Cholinga Kuwunika zovuta zokhudzana ndi fosfomycin (AEs) ndi pharmacokinetics ndi kusintha kwa sodium mu ana akhanda omwe ali ndi sepsis yachipatala.
Pakati pa Marichi 2018 ndi February 2019, ana akhanda 120 azaka ≤28 adalandira maantibayotiki odziwika bwino (SOC) a sepsis: ampicillin ndi gentamicin.
Kulowererapo Tidapereka theka la otenga nawo gawo mwachisawawa kuti alandire fosfomycin yowonjezereka yotsatiridwa ndi oral fosfomycin pa mlingo wa 100 mg/kg kawiri tsiku lililonse kwa masiku 7 (SOC-F) ndikutsatiridwa kwa masiku 28.
Zotsatira za makanda 61 ndi 59 azaka za masiku 0-23 zidaperekedwa ku SOC-F ndi SOC, motsatana. Palibe umboni wosonyeza kuti fosfomycin imakhudza seramu.sodiumkapena zotsatira za m'mimba. Pakati pa nthawi ya 1560 ndi 1565 ya kuwonetsetsa kwa makanda, tinawona 50 AEs mu 25 SOC-F otenga nawo mbali ndi 34 SOC otenga nawo mbali, motero (2.2 vs 3.2 zochitika / masiku 100 akhanda; kusiyana kwa chiwerengero -0.95 makanda / zochitika 100 / makanda tsiku (95% CI -2.1 mpaka 0.20)) .4 SOC-F ndi atatu a SOC adamwalira.Kuchokera ku zitsanzo za pharmacokinetic za 238, chitsanzo chinasonyeza kuti ana ambiri amafunikira mlingo wa 150 mg / kg m'mitsempha kawiri pa tsiku kuti akwaniritse zolinga za pharmacodynamic, ndi kwa akhanda ochepera masiku 7 kapena kulemera kwa <1500 g tsiku lililonse Mlingo udachepetsedwa mpaka 100 mg/kg kawiri.
Kutsiliza ndi Kufunika Kwake Fosfomycin ikhoza kukhala njira yotsika mtengo yochizira sepsis wakhanda ndi njira yosavuta yopangira. Chitetezo chake chiyenera kuwerengedwanso pagulu lalikulu la akhanda ogonekedwa m'chipatala, kuphatikizapo ana obadwa kumene kapena odwala omwe akudwala kwambiri. motsutsana ndi tizilombo tating'onoting'ono kwambiri, choncho tikulimbikitsidwa kugwiritsa ntchito fosfomycin pamodzi ndi wothandizira wina wa antibacterial.
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.
Iyi ndi nkhani yotseguka yoperekedwa pansi pa chilolezo cha Creative Commons Attribution 4.0 Unported (CC BY 4.0), chomwe chimalola ena kukopera, kugawanso, kukonzanso, kusintha, ndi kupanga ntchitoyi pazifukwa zilizonse, pokhapokha atatchulidwa bwino Ntchito yoyambirira. aperekedwa, ulalo wa chiphaso chaperekedwa, ndi chisonyezero chosonyeza ngati zasintha.Onani: https://creativecommons.org/licenses/by/4.0/.
Kukana kwa maantimicrobial kumayika pachiwopsezo ku moyo wa ana akhanda ndipo pakufunika mwachangu njira zatsopano zochiritsira zotsika mtengo.
Pali sodium wolemetsa kwambiri ndi mtsempha wa fosfomycin, ndipo pakamwa fosfomycin mankhwala ali wambirimbiri fructose, koma pali zochepa chitetezo deta akhanda.
Malangizo a ana ndi akhanda a mlingo wa fosfomycin m'mitsempha amasiyana, ndipo palibe malamulo osindikizidwa pakamwa.
Mtsempha ndi m'kamwa fosfomycin pa 100 mg/kg kawiri pa tsiku, motero, analibe mphamvu pa seramu.sodiumkapena zotsatira za m'mimba.
Ana ambiri angafunikire mtsempha wa fosfomycin 150 mg/kg kawiri tsiku lililonse kuti akwaniritse zolinga zake, komanso kwa akhanda osakwana masiku 7 kapena kulemera kochepera 1500 g, mtsempha wa mtsempha wa fosfomycin 100 mg/kg kawiri tsiku lililonse.
Fosfomycin amatha kuphatikizidwa ndi mankhwala ena opha tizilombo toyambitsa matenda kuti athetse matenda a neonatal sepsis popanda kugwiritsa ntchito carbapenems poyambitsa kuwonjezeka kwa antimicrobial kukana.
Antimicrobial resistance (AMR) imakhudza mopanda malire anthu a m’mayiko osauka ndi apakati (LMICs). okhala ndi tizilombo tosamva mankhwala ambiri (MDR) zomwe zimachititsa pafupifupi 30% ya imfa za akhanda a sepsis padziko lonse lapansi.2
WHO imalimbikitsa ampicillin,penicillin, kapena cloxacillin (ngati matenda a S. aureus akuganiziridwa) kuphatikizapo gentamicin (mzere woyamba) ndi cephalosporins wachitatu (mzere wachiwiri) pofuna chithandizo chamankhwala cha neonatal sepsis.3 Pamodzi ndi beta-lactamase (ESBL) yowonjezereka carbapenemase, 4 zodzipatula zachipatala nthawi zambiri zimanenedwa kuti sizikukhudzidwa ndi regimen iyi.5 Kusungidwa kwa carbapenems n'kofunikira kuti MDR ilamulire, 6 ndi kubwezeretsanso maantibayotiki achikhalidwe amalimbikitsidwa kuti athetse kusowa kwa mankhwala atsopano otsika mtengo.7
Fosfomycin ndi chinthu chochokera ku phosphonic acid chomwe sichili ndi mwini wake chomwe chawonedwa kuti "chofunikira" ndi WHO.8 Fosfomycin ndi bactericidal9 ndipo imawonetsa zochita zolimbana ndi mabakiteriya a gram-positive ndi gram-negative, kuphatikizapo methicillin-resistant Staphylococcus aureus, vancomycin-resistant, ESBL opanga ndipo akhoza kulowa mu biofilm.10 Fosfomycin yawonetsa mu vitro synergy ndi aminoglycosides ndi carbapenems 11 12 ndipo amagwiritsidwa ntchito kwambiri kwa akuluakulu omwe ali ndi matenda a MDR mkodzo.13
Pakali pano pali zotsutsana malingaliro pa mlingo wa mtsempha wa fosfomycin kwa ana, kuyambira 100 mpaka 400 mg/kg/tsiku, popanda kusindikizidwa pakamwa mlingo regimen. 25-50 mg / kg.14 15 Kumanga kwa mapuloteni kunali kochepa, ndipo kuchuluka kwakukulu kunali kogwirizana ndi deta ya anthu akuluakulu.16 17 Zotsatira za mabakiteriya zinkaganiziridwa kuti zimagwirizanitsidwa ndi nthawi yomwe ili pamwamba pa chiwerengero chochepa cha inhibitory concentration (MIC) 16 kapena malo omwe ali pansi pamphepete. (AUC):Chiŵerengero cha MIC.18 19
Malipoti okwana 84 a ana akhanda omwe amalandila mtsempha wa fosfomycin pa 120-200 mg/kg/tsiku akusonyeza kuti analekerera bwino.20-24 Poizoni ikuwoneka yotsika mwa akulu ndi ana okulirapo.25 Komabe, fosfomycin ya parenteral ili ndi 14.4 mmol/ 330 mg sodium pa gramu-chomwe chingakhale chodetsa nkhawa kwa ana akhanda omwe sodium reabsorption imagwirizana mosagwirizana ndi msinkhu wa gestational (GA) .26 Kuwonjezera apo, fosfomycin ya pakamwa imakhala ndi fructose katundu wambiri (~ 1600 mg / kg / tsiku), zomwe zingayambitse m'mimba. zotsatira zoyipa ndi kukhudza madzimadzi.27 28
Tinkafuna kuyesa pharmacokinetics (PK) ndi kusintha kwa sodium mu sepsis neonates, komanso zochitika zovuta (AEs) zomwe zimagwirizanitsidwa ndi mtsempha wotsatira oral fosfomycin.
Tinapanga mayeso otseguka osasinthika omwe amafananizidwa ndi maantibayotiki a SOC kuphatikiza IV otsatiridwa ndi oral fosfomycin mwa akhanda omwe ali ndi sepsis kuchipatala ku Kilifi County Hospital (KCH), Kenya.
Ana onse obadwa kumene omwe adalandiridwa ku KCH adayesedwa. Njira zophatikizira zinali: zaka ≤28 masiku, kulemera kwa thupi> 1500 g, mimba> masabata 34, ndi njira zopangira mankhwala opha tizilombo mu WHO3 ndi Kenya29 malangizo. 30 sodium ≥150 mmol/L, creatinine ≥150 µmol/L, jaundice yomwe imafuna kuikidwa magazi, ziwengo kapena contraindication kwa fosfomycin, chizindikiro cha gulu lina la matenda opha maantibayotiki, wakhandayo sanapatsidwe kuchipatala china kapena ayi ku Kilifi County (Chithunzi 1). ).
Yesani flowchart.Chiwerengero choyambirirachi chidapangidwa ndi CWO pamipukutu iyi.CPR, resuscitation cardiopulmonary;HIE, hypoxic-ischemic encephalopathy;IV, mtsempha;SOC, muyezo wa chisamaliro;SOC-F, muyezo wa chisamaliro kuphatikiza fosfomycin.*Zoyambitsa zimaphatikizapo mayi (46) kapena kudwala kwambiri (6) pambuyo pochitidwa opaleshoni, kutulutsidwa m'chipatala (3), kutulutsidwa mosagwirizana ndi malingaliro (3), kusiyidwa ndi amayi (1) komanso kutenga nawo mbali pazachipatala. phunziro lina (1) .† Mmodzi wochita nawo SOC-F anamwalira atamaliza kutsata (Tsiku 106).
Ophunzira adalembetsedwa mkati mwa maola 4 a mlingo woyamba wa maantibayotiki a SOC mpaka Seputembara 2018, pomwe kusintha kwa protocol kudakulitsa izi mpaka mkati mwa maola 24 kuphatikiza kuvomereza usiku wonse.
Ophunzira adapatsidwa (1: 1) kuti apitirize pa maantibayotiki a SOC okha kapena kulandira SOC kuphatikiza (mpaka) masiku a 7 a fosfomycin (SOC-F) pogwiritsa ntchito ndondomeko yowonongeka ndi kukula kwachisawawa (Supplementary Figure S1 pa intaneti) . Kubisika ndi sequentially maenvulopu osindikizidwa osindikizidwa.
Malinga ndi WHO ndi malangizo a ana aku Kenya, ma SOCs amaphatikiza ampicillin kapena cloxacillin (ngati akuganiziridwa kuti ali ndi matenda a staphylococcal) kuphatikiza gentamicin ngati maantibayotiki oyamba, kapena cephalosporins a m'badwo wachitatu (mwachitsanzo, ceftriaxone) ngati maantibayotiki a mzere wachiwiri. -F adalandiranso mtsempha wa fosfomycin kwa maola osachepera 48, kusinthira pakamwa pamene chakudya chokwanira chinaloledwa kuganiza kuti kuyamwa kokwanira kwa mankhwala a m'kamwa. mg/mL fosfomycin sodium solution for intravenous infusion (Infectopharm, Germany) ndi Fosfocin 250 mg/5 mL fosfomycin calcium suspension for oral administration (Laboratorios ERN, Spain) kawiri pa tsiku ndi 100 mg/kg/dose.
Ophunzira adatsatiridwa kwa masiku a 28. Onse omwe adachita nawo adasamaliridwa mu gawo lomwelo lodalira kwambiri kuti ayang'anire kuyang'anira kwa AE. Mawerengedwe athunthu a magazi ndi biochemistry (kuphatikizapo sodium) anachitidwa pa kuvomereza, masiku 2, ndi 7, ndipo mobwerezabwereza ngati akuwonetsedwa kuchipatala.AEs amalembedwa molingana ndi MedDRA V.22.0.Kuvuta kunayikidwa malinga ndi DAIDS V.2.1.AEs adatsatiridwa mpaka kutsimikizika kwachipatala kapena kuweruzidwa kuti ndi osachiritsika komanso okhazikika panthawi ya chithandizo. pa chiwerengerochi, kuphatikizapo kuwonongeka komwe kungatheke pakubadwa (protocol in Supplementary file 1 online).
Pambuyo pa IV yoyamba ndi fosfomycin yoyamba yapakamwa, odwala omwe adatumizidwa ku SOC-F adasinthidwa mosavuta (5, 30, kapena mphindi 60) ndi mochedwa (2, 4, kapena 8 ora) PK chitsanzo. Chitsanzo chachisanu chosasinthika chinasonkhanitsidwa kwa ophunzira omwe adakali m'chipatala pa tsiku la 7. Opportunistic cerebrospinal fluid (CSF) zitsanzo zinasonkhanitsidwa kuchokera ku chipatala chosonyeza lumbar puncture (LP) .Kukonzekera kwachitsanzo ndi miyeso ya fosfomycin ikufotokozedwa mu Supplementary file 2 pa intaneti.
Tidawunikanso zambiri zovomerezeka pakati pa 2015 ndi 2016 ndikuwerengera kuti kuchuluka kwa sodium mwa ana akhanda 1785 olemera > 1500 g anali 139 mmol/L (SD 7.6, range 106-198). Kupatula ana akhanda 132 okhala ndi serum sodium> 150 mmol/L njira zochotsera), otsala a 1653 akhanda anali ndi sodium yochuluka ya 137 mmol / L (SD 5.2) . kutsimikiziridwa ndi> 85% mphamvu kutengera zomwe zagawika kale za sodium.
Kwa PK, kukula kwachitsanzo cha 45 kunaperekedwa> 85% mphamvu yoyerekeza magawo a PK ovomerezeka, kuchuluka kwa kugawa, ndi bioavailability, ndi 95% CIs akuyerekeza kugwiritsa ntchito zofananira ndi kulondola kwa ≥20%. idagwiritsidwa ntchito, kukulitsa zaka ndi kukula kwa ana akhanda, kuwonjezera kuyamwa koyambirira komanso kuganiziridwa kuti ndi bioavailability.31 Kuti tilole zitsanzo zomwe zikusowa, tinali ndi cholinga cholembera ana akhanda a 60 pagulu lililonse.
Kusiyana kwa magawo oyambira kunayesedwa pogwiritsa ntchito mayeso a χ2, t-test ya Student, kapena Wilcoxon's rank-sum test.Kusiyana kwa tsiku la 2 ndi tsiku la 7 sodium, potaziyamu, creatinine, ndi alanine aminotransferase anayesedwa pogwiritsa ntchito kusanthula kwa covariance kusinthidwa kuti zikhale zoyambira. Kwa AEs, zochitika zoopsa kwambiri (SAEs), ndi zotsatira za mankhwala osokoneza bongo, tinagwiritsa ntchito STATA V.15.1 (StataCorp, College Station, Texas, USA).
Kuyerekeza kwachitsanzo kwa magawo a PK kunachitika mu NONMEM V.7.4.32 pogwiritsa ntchito zowerengera zovomerezeka zoyambira ndi kuyanjana, tsatanetsatane wa chitukuko cha chitsanzo cha PK ndi mafananidwe amaperekedwa kwina.32
Kuyang'anira pamalowa kudachitidwa ndi DNDi/GARDP, ndi kuyang'anira koperekedwa ndi komiti yodziyimira payokha yachitetezo cha data ndi kuyang'anira.
Pakati pa Marichi 19, 2018, ndi February 6, 2019, ana 120 akhanda (61 SOC-F, 59 SOC) adalembetsedwa (Chithunzi 1), mwa iwo 42 (35%) adalembetsa isanawunikenso protocol.Gulu.Median (IQR) zaka, kulemera ndi GA zinali tsiku limodzi (IQR 0-3), 2750 g (2370-3215) ndi masabata 39 (38-40), motsatira. pa intaneti Supplementary Table S1.
Bacteremia anapezeka mwa ana awiri akhanda (Supplementary Table S2 pa intaneti) 2 mwa 55 akhanda omwe analandira LP anali ndi ma laboratory-confirmed meningitis (Streptococcus agalactiae bacteremia ndi CSF leukocytes ≥20 cells/µL (SOC-F); positive Streptococcus anti pneumoniae fluide ndi CSF leukocytes ≥ 20 maselo/µL (SOC)).
Mmodzi wakhanda wa SOC-F molakwika adangolandira ma antimicrobial a SOC okha ndipo sanaphatikizidwe pakuwunika kwa PK. Awiri a SOC-Fs ndi SOC Neonatal m'modzi adasiya chilolezo - kuphatikiza data yochotsapo. Onse koma otenga nawo gawo awiri a SOC (cloxacillin kuphatikiza gentamicin (n=1 ) ndi ceftriaxone (n=1)) analandira ampicillin kuphatikiza gentamicin atalandira.Online Supplementary Table S3 ikuwonetsa kuphatikiza kwa maantibayotiki omwe amagwiritsidwa ntchito mwa omwe adalandira maantibayotiki kupatula ampicillin kuphatikiza gentamicin pakuloledwa kapena kusintha kwamankhwala.Omwe adatenga nawo gawo khumi a SOC-F adasinthidwa. ku chithandizo chachiwiri chifukwa cha kuwonjezereka kwachipatala kapena meningitis, asanu mwa iwo anali asanatengere chitsanzo chachinayi cha PK (Supplementary Table S3 pa intaneti) .
Otsatira asanu ndi limodzi (anayi a SOC-F, awiri a SOC) adafera m'chipatala (Chithunzi 1) .Mmodzi wa SOC adamwalira patatha masiku atatu atatulutsidwa (tsiku la 22) . 106 (kunja kwa kafukufuku wotsatira);deta inaphatikizidwa kupyolera mu tsiku la 28. Ana atatu a SOC-F anatayika kuti atsatire. Ana onse / masiku owonetsetsa a SOC-F ndi SOC anali 1560 ndi 1565, motero, omwe 422 ndi 314 anali m'chipatala.
Pa Tsiku la 2, chiwerengero cha (SD) cha plasma sodium kwa otsogolera a SOC-F chinali 137 mmol / L (4.6) motsutsana ndi 136 mmol / L (3.7) kwa ochita nawo SOC;kutanthauza kusiyana + 0.7 mmol / L (95% CI) -1.0 ku +2.4) .kutanthauza kusiyana -2.9 mmol/L (95% CI -7.5 mpaka +1.8) (Table 2).
Patsiku lachiwiri, kuchuluka kwa potaziyamu (SD) mu SOC-F kunali kotsika pang'ono poyerekeza ndi makanda a SOC-F: 3.5 mmol/L (0.7) vs 3.9 mmol/L (0.7), kusiyana -0.4 mmol/L (95% CI -0.7 mpaka -0.1) Panalibe umboni wosonyeza kuti magawo ena a labotale amasiyana pakati pa magulu awiriwa (Table 2).
Tidawona 35 AEs mwa otenga nawo gawo 25 SOC-F ndi 50 AEs mwa otenga nawo gawo 34 SOC;2.2 zochitika / masiku 100 akhanda ndi 3.2 zochitika / masiku 100 akhanda, motero: IRR 0.7 (95% CI 0.4 mpaka 1.1), zochitika za IRD -0.9 / 100 masiku akhanda (95% CI -2.1 ku +0.2, p = 0.11).
Ma SAE khumi ndi awiri adachitika mwa otenga nawo gawo 11 a SOC-F ndi 14 SAEs mwa otenga nawo gawo 12 SOC (zochitika za SOC 0.8/100 masiku akhanda vs 1.0 zochitika / masiku 100 akhanda; IRR 0.8 (95% CI 0.4 mpaka 1.8) , IRnt/100 muzochitika za2. masiku (95% CI -0.9 mpaka +0.5, p=0.59) Hypoglycemia inali yofala kwambiri AE (5 SOC-F ndi 6 SOC); 3 mwa 4 mu gulu lirilonse 3 SOC-F ndi 4 SOC otenga nawo mbali anali ocheperapo kapena ovuta kwambiri. thrombocytopenia ndipo anali kuchita bwino popanda kuikidwa magazi kwa platelet pa tsiku la 28. Otsatira a 13 SOC-F ndi 13 SOC anali ndi AE yomwe imatchedwa "zoyembekezereka" (Supplementary Table S5 pa intaneti) Otsatira a 3 SOC adavomerezedwa (chibayo (n = 2) ndi matenda a febrile Osadziwika bwino (n=1)) Onse anatulutsidwa kwawo ali moyo Mmodzi mwa otenga nawo mbali pa SOC-F anali ndi zidzolo pang'ono za perineal ndipo wina wa SOC-F anali ndi matenda otsekula m'mimba pang'ono patatha masiku 13 atatuluka, zonse zidathetsedwa popanda kutsatana. Ma AEs adathetsedwa ndipo 27 adathetsedwa popanda kusintha kapena zotsatira zake (pa intaneti Supplementary Table S6). Palibe ma AE omwe anali okhudzana ndi kuphunzira mankhwala.
Osachepera chitsanzo chimodzi cha PK cha mtsempha chinasonkhanitsidwa kuchokera kwa anthu a 60. Anthu makumi asanu ndi asanu ndi asanu adapereka zitsanzo zonse zinayi, ndipo ophunzira a 5 anapereka zitsanzo zochepa. Ophunzira asanu ndi limodzi anali ndi zitsanzo zomwe zinasonkhanitsidwa pa tsiku la 7. Chiwerengero cha 238 plasma (119 kwa IV ndi IV ndi IV ndi IV ndi IV) 119 kwa oral fosfomycin) ndi zitsanzo za 15 CSF zinafufuzidwa.Palibe zitsanzo zomwe zinali ndi milingo ya fosfomycin pansi pa malire.
Kukula kwachitsanzo cha anthu a PK ndi zotsatira zofananira zikufotokozedwa mwatsatanetsatane kwina.32 Mwachidule, chitsanzo cha PK chokhala ndi zigawo ziwiri chokhala ndi chipinda chowonjezera cha CSF chinapereka chidziwitso chabwino kwa deta, ndi chilolezo ndi voliyumu pamtunda wokhazikika kwa omwe akugwira nawo ntchito (kulemera kwa thupi) WT) 2805 g, zaka zoberekera (PNA) tsiku la 1, zaka zam'mimba (PMA) masabata a 40) zinali 0.14 L / ola (0.05 L / ola / kg) ndi 1.07 L (0.38 L / kg), motsatira. kukula kwa allometric ndi kukula kwa PMA komwe kukuyembekezeka kutengera ntchito yaimpso31, PNA imalumikizidwa ndi chilolezo chowonjezeka pa sabata yoyamba yobereka. Kuyerekeza kwachitsanzo kwa oral bioavailability kunali 0.48 (95% CI 0.35 mpaka 0.78) ndipo chiŵerengero cha cerebrospinal fluid / plasma chinali 0.32 (95% CI 0.27 mpaka 0,41).
Pa intaneti Supplementary Figure S2 ikuwonetsa mbiri yanthawi yokhazikika ya plasma. Zithunzi 2 ndi 3 zikuwonetsa kuthekera kwa AUC kwa Target Attainment (PTA) kwa anthu ofufuza (kulemera kwa thupi> 1500 g): MIC thresholds for bacteriostasis, 1-log kupha, ndi kuletsa kukana, pogwiritsa ntchito ma MIC kuchokera kwa ana ang'onoang'ono.data to infer.Popeza kuwonjezeka kofulumira kwa chilolezo pa sabata yoyamba ya moyo, zofananirazo zinasinthidwanso ndi PNA (Supplementary Table S7 online).
Zolinga zotheka zomwe zakwaniritsidwa ndi intravenous fosfomycin.Neonatal subpopulations.Gulu 1: WT >1.5 kg +PNA ≤7 masiku (n=4391), Gulu 2: WT>1.5 kg +PNA>masiku 7 (n=2798), Gulu 3: WT ≤1.5 kg + PNA ≤7 Masiku (n = 1534), Gulu 4: WT ≤1.5 kg + PNA > masiku 7 (n = 1277) .Magulu 1 ndi 2 ankaimira odwala ofanana ndi omwe adakwaniritsa zofunikira zathu zophatikizira.Magulu 3 ndi 4 imayimira ma extrapolations kwa ana osaphunzira omwe sanaphunzirepo m'gulu lathu.Chiwerengero choyambirirachi chinapangidwa ndi ZK palembali.BID, kawiri tsiku lililonse;IV, jekeseni wa mtsempha;MIC, ndende yochepa yoletsa;PNA, zaka zakubadwa;WT, kulemera.
Chandamale chotheka chatheka ndi mlingo wa oral fosfomycin.Kuchuluka kwa ana akhanda.Gulu 1: WT>1.5 kg +PNA ≤7 masiku (n=4391), Gulu 2: WT>1.5 kg +PNA>masiku 7 (n=2798), Gulu 3: WT ≤1.5 kg + PNA ≤7 Masiku (n=1534), Gulu 4: WT ≤1.5 kg + PNA>masiku 7 (n=1277) .Magulu 1 ndi 2 ankaimira odwala ofanana ndi omwe adakwaniritsa zofunikira zathu zophatikizira.Magulu 3 ndipo 4 imayimira extrapolation ya ana akhanda asanakwane pogwiritsa ntchito deta yakunja yomwe sinaphunzire mu chiwerengero chathu.Chiwerengero choyambirirachi chinapangidwa ndi ZK palembali.MIC, ndende yochepa yoletsa;PNA, zaka zakubadwa;PO, pakamwa;WT, kulemera.
Kwa zamoyo zomwe zili ndi MIC> 0.5 mg/L, kukana kukana sikunakwaniritsidwe nthawi zonse ndi mitundu ina yamankhwala onyoza (Chithunzi 2 ndi 3) . ya 100% PTA m'magulu onse anayi onyoza (Chithunzi 2) . Ponena za kupha kwa chipika cha 1, kwa magulu a 1 ndi 3 okhala ndi PNA ≤7 masiku, PTA inali 0.84 ndi 0.96 ndi 100 mg / kg iv kawiri tsiku lililonse ndipo MIC inali 32 mg / L, koma gululo linali ndi PTA yochepa, 0.19 ndi 0.60 kwa 2 ndi 4 PNA> masiku 7, motero. Pa 150 ndi 200 mg / kg kawiri tsiku lililonse kudzera m'mitsempha, 1-log kupha PTA kunali 0.64 ndi 0.90 kwa gulu 2 ndi 0.91 ndi 0.98 pagulu 4, motsatana.
Miyezo ya PTA yamagulu a 2 ndi 4 pa 100 mg/kg pakamwa kawiri tsiku lililonse inali 0.85 ndi 0.96, motsatana (Chithunzi 3), ndipo mfundo za PTA zamagulu 1-4 zinali 0.15, 0.004, 0.41, ndi 0.05 pa 32 mg / L, motero.Pha 1-log pansi pa MIC.
Tinapereka umboni wa fosfomycin pa 100 mg / kg / mlingo kawiri pa tsiku kwa makanda opanda umboni wa kusokonezeka kwa plasma sodium (intravenous) kapena osmotic kutsekula m'mimba (oral) poyerekeza ndi SOC.Cholinga chathu chachikulu cha chitetezo, kuzindikira kusiyana kwa plasma sodium m'magazi pakati pa magulu awiri ochiritsira pa tsiku la 2, anali ndi mphamvu zokwanira.Ngakhale kuti kukula kwathu kwachitsanzo kunali kochepa kwambiri kuti tidziwe kusiyana pakati pa magulu pazochitika zina zachitetezo, ana onse akhanda ankayang'aniridwa mosamala ndipo zochitika zomwe zafotokozedwa zimathandizira kupereka umboni wotsimikizira kugwiritsa ntchito fosfomycin mu izi. anthu omwe ali ndi vuto la sepsis alternative empiric therapy.
Tinali ndi cholinga cholembera ana akhanda ≤28 masiku akubadwa ndipo sitinaphatikizepo mwachisawawa kuti ayambe kukayikira kuti amayamba kudwala matenda a sepsis. -36 Tizilombo toyambitsa matenda timene timayambitsa sepsis koyambirira komanso mochedwa (kuphatikiza ESBL E. coli ndi Klebsiella pneumoniae tawonedwa) ku ma epirical antimicrobials,37-39 atha kupezeka m'njira zakulera. monga chithandizo choyamba chingapangitse zotsatira zabwino ndikupewa kugwiritsa ntchito carbapenem.
Monga momwe zimakhalira ndi maantimicrobial ambiri, 40 PNA ndi chinthu chofunikira kwambiri chofotokozera chilolezo cha fosfomycin. Izi, zosiyana ndi GA ndi kulemera kwa thupi, zimayimira kukhwima kwa glomerular kusefera pambuyo pobadwa. /mL15, ndi ntchito yophera mabakiteriya ingafunike>100 mg/kg/dose mtsempha wa ana akhanda kupitirira masiku 7 (Chithunzi 2) Mukakhazikika, ngati kusintha kwa oral fosfomycin kukufunika, mlingowo ukhoza kusankhidwa potengera mwana wakhanda WT, PMA, PNA, komanso tizilombo toyambitsa matenda MIC, koma bioavailability yomwe yanenedwa pano iyenera kuganiziridwa. chitetezo ndi mphamvu ya mlingo wapamwamba uwu womwe ukulimbikitsidwa ndi mtundu wathu wa PK.
Nthawi yotumiza: Mar-16-2022