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Nosocomial pneumonia ndiyo yakajairika uye yakakomba hutachiona hwenosocomial, iyo inofefetera-inosanganiswa nemabayo (VAP) inoita 40%. VAP inokonzerwa nerefractory pathogens ichiri dambudziko rakaoma rekiriniki. Kwemakore, mirayiridzo yakakurudzira nzira dzakasiyana-siyana (zvakadai seyakanangwa sedation, kukwidziridzwa kwemusoro) kudzivirira VAP, asi VAP inowanikwa kusvika ku40% yevarwere vane tracheal intubation, zvichiita kuti vagare kwenguva refu muchipatara, kuwedzera kushandiswa kwemishonga inorwisa mabhakitiriya, uye rufu. Vanhu vanogara vachitsvaga mamwe maitiro ekudzivirira anobudirira.

Ventilator-associated pneumonia (VAP) kutanga kutsva kwepneumonia inokura maawa makumi mana nemasere mushure mekuputika kwetracheal uye ndiyo inowanzoitika uye inouraya hutachiona hwenosocomial muchikamu chekuchengetedza kwakanyanya (ICU). The 2016 American Society of Infectious Diseases Guidelines yakasiyanisa VAP kubva kutsanangudzo yehospital-acquired pneumonia (HAP) (HAP inongoreva pneumonia inoitika mushure mekuiswa muchipatara pasina tracheal chubhu uye haina hukama ne mechanical ventilation; VAP is pneumonia mushure me tracheal intubation uye mechanical ventilation), uye European Society HAP ichiri kukosha [3] rudzi rweVAP.

Mune varwere vanowana mechanical ventilation, chiitiko cheVAP chinotangira kubva ku9% kusvika ku27%, nhamba yekufa inofungidzirwa pa13%, uye inogona kutungamirira kukuwedzera kushandiswa kwemishonga inorwisa mabhakitiriya, nguva yakareba yemhepo yemhepo, kugara kwenguva refu ICU, uye kuwedzera mari [4-6]. HAP / VAP muvarwere vasina-immunodeficient inowanzokonzerwa nehutachiona hwehutachiona, uye kugoverwa kwezvirwere zvakajairika uye maitiro avo ekudzivirira anosiyana nenharaunda, kirasi yechipatara, huwandu hwevarwere, uye kuratidzwa kwemishonga inorwisa mabhakitiriya, uye kuchinja nekufamba kwenguva. Pseudomonas aeruginosa yaitonga utachiona hune hukama hweVAP muEurope neAmerica, nepo mamwe maAcinetobacter baumannii akaparadzaniswa muzvipatara zvepamusoro muChina. Chikamu chimwe chete muzvitatu kusvika kuhafu yevose vanofa-vanokonzerwa neVAP vanokonzerwa zvakananga nehutachiona, nehuwandu hwekufa kwezviitiko zvinokonzerwa nePseudomonas aeruginosa uye acinetobacter yakakwirira [7,8].

Pamusana pehterogeneity yakasimba yeVAP, kuongororwa kwehutano hwemakiriniki ekuratidzwa kwayo, kufungidzira uye kuongororwa kwema laboratori kwakaderera, uye huwandu hwekusiyana kwekuongororwa hwakakura, izvo zvinoita kuti zvive zvakaoma kuongorora VAP munguva. Panguva imwecheteyo, kupikisa kwebhakitiriya kunokonzera dambudziko guru pakurapa kweVAP. Inofungidzirwa kuti njodzi yekuvandudza VAP ndeye 3% / zuva mukati memazuva mashanu ekutanga ekushandisa mechanical ventilation, 2% / zuva pakati pe5 ne10 mazuva, uye 1% / zuva kwenguva yose. Chiitiko chepamusoro chinowanzoitika mushure memazuva manomwe emhepo, saka pane hwindo umo hutachiona hunogona kudzivirirwa kare [9,10]. Zvidzidzo zvakawanda zvakatarisa kudzivirira kweVAP, asi pasinei nemakumi emakore ekutsvakurudza uye kuedza kudzivirira VAP (yakadai sekudzivirira intubation, kudzivirira re-intubation, kuderedza sedation, kusimudza musoro wemubhedha ne 30 ° kusvika 45 °, uye kutarisirwa kwemuromo), chiitiko chacho hachiratidziki chakaderera uye mutoro wezvokurapa unobatanidzwa unoramba wakanyanya kukwirira.

Inhaled mishonga inorwisa mabhakitiriya yakashandiswa kurapa zvirwere zvisingaperi zvemhepo kubva kuma1940. Nemhaka yekuti inogona kuwedzera kuendeswa kwemishonga kunzvimbo inotarirwa yehutachiona (kureva nzira yemhepo) uye kuderedza systemic side effects, yakaratidza kukosha kwekushandisa kwakanaka mune zvakasiyana-siyana zvezvirwere. Mishonga inofemerwa yave kubvumidzwa neUS Food and Drug Administration (FDA) neEuropean Medicines Agency (EMA) kuti ishandiswe mucystic fibrosis. Inhaled antibiotics inogona kuderedza zvakanyanya kurongeka kwebhakitiriya uye kuwanda kwekuwedzera mubronchiectasis pasina kuwedzera zviitiko zvakaipisisa, uye mazano emazuva ano akazviona sekutanga kurapwa kwevarwere vane pseudomonas aeruginosa utachiona uye kuwedzera nguva dzose; Inhaled antibiotics panguva yeperioperative nguva yekuputika kwemapapu inogonawo kushandiswa se adjuvant kana prophylactic mishonga [11,12]. Asi muna 2016 US VAP nhungamiro, nyanzvi dzakashaya chivimbo mukubudirira kweadjuvant inhaled antibiotics nekuda kwekushaikwa kwemiedzo mikuru inodzorwa. Iyo Phase 3 yekuyedza (INHALE) yakaburitswa muna 2020 yakatadzawo kuwana mhedzisiro yakanaka (inhale amikacin yakabatsira intravenous antibiotics yeGram-negative bacterial infection yakakonzerwa nevarwere veVAP, mapofu maviri, asina kurongeka, placebos akadzorwa, chikamu chechitatu chekuedza kushanda, huwandu hwevarwere mazana masere nenomwe, systemic mishonga + yakabatsirwa inhalation yemazuva 10).

Muchirevo chechinyorwa chino, boka rinotungamirirwa nevatsvakurudzi kubva kuRegional University Hospital Center of Tours (CHRU) muFrance rakatora nzira yakasiyana yekutsvakurudza uye yakaita muongorori-akatangwa, akawanda, mapofu maviri, asina kurongeka anodzorwa efficacy test (AMIKINHAL). Inhaled amikacin kana placebo yeVAP kudzivirira yakafananidzwa mu19 icus muFrance [13].

Huwandu hwevarwere vakura 847 vane invasive mechanical ventilation pakati pe72 ne96 maawa vakapihwa zvisina tsarukano 1:1 kufemerwa amikacin (N= 417,20 mg/kg uremu hwakanaka hwemuviri, QD) kana inhalation ye placebo (N = 430, 0.9% sodium chloride yakaenzana) kwemazuva matatu. Mhedziso yekutanga yaive chikamu chekutanga cheVAP kubva pakutanga kwekuita zvisina kujairika kusvika kuzuva 28.

Migumisiro yekuedzwa yakaratidza kuti pamazuva makumi maviri nemasere, varwere ve62 (15%) muboka reamikacin vakanga vagadzira VAP uye varwere ve95 (22%) muboka re placebo vakanga vagadzira VAP (iyo shoma inoreva mararamiro akasiyana eVAP aiva mazuva 1.5; 95% CI, 0.6 ~ 2.5; P = 0.004).

Panyaya yekuchengeteka, varwere vanomwe (1.7%) muboka reamikacin uye varwere vana (0.9%) muboka re placebo vakawana zviitiko zvakakomba zvine chokuita nemiedzo. Pakati peavo vakanga vasina kukuvara kwakanyanya kwetsvo pane randomization, varwere ve11 (4%) muboka reamikacin uye varwere ve24 (8%) muboka re placebo vaiva nekukuvara kwakanyanya kwetsvo pazuva 28 (HR, 0.47; 95% CI, 0.23 ~ 0.96).

Chiyedzo chekiriniki chaive nezvakatanhamara zvitatu. Kutanga, maererano nekugadzirwa kwekudzidza, chirongwa cheAMIKINHAL chinokwevera pamuedzo weIASIS (a randomized, double-blind, placebo-controlled, parallel phase 2 muedzo unosanganisira varwere ve143). Kuongorora kuchengetedzwa uye kushanda kweamikacin - fosfomycin inhalation systemic treatment ye gram-negative bacterial infection inokonzerwa neVAP) uye INHALE kuedza kupedza nemigumisiro yakaipa zvidzidzo zvidzidzo, izvo zvinotarisa pakudzivirira VAP, uye zvakawana migumisiro yakanaka. Nekuda kwehunhu hwekufa kwepamusoro uye kugara muchipatara kwenguva refu kune varwere vane mechanical ventilation uye VAP, kana amikacin inhalation inogona kuwana zvakasiyana zvakasiyana-siyana mukuderedza rufu uye kugara muchipatara kune varwere ava, zvichava zvakakosha kune kliniki yekudzidzira. Zvisineyi, zvichipihwa kusiyana kwekunonoka kurapwa uye kutarisirwa mumurwere wega-wega nenzvimbo yega yega, pane zvinhu zvakati wandei zvinovhiringa zvinogona kukanganisa chidzidzo, saka zvinogona zvakare kunetsa kuwana mhedzisiro yakanaka inokonzerwa nekufemerwa mishonga inorwisa mabhakitiriya. Naizvozvo, chidzidzo chekiriniki chakabudirira chinoda kwete chete yakanakisa dhizaini yekudzidza, asiwo kusarudzwa kweakakodzera ekutanga magumo.

Chechipiri, kunyange zvazvo aminoglycoside antibiotics isingakurudzirwi semushonga mumwe chete mumitemo yakasiyana-siyana yeVAP, aminoglycoside antibiotics inogona kuvhara zvirwere zvinowanzoitika muvarwere veVAP (kusanganisira pseudomonas aeruginosa, acinetobacter, nezvimwewo), uye nekuda kwekutora kwavo kushoma mumapapu epithelial masero, kukwirira kwakanyanya panzvimbo yehutachiona hwehutachiona, uye kuderera. Aminoglycoside antibiotics inofarirwa zvakanyanya pakati pemishonga inofemerwa. Iri pepa rinopindirana nehupamhi hwehuwandu hwehuwandu hwekuita kwekutonga kweintracheal yegentamicin mumasampuli maduku akabudiswa kare, izvo zvinoratidzira pamwe chete kushanda kweaminoglycoside antibiotics inhaled mukudzivirira VAP. Zvinofanira kucherechedzwawo kuti mizhinji yezvidzoro zve placebo zvakasarudzwa muzviedzo zvine chekuita nemishonga inofemerwa nemishonga inofemerwa ndeye saline yakajairika. Zvisinei, tichifunga kuti kufemerwa neatomu yesaline yakajairwa pachayo kunogona kuita rimwe basa mukuderedza sputum uye kubatsira expectorant, saline yakajairika inogona kukonzera kumwe kupindira mukuongororwa kwemhedzisiro yeongororo, iyo inofanirwa kutariswa zvizere muchidzidzo.

Pamusoro pezvo, kuchinjirwa kwemushonga weHAP/VAP kwakakosha, sezvinofanira kuita maantibiotic prophylaxis. Panguva imwecheteyo, zvisinei nehurefu hwenguva yekupinda, iyo ecology yeICU yemunharaunda ndiyo inonyanya kukosha yengozi yehutachiona nehutachiona hwehutachiona hunopesana nemishonga. Naizvozvo, kurapwa kweempirical kunofanirwa kunongedzera kune iyo microbiology data yezvipatara zvemuno zvakanyanya sezvinobvira, uye haigone kutaura nehupofu kune nhungamiro kana ruzivo rwezvipatara zvepamusoro. Panguva imwecheteyo, varwere vanorwara zvakanyanya vanoda mechanical ventilation vanowanzobatanidzwa ne-multi-system zvirwere, uye pasi pekuita kwakasanganiswa kwezvinhu zvakasiyana-siyana zvakadai semamiriro ekudzvinyirira, panogonawo kuva nechiitiko chemukati wemukati microbes crosstalk kumapapu. Iyo yakakwirira yehterogeneity yezvirwere zvinokonzerwa nemukati uye kunze kwepamusoro-soro inotarisawo kuti hukuru hwekliniki kukurudzirwa kwekupindira kutsva kwega kwega inzira yakareba yekuenda.