Usklađenost produžene primene infuzije piperacilina/tazobaktama sa željenim farmakokinetičkim/farmakodinamskim indeksom kod septičnih bolesnika
Sažetak
Uvod/Cilj. Piperacilin (PIP)/tazobaktam (TAZ) – PIP/TAZ je beta laktamski antibiotik koji se koristi u lečenju sepse uzrokovane Gram negativnim bakterijama. Deo intervala doziranja tokom kojeg su koncentracije antibiotika iznad minimalne inhibitorne koncentracije (minimal inhibitory concentration – MIC) (fT> MIC) ili značajnije, četiri puta veće od MIC-a (fT>4xMIC), predstavljaju farmakokinetske indekse koji najbolje koreliraju sa kliničkim ishodom. U svetlu sve veće rezistencije bakterija u jedinicama intenzivne nege (JIN), važno je ispitati farmakokinetske/farmakodinamske (pharmacokinetic/pharmacodynamic – PK/PD) indekse kod različitih režima doziranja PIP/TAZ, da bi se utvrdilo da li će taj uslov biti ispunjen. Cilj rada bio je da se analizira efikasnost produžene intermitentne infuzije PIP/TAZ kod bolesnika sa sepsom u JIN, kako bi se postigao željeni PK/PD indeks. Metode. Prospektivnom, kontrolisanom, neintervencijskom studijom obuhvaćeni su bolesnici sa abdominalnom postoperativnom sepsom. Bolesnici su primali PIP/TAZ u dozi od 4,5 g na 6 sati u produženoj (60-minutnoj) intermitentnoj infuziji u dnevnoj terapijskoj dozi od 18 g, kao propisanu terapiju. Uzorci krvi uzimani su tokom prvih 36 sati, a koncentracije antibiotika određene su primenom tečne hromatografije visokih performansi. U analizu su uključeni najčešći izolati iz hemokulture u JIN koji su bili osetljivi na PIP/TAZ, a MIC-e su preuzeti iz baze European Committee on Antimicrobial Susceptibility Testing (EUCAST). Primarni cilj PK/PD studije bio je da se odrede indeksi fT>MIC i fT>4xMIC kao najbolji pokazatelji terapijske efikasnosti. Za farmakodinamski cilj određeno je da taj period bude ≥ 50% vremena intervala doziranja. Rezultati. Maksimalna koncentracija PIP kod ispitivanih bolesnika iznosila je 130,03 ± 32,43 µg/mL. Na osnovu PK/PD podataka, primenjeni režim doziranja PIP/TAZ bio je efikasan protiv osetljivih sojeva čija je MIC bila ispod 16 µg/mL (fT>MIC = 56%). Uzimanjem fT>4xMIC≥50% kao ciljne vrednosti, taj procenat bio je značajno ispod cilja (27%). Kod sojeva koji uključuju sojeve sa mehanizmom fenotipske rezistencije, vrednosti PK/PD za fT>4xMIC≥50% bile su značajno ispod postavljenog cilja (2–11%), osim za Escherichia coli (79%). Zaključak. Intermitentna 60-minutna infuzija PIP/TAZ ispunjava zahtevani farmakodinamski cilj fT>MIC≥50% za osetljive sojeve bakterija, sa tačkom prekida od 16 µg/mL. Navedeni režim doziranja nije ispunio ciljne PK/PD vrednosti u slučaju rezistentnih sojeva.
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