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Inyumoniya yeNosocomial lolona sulelo luxhaphakileyo kwaye lunobuzaza lwe-nosocomial, apho inyumoniya ehambelana ne-ventilator-associated (VAP) yenza i-40%. I-VAP ebangelwa yi-refractory pathogens iseyingxaki enzima yeklinikhi. Kwiminyaka, izikhokelo zicebise uluhlu lweendlela zokungenelela (ezifana ne-sedation ejoliswe kuyo, ukuphakama kwentloko) ukukhusela i-VAP, kodwa i-VAP iyenzeka ukuya kuthi ga kwi-40% yezigulane ezine-tracheal intubation, okubangelwa ukuhlala ixesha elide esibhedlele, ukwanda kokusetyenziswa kwe-antibiotics, kunye nokufa. Abantu bahlala bekhangela amanyathelo asebenzayo okuthintela.

I-Ventilator-associated pneumonia (VAP) sisiqalo esitsha senyumoniya ekhula kwiiyure ezingama-48 emva kokunyanzeliswa kwe-tracheal intubation kwaye yeyona nto ixhaphakileyo kwaye ibulala intsholongwane ye-nosocomial kwiyunithi yokunyamekela kakhulu (ICU). I-2016 ye-American Society of Infectious Diseases Guidelines ihlukanise i-VAP kwinkcazo ye-pneumonia efunyenwe esibhedlele (HAP) (i-HAP ibhekisela kuphela kwi-pneumonia eyenzeka emva kokulaliswa esibhedlele ngaphandle kombhobho we-tracheal kwaye ayihambelani nokuphuma komoya; i-VAP i-pneumonia emva kwe-tracheal intubation kunye ne-mechanical ventilation), kunye ne-European Society kunye ne-China i-VAP ekhethekileyo.

Kwizigulane ezifumana i-ventilation yomatshini, iziganeko ze-VAP zivela kwi-9% ukuya kwi-27%, izinga lokufa liqikelelwa kwi-13%, kwaye kunokukhokelela ekusetyenzisweni kwenkqubo ye-antibiotics, i-ventilation esebenza ixesha elide, ukuhlala ixesha elide kwe-ICU, kunye neendleko ezikhulayo [4-6]. I-HAP / VAP kwizigulane ezingenayo i-immunodeficient idla ngokubangelwa yintsholongwane ye-bacterial, kwaye ukuhanjiswa kwezifo eziqhelekileyo kunye neempawu zabo zokuchasana ziyahlukahluka kunye nommandla, iklasi yesibhedlele, izigulane, kunye nokuvezwa kwe-antibiotic, kunye nokutshintsha kwexesha. I-Pseudomonas aeruginosa yongamele izifo ezinxulumene ne-VAP eYurophu naseMelika, ngelixa i-Acinetobacter baumannii eninzi yayibekwe yodwa kwizibhedlele zenqanaba lesithathu e-China. Isinye kwisithathu ukuya kwisiqingatha sazo zonke izifo ezinxulumene ne-VAP zibangelwa ngokuthe ngqo lusulelo, kunye nezinga lokufa kwamatyala abangelwa yi-Pseudomonas aeruginosa kunye ne-acinetobacter ephezulu [7,8].

Ngenxa ye-heterogeneity eqinile ye-VAP, ukuxilongwa kweempawu zeklinikhi, iimvavanyo ze-imaging kunye ne-laboratory ziphantsi, kwaye uluhlu lwe-diagnostic diagnostics lubanzi, okwenza kube nzima ukuxilonga i-VAP ngexesha. Ngexesha elifanayo, ukuchasana kwebhaktheriya kubangela umngeni omkhulu kunyango lwe-VAP. Kuqikelelwa ukuba umngcipheko wokuphuhlisa i-VAP yi-3% / ngosuku ngexesha leentsuku zokuqala ze-5 zokusetyenziswa kwe-ventilation yomatshini, i-2% / ngosuku phakathi kwe-5 kunye ne-10 iintsuku, kunye ne-1% / ngosuku lonke ixesha. Isiganeko esiphakamileyo ngokuqhelekileyo senzeke emva kweentsuku ezi-7 zokungena komoya, ngoko kukho ifestile apho usulelo lunokuthintelwa kwangoko [9,10]. Izifundo ezininzi zijonge ukukhuselwa kwe-VAP, kodwa nangona amashumi eminyaka yophando kunye nemizamo yokuthintela i-VAP (njengokunqanda intubation, ukuthintela ukuphinda kufakwe intubation, ukunciphisa i-sedation, ukuphakamisa intloko yebhedi nge-30 ° ukuya kwi-45 °, kunye nokunyamekela komlomo), isiganeko asibonakali sinciphile kwaye umthwalo wezonyango ohambelana nawo uhlala uphezulu kakhulu.

Amayeza okubulala iintsholongwane okuphefumlayo asetyenziselwe ukunyanga usulelo olungapheliyo lomoya ukusukela ngoo-1940. Ngenxa yokuba inokwandisa ukuhanjiswa kwamachiza kwindawo ekujoliswe kuyo yosulelo (okt indlela yomoya) kunye nokunciphisa iziphumo zecala zenkqubo, ibonise ixabiso elihle lokusetyenziswa kwizifo ezahlukeneyo. I-antibiotics e-inhaled ngoku ivunyiwe yi-US Food and Drug Administration (FDA) kunye ne-European Medicines Agency (EMA) ukuze isetyenziswe kwi-cystic fibrosis. I-antibiotics e-inhaled inokunciphisa kakhulu umthwalo webhaktheriya kunye nokuphindaphinda kwe-exacerbation kwi-bronchiectasis ngaphandle kokunyuka kweziganeko ezimbi kakhulu, kwaye izikhokelo zangoku ziye zaqaphela njengonyango lokuqala lwezigulane ezine-pseudomonas aeruginosa ukusuleleka kunye nokunyuka rhoqo; I-antibiotics efakwe kwi-inhaled ngexesha le-perioperative yokutshintshwa kwemiphunga ingasetyenziselwa njenge-adjuvant okanye i-prophylactic drug [11,12]. Kodwa kwizikhokelo ze-VAP ze-2016 zase-US, iingcali zazingenakho ukuzithemba ekusebenzeni kwe-adjuvant inhaled antibiotics ngenxa yokungabikho kwezilingo ezinkulu ezilawulwa ngokungahleliwe. Ulingo lweSigaba sesi-3 (INHALE) olupapashwe ngo-2020 nalo aluphumelelanga ukufumana iziphumo ezilungileyo (ukuphefumla i-amikacin incedise amayeza okubulala iintsholongwane kwi-Gram-negative bacterial infection ebangelwa zizigulane ze-VAP, i-double-blind, i-randomized, i-placebos elawulwayo, ulingo lwesigaba sesi-3 sokusebenza kakuhle, izigulane ezingama-807, iyeza le-systemic + ukuncedisa ukuphefumla iintsuku ezili-10).

Kulo mxholo, iqela elikhokelwa ngabaphandi abavela kwiZiko leZibhedlele zeYunivesithi yeNgingqi yeeNdwendwe (CHRU) eFransi lamkela isicwangciso sophando esahlukileyo kwaye lenze umphandi-oqaliswe, u-multicenter, u-double-blind, uvavanyo olusebenzayo olulawulwa ngokungahleliwe (AMIKINHAL). I-amikacin e-inhaled okanye i-placebo yokuthintela i-VAP yafaniswa kwi-icus ye-19 eFransi [13].

I-847 yabantu abadala izigulane ezine-invasive mechanical ventilation phakathi kwe-72 kunye ne-96 iiyure zabelwe ngokungaqhelekanga i-1: i-1 yokuphefumla i-amikacin (N = 417,20 mg / kg ubunzima bomzimba obufanelekileyo, i-QD) okanye i-inhalation ye-placebo (N = 430, i-0.9% ye-sodium chloride elinganayo) kwiintsuku ze-3. Isiphelo sokuqala sasiyisiqephu sokuqala se-VAP ukususela ekuqaleni kwesabelo esingenamkhethe ukuya kumhla wama-28.

Iziphumo zovavanyo zibonise ukuba kwiintsuku ze-28, izigulane ze-62 (i-15%) kwiqela le-amikacin liye laphuhlisa i-VAP kunye nezigulane ze-95 (22%) kwiqela le-placebo liye laphuhlisa i-VAP (umlinganiselo omncinci wokuphila umahluko we-VAP wawuyientsuku ze-1.5; 95% CI, 0.6 ~ 2.5; P = 0.004).

Ngokokhuseleko, izigulane ezisixhenxe (1.7%) kwiqela le-amikacin kunye nezigulane ezine (0.9%) kwiqela le-placebo ziye zafumana iziganeko ezimbi kakhulu ezinxulumene nolingo. Phakathi kwabo babengenalo ukulimala kwezintso kwi-randomization, izigulane ze-11 (4%) kwiqela le-amikacin kunye nezigulane ze-24 (i-8%) kwiqela le-placebo lalinokulimala kwezintso ezibuhlungu ngosuku lwe-28 (HR, 0.47; 95% CI, 0.23 ~ 0.96).

Ulingo lwezonyango luneengongoma ezintathu. Okokuqala, ngokumalunga noyilo lokufunda, ulingo lwe-AMIKINHAL lutsala uvavanyo lwe-IASIS (uvavanyo olungahleliwe, oluyimfama oluphindwe kabini, olulawulwa yi-placebo, oluhambelana nesigaba se-2 esibandakanya izigulane ze-143). Ukuvavanya ukhuseleko kunye nokusebenza kwe-amikacin-fosfomycin inhalation systemic treatment of gram-negative bacterial infection ebangelwa yi-VAP) kunye nolingo lwe-INHALE ukuphelisa ngeziphumo ezibi ezifundiweyo, ezijolise ekuthinteleni i-VAP, kwaye zifumene iziphumo ezilungileyo. Ngenxa yeempawu zokufa okuphezulu kunye nokuhlala esibhedlele ixesha elide kwizigulane ezine-ventilation ye-mechanical kunye ne-VAP, ukuba i-amikacin inhalation inokufikelela kwiziphumo ezihluke kakhulu ekunciphiseni ukufa kunye nokuhlala esibhedlele kwezi zigulana, kuya kubaluleka ngakumbi ekusebenzeni kweklinikhi. Nangona kunjalo, ngokunikezelwa kwe-heterogeneity yonyango olusemva kunye nokhathalelo kwisigulane ngasinye kunye neziko ngalinye, kukho inani lezinto eziphazamisayo ezinokuphazamisa uphononongo, ngoko ke kunokuba nzima ukufumana isiphumo esihle esibangelwa yi-antibiotics. Ke ngoko, uphononongo oluyimpumelelo lweklinikhi alufuni nje uyilo olugqwesileyo lokufunda, kodwa kunye nokukhetha iziphelo ezifanelekileyo eziphambili.

Okwesibini, nangona i-antibiotics ye-aminoglycoside ayikhuthazwa njengeyeza elilodwa kwizikhokelo ezahlukeneyo ze-VAP, i-antibiotics ye-aminoglycoside inokugubungela iintsholongwane eziqhelekileyo kwizigulane ze-VAP (kuquka i-pseudomonas aeruginosa, i-acinetobacter, njl.), kwaye ngenxa yokungeniswa kwabo okulinganiselweyo kwiiseli ze-lung epithelial, ukugxininiswa okuphezulu kwindawo ye-toxicity yenkqubo, kunye neyeza eliphantsi. I-antibiotics ye-aminoglycoside ithandwa kakhulu phakathi kwe-antibiotics. Eli phepha lihambelana noqikelelo olubanzi lobungakanani bempembelelo yokulawulwa kwe-intracheal ye-gentamicin kwiisampuli ezincinci ezipapashwe ngaphambili, ezibonisa ngokudibeneyo umphumo we-antibiotics ye-aminoglycoside inhaled ekukhuseleni i-VAP. Kufuneka kwakhona kuqatshelwe ukuba uninzi lolawulo lwe-placebo olukhethiweyo kulingo olunxulumene namayeza okubulala iintsholongwane aphefumleyo anetyuwa eqhelekileyo. Nangona kunjalo, ngokuqwalasela ukuba ukuphefumla i-athomu ye-saline eqhelekileyo ngokwayo kunokudlala indima ethile ekuxubeni isikhohlela kunye nokunceda i-expectorant, i-saline eqhelekileyo inokubangela ukuphazamiseka okuthile kuhlalutyo lweziphumo zophononongo, ekufuneka ziqwalaselwe ngokubanzi kuphononongo.

Ngaphaya koko, ukulungelelaniswa kwendawo amayeza e-HAP/VAP kubalulekile, njengoko kufanele ukuba ne-antibiotic prophylaxis. Ngexesha elifanayo, kungakhathaliseki ubude bexesha lokungena, i-ecology ye-ICU yendawo iyona nto ibaluleke kakhulu kwingozi yosulelo kunye neebhaktheriya ezichasene neziyobisi ezininzi. Ke ngoko, unyango olunamandla kufuneka lubhekiselele kwidatha ye-microbiology yezibhedlele zasekhaya kangangoko kunokwenzeka, kwaye ayinakubhekisa ngokumfamekileyo kwizikhokelo okanye kumava ezibhedlele eziphakamileyo. Ngexesha elifanayo, izigulane ezigula kakhulu ezifuna umoya wokuphefumula ngoomatshini zihlala zidibaniswa nezifo ezininzi zenkqubo, kwaye phantsi kwesenzo esidibeneyo sezinto ezininzi ezifana nesimo soxinzelelo, kunokubakho isiganeko se-intestinal microbes crosstalk kwimiphunga. I-heterogeneity ephezulu yezifo ezibangelwa yi-superposition yangaphakathi nangaphandle iphinda inqume ukuba ukunyuswa kwekliniki enkulu yokungenelela olutsha kuyindlela ende yokuhamba.