Cov kab mob thiab cov kab mob fungal hauv cov hlab ntsha hauv cov neeg tau txais kev hloov pauv hauv lub cev: Cov txiaj ntsig tau los ntawm ib pawg neeg Danish nrog kev soj ntsuam thoob tebchaws

AbstractLub hom phiaj:Cov kab mob hauv cov hlab ntshav (BSI) muaj ntau dua tom qab kev hloov pauv hauv nruab nrog cev (SOT). Hauv txoj kev tshawb no, peb tsom los tshawb xyuas qhov xwm txheej thiab cov xwm txheej txaus ntshai rau BSI hauvfi uarst 5 xyoo tom qab hloov pauv.Txoj kev:Txoj kev tshawb no suav nrog 1322 SOT (raum, siab, ntsws thiab lub plawv) cov neeg tau txais kev hloov pauv los ntawm 2010 txog 2017 nrog rau tag nrho ntawm 5616 xyoo tom qab. Cov yam ntxwv kho mob thiab microbiology tau txais los ntawm Lub Chaw Haujlwm Zoo Tshaj Plaws rau Tus Kheej Tshuaj Kho Mob ntawm Kab Mob Sib Kis hauv Immune Defi uaciency (PERSIMUNE) cov ntaub ntawv khaws cia nrog kev soj ntsuam thoob tebchaws. Qhov xwm txheej tau tshawb xyuas hauv pawg SOT sib txawv. Cov xwm txheej txaus ntshai cuam tshuam nrog BSI raug soj ntsuam hauv pawg ua ke hauv lub sijhawm hloov kho ntau yam hloov pauv Cox regressions.

Cov txiaj ntsig:Qhov tshwm sim ntawm cumulativefi uarst BSI hauvfi uarst5 xyapost-transplantation txawvhauv cov pab pawg SOT uas muaj qhov tshwm sim tsawg dua hauv cov neeg tau txais kev hloov lub plawv dua li lwm pab pawg SOT (lub siab: 4.4%, CI 0.0e9.7%, raum: 24.6%, CI 20.9e28.2%, siab: 24.7%, CI 19.4e29.9%, thiab lub ntsws: 19.6%, CI 14.5e24.8%, p <0.001). Hnub nyoog tshaj 55 xyoo (HR 1.71, CI 1.2e2.4, p¼0.002) thiab siab dua Charlson comorbidity Performance index (HR ib chav tsev nce: 1.25, CI 1.1e1.4, p<0.001) ntawm kev hloov pauv, kab mob cytomegalovirus (CMV) tam sim no (HR 4.5, CI 2.6e7.9, p<0.001) thiab leukopenia tam sim no (HR 13.3, CI 3.7e47.9, p<0.001) tag nrho yog txuam nrog kev pheej hmoo ntawm BSI.

Xaus:Hauv cov neeg tau txais SOT, qhov tshwm sim ntawm BSI txawv nrog hom kev hloov pauv hauv nruab nrog cev. Qhov kev pheej hmoo ntawm BSI tau siab dua hauv cov neeg tau txais kev laus thiab hauv cov neeg tau txais kev mob comorbidity, tam sim no tus kab mob CMV lossis leukopenia. Yog li, kev saib xyuas ntxiv rau BSI hauv cov neeg tau txais nrog cov yam ntxwv no tau lees paub.Dina Leth Møller, Clin Microbiol Infect 2022; 28:391

Tshuaj ntsuab CISTANCHE EXTRACT nrog 25% ECHINACOSIDE thiab 9% ACTEOSIDE rau lub raum

Taw qhia Kev hloov pauv hauv nruab nrog cev (SOT) yog kev kho kom zoo rau cov neeg mob uas muaj lub cev tsis ua haujlwm kawg [1]. Txawm li cas los xij, kev siv tshuaj tiv thaiv kab mob rau kev tiv thaiv thiab kev kho mob ntawm kev tsis lees paub ua rau muaj kev pheej hmoo kis mob hauv cov neeg tau txais SOT [1]. Cov kab mob hauv cov hlab ntshav (BSI) yog qhov tshwm sim ntau thiab muaj teeb meem loj uas ua rau muaj kev tuag tom qab hloov pauv [2e6]. Cov kev tshawb fawb yav dhau los tau pom tias txog li 40% ntawm cov neeg tau txais SOT tsim BSI hauv thawj xyoo tom qab hloov pauv [7e10], thiab cov teeb meem muaj feem cuam tshuam rau BSI suav nrog kev hloov pauv, kev kho mob ntawm cov tsev kho mob hnyav (ICUs) thiab yav dhau los raug tshuaj tua kab mob ( nrhiav hauv [11]).

Kev paub txog cov kab mob muaj pes tsawg leeg thiab cov qauv tiv thaiv yog qhov tseem ceeb rau kev kho mob empiric thiab yog li qhov tshwm sim ntawm BSI [11]. Nws tau raug pom tias cov kab mob muaj pes tsawg leeg sib txawv nrog hom hloov pauv hauv nruab nrog cev [2]. Txawm li cas los xij, ob peb txoj kev tshawb fawb tau tshawb xyuas qhov sib txawv ntawm cov kab mob sib txawv nyob rau lub sijhawm tom qab hloov pauv thiab kev pom zoo tsis tau mus txog [3,6,12]. Tsis tas li ntawd, BSI muaj pes tsawg leeg hauv cov neeg tau txais SOT, feem ntau, tau hloov pauv hauv ob lub xyoo dhau los nrog kev hloov pauv mus rau cov kab mob Gram-negative tej zaum vim muaj tsawg dua hauv nruab nrab-txuas nrog BSI [2,4,13]. Cov kev hloov pauv no, thiab qhov nce sai ntawm cov kab mob tiv thaiv kab mob ntau yam tshuaj tiv thaiv kab mob (MDRO) [4,9,11], qhia txog qhov xav tau rau kev tshawb fawb tshiab ntawm cov kab mob sib xyaw hauv SOT cov neeg tau txais.

Hauv qhov kev tshawb fawb yav tom ntej no nrog kev soj ntsuam thoob tebchaws, peb tsom mus tshawb xyuas qhov xwm txheej, kab mob muaj pes tsawg leeg, thiab muaj feem cuam tshuam ntawm BSI hauv thawj xyoo thiab thawj 5 xyoo tom qab hloov pauv hauv pawg loj ntawm SOT cov neeg tau txais.

Cov ntaub ntawv thiab cov txheej txheem

Hauv qhov kev tshawb fawb yav tom ntej no, peb suav nrog cov neeg laus ib leeg-lub cev SOT tau txais 18 xyoo nrog lub plawv, ntsws, siab lossis raum hloov pauv ntawm Rigshospitalet, Tsev Kho Mob University of Copenhagen, Denmark, nyob rau lub sijhawm 1 Lub Ib Hlis 2010 txog 31 Lub Kaum Ob Hlis 2017. Rigshospitalet yog ib qho tsev kho mob tertiary thiab ib lub chaw kho mob tshwj xeeb heev. Kev hloov pauv hauv siab thiab ntsws hauv Denmark tsuas yog ua tiav ntawm Rigshospitalet thiab txoj kev tshawb no suav nrog 52% ntawm tag nrho cov neeg tau txais SOT hloov pauv thoob tebchaws thaum lub sijhawm kawm [14]. Cov neeg koom nrog txoj kev tshawb fawb tau suav nrog los ntawm Kev Tswj Xyuas Kev Tiv Thaiv Kab Mob Tom Qab Hauv Tsev Kho Mob Sib Koom Tes (MATCH) pawg [15].

Cov yam ntxwv kho mob suav nrog kev hloov pauv cov ntaub ntawv tshwj xeeb, Charlson comorbidity index (CCI) qhab nia, biochemistry thiab microbiology tau muab los ntawm Lub Chaw Haujlwm Zoo Tshaj Plaws rau Tus Kheej Cov Tshuaj Kho Mob ntawm Kev Tiv Thaiv Kab Mob Tsis Txaus (PERSIMUNE) cov ntaub ntawv khaws cia [16]. Cov ntaub ntawv tau raug tsim los ua ib feem ntawm kev ua haujlwm kho mob thiab sib koom ua ke hauv PERSI MUNE cov ntaub ntawv khaws cia. PERSIMUNE cov ntaub ntawv khaws cia muaj cov ntaub ntawv los ntawm cov chaw kho mob thiab cov ntawv sau npe hauv tebchaws suav nrog Danish Microbiology Database (MiBa), uas muaj cov ntaub ntawv ntawm tag nrho cov ntshav kab lis kev cai, suav nrog cov tshuaj tiv thaiv kab mob, los ntawm txhua Lub Tsev Haujlwm Saib Xyuas Kev Kho Mob Microbiology hauv Denmark nrog kev pabcuam tiav txij li xyoo 2010 [17] . Cov txheej txheem tiv thaiv kab mob tiv thaiv kab mob thiab tshuaj tiv thaiv kab mob tiv thaiv kab mob siv tau tuaj yeem pom hauv cov ntaub ntawv ntxiv (Cov ntaub ntawv ntxiv S1).

Kev muab cov ntaub ntawv rov qab tau pom zoo los ntawm National Committee on Health Research Ethics (H-170024315) thiab Lub Chaw Tiv Thaiv Cov Ntaub Ntawv (04433, RH-2016-47).

Cov kab mob ntshav

Tag nrho cov ntshav kab lis kev cai tau sau los ntawm kev kuaj mob. Cov ntshav kab lis kev cai tau txheeb xyuas siv BACT/ALERT® (Biomerieux, Marcy l'Etoile, Fabkis) lossis BACTEC FX® (Becton, Dickinson thiab Company, Franklin Lakes, USA) microbial detection systems. BSI tau txhais raws li Lub Chaw Tiv Thaiv Kab Mob thiab Tiv Thaiv (CDC) cov txheej txheem raws li kev sib cais ntawm cov kab mob lossis cov kab mob fungal los ntawm kab lis kev cai ntshav tshwj tsis yog cov kab mob tuaj yeem suav tias yog kev sib kis [18]. Cov kab mob kis tau raug tshem tawm tshwj tsis yog lawv raug cais tawm ntawm ob lossis ntau qhov sib cais hauv ob hnub. Ntau kab lis kev cai ntshav nrog tib kab mob tau suav tias yog ib feem ntawm tib BSI yog tias lawv tshwm sim hauv 14 hnub tom qab kab lis kev cai dhau los [19].

Ib qho kev hloov kho ntawm CDC cov qauv [19] tau siv los txhais BSI theem nrab, qhov twg BSI tau muab faib ua theem nrab yog tias lawv tau tshwm sim nyob rau hauv lub sijhawm thib ob BSI cov txiaj ntsig (3 hnub ua ntej kab lis kev cai mus rau 14 hnub tom qab) ntawm kab lis kev cai nrog tib kab mob. (tsuas yog cov zis tso zis nrog 105 CFU/mL nkaus xwb).

Kev faib cov kab mob thiab kev faib tawm ntawm MDRO tuaj yeem pom hauv cov ntaub ntawv ntxiv (Cov ntaub ntawv ntxiv S2 thiab Table S1 ).

Tseem tshuav cov variables thiab txhais

Tus qhab nia CCI [20] tau raug ntsuas nyob rau hnub hloov pauv. Tsis muaj leukopenia tau txhais tias yog cov qe ntshav dawb (WBC) suav hauv qab 1 109 /L [21]. Cov txheeb ze leukopenia tau txhais raws li WBC suav hauv qab 3.5 109 /L sib npaug rau qib qis ntawm peb Lub Tsev Haujlwm Saib Xyuas Kev Kho Mob Biochemistry. Txhawm rau soj ntsuam leukopenia cov ntshav kuaj zaum kawg nrog cov lej leucocyte ua ntej BSI tau siv. Cytomegalovirus (CMV) tau ntsuas hauv ntshav [15]. Tus kab mob CMV tam sim no tau txhais tias yog PCR tus nqi siab dua 1000 daim ntawv luam / mL hauv cov ntshav kawg kuaj rau CMV ua ntej BSI.

Ua raws li

Tag nrho cov neeg tau txais kev pab tau ua raws li txij li hnub hloov mus rau kev hloov pauv, kev tuag, lossis qhov kawg ntawm kev rov qab los ntawm 31 Lub Kaum Ob Hlis 2018, qhov twg los ua ntej. Txhawm rau kom muaj peev xwm tsawg kawg ib xyoos ntawm kev soj ntsuam rau txhua tus neeg koom, suav nrog tau nres rau 31 Lub Kaum Ob Hlis 2017. BSI qhov xwm txheej thiab cov kab mob muaj pes tsawg leeg tau txheeb xyuas thoob plaws plaub lub sijhawm tom qab hloov pauv:<1 month, 2e6 months, 7e12 months and 2e5 years. BSI occurring more than 5 years post-transplantation were not reported.

Kev txheeb cais

Qhov feem pua ​​​​tau nthuav tawm raws li feem pua ​​​​thiab cov ntaub ntawv txuas ntxiv raws li cov neeg nruab nrab nrog qhov sib txawv (IQR). BSI qhov xwm txheej (IR) raug xam raws li tus naj npawb ntawm BSI thawj zaug rau ib tus neeg tau txais ib tus neeg-lub sijhawm muaj kev pheej hmoo hauv lub hlis censoring lub sijhawm soj ntsuam rau hnub tuag, hloov pauv, lossis thaum kawg ntawm lub sijhawm tshawb nrhiav rau plaub qhov sib txawv. Lub sijhawm tshawb nrhiav tom qab hloov pauv. Peb suav 95% CI siv Byar qhov kwv yees rau Poisson faib. Qhov 5- xyoo sib sau ua ke ntawm thawj BSI tau suav nrog kev kwv yees AaleneJohansen nrog kev tuag thiab rov hloov pauv raws li kev pheej hmoo sib tw. Peb tau sim qhov sib txawv ntawm qhov sib txawv ntawm pawg SOT sib txawv los ntawm Grey qhov kev xeem. Qhov nruab nrab nruab nrab ntawm BSI rov tshwm sim tau raug suav thiab siv ntxiv los xam qhov tshwm sim ntawm muaj ob lossis ntau dua BSI tom qab hloov pauv. Qhov sib txawv ntawm cov kab mob muaj pes tsawg leeg ntawm BSI stratified los ntawm kev hloov pauv hauv nruab nrog cev thiab plaub lub sij hawm tom qab hloov pauv tau raug sim siv chi-squared test nrog tom qab kev soj ntsuam tom qab hoc nrog BenjaminieHochberg kho. Cov xwm txheej txaus ntshai rau BSI tau tshawb xyuas nyob rau hauv lub sijhawm hloov kho ntau yam sib txawv Cox cov qauv kev phom sij nrog kev hloov pauv, cov kab mob CMV tam sim no, thiab cov leucopenia tam sim no (tsis muaj tseeb lossis cov txheeb ze) raws li lub sijhawm sib txawv. Tus qauv tau hloov kho rau hnub nyoog, poj niam txiv neej, thiab CCI qhab nia thiab stratified ntawm hom kev hloov pauv. Txhua qhov kev ntsuam xyuas tau ua nyob rau hauv cov ntaub ntawv txheeb xyuas software R version 3.6.1 (R Foundation for Statistical Computing, Vienna, Austria).

Cov txiaj ntsig

Cov yam ntxwv ntawm cov neeg tau txais txiaj ntsig thiab cov ntshav kuaj Cov yam ntxwv ntawm 1322 SOT cov neeg tau txais tau nthuav tawm hauv Table 1. Tag nrho ntawm 13,366 ntshav kab lis kev cai tau sau los ntawm 1096 SOT cov neeg tau txais (83% ntawm pawg neeg) thaum lub sijhawm kawm (Table 2). Ntawm cov no, 1158 (9%) yog qhov zoo, 11 939 (89%) yog qhov tsis zoo thiab 269 (2%) tau suav tias yog kev sib kis. Tom qab siv CDC cov qauv, tag nrho ntawm 523 BSI hauv 261 (20%) tau pom cov neeg tau txais (Table 2).

Qhov tshwm sim ntawm BSI Qhov IR ntawm thawj BSI rau txhua tus neeg tau txais SOT tau siab tshaj plaws hauv thawj lub hlis tom qab hloov pauv (IR ntawm 6.13, CI 4.88e7.62, ib 100 cov neeg tau txais ib hlis) thiab txo qis hauv thawj xyoo tom qab hloov pauv (IR ntawm 1.54, CI 1.25e1.88, thiab 0.66, CI 0.49e0.86, per 100 tus neeg tau txais ib lub hlis ntawm 2e6 lub hlis thiab 7e12 lub hlis, feem) (Table 2). Cov IRs rau txhua lub sijhawm muaj nyob rau hauv Table 2. Qhov tshwm sim ntawm thawj BSI thawj xyoo thiab thawj 5 xyoo tom qab hloov pauv txawv nrog hom kev hloov pauv hauv nruab nrog cev (Daim duab 1 thiab Table 2) thiab qis dua hauv plawv. Hloov cov pab pawg dua li lwm pawg SOT (qhov tshwm sim hauv thawj 5 xyoos tom qab hloov pauv: lub plawv: 4.4%, CI 0.0e9.7%, thiab raum: 24.6%, CI 20.9e28.2%, siab: 24.7%, CI 19.4e29.9%, thiab lub ntsws: 19.6%, CI 14.5e24.8%, Greys kuaj rau qhov sib txawv ntawm qhov tshwm sim: p<0.001). The pathogen composition in the different SOT groups is shown in Fig. 2 and described including MDRO in the supplementary material (Supplementary material text S3 and Table S2).

Fungal BSI

Tag nrho ntawm 19 fungal BSI tau pom nyob rau hauv 17 (1%) cov neeg tau txais (5 (0.8%) raum, 9 (3%) daim siab thiab 3 (1%) cov neeg tau txais lub ntsws) tom qab qhov nruab nrab ntawm 23 hnub (IQR 13e106 hnub) tom qab hloov pauv nrog Candida albicans yog hom kab mob tshaj plaws (42%). Kaum ib tus kab mob BSI (58%) yog BSI thib ob. Tsuas yog ib qho resistant fungal BSI tau pom nrog echinocandin-resistant Candida glabrata. Cov xwm txheej txaus ntshai rau BSI Txhawm rau ntsuas qhov muaj feem cuam tshuam rau kev txhim kho BSI tom qab hloov pauv, peb tau teeb tsa lub sijhawm hloov kho Cox tus qauv kev phom sij (Daim duab 3).

Hnub nyoog tshaj 55 xyoo (HR 1.71, CI 1.2e2.4, p¼0.002) thiab siab dua CCI qhab nia (HR 1.25 rau 1 tus qhab nia nce, CI 1.1e1.4, p<0.001) at transplantation had higher hazards of developing a BSI compared to younger age and less comorbidity, respectively. Furthermore, current CMV infection with a PCR titre above 1000 copies/mL (HR 4.5, CI 2.6e7.9, p<0.001) and current absolute leucopenia with WBC count below 1  109 /L (HR 13.3, CI 3.7e47.9, p<0.001) after transplantation both increased the hazard for BSI significantly. To further assess current relative leucopenia as a risk factor for BSI, we altered absolute leucopenia to relative leucopenia in the previous model (Supplementary material Fig. S1) and found that relative leucopenia with WBC count below 3.5  109 /L (HR 1.81, CI 1.2e2.98, p¼0.009) likewise increased the hazard for BSI significantly

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