Maƙasudi Don kimanta abubuwan da ke da alaƙa da fosfomycin (AEs) da pharmacokinetics da canje-canje a cikin matakan sodium a cikin jarirai tare da sepsis na asibiti.
Tsakanin Maris 2018 da Fabrairu 2019, 120 neonates masu shekaru ≤28 kwanaki sun sami daidaitattun maganin rigakafi (SOC) don sepsis: ampicillin da gentamicin.
Tsangwama Mun sanya rabin mahalarta ba da gangan ba don karɓar ƙarin fosfomycin na ciki da kuma fosfomycin na baka a kashi na 100 mg/kg sau biyu a rana don kwanaki 7 (SOC-F) kuma a biyo baya har tsawon kwanaki 28.
Sakamako 61 da 59 jarirai masu shekaru 0-23 kwanaki an sanya su zuwa SOC-F da SOC, bi da bi. Babu wata shaida cewa fosfomycin yana da tasiri akan magani.sodiumko illa masu illa na gastrointestinal. A cikin lokutan 1560 da 1565 na jarirai-rana lokuta, mun lura da 50 AEs a cikin 25 SOC-F mahalarta da 34 SOC mahalarta (2.2 vs 3.2 events / 100 jarirai kwanakin; bambancin farashin -0.95 abubuwan / 100 jarirai ) rana (95% CI -2.1 zuwa 0.20)) .Hudu SOC-F da uku mahalarta SOC sun mutu. Daga 238 pharmacokinetic samfurori, yin samfurin ya nuna cewa yawancin yara suna buƙatar kashi na 150 mg / kg a cikin jini sau biyu a kowace rana don cimma burin pharmacodynamic, kuma ga jarirai <7 kwanaki ko auna <1500 g kowace rana An rage kashi zuwa 100 mg/kg sau biyu.
Kammalawa da Mahimmanci Fosfomycin yana da yuwuwar azaman zaɓi mai araha don maganin sepsis na jarirai tare da tsari mai sauƙi. Dole ne a ƙara yin nazarin amincinsa a cikin ɗimbin ɗimbin jarirai da ke asibiti, gami da waɗanda ba a kai ga haihuwa ba ko marasa lafiya masu tsanani. a kan mafi m kwayoyin, don haka an bada shawarar yin amfani da fosfomycin a hade tare da wani antibacterial wakili.
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.
Wannan labarin buɗaɗɗen shiga ne wanda aka rarraba ƙarƙashin lasisin Creative Commons Attribution 4.0 Unported (CC BY 4.0), wanda ke ba wa wasu damar kwafi, sake rarrabawa, sake haɗawa, canzawa, da gina wannan aikin don kowace manufa, muddin an buga shi da kyau Aikin asali. an ba da hanyar haɗi zuwa lasisi, da kuma alamar ko an yi canje-canje.Duba: https://creativecommons.org/licenses/by/4.0/.
Juriya na rigakafin ƙwayoyin cuta yana haifar da barazana ga rayuwar jarirai kuma akwai buƙatar gaggawa don sabbin hanyoyin magani masu araha.
Akwai nauyin sodium mai mahimmanci tare da fosfomycin na ciki, kuma shirye-shiryen fosfomycin na baki sun ƙunshi fructose mai yawa, amma akwai iyakataccen bayanan aminci a cikin jarirai.
Shawarwari na maganin yara na yara da jarirai don fosfomycin na cikin jijiya sun bambanta, kuma babu wasu ka'idojin maganin baka da aka buga.
Fosfomycin na ciki da na baka a 100 mg/kg sau biyu a rana, bi da bi, ba su da wani tasiri akan magani.sodiumko illolin gastrointestinal.
Yawancin yara na iya buƙatar fosfomycin na ciki 150 mg/kg sau biyu kowace rana don cimma burin inganci, kuma ga jarirai <7 kwanaki ko auna <1500 g, fosfomycin na ciki 100 mg/kg sau biyu kowace rana.
Fosfomycin yana da yuwuwar a haɗa shi tare da sauran ƙwayoyin cuta don magance cututtukan cututtukan mahaifa ba tare da yin amfani da carbapenems a cikin yanayin haɓakar haɓakar ƙwayoyin cuta ba.
Maganin rigakafin ƙwayoyin cuta (AMR) ba daidai ba yana rinjayar yawan jama'a a cikin ƙananan ƙasashe da masu tsaka-tsaki (LMICs) .Raguwar mace-macen jarirai ya kasance ƙasa fiye da na yara masu girma, tare da akalla kashi ɗaya bisa hudu na mutuwar jarirai wanda aka danganta da kamuwa da cuta.1 AMR yana ƙara wannan nauyin, tare da ƙwayoyin cuta da yawa (MDR) suna lissafin kusan 30% na mutuwar sepsis na jarirai a duniya.2
WHO ta ba da shawarar ampicillin,penicillin, ko cloxacillin (idan ana zargin kamuwa da S. aureus) da gentamicin (layi na farko) da cephalosporins na ƙarni na uku (layi na biyu) don maganin empirical na sepsis na jarirai.3 Tare da Extended-spectrum beta-lactamase (ESBL) da kuma carbapenemase, 4 keɓaɓɓen asibiti sau da yawa ana ba da rahoton cewa ba su da hankali ga wannan tsarin.
Fosfomycin wani nau'in phosphonic acid ne wanda ba na mallakar mallaka ba wanda WHO ta ɗauka "mahimmanci". furodusoshi kuma na iya shiga biofilm.10 Fosfomycin ya nuna a cikin in vitro synergy tare da aminoglycosides da carbapenems 11 12 kuma ana amfani da su a cikin manya masu fama da cututtukan urinary fili na MDR.13
A halin yanzu akwai shawarwari masu cin karo da juna don yin amfani da fosfomycin na ciki a cikin likitocin yara, daga 100 zuwa 400 mg / kg / day, ba tare da wani tsarin maganin maganin da aka buga ba. Nazarin jarirai hudu ya kiyasta kawar da rabin rayuwar 2.4-7 hours bayan gudanarwa na ciki. 25-50 mg / kg.14 15 Haɗin furotin ya kasance kadan, kuma mafi yawan ƙididdiga sun kasance daidai da bayanan manya. (AUC): Matsayin MIC.18 19
Jimlar rahotannin shari'o'i 84 na jariran da ke karɓar fosfomycin na ciki a 120-200 mg/kg/rana sun nuna cewa an jure shi da kyau.20-24 Mai guba ya bayyana ya ragu a cikin manya da manyan yara.25 Duk da haka, fosfomycin parenteral ya ƙunshi 14.4 mmol/ 330 MG sodium a kowace gram-mai yiwuwa damuwa aminci ga jarirai wanda sodium reabsorption ya saba daidai da shekarun haihuwa (GA). illolin da ke shafar ma’aunin ruwa.27 28
Mun yi nufin tantance pharmacokinetics (PK) da sodium matakin canje-canje a asibiti sepsis neonates, kazalika da m aukuwa (AEs) hade da intravenous bin fosfomycin na baka.
Mun gudanar da gwajin gwajin da bazuwar lakabin buɗaɗɗen kwatankwacin maganin rigakafi (SOC) kaɗai tare da SOC da IV tare da fosfomycin na baka a cikin jarirai tare da sepsis na asibiti a asibitin Kilifi County (KCH), Kenya.
Dukkan jariran da aka shigar da su zuwa KCH an gwada su. Sharuɗɗan haɗawa sune: shekaru ≤28 kwanakin, nauyin jiki> 1500 g, gestation> 34 makonni, da kuma ka'idojin maganin rigakafi na ciki a cikin WHO3 da jagororin Kenya29. Idan CPR ya buƙaci, Grade 3 hypoxic-ischemic encephalopathy, 30 sodium ≥150 mmol / L, creatinine ≥150 µmol / L, jaundice da ke buƙatar musayar musayar, rashin lafiyan ko ƙin yarda da fosfomycin, ƙayyadaddun nuni na wani nau'in cututtukan ƙwayoyin cuta, an cire neonate daga wani asibiti ko a'a a Kilifi County (Hoto 1). ).
Gwada jadawali.CWO ce ta ƙirƙira wannan ainihin adadi don wannan rubutun.CPR, farfaɗowar zuciya;HIE, hypoxic-ischemic encephalopathy;IV, na jijiya;SOC, daidaitattun kulawa;SOC-F, misali na kulawa da fosfomycin.* Abubuwan da suka haifar sun hada da uwa (46) ko rashin lafiya mai tsanani (6) bayan tiyata, sallama daga asibiti (3), fitarwa daga shawarwarin (3), watsi da uwa (1) da shiga ciki wani binciken (1) † Ɗaya daga cikin mahalarta SOC-F ya mutu bayan kammala biyan (Ranar 106).
An shigar da mahalarta cikin sa'o'i 4 na kashi na farko na maganin rigakafi na SOC har zuwa Satumba 2018, lokacin da gyare-gyaren yarjejeniya ya tsawaita wannan zuwa cikin sa'o'i 24 don haɗawa da shigar da dare.
An sanya mahalarta (1: 1) don ci gaba da maganin rigakafi na SOC kadai ko don karɓar SOC da (har zuwa) kwanaki 7 na fosfomycin (SOC-F) ta amfani da tsarin bazuwar tare da girman toshe bazuwar (Ƙarin Hoto S1 akan layi) An ɓoye ta bi da bi. ambulaf ɗin da aka rufe masu lamba.
Bisa ga ka'idodin WHO da na yara na Kenya, SOC sun haɗa da ampicillin ko cloxacillin (idan ana zargin kamuwa da cutar staphylococcal) da gentamicin a matsayin maganin rigakafi na farko, ko cephalosporins na uku (misali, ceftriaxone) azaman maganin rigakafi na layi na biyu.3 29 Mahalarta bazuwar zuwa SOC. -F kuma ya karbi fosfomycin na ciki na akalla sa'o'i 48, yana canzawa zuwa baki lokacin da aka ba da isasshen abinci don ɗaukar isasshen sha na maganin na baki. mg/mL fosfomycin sodium bayani don jiko na ciki (Infectopharm, Jamus) da Fosfocin 250 mg/5 mL fosfomycin calcium dakatar don gudanar da baki (Laboratorios ERN, Spain) sau biyu kowace rana tare da 100 mg/kg/dose gudanarwa.
An bi mahalarta don kwanaki 28. Dukkan mahalarta an kula da su a cikin rukunin masu dogara sosai don tsara tsarin kulawa na AE. An yi cikakken kididdigar jini da biochemistry (ciki har da sodium) akan shigarwa, kwanakin 2, da 7, kuma maimaita idan an nuna asibiti.AEs. An ƙididdige su bisa ga MedDRA V.22.0. An rarraba tsanani bisa ga DAIDS V.2.1.AEs an bi su har sai an yanke shawara na asibiti ko yanke hukunci na dindindin da kwanciyar hankali a lokacin jiyya." a cikin wannan yawan jama'a, gami da yuwuwar tabarbarewar lokacin haihuwa (ka'idar a Ƙarin fayil 1 akan layi).
Bayan na farko IV da na farko na baka fosfomycin, marasa lafiya da aka sanya wa SOC-F sun kasance bazuwar zuwa farkon (5, 30, ko 60 minutes) da kuma marigayi (2, 4, ko 8 hours) samfurin PK. An tattara samfurin na biyar mara tsari. ga mahalarta waɗanda har yanzu suna kwance a asibiti a ranar 7. An tattara samfurori masu dacewa na cerebrospinal fluid (CSF) daga wani nau'i na lumbar puncture (LP) na asibiti.
Mun sake nazarin bayanan shiga tsakanin 2015 da 2016 kuma mun ƙididdige cewa ma'anar sodium na 1785 neonates masu nauyi> 1500 g shine 139 mmol/L (SD 7.6, kewayon 106-198). Ban da 132 neonates tare da maganin sodium> 150 mmol / L (mu). Sharuɗɗan cirewa), ragowar 1653 neonates suna da ma'anar sodium na 137 mmol/L (SD 5.2) .Sai aka ƙididdige girman samfurin 45 a kowace ƙungiya don tabbatar da cewa 5 mmol / L bambanci a cikin sodium plasma a ranar 2 zai iya zama. ƙaddara tare da> 85% iko bisa tushen bayanan rarraba sodium na gida.
Don PK, girman samfurin 45 yana ba da> 85% iko don kimanta sigogi na PK don sharewa, ƙarar rarrabawa, da bioavailability, tare da 95% CI da aka kiyasta ta yin amfani da simulations tare da daidaito na ≥20%. an yi amfani da shi, girman shekaru da girman ga jarirai, ƙara sha na farko-farko da kuma zaton bioavailability.31 Don ba da izinin samfurori da suka ɓace, muna da nufin ɗaukar yara 60 a kowace ƙungiya.
An gwada bambance-bambance a cikin sigogi na asali ta amfani da gwajin χ2, T-test Student, ko gwajin darajar darajar Wilcoxon. Bambance-bambance a cikin rana 2 da rana 7 sodium, potassium, creatinine, da alanine aminotransferase an gwada ta amfani da nazarin covariance da aka daidaita don ƙimar asali. Don AEs, manyan abubuwan da ba su da kyau (SAEs), da kuma halayen miyagun ƙwayoyi, mun yi amfani da STATA V.15.1 (StataCorp, Kwalejin Kwalejin, Texas, Amurka).
An yi ƙididdige ƙididdiga na tushen ƙididdiga na PK a cikin NONMEM V.7.4.32 ta amfani da ƙididdiga na farko-farko tare da ma'amala, cikakkun bayanai na ci gaban ƙirar PK da simintin an bayar da su a wani wuri.32
DNDi/GARDP ne ya sanya ido a kan wurin, tare da kulawar da kwamitin tsaro da tsaro na bayanai mai zaman kansa ya bayar.
Tsakanin Maris 19, 2018, da Fabrairu 6, 2019, 120 neonates (61 SOC-F, 59 SOC) an yi rajista (Hoto 1), wanda 42 (35%) aka yi rajista kafin bitar yarjejeniya.Rukuni.Median (IQR) shekaru, nauyi da GA sun kasance 1 rana (IQR 0-3), 2750 g (2370-3215) da 39 makonni (38-40), bi da bi. An gabatar da halaye na asali da sigogi na dakin gwaje-gwaje a cikin Table 1 da kan layi Karin Tebura S1.
An gano kwayoyin cuta a cikin yara biyu (Ƙarin Teburin S2 akan layi).2 na 55 neonates waɗanda suka karbi LP suna da ciwon sankarau-tabbatar da dakin gwaje-gwaje (Streptococcus agalactiae bacteremia tare da CSF leukocytes ≥20 sel / µL (SOC-F); tabbatacce Streptococcus pneumoniae gwajin antigen antigen da CSF leukocytes ≥ 20 Kwayoyin / µL (SOC)).
Ɗaya daga cikin SOC-F neonate ba daidai ba ya karbi SOC antimicrobials kawai kuma an cire shi daga nazarin PK. SOC-Fs biyu da SOC Neonatal guda ɗaya sun janye yarda - ciki har da bayanan cirewa na farko. Duk mahalarta SOC guda biyu (cloxacillin da gentamicin (n=1) ) da ceftriaxone (n = 1)) sun karɓi ampicillin da gentamicin akan shiga. Ƙarin Teburin S3 na kan layi yana nuna haɗin ƙwayoyin rigakafi da aka yi amfani da su a cikin mahalarta waɗanda suka karbi maganin rigakafi banda ampicillin da gentamicin a lokacin shiga ko bayan canjin magani. An canza mahalarta SOC-F goma. zuwa jiyya na layi na biyu saboda rashin lafiyar asibiti ko ciwon sankarau, biyar daga cikinsu sun kasance a gaban samfurin PK na hudu (Ƙarin Teburin S3 akan layi) . Gabaɗaya, mahalarta 60 sun sami akalla kashi ɗaya na fosfomycin na jini kuma 58 sun karbi akalla kashi ɗaya na baki.
Shida (hudu SOC-F, biyu SOC) mahalarta sun mutu a asibiti (Figure 1) .Wani mahalarta SOC ya mutu kwanaki 3 bayan fitarwa (rana 22) .Wani mahalarta SOC-F ya rasa biyan kuɗi kuma an gano shi ya mutu a rana. 106 (a waje da bin bin binciken);An haɗa bayanai ta hanyar rana ta 28. An rasa jariran SOC-F guda uku don biyan su. Jimlar jarirai / kwanakin lura don SOC-F da SOC sun kasance 1560 da 1565, bi da bi, wanda 422 da 314 sun kasance a asibiti.
A ranar 2, ma'anar (SD) ƙimar sodium plasma plasma ga mahalarta SOC-F shine 137 mmol / L (4.6) a kan 136 mmol / L (3.7) don mahalarta SOC;ma'anar bambanci + 0.7 mmol / L (95% CI) -1.0 zuwa + 2.4) .A rana ta 7, ma'anar (SD) ƙimar sodium shine 136 mmol / L (4.2) da 139 mmol / L (3.3);ma'anar bambanci -2.9 mmol/L (95% CI -7.5 zuwa + 1.8) (Table 2).
A rana ta 2, ma'ana (SD) ma'aunin potassium a cikin SOC-F ya ɗan yi ƙasa kaɗan fiye da na jarirai SOC-F: 3.5 mmol/L (0.7) vs 3.9 mmol/L (0.7), bambanci -0.4 mmol/L (95% CI) -0.7 zuwa -0.1) .Babu wata shaida cewa wasu sigogi na dakin gwaje-gwaje sun bambanta tsakanin ƙungiyoyi biyu (Table 2).
Mun lura da 35 AEs a cikin mahalarta 25 SOC-F da 50 AEs a cikin mahalarta 34 SOC;2.2 abubuwan da suka faru / 100 kwanakin jariri da 3.2 abubuwan / 100 kwanakin jariri, bi da bi: IRR 0.7 (95% CI 0.4 zuwa 1.1), IRD -0.9 abubuwan / 100 kwanakin jariri (95% CI -2.1 zuwa + 0.2, p=0.11).
SAE goma sha biyu sun faru a cikin mahalarta 11 SOC-F da 14 SAE a cikin mahalarta 12 SOC (SOC 0.8 events / 100 baby days vs 1.0 events / 100 baby days; IRR 0.8 (95% CI 0.4 to 1.8) , IRD -0.2 events/100 baby baby kwanaki (95% CI -0.9 zuwa +0.5, p=0.59). thrombocytopenia kuma suna da kyau ba tare da ƙarin jini na platelet ba a ranar 28. 13 SOC-F da 13 SOC mahalarta suna da AE wanda aka rarraba a matsayin "wanda ake tsammani" (Ƙarin Teburin S5 akan layi). wanda ba a san asalinsa ba (n=1)) Duk an sallame su gida da rai.Daya daga cikin mahalarta SOC-F yana da rauni mai laushi kuma wani ɗan SOC-F yana da matsananciyar gudawa kwanaki 13 bayan fitarwa; duka biyun sun warware ba tare da wani sakamako ba.Bayan cire mace-mace, hamsin An warware AEs kuma an warware 27 ba tare da wani canji ba ko an warware madaidaicin (Table S6 na Ƙarin kan layi)..
Akalla an tattara samfurin PK guda ɗaya daga cikin mahalarta 60. Masu halartar hamsin da biyar sun ba da cikakkun samfurori guda hudu, kuma mahalarta 5 sun ba da samfurori na samfurori. 119 don fosfomycin na baka) da samfuran CSF 15 an bincika.
An kwatanta ci gaban samfurin PK na yawan jama'a da sakamakon kwaikwayo dalla-dalla a wasu wurare.32 A taƙaice, samfurin disposition na PK guda biyu tare da ƙarin ɗakin CSF ya ba da kyau ga bayanai, tare da sharewa da ƙararrawa a matsayi na musamman ga mahalarta masu dacewa (nauyin jiki (nauyin jiki) WT) 2805 g, shekarun haihuwa (PNA) 1 rana, shekarun haihuwa (PMA) 40 makonni) sun kasance 0.14 L / hour (0.05 L / hour / kg) da 1.07 L (0.38 L / kg), bi da bi. Girman allometric da kuma tsammanin PMA maturation dangane da aikin renal31, PNA yana hade da haɓakar ƙãra a lokacin mako na farko na haihuwa. Ƙididdigar ƙididdiga na tushen samfurin na kwayoyin halitta na baka shine 0.48 (95% CI 0.35 zuwa 0.78) da kuma ƙwayar cerebrospinal / plasma rabo shine 0.32 (95% CI 0.27 zuwa 0.41).
Hoto na Ƙarin kan layi S2 yana kwatanta simulated staady-state plasma maida hankali-lokaci profiles. Figures 2 da 3 gabatar da AUC Probability of Target Attainment (PTA) ga yawan binciken (nauyin jiki> 1500 g): MIC kofofin don bacteriostasis, 1-log. kashe, da hana juriya, ta amfani da madaidaitan MIC daga ƙananan yara.Bayanan da za a iya fahimta. Idan aka ba da saurin haɓakawa a cikin makon farko na rayuwa, abubuwan da aka kwatanta sun kara dagewa ta hanyar PNA (Ƙarin Teburin S7 akan layi).
Maƙasudin yuwuwar da aka cimma tare da fosfomycin na ciki.Neonatal subpopulations.Group 1: WT>1.5 kg +PNA ≤7 kwanaki (n=4391), Rukuni 2: WT>1.5 kg +PNA>7 kwanaki (n=2798), Rukuni 3: WT ≤1.5 kg + PNA ≤7 Kwanaki (n = 1534), Rukuni na 4: WT ≤1.5 kg + PNA> 7 kwanaki (n=1277) .Rukunin 1 da 2 sun wakilci marasa lafiya kamar wadanda suka cika ka'idojin shigar mu.Groups 3 da 4 yana wakiltar kari ga jariran da ba a yi karatu ba a cikin al'ummarmu. ZK ne ya kirkiro wannan ainihin adadi don wannan rubutun.BID, sau biyu a kullum;IV, allurar cikin jijiya;MIC, mafi ƙarancin maida hankali mai hanawa;PNA, shekarun haihuwa;WT, nauyi.
Maƙasudin yuwuwar da aka cimma tare da allurai na fosfomycin na baka. Ƙungiya ta Neonatal.Group 1: WT> 1.5 kg +PNA ≤7 kwanaki (n=4391), Rukuni 2: WT > 1.5 kg +PNA > 7 kwanaki (n=2798), Rukuni 3: WT ≤1.5 kg + PNA ≤7 Kwanaki (n=1534), Rukuni na 4: WT ≤1.5 kg + PNA> 7 kwanaki (n=1277) kuma 4 na wakiltar fitar da jariran da ba su taɓa haihuwa ba ta hanyar amfani da bayanan waje da ba a yi nazari a cikin al'ummarmu ba. Wannan adadi na ainihi ZK ne ya ƙirƙira don wannan rubutun.BID, sau biyu a kullum;MIC, mafi ƙarancin maida hankali mai hanawa;PNA, shekarun haihuwa;PO, baka;WT, nauyi.
Don kwayoyin halitta tare da MIC> 0.5 mg / L, ba a ci gaba da juriya da juriya tare da kowane nau'i na dosing dosing (Figures 2 da 3) . Domin 100 mg / kg iv sau biyu a kowace rana, an sami bacteriostasis tare da MIC na 32 mg / L. na 100% PTA a cikin dukkan nau'i-nau'i hudu na izgili (Figure 2) . Game da 1-log kisa, don ƙungiyoyi 1 da 3 tare da PNA ≤7 kwanaki, PTA ya kasance 0.84 da 0.96 tare da 100 mg / kg iv sau biyu a kowace rana kuma MIC shine 32. mg / L, amma ƙungiyar tana da ƙananan PTA, 0.19 da 0.60 don 2 da 4 PNA> 7 kwanaki, bi da bi. A 150 da 200 mg / kg sau biyu a kowace rana a cikin jini, 1-log kashe PTA ya kasance 0.64 da 0.90 don rukuni na 2. da 0.91 da 0.98 don rukunin 4, bi da bi.
Ma'aunin PTA na ƙungiyoyi 2 da 4 a 100 mg / kg baki sau biyu kowace rana sun kasance 0.85 da 0.96, bi da bi (Hoto 3), kuma ƙimar PTA na ƙungiyoyi 1-4 sun kasance 0.15, 0.004, 0.41, da 0.05 a 32 mg/L, bi da bi.Kashe 1-log a ƙarƙashin MIC.
Mun ba da shaida na fosfomycin a 100 mg / kg / kashi sau biyu a kowace rana a cikin jarirai ba tare da wata shaida na damuwa na sodium na plasma ba (jiki) ko zawo na osmotic (na baka) idan aka kwatanta da SOC. Manufar aminci ta farko, gano bambanci a cikin matakan sodium na plasma tsakanin Ƙungiyoyin jiyya guda biyu a ranar 2, sun kasance da isasshen ƙarfi.Ko da yake girman samfurin mu ya yi ƙanƙanta don ƙayyade bambance-bambance tsakanin rukuni a cikin sauran abubuwan da suka faru na aminci, duk an sa ido sosai akan abubuwan da suka faru kuma abubuwan da aka ruwaito sun taimaka wajen samar da shaida don tallafawa yiwuwar amfani da fosfomycin a cikin wannan. yawan masu saurin kamuwa da cutar sepsis madadin empiric therapy.Duk da haka, tabbatar da waɗannan sakamakon a cikin ƙungiyoyi masu girma kuma mafi tsanani zai zama mahimmanci.
Mun yi nufin daukar ma'aikata ≤28 kwanakin shekaru kuma ba zaɓaɓɓe sun haɗa da wadanda ake zargi da kamuwa da cutar ta farko ba. Duk da haka, 86% na jarirai an kwantar da su a asibiti a cikin makon farko na rayuwa, yana tabbatar da babban nauyin cututtukan cututtuka na farko da aka ruwaito a cikin irin wannan LMICs.33 -36 Kwayoyin cututtukan da ke haifar da farkon farawa da sepsis na ƙarshen farawa (ciki har da ESBL E. coli da Klebsiella pneumoniae an lura da su) zuwa magungunan antimicrobial, 37-39 na iya samuwa a cikin mahaifa. kamar yadda jiyya na farko na iya inganta sakamako kuma ya guje wa amfani da carbapenem.
Kamar yadda yake tare da yawancin maganin rigakafi, 40 PNA shine maɓalli mai mahimmanci wanda ke bayyana fosfomycin. / mL15, da kuma aikin bactericidal na iya buƙatar> 100 mg / kg / kashi a cikin jini a cikin ƙananan yara> 7 days (Figure 2) . Domin manufa na 32 µg / ml, idan PNA> 7 kwanaki, 150 mg / kg sau biyu a rana an bada shawarar don maganin jijiya.Da zarar an daidaita, idan ana buƙatar canzawa zuwa fosfomycin na baka, ana iya zaɓar kashi bisa ga WT na jariri, PMA, PNA, da kuma yiwuwar MIC pathogen, amma bioavailability da aka ruwaito a nan ya kamata a yi la'akari. aminci da ingancin wannan babban kashi wanda samfurin PK ɗinmu ya ba da shawarar.
Lokacin aikawa: Maris 16-2022