Role of asymptomatic bacteriuria on early periprosthetic joint infection after hip hemiarthroplasty. BARIFER randomized clinical trial

BRIEF REPORT Role o asymp oma ic bac e iu ia on ea ly pe ip os he ic join in ec ion a e hip hemia h oplas y. BARIFER andomized clinical ial Dolo s Rod íguez-Pa do 1,2,3 &Ma ía Dolo es del To o 2,3,4 &Lau a Guío-Ca ión 2,3,5 &Rosa Escude o-Sánchez 3,6 & Ma a Fe nández-Samped o 2,3,7 &Miguel Ángel Ga cía-Viejo 3,8 &Ma ía Velasco-A ibas 3,9 & Lau a Solde ila-Boixade 3,10 &Magdalena Femenias 11 &José An onio I iba en 3,12 &Ma ía del Ca men Pulido-Ga cia 13 & Ma ía Dolo es Na a o 2,3,4 &Mayli Lung 2,3,14 &Pablo S. Co ona 2,3,15 &Beni o Almi an e 1,2,3 &Ca les Pig au 1,2,3 Recei ed: 11 Janua y 2021 /Accep ed: 30 Ma ch 2021 #The Au ho (s), unde exclusi e licence o Sp inge -Ve lag GmbH Ge many, pa o Sp inge Na u e 2021 Abs ac Pu pose To e alua e p eope a i e asymp oma ic bac e iu ia (ASB) ea men o educe ea ly-pe ip os he ic join in ec ions (ea ly-PJIs) a e hip hemia h oplas y (HHA) o ac u e. Me hods Open-label, mul icen e RCT compa ing os omycin- ome amol e sus no in e en ion wi h a pa allel ollow-up coho wi hou ASB. P ima y ou come: ea ly-PJI a e HHA. Resul s Fi e hund ed nine y- ou pa ien s en olled (mean age 84.3); 152(25%) wi h ASB (77 ea ed wi h os omycin- ome amol/75 con ols) and 442(75%) wi hou . Despi e he s udy closed wi hou he in ended sample size, ASB was no p edic i e o ea ly-PJI (OR: 1.06 [95%CI: 0.33–3.38]), and i s ea men did no modi y ea ly-PJI incidence (OR: 1.03 [95%CI: 0.15–7.10]). Conclusions Nei he p eope a i e ASB no i s ea men appea s o be isk ac o s o ea ly-PJI a e HHA. ClinicalT ials.go Iden i ie : Eud a CT 2016-001108-47 Keywo ds Asymp oma ic bac e iu ia .Fos omycin- ome amol .Ea ly-pe ip os he ic join in ec ion .Hip hemia h oplas y *Dolo s Rod íguez-Pa do dolo od iguez@ heb on.ne 1 In ec ious Diseases Depa men , Vall d’Heb on Hospi al Uni e si a i, Vall d’Heb on Ba celona Hospi al Campus, Pg. Vall d’Heb on 119-129, 08035 Ba celona, Spain 2 Spanish Ne wo k o Resea ch in In ec ious Diseases (REIPI RD16/0016/0003), Ins i u o de Salud Ca los III, Mad id, Spain 3 S udy G oup on Os eoa icula In ec ions o he Spanish Socie y o Clinical Mic obiology and In ec ious Diseases (GEIO-SEIMC), Mad id, Spain 4 In ec ious Diseases Uni , Hospi al Uni e si a io Vi gen Maca ena, Depa amen o de Medicina, Uni e sidad de Se illa, Ins i u o de Biomedicina de Se illa (IBiS), Se ille, Spain 5 In ec ious Diseases Depa men , Hospi al Uni e si a io C uces, Ba akaldo, Vizcaya, Spain 6 In ec ious Diseases Depa men , Hospi al Uni e si a io Ramón y Cajal, Mad id, Spain 7 In ec ious Diseases Depa men , Hospi al Uni e si a io Ma qués de Valdecilla, San ande , Spain 8 In e nal Medicine Depa men , Hospi al Uni e si a io Pue a de Hie o, Majadahonda, Mad id, Spain 9 In e nal Medicine Depa men (In ec ious Diseases Di ision), Hospi al Uni e si a io Fundación Alco cón, Mad id, Spain 10 In ec ious Diseases Depa men , Hospi al Uni e si a i de Bell i ge, Ba celona, Spain 11 O hopedic Su ge y Depa men , Hospi al Uni e si a io Son Espases, Palma de Mallo ca, Spain 12 In ec ious Diseases Depa men , Hospi al Uni e si a io Donos ia IIS Biodonos ia, San Sebas ián, Spain 13 O hopedic Su ge y Depa men , Hospi al San a C eu i San Pau, Ba celona, Spain 14 Mic obiology Depa men , Vall d’Heb on Hospi al Uni e si a i, Vall d’Heb on Ba celona Hospi al Campus, Ba celona, Spain 15 Sep ic and Recons uc i e Su ge y Uni , O hopedic Su ge y Depa men , Vall d’Heb on Hospi al Uni e si a i, Vall d’Heb on Ba celona Hospi al Campus, Ba celona, Spain h ps://doi.o g/10.1007/s10096-021-04241-2 / Published online: 16 Ap il 2021 Eu opean Jou nal o Clinical Mic obiology & In ec ious Diseases (2021) 40:2411–2419 In oduc ion Ea ly-pe ip os he ic join in ec ion (ea ly-PJI) a e join e- placemen is a challenging complica ion. Ra es o ea ly-PJI a e highe in HHA pa ien s han in o al hip a h oplas y (THA) and ange be ween 1.3 and 9% [1–5]. Bac e ial coloniza ion o he geni ou ina y ac as an in ec- ion cause o hip p os heses due o a hema ogenous seeding o skin con amina ion by con inui y has been sugges ed. This asymp oma ic coloniza ion is called asymp oma ic bac e iu ia (ASB), and i s p e alence eaches 30–50% in olde women in long- e m ca e acili ies [6]. Published s udies demons a ed ha p eope a i e ASB ea men in elec i e o al hip and knee a h oplas ies has no impac in ea ly-PJI a es [7–11]. Howe e , i s impac on HHAs is con o e sial. A single- cen e s udy concluded ha ea ing ASB in ge ia ic pa ien s wi h a emu ac u e dec eases he isk o PJIs [12]. We e alua e p eope a i e ASB ea men ’simpac on he cumula i e incidence o ea ly-PJI in pa ien s unde going HHA o a hip ac u e. We hypo hesized ha p eope a i e ASB ea men in hese popula ions could dec ease he inci- dence o ea ly-PJI caused by G am-nega i e bacilli (GNB). Pa ien s and me hods BARIFER was a phase IV, mul icen e , andomized, open- label, and pa allel-g oup clinical ial conduc ed a 11 si es in Spain designed o e alua e he impac o ea ing ASB on he incidence o ea ly-PJI in HHA. All pa ien s p o ided in o med consen . P o ocol app o al was ob ained om an independen e hics commi ee a each si e. The ial (Eud aCT 2016-001108-47) was pe o med un- de he p inciples o he Decla a ion o Helsinki. Adhe ence o he Consolida ed S anda ds o Repo ing T ials [13] (CONSORT) is suppo ed by he comple ed checklis p o id- ed as Supplemen a y ma e ial. Pa ien s >18 yea s equi ing HHA o ac u e we e ec ui - ed. Exclusion c i e ia include any concomi an in ec ion equi - ing an ibio ics and hip ac u es ea ed wi h sc ews o THA. U ine analysis was pe o med be o e HHA su ge y. ASB e e ed o a u ine cul u e g owing ≥10 5 colony- o ming uni s/ mL o a bac e ial species in a pa ien lacking symp oms o a u ina y ac in ec ion (UTI). S anda d p ocedu es iden i ied all mic oo ganisms isola ed. An imic obial suscep ibili y was pe - o med by mic odilu ion (Vi ek bioMé ieux, F ance). The MIC alues o os omycin we e in e p e ed acco ding o EUCAST c i e ia 2012 ( e sion 2.0) guidelines (www.eucas .o g). Pa icipan s wi h ASB we e andomly assigned in a 1:1 a io, cen alized, and s a i ied by cen e , o ecei e 3 g o os omycin- ome amol (o al ou e) s.no ea men , be ween 24 and 6h be o e su ge y. A pa allel ollow-up coho o HHA candida es wi hou ASB was es ablished. P eope a i e an ibio ic p ophylaxis was decided acco ding o each cen e p o ocol (Supplemen a y Table 1). All pa ien s we e ollowed o h ee mon hs a e HHA o un il ea ly-PJIs o dea h was diagnosed, whiche e occu ed i s . PJIs occu ing wi hin 3 mon hs a e HHA we e conside ed ea ly-PJIs [14]. Pa ien s we e diagnosed wi h a PJI ollowing diagnos ic c i e ia es ablished by he In ec ious Diseases Socie y o Ame ica [15]. In he case o ea ly-PJI, a new isi was comple ed in which he mic oo ganism causing he in ec- ion was eco ded. The p ima y ou come was cumula i e incidence o ea ly- PJI a e p eope a i e ASB ea men . Seconda y analyses in- cluded global incidence o ASB and ea ly-PJI, isk ac o s o ea ly-PJI, and os omycin ea men sa e y. S a is ical analysis Ca ego ical a iables we e p esen ed as numbe s and pe cen ages, and quan i a i e a iables as a median and in e qua ile ange o a mean and s anda d de ia ion, as app op ia e. Compa a i e analyses we e pe o med using X 2 o Fishe ’s es o ca ego ical a iables and S uden ’s es o Mann–Whi ney U es o con inuous a iables. The le el o signi icance was se o p<0.05. P edic o s o ea ly-PJI we e de e mined by uni a ia e analysis. The Kaplan-Meie me hod was used o de- sc ibe cumula i e p obabili y ea ly-PJI s a i ied by s udy g oup. The EAST p og am calcula ed he sample size. We as- sumed a p e alence o ASB up o 20% in men and 50% in women, an incidence o 9% o ea ly-PJI, and an expec ed 50% educ ion wi h os omycin ea men wi h a es powe o 90% and alpha e o o 0.05. We needed 1394 pa ien s (697 in each ea men g oup). An in e im analysis was planned o s op he s udy i i would no be possible o es he hypo hesis. Analyses we e pe o med wi h he STATA 15.1 so wa e (S a aCo p, TX, USA) in he in en ion- o- ea (ITT) popula ion. Resul s A o al o 594 pa ien s we e included om Sep embe 2016 o No embe 2018. O e all, 420 (71.0%) we e women, and he mean age was 84.3 yea s. ASB was diagnosed in 152 (25%) pa ien s, 77 ea ed wi h os omycin and 75 un ea ed con ols. Figu e 1shows he low cha o pa ien s’dis ibu ion. Pa ien s wi h ASB e sus he non-ASB g oup mainly we e women, wi h a highe Cha lson como bidi y index sco e and mo e commonly wi h u ina y incon inence (Table 1). Supplemen a y Table 2shows causa i e iso- la es o ASB. As expec ed, 82% we e GNB (Mos ly Esche ichia coli and Klebsiella spp.), o which 89% 2412 Eu J Clin Mic obiol In ec Dis (2021) 40:2411–2419 Asymp omac ega ding HHA, N=59/75 (78.7%) Loss ollow-up, N=4/75 (5.3%) Dea h, N= 9/75 (12%) PJI, N=2/75 (2.7%) P o hesis emo al (o hopedic easons), N=1/75 (1.3%) Assessed o eligibili y (N=1039) Paen s included (N=594, 100%) Paen s wi hou ASB (N=442, 74.4%) Paen s wi h ASB he e o e Randomised (N=152, 25.6%) T ea ed wi h Fos omycin (N = 77, 12.9%) No ea ed wi h Fos omycin (N =75, 12.6% ) Asymp omac ega ding HHA, N=56/77 (72.3%) Dea h, N=11/77 (14.3%) Loss ollow-up, N=8/77 (10.4%) PJI , N=2/77 (2.6%) Asymp omac ega ding HHA, N=369/442(83.5%) Dea h, N=34/442(7.7%) Loss ollow-up, N= 25/442(5.6%) PJI, N=11/442(2.5%) P o hesis emo al (o hopedic easons), N=3/442(0.7%) Ou come a 12 weeks ollow-up In enon- o- ea populaon (ITT) N= 594 445 we e no eligible •146 we e ope a ed be o e being andomized •89 had concomi an in econ equi ing anbiocs •48 u ine cul u e could no be ob ained be o e HHA •45 symp omac UTI •44 li e expec ancy < 3 mon hs •22 paen s a isk o Fos omycin esis ance •17 os omycin was adminis e ed be o e andomizaon •16 mis akes in da abase en y •10 in o med consen was no ob ained •8 did no ole a e os omycin/o al medicaon Fig. 1 O e all low cha and ou come o pa ien s included in BARIFER clinical ial (ITT analyses), N= 594. Abb ebia ions: ITT, in en ion o ea ; UTI, u ina y ac in ec ion; ASB, asymp oma ic bac e iu ia; PJI, pe ip os he ic join in ec ion. Twen y- wo pa ien s wi h ASB we e conside ed a isk o Fos omycin esis ance as hey we e unde ch onic an ibio ic p ophylaxis wi h Fos omycin- ome amol o ecu en cys i is. The e o e, hey we e no andomized Table 1 Baseline demog aphics and clinical cha ac e is ics o pa ien s (ITT analysis) Cha ac e is ics Pa ien s wi h ASB (n= 152, 100%) Pa ien s wi hou ASB (n= 442, 100%) To al (n= 594,100 %) p alue OR (95% CI) Age, mean (SD) 84.5 (7.9) 84.2 (8.5) 84.3 (8.34) 0.7725 1.003 (0.981; 1.026) Median (Q1–Q3), yea s 86.0 (81.7; 89.6) 86.0 (80.6;89.7) 86.0 (80.7; 89.7) Female sex 124 (81.6%) 296 (67.0%) 420 (70.7%) 0.0008 2.18 (1.39; 3.44) Como bid condi ions BMI mean (SD) 24.4 (4.5) 24.3 (3.5) 24.4 (3.8) 0.8319 1.01 (0.95; 1.07) Median (Q1–Q3), kg/m 2 24.8 (21.5;26.6) 24.2 (21.6;26.6) 24.2 (21.6;26.6) Obesi y (BMI ≥30 kg/m 2 ) 9 (8.3%) 14 (5.3%) 23 (6.2%) 0.2886 1.46 (0.73; 2.95) Ca diac ailu e 19 (12.6%) 45 (10.2%) 64 (10.8%) 0.4124 1.27 (0.72; 2.25) Pe iphe al asculopa hy 15 (9.9%) 41 (9.3%) 56 (9.4%) 0.8114 1.27 (0.58; 2.01) Diabe es 45 (29.8%) 106 (24.0%) 151 (25.4%) 0.1573 1.35 (0.89; 2.03) Demen ia 50 (33.1%) 118 (26.7%) 168 (28.3%) 0.1317 1.36 (0.91; 2.03) Ch onic b onchopa hy 19 (12.6%) 49 (11.1%) 68 (11.5%) 0.6184 1.15 (0.66; 2.03) Ci hosis 6 (3.97%) 6 (1.4%) 12 (2.0%) 0.0600 3.01 (0.95; 9.47) Ch onic enal ailu e 28 (18.4%) 67 (15.1%) 95 (16.0%) 0.3446 1.26 (0.78; 2.05) Cha lson index sco e* Mean (SD) 6.1 (2.2) 5.6 (1.9) 5.8 (2.0) 0.0146 1.12 (1.02; 1.22) Median (Q1–Q3) 6.0 (5.0; 7.0) 5.0 (4.0; 7.0) 6.0 (4.0; 7.0) U ina y incon inence 52 (34.4%) 78 (17.7%) 130 (22.0%) <0.0001 2.44 (1.61; 3.70) Rheuma oid a h i is 1 (0.7%) 8 (1.8%) 9 (1.5%) 0.3395 0.36 (0,04;2.92) Immunosupp esso s** 7 (4.6%) 25 (5.6%) 32 (5.4%) 0.6121 0.81 (0.34;1.90) Malignancy 11 (7.2%) 32 (7.2%) 43 (7.2%) 0.9990 1.00 (0.491; 2.04) An icoagulan ea men 40 (26.5%) 101 (22.8%) 141 (23.8%) 0.3649 1.22 (0.80; 1.86) An ipla ele ea men 44 (29.1%) 130 (29.4%) 174 (29.3%) 0.9493 0.36 (0.04; 2.92) Unless o he wise speci ied, da a ep esen no. (%) o pa ien s ITT, in en ion o ea analysis; ASB, asymp oma ic bac e iu ia; OR, odds a io; CI, con idence in e al; SD, s anda d de ia ion; BMI,bodymassindex *Cha lson index sco e is adjus ed by age **Immunosupp esso s includes s e oids, classic immunosupp esso s (i.e., me ho exa e, aza hiop ine, mycophenola e), biological d ugs, and chemo he apy 2413Eu J Clin Mic obiol In ec Dis (2021) 40:2411–2419 we e suscep ible o os omycin. Table 2compa es base- line cha ac e is ics o ea ed and un ea ed pa ien s wi h ASB. HHA implan s we e 65.46% cemen ed wi h an ibio ics (64% wi h single-an ibio ic and 36% wi h dual-an ibio ic Vancogenx®). Table 2 Baseline cha ac e is ics o T ea ed and Un ea ed Pa ien s wi h ASB Cha ac e is ic Pa ien s, no. (%) To al (N=152, 100%) Un ea ed ASB (N= 75, 100%) ASB ea ed wi h os omycin (N=77, 100%) Age, mean (SD), yea s 84.2 (8.6) 84.6 (7.2) 84.5 (7.9) Median (Q1–Q3), yea s 85.9 (81.6;89.9) 86.15 (81.7;89.4) 85.96 (81.7;89.6) Female sex 59 (78.7%) 65 (84.4%) 124 (81.6%) Como bid condi ions BMI a mean (SD), yea s 24.6 (4.7) 24.2 (4.1) 24.4 (4.46) Median (Q1–Q3), yea s 24.9 (21.6;26.7) 23.5 (21.5;26.6) 24.8 (21.5;26.6) Ca diac ailu e 11 (14.9%) 8 (10.4%) 19 (12.6%) Pe iphe al asculopa hy 8 (10.8%) 7 (9.1%) 15 (9.9%) Ce eb al asculopa hy 14 (18.9%) 13 (16.9%) 27 (17.9%) Demen ia 22 (29.7%) 28 (36.4%) 50 (33.1%) Ch onic b onchopa hy 12 (16.2%) 7 (9.1%) 19 (12.6%) Ci hosis 3 (4.0%) 3 (3.1%) 6 (4.0%) Diabe es 24 (32.4%) 21 (27.3%) 45 (29.8%) Ch onic enal ailu e 14 (18.7%) 14 (18.2%) 28 (18.4%) Malignancy 6 (8.7%) 5 (6.5%) 11 (7.3%) Immunosupp esso s** 7 (9.3%) 1 (1.3%) 8 (5.3%) An icoagulan ea men 20 (27.0%) 20 (26.0%) 40 (26.5%) An ipla ele ea men 23 (31.1%) 21 (27.3%) 44 (29.1%) Rheuma oid a h i is 1 (1.3%) 0 (0%) 1 (0.7%) U ina y incon inence 27 (36.5%) 25 (32.5%) 52 (34.4%) Cha lson index sco e* Mean (SD) 6.19 (2.3) 6.0 (2.2) 6.1 (2.2) Median (Q1–Q3) 6.0 (5.0;8.0) 6.0 (4.0;7.0) 6.0 (5.0;7.0) Days om admission o HHA* Mean (SD) 4.3 (6.9) 3.7 (2.2) 4.0 (5.1) Median (Q1–Q3) 3.0 (2.0;5.0) 3.0 (2.0;5.0) 3.0 (2.0;5.0) Du a ion o HHA su ge y Mean (SD), min 94.9 (27.2) 93.26 (23.4) 94.1 (25.4) Median (Q1–Q3), min 90.0 (75.0;120.0) 90.0 (80.0;5.0) 90.0 (75.0;115.0) Du a ion o HHA su ge y > 75 h pe cen ile 17 (28.3%) 12 (21.0%) 29 (24.8%) An ibio ic cemen ed HHA 67 (89.3%) 66 (89.2%) 133 (89.3%) HHA disloca ion 4 (5.3%) 4 (5.2%) 8 5 (26%) Pos ope a i e UTI 6 (8%) 7 (9.1%) 13 (8.5%) Pos ope a i e in ec ion o he han UTI 4 (5.3%) 3 (3.9%) 7 (4.6%) Pa ien s ans e ed o a con alescence cen e 28 (40%) 35 (50%) 53 (37.9%) Unless o he wise speci ied, da a ep esen no. (%) o pa ien s ASB, asymp oma ic bac e iu ia; BMI,bodymassindex;ASA, Ame ican socie y o anaes hesiologis s; HHA, hip hemia h oplas y; UTI, u ina y ac in ec ion; PJI, pe ip os he ic join in ec ion a Da a a ailable o 109 pa ien s (58 un ea ed ASB and 51 ea ed ASB) *Cha lson index sco e is adjus ed by age **Immunosupp esso s includes s e oids, classic immunosupp esso s (i.e., me ho exa e, aza hiop ine, mycophenola e), biological d ugs, and chemo he apy 2414 Eu J Clin Mic obiol In ec Dis (2021) 40:2411–2419 O e all, 558(93.9%) pa ien s (140 wi h ASB and 418 wi h- ou ) comple ed h ee mon hs o ollow-up (Table 3). Ea ly-PJI a e was 2.5% (15 o 594 pa ien s). O hese 15 pa ien s, 4 (2.7%) showed p e ious ASB, bu only wo ecei ed os omycin (Table 3). Ou ial showed ha ea ing p eope - a i e ASB does no modi y he incidence o ea ly-PJI (OR: 1.03 [95%CI: 0.15–7.10], p= 0.9787). O no e, all ea ly-PJI occu ed wi hin 60 days a e HHA (Fig. 2). Table 4shows he e iology o he 15 ea ly-PJIs. We obse ed a lack o co e- spondence be ween ASB and ea ly-PJI causing mic oo gan- isms. Uni a ia e analysis o isk ac o s o ea ly-PJI is p e- sen ed in Table 5. P eope a i e ASB was no a p edic o o ea ly-PJI (OR: 1.06 [95%CI: 0.33–3.38], p= 0.9228). AEs ela ed o os omycin occu ed in 4 pa ien s, all o hem o mild in ensi y. Th ee pa ien s su e ed om nausea, and one epo ed dizziness (Supplemen a y Table 3). Table 3 O e all ou comes (ITT analysis) Ou come ASB pa ien s Non-ASB pa ien s 442 (100%) To al 594 (100%) No ea ed wi h os omycin 75 (100%) T ea ed wi h os omycin 77 (100%) No HHA in ec ion a e 12 weeks 59 (78.7%) 56 (72.7%) 369 (83.5%) 484 (81.7%) Dea h wi hin 12 weeks 9 (12%) 11 (14.3%) 34 (7.7%) 54 (9%) Ea ly-PJI 2 (2.7%) 2 (2.6%) 11 (2.5%) 15 (2.5%) Loss o ollow-up 4 (5.3%) 8 (10.4%) 25 (5.6%) 36 (6.1) P os heses emo ed due o o hopedic easons 1 (1.3%) 0 (0%) 3 (0.7%) 4 (0.7%) ITT, in en ion o ea ; ASB, asymp oma ic bac e iu ia; HHA, hip hemia h oplas y; PJI, pe ip os he ic join in ec ion Table 4 E iology, ela ionship wi h ASB, and ou come o ea ly-PJI in ec ions Pa ien s Pa ien s wi hou ASB Pa ien s wi h ASB E iology o ea ly-PJI E iology o ASB T ea ed wi h os omycin No ea ed wi h os omycin 1x MSSA 2x S. epide midis E. coli 3x MSSA 4xC. s ia um K. pneumoniae 5x E. coli ESBL p oduce 6x E. coli ESBL p oduce 7x MRSA. 8x K. pneumoniae 9x MRSA E. coli ESBL p oduce 10 x E. coli ESBL p oduce * 11 x S. epide midis 12 x S. epide midis Bacillus spp. S. haemoly icus E. coli 13 x Nega i e cul u e ≠ 14 X Nega i e cul u e ≠ 15 x E. aecalis HHA, hip hemia h oplas y; ASB, asymp oma ic bac e iu ia; PJI, p os he ic join in ec ion; MSSA, me hicillin suscep ible S. au eus;MRSA, me hicillin esis an S. au eus;ESBL p oduce , ex ended spec um be a-lac amase p oduce *This pa ien was diagnosed wi h a pos ope a i e UTI caused by E. coli ESBL p oduce ≠ Al hough pu ulence was obse ed a su gical deb idemen in hose 2 cases, bo h unde b oad-spec um an ibio ic ea men a ha ime, cul u es we e nega i e 2415Eu J Clin Mic obiol In ec Dis (2021) 40:2411–2419 Discussion Iden i ying po en ially modi iable p eope a i e isk ac o s o PJIs is o g ea in e es . Expe s adi ionally ecommended ea ing ASB be o e THA [16–19], al hough he la es pub- lished s udies con adic his ecommenda ion [7,8,10,11]. The e a e only wo p e ious andomized con olled ials ad- d essing his in THA and HHA [7,8]. Ou indings sugges ha p eope a i e ASB ea men does no impac on he e- duc ion o ea ly-PJI a e HHA. BARIFER is he i s andom- ized ial ha only en olled his subg oup o pa ien s. ASB p e alence in ou coho was 25% highe han in THA candida es [7,8,16] and consis en wi h da a epo ed o HHA [20]. Female sex, adjus ed Cha lson index, and u i- na y incon inence a e signi ican ly mo e p e alen in he ASB g oup as p e iously epo ed [7]. Table 5 Uni a ia e analysis o isk ac o s o ea ly-PJI (ITT analysis) Risk ac o Pa ien s, no. (%) N=594 Uni a iable analysis No HHA in ec ion N= 579, 100% HHA in ec ion N=15, 100% p alue OR (95%CI) Age, mean (SD), yea s 84.3 (8.4) 85.1 (5.0) 0.7163 1.01 (0.95;1:08) Age, median (Q1–Q3), yea s 85.96 (80.7;89.7) 86.0 (81.1;88.9) Female sex 409 (70.6%) 11 (73.3%) 0.8210 1.14 (0.36;3.64) Como bid condi ions P eope a i e ASB 148 (25.6%) 4 (26.7%) 0.9228 1.06 (0.33;3.38) BMI mean (SD) 24.3 (3.8) 25.6 (2.5) 0.2712 Median (Q1–Q3), kg/m 2 24.2 (21.7;26.5) 25.9 (22.9;27.3) Obesi y (BMI ≥30 kg/m 2 ) 22 (6.1%) 1 (9.1%) 0.5103 1.00 (1.00;1.00) Ischemic hea disease 48 (8.3%) 1 (6.7%) 0.8205 0.79 (0.10;6.13) Demen ia 161 (27.1%) 7 (46.7%) 0.1197 2.27 (0.81; 6.35) Ci hosis 11 (1.9%) 1 (6.7%) 0.2270 3.68 (0.44;30.51) Diabe es 147 (25.4%) 4 (26.7%) 0.9138 1.07 (0.33;3:40) Cha lson index sco e* Mean (SD) 5.7 (2.0) 6.4 (2.9) 0.2198 1.15 (0.92;1.44) Median (Q1–Q3) 6.00 (4,0; 7.0) 6.0 (4.0; 7.0) Immunosupp esso s** 32 (5.5%) 0 (0%) 0.3492 1.00 (1.00; 1.00) Malignancy 40 (6.9%) 3 (20%) 0.0682 3.37 (0.91;12.43) An icoagulan ea men 136 (23.5 %) 5 (33.3%) 0.3659 1.63 (0.55;4.84) An ipla ele ea men 171 (29.5%) 3 (20%) 0.4258 0.60 (0.17;2.14) Days since admission o HHA Mean (SD) 4.26 (4.8) 4.7 (2.9) 0.7412 1.01 (0.93;1.10) Median (Q1–Q3) 3.00 (2.0; 5.0) 4.00 (3.0; 6.0) Days since admission o HHA > 75 h pe cen ile 113 (19.5%) 5 (33.3%) 0.1957 2.06 (0.69;6.14) Du a ion o HHA su ge y Mean (SD), min 93.97 (25.57) 100.0 (17.3) 0.6863 1.01 (0.96;1.06) Median (Q1–Q3), min 90 (75.0; 115.0) 90 (90.0; 120.0) Du a ion o HHA su ge y > 75 h pe cen ile 28 (24.6%) 1 (33.3%) 0.7302 1.54 (0.13;17.58) An ibio ic cemen ed HHA 372 /568 (65.6%) 9 /15 (60%) 0.7351 0.83 (0.29;2.38) HHA disloca ion 13 (2.2%) 1 (6.7%) 0.2901 3.11 (0.38;25.45) Any pos ope a i e in ec ion 36 (6.2%) 4 (26.7%) 0.0052 5.48 (1.66;18.08) Unless o he wise speci ied, da a ep esen no. (%) o pa ien s PJI, p os he ic join in ec ion; ITT, in en ion o ea analysis; HHA, hip hemia h oplas y; BMI, body mass index; ASB, asymp oma ic bac e iu ia; OR, odds a io; CI, con idence in e al; SD, s anda d de ia ion. *Cha lson index sco e is adjus ed by age **Immunosupp esso s includes s e oids, classic immunosupp esso s (i.e., me ho exa e, aza hiop ine, mycophenola e), biological d ugs, and chemo he apy N/N wi h da a a ailable when app op ia e 2416 Eu J Clin Mic obiol In ec Dis (2021) 40:2411–2419 In ou ial, almos 90% o he iden i ied GNB causing ASB we e suscep ible o os omycin as p e iously published [21,22]. The e icacy o a single dose o os omycin- ome amol o uncomplica ed lowe UTI maybe be compa a- ble o s anda d egimens wi h luo oquinolones o ime hop im/sul ame hoxazole [23] and easie o adminis e . On his basis, i was chosen as p eope a i e ea men . Fos omycin has a good ole abili y wi h a low incidence o ad e se e en s (AEs), mainly mild and ansien gas oin es i- nal symp oms [23]. This coincides wi h ou s udy as only ou pa ien s expe ienced associa ed nausea o dizziness. Only ou pa ien s wi h ASB showed an ea ly-PJI which ep esen s an incidence o 2.7%. Al hough his is lowe han expec ed [4,7,8], i is consis en wi h he la es da a collec ed in he VINCa egis y (su eillance da abase o nosocomial in ec ions in Ca alonia) [5]. When in es iga ing isk ac o s o ea ly-PJI, ou s udy ocuses on p eope a i e ASB. Among ou se ies, ASB is no a isk ac o o ea ly-PJI unlike o he published da a s a ing ha , al hough he isk o PJI is no in luenced by ASB ea men , he e seems o be an inc eased isk o PJI in his popula ion [7]. I should also be no ed ha in no case, he mic oo ganism causing ASB was he same as he one causing ea ly-PJI and his has also been desc ibed by o he au ho s [7,24]. Ou expe ience shows ha ASB ea - men does no modi y he incidence o ea ly-PJI. Al hough we obse ed a delay om HHA su ge y o onse o in ec ion o abou 10 days highe in pa ien s ea ed wi h os omycin, he excep ionally low numbe o e en s p e en s us om eaching any conclusion. Consequen ly, since we could no demons a e a po en ial bene i in ea ing p eope a i e ASB, we do no ecommend sys ema ic u inalysis sc eening and ea men . Besides, he pe cen age o an ibio ic-loaded cemen used is also signi ican . Published s udies show ha i educes he a e o PJIs in HHA wi h no associa ed inc ease in complica ions [25–27]. This app oach could jus i y a global educ ion o ea ly-PJ a es compa ed o ou p e ious incidence be ween 2011 and 2013 [4]. Finally, global mo ali y in ou s udy is high (9%) and can be explained by he popula ion’s age and como bidi y, pa ic- ula ly among hose wi h ASB, as e idenced by he high Cha lson como bidi y index alues [1,28]. The main limi a ion o ou s udy is he small sample size. The di icul y o ob aining he in o med consen signed and all s udy equi emen s a leas 6 h be o e su ge y made ou inclu- sion a e slow. We did an in e im analysis ha showed ha i would no be possible o es he hypo hesis so we decided o end he s udy. I is also possible ha we o e es ima e ASB and ea ly-PJI a e HHA incidences since ou calcula ions we e based on ou p e ious expe ience [4] and da a published e- ga ding ASB p e alence in he elde ly [29]. ASB and ea ly- PJI a e HHA incidences we e lowe han expec ed so he s udy migh be unde powe ed o con i m he hypo hesis. The s udy’s main s eng hs a e i s andomized design and ec ui ing ge ia ic pa ien s (o en unde ep esen ed in clinical ials) all o hem unde going HHA. In conclusion, ou esul s sugges ha ASB appea s no o be anindependen isk ac o o ea ly-PJ, and i s ea men did Fig. 2 Dis ibu ion o he ime o ea ly-PJI acco ding o s udy g oup. Ea ly-PJI, ea ly pe ip os he ic join in ec ion 2417Eu J Clin Mic obiol In ec Dis (2021) 40:2411–2419 no educe he incidence o ea ly-PJI a e HHA. The e o e, we canno ecommend ou ine sc eening and ea men o p e- ope a i e ASB in HHA su ge y. Pa o his s udy was p esen ed a he XXIII Cong eso Nacional de la Sociedad Española de En e medades In ecciosas y Mic obiología Clínica, which ook place in Mad id, on May 23–25, 2019. Supplemen a y In o ma ion The online e sion con ains supplemen a y ma e ial a ailable a h ps://doi.o g/10.1007/s10096-021-04241-2. Acknowledgemen s We hank Ma ia Rome o (T ialance, S.C.C.L.) o medical w i ing suppo , San iago Pe ez Hoyos (Uni a d’Es adís ica i Bioin o mà ica (UEB)) o he s a is ical calcula ions, and Me cedes Vila o he assis ance in he me hodology and implemen a ion o he p ojec . Lis o collabo a o s/g oup o in es iga o s o BARIFER clinical ial This is a mul icen e s udy. In each ins i u ion, he e a e many esea che s ha ha e helped o make his s udy possible. We a e deeply indeb ed o hese collabo a o s, who a e: Jaume Mes e and Ma ia del Ma Villa (In e nal Medicine Depa men , Hospi al Uni e si a i Vall d’Heb on, Uni e si a Au ònoma de Ba celona, Ba celona, Spain) Ál a o Co ales Díaz and My iam Rod íguez Rod íguez (O hopedic Su ge y Depa men Hospi al Uni e si a io Vi gen Maca ena, Se ille, Spain) Ne ea He nández González and Lo ena Díez López (O hopedic Su ge y Depa men , Hospi al Uni e si a io C uces, Vizcaya, Spain) Ja ie Cobo (In ec ious Diseases Depa men , Hospi al Uni e si a io Ramón y Cajal, Mad id, Spain) and Isabel Pe ez Millán (Ge ia ics Depa men , Hospi al Ramón y Cajal, Mad id, Spain). M a Isabel Pe ez Núñez (O hopedic Su ge y Depa men , Hospi al Uni e si a io Ma qués de Valdecilla, San ande , Spain), M Ca men Fa iñas Al a ez (In ec ious Diseases Depa men , Hospi al Uni e si a io Ma qués de Valdecilla, San ande , Spain), Hospi al and Zoilo Yus a Escude o (Ge ia ics Depa men , Hospi al Uni e si a io Ma qués de Valdecilla, San ande , Spain), Elena Muñez Rubio, Isabel Sánchez Rome o (Hospi al Uni e si a io Pue a de Hie o, Majadahonda, Spain). C is ina Daude Gallego (O hopedic Su ge y Depa men , Hospi al Uni e si a io Fundación Alco cón. Mad id, Spain), O iol Ma in Sega a (In e nal Medicine Depa men , In ec ious Diseases Di ision, Hospi al Uni e si a io Fundación Alco cón. Mad id, Spain), Jesús Ignacio Collado Ál a ez and M a Ma Be mejo Olano (In e nal Medicine Depa men Hospi al Uni e si a io Fundación Alco cón. Mad id, Spain). Osca Mu illo (In ec ious Diseases Depa men , Hospi al Uni e si a i de Bell i ge, Ba celona, Spain), Sal ado Ped e o (O hopedic Su ge y Depa men Hospi al Uni e si a i de Bell i ge, Ba celona, Spain). Melcio Rie a (In e nal Medicine Depa men , Hospi al Uni e si a io Son Espasses, Palma de Mallo ca, Spain). Ma ía Gomá iz Díaz (Mic obiology Depa men . Hospi al Uni e si a io Donos ia), Gaspa De la He án (O hopedic Su ge y Depa men . Hospi al Uni e si a io Donos ia), H. Azkune (In ec ious Diseases Depa men Hospi al Uni e si a io Donos ia, San Sebas ián, Spain). Ma a Almena a Fe nández, Edua d Ramí ez Be mejo, Judi Ma ínez Za agoza, (In ec ious Diseses Depa men , Hospi al San a C eu i San Pau, Ba celona, Spain) Fe an Na a o Risueño (Mic obiology Depa men , Hospi al San a C eu i San Pau, Ba celona, Spain) Au ho con ibu ion D Rod iguez-Pa do and D Pig au con ibu ed o i s concep ion, clinical ial design, p o ocol, da a collec ion, pa ien e- c ui men , da a analysis, and w i ing he pape wi h he assis ance o a medical w i e . D Co ona and D Almi an e con ibu ed o i s concep- ion, clinical ial design, and e iewing and edi ing he manusc ip . All he o he au ho s pa icipa ed in pa ien ec ui men , da a collec ion, and e iewing and edi ing he manusc ip . All au ho s app o ed he submi ed e sions, had ull access o he da a (unde con iden iali y ag eemen s), and ouch o he accu acy and comple eness o he da a and o he ideli y o he ial o he p o ocol. Funding This wo k was suppo ed by he Spanish Clinical Resea ch Ne wo k (SCReN), co- inaced by he ISCIII-Subdi ección Gene al de E aluación y Fomen o de la In es igación, h ough he p ojec PI15/ 02161 and by he Plan Nacional de I+D+i 2013-016 and ISCIIII, Subdi eccion Gene al de Redes y Cen os de In es igacion Coope a i a, Minis e io de Economia, Indus ia y Compe i i idad, Spanish Ne wo k o Resea ch in In ec ious Diseases (REIPI RD16/0016/0003)-co- inanced by Eu opean De elopmen Regional Fund “A way o achie e Eu ope,”Ope a i e p og am In elligen G ow h 2014-2020. Decla a ions Compe ing in e es s The au ho s decla e no compe ing in e es s. Re e ences 1. Edwa ds C, Counsell A, Boul on C, Mo an CG (2008) Ea ly in ec- ion a e hip ac u e su ge y. J Bone J Su g Se B 90:770–777. h ps://doi.o g/10.1302/0301-620X.90B6.20194 2. Co de o-Ampue o J, De Dios M (2010) Wha a e he isk ac o s o in ec ion in hemia h oplas ies and o al hip a h oplas ies? 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Clin In ec Dis 40:643–654. h ps://doi.o g/10.1086/427507 Publishe ’sno e Sp inge Na u e emains neu al wi h ega d o ju isdic- ional claims in published maps and ins i u ional a ilia ions. 2419Eu J Clin Mic obiol In ec Dis (2021) 40:2411–2419