Key words β I
Table. Observationandtestschedule Testschedule Observation/Tests Beforetreatment Endoftreatment 5 9days aftercompletion oftreatment 4 6weeks aftercompletion oftreatment Informedconsent Patientbackground Atanytime Drugadministrationcompliance Symptoms Adverseevent Atanytime Pyuria No.ofbacteriainurine Bacteriologicaltests Clinicallaboratorytests required asneeded Escherichia coli µ γ
Table. Patientsevaluated Group Enroled Overalsafety Earlyevaluation(endoftreatment) Overalclinicaleficacy Lateevaluation(5 9daysaftercompletionoftreatment) microbiologicaloutcome clinicaloutcome Folow-upevaluation(4 6weeksaftercompletionoftreatment) microbiologicaloutcome clinicaloutcome Subjects 8 85 5 56 36 9 8 Corynebacterium Lactobacillus II
Table3. Treatmentduration No.ofsubjects Diagnosis(days) 3 4 5 6 8 3 Total Pyelonephritis 0 0 0 0 8 0 9 9 Cystitis 0 80 66 Total 3 85 0 89 85 Diagnosis Gender Age(yr) Bodyweight(kg) Symptoms UTIgroup Characteristics pyelonephritis cystitis male female mean±sd mean±sd No Yes G- G-3 G-4 G-6 Table4. Patientprofiles Treatment(days) n= (%) (9.) 0(90.9) 48(6.3) 9(3.) 0.±.5 56.±9.5 (5.6) 65(84.4) 0 3(3.9) 44(5.) 30(39.0) n= 80(%) 8(0.0) (90.0) 44(55.0) 36(45.0).3±9. 59.4±.0 8(0.0) (90.0) 0 5(6.3) 40(50.0) 35(43.8) Total n= 5(%) 5(9.6) (90.4) 9(58.6) 65(4.4).0±. 5.8±0.4 0(.) 3(8.3) 0 8(5.) 84(53.5) 65(4.4) Underlyingdisease a) neurogenicbladderdysfunction 50(.9) 44(55.0) 94(59.9) benignprostatichypertrophy (35.) 34(4.5) 6(38.9) Surgicalhistory Self-catheterization urinarycalculus other No Yes No Yes 6(.8) 5(9.5) 6(8.0) 0(3.0) (83.) 3(6.9) 0(.5) (.5) (90.0) 8(0.0) (96.3) 3(3.8) 6(0.) 3(3.6) 39(88.5) 8(.5) (89.8) 6(0.) Pretreatment with No 5(9.4) 8(9.5) 53(9.5) antimicrobialagents Yes (.6) (.5) 4(.5) Concomitantdrug Creatinineclearance (Cockcroft) (ml/min) a) Duplicatetotal No Yes < 50 50 to< 80 80 mean±sd (.3) 66(85.) 5(9.5) 4(54.5) 0(6.0) 0.8±30.8 8(0.0) (90.0) 0(.5) 49(6.3) (6.3) 69.5±9. 9(.) 38(8.9) 5(5.9) 9(58.0) 4(6.) 0.±5.4
Bacteriuria(days) Eliminated Decreased Replaced Unchanged Efectonpyuria(%) Table5. Overalclinicaleficacy(evaluationatendoftreatment) Pyuria Cleared 4 49 4 45(58.4) 56(0.0) Decreased 6 9 6(.8) (5.0) Unchanged 6 3 6(33.8) (5.0) Efecton bacteriuria(%) 59(6.6) (80.0) (.6) (.5) 3(3.9) 5(6.3) 3(6.9) 9(.3) (00) 80(00) Excelent 4(53.) Overaleficacy(%) (%) 49(6.3) -daystreatment 6/(80.5) Moderate (.3) -daystreatment 69/80(86.3) (%) 0(5.0) total 3/5(83.4) Poor(%) 5(9.5) (3.8) Table6. Overaleficacy(evaluationatendoftreatment) Treatment(days) Total(%) Total 6/(80.5) 69/80(86.3) 3/5(83.4) Pyelonephritis Cystitis 4/(5.) 58/0(8.9) /8(8.5) 6/(86.) /5(3.3) 0/(84.5) µ E. coli Enterococcus faecalis Klebsiella pneumoniae Pseudomonas aeruginosa µ µ µ µ E. coli E. faecalis
Table. BacteriologicalresponsebyMIC(evaluationatendoftreatment) MIC(μ g/ml) Isolates 0.06 0. 0.5 0.5 4 8 6 3 GPBsubtotal 0/0 8/8 / 4/45 5/5 / 5/5 /6 Staphylococcusaureus / / / / S.aureus(MRSA) / Staphylococcusepidermidis / / / Staphylococcussaprophyticus / Staphylococcuscapitis / / Coagulase-negativeStaphylococci 6/6 / / / / Streptococcusagalactiae 3/3 / / 4/5 Streptococcussalivarius / Enterococcusfaecalis 6/6 35/38 4/4 / 6/8 Enterococcusfaecium / / 0/ Enterococcusavium / Enterococcusdurans Enterococcusgalinarum / GNBsubtotal /3 4/4 6/6 / 5/5 5/5 3/4 /4 4/ /4 Escherichiacoli 43/44 / 4/4 5/5 / / 3/4 /3 4/9 0/ E.coli(ESBL) / /3 0/ Citrobacterfreundi / Citrobacterkoseri / Klebsielapneumoniae / / / / Klebsielaoxytoca / Enterobacteraerogenes / Enterobactercloacae / / 0/ Enterobacteriaceae / Proteusmirabilis 3/3 / Morganelamorgani 4/4 / Seratiamarcescens / / / Providenciaalcalifaciens / Pseudomonasaeruginosa 5/5 / / 0/ Burkholderiacepacia / Acinetobactercalcoaceticus / Acinetobacterlwofi 0/ Total /3 / / 4/4 4/50 0/0 5/6 /4 9/6 3/0 (eradication,%) (98.6) (00) (00) (00) (94.0) (00) (83.3) (56.3) (65.0) GPB:Gram-positivebacteria,GNB:Gram-negativebacteria /5 0/ 0/3 / / / / 3/ (4.9) 8 > 8 /4 /4 /4 /4 Total(%) 99/ (88.4) 8/0 (80.0) 3/5 5/5 / 3/3 /3 (9.3) / (9.) / 5/60 (86.) /3 / / / 6/30 65/5 3/5 / / 6/6 / / 3/4 / 4/4 5/6 4/4 / 8/9 / / 0/ 5/4 (88.8) (89.) (86.) (00) (88.9)
Table8. MICsversusPFGEpaternbetweenisolatesfrom patientsreceivedbeforeand aftertreatment No. Isolatespersisting Escherichiacoli Enterococcusfaecalis 3 Enterococcusfaecalis 4 Enterococcusfaecalis 5 Escherichiacoli 6 Escherichiacoli Pseudomonasaeruginosa 8 Escherichiacoli 9 Enterobactercloacae 0 Escherichiacoli Escherichiacoli Acinetobacterlwofi 3 Escherichiacoli Escherichiacoli 5 Streptococcusagalactiae 6 Enterococcusfaecalis Enterococcusfaecalis 8 Enterococcusfaecium 9 Morganelamorgani 0 Escherichiacoli Escherichiacoli Enterococcusfaecalis 3 Coagulase-negativeStaphylococci 4 Enterococcusfaecalis 5 Enterococcusfaecalis 6 Staphylococcusaureus Staphylococcusaureus(MRSA) PFGE:pulsed-fieldgelelectrophoresis LVFX MIC(μ g/ml) Before treatment 0.06 4 8 8 6 6 6 6 6 6 6 3 3 3 3 3 3 3 > 8 > 8 Endof treatment 3 8 3 3 8 6 3 3 3 6 6 > 8 6 3 3 3 3 3 3 3 3 > 8 > 8 PFGE Disagree Disagree Disagree Disagree Disagree Similar unknown Similar Similar E. coli K. pneumoniae E. faecalis P. aeruginosa
Table9. Strainsappearingaftertreatment Isolates Staphylococcusaureus(MRSA) Staphylococcusepidermidis Staphylococcuscapitis Coagulase-negativeStaphylococci GPB Streptococcusagalactiae Enterococcusfaecalis Enterococcusfaecium Enterococcusavium Enterococcussp. Escherichiacoli Escherichiacoli(ESBL) Klebsielapneumoniae Enterobacteriaceae Morganelamorgani GNB Pseudomonasaeruginosa Stenotrophomonasmaltophilia Alcaligenesfaecalis Chryseobacterium meningosepticum Glucosenon-fermentinggram-negativerods Candidaalbicans Others Candidaglabrata Totalstrains Patientsinwhom strainsappeared/alpatients (%) GPB:Gram-positivebacteria,GNB:Gram-negativebacteria Endoftreatment 0 0 CFU/mL 3 5 3 5 4 9 5/5 (5.9) 5 9daysaftertreatment 0 0 3 CFU/mL 0 4 0 CFU/mL 3 8 6 5 0 4 55 8 4/50 /50 (.3) (.0) Table0. Microbiologicaleradicationandclinicalcure(evaluation5 9daysaftercompletionoftreatment) Evaluation Microbiological eradication Diagnosis total pyelonephritis cystitis total -daytreatment 40/6(5.6) /(8.6) 38/69(55.) 40/(6.5) -daytreatment 55/80(68.8) /8(8.5) 48/(66.) 4/(56.9) Total(%) 95/56(60.9) 9/5(60.0) 86/(6.0) 8/36(59.6) Clinicalcure pyelonephritis /6(33.3) 5/(.4) /3(53.8) cystitis 38/58(65.5) 36/65(55.4) 4/3(60.)
Table. BacteriologicalresponsebyMIC(evaluation5 9daysaftercompletionoftreatment) MIC(μ g/ml) Isolates 0.06 0. 0.5 0.5 4 8 6 3 GPBsubtotal 0/0 8/8 / 39/44 /5 / 4/5 9/6 /5 Staphylococcusaureus / / / / S.aureus(MRSA) / Staphylococcusepidermidis / / / Staphylococcuscapitis / / Coagulase-negativeStaphylococci 6/6 / / / 0/ 0/ Streptococcusagalactiae 3/3 / / 3/5 Streptococcussalivarius / Enterococcusfaecalis 6/6 3/3 /4 / 5/8 0/3 Enterococcusfaecium / / 0/ Enterococcusavium / Enterococcusdurans / Enterococcusgalinarum / GNBsubtotal 0/ 4/4 4/6 0/ 4/5 4/5 /4 /4 5/8 3/4 / Escherichiacoli 43/44 / 3/4 4/4 / / /4 /3 4/6 / / E.coli(ESBL) 0/ / / Citrobacterfreundi / Citrobacterkoseri / Klebsielapneumoniae / / 0/ / Klebsielaoxytoca / Enterobacteraerogenes / Enterobactercloacae / / 0/ Enterobacteriaceae / Proteusmirabilis 3/3 0/ Morganelamorgani 3/3 / Seratiamarcescens / / 0/ 0/ Providenciaalcalifaciens / Pseudomonasaeruginosa 4/5 / / 0/ Burkholderiacepacia / Acinetobactercalcoaceticus / Acinetobacterlwofi / Total 0/ / / / 43/49 6/0 4/6 /4 9/3 /0 / (eradication,%) (98.6) (00) (85.) (95.5) (8.8) (60.0) (66.) (69.) (60.0) (8.6) GPB:Gram-positivebacteria,GNB:Gram-negativebacteria 8 > 8 /4 /4 /4 /4 Total(%) 88/0 (80.0) 8/0 (80.0) 3/5 5/5 3/3 0/3 (6.9) 0/ (83.3) / 45/59 (6.3) /3 / / / 08/4 (8.) 63/ (88.) 3/4 / / /5 (93.3) / / 3/4 / 3/4 4/5 /4 / /9 (.8) / / / 96/34 (83.8) γ III E. coli µ
Table. Microbiologicaleradicationandclinicalcure(evaluation4 6weeksaftercompletionof treatment) Evaluation Microbiological eradication Diagnosis total pyelonephritis cystitis total -daytreatment 8/36(.8) /(00) 6/34(6.5) 6/33(8.8) -daytreatment 4/55(6.4) 4/(5.) 38/48(9.) 34/49(69.4) Total(%) 0/9(6.9) 6/9(66.) /8(8.0) 60/8(3.) Clinicalcure pyelonephritis /(00) 5/6(83.3) 6/(85.) cystitis 5/3(8.) 9/43(6.4) 54/5(.0) Table3. Adversedrugreactionsincidence Treatment(day) <_ Total Patientsevaluatedforsafety 96 89 85 Patientswithadversedrugreactions 9(9.8) (5.) 33(.8) 95%CI (.8,.8) (8.,3.3) (.3,3.4) Events 9 46 System organclassandpreferedterm a) Patients(%) Patients(%) Patients(%) Metabolism andnutritiondisorders (.) (.) Anorexia (.0) (0.5) Decreasedappetite (.0) (0.5) Psychiatricdisorders (.) (.) Initialinsomnia (.) (.) Nervoussystem disorders 3(3.) 3(.6) Dizziness 3(3.) 3(.6) Hypoaesthesia (.0) (0.5) Eyedisorders (.0) (0.5) Eyelidoedema (.0) (0.5) Vasculardisorders (.0) (0.5) Hotflush (.0) (0.5) Gastrointestinaldisorders (.3) (.9) (.6) Constipation (.) (0.5) Diarhoea 5(5.) (.) (3.8) Dyspepsia (.0) 3(3.4) 4(.) Nausea (.0) (0.5) Stomachdiscomfort (.0) (0.5) Vomiting (.) (.) Epigastricdiscomfort (.) (0.5) Skinandsubcutaneoustissuedisorders (.) (.) Pruritus (.) (0.5) Rash (.) (0.5) Generaldisordersandadministrationsiteconditions 4(4.) 4(.) Feelingabnormal (.) (.) Oedemaperipheral (.0) (0.5) Thirst (.0) (0.5) Investigations 3(3.) 5(5.6) 8(4.3) Alanineaminotransferaseincreased (.) (.) Aspartateaminotransferaseincreased (.) (.) Bloodcreatinephosphokinaseincreased (.0) (.) 3(.6) Eosinophilcountincreased (.) (0.5) Gamma-glutamyltransferaseincreased (.) (.) Glucoseurinepresent (.0) (0.5) Whitebloodcelcountdecreased (.0) (0.5) Bloodalkalinephosphataseincreased a) MedDRAV.9. (.) (0.5)
µ µ E. coli µ