Intego Gusuzuma fosfomycine ijyanye nibintu bibi (AEs) hamwe na pharmacokinetics hamwe nimpinduka murwego rwa sodium muri neonates hamwe na sepsis clinique.
Hagati ya Werurwe 2018 na Gashyantare 2019, 120 neonates bafite iminsi 28 y'amavuko bahawe ubuvuzi bwa antibiyotike (SOC) ya septis: ampisilline na gentamicin.
Intervention Twahisemo guhitamo kimwe cya kabiri cyabitabiriye kwakira fosfomycine yinyongera ikurikirwa na fosfomycine yo mu kanwa ku gipimo cya mg / kg 100 kabiri kumunsi iminsi 7 (SOC-F) hanyuma tugakurikirana iminsi 28.
Ibisubizo 61 na 59 impinja zifite iminsi 0-23 zahawe SOC-F na SOC.Nta kimenyetso cyerekana ko fosfomycine igira ingaruka kuri serumusodiumcyangwa ingaruka za gastrointestinal.Mu gihe cyo kwitegereza iminsi 1560 na 1565, twabonye 50 AEs muri 25 bitabiriye SOC-F na 34 ba SOC, (2.2 vs 3.2 ibyabaye / iminsi 100 yumwana; itandukaniro ryibipimo -0.95 byabaye / 100 impinja) ) umunsi (95% CI -2.1 kugeza 0.20)) .Bane ba SOC-F na batatu bitabiriye SOC bapfuye. Kuva 238 ya farumasi ya farumasi, kwerekana ko abana benshi basabye ikinini cya mg / kg 150 mumitsi inshuro ebyiri kumunsi kugirango bagere kuntego za farumasi, kandi kuri neonates <iminsi 7 cyangwa ipima <1500 g kumunsi Dose yagabanutse kugera kuri mg / kg kabiri.
Umwanzuro n'akamaro Fosfomycin ifite ubushobozi nkuburyo buhendutse bwo kuvura neonatal sepsis hamwe nuburyo bworoshye bwo gufata imiti. Umutekano wacyo ugomba kurushaho kwigwa mugice kinini cya neonate yibitaro, harimo na neonate batagejeje igihe cyangwa abarwayi barembye.Guhagarika kurwanya birashobora kugerwaho gusa. kurwanya ibinyabuzima byoroshye cyane, birasabwa rero gukoresha fosfomycine hamwe nindi miti igabanya ubukana.
Data is available upon reasonable request.Trial datasets are deposited at https://dataverse.harvard.edu/dataverse/kwtrp and are available from the KEMRI/Wellcome Trust Research Program Data Governance Committee at dgc@kemri-wellcome.org.
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Kurwanya mikorobe birabangamira ubuzima bwimpinja kandi hakenewe byihutirwa uburyo bushya bwo kuvura buhendutse.
Hariho umutwaro ukomeye wa sodium hamwe na fosfomycine yo mu mitsi, kandi imyiteguro ya fosfomycine yo mu kanwa irimo fructose nyinshi, ariko hariho amakuru make yumutekano muri neonates.
Icyifuzo cyo kuvura abana na neonatal ibyifuzo bya fosfomycine yimitsi iratandukanye, kandi ntanuburyo bwo gutangaza umunwa.
Fosfomycine yinjira mu kanwa no mu kanwa 100 mg / kg kabiri buri munsi, nta ngaruka byagize kuri serumusodiumcyangwa ingaruka za gastrointestinal.
Abana benshi barashobora gusaba fosfomycine yimitsi 150 mg / kg kabiri kumunsi kugirango bagere ku ntego nziza, naho kuri neonates <iminsi 7 cyangwa ipima <1500 g, fosfomycine yinjira 100 mg / kg kabiri kumunsi.
Fosfomycine ifite ubushobozi bwo guhuzwa nindi mikorobe kugirango ivure sepsis ya neonatal idakoresheje karbapenem mugihe cyo kongera imiti igabanya ubukana.
Kurwanya mikorobe (AMR) bigira ingaruka ku buryo butagereranywa ku baturage bo mu bihugu bikennye kandi biciriritse (LMICs) .Igabanuka ry’imfu z’abana bavuka ryaragabanutse ugereranije n’abana bakuze, byibuze kimwe cya kane cy’impfu zivuka ziterwa no kwandura.1 AMR yongeraho uyu mutwaro, hamwe na virusi itera imiti myinshi (MDR) igera kuri 30% by'impfu za neonatal sepsis ku isi.2.
NINDE usaba ampisilline,penisiline, cyangwa cloxacillin (niba ikekwa ko S. aureus ikekwa) wongeyeho gentamicin (umurongo wa mbere) hamwe na cephalosporine yo mu gisekuru cya gatatu (umurongo wa kabiri) kugirango bavure sepsis ya neonatal.3 Hamwe na beta-lactamase (ESBL) na karbapenemase, 4 ivuriro ryigenga bikunze kuvugwa ko ititaye kuri ubu buryo.5 Kugumana karbapenem ni ngombwa mu kugenzura MDR, 6 no kongera kuvugurura antibiyotike gakondo birasabwa gukemura ikibazo cyo kubura antibiyotike nshya ihendutse.7.
Fosfomycine ni fosifonike idafite fosifike ikomoka kuri OMS8 Fosfomycine ni bactericidal9 kandi ikagaragaza ibikorwa birwanya Gram-positif na Gram-mbi, harimo na methicilline irwanya Staphylococcus aureus, vancomycine irwanya Enterococcus, ESBL. ababikora kandi barashobora kwinjira muri biofilm.10 Fosfomycine yerekanye muri vitro synergie hamwe na aminoglycoside na karbapenem 11 12 kandi ikoreshwa mubantu bakuru bafite ubwandu bwinkari za MDR.13
Muri iki gihe hari ibyifuzo bivuguruzanya kubijyanye no kunywa fosfomycine yinjira mu buvuzi bw'abana, kuva kuri 100 kugeza 400 mg / kg / ku munsi, nta buryo bwo gufata imiti bwo mu kanwa bwatangajwe. 25-50 mg / kg. (AUC): Ikigereranyo cya MIC.18 19
Raporo zose hamwe 84 zerekana ko neonates yakira fosfomycine yinjirira kuri 120-200 mg / kg / kumunsi yerekanaga ko yihanganiye.20-24 Uburozi busa nkaho buri hasi mubantu bakuru ndetse nabana bakuru.25 Ariko, fosfomycine y'ababyeyi irimo 14.4 mmol / Sodium ya mg 330 kuri garama-ishobora guhungabanya umutekano kuri neonates ifite reabsorption ya sodiumi ihwanye nigihe cyo gutwita (GA) .26 Byongeye kandi, fosfomycine yo mu kanwa irimo umutwaro mwinshi wa fructose (~ 1600 mg / kg / kumunsi), ushobora gutera gastrointestinal ingaruka mbi kandi bigira ingaruka kumazi.27 28
Twari tugamije gusuzuma imiti ya farumasi (PK) nimpinduka za sodium muri neonates ya sepsis clinique, hamwe nibintu bibi (AEs) bifitanye isano no kwinjiza imitsi ikurikira fosfomycine.
Twakoze igeragezwa rifunguye ryagereranijwe kugereranya antibiyotike yubuvuzi (SOC) yonyine hamwe na SOC wongeyeho IV ikurikirwa na fosfomycine yo mu kanwa muri neonates hamwe na sepsis ivuriro mubitaro bya Kilifi County (KCH), Kenya.
Abana bose bavutse bemerewe muri KCH barapimwe. Ibipimo byashyizwemo ni: imyaka days iminsi 28, uburemere bwumubiri> 1500 g, geste> ibyumweru 34, hamwe nibisabwa kugirango antibiyotike yinjirira mumabwiriza ya OMS na Kenya 29. Niba CPR isabwa, icyiciro cya 3 hypoxic-ischemic encephalopathie, 30 sodium ≥150 mmol / L, creinine ≥150 µmol / L, jaundice isaba guhererekanya, allergie cyangwa kwanduza fosfomycine, byerekana neza ikindi cyiciro cyindwara ya antibiotique, neonate ntiyakuwe mubindi bitaro cyangwa ntabwo biri mu ntara ya Kilifi (Ishusho 1 ).
Gerageza igicapo.Iyi shusho yumwimerere yakozwe na CWO kuriyi nyandiko yandikishijwe intoki.CPR, resuscitation yumutima;HIE, hypoxic-ischemic encephalopathie;IV, imitsi;SOC, ubuvuzi busanzwe;SOC-F, ubuvuzi busanzwe wongeyeho fosfomycine. ubundi bushakashatsi (1). † Umwe mu bitabiriye SOC-F yapfuye nyuma yo kurangiza gukurikirana (Umunsi wa 106).
Abitabiriye amahugurwa biyandikishije mu masaha 4 uhereye ku ncuro ya mbere ya antibiyotike ya SOC kugeza muri Nzeri 2018, igihe ivugurura rya protocole ryongerewe ibi mu masaha 24 kugira ngo ryinjire mu ijoro.
Abitabiriye amahugurwa bahawe (1: 1) gukomeza kuri antibiyotike ya SOC yonyine cyangwa kwakira SOC wongeyeho (kugeza) iminsi 7 ya fosfomycine (SOC-F) ukoresheje gahunda yo guhitamo hamwe nubunini bwahagaritswe (Ishusho yinyongera S1 kumurongo) .Byahagaritswe bikurikiranye. nomero ya opaque ifunze amabahasha.
Dukurikije amabwiriza ya OMS na Kenya yo mu rwego rw'abana, SOCs irimo ampisilline cyangwa cloxacillin (niba ikekwa ko yanduye staphylococcal) wongeyeho gentamicin nka antibiyotike yo ku murongo wa mbere, cyangwa sefalosporine yo mu gisekuru cya gatatu (urugero, ceftriaxone) nka antibiyotike yo ku murongo wa kabiri.3 29 Abitabiriye amahugurwa batoranijwe kuri SOC. -F yakiriye kandi fosfomycine yimitsi byibura amasaha 48, ihinduranya umunwa mugihe ibiryo bihagije byihanganiye gufata imiti ihagije. mg / mL fosfomycine sodium yumuti wo kwinjiza imitsi (Infectopharm, Ubudage) na Fosfocine 250 mg / 5 mL fosifomycine calcium yo guhagarika umunwa (Laboratorios ERN, Espagne) kabiri kumunsi hamwe na 100 mg / kg / dose yatanzwe.
Abitabiriye amahugurwa bakurikiranwe iminsi 28. Abitabiriye amahugurwa bose bitabwaho mu gice kimwe gishingiye cyane kugirango bagenzure igenzura rya AE. Kubara amaraso yuzuye hamwe na biohimiya (harimo na sodium) byakorewe ku kwinjira, iminsi 2, na 7, kandi bigasubirwamo niba byerekanwe mubuvuzi.AEs byandikwa kuri MedDRA V.22.0.Ibihe byose byashyizwe mu byiciro hakurikijwe DAIDS V.2.1.AEs zarakurikijwe kugeza igihe cyemezo cy’amavuriro cyangwa cyemejwe ko kidakira kandi gihamye mugihe cyo kwivuza. "Byari byitezwe" AEs zasobanuwe mbere nkuko byari biteganijwe kuba rusange muri aba baturage, harimo kwangirika kuvuka (protocole muri dosiye yinyongera 1 kumurongo).
Nyuma ya IV ya mbere na fosfomycine yo mu kanwa ka mbere, abarwayi boherejwe muri SOC-F batoranijwe kugeza kare (iminota 5, 30, cyangwa 60) naho umwe watinze (2, 4, cyangwa 8) icyitegererezo cya PK.Hakusanyirijwe hamwe icyitegererezo cya gatanu kidafite gahunda kubitabiriye amahugurwa bari bakiri mu bitaro kumunsi wa 7.Icyitegererezo cya cerebrospinal fluid (CSF) cyegeranijwe cyakuwe mubitaro byerekanwe na clinique (LP) .Icyitegererezo cyo gupima no gupima fosfomycine bisobanurwa muri dosiye yinyongera 2 kumurongo.
Twasuzumye amakuru yinjira hagati ya 2015 na 2016 hanyuma tubara ko hagati ya sodium ya 1785 neonates ipima> 1500 g yari 139 mmol / L (SD 7.6, intera 106-198) .Hariho neonate 132 hamwe na sodium ya serumu> 150 mmol / L (yacu Ibipimo byo guhezwa), neonates isigaye 1653 yari ifite sodium ya 137 mmol / L (SD 5.2) .Ubunini bw'icyitegererezo bwa 45 kuri buri tsinda bwabazwe kugirango harebwe niba itandukaniro rya 5 mmol / L muri sodium ya sodium kumunsi wa 2 rishobora kuba kugenwa hamwe na> 85% imbaraga zishingiye kubibanza byambere bya sodium.
Kuri PK, ingano yicyitegererezo ya 45 yatanzwe> 85% imbaraga zo kugereranya ibipimo bya PK kugirango bisobanurwe, ingano yo kugabura, hamwe na bioavailability, hamwe na 95% CIs igereranya ukoresheje simulation ifite ukuri kwa ≥20% .Ku kurangiza, icyitegererezo cyabantu bakuru. yarakoreshejwe, gupima imyaka nubunini kuri neonates, wongeyeho uburyo bwa mbere bwo kwinjiza no gufata bioavailability.31 Kugira ngo twemere kubura ingero, twashakaga gushaka neonate 60 kuri buri tsinda.
Itandukaniro mubipimo fatizo ryageragejwe hakoreshejwe ikizamini cya χ2, ikizamini cya t-cyumunyeshuri, cyangwa ikizamini cyamanota ya Wilcoxon. Itandukaniro kumunsi wa 2 numunsi wa 7 sodium, potasiyumu, creatinine, na alanine aminotransferase byageragejwe hakoreshejwe isesengura rya covariance yahinduwe kubiciro byibanze. Kuri AEs, ibintu bikomeye bibi (SAEs), hamwe nibiyobyabwenge bibi, twakoresheje STATA V.15.1 (StataCorp, Sitasiyo ya Koleji, Texas, USA).
Ikigereranyo gishingiye ku cyitegererezo cyibipimo bya PK byakorewe muri NONMEM V.7.4.32 ukoresheje igenamigambi rya mbere risabwa hamwe n’imikoranire, ibisobanuro birambuye byiterambere rya PK hamwe nibigereranyo bitangwa ahandi.32
Gukurikirana ku rubuga byakozwe na DNDi / GARDP, hamwe n'ubugenzuzi butangwa na komite yigenga ishinzwe umutekano no gukurikirana amakuru.
Hagati ya 19 Werurwe 2018, na 6 Gashyantare 2019, abiyandikishije 120 (61 SOC-F, 59 SOC) bariyandikishije (Ishusho 1), muri bo 42 (35%) bariyandikishije mbere yo gusubiramo protocole.Itsinda.Abamedi (IQR) imyaka, uburemere na GA byari umunsi 1 (IQR 0-3), 2750 g (2370-3215) nicyumweru 39 (38-40), ibiranga ibyingenzi nibipimo bya laboratoire bigaragara mumeza 1 na kumurongo Winyongera Imbonerahamwe S1.
Indwara ya bagiteri yagaragaye muri neonates ebyiri (Imbonerahamwe y'inyongera S2 kumurongo) .2 kuri 55 neonates yakiriye LP yari ifite laboratoire yemewe na laboratoire (Streptococcus agalactiae bacteremia hamwe na CSF leukocytes cells20 selile / µL (SOC-F); na CSF leukocytes cells 20 selile / µL (SOC)).
Neonate imwe ya SOC-F yakiriye nabi mikorobe ya SOC gusa kandi ntiyakuwe mubisesengura rya PK.Biri SOC-Fs hamwe na SOC Neonatal umwe yakuyeho uruhushya - harimo amakuru yabanje kubikuramo. Bose ariko babiri bitabiriye SOC (cloxacillin wongeyeho gentamicin (n = 1) . kugeza kumurongo wa kabiri kubera ubuvuzi bukabije cyangwa meningite, batanu muribo bari mbere yicyitegererezo cya kane cya PK (Supplementary Table S3 kumurongo) .Muri rusange, abitabiriye 60 bahawe nibura dose imwe yimitsi ya fosfomycine naho 58 bahabwa byibuze ikinini kimwe.
Batandatu (bane ba SOC-F, babiri ba SOC) bitabiriye ibitaro (Igicapo 1) .Umwe mu bitabiriye SOC yapfuye nyuma yiminsi 3 asohotse (umunsi wa 22) .Umwe mu bitabiriye SOC-F yabuze gukurikirana nyuma baza gusanga yapfuye ku munsi 106 (hanze yinyigisho ikurikirana);imibare yashyizwemo kumunsi wa 28. Impinja eshatu za SOC-F zabuze gukurikiranwa. Impinja zose / iminsi yo kwitegereza SOC-F na SOC ni 1560 na 1565, muribo 422 na 314 bari mubitaro.
Ku munsi wa 2, agaciro (SD) plasma sodium kubitabiriye SOC-F yari 137 mmol / L (4.6) na 136 mmol / L (3.7) kubitabiriye SOC;bivuze itandukaniro +0.7 mmol / L (95% CI) -1.0 kugeza +2.4) .Ku munsi wa 7, indangagaciro ya sodium (SD) yari 136 mmol / L (4.2) na 139 mmol / L (3.3);bivuze itandukaniro -2.9 mmol / L (95% CI -7.5 kugeza +1.8) (Imbonerahamwe 2).
Ku munsi wa 2, bivuze (SD) potasiyumu yibanze muri SOC-F yari hasi gato ugereranije nimpinja za SOC-F: 3.5 mmol / L (0.7) vs 3,9 mmol / L (0.7), itandukaniro -0.4 mmol / L (95% CI -0.7 kugeza -0.1) .Nta kimenyetso cyerekana ko ibindi bikoresho bya laboratoire bitandukanye hagati yaya matsinda yombi (Imbonerahamwe 2).
Twabonye 35 AEs mubitabiriye 25 SOC-F na 50 AE muri 34 bitabiriye SOC;2.2 ibyabaye / iminsi 100 yimpinja na 3.2 ibyabaye / iminsi 100 yumwana, IRR 0.7 (95% CI 0.4 kugeza 1.1), IRD -0.9 ibyabaye / iminsi 100 yimpinja (95% CI -2.1 kugeza +0.2, p = 0.11).
SAE cumi na zibiri zabaye mubitabiriye 11 ba SOC-F na 14 SAE mubitabiriye 12 ba SOC (SOC 0.8 ibyabaye / iminsi 100 yimpinja vs 1.0 ibyabaye / iminsi 100 yimpinja; IRR 0.8 (95% CI 0.4 kugeza 1.8), IRD -0.2 ibyabaye / 100 impinja iminsi (95% CI -0.9 kugeza +0.5, p = 0.59). Hypoglycemia yari AE yakunze kugaragara cyane (5 SOC-F na 6 SOC); thrombocytopenia kandi yakoraga neza nta guterwa kwa platine kumunsi wa 28. 13 Abitabiriye SOC-F na 13 SOC bari bafite AE bashyizwe mubikorwa "byateganijwe" (Imbonerahamwe y'inyongera S5 kumurongo). inkomoko itazwi (n = 1)) Bose basohotse murugo ari bazima.Umwe mu bitabiriye SOC-F yagize uburibwe bworoheje kandi undi witabiriye SOC-F yarwaye impiswi zidakabije nyuma yiminsi 13 asohotse; byombi byakemuwe nta rukurikirane. Nyuma yo gupfa, 50 AEs yakemuwe na 27 ikemurwa nta gihindutse cyangwa ibikurikira byakemuwe (Imbonerahamwe yinyongera kumurongo S6) Nta AEs yari ifitanye isano no kwiga ibiyobyabwenge.
Nibura icyitegererezo kimwe cya PK cyakusanyirijwe mubitabiriye 60. Abitabiriye mirongo itanu na batanu batanze ibyitegererezo bine byuzuye, naho 5 bitabiriye amahugurwa batanze urugero rwicyiciro. 119 kuri fosfomycine yo mu kanwa) hamwe na 15 CSF byasesenguwe.Nta ngero zigeze zifite fosfomycine munsi yumubare wabyo.32
Iterambere ryabaturage rya PK hamwe nigisubizo cyigero cyasobanuwe muburyo burambuye ahandi.32 Muri make, icyerekezo cya PK igizwe nibice bibiri hamwe na CSF yongeyeho itanga neza bihuye namakuru, hamwe nibisobanuro hamwe nubunini kuri reta ihagaze kubantu basanzwe (uburemere bwumubiri ( WT) 2805 g, imyaka yo kubyara (PNA) umunsi 1, imyaka yimihango (PMA) ibyumweru 40) yari 0.14 L / isaha (0.05 L / isaha / kg) na 1.07 L (0.38 L / kg), usibye kugenwa neza imikurire ya allometrici kandi iteganijwe gukura kwa PMA ishingiye kumikorere yimpyiko31, PNA ifitanye isano no kwiyongera mugihe cyicyumweru cyambere nyuma yo kubyara.Ikigereranyo gishingiye ku cyitegererezo cyerekana ko bioavailable yo mu kanwa yari 0.48 (95% CI 0.35 kugeza 0.78) naho ubwonko bwa cerebrospinal fluid / plasma bwari 0.32 (95% CI 0.27 kugeza 0.41).
Kwiyongera kumurongo Igicapo S2 cyerekana kwigana imiterere ya plasma yibanda-igihe cyo kwerekana.Ishusho ya 2 n'iya 3 zerekana AUC Ikibazo cyo Kugera ku ntego (PTA) kubantu biga (uburemere bw'umubiri> 1500 g): MIC yinjira kuri bacteriostasis, 1-log kwica, no kubuza kurwanya, ukoresheje MIC imbago ziva kuri neonates nto.amakuru yo gushishoza. Tanga ubwiyongere bwihuse bwibisobanuro mucyumweru cya mbere cyubuzima, ibigereranyo byashyizwe hamwe na PNA (Imbonerahamwe yinyongera S7 kumurongo).
Intego zishoboka zagerwaho hamwe na fosfomycine yimitsi. Subpopulations zivuka. Itsinda rya 1: WT> 1.5 kg + PNA days iminsi 7 (n = 4391), Itsinda rya 2: WT> 1.5 kg + PNA> iminsi 7 (n = 2798), Itsinda rya 3: WT ≤1.5 kg + PNA ≤7 Iminsi (n = 1534), Itsinda rya 4: WT ≤1.5 kg + PNA> iminsi 7 (n = 1277) .Itsinda rya 1 na 2 ryagereranyaga abarwayi basa nabujuje ibyo dushyiramo. Amatsinda 3 na 4 bagereranya extrapolations kuri neonates itarize mubaturage bacu.Iyi shusho yumwimerere yakozwe na ZK kuriyi nyandiko yandikishijwe intoki.BID, kabiri kumunsi;IV, inshinge;MIC, byibuze kwibandaho;PNA, imyaka yo kubyara;WT, uburemere.
Intego yibibazo yagezweho hamwe na dosiye ya fosfomycine yo mu kanwa. Subpopulations zivuka. Itsinda rya 1: WT> 1.5 kg + PNA days iminsi 7 (n = 4391), Itsinda rya 2: WT> 1.5 kg + PNA> iminsi 7 (n = 2798), Itsinda rya 3: WT ≤1.5 kg + PNA ≤ Iminsi (n = 1534), Itsinda rya 4: WT ≤1.5 kg + PNA> iminsi 7 (n = 1277) .Itsinda rya 1 na 2 ryagereranyaga abarwayi basa nabujuje ibyo dushyiramo. Amatsinda 3 na 4 byerekana extrapolation ya preonm neonates ukoresheje amakuru yo hanze atize mubaturage bacu.Iyi shusho yumwimerere yakozwe na ZK kubwiyi nyandiko yandikishijwe intoki.BID, kabiri kumunsi;MIC, byibuze kwibandaho;PNA, imyaka yo kubyara;PO, umunwa;WT, uburemere.
Ku binyabuzima bifite MIC> 0.5 mg / L, guhagarika kurwanya ntibyigeze bigerwaho hamwe na hamwe muburyo bwo gufata urw'agashinyaguro (Ishusho 2 na 3) .Ku 100 mg / kg iv inshuro ebyiri kumunsi, bacteriostasis yagezweho hamwe na MIC ya 32 mg / L ya 100% PTA mubice bine byose by'agashinyaguro (Ishusho 2) .Ku bijyanye no kwica 1-log, kubitsinda 1 na 3 hamwe na PNA days7, PTA yari 0.84 na 0.96 hamwe na 100 mg / kg iv kabiri kumunsi kandi MIC yari 32 mg / L. na 0,91 na 0,98 kubitsinda rya 4.
Indangagaciro za PTA kumatsinda 2 na 4 kuri 100 mg / kg kumunwa kabiri kumunsi byari 0,85 na 0,96, (Ishusho 3), naho PTA agaciro kumatsinda 1-4 yari 0.15, 0.004, 0.41, na 0.05 kuri 32 mg / L.Kwica 1-log munsi ya MIC.
Twatanze ibimenyetso bya fosfomycine kuri 100 mg / kg / dose inshuro ebyiri kumunsi ku bana badafite ibimenyetso byerekana ihungabana rya plasma sodium (intravenous) cyangwa impiswi ya osmotic (umunwa) ugereranije na SOC.Intego yacu yibanze yumutekano, tumenye itandukaniro riri hagati ya plasma sodium hagati ya amatsinda abiri yo kuvura kumunsi wa 2, yari afite imbaraga zihagije.Nubwo ingano yicyitegererezo yacu yari nto cyane kugirango tumenye itandukaniro ryamatsinda mubindi bikorwa byumutekano, neonates zose zarakurikiranwe hafi kandi ibyabaye byavuzwe bifasha gutanga ibimenyetso bifatika byerekana ikoreshwa rya fosfomycine muribi abaturage byoroshye na sepsis ubundi buryo bwo kuvura.Nyamara, kwemeza ibisubizo mubinini binini kandi bikomeye bizaba ingenzi.
Twari tugamije gushaka neonates days28 yumunsi kandi ntitwigeze dushyiramo abakekwaho kuba sepsis hakiri kare.Nyamara, 86% bya neonate bari mubitaro mugihe cyicyumweru cyambere cyubuzima, byemeza umutwaro uremereye wuburwayi bwa neonatal kare byavuzwe muri LMIC.33 -36 Indwara itera indwara ya septi hakiri kare na nyuma yo gutangira (harimo na ESBL E. coli na Klebsiella pneumoniae byagaragaye) kuri mikorobe yica mikorobe, 37-39 irashobora kuboneka mubyara. nkumurongo wambere wubuvuzi urashobora kunoza ibisubizo no kwirinda gukoresha karbapenem.
Kimwe na mikorobe myinshi, 40 PNA ni covariate yingenzi isobanura neza fosfomycine. Izi ngaruka, zitandukanye na GA hamwe nuburemere bwumubiri, byerekana gukura byihuse kwungurura isi nyuma yo kuvuka. Mubisanzwe, 90% bya Enterobacteriaceae MIC ya fosfomycine MIC ya ≤32 µg . kuvura imitsi. Iyo bimaze guhinduka, niba bisabwa guhinduranya fosfomycine yo mu kanwa, igipimo gishobora gutoranywa hashingiwe kuri neonatal WT, PMA, PNA, ndetse na MIC ishobora gutera indwara, ariko bioavailability ivugwa hano igomba kwitabwaho. Harakenewe abanyeshuri kugirango basuzume neza umutekano ningirakamaro byiyi dose yo hejuru isabwa na moderi ya PK.
Igihe cyo kohereza: Werurwe-16-2022