a central line coated with heparin (an anti-clotting medication), or
  • a standard central line, not coated with anything.

Infection was monitored 48 hours after the catheter was inserted, for 48 hours after it was removed, and deaths were measured up to six months.

Doctors inserting the central line were aware of the type of line inserted, but children, their parents and the intensive unit personnel in charge of their care, were not. Dropout rates were low and similar across treatment groups (range) 7 to 11%. These are signs the trial is unlikely to be biased.

What did it find?

  • Bloodstream infection occurred in significantly fewer children given an antibiotic coated catheter (1.44%) compared to those treated with a standard (3.59%) or heparin coated catheter (3.42%). Bloodstream infection rates using heparin coated catheters did not differ significantly from the standard type.
  • The same pattern of differences was observed for catheter-related bloodstream infections; fewer than 1% infections using antibiotic coated central lines compared with 2% for both standard and heparin coated.
  • Time to get a bloodstream infection was sooner in children given an antibiotic coated catheter (6.9 days) compared with a standard catheter (7.5 days) but later than for those given heparin coated central lines (4.2 days).
  • Forty seven children (95% confidence interval 25 to 500) needed to be treated with an antibiotic coated central line instead of the standard to prevent one case of bloodstream infection (absolute risk difference 2.15%).
  • Central line-related adverse event rates were similar across the three groups: adverse events occurred in 2 to 3% of children.

What does current guidance say on this issue?

There are no NICE recommendations on using antibiotic or heparin coated central venous catheters to prevent bloodstream infections in children in paediatric intensive care units.

Previous initiatives for adults in England aimed at reducing infection include:

  • a 2007 Department of Health best practice guidance on central venous catheter insertion and management through its Saving Lives programme and the 2009/2010
  • a Matching Michigan scheme to prevent central venous catheter bloodstream infection in intensive care units.

What are the implications?

This high-quality trial showed that antibiotic coated central lines significantly reduced the risk of bloodstream infections for children in intensive care compared with standard and heparin coated central lines.

Preventing healthcare-associated infections, including catheter-associated bloodstream infections, is an NHS priority so widespread use of antibiotic coated central lines in children’s intensive care units should form part of this.

The researchers plan to publish a cost-effectiveness analysis using data collected during this trial.

Citation and Funding

Gilbert RE, Mok Q, Dwan K, et al. Impregnated central venous catheters for prevention of bloodstream infection in children (the CATCH trial): a randomised controlled trial. The Lancet. 2016;387(10029):1732-42.

This project was funded by the National Institute for Health Research Health Technology Assessment programme (project number 08/13/47).

Bibliography

DH. Saving Lives: reducing infection, delivering clean and safe care. London: Department of Health; 2007.

Harron K, Mok Q, Dwan K, et al. CATheter Infections in CHildren (CATCH): a randomised controlled trial and economic evaluation comparing impregnated and standard central venous catheters in children. Health Technol Assess. 2016;20(18).

NICE. Healthcare-associated infections: prevention and control in primary and community care. CG139. London: National Institute for Health and Care Excellence; 2012.

O’Grady NP, Alexander M, Burns LA et al. Guidelines for the prevention of intravascular catheter-related infections. Clin Inf Dis.2011;52(9):e162-93.

Why was this study needed?

Bloodstream infections can harm patients and raise healthcare costs.

NICE guidance (Healthcare-associated infections) reported MRSA bloodstream and clostridium difficile infections were recorded as the underlying cause or contributory factor in approximately 9,000 deaths in England in 2007.

Paediatric intensive care units have one of the highest reported rates of hospital-acquired bloodstream infections compared to other specialties, with central lines being a frequent suspected cause. Most children who are admitted to children’s intensive care units have their medicines given to them into their veins using a narrow tube called a central venous catheter or central line. Some hospitals use catheters coated with antibiotics, which might prevent infections by killing bacteria, some use catheters coated with heparin – an anti-clotting medicine, and some use standard catheters.

Antibiotic or heparin coated central lines are used successfully in adults to reduce bloodstream infections but the evidence was lacking for effectiveness in children.

The NIHR funded this trial to help the NHS understand whether antibiotic or heparin coated central lines were better than standard central lines for reducing blood infections in children needing intensive care, and which, if any, of the two coated central line types was best.

What did this study do?

This randomised controlled trial recruited 1,485 children under 16 years admitted to 14 paediatric intensive care units in England between 2010 and 2012.

Children were included only if they were expected to need a central line for three or more days. They were randomised to receive a:

  • a central line coated with antibiotics
  • a central line coated with heparin (an anti-clotting medication), or
  • a standard central line, not coated with anything.

Infection was monitored 48 hours after the catheter was inserted, for 48 hours after it was removed, and deaths were measured up to six months.

Doctors inserting the central line were aware of the type of line inserted, but children, their parents and the intensive unit personnel in charge of their care, were not. Dropout rates were low and similar across treatment groups (range) 7 to 11%. These are signs the trial is unlikely to be biased.

What did it find?

  • Bloodstream infection occurred in significantly fewer children given an antibiotic coated catheter (1.44%) compared to those treated with a standard (3.59%) or heparin coated catheter (3.42%). Bloodstream infection rates using heparin coated catheters did not differ significantly from the standard type.
  • The same pattern of differences was observed for catheter-related bloodstream infections; fewer than 1% infections using antibiotic coated central lines compared with 2% for both standard and heparin coated.
  • Time to get a bloodstream infection was sooner in children given an antibiotic coated catheter (6.9 days) compared with a standard catheter (7.5 days) but later than for those given heparin coated central lines (4.2 days).
  • Forty seven children (95% confidence interval 25 to 500) needed to be treated with an antibiotic coated central line instead of the standard to prevent one case of bloodstream infection (absolute risk difference 2.15%).
  • Central line-related adverse event rates were similar across the three groups: adverse events occurred in 2 to 3% of children.

What does current guidance say on this issue?

There are no NICE recommendations on using antibiotic or heparin coated central venous catheters to prevent bloodstream infections in children in paediatric intensive care units.

Previous initiatives for adults in England aimed at reducing infection include:

  • a 2007 Department of Health best practice guidance on central venous catheter insertion and management through its Saving Lives programme and the 2009/2010
  • a Matching Michigan scheme to prevent central venous catheter bloodstream infection in intensive care units.

What are the implications?

This high-quality trial showed that antibiotic coated central lines significantly reduced the risk of bloodstream infections for children in intensive care compared with standard and heparin coated central lines.

Preventing healthcare-associated infections, including catheter-associated bloodstream infections, is an NHS priority so widespread use of antibiotic coated central lines in children’s intensive care units should form part of this.

The researchers plan to publish a cost-effectiveness analysis using data collected during this trial.

Citation and Funding

Gilbert RE, Mok Q, Dwan K, et al. Impregnated central venous catheters for prevention of bloodstream infection in children (the CATCH trial): a randomised controlled trial. The Lancet. 2016;387(10029):1732-42.

This project was funded by the National Institute for Health Research Health Technology Assessment programme (project number 08/13/47).

Bibliography

DH. Saving Lives: reducing infection, delivering clean and safe care. London: Department of Health; 2007.

Harron K, Mok Q, Dwan K, et al. CATheter Infections in CHildren (CATCH): a randomised controlled trial and economic evaluation comparing impregnated and standard central venous catheters in children. Health Technol Assess. 2016;20(18).

NICE. Healthcare-associated infections: prevention and control in primary and community care. CG139. London: National Institute for Health and Care Excellence; 2012.

O’Grady NP, Alexander M, Burns LA et al. Guidelines for the prevention of intravascular catheter-related infections. Clin Inf Dis.2011;52(9):e162-93.

Impregnated central venous catheters for prevention of bloodstream infection in children (the CATCH trial): a randomised controlled trial

Published on 4 March 2016

Gilbert RE, Mok Q, Dwan K, Harron K, Moitt T, Millar M, Ramnarayan P, Tibby SM, Hughes D, Gamble C

Lancet The , 2016

Background Impregnated central venous catheters are recommended for adults to reduce bloodstream infections but not for children because there is not enough evidence to prove they are effective. We aimed to assess the effectiveness of any type of impregnation (antibiotic or heparin) compared with standard central venous catheters to prevent bloodstream infections in children needing intensive care. Methods We did a randomised controlled trial of children admitted to 14 English paediatric intensive care units. Children younger than 16 years were eligible if they were admitted or being prepared for admission to a participating paediatric intensive care unit and were expected to need a central venous catheter for 3 or more days. Children were randomly assigned (1:1:1) to receive a central venous catheter impregnated with antibiotics, a central venous catheter impregnated with heparin, or a standard central venous catheter with computer generated randomisation in blocks of three and six, stratified by method of consent, site, and envelope storage location within the site. The clinician responsible for inserting the central venous catheter was not masked to allocation, but allocation was concealed from patients, their parents, and the paediatric intensive care unit personnel responsible for their care. The primary outcome was time to first bloodstream infection between 48 h after randomisation and 48 h after central venous catheter removal with impregnated (antibiotic or heparin) versus standard central venous catheters, assessed in the intention-to-treat population. Safety analyses compared central venous catheter-related adverse events in the subset of children for whom central venous catheter insertion was attempted (per-protocol population). This trial is registered with ISRCTN number, ISRCTN34884569. Findings Between Nov 25, 2010, and Nov 30, 2012, 1485 children were recruited to this study. We randomly assigned 502 children to receive standard central venous catheters, 486 to receive antibiotic-impregnated catheters, and 497 to receive heparin-impregnated catheters. Bloodstream infection occurred in 18 (4%) of those in the standard catheters group, 7 (1%) in the antibiotic-impregnated group, and 17 (3%) assigned to heparin-impregnated catheters. Primary analyses showed no effect of impregnated (antibiotic or heparin) catheters compared with standard central venous catheters (hazard ratio [HR] for time to first bloodstream infection 0·71, 95% CI 0·37–1·34). Secondary analyses showed that antibiotic central venous catheters were better than standard central venous catheters (HR 0·43, 0·20–0·96) and heparin central venous catheters (HR 0·42, 0·19–0·93), but heparin did not differ from standard central venous catheters (HR 1·04, 0·53–2·03). Clinically important and statistically significant absolute risk differences were identified only for antibiotic-impregnated catheters versus standard catheters (–2·15%, 95% CI –4·09 to –0·20; number needed to treat [NNT] 47, 95% CI 25–500) and antibiotic-impregnated catheters versus heparin-impregnated catheters (–1·98%, –3·90 to –0·06, NNT 51, 26–1667). Nine children (2%) in the standard central venous catheter group, 14 (3%) in the antibiotic-impregnated group, and 8 (2%) in the heparin-impregnated group had catheter-related adverse events. 45 (8%) in the standard group, 35 (8%) antibiotic-impregnated group, and 29 (6%) in the heparin-impregnated group died during the study. Interpretation Antibiotic-impregnated central venous catheters significantly reduced the risk of bloodstream infections compared with standard and heparin central venous catheters. Widespread use of antibiotic-impregnated central venous catheters could help prevent bloodstream infections in paediatric intensive care units. Funding National Institute for Health Research, UK.

A central venous catheter, also known as a central line, is a tube placed via a smaller vein, in the neck for example, which has its tip in one of the large veins near the heart. This can be used to measure the pressure of blood filling the heart, to give intravenous medicines and to take blood samples. They are used in most children (and adults) who need intensive care.

Central venous catheters carry a risk of infections from skin or other bacteria which travel down the central catheter and enter the blood. A catheter-associated bloodstream infection is serious and usually requires the removal of the central line, antibiotic treatment and placement of another central line.

Expert commentary

This is an important multi-centre study for those working in paediatrics, where guidance lags behind that in adult populations because of a lack of evidence on which to make recommendations. Possibly because of limited power and a low baseline rate, primary analyses demonstrated no significant effect in the time to first bloodstream infection however despite these limitations secondary analyses demonstrated a benefit from the use of antibiotic-impregnated catheters in reducing infection rates by over 50%. Further studies that compare catheter types and cost-effectiveness of use of impregnated catheters are required.

Martin Kiernan, Nurse Consultant, Infection Prevention and Control, Southport and Ormskirk Hospital NHS Trust

Expert commentary

The results of the CATCH trial provide valuable evidence to support the use of antibiotic impregnated central venous catheters in reducing blood stream infections in children as much of the existing evidence base is derived from studies in adults. However, the study was unable to identify any differences in secondary outcomes such as mortality or duration of central venous catheter placement when antibiotic impregnated central venous catheters were compared with standard or heparin impregnated catheters. A cost benefit analysis on the use of antibiotic impregnated central venous catheters will be an important next step.

Carole Fry, Department of Health Nursing Lead on Infectious Disease