This was a randomized controlled pilot study of Lactobacillus rhamnosus GG versus standard of care to prevent gastrointestinal multidrug-resistant organism (MDRO) colonization in ICU patients. Seventy subjects were included in analyses. There were no significant differences in acquisition or loss of any MDROs (p>0.05). There were no probiotic-associated adverse events

Babcock, Hilary M

Bommarito, Kerry M

Burnham, Carey-Ann D

Dubberke, Erik R

Fraser, Victoria J

Hink, Tiffany

Kollef, Marin H

Kwon, Jennie H

Reske, Kimberly A

Seiler, Sondra M

English

PubMed

This was a randomized controlled pilot study of Lactobacillus rhamnosus GG versus standard of care to prevent gastrointestinal multidrug-resistant organism colonization in intensive care unit patients. Among 70 subjects, there were no significant differences in acquisition or loss of any multidrug-resistant organisms (P&gt;.05) and no probiotic-associated adverse events.Infect. Control Hosp. Epidemiol. 2015;36(12):1451–1454</jats:p

Jennie H. Kwon

Kerry M. Bommarito

Kimberly A. Reske

Sondra M. Seiler

Tiffany Hink

Hilary M. Babcock

Marin H. Kollef

Victoria J. Fraser

Carey-Ann D. Burnham

Erik R. Dubberke

Crossref

Infection Control and Hospital Epidemiology

Randomized Controlled Trial to Determine the Impact of Probiotic Administration on Colonization With Multidrug-Resistant Organisms in Critically Ill Patients

Digital Commons@Becker

Washington University School of MedicineDigital Commons@BeckerOpen Access Publications2015Randomized controlled trial to determine theimpact of probiotic administration on colonizationwith multidrug-resistant organisms in critically illpatientsJennie H. KwonWashington University School of Medicine in St. LouisKerry M. BommaritoWashington University School of Medicine in St. LouisKimberly A. ReskeWashington University School of Medicine in St. LouisSondra M. SeilerWashington University School of Medicine in St. LouisTiffany HinkWashington University School of Medicine in St. LouisSee next page for additional authorsFollow this and additional works at: https://digitalcommons.wustl.edu/open_access_pubsThis Open Access Publication is brought to you for free and open access by Digital Commons@Becker. It has been accepted for inclusion in OpenAccess Publications by an authorized administrator of Digital Commons@Becker. For more information, please contact engeszer@wustl.edu.Recommended CitationKwon, Jennie H.; Bommarito, Kerry M.; Reske, Kimberly A.; Seiler, Sondra M.; Hink, Tiffany; Babcock, Hilary M.; Kollef, Marin H.;Fraser, Victoria J.; Burnham, Carey-Ann D.; and Dubberke, Erik R., ,"Randomized controlled trial to determine the impact of probioticadministration on colonization with multidrug-resistant organisms in critically ill patients." Infection Control & HospitalEpidemiology.36,12. 1451-1454. (2015).https://digitalcommons.wustl.edu/open_access_pubs/4680AuthorsJennie H. Kwon, Kerry M. Bommarito, Kimberly A. Reske, Sondra M. Seiler, Tiffany Hink, Hilary M.Babcock, Marin H. Kollef, Victoria J. Fraser, Carey-Ann D. Burnham, and Erik R. DubberkeThis open access publication is available at Digital Commons@Becker: https://digitalcommons.wustl.edu/open_access_pubs/4680Infection Control & Hospital Epidemiologyhttp://journals.cambridge.org/ICEAdditional services for Infection Control & Hospital Epidemiology:Email alerts: Click hereSubscriptions: Click hereCommercial reprints: Click hereTerms of use : Click hereRandomized Controlled Trial to Determine the Impact of Probiotic Administration on Colonization WithMultidrug-Resistant Organisms in Critically Ill PatientsJennie H. Kwon, Kerry M. Bommarito, Kimberly A. Reske, Sondra M. Seiler, Tiffany Hink, Hilary M. Babcock, Marin H.Kollef, Victoria J. Fraser, Carey-Ann D. Burnham and Erik R. DubberkeInfection Control & Hospital Epidemiology / Volume 36 / Issue 12 / December 2015, pp 1451 - 1454DOI: 10.1017/ice.2015.195, Published online: 27 August 2015Link to this article: http://journals.cambridge.org/abstract_S0899823X15001956How to cite this article:Jennie H. Kwon, Kerry M. Bommarito, Kimberly A. Reske, Sondra M. Seiler, Tiffany Hink, Hilary M. Babcock, Marin H.Kollef, Victoria J. Fraser, Carey-Ann D. Burnham and Erik R. Dubberke (2015). Randomized Controlled Trial to Determinethe Impact of Probiotic Administration on Colonization With Multidrug-Resistant Organisms in Critically Ill Patients. InfectionControl & Hospital Epidemiology, 36, pp 1451-1454 doi:10.1017/ice.2015.195Request Permissions : Click hereDownloaded from http://journals.cambridge.org/ICE, IP address: 128.252.16.235 on 21 Mar 2016c on c i s e c ommun i c a t i o nRandomized Controlled Trial to Determinethe Impact of Probiotic Administration onColonization With Multidrug-ResistantOrganisms in Critically Ill PatientsJennie H. Kwon, DO;1 Kerry M. Bommarito, PhD, MPH;1Kimberly A. Reske, MPH;1 Sondra M. Seiler, BA;1Tiffany Hink, BS;1 Hilary M. Babcock, MD, MPH;1Marin H. Kollef, MD;2 Victoria J. Fraser, MD;1Carey-Ann D. Burnham, PhD;3 Erik R. Dubberke, MD,MSPH1 for the Centers for Disease Control and Prevention(CDC) Prevention EpicentersThis was a randomized controlled pilot study of Lactobacillusrhamnosus GG versus standard of care to prevent gastrointestinalmultidrug-resistant organism colonization in intensive care unitpatients. Among 70 subjects, there were no signiﬁcant differences inacquisition or loss of any multidrug-resistant organisms (P> .05) andno probiotic-associated adverse events.Infect. Control Hosp. Epidemiol. 2015;36(12):1451–1454Infections with multidrug-resistant organisms (MDROs) are aserious threat to critically ill patients, leading to increasedmorbidity and mortality.1,2 Gastrointestinal colonization withMDROs increases patients’ risk of infection, and colonizedpatients are the major reservoir for MDRO transmission toother hospitalized patients.3 One potential strategy to preventMDRO colonization is to use probiotics to promote healthyintestinal ﬂora, but data on probiotics in intensive care unit(ICU) patients are limited. We conducted a prospective,randomized controlled pilot study to determine whetherLactobacillus rhamnosus GG could safely prevent intestinalcolonization with MDROs in a critically ill population.methodsThis study was conducted at Barnes-Jewish Hospital inSt. Louis, Missouri, a 1,250-bed university-afﬁliated hospital,from February 2012 through October 2013 and was approvedby the Washington University Human Research ProtectionOfﬁce. The primary outcome was the acquisition of gastro-intestinal MRDO colonization. The secondary end points weresafety and loss of MDRO colonization.Inpatients aged at least 18 years admitted to the medicalor coronary ICUs with anticipated length of stay greaterthan 48 hours were eligible. Exclusion criteria includedpregnancy, immunosuppression, human immunodeﬁciencyvirus infection with CD4 less than 200 cells/mcL, absoluteneutrophil count less than 500 K/mm3, transplant recipients,ongoing chemotherapy, prosthetic valve or valvuloplasty,vascular graft, left ventricular assist device, balloon pump,cardiac arrest, cardiac trauma, pancreatitis, endocarditis,history of rheumatic fever, congenital cardiac abnormality,tracheostomy, gastrointestinal bleeding or injury, esophagealvarices, oropharyngeal mucosal injury, diarrhea, and unwillingnessor inability to consent.Subjects were randomly assigned to the probiotic orstandard of care (SOC) group in a 1:1 ratio using permutationblocks (4 per block) by Acute Physiology and Chronic HealthEvaluation II scores. Study assignment was not masked.Subjects randomized to the probiotic group received 1 capsulecontaining 1 × 1010 cells of L. rhamnosus GG (Culturelle;i-Health) twice a day. If subjects were unable to swallow owingto intubation or presence of a nasogastric tube, the probioticwas administered in a saline slurry via syringe through the tubeafter removal of the gelatin capsule. Subjects in the probioticgroup received probiotic for 14 days or until study exit (deathor hospital discharge), whichever came ﬁrst.Stool samples or rectal swab samples were obtained at studyenrollment (prior to the ﬁrst dose of probiotic), study day 3,and every 3 days until study exit. Study exit was deﬁned asdeath or day 14 after enrollment, whichever came ﬁrst.Patients were included in outcomes analyses if they had at least3 samples. Acquisition of MDRO was deﬁned as negativeculture results on enrollment and positive culture results onday 3 and/or at study exit. Loss of MDRO colonization wasdeﬁned as positive culture results on enrollment and negativeculture results on day 3 and study exit.Selective media were used to isolate MDROs as follows: forcarbapenem-resistant Enterobacteriaceae, HardyCHROMCRE Agar (Hardy Diagnostics); for vancomycin-resistantEnterococcus (VRE), ChromID VRE Agar (bioMérieux); forextended-spectrum beta-lactamase (ESBL), HardyCHROMESBL Agar (Hardy Diagnostics); and for Pseudomonas,HardyCHROM ChromID Pseudomonas Agar (bioMérieux).Cycloserine-cefoxitin mannitol broth with taurocholatelysozyme cysteine (Anaerobe Systems) was used for Clostridiumdifﬁcile culture as previously published.4 Organisms recoveredfrom selective media were identiﬁed using the Vitek MSmatrix-assisted laser desorption ionization–time of ﬂight massspectrometry system, IVD version 2.0 (bioMérieux).Data collected included demographic characteristics,medical history, Acute Physiology and Chronic HealthEvaluation II scores, length of stay, type of ICU, inpatientmedication exposures, ventilation status, hospital mortality,and diagnosis of infections due to L. rhamnosus GG. Theχ2 test, univariate logistic regression, and Mann-Whitney testwere performed as appropriate. P≤ .05 was consideredsigniﬁcant. SPSS, version 21 (IBM), was used.infection control & hospital epidemiology december 2015, vol. 36, no. 12resultsOne hundred three patients were enrolled and randomizedto probiotics or SOC. Seventy patients had at least 3 specimensavailable for analyses: 30 (43%) in the probiotic groupand 40 (57%) in the SOC group (Figure 1). There were nosigniﬁcant differences between groups in demographiccharacteristics, pre-enrollment length of stay, or severity ofillness (Table 1). There was a trend towards older age in theprobiotic group (median age, 65 vs 59 y; P= .06). Patients inthe probiotic group were more likely to have received aztreo-nam before enrollment (17% vs 0%; P= .01) (Table 1).Colonization status throughout enrollment is summarized inTable 2. There was no signiﬁcant difference in colonization withany MDROs on enrollment (43% of probiotic group vs 33% ofSOC group; P= .35). Only 1 subject was colonized with an ESBLand 1 with Pseudomonas aeruginosa at enrollment. More patientswere colonized with VRE and C. difﬁcile, and rates were similarbetween groups (P= .34 and P= .80, respectively).There was no signiﬁcant difference in overall acquisition of anyMDROs between the 2 groups (10% of probiotic group vs 15%of SOC group; P= .72). Two patients (7%) in the probiotic groupacquired ESBL colonization (P= .19). Seventeen percent of theprobiotic group vs 9% in the SOC group acquired VRE (P= .42).Seven percent of the probiotic group and 8% of the SOC groupacquired P. aeruginosa (P> .99). No patients in the probioticgroup and 6% in the SOC group acquired C. difﬁcile (P= .50).The single patient colonized with an ESBL-producingEnterobacteriaceae on enrollment (SOC group) remainedcolonized throughout hospitalization. No patients in anygroup lost colonization with VRE or P. aeruginosa. One SOCpatient lost C. difﬁcile colonization (P> .99).All 103 patients were included in the safety assessment.There were no signiﬁcant differences between probiotic andSOC patients in the number of patients who died (22% pro-biotic group vs 21% SOC; P= .88). There were no infectionsdue to probiotic or clinical cultures positive for L. rhamnosusGG in either group. No adverse events associated with theprobiotic occurred.discussionNo differences in acquisition or loss of MDRO colonizationbetween the probiotic and SOC group were identiﬁed in thisstudy. These results may indicate that either our sample size wasnot large enough to detect a difference between groups, ourstudy duration was too short, or that L. rhamnosus GG at thedose used did not affect MDRO colonization. There were noinfections related to probiotics, suggesting that probiotics may besafe in a select cohort of critically ill patients, with care to mini-mize probiotic contamination when administered by tube.Previous studies evaluating probiotics have had conﬂictingresults.5–8 A meta-analysis found that probiotics in critically illtable 1. Pre-enrollment Patient CharacteristicsVariable Probiotic (n= 30) Standard of care (n= 40) P valueAge, median (range), y 65 (29–82) 59 (32–82) .06Female sex 18 (60) 20 (50) .41Nonwhite race 11 (37) 16 (40) .78Pre-enrollment hospital LOS, median (range), d 6.0 (1–17) 4.5 (1–23) .31Pre-enrollment ICU LOS, median (range), d 4.5 (1–16) 3.5 (1–22) .18Patient locationCardiac ICU 13 (43) 14 (35) ReferenceMedical ICU 17 (57) 26 (65) .48Pre-enrollment mechanical ventilation 20 (67) 20 (50) .16APACHE II1–17 12 (40) 17 (43) Reference18–24 12 (40) 15 (38) .82≥25 6 (20) 8 (20) .93Pre-enrollment medication exposures ≥12 hoursAztreonam 5 (17) 0 (0) .01Carbapenems 4 (13) 6 (15) > .99Cephalosporins 12 (40) 20 (50) .41Metronidazole PO/IV 5 (17) 2 (5) .13Penicillins 2 (7) 3 (8) > .99Vancomycin IV 13 (43) 18 (45) .89Any antibiotic 22 (73) 25 (63) .34PPI/H2 blocker 20 (67) 25 (63) .72NOTE. Data are no. (%) of subjects unless otherwise indicated. APACHE II, Acute Physiology and Chronic Health EvaluationII; H2 blocker, H2 receptor antagonists; ICU, intensive care unit; IV, intravenous; LOS, length of stay; PO, by mouth;PPI, proton pump inhibitor.1452 infection control & hospital epidemiology december 2015, vol. 36, no. 12adults did not signiﬁcantly reduce mortality but did reduceICU-acquired pneumonia and ICU length of stay.9 Anothermeta-analysis indicated probiotics were associated with reduc-tions in infectious complications but had no effect on mortalityor length of stay.10 These differences may be due to varyingsample size, rates of MDRO carriage, types and doses ofprobiotic used, or the underlying complexity of the microbiome.This study has limitations, including small sample size,duration of follow-up, and inclusion of a single type and doseof probiotic. We did not survey for gastric or upper airwaycolonization, which may be an important site for MDROcolonization. Finally, our extensive exclusion criteria may limitthe generalizability of this study.There are unresolved controversies regarding probiotics,including the type of patients who may beneﬁt most from pro-biotics, the ideal probiotic organism(s), and the dose. The effectof prolonged probiotic administration on the gut microbiome isan area for further investigation. Larger studies are needed toevaluate the effectiveness of probiotics in preventing intestinalcolonization due to MDROs in critically ill patients.acknowledgmentsFinancial support. CDC Prevention Epicenter (grant U54CK000162). Theprobiotic Lactobacillus rhamnosus GG (Culturelle) was provided free by iHealth.iHealth took no part in study design, data collection, management, analysis,interpretation, presentation of data, description of ﬁndings, or ﬁnal manuscript.Potential conﬂicts of interest. C.-A.D.B. reports that she has received grantsfrom bioMérieux, Cepheid, and Accelerate Diagnostics, and personal fees frombioMérieux, Thermoﬁsher, and Nanosphere, outside the submitted work.V.J.F. reports that she has received grants from the CDC and nonﬁnancialsupport from iHealth during the conduct of the study. All other authors reportno conﬂicts of interest relevant to this article.Afﬁliations: 1. Division of Infectious Diseases, Washington UniversitySchool of Medicine, St. Louis, Missouri; 2. Division of Pulmonary and Cri-tical Care Medicine, Washington University School of Medicine, St. Louis,Missouri; 3. Departments of Pathology & Immunology and Pediatrics,Washington University School of Medicine, St. Louis, MissouriAddress correspondence to Jennie H. Kwon, DO, Washington UniversitySchool of Medicine, Division of Infectious Diseases, 6600 S Euclid Ave,Campus Box 8051, St. Louis, MO 63110 (JKwon@dom.wustl.edu).Received May 20, 2015; accepted July 18, 2015; electronically publishedAugust 27, 2015© 2015 by The Society for Healthcare Epidemiology of America. All rightsreserved. 0899-823X/2015/3612-0012. DOI: 10.1017/ice.2015.195references1. Lambert ML, Suetens C, Savey A, et al. Clinical outcomes ofhealth-care-associated infections and antimicrobial resistance inpatients admitted to European intensive-care units: acohort study. Lancet Infect Dis 2011;11:30–38.2. Brusselaers N, Vogelaers D, Blot S. The rising problem ofantimicrobial resistance in the intensive care unit. Ann IntensiveCare 2011;23:47.3. Donskey CJ. The role of the intestinal tract as a reservoir andsource for transmission of nosocomial pathogens. Clin Infect Dis2004;39:219–226.table 2. Colonization Status Throughout EnrollmentOrganismProbiotic(n= 30)Standard ofCare (n = 40) P valueColonization at enrollmentESBL/CRE 0 (0) 1 (3)a >.99VRE 7 (23) 5 (13) .34Pseudomonas aeruginosa 1 (3) 0 (0) .43Clostridium difﬁcile 6 (20) 9 (23) .80Acquisition of colonizationbESBL/CRE 2/30 (7) 0/39 (0) .19VRE 4/23 (17) 3/35 (9) .42P. aeruginosa 2/29 (7) 3/40 (8) >.99C. difﬁcile 0/24 (0) 2/31 (6) .50Loss of colonizationcESBL/CRE N/A 0/1 (0)VRE 0/7 (0) 0/5 (0)P. aeruginosa 0/1 (0) N/AC. difﬁcile 0/6 (0) 1/9 (11) >.99NOTE. CRE, carbapenem-resistant Enterobacteriaceae; ESBL,extended-spectrum beta-lactamase; N/A, not applicable;VRE, vancomycin-resistant Enterococcus.aThis was ESBL.bNegative culture results on enrollment and positive culture results onday 3 and/or study exit, excluding those colonized at day 0.cPositive culture results on enrollment and negative culture results onday 3 and/or study exit.ﬁgure 1. Flowchart of study protocol.#Submitted < 3 samples.*Submitted ≥ 3 samples.impact of probiotics on mdros in icu patients 14534. Hink T, Burnham CA, Dubberke ER. A systematicevaluation of methods to optimize culture-based recovery ofClostridium difﬁcile from stool specimens. Anaerobe 2013;19:39–43.5. de Regt MJ, Willems RJ, Hene RJ, et al. Effects of probiotics onacquisition and spread of multiresistant enterococci. AntimicrobAgents Chemother 2010;54:2801–2805.6. Allen SJ, Wareham K,Wang D, et al. Lactobacilli and biﬁdobacteriain the prevention of antibiotic-associated diarrhoea and Clostridiumdifﬁcile diarrhoea in older inpatients (PLACIDE): a randomised,double-blind, placebo-controlled, multicentre trial. Lancet 2013;382:1249–1257.7. Goldenberg JZ, Ma SS, Saxton JD, et al. Probiotics for the pre-vention of Clostridium difﬁcile-associated diarrhea in adults andchildren. Cochrane Database Syst 2013;5:CD006095.8. Plummer S, WeaverMA, Harris JC, et al. Clostridium difﬁcile pilotstudy: effects of probiotic supplementation on the incidence ofC. difﬁcile diarrhoea. Int Microbiol 2004;7:59–62.9. Barraud E, Bollaert PE, Gibot S. Impact of the administration ofprobiotics on mortality in critically ill adult patients: a meta-analysis of randomized controlled trials. Chest 2013;143:646–655.10. Petrof EO, Dhaliwal R, Manzanares W, et al. Probiotics in thecritically ill: a systematic review of the randomized trial evidence.Crit Care Med 2012;40:3290–3302.1454 infection control & hospital epidemiology december 2015, vol. 36, no. 12

Randomized controlled trial to determine the impact of probiotic administration on colonization with multidrug-resistant organisms in critically ill patients

Randomized controlled trial to determine the impact of probiotic administration on colonization with multidrug-resistant organisms in critically ill patients

Abstract

Similar works

Full text

Available Versions

Crossref

Digital Commons@Becker