Infections
Infectious
Complications
After
Laser
Vaporization
of
Urinary
Stones
During
Retrograde
Intrarenal
Surgery
Are
Not
Associated
with
Spreading
of
Bacteria
into
Irrigation
Fluid
but
with
Previous
Use
of
Fluoroquinolones
Tommaso
Cai
a,*
,
Andrea
Cocci
b,
Franco
Coccarelli
a,
Lorenzo
Ruggera
c,
Paolo
Lanzafame
d,
Patrizio
Caciagli
e,
Gianni
Malossini
a,
Alfonso
Crisci
b,
Alberto
Trinchieri
f,
Giampaolo
Perletti
g,h,
Marco
Carini
b,
Gernot
Bonkat
i,
Riccardo
Bartoletti
j,
Truls
E.
Bjerklund
Johansen
kaDepartmentofUrology,SantaChiaraHospital,Trento,Italy;bDepartmentofUrology,UniversityofFlorence,Florence,Italy;cDepartmentofUrology, UniversityofPadua,Padua,Italy;dDepartmentofMicrobiology,SantaChiaraRegionalHospital,Trento,Italy;eDepartmentofLaboratoryMedicine,Santa ChiaraRegionalHospital,Trento,Italy;fUrologyUnit,ManzoniHospital,Lecco,Italy;gDepartmentofBiotechnologyandLifeSciences,SectionofMedicaland Surgical Sciences, Università degli Studi dell'Insubria, Varese,Italy; hFacultyof Medicine and Medical Sciences, Ghent University, Ghent, Belgium; iDepartmentofUrology,altauroAG,Basel,Switzerland;jDepartmentofUrology,UniversityofPisa,Pisa,Italy;kDepartmentofUrology,OsloUniversity Hospital,Oslo,Norway
a v ai l a b l e a t w w w . s c i e n c e d i r e c t . c o m
j o u r n al h o m e p a g e : w w w . e u r o p e an u r o l o g y . c o m / e u f o c u s
*Correspondingauthor.DepartmentofUrology,SantaChiaraHospital,LargoMedaglied'Oro9, Trento,Italy.Tel.:+390461903306;Fax:+390461903101.
E-mailaddress:[email protected](T.Cai).
Articleinfo Articlehistory: AcceptedFebruary25,2019 AssociateEditor: RichardLee Keywords: Bacteriuria
Retrogradeintrarenalsurgery Antibioticresistance
Urinarytractinfection Urinarystones
Abstract
Background: Thepathogenesisofinfectiouscomplicationsafterretrogradeintrarenal surgery(RIRS)isnotfullyunderstood.
Objective: ToevaluatespreadingofbacteriaintoirrigationfluidandbloodduringRIRS forstonemanagementandtocorrelatesuchspreadingwithinfectiouscomplications.
Design,setting,and participants: FromJanuarytoDecember 2017, 38 patientswho underwentRIRSforstonesintwourologicalunitswereenrolledinthisprospective, longitudinalcohortstudy.
Intervention: Aurineculturewastakenbeforesurgeryandantimicrobialprophylaxis was given in line withthe European Association of Urology guidelines. Blood and irrigationfluidsampleswerecollectedatthestartoftheendoscopicprocedure and every30minduringtheprocedure.Allsamplesweremicrobiologicallyexaminedand findingswerecomparedwithclinicaldata.
Outcomemeasurementsandstatisticalanalyses: Symptomaticandasymptomatic uri-narytractinfectiouscomplications werecorrelatedwithmicrobiologicalandclinical data,usingStudentttestorMann–WhitneyUtest.
Resultsandlimitations: Tenpatientsshowedsignificantbacterialgrowthinirrigation fluidsamples(sevenEscherichiacoli,twoKlebsiellapneumoniae,andonePseudomonas aeruginosa).Eightpatients(21%)gotfebrileurinarytractinfectionsduringhospitalstay: two had bacterialgrowthin theirrigationfluid (25%) and onealsohad bacteremia (12.5%).Nocorrelationwasfoundeitherbetweenthebacterialgrowthintheirrigation fluidsamplesandtheurineculturesthatweretakenbeforetheprocedure,orbetween thebacterialgrowthintheirrigationfluidsamplesandthedevelopmentof postopera-tiveinfectiouscomplications.Previoususeoffluoroquinolonesandahistoryofurinary tractinfectionswereassociatedwithinfectiouscomplicationsafterRIRS.
https://doi.org/10.1016/j.euf.2019.02.018
1. Introduction
Overthelast10yr,retrogradeintrarenalsurgery(RIRS)has becomeanincreasinglyimportantoptionforthetreatment ofkidneystones[1,2].Despiteahighsafetyprofile,severe complications such as urosepsis and death have been described [3,4]. Urinary tract infection (UTI) is the most commoncomplicationafterstonetreatment,anda4.4%risk of postoperative fever and 0.7%risk of sepsis have been reporteddespiteadequateperioperativeantimicrobial pro-phylaxis(PAP)[5].Themostlikelypathogeneticmechanism forinfectiouscomplicationsisthatstone-contained bacte-riaentertheurinewithsystemictransudation,resultingin symptomaticUTIorsepsis[6].Inordertoreducetheriskof
symptomaticUTIandurosepsisafterRIRS, American Uro-logical Associationguidelines suggestto operate only on patientswithsterileurine,toadministerprophylactic anti-bioticsinallpatients,toirrigatewithcautionwhile check-ingthecontinuousoutflow,nottoexceed2hofoperation time,andtoobservepatientscarefullyinthefirst6 postop-erativehours[7].Onthecontrary,theEuropeanAssociation of Urology (EAU) guidelines suggest using PAP only in patientsatahighriskofinfectionscomplications.Potential riskfactorsarestonesize,locationofthestone,bleeding, andthe surgeon’s experience[8].However, despitethese recommendations,untiltodaynostudyhasdemonstrated spreadingofbacteriainto irrigationfluidorblood during RIRS. Filling this knowledge gap would improve the Conclusions: Wedemonstratedspreading ofbacteriaintotheirrigationfluidduring RIRS procedures, but this spreading was not associated with the development of infectiouscomplications. Particular attentionshouldbegiven topreviousantibiotic treatmentbeforeadministrationofantimicrobialprophylaxis.
Patientsummary: Bacterialspreadingintoirrigationfluidisacommonfindingduring retrogradeintrarenalsurgery,butitisnotassociatedwithinfectiouscomplicationsafter theprocedure. Particularattentionshouldbegiventopreviousantibiotictreatment beforeadministrationofantimicrobialprophylaxis.
©2019EuropeanAssociationofUrology.PublishedbyElsevierB.V.Allrights reserved.
Patients can didate to RIRS for intraenal
stones Urine culture: targeted therapy if needed Antibiotic prophylaxis (EAU guidelines) Blood and irrigation fluid sample collection: - At the start - Every 30 min - At the end Microbiological analysis Clinical, instrumental, labrortory evaluation, and correlation with microbiological findings (during hospital stay, at
discherge and at 30 d after hospital discharge) After surgery Operating theater (retrograde intrarenal surgery) Before surgery Setting Exclusion criteria: - <18 yr -No preoperative CT -Pelviureteric mass -Musculoskeletal or renal malformation -Multistage procedure RIRS
Fig.1–StudyscheduleaccordingSTROBEguidelines.CT=computedtomography;EAU=EuropeanAssociationofUrology;RIRS=retrogradeintrarenal surgery.
rationale forPAP, andhelpidentify themostappropriate antibiotic and the administration schedule. We aim to analyzespreadingofbacteriainto theirrigation fluidand blood during RIRS for intrarenal stones, and to correlate findingswithclinicalparametersandthedevelopmentof infectiouscomplicationsaftertheprocedure.
2. Patientsandmethods
2.1. Studypopulation,design,andschedule
FromJanuary2017toDecember2017,werecruited38patientsintwo urologicalunitsforthislongitudinalcohortstudy.Allpatientsunderwent RIRSforintrarenalstones.Urineculturesweretakenbeforesurgeryand PAPwasadministeredinlinewithEAUguidelines[8].Incaseofpositive urineculturebeforetheRIRS,atargetedtherapywasadministeredanda newurinesamplewasanalyzedbeforesurgeryinordertodemonstratea negativeculture.Bloodandirrigationfluidsampleswerecollectedatthe start ofthe endoscopicprocedure andevery 30min thereafteruntiltheend oftheprocedure.Reportedsymptomaticandasymptomaticurinarytract infectiouscomplicationswererecorded,andcorrelatedwith microbiolog-icalandclinicaldata.Figure1showsthestudyschedule.Thestudyprimary endpointwastheprevalenceoffebrileorafebrileinfectiouscomplications afterRIRS,andthe correlationbetween thesecomplicationsandthe bacterialspreadingintotheirrigationfluidandblood,takenduringthe procedure.Thisstudywasperformedasalongitudinalcohortstudy[9],in linewiththeSTROBEstatement(http://www.strobe-statement.org/).
2.2. Clinicalandproceduralconsiderations
AllpatientsunderwentRIRSinlinewiththeEAUguidelineson urolith-iasis[10].Allprocedureswereperformedbytwodedicatedand experi-encedendourologists(F.C.,Trento,andA.C.,Florence).Stoneburden, collectingsystemanatomy,andstonecharacteristics were preopera-tivelyevaluatedbyacomputedtomography(CT)scan.Stonesizewas calculatedbymeasurementofthelongestdiameters.Allpatientswere positionedinthedorsallithotomyposition.BeforeRIRS,adiagnostic semirigidureterorenoscopy(8Fr;KarlStorz,Tuttlingen,Germany)was performed.Thisprocedurewasalsoroutinelyusedfordilatationofthe ureter.Afterthata9.5-or11.5-Frureteralaccesssheath(CookMedical) wasplacedinposition.A7.5-FrFlex-X2flexibleureteroscope(KarlStorz) wasinsertedthroughtheaccesssheath.Normalsalineirrigationwas usedwithastandardpressurizedirrigationsystem(100mmHg).A 272-mmlaserfiberwasusedfortreatmentofallstones.Theholmiumlaser powerwassetto10W.Fragmentedstoneswereremovedsuccessively. Followingthecompletionofstoneremoval,theureterwasvisualizedall alongitslengthto seeanyureteralinjury. Aureteralstent wasnot routinelyplacedafterthe procedure;itwasplacedwhentherewas mucosaledemaorinjuryofthemucosa,orthedurationoftheprocedure was 2h. The ureteral stent was usually removed within 2–4 wk postoperatively [11]. Moreover, intraoperative pyelograms were not routinelyperformed,butonlyinselectedcases.Thediagnosisof symp-tomaticUTIafterRIRSwasbasedonthefollowingparameters:patient interviewandpatient-reportedsymptoms,physicalexamination, bed-sidedipstickurinalysis,andurineculture[8].Previousantibiotictherapy andhistoryofUTIweredefined,respectively,astheuseofantibioticsfor themanagementofUTIintheprevious6mo[12],andoneormoreUTI episodesinthepastyear[13].Weexcludedallpatients<18yr old; patientswithnoavailablepreoperativeCTimages,withapelviureteric mass,andwithmusculoskeletalorrenalmalformation;andpatients withamultistageprocedure.RIRSwasconsideredsuccessfulinpatients whobecamecompletelystonefreeorhadclinicallyinsignificantresidual (<3mm)atthepostoperativeimaging.
2.3. Microbiologicalandlaboratoryexaminations
Themicrobiologicalandlaboratoryanalysesusedhavebeendescribedby usinpreviousreports[14,15].Allclean-catchmidstreamurinesamples werecollectedclosetotheprocedureandimmediatelybeforethePAP wasgiven.DuringRIRS,avenousbloodsamplewascollectedfromthe patient’sarmbythenurseanesthetistintheoperatingtheatreatthe startoftheendoscopicprocedureandevery30minuntiltheendofthe procedure.A10ccsampleofirrigationfluidwascollectedthroughthe working/irrigationchannelintherenalpelvisimmediatelybeforethe stone fragmentation.The collectionmethodsandthe volumeofthe
Table1–Clinical,instrumental,andlaboratorycharacteristicsof patients.
No.ofpatients 38
Medianage(SD) 48.1(7.5) CharlsonComorbidityIndex 1(0–2) Comorbidities
Diabetes 3(7.8)
Hypertension 12(31.5)
Chroniccardiovasculardiseases 1(2.6) Sex
Male 18(47.3)
Female 20(52.7)
BMI,kg/m2(SD)
24.3(2.5) HistoryofUTIandantibioticuse
Yes 7(18.4)
No 31(81.6)
HistoryofpreviousstonesurgeryorDJplacement
Yes 5(13.2) No 33(86.8) Stonesize,mm(SD) 25.3(11.3) Stonecomposition Calciumoxalate 30(78.9) Struvite 2(5.3) Uricacid 2(5.3) Calciumphosphate (7.9) Cystine 1(2.6) Stonelocation Renalpelvis 14(36.8) Uppercalyx 3(7.8) Middlecalyx 11(29.1) Lowercalyx 10(26.3)
Meanstonedensity(HUunit) 815.7353.5 Side
Rightkidney 21(55.2)
Leftkidney 17(44.8)
Presenceofhydronephrosis 3(7.8) Operationtime(min),meanSD 4811.8
Stone-freerate 27(71.1)
Irrigationvolume(ml),meanSD 2008.4756.8 Irrigationflow/rate(ml/min),meanSD 41.010.4 Hospitalizationtime(d),mean(range) 3(1–7) Urinecultureresultbeforesurgery
Negative 32(84.3)
Positive* 6(15.7)
Isolatedstrainsfromurineculture*
E.coliESBL 4(66.6)
Citrobacterfreundii 1(16.7) K.pneumoniaeESBL 1(16.7) Antimicrobialprophylaxis(drug)on32patients
withnegativepreoperativeurineculture
Aminoglucoside 6(18.7)
Ampicillin/sulbactam 6(18.7)
Cephalosporins 3(9.4)
Fluoroquinolones 17(53.2)
BMI=body mass index; DJ=doubleJ; ESBL =negative extended-spectrum b-lactamasestrain;HUunit=Hounsfieldunit; SD=standard deviation;UTI=urinarytractinfection.
samplehadbeendiscussedwiththemicrobiologistsbeforethestartof thestudy.Anirrigationfluidsamplewascollectedevery30minuntilthe endoftheprocedure.Allurineandbloodsampleswereimmediately takentothelaboratoryunderrefrigeratedconditions.Microbiological cultureswereperformedaccordingtoHootonetal[16].For microbio-logicaldiagnosis,acolonycountof105units/mlwasconsideredthe cutoffforsignificantbacterialfinding.
2.4. Statisticalanalysisandethicalconsiderations
Continuousvariablesweregivenas means(standarddeviations)and comparedusingStudentttestorMann–WhitneyUtest.Owingtothe studydesign,nosamplesize calculationwasneeded.Allreportedp valuesweretwosided.StatisticalanalyseswereperformedusingIBM SPSS 20.0 software for Apple-Macintosh (IBM, NY, USA). Dedicated informedconsentwasnotrequiredasallprocedureswereperformed accordingtostandardroutines.Allpatientssignedtheinformedconsent relatedtothesurgicalprocedure,andwereinformedaboutthenatureof thestudyandthebloodandirrigationfluidsamplecollectionduringthe procedure.Theywereinformedthatthesamplecollectionwouldnot prolongtheoperatingtimeandwouldnotimpacttheRIRSoutcome.Our studywasconductedinlinewiththeGoodClinicalPracticeguidelines andtheethicalprincipleslaiddowninthelatestversionofthe Declara-tionofHelsinki.Allanamnestic,clinical,andlaboratorydatacontaining sensitiveinformationaboutpatientsweredeidentifiedinordertoensure analysis of anonymous data only. The deidentification process was performedbynonmedicalstaffbymeansofdedicatedsoftware.
3. Results
Allanamnestic,laboratory,instrumental,and microbiolog-ical characteristics of analyzed patients are described in
Table1.Threepatients showed agradeI hydronephrosis.
Thestone-freerateafterRIRSisdisplayedinTable1.Sixout of38patientsshowedpositiveurinecultures beforeRIRS and were treated in line with antibiogram results. All microbiologicalfindingsandtreatmentschedulesarealso describedinTable1.
3.1. Microbiologicalfindingsandcorrelationwithinfectious complications
Ninety-sixirrigationfluidand93bloodsampleswere col-lected. About 3.5 samples per patientwere collected. In threepatients,thelastbloodsamplewasnotcollecteddue to anesthesiological problems. Among all patients, 10 showed significant bacterial growth in the irrigation fluid samples. In this group, all patients had significant bacterial growth in one ormore irrigation fluid samples (range 1–3). By contrast, one patient showed bacterial growth intheblood duringthe procedure.Eightpatients (21%)developed febrileUTIsduring hospitalstay.Among patientswithinfectiouscomplications,twoshowed bacte-rialgrowthintheirrigationfluid(25%)andonealsoshowed bacteremia (12.5%). On the contrary, among all patients without complications, eight out of 30 showed bacterial growth intheirrigationfluid(26.6%).Nomultiplestrains wereisolated.Allmicrobiologicalfindingsaredisplayedin
Tables2and3.Twenty-onepatients(55.2%)showed
asymp-tomaticbacteriuria(ABU)duringhospitalstay.Inlinewith the EAU guidelines on urological infections, no patients were treatedforthisABU.Moreover, eightpatients(21%) showed febrile UTIs after the procedure, whichrequired antibiotictreatment.Sixpatientsrequiredalongerperiodof hospitalization and parenteral broad-spectrum antibiotic treatment. No severe complications were reported. The most common causative pathogen was fluoroquinolone-resistantEscherichiacoli.Amongallpatientswithout infec-tiouscomplicationsafterRIRS,fourreportedprevioususeof fluoroquinolonesandahistoryofUTI(13.3%).
3.2. SubanalysisofallpatientswithsymptomaticUTI
Eightof38patients(21%)reportedsymptomaticUTIafter theprocedure.Inthiscohort,onepatientshowedspreading Table2–Microbiologicalfindingsduringproceduresandfollow-upresults.
No.oftotalcollectedsamples(bloodandurine) 189
No.ofsamplescollectedforpatient,median(range) 3.5(2–6) Bacterialgrowth
Total 11(28.9)
Irrigationfluid 10
Blood 1
Isolatedstrainsfromirrigationfluid
E.coli 7
K.pneumoniae 2
P.aeruginosa 1
Patientswithsymptomaticandasymptomaticbacteriuriaafterprocedure
Symptomatic(febrile)UTI 8
Asymptomaticbacteriuria 21
PatientswithsymptomaticUTIafterprocedure PatientswithasymptomaticUTIafterprocedure Total
Bacterialgrowth
Irrigationfluid 2(25)(E.coli) 5(16.6)(E.coli) 7
2(6.6)(Kpneumoniae) 2
1(3.3)(P.aeruginosa) 1
Blood 1(12.5)(P.aeruginosa) 0 1
Nobacterialgrowth 5 22 27
Total 8 30 38
of bacteria into the blood (Pseudomonas aeruginosa— extended-spectrum
b
-lactamase- and fluoroquinolone-resistantstrain).AllthesepatientshadreceivedPAPwith fluoroquinolones,andinonecase,acombinationof fluoro-quinolone and an aminoglycoside. No clinically relevant comorbidities were reported. In three cases, a historyof previousUTI andprevioususeofantibiotic (fluoroquino-lones)werereported(37.5%).Nopatientsshowedbacterial growthaturineculture beforeRIRS. Nosignificant differ-enceswerereportedintermsofsite/sizeofstones,history of previous stone surgery, or DJ placement betweenthis cohort and the other patients who did not report any symptomaticUTIaftertheprocedure(Table4).No signifi-cant relationship between irrigation volume, duration of theprocedure,andinfectiouscomplications wasreported afterRIRS.Amongall patients whoreportedinfectious complica-tions,twoshowedbacterialgrowth(25%),whileeightoutof 30 patients without complications (26.6%) had bacterial growth.Nocorrelationwasfoundbetweenbacterialgrowth intheirrigationfluidsamplesandpostoperative symptom-aticorasymptomaticinfectiouscomplications(p=1.0).No correlation was found between bacterial growth in the irrigation fluid samples and urine cultures taken before theprocedure.
4. Discussion
4.1. Mainfindings
Spreadingofbacteriaintotheirrigationfluidiscommonly found duringRIRS procedures, butnot bacteremia. How-ever, we found no correlation between the spreading of bacteria intotheirrigation fluidandinfectious complica-tions after RIRS. Moreover, patients withprevious useof fluoroquinolonesseem to beatahighriskof developing infectiouscomplicationsafterRIRS.
4.2. Resultscomparedwithpreviousstudies
Mitsuzukaandcoworkers[17]recentlydemonstratedthat despitePAP,thedegreeofpreoperativepyuriawas associ-atedwiththerateofinfectiouscomplicationsafter uretero-scopy. Careful management of patients with pyuria or a historyofupperUTIsisneededinordertoreducetheriskof postoperativefebrileUTIorurosepsis[17].Severalauthors demonstrated that pyuria is an important riskfactor for developing infectious complications after the procedure andPAPisabletoreducethisrisk[18].Arecentsystematic reviewandmeta-analysisdemonstratedthatasingledose Table3–Susceptibilityofallisolatedstrains.
Patientswithsymptomaticinfectiouscomplications(8)
Irrigationfluid E.coli(2strains) Sensitive/resistant Strain1 Strain2 Amikacin S S Amixo/clavulanicacid R S Ceftazidime R S Ciprofloxacin R R Gentamicin S S Imipenem S S Levofloxacin R R Piperacillin-tazobactam R S Sulfamethoxazole R R ESBL + – Blood Paeruginosa Sensitive/resistant Amikacin S Amixo/clavulanicacid R Cefepime R Ceftazidime R Ciprofloxacin R Colistina S Gentamicin S Imipenem S Levofloxacin R Piperacillin-tazobactam S Sulfamethoxazole R ESBL +
Patientswithoutsymptomaticinfectiouscomplications(30) Irrigationfluid E.coli(5strains) Sensitive/resistant Strain1 Amikacin S Amixo/clavulanicacid S Ceftazidime S Ciprofloxacin S Gentamicin S Imipenem S Levofloxacin S Piperacillin-tazobactam S Sulfamethoxazole R ESBL – K.pneumoniae(2strains) Sensitive/resistant Strain1 Strain2 Amikacin S S Amixo/clavulanicacid S R Ampicillin R R Cefepime S S Ciprofloxacin S S Gentamicin S S Imipenem S S Levofloxacin S S Piperacillin-tazobactam S S Sulfamethoxazole S R ESBL – – P.aeruginosa(1strains) Sensitive/resistant Strain1 Amikacin R Amixo/clavulanicacid R Cefepime S Ceftazidime S Ciprofloxacin S Gentamicin S Imipenem S Levofloxacin S Piperacillin-tazobactam R Table3(Continued)
Patientswithsymptomaticinfectiouscomplications(8)
Sulfamethoxazole R
ESBL –
ofprophylacticantibioticsisbeneficialinreducingtherate ofpostoperativepyuriaandbacteriuria,althoughtherewas nostatisticallysignificantbenefitinreducingpostoperative UTIs[19].TheefficacyofPAPinreducingtheriskof infec-tiouscomplicationsis,theoretically,duetotheeffectofthe antibioticonthespreadingofbacteriainthekidneyduring lithotripsy.Forthesereasons,internationalguidelines sug-gesttouseantibioticswithahighconcentrationintheurine inordertocontrolthisbacterialspread.This recommenda-tionisnotbasedonaccurateknowledgeofthepathogenesis ofthepostoperativeinfectiouscomplicationsafterRIRS,but isbasedonclinicalstudies[7,8,20].Evenifthe recommen-dationsforPAParebasedonclinicaltrialdata,thepresent studygivesimportantnewinformationforabroader com-prehensionofthepathophysiologyofinfectious complica-tionsaftermodernlithotripsy.
Spreadingofbacteriaintotheirrigationfluidduringthe surgical procedure haspreviouslybeenhypothesized but not documented. Ourfinding thatthere isno correlation betweenthespreadingofbacteriaintotheirrigationfluid andthedevelopmentofsymptomaticinfectious complica-tions after procedure extends our comprehensionof the pathogenesisofinfectiouscomplicationsafterRIRS.Tokas et al [21] highlighted the role of irrigation volume and irrigation flow rate as independent risk factors for SIRS afterRIRS[22].Moreover,increasingtheirrigationvolume iscorrelatedwithanincreaseinintrarenalpressuresanda subsequentincreasedriskofinfectiouscomplications.Here, wedidnotfindanysignificantcorrelationbetween irriga-tionvolumeandinfectiouscomplications.Thisisprobably duetothefactthatweusedaureteralaccesssheathinall
procedures inorderto maintaina lowlevelofintrarenal pressure, as recommended [23]. However, this is only a hypothesis because we did not measure the intrarenal pressure. According to Tokas et al [21], measurement of intrarenalpressureisnotastandardizedprocedure,andthe reproducibilityandaccuracyarelow.However,wetotally agree that increased intrarenal pressure remains a neglected predictorofupper tractendourology complica-tionsandthatintraoperativemonitoringshouldbe consid-ered.Onthecontrary,theabsenceofacorrelationbetween preoperativeurinecultureresults,bacterialspreading,and developmentofinfectiouscomplicationscallsforarethink of the principles of PAP. The aim of PAP should be to decrease bacterial load in the surgical field in order to decrease theriskof infectiouscomplications. Inthe RIRS procedure, the surgical fieldis the urinary tract, butthe infectiouscomplicationsaretheresultsofbacterialspread intothebloodwithsubsequentsystemicinfection.Hence, theidealantibiotictouseforpreventinginfectious compli-cationsafterRIRSshouldachieveahigherblood concentra-tionthanminimalinhibitoryconcentrationforallcausative pathogens. In our study, eight patients developed symp-tomaticUTIafterRIRS(21%).On analysisofthiscohortof patients, we found thatin onlyone case, spreadingof a bacteriumintothebloodwasreported.Inthiscase,previous use offluoroquinolonesandaUTIhistory werereported. Moreover,intwootherpatientswithinfectious complica-tionsafterRIRS,previoustreatmentwithfluoroquinolones for UTI was reported too. Accurate evaluation of the patient’scharacteristicsandanamnesticdataisimportant beforePAPisdecided.Anotherpointtoconsideristhelocal Table4–ComparisonbetweenpatientswithUTIandwithoutUTIafterRIRS.
WithoutsymptomaticUTI WithsymptomaticUTI pvalue
Numberofpatients 30 8
Timetodevelopinfectiouscomplications(postoperativeday,mean(range) – 1(1–3)
Medianage(SD) 47.5(3.2) 49.3(5.4) 0.23
Sex
Male 13(43.3) 5(62.5) 0.43
Female 17(56.7) 3(37.5)
CharlsonComorbidityIndex 1(0–2) 1(0–2) –
PrevioushistoryofUTIandantibioticuse
Yes 4(13.3) 3(37.5) 0.14
No 26(86.7) 5(62.5)
HistoryofpreviousstonesurgeryorDJplacement
Yes 4(13.3) 1(12.5) 1.0
No 26(86.7) 7(87.5)
Stonesize,mm(SD) 24.8(12.1) 25.8(10.1) 0.83
Urinecultureresultbeforesurgery
Negative 24(80) 8(100) 0.30
Positive 6(20) –
Antimicrobialprophylaxison32patientswithnegativepreoperativeurineculture
Fluoroquinolones 20(66.6) 7(87.5) 0.74
Fluoroquinolones+aminoglucoside – 1(12.5)
Cephalosporins 3(10) –
Ampicillin/sulbactam 1(3.3) –
Presenceofhydronephrosis 2(6.6) 1(12.5) 0.51
Operationtime,min(meanSD) 47.911.9 48.211.6 0.94 Irrigationvolume,ml(meanSD) 2000.3768.7 20011.7747.3 0.97 Irrigationflow/rate,ml/min(meanSD) 40.712.1 42.19.8 0.76 DJ=doubleJ;RIRS=retrogradeintrarenalsurgery;SD=standarddeviation;UTI=urinarytractinfection.
bacterial resistance rate. Today, resistance to nearly all classesofantibioticsisgrowingdramatically[24].Therefore, the prescription offluoroquinolone-based PAP should be avoided,andshouldonlybeusedbyexceptioninpatients whodidnotreceivefluoroquinolonedrugsinthelast6mo andwhodonot liveinanareawithahighprevalenceof fluoroquinolone-resistantstrains[12].
4.3. Strengthsandlimitationsofthisstudy
Animportantpointtohighlightistheprospectivenatureof this study that allows reducing the bias related to data collection.Moreover,asingleexperiencedsurgeonineach centershouldalsobeconsideredastrengthofthisstudy.On thecontrary,thelimitednumberofenrolledpatientscould beconsideredalimitation, butthecomplexityof sample collectionandanalysisshouldbetakenintoaccount. Fur-thermore,thelackofstonecultures isalimitation ofour study.Severalauthorsreportedthevalueofobtainingurine directlyfromtherenalpelvisforcultureinordertoguide promptandappropriate antibiotic treatmentfor patients whodeveloppostoperative infectiouscomplications after stonesurgery[25,26].However,inourcenters,wedonot routinely perform stone culture. The lack of intrarenal pressuremeasurementshouldalsobeconsidereda limita-tionofthisstudy.
5. Conclusions
Thisstudyshowedspreadingofbacteriaintotheirrigation fluidbutnotintothebloodduringRIRS.Moreover,bacterial spreading into the irrigation fluid is not associated with infectiouscomplicationsafterRIRS.Futurestudiesshould beplannedtoconfirmtheseresults,butourfindingscallfor arethinkoftheprinciplesofusingPAPbeforeRIRS.
Authorcontributions:TommasoCaihadfullaccesstoallthedatainthe studyandtakes responsibilityfor the integrityof the dataandthe accuracyofthedataanalysis.
Studyconceptanddesign:Cai,Coccarelli,Cocci. Acquisitionofdata:Crisci,Coccarelli,Cocci.
Analysisandinterpretationofdata:Cai,Ruggera,Lanzafame,Caciagli. Draftingofthemanuscript:Cai,Cocci.
Critical revision of the manuscript for important intellectual content: Trinchieri,Bonkat,Johansen.
Statisticalanalysis:Cai. Obtainingfunding:None.
Administrative,technical,ormaterialsupport:None. Supervision:Perletti,Malossini,Carini,Bartoletti. Other:None.
Financialdisclosures:TommasoCaicertifiesthatallconflictsofinterest, includingspecificfinancialinterestsandrelationshipsandaffiliations relevanttothesubjectmatterormaterialsdiscussedinthemanuscript (eg,employment/affiliation,grantsorfunding,consultancies,honoraria, stockownershiporoptions,experttestimony,royalties,orpatentsfiled, received,orpending),arethefollowing:None.
Funding/Supportandroleofthesponsor:None.
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