Chapter 10 Continuous Infusion of Beta-lactam Antibiotics ‘Anouk E Maller and Johan W, Mouton {table hrpy Prensa det and vio tude bv thw insion over ermine dving i heal ocome sisi rt fen docs ‘ented seca apoap, ua ecaly pts pated was Kareucrpile teemoignuins Methods to eae Gove Ging comtnott infusion sal peat laoey sch a sy of slic! slain Contos infsion amaccyoai ge, List of Abbreviations Ce Cystestoss Bea ee aes atom te oe ‘AA ns al) endoml AnttPamasns a ‘et hemaatnomn oto onsreasette ‘Sopp Ser Bus bee ew leEVI Wan exaled dering th et scond of ocean mans vc Faced ia spay wl ant of at cn fry be bw IVPM evo pouraccineephascadymani PRI) madls MeS/ Mone Cals malts MSW Mstiionleston window 50 Daly ove requ protec 50% ofthe anal fom morality PK Poumacokneter ‘TC Twal bay clewtance Si/T>MUC Peep of Une tlhe unbound concerns i above he AIC Introduction ef ete sine te ater of pei. Wes sso tha mae eae Sosig of pein sel» pet oacome cared once ote aly ering ape etl 1950, 19530 Seosand Waly 131 Fave 1 Scot fal 15) Nowiins, dont on secng blacan dong Opie a ‘cea acy snd mainte lied oncom longing satan St ct a ety ch fe Istodbcion of aac in lai pati oe 0 years ao, ben of ‘leciou dca seman igh and wi te acresing evelopment of hae restane oping of asiauobal hey moe ba ward Knpoved Capa wath eps (Garach-Monero ea 2005, 2000 Hb eta Sob Kali eta 955) ‘he wr of coins infin over net onan, hor ed ‘on ew ewe of cocoon noel ce stabil eager he eke cls dence oui comnts te diced hay hlp ina povide the node of admin,PRIPD of Heta-tactams Sov pumsccknetilparmicdynamic (PKIPDHnces of sical ‘gots hve fren dese corel with eeey or oom se Chop). ‘he dation oie oer which he vod Or ence Fain above ie ‘inimam ino concentration (MIC: /T>MIC) (Woman tal 98: ras 190; Cig nl Er 192: le 2013). Ths charac ese an ‘pment air stata antsy omnes nen The evidense {In Vitro Pharmacodynamic Effets ‘The ling stv of ttt atimirbia agit Grat-ngaive os x ‘ing stein ces Fg 0. naan ‘pone Wo varyngconcentaton of elite expe wale cf ‘Minimum tice Cooenraon MI. mg/L. The Hae sows ht snc Shogegher at por four tes te MIC the MIC of thi ss an Ting notes in icra Alia. Beal liga concent ions preter hin 45 tines the NIC des notice with Excrobceracse, Staples aureus or Paewomonas aeragione ate a 198: Bower ns : ae ent . Bee Hose Og a] oe tat ee : ar 3 meth)ee Rasen canine ting terra hae {Sohbet ‘Ge Sy Roe nm Se A oven fa 1896, Motor and Vike 2005. Slt dferaces in dgee ase of ling say ait Seren pein, ceptalopoine nd capers, wih {stbpeooms being most ally bce an peeing est gual Gr este punt (Pei and Neale 1595) conta to the eat. ‘eve ober asics scning sights shaw aces concen ‘pend gic ig of cents wth sheng coeeaon (Megumi 1988, cdrom be ilu prin udesere ar fenton of ances (Boston od Ves 2050) Thar skownia ig 102 Moun a aks 20055). Hace rom an be conclaed tht the tata Al ate of etre snd ‘et of Weta raced far nes the MEG aod ibe onenetons ‘edt hig peak enceneaons fet strnstentifson 9 onto ‘cacy, whereas prolonged coneeson below he MIC resin rosed ef MIC it pee above ou ues the MIC dite te whole cog ea ‘Soul ean poanged sy Tea slain say, we detonated that fticay mss whe ee dug coteauoons ae hae cones oor teat mama atl ety, tu outer he IC os se Vek 20055),onal lmmuncompromised oso oa day dose a) 18 Rati hmv nh mina pm ee ae ea eae ‘Studies in Animate ‘Aer lysis te te dco of pena Bag a. 1950, 1938 Sean Waly 151; ant 9c; Sata 999) tac sever caer efor smestgaasloked a the spel oe dosing eae ota (Legge 1999, 190) Inan ata ever by Cra and Be (982, Scat engee hnty ba ‘et were, tee of exponent ey, aay few: Exesve oie Conpirg cannulae chiara ifson were peromed by oe (pony of BabkecWoudeaerg (Rowena et al 195, 985, 1907, 180 Rootedal and Rakke-Wendebeg 190), Us « newtopenic tt tal of ‘secs ands ese rtn fds, thee veg showed hl en nue inftsin ofetaine es spear toner dng Fg 10) Tae (ly dae rege to prot 30% of esa ftom marty (PDS) wat "Sep win conte lain nn mg ag he ih dose ee ‘taco 1 ference. However hen he cs ofthe doing tz tn 0 ‘eorepne amar were compu, PDSts (03 an 0.35 gh) obo ng ‘epitee was lowe than a neiodeet ea the fers betwern he Ut eet iain coud be petty afl peal wh a sepa Immne tem Alternates; he erence insect ecw cntiooar anneste ain innocent sia vil aoe sd is ‘ayy expan gute hy ce is ae fal sow ean Sitcrce i neal one In utes Coe snd clear (208 com pare conan es crite fs ns pmacokeealy bana Emisocanpetat abit noe sod fod a ontauosifaion wa oe tfiecos tan ees ifn tn bony fondo eo oe Stusn Conianur venenatis of crore ge itecton models max ue by Nase (1995) a Ligon a Wang (i99 Ia botk wade census usm putermed sg eta as ltr ntision A ee appeoch in compan eo mes of cis tion na es by Beta 007 Ty lok ated se sn er inary makes gan te abit of eta ad mete "yon, pessoas he ely don he bn of Studies in Tn Vtro Models Simulating Human Pharmacokinetics Atoeth eres of ima dis cet inet ht ono infant ‘Rpecorinaeopense nese of te ounces i hate alee tetelactune od te rg) ia oc me short ais bas al ee forethe mga ofrore ets conng mre pronounced ine smal Ta ito Phassecoinebe-prteajnamie (PPD) mls VPM) hae bea wed Io toe ees tan cease given ee times daly agit Parginaie (Seowon and den loaner 19d). Tlomever,reseuot suns energed when foncetaians wet ate te NOC, at ing was ao less pone in (Aina eta 205: Cope ta 195) Sine the et of he mane ye ‘eet inthe IVPM the rea ikl tobe mote ee wih ave Sod Conclusions from Preclinical Models om tet pre-siniclade,itcan be conced dh igh pe onetsrons rath tin of ns ig ph oe ie Seite ean dng re(Comparative Studies in Humans ‘Compaive dein amas ca be sided in te eerie, Ie he teat fusions The pay aim of tie sts asl compar tbe Une Concertos poder of the direst modes of mieten nd cae ‘iferorer in /T> MAIC. Ome ies and ce ar ste comparing acd tateome betwen pats eeing ee or eons iso. Fay Fesmualy bed ean Pharmacokinetic Studies | siguicat nombre sats ave appeared tat have noida he harmo Solar (Moto 180: Mason and Mice! 191; Burges sod Wale $007 Burges etal 198200) aed vaio pala option Lede a. 195 Bento ol 20), lvdinenentepeni aes Pensa 20, Dalle ta 00% Daenen el 199), pent water Ebeons Ota 2001 Rader sta 200 bee a 290; Vn e994, 19m 1957, 290) and pena We neve Cae Ut (Base ta. 2003, 2002; Men ta 1994 Hanes ta ‘of pate, such as ICU patie. pharmacokinetic profiles might fe ftom other Peas Alou sade peotermed a CU pens hey how arma Popes tha ier fom hose of mo0CU pate, manly df ah steesed ‘ow groupe of pat ave seldom been found brvesn the tee Inder of ‘nineraton In gener, $/T>MIC i pate sed wth anno non ‘as fou tte anger compara S/T>AMIC ig atts tated ner! Ses Therefore therein the een of teams steed With rsdn the vce ston ween pe a dir pate rps, Ima suy by Bajo AL. 00D, we deine parece poi of Cetandine ne ICU veting Pigs 10 sow be concentatos of efanne wo ine pints nthe ong Sasa) and at eed ae aeroon pa) orontys tre sigan vrton bowers pate bt lo get ton Shing the ay. Ts rlately ene vray ass removed tthe Pea eal 2008, Hanes ea 2090 Gates a 008 De Toh Sib Is pact ashe ty by De Jongh re varity wat observed ‘arc in posing ber erbting to the raya eve de‘stein AS aon ‘rot eRes se eh) ceonentatos a hen conemtatoas ding conus iafien fet Smear wily betwen patents pe 0-17 year ep chen ounger han wee Berets ea 208), “Te vii ve the day os mex the ieee in roi erween ‘wheter heaped monitors wae nese patents Sos is fieacy Stuties Sealy signi fierce in cial aucune eon cotinine ‘on ret ikl oer he oer asta ee ihe an he (rong cance ning train if snd he emp Coes elon he MIC” At ow MICS, sen nmin doing eins wil est a 100% TMC aniferncs ar a ly to be present Sac MICS mie guns ile in tent th Heel f cots sion al gays Be ‘Sos an the per of these compat sta eth relay low Een ties! to vate coins inion vere nmin sin fed ‘domed in the table, ad five of those consisted of high-dose aminoglycosides (sce tale for deta). The mmber fps m mot se eae sal ith [No comparative ses ae alien he eal uct population td st ‘ex inspesi ppulon ae dca in tat para “To it rer dy ta i lok icy pts was by Bay (0979). These investi compard como ison of efamanse vers Incrmitentinfson. A id arm of the ty nove contin info ofutc found Wewees he ope resivingsfamnedle 4 coon ot Steet nin» stan fouinng on pane with erent nee ‘edi how an advantage of conssuou ifnn secon st) tat som © Slfeence in lel oteome wat» iy by Rober oa (207) hat emp Ceotnouiluion of eftancoe wiles cate day repens upiat ted. Wee te diferenes novel astcomes mee fend nthe ton tex say {yo et deseo a valle pes wt ow APACS ‘eo towed dri sacs ownre etiousfaien tile log te rerio sn p= 008 The aor conc a gee ay raat The reson My hse ats i ew eace we be aj of Teter er rc beta once ay dosing efacone fn teICU ‘ng eed meu ia al S/TOMIC oe eat The nest Serie ths, however Arbre) showed » eee Ip ese ote ‘Scorer mere ac eght tena iy pes. Ta tag cette Ssfasonon he APACHE sere mar tongs ot second fourth a Raa fal 20s), Ose hand st uso deeces wer dense Fly ie ‘ay of Haber ea compar cefandine erent ing er cote ‘anon ia CF patent cloned wis Parana set a 209) Aton te difcaes betwen te two trans groups wet sees lly «bands tearm donno pet coloned wih Peerage ss tte Test cetitine Ree; Daly ea 20) pemed eae ng ‘f ppeeclinarobactan,meopeer an ercinleaiate in ICU patie. ‘Tay ind ig inal enh cannes rep 10 tt PSD05P, btn dteece i ICU days oe ia Repl via Soe of he ‘eset cfr sete doing, ‘Or te sonsandamsed sues he stay of Larne ta. (2005) showed nue feces nee ne btwn openness ep in ova Ceotnous nari (OR 4 (95 Se C11 9722105; pe) i a rerrpecne ci ty coming ces en sane Yor “Ty peorae nr slr pipeatiaaebuctam (N=) Ta sy ts prone nates eater VAP andthe fond sua ire ‘ecm nemiteat Sonne However, the svaages were oly rte in patent trated ornfecons ith ier aranarne with an MIC gl Larne ea Som (et nghe OR “10-795 CEL OL-S4824 p04 and ME Tg (ORe22 45 95 8 1115418009; p00, Gram eal compe eben of session (Gane 02} V9) Alhogh cee was bo eierence in cia sucess beeen the mo romp =.) yo rroaltaon citar we sty oer ten on p= 01)Feasibility Studies | ge ober of sais were designed 1 ook the fest of continous cog wel ig Admini ini tn ee ag evr pamp pee a eal. Howewecosnousilsiea ie buns ‘plied wing pole pup ur wel enabling patents to tain ably (Qa ea fob, 006 1¥T Zeer ial 200 Wat ea 2007, tape ontnou fsa rng wed sg ome etme Dense cosines $n prelsdes the seca of ean eon bags epee aig he a Selon Inthe hrpal sting thee of portable np dtneting «coins “auras pts pal whichis fen ele, Was escibedby Cs sal Galt. Hens pape adi he extended nd onan fon of betelastuns tae an ito dea itn pace. The inion ie deat pce mgt renin scomplt sninetetion a he dag. Erpecaly. pent wi ie ‘rk Cae ct al (2010) desebed Wat every replat ofthe aon ie Slee wi «compote sls fie he amb nse. On be te ba emreplacenest ft isin ne ead pce nerd et fr he Segzaed proto a pclae of surf bi of merpene s ‘elton athe resid volume was inane et minof he rabeouet 8 Surca Relcemeat of dead pce tlune hector etc ose. Aeon ‘sto bpd this ure and he eof thee expeaive presi pape, thc the infcon dead sac ler than lymph be cen fr ICU Fates n parlor (reste) aco td pea wih Bid esttons easrcea 019, Suabily ‘Testy ofan abit oon san peat onsen when chosing ‘etl atts octane inaion (Ses 1995 Cb 19 {egg 200, Drags fercninar ion neon nine ng» Forble pn rerlngnexpontion ie oon ros empties nl Besos tenpersce pu fom th dace i ace Ss hr may eo ie ‘anon densi icin tne ein peaby neritet dosing o prolonged nin i posse Tipe prepa rely. 102 yowdes the aby dug slows. Amon a i Feeomtended. Merpenein td efuroine have eter Mably othe tobe feplned every fll. Cld ce packs ve Dred eee he say of ‘Benpens nnd ow epee ry 288 i tel 200, cor {peadomooal belactamefor cominour inion, oho cei, ep ‘hen eget or tent da (Vinee 1995; Ses eta 1989, ese Flacy 198) and exltatineiali bl for 248, Prolonged eporte ea fies shove 25°C heres may asia veda say making sve se bine eitedfor tvery vnn bulory pop ued lee on oy (andere clothing (ies al 200 Baan ea 200. Sen and Tens Sin Forse the cts tdi be YOU vein, tay faves ‘ude longed ison nat well dorumesed (al 2009) Bele ts ‘ferme booms avalible, hse olson shoal be considered a ited fr Toxicity Dieseces intone nd aves fects betwee erste dosing scons resus mete ot ad mt of hes elated the sult wat Sos repr sabe prcenagerof steele, ranging fom Reale flat 200 Beak e 1996, Thabame ea 899) 1072 for ceftaa GE patents abe ota 2009) Marten sopned ede fats ne ‘anna pun muse, coe beoptae and Beas. Seo ae ‘Xetrsch a pimnary esertone ad setae semi so ee Arguments Against Continuous Infusion ‘ne of agueats ast he we of contin infsan fx betata a ive ele ste clea undo obtain FDA spova and ove ‘nde ses ont adres he estan profes centered i iedTE eaesomopeat (Loin a Buti 201), sor waved tht plarnscodyeanic opera animirobil gett port dein dong reine cenentae: Toe log baie woald este « 9/T>MIC tt clot 10% ‘got te lgh coger of pon ading For cape eugene i Bly ‘bi band (5-85 in ana to meropenes (2% abr Bound, ned Conde exes elation mle Eapenem seco semstced ‘nly ence diy, However, tenes av show at ypotboniae at Conder mp one parma of rtapesem Baar ef (2007) ‘Bowed tb! be Vii ey il peat nthe ype of VAP bd» Va {aL 200) coated oe lnings ney pt ih eps nd Basel {se conimed te fodogs in paons with velaturascaed pesmi (Bova eal 2005, Foreteaane, sda agunet ei Ceinon as ees ‘eds cominou inion in compaiv al nd ws sown oat beet "Au hopean geet aps conten fon i he eotane of ri tase ding testes shich an ereaig pad Peron 900), Reine ‘en emeege both he fern ure eran) arin clang som fie Derng eset of ine the host noma fer i eaten {spose io sain ich may ea o vcendary clein By peal Fatbogenie, often ulipestoevesivact prs (Salat Mls 203 is topes afr isan an Pring Ge opin eng scene. ‘Goes a (0107 demonstrated hat ete ith ener cepa LEmcrobacer cloacae a eugene of esate sl ol of eee incon A ong reactant eid eaeple hacen ai sae ‘in kein f ping ssn Sts wa ec ‘elatvedy all dost reed mote eergeace of tevance ha neqiet {ane that cide plat level fll ile hema seta don entnoue son im many cel nan IVPM, coon ion Sling seerntaon low &xMC reed ance fear Mion {ne ner 198: Teche sues, tee sno esece ed naa Te vuepuy ote eel sas une the Wo caing reine eons ‘ninemsn ane nt fn tang a he omega Pers (tate eal 200% Siew tal 201)nner af tteeoou cere, becate consi rege oe ‘olution re isonpable wth ech oie One a slut eben ‘An Alternative to Continuous Infusion: Extended Infusion Since cosnous fsion i comple for ee beet: eis deo nied aly ri ome stuaons ceo patel ecient opson io time lating 5-1, or even tae fsin dine, oe dna of roe {ing polonged or eneded inns ats 3 eal 30 of ong ite ‘al MacGowan 2011 Tor sever betas anit, ster onthe pharmacokinetic wing srt inion wate pion 2003) eed te Po eto sig terest extent repens and peared MCS. They coc hate tegetatamest PTA) The PTA a lepine could be inproved extended fen none nuns (Tam ea 200), For piperclioaabartam, Flos (2012) sted the oni PKs I hoped paces with enol: thle evened info ery Gort hresched ssa age stanie of isd 42% spect, for on MIC of 16mg The lng tat he tended lesion pgeteinacobictas eps Was atzacodvanal pee To {ners pin scone hy Pal apts with 2 ‘ovocoil poral Pat et 2010) They compared 3g ipsa ‘Sumi fun every 8 wh 8379 pgasbacan 9 a4 infos Chery Ba However bt regines ce wsected wih bop pb of {gt atime: fr MC of 2 me especie of tefl fncion Patel L201) soma, ths fhe Mase Ca lato get hat Stange eel pci omnbolosdsieg oak exended tsi woul pone tepttosent ee randooaed nls ate cise Logie es (07) ptfered coho 0) fn Pyro 0375 gare ove 30min ee & or) wih etended Eason (S75 ged over dh every $8) ALP sergio iy ere se theo ppetcionatbuctum In pets ah APACHE I (Y=79. 38 ite tesanetenendedinfeon) hrewara incase diferente Le daye morality (25 90 316%, rpectnely p=004 sa he agi a ata tay aye2. 38days:p=002) ower ese grep penned aoe sty pata ‘rh lw deat seer of esse wh inecions h sans Grueneane {voip (N=58 far shetent dosing 97=70 for eons doi) fre (eee ot hepa vny an te 9-nymalty Perle explanations a at Utes esntenstent dosing up, the ds of pperiiraobaet as es 183 onde dosing vas ol aud for mpied eal nin, Patera ede sage of dae sed puihogens wee sated al et 2009-Te stay {Yo and Cappel C1) sade TE pens wih exeoded isin of Prreclinatebacam nee ope 8 na eee tay, bt cmp Se i pt ng ven Sng of th thee esgic tere! ease eet! soos wet aly com parle in he petcentage of coconut stnapyanid we, ponte cares Prsed two ioaps of pets teed fr hopalsegued preston with Pasties malpresiantAcintbatr fauna (Wan 2033) ' meropnen 500 ah asd one 3 (ag 200), tye, bat compare ls oe nnd dense ay Dosing doe ing ste ave es perotaed In cla pact apps ne enon beng eth Stand mots pons to acme eae tt dn dn tis no coy nie ig ete MIC of he pete) mrtg ewsing the nection conaring ‘atthe purnacodyunicpopres af beac seed th mats iva eaebed wt ouectins not hgh tas four ines te MOC Tats lineal practice, previously published nomagram can be wed, Tis Barbora {ebused a te shove deve res cones eae oon a Vike os) atdohows ia Fig 10. Te ly dose ring onto asain ‘eet ed frm te fag with ott ody cece (TRC) the ag nad The MIC vale of he re ncooranon sap The lie eeelaon ermees etal dy eiarace apd the cen clare For he betel ‘eoed ar approximation of thet hadycleance To eee he resnneBEE 85 8 ane onttay! 0-20 40 G0 0 100 1B) 140 160 180 200 ‘learanee lin) es ai newt fo gy wd Sh taal n= [10 ager} [set] ~1a3/[ernmen mol) Chai120 -ar(yae)) fete] senem ereainine| ng /)] Cham) = Ch ei} x095 Altcnatvely the daly dove cn be deamined doety te folowing toons Daily desma bx THC(L 4) target concentration gL) ao ate suring conan, loading ores qed Th lading dose ‘cay be eon allows Looting doves) Target concen Lele of dart) For mot belcas he olane of debton of heathy volute ix sprint 01-0 3 Lig byt Homer Eypalmsnuemis eqs eu n ICU paso kl fo sstse he apa al vine of esos Ved) and clearne (CL af eda eo ower patem dig whch cole ‘rio lone abu expose th might compromise the tase of Pwmacagymanic tapes, eipecly fr dimedependen anther {Ulnnotne sa 2011) Low ren alsin les ey emma intel Upaens, with epcedineidnee argh 20-50 (eon a. 2011) (arth te ban he fenton stn ay be aan hyp bets, wk for dug wath telly hgh poten bang a cl Atheros ih nn inte Vi pts whos won Antena semnisered to heathy asus 4 Vf 06200) Lk, bees he ‘Vain npn eben deseo be O21 20.08 Ling nh et 1981, or ingen higher vale fr Vd were nlp nbn pats coe peed they ae Daly 201 or ul seine ico thea, comprehensive PRD mode ‘hued appoae aingcncal sofware hate ben dese (Vik? 289 fom poplaion nals ae protamine’ spe popalaton model sebing ‘empon ashton wed cteon oe dag latest att pete Ponce such safe, weigh, dese se aod tena neon. Paeat de ‘Dai hd lacl ta og wit eed age! eaten eae ino ‘mace einen required opal acho te tgetconerratans genes Peace) ls abrtery its a inl cepted eed {Gupte thf del aed est em ning epics feces Theat ‘eb for upg of Bayesian aes ave te Interacting Mug Model(200 een lcm which cetyl agin ne aie ony fr tacking mannan res (Bayard a elie 205) ‘Special Situations or Patent Populations asec ppp, ct abe dig et eh Therapy Thor pats may develop ptoptiolgia changes tat alee PK 1 te preserbed aioe oning tat cos nt scout for hse changes May lea a sade concentaon aad Berge fle To eat Bat PRD tugs ze rated eet apron ay Be eee compat ope wi (Critically 1 Patients May physio cages tke plein cell pea tee ie PK of eve paens te ei dtc gd rhe au cnet fan cn be dectsed Renal eae ros shange i hte pee “Tea nd don regan gh at palin age) pte. “Se of evel beatae showed at higher abi mre eae age comtnnosifason and were mare kt to rac sieges PRI tare (Hoes eta 200; Georges eta 2005) ciel ill pate Bota pls and IBtmus higher cncentaecr were reed wang etimot ifn carpe eateries ong seinen Hones he exe lle a /T>SAC each sing hie eines sal depended obthe MIC he mio ‘Sr easing be tne, Tw dees fn 9/T>MAC i Led tenes Inenites exteded and coniavoeifeans forsee nog (Mhahamier al 199" Robers ea 20553) ‘Mos sds comping he ll fev fenton afsion sei ‘kas cron mechan veausion cecrase sn Creacive pte anda: Tope impotent Robes ea (2008) anda Hae ea (0 conse ete advange oto uth states. Novels Some ses ae {aly ilar ICU pat showed sian dernces bee he wo eset ‘eer compte 0 triten sing nates with om APACHE! ere snd ‘Spans wo were pol orale (Reber el. 2007), Fr perc re trae tnpraiy pave ect onthe APACHE soe wih cont efton (Rafat etal 3005) In vever ae, he eared tard eter uote et footnou lation, ewwre ifeacr wit rina dosing we fn ntusa sgaicun, pany cae of low power esis Reset Daly et a (2015) owed tt TCU pts cance wat ignieny er forcomtous infos compared t ntrmstest bala dong (P0037 Neves: ICU ee dy al ospl sul i ut show sient ou {hic eto onions aaron lle adrsages ol espaod pate poultions is ike to be bese er specie ops teh ‘eel pent of pase inected he sep mre Cystic Fibrosis CF pets with pony exacrbins cnc colaaton iP ae ‘os cefusdine combined wih oranges ten oie Seer ees co fompuredioatce daly dosing epme.Tebameins given one da, bese Wheeling et of anova ie epee on he C/I a eat PR ses inte ht dso ese ang canine nine eaisine pronides more sunt conentaon a puma ees above he MIC wae oncentaon with iter daring dete os ee Del he IC athe ene [te ovng intra Bene 209; Reps ea 290, Coston stun eeprom CF pel hasbeen sow es aden ances ‘eon bo stent pada the ity fhe or pipes, he pharmcasnetes dag ohne dving well as ceotnaoas ding CP patents was sown ob tla in oe Vike {at 2008. Tr neces ingot pean ocean he st sel for coos ison Dering csatons sin of he sane tl aly 69 5) lover thn speed bused on ieee infin pharmcolaee Peameecesimae Te noise population humane modes deeaped er of pats wa CE (Vik tal 20), las secondo fred expsiny miner ste ose ee fl ang ‘spac and FV (ced i apc ttl saat fa at ca fey Be ‘wa cu ale fu inypiata) to detec the plenary perormane is CE Pens Tere mee no Fatally sgh erences in ptooary pea {Eines betwven pets and wi colin by eons fo ceed teinermitestitaon (Rituals eal 2009; Habe eal 2909), However be ced totems infusion whe by wee elied ah cettadane essa I lrinons an (Hobe ea 208) Bararmare Here (205) shone Tlie nerves abo pods was ge ae enti nos "hen ater inert (p=008).Perioperative Prophylaxis Tiina pee polit pe papan cn p ‘toy dei Bod cts we wed el so Shivonac of wig tthicies ls poten bec he te ‘ec eraminao i sknown sd may oar ving tei proedre eg ‘ous enamine cer aeay tne al wean clr Bape, thee contamination coat wt ead of oe dig inert ones Plot oe oo low Therefore, the 8/2 MIC nega be 10 rar thas "han ingest Bae a 205) soos before he induction of assis dwn cians fson. he ater ‘en afer an abl info (ape 2002 Agr etal 2010; Bue Sa Bo RID et ong TMC 10 de an Serie ele, Outpatient Intravenous Therapy ‘ner for ianenus tenes a hme ee tren hry Impasse ote the hsp sting, Wig orale nisin pu Cr the elves dees) for emianosndnatton bane bs ee show Se “Aston we fri pape Bave to be se at coon urge oie ya body epee when delivery deve aed une he hing 10 veto beetle sate The gst ata epee asta x Pe te home eo etme sn pent ath CF. The capi ale os Teper ba 37 "Ci nly ale or Teepe paps wats ‘etd tld beled very thor ato be worn de loing o a- Sag warm emene (Vinee el 2002, “Aten sie ave Den perio pate wh neo ot infecons. Pein G administered contasury wae fonda be fesse ether bned estes of» vac of despre tetas (Walon a 207. al (G5) mae etiam 100 pases sh bone of etna Ta sid ‘ed of whom in 3 etre doe war lamers resin in» presageadv fect of 48%. Hghyight patents allow of tes 12 mone ‘h93 Seno gneotnectont st olomanp. There wet fe aes whale ‘hth ame svepe vrs lSaurene No obvious uae le cube Taeniged Treen with eeusia ws on cote with etait or it Fein Toe IDEA pdlnes sata for cosa dig ws tartan,» ‘ft gi wl ig ot leptin n+ Cooly beck eer eaeynes wee (ce 2000. tnsunnay cots ‘ination of bots uo ato elcve tere ong io ‘tpn sting (alert al 20 Lon and Rehr 00 Berard 2) Pater iene! fe pas att ae Zale ea 20 Bemargeat 3005) Continuous Infusion forthe Treatment of Resistant Microorganisms Since the sept of mirocegisiens to vagus betel decree bene a netgear fein, be se of aended er ous aies coming mare adtatageus fr aiming he probabil of saning RIPD ‘gt eating with ea, For acorns wih low MIC it FRIED Uegtsealyaetived. even he the mbites ae ot ove opimal ar ‘creanuttae wih igh BUC rly, onng it ee ced. Robe {Goins showed he dieses org atime for ao NIC ales rbot IMCS) pectormed hs sty show tl for microns a gh MICE (G16 mgt te a of exended or cosines info computed nem “Etuson iy ob avantngnoa to cee oe PRIPD ret of €0% FBC (Pig. 100, Por example, coaderng x rntegave roots with 38 MIC a the probabity atthe Ueto 0 8 TOMI will beresbed 2688 fee wietmitet dosing of 000g eth, whces he pod oa as {pti nd 100 foc exended scotia fsan eget abe fat 20000, Tye improve! of 7T>MIC fo Rgher MICs ae Bowe ng {nin wae phamacodyeane model octane proed wits Svs choren {econ vale obtained nc pets (Alu ta 2005) anaogo fo nan one Cn sad den Hola 1990) Leet ota, (90) sowed ‘oa pests wate spp fe vnnteranneaed pes ‘eis, ut the adanages were nly for morgane casing he VAP ts ‘DMC of mina mp (OR=10.9,95 4 110-888. p=0.08) "Theta athe ifecece bomen nee and extended conan sion eon important fortress wt hgh Mice ag bet ete a "Hoe cinel tes dd ot show signa eas Detwee he eae apTein war tom POM rpm“Tis upprtey dla Haber ta 200) owen tat ce mee sg nt retina anda closer dy tog cede CF pies col ‘ed wats Parana But afer tly fhe sagopa closes tribceseua anor tee war asigaett diene <0) ili once [favour of eantinanunfac. On the ete an Pal eta (2009) eden ‘insane tacbacan ine erp er dy ed ond a derece anh nay monty ate atexton by MIC ae. Conctusion Pca sts ae shown ar advantage of coaou fusion. Genel fries comparing he plsine Pk of ere ad conse dist of ‘Spor encenrstons ugha he ese: peso and te PTA higher “The apenas erin ste comparing ce somes, ed ge oxnprv lily needed, Dieece in lil orn a ot oe Soeumented in ayes of spi sbgoaps, sch a eciealy pes of Peas with rao use y resol meeps References Se tr mr ace ney gn Som ssh Ger A ii Gort ioStnin ences) ums Chan st Sea syed Ven pr sie hrs ‘cla hn naps heaped mena co ‘Ramis gas hier io 900-808 enn har 08 mpgve sn in i A, aay nee Hm a 58 ore sc Mee 7, Maan W, Covad TH, Yn HA ot) sos sonnet int same Em Se a fee Sete eno aoe lace chet et che eta ne ue le 200 Pama stat! pia vt en ane Pes ne Se me tee are eee oe veil cb tau recep pce rsaects t2a? capt a "ay St Pe 8 ya MY 05) ards oc Sestaasheeceptantnome et conti et conn te ny i (edad prs ind Asses Ages snoasese 20) pasoina remcta te oo Nar Tet, ct a it ni See ee Senate tec ona tao re erm SSrca Hae cst ars tas SDN eSncas NR ‘ota TW, Hope WW, Losasto BM Beserild IM, Kore AL, Drotapy GL al 2012) en ay matte ated et Snes nt rar nt mem octet ts nc Seer a ere ost pe tn ga moire ming a na saucer ot Seo egaees mea sane onsite Se sey on igi“roses fide nin or sity aan peal. An) Sc 78086-40 scape eectter ebm coe TREC IT ES onan arene cog SRR ey amet rere tore ae TG ent cease eras ae ae ee SES nen oe ache aes crameramnomemr a semen, EES eerie ‘en fein ens mca von) Aamo Chemie seage rat Ben Fon Nena Ce W a 198 Cp ae ee Ee wearer Ea ceraras cn catier ttm ements (Btn Geiger mata A Sy 18308-207 diorama Sag Loe Loma 8 Bas GL DSN fips Gr Prbonnarg iene St 3 nec AM A, 2006 apy cn “eSntdetet Acat ea se“Spam see see Sp tn) 206 Cuda a ato ie A 9 soa ho bs ay ile? ea is Pap anikmbin at n secs Bi ra bt Ca i Ce ser AE ea i Op cr ae ra ei sees omy WD RANE ond me sa matings a becoming ote i co). i SK Gann ing Cha ve ad GW ost ry ne 5, Aa al 209 One ded ‘conn porliaararam er GountCumacpa ts Bag sn! Jee becagaci aN shinee ode 210 ein pal den ‘retrain nce pana hong pn rata Daal, fona faa Fae 0) Cte toi “ets pn ions hip ctr ia inne ise remains Aten Spo Come SO) SEALE thc ng el ose ER GO Sie nce al: ge of tl “tog ean Cnet Sop sie Sti mir ako a ry gsi ava“ery soviet omg bron dong sep ee gpa nnd 2AM Pt Be Rote M ND Coie nie “aac paeips nineteen nat si ge otc TM Kova Krak alga tau Annie arose “ som Rumer Robt Rona Daly Lapa 2 Mepenn “Sein ny ts ee em PSone mm barn sce Ge Ca eo a0 1 gm Repent psn mins ge etalk bout 8 Da ec nb tony oS Sa tam eM, a ‘So pur ate pen ta Ao As Cee ‘he il eine Pm Nebo] Asap uD onl bins IA ann bee ae Mk Bg ‘inh ning etna tn i pn ect mre ony me es SS pli lr paw fate Say pn 6 Pm ape Ses fer Silty oft ideeSree cetn Taaaat Src cece eae SSS esa werk ae cat richer acon in AA i Te tea of aan Pama dn dvoid a ESC a hse ana ae im rn ne Samer teen a i Se en em rc ae etc ts aeeereerarrenanee Sane coe eas‘chu tp irs nin tw pono asp he Set Rea vel a em C8. 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