AACN Advnced Criticl Cre Volume 24, Number 1, pp.6 12 2013, AACN Complex Rhythms Ernest Alexnder, PhrmD, nd Gregory M. Susl, PhrmD Deprtment Editors Ventriculoperitonel Shunt Infections in Adult Ptients Din L. Wells, PhrmD, BCPS John M. Allen, PhrmD, BCPS Ventriculoperitonel (VP) shunt infections re common compliction in ptients with these devices. Becuse children with cerebrospinl fluid (CSF) shunts re more likely to experience infections, considerbly more studies evluting this compliction in children re vilble thn studies evluting this compliction in dults. 1 3 The vilble literture on VP shunt infections in dults consists minly of retrospective chrt reviews nd cse reports, mking it difficult to determine the optiml cre these ptients should receive when they hve n cute infection. As result of the potentil complictions of VP shunt infections, ptients often re treted in the intensive cre unit nd nurses ply mjor role in ensuring the optiml cre for these ptients. This column summrizes the published dt describing the incidence nd risk fctors, microbiology, dignosis, tretment, nd prevention of VP shunt infections in dult ptients. VP Shunts Cerebrl shunts re primrily used to mnge hydrocephlus, condition in which buildup of excess CSF ccumultes in the ventricles of the brin. The use of cerebrl shunts to mnge hydrocephlus dtes bck to the mid-20th century. 4 Left untreted, hydrocephlus cn led to increses in intrcrnil pressure, cerebrl edem, nd ultimtely hernition of brin tissue. Vrious types of cerebrl shunts re vilble, nd they re clssified by nme, ccording to where the distl end of the shunt ctheter routes CSF, or by vlve type. 5 Exmples of different types of shunts include ventriculotril, ventriculopleurl, nd VP. Ventriculoperitonel shunts route excess CSF from the ventricles into the peritonel spce. Conditions tht routinely require the plcement of VP shunts re listed in Tble 1. Complictions resulting from VP shunt plcement re common, prticulrly erly fter plcement. Following VP shunt plcement, the 1-yer shunt filure rte is pproximtely 40%, nd the 2-yer shunt filure rte hs been reported to be s high s 50%. 5 Complictions include intrventriculr hemorrhge, obstruction, overdringe of CSF, nd infection. Among these complictions, infection is one of the most serious, often requiring prompt mngement. Din L. Wells is Assistnt Clinicl Professor, Deprtment of Phrmcy Prctice, Auburn University Hrrison School of Phrmcy, 1321 Wlker Bldg, Auburn, AL 36849 (din.wells@uburn.edu). John M. Allen is Assistnt Clinicl Professor, Deprtment of Phrmcy Prctice, Auburn University Hrrison School of Phrmcy, nd Adjunct Assistnt Professor, Deprtment of Surgery, University of South Albm College of Medicine, Mobile, Albm. The uthors declre no conflicts of interest. DOI: 10.1097/NCI.0b013e31827be1d1 6
VOLUME 24 NUMBER 1 JANUARY MARCH 2013 Drug Updte Tble 1: Indictions for Ventriculoperitonel Shunts Hydrocephlus Brin tumor (benign or mlignnt) Spin bifid Congenitl queductl stenosis Crniosynostosis Dndy-Wlker syndrome Archnoid cyst Idiopthic intrcrnil hypertension Bsed on dt from George et l 1 nd Schoenbum et l. 21 Incidence nd Risk Fctors for Infection Hydrocephlus tht requires the plcement of VP shunt my occur for mny resons, but the cuse of hydrocephlus does not seem to ffect the risk for shunt infection. 6 The incidence of VP shunt infections in dults is between 1.6% nd 16.7%. 1, 6 10 Such wide rnges of infection rtes re due in prt to vrying definitions of shunt infections nd ptient demogrphics reported throughout the literture. Presently, no guideline recommendtions re vilble for the dignosis of CSF shunt infection; however, stndrdized pproches hve recently been proposed. 11 The highest rte of shunt infection occurs erly fter shunt plcement or revision (eg, within 1 month); therefore, most contmintion with microorgnisms is thought to occur 1, 10, 12 intropertively. The infection rte increses with the number of surgicl revisions. 1, 6 In fct, dult ptients with previous revisions for mechnicl shunt dysfunction re 3 times more likely to develop n infection thn those who hve not undergone ny surgicl revisions. 6 These numbers re importnt to consider becuse n estimted 50% or more of ll ptients with CSF shunt require t lest 1 10, 13 surgery for revision. Some evidence lso suggests tht history of crniotomy or externl ventriculr drin (EVD) prior to shunt plcement doubles the risk for shunt infection. 6 Despite the limited evidence, helthcre providers cn resonbly consider these procedures s possible risk fctors, given tht both procedures hve the potentil to introduce microorgnisms into the sterile environment of the CSF. Other risk fctors include younger ge, holes in surgicl gloves, postopertive CSF lek, nd shunt insertion performed by neurosurgeons with limited experience. 1, 2, 6 Microbiology Shunt infections re often the result of contmintion of the proximl end of the shunt with norml skin flor. Among these flor, cogulse-negtive Stphylococci nd Stphylococcus ureus re the most common pthogens ssocited with the development of VP shunt infection. Infections cused by these pthogens ccount for 50% nd 33% of ll shunt infec- 14, 15 tions, respectively. Timing of the infection ppers to be relted to the specific microbiology of VP shunt infection. Erly VP shunt infections (within weeks of insertion nd revision) re typiclly cused by skin flor, such s cogulse-negtive Stphylococci nd S ureus. However, lte VP shunt infections (severl months fter insertion nd revision) re usully cused by Streptococcus spp nd grm-negtive pthogens, such s Pseudomons eruginos, nd occur s direct result of bowel perfortion or peritonitis. Other rre pthogens ssocited with lte VP shunt infections include Cndid lbicns, Corynebc- 16 19 terium jeikeium, nd Mycobcterium spp. Tble 2 lists dditionl pthogens ssocited 14, 16 with VP shunt infections. Dignosis Initilly, VP shunt infection my not elicit obvious neurologicl symptoms. 20 However, symptoms cn develop when the infection cuses shunt obstruction nd subsequent Tble 2: Common Pthogens Associted With Ventriculoperitonel Shunt Infections Erly Infection ( 85% of Shunt Infection) (Within Weeks of Shunt Plcement or Revision) Cogulse-negtive Stphylococci (ie, S. epidermidis ) 50% Stphylococcus ureus 33% Corynebcterium Propionibcterium cnes Bsed on dt from references 14-16. Lte Infection ( 15% of Shunt Infection) (Severl Months After Shunt Plcement or Revision) Pseudomons eruginos Serrti mrcescens Stenotrophomons Cndid lbicns 7
Drug Updte WWW.AACNADVANCEDCRITICALCARE.COM increses in intrcrnil pressure. These symptoms include hedche, nuse, vomiting, nd ltered mentl sttus. Clinicl suspicion for VP shunt infection wrrnts evlution of CSF, blood cultures, nd neuroimging studies. Cerebrospinl fluid for nlysis should be obtined directly from the VP shunt rther thn vi lumbr puncture, if possible, nd should include white blood cell (WBC) count with differentil, glucose, nd protein concentrtions. Grm stin nd CSF culture should lso be performed becuse identifiction of pthogens is necessry for successful directed ntibiotic therpy. A positive CSF nlysis will yield elevtions in WBC count (1000-5000/mcL), with high percentge of neutrophils ( 80%) nd protein concentrtion (100-500 mg/dl). Cerebrospinl fluid glucose concentrtions re usully decresed ( 40 mg/dl). Clinicins should note tht interprettion of CSF nlysis my be more difficult in certin circumstnces. For exmple, trumtic lumbr puncture, generlized seizures, or intrcerebrl or subrchnoid hemorrhge my cuse spurious elevtions in CSF WBC count. The use of blood cultures to help dignose shunt infections hs been shown to yield inconsistent results. Previous studies 21, 22 report positive blood cultures in only 23% of VP shunt infections, wheres 95% of ventriculotril shunt infections produced positive blood cultures. Neuroimging is useful to identify ventriculitis nd obstruction of CSF. Abdominl imging cn lso be used to help identify blockge of the distl end of the shunt. Recently more stndrdized dignostic criteri for definite nd probble shunt infections hve been proposed nd re summrized in Tble 3. 11 Tretment Most infections rise from skin flor rther thn from n bdominl source, resulting in n infection of the centrl nervous system (CNS). 1 Becuse meningitis is common result of VP shunt infections, strong emphsis on pproprite tretment 1, 23, 24 is needed. Although the mngement of VP shunt infections is not stndrdized, the Infectious Diseses Society of Americ s guidelines 23 offer some direction in the tretment pproch for ptients with meningitis who hve CSF shunt. The mngement of the infection often involves the removl of the infected shunt with plcement of Tble 3: Overturf s 11 Dignostic Criteri for Ventriculoperitonel Shunt Infection Definite Shunt Infection Comptible clinicl signs nd symptoms PLUS Isoltion of bcteril pthogen from device puncture, lumbr puncture, or other significnt site (overlying shunt wound, cellulitus, or shunt tubing) Abbrevition: CSF, cerebrospinl fluid. Used with permission from Overturf. 11 Probble Shunt Infection Comptible signs nd symptoms CSF consistent with bcteril infection Negtive blood, CSF, nd device cultures for bcteri temporry EVD if needed, culture of vrious sites (wound, shunt tip, CSF from vlve, ventriculr CSF, lumbr CSF, nd/or blood), nd tretment with intrvenous nd possibly intrventriculr ntibiotics. Becuse the distl end of VP shunt lies within the peritonel cvity, the risk for infection with grm-negtive bcteri is lso possibility, nd empiric ntibiotic choices should 23, 24 include coverge for these pthogens. Systemic Antibiotics Most VP shunt infections require tretment with systemic ntibiotics. For empiric ntibiotic selection, the clinicin should ssume tht ntimicrobil resistnce is possibility nd choose brod-spectrum coverge until culture identifiction nd susceptibility dt re vilble. Current guidelines recommend combintion therpy with vncomycin plus one of the following gents: cefepime, ceftzidime, or meropenem. 23 Common dosing requirements for these ntibiotics re listed in Tble 4. The ntibiotic choice nd dosing re bsed on the need for dequte penetrtion of the drug into the CSF for bctericidl efficcy ginst the infection in the setting of meningitis. 23 Intrventriculr Antibiotics In ptients with infections tht re difficult to cure or in those who cnnot undergo removl of the infected shunt, the current guidelines recommend tht clinicins consider direct dministrtion of ntibiotics into the ventricles. 23 Note tht the specific indictions for intrventriculr 8
VOLUME 24 NUMBER 1 JANUARY MARCH 2013 Drug Updte Tble 4: Common Intrvenous Antimicrobil Tretment Regimens for Ventriculoperitonel Shunt Infections Bsed on Custive Pthogen Microorgnism Cogulse-negtive Stphylococci (eg, S epidermis ) Tretment of Choice Common Intrvenous Dosing Requirements (Norml Renl Function) Tretment Durtion, d Vncomycin 15 mg/kg every 8-12 h 7 Stphylococcus ureus MRSA: Vncomycin 15 mg/kg every 8-12 h 10 MSSA: Nfcillin 2 g every 4 h Grm-negtive bcilli (eg, P eruginos ) Ceftzidime 2 g every 8 h 10-14; depending on clinicl response Cefepime 2 g every 8 h Meropenem 2 g every 8 h Abbrevitions: MRSA, methicillin-resistnt Stphylococcus ureus ; MSSA, methicillin-sensitive Stphylococcus ureus. Bsed on informtion from meningitis guidelines nd Tunkel et l. 23,24 ntibiotic dministrtion hve not been defined. Limited dt re vilble for the use of intrventriculr ntibiotics for the tretment of VP shunt infection in dults, nd no ntibiotics re currently pproved for this use by the Food nd Drug Administrtion. However, this prctice is used often in the clinicl setting on the bsis of 18, 25, 26 severl cse reports. Vncomycin is the most widely studied ntibiotic for intrventriculr dministrtion in dults. In retrospective cse series by Byston et l, 25 50 cses of ventriculitis cused by CSF shunt infections in peditric nd dult ptients were treted with intrventriculr vncomycin. Cerebrospinl fluid culture dt reveled tht ll infections were susceptible to vncomycin, nd the most commonly identified pthogen ws cogulse-negtive S ureus. Doses rnged from 5 to 20 mg once dily; however, most ptients (76%) received 20 mg/d. Lower doses were primrily used in the peditric popultion. Becuse of the retrospective study design, the tretment regimens were not stndrdized, nd most ptients received combintion of pproches, including intrvenous, intrventriculr, nd orl ntibiotics in ddition to shunt removl nd/or plcement of n EVD. Tretment continued up to 3 to 4 dys fter negtive CSF cultures were obtined. Follow-up to determine tretment success occurred between 3 months nd 4 yers fter ntibiotics were discontinued. The overll cure rte ws 66%; however, those who received the tretment combintion of shunt removl, 20 mg of intrventriculr vncomycin dily, nd systemic ntibiotics experienced 92% cure rte, nd no reports of vncomycin toxicity were noted. Infections in which the CSF shunt ws not removed were ssocited with significnt increse in the number of subsequent shunt revisions due to complictions from the infection (eg, blockge of the distl ctheter). On the bsis of these findings, the uthors concluded tht the tretment combintion of shunt removl, 20 mg/d of intrventriculr vncomycin, nd systemic ntibiotics ws both sfe nd effective for CSF shunt infections. 25 In nother cse series of dult nd peditric ptients, Swyne et l 26 describe their results with similr tretment pproch to Byston nd collegues. 25 Twenty episodes of CSF shunt infections in 15 ptients were treted with shunt removl, plcement of n EVD, nd intrventriculr vncomycin (dults: 20 mg/d [n 6]; peditric ptients: 10 mg/d [n 9]). One of the mjor differences in this tretment pproch from the previous is the plcement of n EVD, which llowed both ccess to the ventricle for ntibiotic dministrtion nd control of CSF pressure for the durtion of tretment. Similr to the previous study, most ptients received concomitnt systemic ntibiotics, including vncomycin, gentmicin, flucloxcillin, trimethoprim, nd cotrimoxzole. Antituberculosis ntibiotics were lso dministered for 3 of the reported infections; however, the nmes of these ntibiotics were not reported. Interestingly, intrventriculr vncomycin ws the only ntibiotic dministered in 4 of the study ptients. All study ptients, however, hd follow-up CSF smples tht were sterile nd free of pus, suggesting tht the tretments led to n cute resolution of CSF shunt infections. Stphylococcus epidermidis ws the most common pthogen identified, 9
Drug Updte WWW.AACNADVANCEDCRITICALCARE.COM nd not ll isoltes were sensitive to the systemic ntibiotics used, which suggests tht the intrventriculr ntibiotic lone ws effective in mny reported cses; the uthors concluded tht in uncomplicted cses of shunt infections with grm-positive cocci, monotherpy with intrventriculr vncomycin is n effective tretment option. 26 Knudsen et l 18 described their success with intrventriculr vncomycin for the tretment of VP shunt-relted ventriculitis due to Corynebcterium jeikeium in 52-yer-old womn. After n unsuccessful tretment regimen with intrvenous vncomycin (1 g intrvenously every 12 hours), the ptient ws subsequently treted with shunt removl nd intrventriculr vncomycin (10 mg/d for 4 dys), followed by orl rifmpicin nd fusidic cid. The totl durtion of tretment ws 15 dys. As of 1 yer fter dischrge, the ptient did not experience ny relpse of infection. 18 In summry, for complicted VP shunt infections (eg, meningitis), clinicins should consider dministrtion of intrventriculr ntibiotics in ddition to systemic ntibiotics, preferbly fter the infected shunt hs been removed, s cure rtes re highest with this tretment 18, 23 26 pproch. Both systemic nd intrventriculr ntibiotics should be de-esclted to trget the custive pthogen on the bsis of the vilble culture nd sensitivity dt. Uncomplicted infections my be treted successfully with intrventriculr vncomycin lone if susceptible pthogen is identified from the CSF or drin culture. Mny other ntimicrobil gents, including minoglycosides nd colistin, hve been dministered intrventriculrly. 23 Tble 5 summrizes the recommended dosges for intrventriculr use of these gents. The optiml dosing strtegy is not well estblished; however, mintining trough CSF concentrtions of t lest 5 to 10 times the minimum inhibitory concentrtion of the custive pthogen is recommended. Although no cler recommendtion exists for durtion of tretment with intrventriculr ntibiotics, clinicl signs of infection should be resolved nd negtive CSF cultures should be 23, 27 obtined prior to discontinution. Prophylctic Antibiotics to Aid in Prevention of Infection Current guidelines for the use of periopertive ntibiotics recommend cefzolin for clen procedures (ie, n uninfected opertive wound in which Tble 5: Recommended Dosges of Antimicrobil Agents Administered by the Intrventriculr Route,b Dily Intrventriculr Antimicrobil Agent Dose, mg Vncomycin 5-20 c Gentmicin 1-8 d Tobrmycin 5-20 Amikcin 5-50 e Polymyxin B 5 f Colistin 10 Quinupristin/dlfopristin 2-5 Teicoplnin 5-40 g Used with permission from Tunkel et l. 23 b There re no specific dt tht define the exct dose of n ntimicrobil gent tht should be dministered by the intrventriculr route. c Most studies hve used dose of 10 mg or 20 mg. d Usul dily dose is 4 to 8 mg for dults nd 1 to 2 mg for children. e Usul dily dose is 30 mg. f Dosge in children is 2 mg dily. g Teicoplnin is glycopeptide ntibiotic tht is used outside the United Sttes. Dosge of 5 to 10 mg every 48 to 72 hours ws used in one peditric study. 33 no inflmmtion is encountered nd the respirtory, limentry, genitl, or uninfected urinry trct is not entered) such s CSF shunt insertion. If ptient is llergic to cephlosporin gents, clinicins re recommended to use n lterntive gent such s vncomycin for grm-positive coverge. 28 However, primry literture in support of this recommendtion, specificlly for CSF shunt insertion in dult ptients, is lcking. In light of the incresing incidence of methicillin-resistnt strins of S ureus, Tcconelli et l 29 compred infection rtes in dult ptients who received vncomycin 1 g intrvenously over 60 minutes (n 88) versus cefzolin 1.5 g intrvenously over 30 minutes (n 88) prior to CSF shunt implnttion in prospective, rndomized tril. Ptients in the cefzolin group received doses every 4 hours until surgery ws completed. By 4 weeks fter the procedure in n intention-to-tret nlysis, shunt infections developed in 4 ptients who received vncomycin (4.5%) nd 12 ptients who received cefzolin (13.6%) (reltive risk: 0.27; 95% confidence intervl: 0.44-0.04; P.04). The durtion of postopertive hospitliztion ws longer (men SD: 38 37 vs 54 78 dys, respectively; P.03) nd the mortlity rte mong ptients with postsurgicl infections ws greter (number: 0 10
VOLUME 24 NUMBER 1 JANUARY MARCH 2013 Drug Updte vs 5; P.02) for those who received cefzolin. The uthors reported tht prior to the study period, 39% of Stphylococci isolted from neurosurgicl infections t their institution were methicillin resistnt; however, ll Stphylococci isolted from the CNS shunt infections during the study period were methicillin resistnt. Given the lower incidence of infection, shorter hospitl sty, nd lower overll mortlity rte from postsurgicl infections in ptients who received vncomycin, this study supports the routine use of intrvenous vncomycin rther thn cefzolin prior to CNS shunt insertion for infection prophylxis. These findings would likely best be pplied in clinicl settings of dult ptients with similr rtes of methicillin-resistnt Stphylococci. Currently, no other prospective, rndomized studies re vilble to confirm the findings of Tcconelli et l. 29 Intrventriculr ntibiotic dministrtion lso hs been evluted for prophylxis of CNS shunt infections. In retrospective study of dult ptients who hd undergone CNS shunt implnttion for hydrocephlus, Rgel nd collegues 12 compred the risk of shunt infections mong groups of ptients who hd received vrious methods of ntibiotic prophylxis. A totl of 802 procedures for shunt plcement were performed in 534 ptients during the study period. All ptients received intrvenous ntibiotic prophylxis with 1 to 2 g of cefzolin or 1 g of vncomycin prior to skin incision, with doses typiclly continued for 24 hours fter the procedure. In ddition, some ptients received intrventriculr ntibiotic prophylxis. Ptients were observed for 90 dys following shunt implnttion to evlute the incidence of infection. The uthors compred outcomes for 4 groups of ptients: group 1, 4 mg of intrventriculr gentmicin (before My 16, 1999); group 2, 4 mg of intrventriculr gentmicin plus 10 mg of intrventriculr vncomycin (fter My 16, 1999); nd 2 control groups who did not receive intrventriculr ntibiotic prophylxis (groups 3 nd 4: before nd fter My 16, 1999, respectively). Ptients who received both intrventriculr gentmicin nd vncomycin hd significntly fewer infections thn ptients in ll other groups (percentge of ptients with infections in groups 1 4 were 5.45%, 0.41%, 6.21%, nd 6.74%, respectively). No decrese in infection rte ws observed in ptients who received only intrventriculr gentmicin; therefore, the uthors concluded tht the combintion of intrventriculr gentmicin nd vncomycin ws n effective method to prevent CNS shunt infection. 12 Whether ntibiotic prophylxis for VP shunt plcement should be routinely used in dults is debtble, given the lck of well-controlled studies nd guideline recommendtions. A Cochrne review from 2006, which evluted trils involving ll ge groups, indicted significnt difference in fvor of systemic ntibiotic prophylxis for up to 24 hours following the plcement of internl CNS shunts. 30 Clinicins re dvised to dminister ntibiotic prophylxis for VP shunt insertion; however, well-controlled trils evluting the efficcy of this prctice in preventing infections re needed. Another method of infection prevention is using ntibiotic-impregnted shunts, prctice tht hs been evluted in severl studies. 30 32 The efficcy of ntibiotic-impregnted shunts hs not been consistently demonstrted; therefore, the use of these devices is not the stndrd of cre. Conclusion The pproprite dignosis, tretment, nd prevention of infections re importnt elements to optimize cre for dult ptients with VP shunt infections. In the setting of CSF shunt infections, objective informtion from the ptient s physicl exmintion nd vilble culture dt should be used to guide tretment. Initil systemic ntibiotic selection should cover brod rnge of pthogens, followed by de-escltion of ntibiotics once the microorgnism is identified. The best tretment results occur when ntibiotics re dministered in ddition to device removl. Certinly, further studies re needed in this ptient popultion to determine the most pproprite tretment pproch. REFERENCES 1. George RL, Leibrock L, Epstein M. Long-term nlysis of cerebrospinl fluid shunt infections: 25-yer experience. J Neurosurg. 1979 ; 51 ( 6 ): 804 811. 2. Kulkrni AV, Drke JM, Lmberti-Psculli M. Cerebrospinl fluid shunt infection: prospective study of risk fctors. J Neurosurg. 2001 ; 94 ( 2 ): 195 201. 3. Reddy GK, Bollm P, Cldito G. Ventriculoperitonel shunt surgery nd the risk of shunt infection in ptients with hydrocephlus: long-term single institution experience. World Neurosurg. 2012 ; 78 : 155 163. 4. Nulsen FE, Spitz EB. Tretment of hydrocephlus by direct shunt from ventricle to jugulr vein. Surg Forum. 1951 : 399 403. 5. Drke JM, Kestle JRW, Tuli S. CSF shunts 50 yers on pst, present nd future. Child s Nerv Syst. 2000 ; 16 : 800 804. 6. Korinek AM, Full-Oller L, Boch AL, Golmrd JL, Hdiji B, Puybsset L. Morbidity of ventriculr cerebrospinl fluid shunt surgery in dults: n 8-yer study. Neurosurgery. 2011 ; 68 : 985 995. 11
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