Effect of the use of an antiseptic barrier cap on the rates of central line–associated bloodstream infections in neonatal and pediatric intensive care

ARTICLE IN PRESS American Journal of Infection Control 000 (2019) 1−8

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Major Article

Effect of the use of an antiseptic barrier cap on the rates of central line−associated bloodstream infections in neonatal and pediatric intensive care Onno K. Helder PhD, RN a,b,*, Joost van Rosmalen PhD c, Anneke van Dalen MSc, RN d, Laura Schafthuizen MSc, RN e, Margreet C. Vos PhD, MD f, Robert B. Flint PhD a,g, Enno Wildschut PhD, MD d,  F. Kornelisse PhD, MD a, Erwin Ista PhD, RN d,e Rene a

Department of Pediatrics, Division of Neonatology, Erasmus MC-Sophia Children’s Hospital, Rotterdam, the Netherlands Erasmus MC Create4Care, Erasmus MC, Rotterdam, the Netherlands c Department of Biostatistics, Erasmus MC, Rotterdam, the Netherlands d Department of Intensive Care, Erasmus MC-Sophia Children’s Hospital, Rotterdam, the Netherlands e Department of Internal Medicine, Section of Nursing Science, Erasmus MC, Rotterdam, the Netherlands f Department of Medical Microbiology and Infectious Diseases, Erasmus MC, Rotterdam, the Netherlands g Department of Pharmacy, Erasmus MC, Rotterdam, the Netherlands b

Key Words: Prevention and control Adherence Nursing Sepsis Infection control

Background: The use of antiseptic barrier caps reduced the occurrence of central line−associated bloodstream infections (CLABSI) in adult intensive care settings. We assessed the effect of the use of antiseptic barrier caps on the incidence of CLABSI in infants and children and evaluated the implementation process. Methods: We performed a mixed-method, prospective, observational before-after study. The CLABSI rate was documented during the “scrub the hub method” and the antiseptic barrier cap phase. Main outcomes were the number of CLABSIs per 1,000 catheter days (assessed with a Poisson regression analysis) and nurses’ adherence to antiseptic barrier cap protocol. Results: In total, 2,248 patients were included. The rate of CLABSIs per 1,000 catheter days declined from 3.15 to 2.35, resulting in an overall incidence reduction of 22% (95% confidence interval, −34%, 55%; P = .368). Nurses’ adherence to the antiseptic barrier cap protocol was 95.2% and 89.0% for the neonatal intensive care unit and pediatric intensive care unit, respectively. Discussion: The CLABSI reducing effect of the antiseptic barrier caps seems to be more prominent in the neonatal intensive care unit population compared with the pediatric intensive care unit population. Conclusions: The antiseptic barrier cap did not significantly reduce the CLABSI rates in this study. © 2019 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Central venous catheters (CVCs) and needleless connectors are widely used in intensive care units (ICUs). There is a risk, however, that microorganisms enter the extraluminal side (from the skin during and after catheter insertion) or the intraluminal side (from contaminated catheter hub connectors or intravenous [IV] fluids or bacteremia).1,2 The extraluminal skin route can be protected by applying chlorhexidine gluconate for skin preparation prior to catheter insertion.3 Different studies have shown that intraluminal

*Address correspondence to Onno K. Helder, PhD, RN, Department of Pediatrics, Division of Neonatology, Erasmus MC−Sophia Children’s Hospital, Dr Molewaterplein 60, 3000CB Rotterdam, the Netherlands. E-mail address: [email protected] (O.K. Helder). Conflicts of interest: None to report.

contamination is an important risk for central line−associated bloodstream infections (CLABSIs).1,4,5 Across these studies, the percentage of CLABSI infections attributed to intraluminal contamination ranged from 50%-67%.1,4,5 Needleless connectors were introduced at the end of the previous century to prevent needlestick injuries in health care professionals, and their use is recommended by the US Centers for Disease Control and Prevention (CDC).6,7 On the downside, disinfection of the surface of a needleless connector is more complex than that of a connector with a classic septum. The introduction of needleless ports came along with CLABSI outbreak reports.8 A systematic review and meta-analysis has found that the use of CVC insertion and maintenance bundles effectively reduce the CLABSI

https://doi.org/10.1016/j.ajic.2019.11.026 0196-6553/© 2019 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

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rate.9 One element of the maintenance bundle is disinfection of the needleless connector with chlorhexidine, povidone-iodine, or 70% alcohol before administration of IV medication or fluids.6,10 The disinfection procedure is time-consuming; when done appropriately it takes at least 40 seconds. In practice, this is difficult to achieve, however, given the high workload of nurses.1,11,12 Additionally, there is no consensus concerning the optimal active rubbing time (eg, 10, 15, or 20s).13 In daily practice, nurses often do not correctly apply this disinfection procedure.14 Some 33%-45% of the connector hubs have been found to be contaminated.1,15 To improve the needleless connector disinfection procedure, Menyhay and Maki (2006) developed an antiseptic barrier cap.16 This is a plastic cap placed on the needleless connector, which contains an impregnated sponge saturated with 70% isopropyl alcohol (IPA) that passively disinfects the needleless connector.13 Currently, antiseptic barrier caps are being used in some hospitals, predominantly in adult ICU settings.4,11,17-26 A systematic literature review and meta-analysis showed that this device is associated with a lower incidence of CLABSI in predominantly adult settings, and is worth adding to CVC maintenance bundles.27,28 The effectiveness of the antiseptic barrier cap has not been well studied in children and infants, although specific evidence in these populations is urgently needed as they are characterized by different port-de-entrees of pathogens and possibly other levels of immune compromised patients. One study was performed in a pediatric postacute care hospital, but the authors provided no data on the CLABSI rate.25 Therefore the aims of the study reported here were (1) to assess the effect of the use of antiseptic barrier caps on the CLABSI rate in infants and children admitted to a neonatal intensive care unit (NICU) or pediatric intensive care unit (PICU); and (2) to evaluate the implementation process and nurse’s satisfaction with the use of the antiseptic barrier cap.

METHODS Design and setting We performed a mixed-method, prospective, observational before-after study with a preintervention period and an intervention period. Numbers of CLABSI per 1,000 CVC days and type of pathogens causing CLABSI were measured during the entire study period. During the intervention period, we performed a qualitative study concerning the implementation: feasibility and reasons for (non) adherence to the antiseptic barrier cap. The study was performed in a large tertiary academic children’s hospital in the Netherlands. The NICU is a 34-bed ward with approximately 750 annually admissions, and the PICU is a 28-bed ward with approximately 1,500 annually admissions both divided over 4 units and both including a 6-bed high dependency transfer unit. The NICU and PICU are equipped to provide complex medical treatment, that is, care for extremely low-birth-weight infants (<1,000 grams), surgical repair of complex congenital cardiac malformations, and extra corporal membrane oxygenation. The preintervention period was a 24-month period starting on May 1, 2014, and ending April 30, 2016; the 12 months intervention period started on May 1, 2016, and ended April 30, 2017. All infants admitted to the NICU or PICU of the children’s hospital who had a CVC in place were included in this study according to the ad hoc barrier cap protocol used in both departments. The institutional review board of the University Medical Center considered and approved the study protocol (MEC-2106-061) and waived the need for informed consent. During the intervention period, the antiseptic barrier cap was provided as standard care. The study protocol was registered in the trial register (registration number NTR5833).

Preintervention, intervention, and implementation In the preintervention period, nurses disinfected the needleless connectors according the hospital protocol by short rubbing, <5 seconds, with a gauze impregnated with 70% alcohol combined with 10% IPA and applying an air-dry time of 30 seconds. During the intervention period, the antiseptic barrier cap (Curos, 3M, St. Paul, MN) was introduced. After each access, a new antiseptic barrier cap was placed onto the needleless connector (Q-site, BD Medical, Franklin Lakes, NJ). Barrier caps that are not used in 7 days should be replaced by a new cap. Disinfection between multiple consecutive drug administration was not needed in case a no touch technique was used. Only needleless connectors attached to a CVC that were used or planned to be used for the administration of IV medication were marked with a green sticker with the text “IV administration point.” Antiseptic barrier caps were not used for needleless connectors on a CVC that was used for administration of vasoactive medication to reduce the risk for unwanted hemodynamic changes caused by flushing. The NICU and PICU implemented the use of an antiseptic disinfection cap on needleless connectors on IV medication administration ports on CVCs. At the NICU the antiseptic barrier cap was also applied to immune compromised infants with a peripheral IV catheter (PIV) and/or CVC who are at high risk for bloodstream infections related to either CVCs or PIVs.29 All barrier caps were individually packed and a stock of 5 or a multiple of 5 were stored in a dedicated, cleaned, and lockable box at the patients’ bedside. The housekeeping staff supplemented the stock twice a day, and remaining stock was thrown away after a patient’s discharge. Prior to the start of the intervention period, all nurses were educated and/or trained on how to apply the caps according to the protocol. For this purpose, an instruction video was available on the institutional intranet; 6 training sessions were offered (by O.H., E.I., and L.S.); instruction cards were presented at the medication preparation rooms adjusted for the NICU or the PICU setting; an announcement and instruction was offered in the NICU and PICU newsletter; 4 different screen savers presented at all computer screens of the 2 departments visually reminded all health care professionals of the introduction of the new device, and another series of screen savers providing current data on adherence to the antiseptic barrier cap protocol weekly during the first 6 weeks following on a regular basis.30 CLABSI definition The presence of a CLABSI was defined according to the CDC as “A laboratory-confirmed bloodstream infection (LCBI) where a central line (CL) or umbilical catheter (UC) was in place for >2 calendar days on the date of event, with day of device placement being day 1, AND the line was also in place on the date of event or the day before. If a CL or UC was in place for >2 calendar days and then removed, the day of event of the LCBI must be the day of discontinuation or the next day to be a CLABSI.” Additionally, a common skin contaminant should be identified from 2 or more blood cultures drawn on separate occasions.31 We define a CVC as a tunneled or nontunneled catheter whose proximal part terminated in a large vein, for example, peripherally inserted central catheter, catheter in an umbilical vein, a jugular vein, a femoral vein, or a subclavian vein. Implanted access ports were excluded in this study. Outcome measures The primary outcome measure in both periods was the CLABSI rate per 1,000 CVC days. A secondary outcome was related to the implementation of the barrier cap: implementation feasibility. Implementation feasibility refers to the extent to which nurses adhered to

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the antiseptic barrier cap protocol, and what they perceived as barriers and facilitators for its use. Data collection Data on CLABSI and pathogens causing CLABSI were collected during the entire study period from May 1, 2014 until April 30, 2017. If a patient had a CVC in place and had a positive blood culture, 1 of the researchers (O.H., A.vD., E.I.) reviewed if the definition for CLABSI was met. A NICU neonatologist (R.K.) or PICU intensivist (E. W.) was consulted to solve unclear cases of CLABSI. During the intervention period, adherence to the antiseptic barrier cap protocol was assessed by a nurse practitioner (A.vD.) and nursing research assistants (L.S., J.S.) by direct observation rounds conducted once or twice a week on randomly chosen days. Data concerning compliance or noncompliance were collected for all patients admitted to the NICU and PICU. Adherence was defined as an antiseptic barrier cap being in place at the dedicated needleless medication access point or points. For postoperative patients, this must have been done within 3 hours after arrival on the NICU or PICU. The rate of correctly placed antiseptic barrier caps was calculated by dividing the number of capped needleless connectors by the total number of available needleless connectors. We aimed at achieving an adherence rate above 80%. Feedback on compliance rates of the NICU and PICU departments was shared with the staff. The following demographic data were collected: sex, gestational age (NICU), current age including age category (PICU), birth weight (NICU), weight (PICU), diagnosis, length of stay, and invasive and noninvasive ventilation days. Other collected data were number of positive blood cultures, the found microorganism, and number of CVC days. Adverse events, for example, malfunction of needless access points or unwanted release of the antiseptic barrier caps were standard collected in the general hospital safety reporting system. To explore the feasibility of implementation for users, data were collected by a quantitative questionnaire and interviews. The questionnaire aimed to explore whether the use of the barrier cap fulfilled nurses’ expectations; it was randomly distributed after the start of intervention to 15 NICU nurses and 15 PICU nurses. It contained 5 items concerning the comparison of the conventional disinfection method and the use of the antiseptic barrier cap, daily practical experience, and satisfaction with the use of the antiseptic barrier cap: from 1 (very dissatisfied) to 10 (extremely satisfied). To study patient factors, contextual factors, and user factors of influence that facilitated or impeded the daily usage of the antiseptic barrier cap, we held semistructured interviews with 5 NICU and 6 PICU nurses with at least 18 months’ work experience at the unit in question, and together covering all age and work experience ranges. All interviews were digitally recorded, and transcribed verbatim and thematically analyzed.32

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during the preintervention period was compared with that during the intervention period. CLABSI data were aggregated over 3-month periods. Analyses were performed for the combined dataset and separately for the NICU and PICU. Subgroup analyses were performed on a special vulnerable patient group; that is, infants with birth weight <1,500 grams. A Poisson regression (ie, a generalized linear model with a Poisson error distribution and a logarithmic link function) was used to determine the effect of the use of antiseptic barrier cap on CLABSI rates per 1,000 CVC days. The time at risk in the Poisson model was the number of CVC days per 3-month period. The independent variables in the model were type of ICU (NICU vs PICU) and study period (preintervention vs intervention period). The goodness of fit of the Poisson models was evaluated using the deviance statistic (also known as the log-likelihood ratio test). IBM SPSS version 24 (IBM Corporation, Armonk, NY) and R Statistical Software Version 3.1.3 (R Foundation of Statistical Computing, Vienna, Austria, http:// www.r-project.org) were used for statistical analysis. Two-sided P values of <0.05 were considered statistically significant. RESULTS Data of 2,248 consecutive patients meeting the inclusion criteria were analyzed (Fig 1). None of the patients were excluded from the analyses and/or lost to follow-up, and no patient data were missing. None of the patient characteristics were significantly different between the preintervention and intervention periods (Tables 1 and 2). In the NICU, however, the rate of prematurely born infants in the intervention period was higher than in the preintervention period, and the rate of infants receiving respiratory support was lower in the intervention group than in the preintervention group. In total, fewer infants needed respiratory support in the intervention period. Among those receiving respiratory support at the NICU, the rate of invasive ventilation was higher than that in the preintervention period (Table 1). In the PICU, during the intervention period, more children had been admitted after cardiac surgery compared with the preintervention period. In addition, during the intervention period the rates of infants invasively and noninvasively ventilated in the PICU were higher than those in the preintervention period. More children received invasive ventilation in the intervention period (Table 2). CLABSI rate Overall, the rate of CLABSI per 1,000 CVC days declined from 3.2 in the preintervention period to 2.4 in the intervention period. Thus the overall incidence reduction was 22% (95% confidence interval, −34%, 55%; P = .368). The goodness of fit of the Poisson models was 18.484 (df = 21; P = .618). Detailed data on CLABSIs are given in Table 3. In the subgroup of very low-birth-weight infants, the CLABSI per 1,000 CVC days rate declined from 6.3% in the preintervention period to

Power calculation Historical data showed rates of 4.1 and 7.1 CLABSIs per 1,000 CVC days for the NICU and PICU, respectively. A combined sample size of approximately 8,000 CVC days would be required to detect a 60% reduction of the CLABSI rate (70% power with a 2-sided significance level of 0.05). Statistical analysis Demographics, overall user rating, and adherence are presented as frequencies, median (interquartile range), or mean (SD). The Fisher exact test, the Pearson x2 test, or the Mann-Whitney U test were used for statistical comparison of categorical variables and continuous variables that were not normally distributed. The CLABSI rate

Fig 1. Distribution overview of the recruited NICU and PICU patients. NICU, neonatal intensive care unit; PICU, pediatric intensive care unit.

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Table 1 Clinical characteristics of the infants admitted to the neonatal intensive care unit Characteristics

Preintervention (n = 537)

Intervention (n = 286)

P value

Sex (female; n, %) Gestational age (weeks)y Birth weight (kg)y Number of VLBWz (n, %) Diagnosis (n, %) Prematurityx Respiratory failureǁ Asphyxia{ Congenital abnormalities# Small for gestational age** Early onset sepsisyy Others Ventilation (noninvasive or invasive) Type of ventilation Invasive (n, %) Noninvasive (n, %) Length of stay (days)y

238 (44.3) 30.3 (27.1-35.5) 1.26 (0.92-2.40) 315 (58.7)

123 (43.2) 29.3 (27.1-34.5) 1.27 (0.91-2.16) 172 (60.1)

.768zz .233ǁǁ .545ǁǁ .710zz .011*,xx

243 (45.3) 91 (16.9) 53 (9.9) 42 (7.8) 20 (3.7) 15 (2.8) 73 (13.6) 428 (79.7)

169 (59.1) 25 (8.7) 17 (5.9) 22 (7.7) 6 (2.1) 11 (3.8) 36 (12.6) 192 (67.4)

342 (80.0) 86 (20.0) 13.0 (7.0-34.0)

171 (89.1%) 21 (10.9) 13.0 (7.0-30.0)

.001*,zz .009*,zz

.963ǁǁ

y

Median (interquartile range). z VLBW, very low-birth-weight infants (birth weight <1,500 grams). x Less than 37 weeks gestational age. k Need (non) invasive respiratory support. { Inadequate intake of oxygen before, during, or just after birth. # Structural or functional anomalies that occur during intrauterine life. **An infant having a birth weight lower than expected for its gestational age. yy Sepsis that occurs in the first week of life. zz Fisher exact test. xx Pearson x2 test. kk Mann-Whitney U test.

4.1% in the intervention period. In the NICU, the median time (interquartile range) of CLABSI occurrence after CVC insertion was increased by 3 days in the intervention period and had declined by 2 days in the PICU (Table 3). The incidence reduction was more prominent in the NICU than in the PICU group (Fig 2A and B), however, the difference in incidence reduction between wards was not statistically significant (P = .654). The upper and lower bounds of the 95% confidence interval showed large variations in CLABSI rates in both ICUs, as well as during the preintervention and intervention periods. Table 2 Clinical characteristics of the children admitted to the pediatric intensive care unit

Characteristics Sex (female; n, %) Age (months)y Age category (n, %) Neonatesz 28 days to 1 year 1-4 years 4-12 years >12 years Reasons for admission (n, %) Cardiac and cardiac surgery Postoperative Respiratory failure Congenital abnormalities Neurologic disorders Others Ventilation (noninvasive or invasive; n, %) Type of ventilation Invasive Noninvasive Length of stayy y

Preintervention (n = 945)

Intervention (n = 480)

P value

414 (43.8) 10.0 (1.0-78.0)

208 (43.3) 8 (1.0-65.0)

.910x .190{

211 (22.4) 298 (31.6) 130 (13.8) 166 (17.6) 140 (14.8)

118 (24.6) 155 (32.3) 68 (14.2) 76 (15.8) 63 (13.1)

373 (39.5) 185 (19.6) 125 (13.2) 94 (9.9) 79 (8.3) 89 (9.9) 564 (59.7)

234 (48.8) 79 (16.5) 49 (10.2) 45 (9.1) 43 (9.0) 30 (6.3) 323 (67.3)

.012*,ǁ

.006*,x .663x

548 (97.2) 16 (2.8) 3.0 (1.0-11.0)

Median (interquartile range). An infant during the first 28 days after birth. x Fisher exact test. k Pearson x2 test. { Mann-Whitney U test. z

.736

ǁ

316 (97.8) 7 (2.2) 3.0 (1.0-9.0)

.334{

Gram-negative pathogens were involved in 50 out of the total 66 identified CLABSIs, most of which were Escherichia coli and Enterobacter spp; gram-positive pathogens were involved in 6 CLABSIs, Table 3 Number of CVCs, duration CVC, and analysis of antiseptic barrier cap effectiveness

Total CVC days NICU PICU Number of CVCs >48 hours (%) NICU PICU Total Duration CVCs (days)* NICU PICU Total Number of CLABSIy NICU PICU Total Incidence of CLABSI/1,000 CVC days NICU PICU Total High-risk group (VLBWz infants) NICU Number of VLBW infants Number of CLABSI/1,000 CVC days (%) Day of occurrence CLABSI (after insertion) NICU* PICU*

Preintervention (24 months)

Intervention (12 months)

15,225 6,479 8,776

7,366 3,392 3,974

481 (89.6) 540 (57.1) 1,021 (68.9)

262 (92.0) 260 (54.7) 522 (68.1)

8 (5-14) 3 (2-8) 5 (2-10)

8 (5-13) 3 (2-8) 5 (2-10)

20 28ǁ 48

7 11{ 18

3.1 3.2 3.2

2.1 2.6 2.4

315 20 (6.3) 7.5 (5.2-15.3) 15 (7.5-28.5)

171 7 (4.1) 9 (6-12) 13 (4-19)

CLABSI, central line−associated bloodstream infection; CVC, central venous catheter; NICU, neonatal intensive care unit; PICU, pediatric intensive care unit; VLBW, very lowbirth-weight. *Median (interquartile range). y All CLABSIs occurred in patients with a CVC duration >48 hours. z Very low-birth-weight infants (birth weight <1,500 grams). k Four patients had 2 CLABSIs during admission. { Two patients had 2 CLABSIs during admission.

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Fig 2. (A) Effect of the intervention on CLABSI rates per 1,000 CVC days. CLABSI NICU data aggregated across quarters. ‘Pre’ indicates preintervention and ‘int’ indicates intervention period. (B) Effect of the intervention on CLABSIs per 1,000 CVC days. CLABSI PICU data aggregated across quarters. ‘Pre’ indicates preintervention and ‘int’ indicates intervention period. CI, confidence interval; CLABSI, central line−associated bloodstream infection; CVC, central venous catheter, ICU, intensive care unit.

predominantly coagulase-negative staphylococci (Table 4). Grampositive pathogens were relatively equally found in both study periods. During the intervention period, we did not observe adverse events or malfunction in needleless access points. Implementation outcomes Adherence to use of the barrier cap protocol was observed in 118 direct observation sessions: 73 and 45 at the NICU and PICU, respectively. The adherence rate at the NICU was lowest in the first month with 87.7% and rose to 95.0% or higher (mean adherence rate 95.2% [SD, 3.5]). Adherence to the protocol at the PICU was lowest in the

first month with 86.5% and declined to 75.0% in November (mean adherence rate 89.0% [SD, 7.7]). Twenty-eight out of the 30 invited nurses completed the questionnaire. It appeared that they highly appreciated the use of the antiseptic barrier cap and valued its practicality compared with the rubbing method; they intended to use the antiseptic barrier cap in the future. The mean overall rating score was 9.2 (SD, 0.86) and 8.6 (SD, 0.99) by NICU and PICU nurses, respectively. Facilitators mentioned by the 11 interviewees were the time-saving aspect, the user-friendly design, the improved patient safety, the clear introduction of the antiseptic barrier cap, and the green color clearly indicating the medication access point. PICU nurses stated as a possible barrier that it was not clear whether the antiseptic barrier

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Table 4 Organisms causing CLABSI preintervention and intervention period Department

Preintervention (24 months)

NICU

Gram-positive CoNS Staphylococcus aureus Streptococcus agalactiae

PICU

NICU and PICU

Gram-negative Escherichia coli Enterobacter spp Enterococcus faecalis Klebsiella spp and Pseudomonas spp Others Subtotal NICU Gram-positive CoNS Staphylococcus aureus and CoNS Staphylococcus aureus Gram-negative Escherichia coli Enterobacter spp Citrobacter freundii Enterococcus spp Pantoea septica Klebsiella spp Acinetobacter spp Ralstonia pickettii Raoultella ornithinolytica Others Subtotal PICU Total gram-positive organisms Total CLABSIs

Number

1 1 1

9 4 1 1 2 20 5 1 1

3 3 2 2 1 1 1 1 1 5 28 10 48

Intervention (12 months)

Number

Gram-positive Staphylococcus aureus and CoNS

1

Gram-negative Escherichia coli Klebsiella pneumoniae

2 1

Others

3

7 Gram-positive CoNS Staphylococcus aureus

4 1

Gram-negative Klebsiella spp Stenotrophomonas maltophilia Escherichia coli

1 1 1

Others

2

10 6 18

CLABSI, central line−associated bloodstream infection; CoNS, coagulase-negative staphylococci; NICU, neonatal intensive care unit; PICU, pediatric intensive care unit.

cap should be used if a patient had only a PIV access point; according to the PICU protocol, this needleless access point should not be capped. Furthermore, the operating room assistants did not use the antiseptic barrier cap. Due to many acute interventions during the first hours after admission at the PICU, the ward nurses were too busy, and therefore often placed the caps past the protocol-stated interval of 3 hours.

DISCUSSION To our knowledge, this is the first study that evaluates the effect of the use of antiseptic barrier caps on the occurrence of CLABSIs in a combined NICU and PICU setting. We found that the use of antiseptic barrier caps did not significantly reduce the CLABSI per 1,000 CVC days rate as compared with the preintervention period in which they were not used. Still, nurses highly valued the use of the barrier cap: nurses experienced the antiseptic barrier cap time saving and believed it increased patient safety. The adherence rate was high, not least as a result of the well-prepared implementation of the innovation in the daily workflow. The overview of the CLABSI rates per 1,000 CVC days over time shows fluctuations despite aggregation over 3-month periods. The reducing effect of the use of antiseptic barrier caps on the occurrence of CLABSI per 1,000 CVC days seems to be more prominent in the NICU population compared with the PICU population. A possible explanation is the longer median CVC insertion duration in the NICU compared with the PICU, respectively 8 and 3 days. The antiseptic barrier cap only prevents intraluminal contamination. We assume that the prolonged duration of CVC insertion was associated with a higher number of administrations of IV medication.

The effect of the antiseptic barrier cap in individual studies varied. Four out of 8 studies4,11,17,20 showed a reduction in CLABSI per 1,000 CVC days that was not statistically significant, or significance was not presented. The 4 other studies showed a significant reduction of CLABSI per 1,000 CVC days.19,22-24 Other studies combined the introduction of the antiseptic barrier cap with 1 or more other interventions, for example, a negative displacement connector, IV line scrub, protective vest, dressing protocol, and priming IV sets, which impedes to single out the sole effect of the use of antiseptic barrier caps.25,26,33 The 22% CLABSI per 1,000 CVC days rate reduction in the current study is lower compared with other studies, with rates that ranged between >40% and 68.0%.4,11,17 Gram-negative pathogens were the predominant causative pathogens for CLABSI. Still, it is more likely that patients admitted to our NICU and PICU suffer from bacteremia due to gram-positive microorganisms.34 We suppose that applying the strict CDC definition of laboratory-confirmed bloodstream infections in infants admitted to a NICU leads to underreporting of many coagulase-negative staphylococci. In these settings, taking 2 blood samples drawn on 2 separate occasions is often not opportune, especially in the very ill, and is a subjective decision of the physician. In addition, the clinical signs of bloodstream infection (fever [>38.0°C], hypothermia [<36.0°C], apnea, or bradycardia) in patients under the age of 1 year can be influenced by the incubator thermoregulation and the ventilator can mask apneas or bradycardias.31 To overcome underreporting and identify “real” bloodstream infections we suggest using another definition, for example, the 1 from Stoll et al35: infection occurring >72 hours after admission with at least 1 positive blood culture and an elevated C-reactive protein concentration (>10 mg/L). This definition refers to infants only, and therefore hinders comparison between infants and older populations.

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The use of the antiseptic barrier cap on the needleless connector hub could have led to IV injection of IPA that had not yet been evaporated, although it is not clear to what extent. In the worst case, a maximum of 0.44 mmol IPA could have been injected after each removal of the barrier cap, based on a maximum IPA film layer thickness of 1.0 mm,36 and a 13.2 mm2 surface of the syringe connection to the spilt-septum needleless connector (Q-site, BD Medical). Considering the same approach as Sauron et al,37 with a volume of distribution of 0.9 L/kg, a 500 gram preterm infant could reach at most an IPA concentration of 0.97 mmol/L after each IV fluid administration. This is much lower than the assumed critical concentration of 14 mmol/L, also considering that in neonatal practice, drugs are administered at most 8 time points per day. Moreover, only a limited part of the IPA film on the septum’s surface may be injected, owing to the split septum design of the needleless connectors, the spout of a syringe will push aside the valves. In contrast to the report by Sauron et al,37 we observed no damage to the valve owing to contact with IPA. The considerable exposure to alcohol in the test-composition by Sauron et al37 after the use of the SwabCap (Excelsior Medical, Neptune City, NJ) may have been worsened by damage to the valves from IPA exposure. Our undamaged valves may have contributed to an even lower alcohol exposure. This comforting finding confirms that certain materials are compatible and can safely be combined, whereas others should be avoided. Overall in our study, CLABSIs occurred in a small percentage of patients, with CVC lines in place for longer than a median of 7 days (PICU) or 13 days (NICU). The median placement duration in the PICU is significantly shorter than that in the NICU, probably because of a large postoperative patient population. CVC lines are quickly removed in this population and the protective effect of the antiseptic barrier cap is achieved only for a short time. In addition, the CVC lines used differ between the 2 departments; in the NICU Peripherally Inserted Central Catheter and umbilical lines, and in the PICU jugular and femoral lines are predominantly used. Patients with prolonged CVC placement are high-risk patients with ongoing hemodynamic and respiratory instability, and potential other foci for invasive infections such as skin or surgery lesions, open sternum after cardiac surgery, or ongoing abdominal obstruction or hypoperfusion. It is less likely that the somewhat lower adherence to the use of the antiseptic barrier cap in the PICU has resulted in a moderate effect on CLABSI reduction of 18.6%. Still, the adherence rate in the PICU was higher than that in other studies, which have reported rates ranging from 63%-85%.19,20 Besides studying the effect of the use of the antiseptic barrier cap, we studied implementation outcomes (feasibility and fidelity) to understand the use and adherence of the intervention in daily practice. Reducing the number of health care−associated infections by implementing interventions remains challenging, not least because it requires a behavioral change of health care professionals. Various implementation approaches were taken based on removing potential barriers or facilitating factors for successful implementation of infection prevention strategies. Factors such as additional value and time saving are seen as facilitators for implementing the use of the antiseptic barrier cap, and these factors are also recognized in the literature.4,17 Further, the introduction of the antiseptic barrier cap was aimed to improve patient care and support nurses’ workflow, so as to benefit nurses’ goals and needs in general. This bottom-up approach supports nurses’ capability to improve patient safety and is likely to be effective in other settings. Limitations Several limitations of the study need to be addressed. First, the before-after design introduced different patient characteristics within the 2 study arms. The effect of the inclusion of a higher

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proportion of prematurely born infants during the intervention period in the NICU on the CLABSI incidence is not clear. This holds as well for the lower number of patients on ventilation support in the intervention period, probably because more infants received high flow respiratory support. However, ventilation support like (high flow) nasal cannula was not registered. The same uncertainty applies to the higher number of cardiac patients combined with the higher proportion of ventilator-supported children at the PICU in the intervention period. The higher proportion of cardiac patients in the intervention period was caused by the decision of another cardiac center in the Netherlands to no longer perform cardiac surgery. Second, the power calculation was based on historical CLABSI rates. However, in the preintervention period the CLABSI rates were lower. Therefore this study is probably underpowered. Additionally, the CLABSI rate variation, the somewhat limited number of patients, and the relatively low CLABSI rates impeded detection of a significant CLABSI rate reduction. Third, CLABSI causes and prevention measures are both multifaceted. We cannot rule out that other outcome-relevant elements apart from the introduction of the antiseptic barrier cap were altered during the study period. Still, major potential confounders, such as the antibiotic protocol and the CVC insertion procedures, did not change during the study period. CONCLUSIONS The use of the antiseptic barrier cap did not significantly reduce the CLABSI rates. However, nurses easily adopted the innovation and they valued the time-saving and user-friendly aspects. Large multicenter (cluster), randomized controlled studies are needed to establish a potential reduction effect. Acknowledgements The authors thank Ko Hagoort for editorial advice, and Josianne Smeets and Elise Dijkshoorn for data collection. References 1. Moureau NL, Flynn J. Disinfection of needleless connector hubs: clinical evidence systematic review. Nurs Res Pract 2015;2015:796762. 2. Devrim I, Demiray N, Oruc Y, Sipahi K, Caglar I, Sari F, et al. The colonization rate of needleless connector and the impact of disinfection for 15 s on colonization: a prospective pre- and post-intervention study. J Vasc Access 2019;20:604-7. 3. Marschall J, Mermel LA, Fakih M, Hadaway L, Kallen A, O’Grady NP, et al. Strategies to prevent central line-associated bloodstream infections in acute care hospitals: 2014 update. Infect Control Hosp Epidemiol 2014;35(Suppl 2):89-107. 4. Wright MO, Tropp J, Schora DM, Dillon-Grant M, Peterson K, Boehm S, et al. Continuous passive disinfection of catheter hubs prevents contamination and bloodstream infection. Am J Infect Control 2013;41:33-8. 5. Stevens TP, Schulman J. Evidence-based approach to preventing central line-associated bloodstream infection in the NICU. Acta Paediatr 2012;101:11-6. 6. O’Grady NP, Alexander M, Burns LA, Dellinger EP, Garland J, Heard SO, et al. Guidelines for the prevention of intravascular catheter-related infections. Clin Infect Dis 2011;52:e162-93. 7. Tan L, Hawk JC 3rd, Sterling ML. Report of the Council on Scientific Affairs: preventing needlestick injuries in health care settings. Arch Intern Med 2001;161: 929-36. 8. Mermel LA. What is the predominant source of intravascular catheter infections? Clin Infect Dis 2011;52:211-2. 9. Ista E, van der Hoven B, Kornelisse RF, van der Starre C, Vos MC, Boersma E, et al. Effectiveness of insertion and maintenance bundles to prevent central-line-associated bloodstream infections in critically ill patients of all ages: a systematic review and meta-analysis. Lancet Infect Dis 2016;16:724-34. 10. Loveday HP, Wilson JA, Pratt RJ, Golsorkhi M, Tingle A, Bak A, et al. Epic3: national evidence-based guidelines for preventing healthcare-associated infections in NHS hospitals in England. J Hosp Infect 2014;86(Suppl 1):1-70. 11. Merrill KC, Sumner S, Linford L, Taylor C, Macintosh C. Impact of universal disinfectant cap implementation on central line-associated bloodstream infections. Am J Infect Control 2014;42:1274-7. 12. Hong H, Morrow DF, Sandora TJ, Priebe GP. Disinfection of needleless connectors with chlorhexidine-alcohol provides long-lasting residual disinfectant activity. Am J Infect Control 2013;41:e77-9.

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