Pahuhopu E loiloi i nā hanana ʻino e pili ana i ka fosfomycin (AEs) a me nā pharmacokinetics a me nā loli i nā pae sodium i nā neonates me ka maʻi sepsis.
Ma waena o Malaki 2018 a me Feberuari 2019, ua loaʻa i 120 neonates makahiki ≤28 lā nā lāʻau lapaʻau maʻamau o ka mālama (SOC) no ka sepsis: ampicillin a me gentamicin.
Hoʻopili Ua hoʻokaʻawale mākou i ka hapalua o ka poʻe i komo e loaʻa i ka fosfomycin intravenous hou a ukali ʻia e ka fosfomycin waha ma kahi ʻano o 100 mg/kg ʻelua i kēlā me kēia lā no 7 mau lā (SOC-F) a hahai ʻia no nā lā 28.
Nā hualoaʻa 61 a me 59 pēpē makahiki 0-23 lā i hāʻawi ʻia iā SOC-F a me SOC, kēlā me kēia.sodiuma i ʻole nā hopena ʻaoʻao o ka ʻōpū. I ka wā o ka nānā ʻana i nā lā pēpē 1560 a me 1565, ʻike mākou i 50 AE ma 25 SOC-F i komo a me 34 SOC i komo, i kēlā me kēia (2.2 vs 3.2 hanana / 100 mau lā pēpē; ʻokoʻa helu -0.95 hanana / 100 pēpē. ) lā (95% CI -2.1 i 0.20)) .Eha SOC-F a me ekolu SOC i make. Mai ka 238 pharmacokinetic samples, modeling i hoike i ka nui o na keiki e koi aku i ka nui o 150 mg/kg intravenously elua i kela la i keia la no ka hoʻokō pharmacodynamic pahu hopu. no nā neonates <7 mau lā a i ʻole ke kaumaha <1500 g i kēlā me kēia lā Ua hoʻemi ʻia ka nui i 100 mg/kg ʻelua.
Nā hopena a me ka pili ʻana ʻo Fosfomycin i hiki ke koho i kahi koho lapaʻau kūpono no ka sepsis neonatal me kahi regimen dosing maʻalahi. e kūʻē i nā meaola koʻikoʻi loa, no laila ua ʻōlelo ʻia e hoʻohana i ka fosfomycin i hui pū me kahi mea antibacterial ʻē aʻe.
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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ʻO ke kū'ē antimicrobial he mea hoʻoweliweli i ke ola o nā keiki hānau hou a aia kahi koi wikiwiki no nā koho lapaʻau hou kūpono.
Aia kekahi kaumaha sodium nui me ka fosfomycin intravenous, a ʻo ka hoʻomākaukau ʻana o ka fosfomycin waha he nui ka nui o ka fructose, akā aia nā ʻikepili palekana i nā neonates.
ʻOkoʻa nā ʻōlelo paipai no ka hoʻopaʻa ʻana o nā keiki a me nā neonatal no ka fosfomycin intravenous, a ʻaʻohe mea i paʻi ʻia i ka hoʻopaʻa ʻana o ka waha.
Intravenous a me waha fosfomycin ma 100 mg / kg ʻelua mau lā i kēlā me kēia lā, ʻaʻohe hopena i ka serum.sodiuma i ʻole nā hopena ʻaoʻao o ka ʻōpū.
Pono paha ka hapa nui o nā keiki i ka fosfomycin intravenous 150 mg/kg ʻelua i kēlā me kēia lā no ka hoʻokō ʻana i nā pahuhopu efficacy, a no nā neonate ma lalo o 7 mau lā a i ʻole ke kaumaha ma lalo o 1500 g, intravenous fosfomycin 100 mg/kg ʻelua i kēlā me kēia lā.
Hiki i ka Fosfomycin ke hui pū me nā antimicrobial ʻē aʻe e mālama i ka sepsis neonatal me ka ʻole o ka hoʻohana ʻana i nā carbapenems i ka hoʻonohonoho ʻana o ka hoʻonui ʻana i ka antimicrobial resistance.
Hoʻopilikia ka antimicrobial resistance (AMR) i ka heluna kanaka ma nā ʻāina haʻahaʻa a me waena (LMICs). me nā maʻi pathogens multidrug-resistant (MDR) e helu ana ma kahi o 30% o ka make ʻana o nā neonatal sepsis ma ka honua.2
Paipai ʻo WHO i ka ampicillin,penicillin, aiʻole cloxacillin (inā kānalua ʻia ka maʻi S. aureus) me ka gentamicin (laina mua) a me nā cephalosporins o nā hanauna ʻekolu (laina lua) no ka hoʻomaʻamaʻa empirical o ka sepsis neonatal.3 Me ka extended-spectrum beta-lactamase (ESBL) a me ʻO ka carbapenemase, 4 mau mea hoʻokaʻawale maʻi i hōʻike pinepineʻia he meaʻole i kēia regimen.5 He mea nui ka mālamaʻana i nā carbapenems no ka mālamaʻana i ka MDR, 6 a hoʻokomo houʻia nā lāʻau'alopelo kuʻuna e hoʻoponopono i ka nele o nā lāʻau'alopelo hou.7
ʻO ka Fosfomycin he mea waiwai phosphonic acid derivative i manaʻo ʻia e ka WHO.8 Fosfomycin he bactericidal9 a hōʻike i ka hana kūʻē i ka Gram-positive a me Gram-negative bacteria, me ka methicillin-resistant Staphylococcus aureus, Vancomycin-resistant Enterococcus, ESBL nā mea hana a hiki ke komo i ka biofilm.10 Ua hōʻike ʻo Fosfomycin i loko o ka vitro synergy me nā aminoglycosides a me carbapenems 11 12 a hoʻohana mau ʻia i nā pākeke me nā maʻi ʻeha mimi MDR.13
Aia nā manaʻo kū'ē i kēia manawa no ka hoʻohana ʻana i ka fosfomycin intravenous i loko o nā pediatrics, mai 100 a 400 mg / kg / lā, me ka hoʻopuka ʻole ʻia o ka dosing regimen. 25-50 mg/kg.14 15 He mea liʻiliʻi ka hoʻopaʻa ʻana i ka protein, a ua kūlike ka nui o ka nui me ka ʻikepili kanaka makua. (AUC):MIC ratio.18 19
He 84 mau hōʻike hihia o nā neonates e loaʻa ana i ka fosfomycin intravenous ma 120-200 mg / kg / lā i hōʻike ʻia ua ʻae maikaʻi ʻia. 330 mg sodium no ka gram—he pilikia palekana no nā neonates nona ka sodium reabsorption inversely proportional to gestational age (GA). hopena ʻaoʻao a pili i ke koena wai.27 28
Ua manaʻo mākou e loiloi i ka pharmacokinetics (PK) a me ka hoʻololi ʻana o ka pae sodium i nā neonates sepsis maʻi, a me nā hanana ʻino (AE) pili me ka intravenous ma hope o ka fosfomycin waha.
Ua alakaʻi mākou i kahi hoʻāʻo hoʻāʻo i hoʻopaʻa ʻia i ka hoʻohālikelike ʻana i nā lāʻau antibiotic maʻamau (SOC) wale nō me SOC a me IV a ukali ʻia e ka fosfomycin waha i nā neonates me ka maʻi sepsis ma Kilifi County Hospital (KCH), Kenya.
ʻO nā keiki hānau hou a pau i komo i ka KCH ua nānāʻia.ʻO nā mea i hoʻokomoʻia he: makahiki ≤28 mau lā, ke kaumaha o ke kino> 1500 g, ka hānauʻana> 34 wiki, a me nā pae hoʻohālike no nā lāʻau'alopelo intravenous ma WHO3 a me Kenya29 alakaʻi. Inā pono CPR, Grade 3 hypoxic-ischemic encephalopathy, 30 sodium ≥150 mmol/L, creatinine ≥150 µmol/L, jaundice e koi ana i ka transfusion hoʻololi, allergy a i ʻole contraindication i fosfomycin, hōʻike kikoʻī o kekahi papa o ka maʻi antibiotic, ua hoʻokaʻawale ʻia ka neonate mai kahi haukapila ʻē aʻe a i ʻole ma Kilifi County (Figure 1 ).
E ho'āʻo i ka papa kuhikuhi holoʻokoʻa. Ua hana ʻia kēia kiʻi kumu e CWO no kēia manuscript.CPR, cardiopulmonary resuscitation;HIE, hypoxic-ischemic encephalopathy;IV, i loko o ke koko;SOC, maʻamau o ka mālama;SOC-F, maʻamau o ka mālama a me ka fosfomycin.* ʻO nā kumu e pili ana i ka makuahine (46) a i ʻole ka maʻi nui (6) ma hope o ka pauku caesarean, ka hoʻokuʻu ʻana mai ka haukapila (3), ka hoʻokuʻu ʻana i ka manaʻo (3), haʻalele ʻia e ka makuahine (1) a me ke komo ʻana i loko haʻawina hou (1).†Ua make kekahi mea komo SOC-F ma hope o ka pau ʻana o ka hahai ʻana (La 106).
Ua hoʻopaʻa inoa ʻia nā mea komo i loko o 4 mau hola o ka hopena mua o nā lāʻau antibiotic SOC a hiki i Kepakemapa 2018, i ka wā i hoʻonui ʻia ai nā hoʻololi protocol i loko o 24 mau hola e hoʻokomo i nā komo ʻana i ka pō.
Ua hāʻawi ʻia nā mea komo (1: 1) e hoʻomau i nā lāʻau antibiotic SOC wale nō a i ʻole e loaʻa iā SOC hoʻohui (a hiki i) 7 lā o fosfomycin (SOC-F) me ka hoʻohana ʻana i kahi papa hana randomization me ka nui o ka poloka (Supplementary Figure S1 online). Huna ʻia e ka sequentially helu ʻia nā envelopes i hoʻopaʻa ʻia.
Wahi a WHO a me Kenyan pediatric guidelines, SOCs he ampicillin a cloxacillin (inā he ma'i staphylococcal i mana'o 'ia) me ka gentamicin ma ke ano he antibiotic mua, a i ole cephalosporins o ka hanauna ekolu (e like me ka ceftriaxone) ma ke ano he laau lapaau laina lua. Ua loaʻa pū ʻo F i ka fosfomycin intravenous no ka liʻiliʻi loa he 48 mau hola, e hoʻololi ana i ka waha ke ʻae ʻia ka hānai kūpono e manaʻo i ka absorption kūpono o ka lāʻau lapaʻau waha. mg/mL fosfomycin sodium solution for intravenous infusion (Infectopharm, Germany) and Fosfocin 250 mg/5 mL fosfomycin calcium suspension for oral administration (Laboratorios ERN, Spain) ʻelua manawa i kēlā me kēia lā me 100 mg/kg/dose.
Ua ukali ʻia nā mea komo no nā lā 28. Ua mālama ʻia nā mea komo a pau i ka hui hilinaʻi nui e hoʻoponopono i ka nānā ʻana AE. Ua hana ʻia nā helu koko piha a me ka biochemistry (me ka sodium) i ke komo ʻana, nā lā 2, a me 7, a hana hou ʻia inā hōʻike ʻia.AEs ua helu ʻia e like me MedDRA V.22.0. Ua hoʻokaʻawale ʻia ke koʻikoʻi e like me DAIDS V.2.1.AEs i ukali ʻia a hiki i ka hoʻoholo ʻana a i ʻole ka hoʻoholo ʻana i ka maʻi a paʻa i ka manawa o ka mālama ʻana. i loko o kēia heluna kanaka, me ka hiki ke hōʻino i ka hānau ʻana (protocol in Supplementary file 1 online).
Ma hope o ka IV mua a me ka fosfomycin waha mua, ua hoʻokaʻawale ʻia nā mea maʻi i hāʻawi ʻia i ka SOC-F i hoʻokahi mua (5, 30, a i ʻole 60 mau minuke) a me hoʻokahi hōʻailona PK hope (2, 4, a i ʻole 8 hola). no ka poʻe i komo i ka hale maʻi i ka lā 7. Ua hōʻiliʻili ʻia nā laʻana cerebrospinal fluid (CSF) mai kahi maʻi lumbar puncture (LP) i hōʻike ʻia.
Ua nānā mākou i ka ʻikepili komo ma waena o 2015 a me 2016 a helu ʻia ʻo ka mean sodium content o 1785 neonates ke kaupaona ʻana >1500 g he 139 mmol/L (SD 7.6, range 106-198). ʻO nā pae hoʻohālikelike hoʻokaʻawale), ʻo ke koena 1653 neonates i loaʻa ka mean sodium content o 137 mmol / L (SD 5.2). A laila helu ʻia kahi nui o 45 i kēlā me kēia hui e hōʻoia i ka ʻokoʻa 5 mmol / L i ka sodium plasma i ka lā 2 hiki ke loaʻa. hoʻoholo ʻia me ka mana> 85% e pili ana i ka ʻikepili hoʻoili sodium mua.
No PK, ua hāʻawi ʻia kahi laʻana nui o 45> 85% mana e koho i nā ʻāpana PK no ka hoʻomaʻemaʻe ʻana, ka nui o ka hāʻawi ʻana, a me ka bioavailability, me 95% CI i manaʻo ʻia e hoʻohana ana i nā simulation me ka pololei o ≥20%. No kēia hopena, kahi kumu hoʻohālike kanaka makua ua hoʻohana ʻia, e hoʻonui ana i ka makahiki a me ka nui i nā neonates, e hoʻohui i ka absorption mua a me ka manaʻo bioavailability.31 No ka ʻae ʻana i nā laʻana i nalowale, ua manaʻo mākou e kiʻi i nā neonates 60 i kēlā me kēia hui.
Ua ho'āʻo ʻia nā ʻokoʻa o nā palena palena ma ka hoʻohana ʻana i ka ho'āʻo χ2, ka ho'āʻo t-haumāna, a i ʻole ka ho'āʻo rank-sum a Wilcoxon. Ua hoʻāʻo ʻia nā ʻokoʻa o ka lā 2 a me ka lā 7 sodium, potassium, creatinine, a me alanine aminotransferase me ka hoʻohana ʻana i ka covariance i hoʻoponopono ʻia no nā kumu waiwai. No nā AE, nā hanana ʻino koʻikoʻi (SAEs), a me nā hopena lāʻau ʻino, ua hoʻohana mākou i STATA V.15.1 (StataCorp, College Station, Texas, USA).
Ua hana ʻia nā manaʻo kumu hoʻohālike o nā ʻāpana PK ma NONMEM V.7.4.32 me ka hoʻohana ʻana i nā koho kūlana mua me ka launa pū ʻana, hāʻawi ʻia nā kikoʻī piha o ka hoʻomohala ʻana i nā kumu hoʻohālike PK a me nā hoʻohālike i nā wahi ʻē aʻe.32
Ua mālama ʻia ka nānā ʻana ma ka pūnaewele e DNDi/GARDP, me ka nānā ʻana i hāʻawi ʻia e kahi kōmike palekana a me ka nānā ʻana.
Ma waena o Malaki 19, 2018, a me Pepeluali 6, 2019, 120 neonates (61 SOC-F, 59 SOC) i kākau inoa ʻia (Figure 1), nona ka 42 (35%) i kākau inoa ʻia ma mua o ka loiloi protocol.Group.Median (IQR) makahiki, kaumaha a me GA he 1 la (IQR 0-3), 2750 g (2370-3215) a me 39 pule (38-40), pakahi. online Pākuʻi Pākuʻi S1.
Ua ʻike ʻia ʻo Bacteremia i loko o ʻelua neonates (Supplementary Table S2 online). 2 o 55 neonates i loaʻa i ka LP i loaʻa i ka maningitis i hōʻoia ʻia e ka laboratory (Streptococcus agalactiae bacteremia me CSF leukocytes ≥20 cell/µL (SOC-F); positive Streptococcus pneumoniae cerebrospinal fluid antigen test a me nā leukocytes CSF ≥ 20 pūnaewele/µL (SOC)).
Hoʻokahi SOC-F neonate i loaʻa hewa ʻole i ka SOC antimicrobials a ua kāpae ʻia mai ka PK analysis. ) a me ceftriaxone (n=1)) i loaʻa ka ampicillin me ka gentamicin i ke komo ʻana. Hōʻike ʻia ka papa kuhikuhi S3 Online i nā hui antibiotic i hoʻohana ʻia i nā poʻe i loaʻa i nā lāʻau ʻokoʻa ma waho o ka ampicillin me ka gentamicin i ke komo ʻana a i ʻole ma hope o ka hoʻololi ʻana. i ka lua-laina lāʻau lapaʻau ma muli o ke kino worsening a meningitis, elima o lakou i mua o ka hā PK hāpana (Supplementary Table S3 online). Ma keʻano holoʻokoʻa, 60 komo i loaʻa ma ka liʻiliʻi loa hoʻokahi intravenous dose o ka fosfomycin a me 58 i loaʻa ma ka liʻiliʻi loa o hoʻokahi waha.
ʻEono (ʻehā SOC-F, ʻelua SOC) i make i ka haukapila (Figure 1). Ua make kekahi mea komo SOC i nā lā 3 ma hope o ka hemo ʻana (lā 22). 106 (ma waho o ka hahai ʻana i ke aʻo ʻana);Ua hoʻokomo ʻia ka ʻikepili a hiki i ka lā 28. Ua nalowale nā pēpē SOC-F ʻekolu i ka hahai ʻana. ʻO ka nui o nā pēpē / lā o ka nānā ʻana no SOC-F a me SOC ʻo 1560 a me 1565, ʻo ia ka 422 a me 314 i mālama ʻia i ka haukapila.
Ma ka lā 2, ʻo ka mean (SD) plasma sodium waiwai no nā mea komo SOC-F he 137 mmol/L (4.6) me 136 mmol/L (3.7) no nā mea komo SOC;ʻokoʻa ʻokoʻa +0.7 mmol/L (95% CI) -1.0 a i +2.4). I ka lā 7, ʻo ka mean (SD) sodium waiwai ʻo 136 mmol/L (4.2) a me 139 mmol/L (3.3);ʻokoʻa ʻokoʻa -2.9 mmol/L (95% CI -7.5 a +1.8) (Papa 2).
Ma ka lā 2, ʻoi aku ka haʻahaʻa o ka mean (SD) potassium ma SOC-F ma mua o nā pēpē SOC-F: 3.5 mmol/L (0.7) vs 3.9 mmol/L (0.7), ʻokoʻa -0.4 mmol/L (95% CI. -0.7 a -0.1) ʻAʻohe mea hōʻike e ʻokoʻa nā ʻokoʻa ʻē aʻe ma waena o nā pūʻulu ʻelua (Table 2).
Ua nānā mākou i 35 AE ma 25 SOC-F hui a 50 AE i 34 SOC hui;Nā hanana 2.2 / 100 mau lā pēpē a me nā hanana 3.2 / 100 mau lā pēpē, i kēlā me kēia: IRR 0.7 (95% CI 0.4 i 1.1), IRD -0.9 hanana / 100 mau lā pēpē (95% CI -2.1 i +0.2, p = 0.11).
He ʻumikūmālua SAE i loaʻa ma 11 SOC-F hui a me 14 SAE ma 12 SOC hui (SOC 0.8 hanana / 100 mau lā pēpē vs 1.0 hanana / 100 mau lā pēpē; IRR 0.8 (95% CI 0.4 a i 1.8), IRD -0.2 hanana / 100 pēpē nā lā (95% CI -0.9 i +0.5, p=0.59). ʻO ka Hypoglycemia ka AE maʻamau (5 SOC-F a me 6 SOC); 3 o 4 i kēlā me kēia hui 3 SOC-F a me 4 SOC i loaʻa i ka haʻahaʻa a koʻikoʻi paha. thrombocytopenia a ke hana maikaʻi nei me ka ʻole o ka hoʻokahe platelet i ka lā 28. Ua loaʻa i nā poʻe 13 SOC-F a me 13 SOC kahi AE i helu ʻia ma ke ʻano he "manaʻo ʻia" (Supplementary Table S5 online). ʻAʻole ʻike ʻia ke kumu (n=1)) Ua hoʻokuʻu ʻia nā mea a pau i ka home. Ua hoʻoholo ʻia nā AE a ua hoʻoholo ʻia ʻo 27 me ka ʻole o ka hoʻololi a i ʻole ka hopena i hoʻoholo ʻia..
Ua hōʻiliʻili ʻia hoʻokahi laʻana PK intravenous mai nā poʻe komo 60. Ua hāʻawi ʻia nā poʻe he kanalimakumamālima i nā pūʻulu hoʻohālike piha ʻehā, a ua hāʻawi ʻo 5 i nā ʻāpana ʻāpana. 119 no ka fosfomycin waha) a me 15 mau la'ana CSF.
Hōʻike ʻia ka hoʻomohala ʻana i nā kumu hoʻohālike o ka heluna kanaka a me nā hopena hoʻohālike ma nā wahi ʻē aʻe.32 Ma ka pōkole, ʻo kahi ʻano hoʻohālike PK ʻelua ʻāpana me kahi ʻāpana CSF hou i hāʻawi i kahi kūpono maikaʻi i ka ʻikepili, me ka ʻae a me ka leo ma ke kūlana paʻa no nā poʻe maʻamau (ke kaumaha o ke kino ( WT) 2805 g, makahiki postnatal (PNA) 1 lā, makahiki postmenstrual (PMA) 40 wiki) he 0.14 L / hola (0.05 L / hola / kg) a me 1.07 L (0.38 L / kg), i kēlā me kēia. ʻO ka ulu ʻana o ka allometric a me ka hoʻomohala ʻana o ka PMA i manaʻo ʻia e pili ana i ka hana renal31, pili ka PNA me ka hoʻonui ʻana i ka wā o ka pule postnatal mua. (95% CI 0.27 i 0.41).
Hōʻike ʻia ʻo S2 Supplementary Figure i ka simulated steady-state plasma concentration-time profiles. Hōʻike nā kiʻi 2 a me 3 i ka AUC Probability of Target Attainment (PTA) no ka heluna kanaka noiʻi (ke kaumaha o ke kino>1500 g): nā paepae MIC no ka bacteriostasis, 1-log pepehi kanaka, a me ka pale 'ana, me ka hoʻohana 'ana i nā paepae MIC mai nā keiki hou liʻiliʻi.ikepili i infer.Ma muli o ka piʻi wikiwiki o ka hoʻomaʻemaʻe i ka pule mua o ke ola, ua hoʻonui hou ʻia nā simulation e PNA (Supplementary Table S7 online).
Loaʻa nā pahuhopu kūpono me ka fosfomycin intravenous.Nā keiki hou. Pūʻulu 1: WT >1.5 kg +PNA ≤7 lā (n=4391), Pūʻulu 2: WT >1.5 kg +PNA >7 lā (n=2798), Pūʻulu 3: WT ≤1.5 kg +PNA ≤7 Nā lā (n=1534), Pūʻulu 4: WT ≤1.5 kg + PNA >7 lā (n=1277). ʻO nā hui 1 a me 2 i hōʻike i nā maʻi e like me ka poʻe i hālāwai i kā mākou mau koi hoʻokomo. 4 e hōʻike ana i nā extrapolations i nā keiki hānau mua ʻaʻole i aʻo ʻia i ko mākou heluna.IV, hoʻokomo i loko o ke koko;MIC, ka palena haʻahaʻa haʻahaʻa;PNA, makahiki ma hope o ka hānau ʻana;WT, kaumaha.
Loaʻa ka pahuhopu kūpono me nā doses fosfomycin waha. Ka heluna kanaka hou. Pūʻulu 1: WT >1.5 kg +PNA ≤7 lā (n=4391), Pūʻulu 2: WT >1.5 kg +PNA >7 lā (n=2798), Pūʻulu 3: 3 a ʻo 4 e hōʻike ana i ka extrapolation o nā neonates preterm me ka hoʻohana ʻana i ka ʻikepili o waho i aʻo ʻole ʻia i ko mākou heluna.MIC, ka palena haʻahaʻa haʻahaʻa;PNA, makahiki ma hope o ka hānau ʻana;PO, waha;WT, kaumaha.
No nā mea ola me ka MIC> 0.5 mg / L,ʻaʻole i hoʻokō mauʻia ka hoʻopauʻana i ke kū'ē me kekahi o nā papa hana hoʻohenehene (Figures 2 a me 3). o 100% PTA ma nā papa hoʻoheneheneʻehā (Figure 2). No ka pepehi kanaka 1-log, no nā hui 1 a me 3 me PNA ≤7 lā,ʻo 0.84 a me 0.96 ka PTA me 100 mg / kg iv iʻelua manawa i ka lā aʻo ka MIC he 32. mg / L, akā he PTA haʻahaʻa ko ka hui, 0.19 a me 0.60 no 2 a me 4 PNA> 7 mau lā, i kēlā me kēia. Ma 150 a me 200 mg / kg ʻelua manawa i kēlā me kēia lā intravenously, ʻo ka 1-log kill PTA he 0.64 a me 0.90 no ka hui 2 a me 0.91 a me 0.98 no ka hui 4.
ʻO nā waiwai PTA no nā hui 2 a me 4 ma 100 mg / kg i ʻelua manawa i kēlā me kēia lā he 0.85 a me 0.96, i kēlā me kēia (Figure 3), a ʻo nā waiwai PTA no nā hui 1-4 he 0.15, 0.004, 0.41, a me 0.05 ma. 32 mg/L, kēlā me kēia.E pepehi i ka 1-log ma lalo o MIC.
Hāʻawi mākou i nā hōʻike o ka fosfomycin ma 100 mg / kg / dose ʻelua i kēlā me kēia lā i nā pēpē me ka ʻole o ka hōʻike ʻana o ka sodium plasma disturbance (intravenous) a i ʻole osmotic diarrhea (oral) i hoʻohālikelike ʻia me SOC. ʻO kā mākou pahuhopu palekana nui, ʻike i ka ʻokoʻa o nā pae sodium plasma ma waena o ka ʻelua mau pūʻulu lapaʻau i ka lā 2, ua lawa ka mana. ʻOiai he liʻiliʻi ka nui o kā mākou laʻana e hoʻoholo ai i nā ʻokoʻa ma waena o ka hui i nā hanana palekana ʻē aʻe, ua nānā pono ʻia nā neonates āpau a kōkua nā hanana i hōʻike ʻia e hāʻawi i nā hōʻike e kākoʻo i ka hoʻohana ʻana o ka fosfomycin i kēia. ka heluna kanaka maʻalahi me ka sepsis alternative empiric therapy. Akā naʻe, he mea nui ka hōʻoia ʻana o kēia mau hopena i nā hui nui a ʻoi aku ka koʻikoʻi.
Ua manaʻo mākou e kiʻi i nā neonates ≤28 mau lā o ka makahiki a ʻaʻole i koho koho i ka sepsis i hoʻomaka mua ʻia. -36 ʻO nā pathogens e hoʻomaka ai i ka hoʻomaka mua a me ka hoʻomaka ʻana o ka maʻi sepsis (me ka ESBL E. coli a me Klebsiella pneumoniae i ʻike ʻia) i nā antimicrobial empirical, 37-39 hiki ke loaʻa i ka obstetrics. no ka mea hiki i ka lāʻau lapaʻau mua ke hoʻomaikaʻi i nā hopena a pale i ka hoʻohana ʻana i ka carbapenem.
E like me nā antimicrobials he nui, ʻo 40 PNA kahi covariate koʻikoʻi e wehewehe ana i ka hoʻomaʻemaʻe fosfomycin. ʻO kēia hopena, ʻokoʻa mai ka GA a me ke kaumaha o ke kino, e hōʻike ana i ka oʻo wikiwiki ʻana o ka kānana glomerular ma hope o ka hānau ʻana. /mL15, a me ka hana bactericidal hiki ke koi i> 100 mg / kg / dose intravenously i nā neonates> 7 lā (Figure 2). Intravenous therapy. Ke hoʻopaʻa ʻia, inā makemake ʻia kahi hoʻololi i ka fosfomycin waha, hiki ke koho ʻia ke ʻano ma muli o ka WT neonatal, PMA, PNA, a me MIC pathogen paha, akā pono e noʻonoʻo ʻia ka bioavailability i hōʻike ʻia ma aneʻi. Pono nā haʻawina e loiloi hou i ka ka palekana a me ka maikaʻi o kēia ʻano kiʻekiʻe i ʻōlelo ʻia e kā mākou kumu hoʻohālike PK.
Ka manawa hoʻouna: Mar-16-2022