Pilot randomized controlled trial (180 patients) of needleless connector decontamination. Central line-associated bloodstream infection occurred in 2% (1/61) of 70% isopropyl alcohol (IPA) wipe, 2% (1/59) of 70% IPA cap, and zero (0/58) infections in 2% chlorhexidine gluconate in 70% IPA wipe patients. Larger definitive trials are feasible and needed

Chopra, Vineet

Flynn, Julie

Gavin, Nicole

Keogh, Samantha

Kleidon, Tricia

Larsen, Emily

Marsh, Nicole

McCarthy, Alexandra L.

Mihala, Gabor

Playford, E Geoffrey

Rickard, Claire M.

Rocha, Patricia Kuerten

Shaw, Joanie

Ullman, Amanda

Zhang, Li

University of Southern Queensland ePrints

American Journal of Infection Control 49 (2021) 269−273Contents lists available at ScienceDirectAmerican Journal of Infection Controljournal homepage: www.aj ic journal .orgBrief ReportNeedleless connector decontamination for prevention of central venousaccess device infection: A pilot randomized controlled trialClaire M Rickard PhD a,b,c,*, Julie Flynn a,b,c,d, Emily Larsen GDHealthRes a,b,c, Gabor Mihala GCBiostats a,e,E Geoffrey Playford PhD a,f, Joanie Shaw GCCancerNurs g, Samantha Keogh PhD a,c,d,Amanda Ullman PhD a,b,c,h, Li Zhang PhD a,i, Nicole Gavin PhD a,c,d, Tricia Kleidon MN (NursePractitioner) a,b,h,Vineet Chopra MD a,j, Alexandra L. McCarthy PhD a,k, Patricia Kuerten Rocha PhD a,l, Nicole Marsh PhD a,b,ca Alliance for Vascular Access Teaching and Research, Menzies Health Institute Queensland, Griffith University, Brisbane, Queensland, Australiab School of Nursing and Midwifery, Griffith University, Brisbane, Queensland, Australiac Centre for Clinical Nursing, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australiad School of Nursing, Queensland University of Technology, Kelvin Grove, Queensland, Australiae School of Medicine, Griffith University, Nathan, Queensland, Australiaf Infection Management Services, Princess Alexandra Hospital, Buranda, Queensland, Australiag Cancer, Immunology and Palliative Care, Gold Coast Health, Southport, Queensland, Australiah Queensland Children’s Hospital, South Brisbane, Queensland, Australiai School of Dental Health Science, Griffith University, Gold Coast, Queensland, Australiaj Internal Medicine, University of Michigan, Ann Arbor, MIk School of Nursing, University of Queensland, St Lucia, Queensland, Australial Federal University of Santa Catarina, Florianopolis, SC, BrazilKey Words:* Address correspondence to Claire M Rickard, PhD,wifery, Griffith University, 170 Kessels Road, Nathan 411E-mail address: c.rickard@griffith.edu.au (C.M. RickarConflicts of Interest: C.M.R\220s employer, Griffith Ustricted investigator-initiated research grants on her beHealth), and consultancy payments on her behalf fromBD-Bard). E.L.\220s employer, Griffith University, has rectigator-initiated grant from Cardinal Health (formerly Meducational (conference) scholarship from Angiodynami(QUT) has received unrestricted educational grants on hfacturers (BD Medical). Griffith University (affiliated instancy payments on her behalf from manufacturers (BD MGriffith University has received unrestricted researchttps://doi.org/10.1016/j.ajic.2020.07.0260196-6553/© 2020 Association for Professionals in Infect(http://creativecommons.org/licenses/by-nc-nd/4.0/)Pilot randomized controlled trial (180 patients) of needleless connector decontamination. Central line-asso-ciated bloodstream infection occurred in 2% (1/61) of 70% isopropyl alcohol (IPA) wipe, 2% (1/59) of 70% IPAcap, and zero (0/58) infections in 2% chlorhexidine gluconate in 70% IPA wipe patients. Larger definitive trialsare feasible and needed.© 2020 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc.This is an open access article under the CC BY-NC-ND license.(http://creativecommons.org/licenses/by-nc-nd/4.0/)CatheterizationCentral venousCatheter related infectionsChlorhexidine gluconateIsopropyl alcoholInfection controlSchool of Nursing and Mid-1, Queensland, Australia.d).niversity, has received unre-half from (BD-Bard; Cardinalmanufacturers (3M, BBraun,eived on her behalf, an inves-edtronic); E.L. has received ancs. S.K.\220s current employerer behalf from product manu-titution) has received consul-edical). A.J.U.\220s employerh grants and payments foreducational lectures from 3M, Becton Dickinson [BD]-Bard, BBraun, and CardinalHealth on her behalf (unrelated to current project). T.M.K.\220s employer, Griffith Uni-versity, has received funding on her behalf for investigator-initiated research or educa-tion grants from BD-Bard and Cardinal health; in addition to funding on her behalf forconsultancy lectures or advice from 3M, Access Scientific, BD-Bard, Medical SpecialtiesAustralia and Vygon. V.C. has received grant support from the Agency for HealthcareResearch and Quality and the American Hospital Association. He has also received roy-alties from Wolters Kluwer Health and Oxford University Press related to books he hasauthored. N.M.\220s previous employer Griffith University has received on her behalfinvestigator-initiated research grants from Becton Dickinson, and Cardinal Health anda consultancy payment provided to Griffith University from Becton Dickinson for clini-cal feedback all things (unrelated to the current project). No other conflicts to report.ion Control and Epidemiology, Inc. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license.BACKGROUNDCentral venous access devices (CVADs) risk central line-associatedbloodstream infection (CLABSI) which increase costs, morbidity andmortality.1 The intraluminal infection source can be minimized byneedleless connector (NC) decontamination prior to each use usingchlorhexidine gluconate (CHG), povidone-iodine, or 70% isopropylalcohol (IPA).1 The optimal antiseptic is unknown, although povi-done-iodine’s slow dry-time presents challenges in clinical practice.2Combination CHG/IPA wipes,3,4 or IPA in a cap format5,6 may be supe-rior to traditional intermittent 70% IPA wipes, but no randomizedcontrolled trials (RCTs) have been completed. Our aim was to270 C.M. Rickard et al. / American Journal of Infection Control 49 (2021) 269−273generate feasibility and pilot data comparing 70% IPA wipes, 2% CHGin 70% IPA wipes, and 70% IPA caps.MATERIALS ANDMETHODSSetting and study designThree-arm pilot RCT at the Royal Brisbane and Women’s Hospitaland Gold Coast University Hospital in Australia. We had Universityand Hospital Ethics Committees approval (2016/410; HREC/15/QRBW/553) and Australian New Zealand Clinical Trials Registry regis-tration: 12615001120561. The 4-week intervention had follow-upuntil 48 hours post study completion, hospital discharge or deviceremoval. We surveyed registered nurses (RNs) for protocol compli-ance and satisfaction.Participants and sample sizeEligibility criteria: ≥18 years of age; CVAD (peripherally insertedcentral catheter or tunneled, cuffed CVAD) inserted <24 hours;CVAD required for ≥7 days; and written consent. Exclusions: base-line bloodstream infection, non-English speaking without inter-preter, or previous enrolment. Research nurses (ReNs) screeneddaily, gave trial information, and obtained consent. The target was60 per group (1 CVAD per patient) with recruitment July 31, 2017 toApril 5, 2019.7Randomization and blindingCentralized, computer-generated randomization (https://randomisation.griffith.edu.au) using randomly varying permuted blocks of 3and 6 (1:1:1 ratio): (1) 70% IPA wipes, (2) 2% CHG in 70% IPA wipes,or (3) 70% IPA caps. Clinical outcome assessors and data analystswere masked.Interventions Seventy percent IPA wipes: 0.6 mL Alcohol Prep Pads (Reynard,New Zealand) applied vigorously to NC for 5 seconds (manufac-turer recommended and hospital policy), visibly dry prior to CVADaccess; Two percent CHG in 70% IPA wipes: 0.6 mL Alcohol and CHG PrepPads (Reynard, New Zealand), applied vigorously to NC for 15 sec-onds (guideline recommendation8), visibly dry prior to CVADaccess; Seventy percent IPA cap: Luer access valve cap Swabcap (intensivecare unit [ICU] Medical, San Clemente) screwed onto NCs for mini-mum 5 minutes (manufacturer-recommended) prior to eachaccess (70% IPA wipes were also used), then replaced with a newcap.NCs were Smartsite Needle-Free Valve or Max Plus (both Carefu-sion/BD, San Diego), attached to the CVAD hubs and all entry pointsof infusion systems.ReNs provided education (clinical staff undertook the interven-tion) and visited twice weekly to collect data, supply products, andreinforce the protocol. Decisions to culture blood/CVAD tips, orremove CVADs were made by medical staff (not investigators).Primary outcome(s)Protocol feasibility was assessed as: (1) eligibility, (2) retentionand attrition, (3) protocol adherence, (4) missing data, and (5) RN sat-isfaction.Secondary outcome(s)(i) CLABSI9 (2018 National Health and Safety Network definition)assessed by masked infectious diseases specialist;(ii) Mortality (all-cause) during trial;(iii) Primary bloodstream infection (laboratory confirmed bloodstreaminfection)9;(iv) CVAD (tip) colonization (≥15 colony-forming units, semi-quantita-tive culture).1Adverse eventsWe captured all potentially intervention-related events, and all-cause ICU admission (serious adverse event).Statistical analysisResearch Electronic Data Capture (REDCap, Nashville, TN) andStata 15 (College Station, TX) were used. Feasibility outcomes wereanalyzed against predetermined criteria (>80% of screened patientseligible and >80% eligible patients recruited; ≥95% retention andattrition (not withdrawn/lost to follow-up); >90% study visits withcorrect products in use, and self-reported RN adherence to applica-tion/dry times; 5% missing data (CLABSI endpoint); RN satisfaction on1-10 numerical rating scale.Clinical outcomes were compared using Fisher’s exact and log-rank tests, incidence rates and Kaplan-Meier survival estimates (P <.05 statistically significant; patients censored at discharge). A modi-fied intention-to-treat analysis excluded only randomized patientswho never received a CVAD.RESULTSPatient/device characteristics are presented in Table 1 andSupplementary Table 1. Average CVAD dwell-times were 11.3, 9.3,and 7.4 days in the 70% IPA, 2% CHG in 70% IPA, and 70% IPA capgroups, respectively.Primary outcomesSeventy percent (211/303) of screened patients were eligible and85% (180/211) were randomized (31 declined, missed, or had CHGallergy; Fig 1). Two patients were excluded postrandomization dueto CVAD insertion failure. There was 100% retention, 0% attrition,and 0% missing CLABSI endpoints (Fig 1). Thus, 178 patients wereanalyzed.Observed protocol adherence was 98% (174/178); all but three 2%CHG in 70% IPA wipe and two 70% IPA cap patients commenced thecorrect intervention. 70% IPA wipe patients had no protocol devia-tions. At least one incorrect product use occurred in 5% (3/58) 2%CHG in 70% IPA, and 10% (6/59) 70% IPA cap patients.Of 35 RNs (40 surveyed, response rate 88%), protocol-adherentscrub times were reported by 31 (89%) for 70% IPA wipe, and 26(74%) for 2% CHG in 70% IPA wipe. Median satisfaction was 9 (inter-quartile range: 2), 10 (2), and 9 (2) for 70% IPA wipes, 2% CHG in 70%IPA wipes, and 70% IPA caps, respectively (N = 22 for 70% IPA caps;not all RNs had used these).Secondary outcomesCLABSI occurred in 1/61 (2%) 70% IPA wipe, 0/58 (0%) 2% CHG in70% IPA wipe, and 1/59 (2%) 70% IPA cap patients (P = 1.0, Fig 2).CLABSI incidence per 1,000 catheter-days was 1.38 (95% confidenceinterval [CI]: 0.19-9.81), nil (no outcomes), and 1.70 (95% CI:Table 1Participant (N = 180) and device (N = 178) characteristics at baseline70% IPA 2% CHG in 70% IPA 70% IPA cap TotalParticipants per study groups* 61 (34) 59 (33) 60 (33) 180 (100)Age (years)y 61 (50-67) 60 (47-67) 63 (50-72) 61 (50-70)Sex: male 31 (51) 28 (47) 37 (62) 96 (53)Cancer treatmentz 19 (31) 18 (31) 17 (28) 54 (30)Admission type- surgical 47 (77) 46 (78) 49 (82) 142 (79)- haematology 12 (20) 10 (17) 10 (17) 32 (18)- medical 1 (2) 3 (5) 1 (2) 5 (3)- medical oncology 1 (2) 0 (0) 0 (0) 1 (1)Comorbidities- nil or one 17 (28) 17 (29) 16 (27) 50 (28)- two or three 20 (33) 16 (27) 20 (33) 56 (31)- four or more 24 (39) 26 (44) 24 (40) 74 (41)Leucocytesx <500/ml (n=179) 5 (8) 5 (9) 5 (8) 15 (8)Pre-existing infection 27 (44) 32 (54) 34 (57) 93 (52)Devices by study groups* 61 (34) 58 (33) 59 (33) 178 (100)Device type- PICC 57 (93) 54 (93) 56 (95) 167 (94)- TC 4 (7) 4 (7) 3 (5) 11 (6)No. of lumens- one 16 (26) 21 (36) 20 (34) 57 (32)- two 45 (74) 37 (64) 39 (66) 121 (68)Location- upper arm 57 (93) 54 (93) 56 (95) 167 (94)- chest 4 (7) 4 (7) 3 (5) 11 (6)IV medications- antibiotics 43 (70) 39 (67) 42 (71) 124 (75)- fluids 24 (39) 25 (43) 21 (36) 70 (39)- blood product 9 (15) 13 (22) 5 (8) 27 (15)- antiemetic 9 (15) 7 (12) 9 (15) 25 (14)- parenteral nutrition 12 (20) 6 (10) 6 (10) 24 (13)- potassium chloride 6 (10) 6 (10) 4 (7) 16 (9)- chemotherapy 4 (7) 5 (9) 5 (8) 14 (8)- antifungal/antiviral 4 (7) 1 (2) 2 (3) 7 (4)- other medication 29 (48) 25 (43) 17 (29) 71 (40)No medications (fluids only) 5 (8) 6 (10) 7 (12) 18 (10)Frequencies and column percentages shown unless otherwise noted.*Row percentage shown.yMedian and interquartile range (25th and 75th percentiles) shown.zIn previous 6 months.xAbsolute, within 72 hours of trial entry.C.M. Rickard et al. / American Journal of Infection Control 49 (2021) 269−273 2710.24-12.1) for 70% IPA wipes, 2% CHG in 70% IPA wipes, and 70% IPAcaps, respectively (P = .637).Primary bloodstream infections occurred in 2/61 (3%) 70% IPAwipe, 2/58 (3%) CHG in 70% IPA wipe (1 of these was a mucosal bar-rier infection), and 1/59 (2%) 70% IPA cap patients. There were nodeaths and no positive catheter tips (N = 10 cultured).Adverse eventsTwo 70% IPA cap NCs became opaque (IPA appeared to seepbetween the rubber inner and outer plastic, denaturing the plasticbut with no effect on patients). Four patients required transfer to ICUfor unrelated reasons (n = 3, 70% IPA wipe; n = 1, 70% IPA cap).DISCUSSIONNC decontamination is a high-volume, high-value practice thaturgently needs high-quality evidence to prevent CLABSI. This pilotRCT confirms the feasibility of large RCTs, with acceptable recruit-ment, protocol adherence, and RN satisfaction, as well as high reten-tion, low attrition and no missing data. Eligibility at 70% could beimproved with amplified research nurse availability at device inser-tion to promote recruitment.CLABSI incidence was low in both groups using 70% IPA, and 0when this antiseptic was combined with CHG. These results areconsistent with laboratory data,3 and a large RCT on pre-CVAD inser-tion skin decontamination which both favored combination CHG andIPA10; a larger RCT would be needed to substantiate these findings inNCs. Although scrub times differed (15 seconds for 2% CHG in 70% IPAwipe as per guidelines,8 and 5 seconds for 70% IPA wipes as per man-ufacturers and hospital policy), recent data indicates no difference ineffectiveness with 5, 10, or 15 second scrub times.4CLABSI was infrequent, however as >50% were patients were dis-charged during follow-up, future RCTs should study the entire CVADdwell (including home care) to ensure adequate sample size to testhypotheses and generalizability. Nevertheless, our CLABSI of approxi-mately 1 per 1,000 catheter-days, is similar to reported USA rates,but may not be generalizable where rates are higher.11 Despite lowfrequency, CLABSI remains the most appropriate outcome to assessNC disinfection efficacy. Other methods such as routine CVAD tip cul-ture have poor positive predictive value.12Insertion bundles have reduced CLABSI, with focus now neededon techniques to prevent postinsertion, intraluminal bacterial entry.Currently, 70% IPA wipes are dominant due to low cost, availabilityand rapid drying2 however the addition of CHG likely increases effi-cacy,3,4 and nonrandomized studies support 70% IPA caps.5,6 PilotRCTs are not designed to test statistical differences in outcomes or forthe effect of potential confounders or covariates such as NC/devicetype or patient factors. Large RCTs are needed to examine variousmodes and strengths of antiseptics, NC materials/designs, andFig 2. Kaplan-Meier survival estimates for central line-associated bloodstream infection by study group. CHG, chlorhexidine gluconate; IPA, isopropyl alcohol.Fig 1. CONSORT flowchart. CHG, chlorhexidine gluconate; CVAD, central venous access device; IPA, isopropyl alcohol;mITT, modified intention-to-treat.272 C.M. Rickard et al. / American Journal of Infection Control 49 (2021) 269−273C.M. Rickard et al. / American Journal of Infection Control 49 (2021) 269−273 273monitor possible new adverse events as solutions are exposed to NCsand potentially the bloodstream.AcknowledgmentsWe thank Marie Cooke, Peter Mollee, Paul Scuffham, and JoanWebster for assistance in obtaining funding and Aidan Menzies forformatting assistance. We thank Christine Woods, Alyson Eastgate,Elise Sturgeon and Melissa Williams for assistance with patientrecruitment and data collection. We thank the patients, relatives andstaff of the participating hospitals.SUPPLEMENTARY MATERIALSSupplementary material associated with this article can be foundin the online version at https://doi.org/10.1016/j.ajic.2020.07.026.References1. O'Grady NP, Alexander M, Burns LA, et al. Guidelines for the prevention of intra-vascular catheter-related infections. Clin Infect Dis. 2011;52:e162–e193.2. Slater K, Fullerton F, Cooke M, Snell S, Rickard CM. Needleless connector dryingtime-how long does it take? Am J Infect Control. 2018;46:1080–1081.3. Flynn JM, Rickard CM, Keogh S, Zhang L. Alcohol caps or alcohol swabs with andwithout chlorhexidine: An in vitro study of 648 episodes of intravenous device nee-dleless connector decontamination. Infect Control Hosp Epidemiol. 2017;38:1–3.4. Slater K, Cooke M, Fullerton F, et al. Peripheral intravenous catheter needlelessconnector decontamination study-Randomized controlled trial. Am J Infect Control.2020;48:1013-1018.5. Wright M-O, Tropp J, Schora DM, et al. Continuous passive disinfection of catheterhubs prevents contamination and bloodstream infection. Am J Infect Control. 2013;41:33–38.6. Casey AL, Karpanen TJ, Nightingale P, Elliott TSJ. An in vitro comparisonof standard cleaning to a continuous passive disinfection cap for the decontamina-tion of needle-free connectors. Antimicrob Resist Infect Control. 2018;7:50.7. Whitehead A, Julious S, Cooper C, Campbell M. Estimating the sample size for apilot randomised trial to minimise the overall trial sample size for the externalpilot and main trial for a continuous outcome variable. Stat Methods Med Res.2016;25:1057–1073.8. Loveday HP, Wilson JA, Pratt RJ, et al. epic3:national evidence-based guidelines forpreventing healthcare-associated infections. J Hosp Infect. 2014;86:S1–70.9. NHSN. National healthcare safety network (NHSN) patient safety component manual.CDC, Ed. Atlanta, GA; 2018:1−38.10. Mimoz O, Lucet JC, Kerforne T, et al. Skin antisepsis with CHG-alcohol vs povidoneiodine-alcohol, with and without skin scrubbing, for prevention of intravascular-catheter-related infection (CLEAN): an open-label, multicentre, two-by-two facto-rial RCT. Lancet. 2015;386:2069–2077.11. Rosenthal VD, Maki DG, Mehta Y, et al. International Nosocomial Infection ControlConsortium (INICC) report, data summary of 43 countries for 2007−2012. Device-associated module. Am J Infect Control. 2014;42:942–956.12. Peterson LR, Smith BA. Nonutility of catheter tip cultures for the diagnosis ofcentral line−associated bloodstream infection. Clin Infect Dis. 2015;60:492–493.

Needleless connector decontamination for prevention of central venous access device infection: A pilot randomized controlled trial

Rickard, Claire M

University of Queensland eSpace

Needleless connector decontamination for prevention of central venous access device infection: a\ua0pilot randomized controlled trial

http://eprints.usq.edu.au/44659/1/Needleless%20connector%20decontamination%20for%20prevention%20of%20central%20venous%20access%20device%20infection.pdf

Needleless connector decontamination for prevention of central venous access device infection: A pilot randomized controlled trial

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