Management of urinary tract infections in female general practice patients

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1 The Author (2005). Published by Oxford University Press. All rights reserved. For Permissions, plese emil: doi: /fmpr/cmh720 Fmily Prctice Advnce Access originlly published online on 7 Jnury 2005 Mngement of urinry trct infections in femle generl prctice ptients Ev Hummers-Prdier, Ann Mrit Ohse, Mtthis Koch b, Wolfgng R Heizmnn c nd Michel M Kochen Hummers-Prdier E, Ohse AM, Koch M, Heizmnn WR nd Kochen MM. Mngement of urinry trct infections in femle generl prctice ptients. Fmily Prctice 2005; 22: Bckground. Though guidelines for the mngement of urinry trct infections (UTI) exist in severl Europen countries, little is known bout GPs dherence, nd the ppropriteness of their mngement with regrd to ntibiotic resistnce. Objectives. To describe Germn GPs mngement of femle ptients with symptoms of UTI, to ssess the dignostic ccurcy of dipsticks in Germn generl prctice setting, to develop dignostic prediction rules for culture-confirmed UTI, nd to compre the dequcy of empiricl tretment strtegies nd GPs ctul prescriptions. Methods. In 36 (of 118 invited) teching generl prctices, urine cultures nd resistnce testing were performed during 4 months on ll symptomtic ptients. GPs completed questionnire on ech ptients symptoms, risk fctors nd tretment. Adequcy of different tretment pproches ws clculted bsed on culture results. Results. 445 dult women (76% of ll ptients) were included, with medin ge of 53 yers. Complicting fctors were present in 27%. Urine culture reveled UTI in 77%. GPs dignostic ccurcy, using both dipsticks nd clinicl impressions, ws low. A positive nitrite test, dysuri nd older ge were the only predictive fctors of culture-confirmed UTI, however the negtive predictive vlue of dipsticks is low (35%). Empiricl tretment of ll symptomtic ptients with either nitrofurntoin or fluoroquinolones would result in higher rte of pproprite therpies thn the individulized pproch chosen by the GPs. Conclusion. Most ptients with urinry symptoms were not treted ccording to current guidelines, nd GPs dignostic nd therpeutic ccurcy ws low. Empiricl tretment of ll symptomtic ptients is probbly the most effective policy, but implies unnecessry ntibiotic prescriptions. Keywords. Anti-bcteril gents/therpeutic use, fmily prctice, femle, physicin s prctice ptterns, sensitivity nd specificity, urinry trct infection. Introduction Urinry trct infections (UTIs) re common in women, nd frequent reson to prescribe ntibiotics in generl prctice. Guidelines on mngement hve been published in severl Europen countries, nd in the US. Recommendtions for the decision to tret nd first line ntibiotics re summrized in Tble Received 10 June 2004; Accepted 27 Spetember Deprtment of Generl Prctice, University of Göttingen, Humboldtllee 38, Göttingen, b Medicl prtnership Wgner Stibbe Kst Bispink & Prtner, Werner-von-Siemens- Str. 10, Göttingen nd c Institute for Microbiology nd Infectiology, Mhlower Str. 24, Berlin, Germny. Correspondence to Dr Ev Hummers-Prdier, Deprtment of Generl Prctice, University of Göttingen, Humboldtllee 38, Göttingen, Germny; Emil: ehummer@gwdg.de Empiric tretment with first choice ntibiotics (trimethoprim, nitrofurntoin, in the US: cotrimoxzole) is usully recommended, either for ll symptomtic women without dditionl risk fctors, or fter using dipsticks to identify ptients with high probbility of UTI. However, recently, there hs been some discussion on pproprite dignosis nd trgeting of ntiobiotic prescriptions to contin rising resistnce levels in urinry pthogens. 7 9 The ims of our study were: to describe Germn GPs mngement of femle ptients with symptoms of UTI; to ssess the dignostic ccurcy of dipsticks in Germn generl prctice setting; to develop dignostic prediction rules for microbiologiclly confirmed UTI; 71

2 72 Fmily Prctice n interntionl journl TABLE 1 Interntionl guidelines on mngement of uncomplicted urinry trct infections in women Country Tret in presence of First choice drugs (empicl tretment) Germny 1 Symptoms nd both nitrite nd leucocytes on dipstick Trimethoprim or nitrofurntoin The Netherlnds 2 Symptoms nd nitrite on dipstick or dipstick negtive but Nitrofurntoin or trimethoprim bcteri on sediment microscopy or dipslide Norwy 3 Symptoms (urine exmintion not recommended) Trimethoprim or nitrofurntoin UK 4 Symptoms nd either leucocytes or nitrite on dipstick or Trimethoprim or nitrofurntoin or ceflexin leucocytes nd bcteri in ntive urine microscopy USA/Cnd 5 Symptoms nd history of UTI (phone mngement) Cotrimoxzole or symptoms nd leucocytes in dipstick or microscopy USA 6 Symptoms (phone mngement) or symptoms nd pyuri Cotrimoxzole or trimethoprim to estimte the ppropriteness of different pproches: empiric therpy of ll symptomtic ptients or tretment decisions bsed on dipstick results; nd to ssess the ppropriteness of GPs therpy with regrd to ntibiotic resistnce. Methods This survey is prt of lrger study on urinry trct infection in Germny, nd methods hve lredy been described elsewhere. 10 The locl ethics review bord hd no objections to the study. All 118 teching generl prctices of the Deprtment of Generl Prctice, University of Göttingen, were invited for this study nd 36 (31%) greed to prticipte (8 femle GPs, 14 working in group prctices with 2 4 prtners). During the study period of 4 months (November 2000 Februry 2001), ctive prticiption ws encourged by regulr telephone monitoring of the prctices. To mximise generlizbility nd to reflect dily prctice, we choose rther open inclusion criteri for consecutive smple: ll ptients presenting to the prticipting prctices in whom the GPs suspected UTI bsed on symptoms were to be recruited prospectively, including those with risk fctors, comorbidity or recent ntibiotic tretment. Only ptients with n obvious other dignosis explining their symptoms (i.e. vginitis) should be excluded. Ptients were to be mnged s usul ccording to the GPs judgement. The use of dipsticks s well s prescription of empiricl tretment ws t GPs discretion. Ech ptient s ge, sex, current symptoms nd risk or complicting fctors s well s results of dipstick tests nd dignostic procedures (if performed) nd tretment were documented on short, structured form identified by ptient code number. The reference stndrd for this study ws conventionl urine culture. In ddition to their usul proceeding nd for the purpose of this study, GPs were required to order culture for ll ptients (regrdless of dipstick results) before beginning tretment, but to wit for the culture results only if this would hve been their usul policy. According to current recommendtions, GPs were to smple freshly voided urine only, but midstrem smpling ws not required. 1,4,11 Urine smples were stored in sterile continers supplied by the lbortory nd kept refrigerted until processing the sme dy t the lbortory. A urine culture ws performed nd ntibiotic susceptibility tested in cse of bcteril growth, using interntionlly recommended stndrd procedures. 12,13 All cultures nd susceptibility tests were performed by three trined microbiology technicins in the sme specilised lbortory (Medicl Prtnership Wgner Stibbe Kst Bispink & Prtners). Technicins were informed of ny prticulr question or informtion the GPs hd noted on the order form (usully nothing). However, they hd no ccess to the documenttion form, dipstick results, or other clinicl informtion. Susceptibility testing ws performed in smples with more thn 10 2 CFU/ml nd less thn 3 pthogens, though interntionl literture now suggests tht 10 2 CFU/ml re consistent with UTI. 14,15 Therefore, we did not restrict our nlysis to trditionlly defined high count UTI ( 10 5 CFU/ml), but lso included cultures yielding low count bcteriuri ( 10 2 CFU/ml) or mixed growth in our definition of UTI. Culture results were lbelled with the ptients code numbers nd communicted to the deprtment of generl prctice. Prticipting GPs were informed of culture results ssigned to ptients nmes. Documenttion forms were collected by the lbortory s trnsport service together with the urine smples for the GPs convenience. They were then sent to the deprtment of generl prctice without ny further processing nd without disclosing ptients identity. There, ll dt were entered into SAS, Version 8; 16 ptients documenttion nd lbortory results were linked with the ptient code number. Descriptive sttistics, 2 2 contingency tbles nd logistic regression models [odds rtios (OR), 95% confidence intervls (CI)] were clculted in SAS. Age (younger thn 50, 50 74,

3 Mngement of urinry trct infections 73 older thn 74), dysuri, urgency/ frequency, flnk pin, fever, relpse (within 2 weeks of lst episode) or recurrent UTI (more thn 2 weeks since lst episode), presence of ny dditionl risk fctors, s well s leucocytes nd nitrite on dipsticks were used s independent vribles to compre GPs dignostic decision with prediction of culture-confirmed UTI. In order to ssess the dequcy of different tretment pproches, dummy vribles were used. The tretment prescribed by the study GPs ws ssessed using dummy vrible indicting resistnce to the ntibiotic chosen. Generlly, not treting culture-confirmed UTI with ntibiotics ws considered indequte, s well s tretment with n ntibiotic to which the pthogen ws resistnt (cultures with intermedite susceptibility to fluoroquinolones were considered susceptible). Antibiotic tretment for ptients with sterile urine ws lso considered indequte. Not treting ptients with sterile urine nd treting ptients with UTI with n ntibiotic to which the pthogen is susceptible is considered dequte. If informtion ws missing, i.e. either dipsticks or susceptibility testing hd not been performed or the ntibiotic prescribed hd not been specified by the GP, dequcy ws defined s unknown. Tretment durtion ws not considered when ssessing dequcy, s no precise recommendtions re vilble for elderly ptients. Results Of the 118 invited GPs, 36 (31%) prticipted in the study (8 women, 14 working in group prctices with 2 4 prtners). 585 ptients of both sexes were recruited within 4 months. Only the subgroup of dult women (76%, n = 445) is considered here. Results of mle ptients hve been nlysed nd published seprtely, 10 s well s detiled nlysis of fctors predicting ntibiotic resistnce. Symptoms were documented on the study sheet in 89% of the women; medin durtion of symptoms ws 3 dys. Ptients chrcteristics, symptoms nd risk fctors re presented in Tble 2. GPs dignostic procedures, dignoses nd prescriptions re presented in Tble 3. Medin ntibiotic tretment durtion ws 5 dys, irrespective of ptients ge nd presence of complicting fctors. 70% of young ptients with uncomplicted UTI were treted for longer thn 3 dys. On the other hnd, 25% of ptients of ny ge with dditionl risk fctors (complicted UTI) received ntibiotics for 3 dys or less. One fifth (19.3%) of the ptients were not prescribed ntibiotics though their GPs hd dignosed UTI. These ptients were less likely to hve dipsticks positive for nitrite (OR 0.38, 95% CI ) nd leucocytes (OR 0.48; 95% CI ) thn those who hd been prescribed ntibiotics. Ptients who hd flnk pin, but in whom GPs hd dignosed UTI rther thn pyelonephritis were less likely to receive ntibiotics thn other ptients with TABLE 2 Chrcteristics of dult femle ptients with suspected UTI (n=445) Age (medin, interqurtile rnge) 53 (33 71) 50 yers 45% yers 33% 75 yers 22% Relpse within 14 dys since lst episode 12% Reinfection 14 dys since lst episode 23% Symptoms 89% Urgency/frequency 55% Dysuri 52% Kidney/flnk pin 17% Suprpubic pin 14% Others 12% Additionl risk fctors 27% Dibetes 9% Antibiotics in the lst 2 weeks 7% Indwelling ctheter 3% History of urinry surgery 3% Neurologic voiding dysfunction 3% Renl filure 4% Pregnncy 1% Others 12% TABLE 3 GPs mngement of women with suspected UTI (n 445) Dignostic procedures Dipstick test 92% Sediment microscopy 44% Physicl exmintion 38% Ultrsound of urinry trct 15% Referrl 3% Control consulttion recommended 43% GPs dignosis UTI 64% Urethrl syndrome 16% (Suspected) pyelonephritis 5% Others 7% Helthy/no dignosis 8% GPs prescriptions None 36% Antibiotics 56% Cotrimoxzole 46% Fluoroquinolones 33% Nitrofurntoin 2% Trimethoprim 13% Cefixim/cefuroxime 2% Others 4% Spsmolytics 2% Herbl drug 9% Other/not specified 3% Durtion of ntibiotic tretment (medin/dys) Uncomplicted, ge 50 5 Uncomplicted, ge Uncomplicted, ge 74 5 Complicted (ny ge) 5 Ptients with suspected pyelonephritis excluded. UTI (OR 2.94; 95% CI ). Treted nd untreted ptients with GP-dignosed UTI did not differ with regrd to other symptoms, ge, recurrent UTI or risk fctors.

4 74 Fmily Prctice n interntionl journl Urine culture results were vilble for 430 ptients (97%); results re shown in Tble 4. Bcteril species were identified in the 282 ptients with 10 3 cfu/ml or more nd no more thn two pthogens: 67.7% were TABLE 4 Results of urine cultures (vilble for n 430 ptients) n % Sterile urine % UTI 10 2 cfu/ml, single growth % UTI 10 2 cfu/ml, 2 pthogens % UTI 10 2 cfu/ml, 3 pthogens % Low count UTI 10 2 cfu/ml % Resistnce levels in ll cultures with more thn 10 2 cfu/ml nd less thn 3 pthogens (n = 298 ) Antibiotic % resistnt pthogens Amoxicillin 36.9 Co-moxiclv 28.5 Cefzolin 38.6 Cefixime 16.1 Gentmicin 21.5 Ofloxcin b 6.7 Ciprofloxcin b 6.4 Co-trimoxzole 31.5 Trimethoprim 33.6 Nitrofurntoin 13.1 Refers to 265 ptients; in 33 ptients two pthogens were tested for susceptibility. b 17% of ll pthogens hd intermedite susceptibility to ofloxcin nd ciprofloxcin. As fluoroquinolones re likely to be cliniclly effective for UTI in these ptients, they were considered susceptible. infected with Escherichi coli, 10.3% with enterococci, 9.6% with Proteus spp., 7.4% with Streptococcus glctie, severl others were found in 1 4 urine smples, respectively. Prediction rule for UTI GPs pprently dignosed UTI bsed on both their clinicl ssessment nd dipstick tests, which hd been performed in 91.6% of ll ptients. Detiled documenttion of stepwise pproch ws not vilble for fesibility resons. Tble 5 illustrtes the dignostic vlue of dipsticks with regrd to culture results. Tble 6 compres predictors for GPs dignosis of infection (either UTI or pyelonephritis) nd cultureconfirmed bcteriuri. Fever (OR 6.44, 95% CI ) nd flnk pin (OR 22.06, 95% CI ) were the only significnt predictors for dignosis of pyelonephritis; however, one in 5 ptients with either fever or flnk pin ws dignosed s not hving pyelonephrits (dt not shown). Using cultureconfirmed UTI ( 10 2 CFU/ml) s gold stndrd, GPs dignosis hd sensitivity of 70.8% nd specificity of 38.8%, the positive predictive vlue (PPV) ws 79.7%, the negtive predictive vlue (NPV) 28.2%. Adequcy of different tretment pproches Figure 1 illustrtes the ppropriteness of tretment decisions for ll ptients in this study in flow chrt. 60.2% of the 332 ptients with culture-confirmed UTI received ntibiotics, nd 42.9% of those with sterile urine (n = 98). 39.8% of ll women with UTI received no tretment. In 24% of the women with UTI who were prescribed ntibiotics, pthogens were resistnt to the tretment nd this occurred significntly more often in ptients with complicting fctors (52.1 versus 22.5%; OR 3.74; 95% CI ). TABLE 5 Dipstick test results nd dignostic vlue with regrd to ny UTI 10 2 CFU/ml, including mixed growth Totls Nitrite Nitrite Leucocytes Leucocytes Both positive At lest positive negtive positive negtive one positive UTI Sterile urine Totls Sensitivity (%) Specificity (%) PPV b (%) NPV c (%) Pos. likelihood rtio Post-test probbility (%) Dipstick nd cultures hd been performed in ll ptients. Urine culture ws not vilble for 15 ptients; dipsticks hd not been performed in 36 ptients. b Positive predictive vlue. c Negtive predictive vlue.

5 Mngement of urinry trct infections 75 A simultion of different therpeutic strtegies is presented in Tble 7; nd the dequcy of empiric tretment with severl ntibiotics of either ll ptients with suspected UTI or ptients with positive nitrite test is compred with the tretment prescribed by the GPs in our study. Discussion Our cross-sectionl study combines results of systemtic urine cultures with n observtionl survey of GPs TABLE 6 Comprison of fctors predicting GPs dignosis nd culture results (multivrite logistic regression; significnt predictors in bold type) Independent vrible UTI or pyelonephritis Culture-confirmed dignosed UTI 10 2 cfu/ml by GP OR (95% CI) OR (95% CI) Nitrite on dipstick 2.77 ( ) 3.41 ( ) Leucocytes on dipstick 3.53 ( ) 1.57 ( ) Complicting fctors 1.04 ( ) 1.16 ( ) Dysuri 7.59 ( ) 1.97 ( ) Flnk pin 6.39 ( ) 0.44 ( ) Urgency/frequency 2.28 ( ) 0.87 ( ) Suprpubic pin 1.67 ( ) 0.88 ( ) Fever ( ) 2.37 ( ) Relpse 1.66 ( ) 0.61 ( ) Reinfection 2.30 ( ) 1.51 ( ) Older ge ( 50, 1.36 ( ) 1.48 ( ) 50 74, 74) mngement in of women with suspected UTI, llowing us to ssess the ppropriteness of GPs prescriptions. GPs dignosed UTI on bsis of both dipsticks nd clinicl impression of symptoms, resulting in reltively low positive nd negtive predictive vlues when compred to culture results. Dipsticks cn confirm UTI, but re not very helpful in identifying ptients with sterile urine. Ptients with uncomplicted UTI were often treted for longer thn recommended, nd secondchoice ntibiotics were prescribed to lrge proportion of ll ptients. Both under-tretment of ptients with UTI nd over-tretment of ptients with sterile urine occurred frequently. Similr non-dherence to UTI guidelines hs been described in other countries. 17 GPs prticipting in our survey were not routinely involved in reserch, they prctice in both rurl nd urbn settings. Though there my be selection bis concerning GPs, their ptients re not likely to differ from ptients in non-prticipting prctices. Typicl for generl prctice studies in countries without prctice lists, we do not know the precise ctchment rte of our study, but hd to rely on prticipting GPs to include ll their eligible ptients. 18,19 We ttempted to ensure ctive prticiption though regulr telephone monitoring. The number of included ptients (of both sexes) corresponds to the prctice prevlence reported in other Germn studies on UTI. 20,21 All urine cultures nd susceptibility tests were performed in single lbortory, but dipsticks were ssessed by the individul GPs (or their prctice stff), who reported their reding. Though GPs reding of urinry dipsticks is known to vry, our pproch reflects prctice relity better thn stndrdised reding in study centre (which ws not done for fesibility resons). 22, ptients 249 ntibiotics 196 no ntibiotics 7 no culture vilble 200 UTI 42 sterile urine 56 sterile urine 132 UTI 8 no culture vilble 148 UTI > 10² cfu/ml 20 UTI 10² cfu/ml 32 mixed growth 82 UTI > 10² cfu/ml 30 UTI 10² cfu/ml 20 mixed growth 111 susceptible 9 susceptible 11 ntibiogrm 33 resistnt 15 resistnt 9 no ntibiogrm 4 ntibiotic not specified 8 no ntibiogrm, 3 species FIGURE 1 Adequcy of ll ptients mngement with regrd to the presence of culture-confirmed UTI nd susceptibility to the individul ntibiotic prescribed in ech cse

6 76 Fmily Prctice n interntionl journl TABLE 7 Clculted dequcy of different tretment pproches (n=445 ptients) Tretment option Adequtely Indequtely Adequcy treted treted cnnot be ptients ptients judged, missing n (%) n (%) informtion n (%) Tretment s 176 (39.5) 222 (49.9) 47 (10.6) prescribed by GPs Empiricl tretment 222 (49.9) 137 (30.8) 86 (19.3) nitrofurntoin Empiricl tretment 168 (37.8) 191 (42.9) 86 (19.3) trimethoprim Empiricl tretment 241 (54.2) 118 (26.5) 86 (19.3) fluoroquinolone Nitrofurntoin if 165 (37.1) 167 (37.5) 113 (25.4) nitrite positive Trimethoprim if 141 (31.7) 191 (42.9) 113 (25.4) nitrite positive Fluoroquinolone if 175 (39.3) 157 (35.3) 113 (25.4) nitrite positive GPs used dipsticks in most ptients, nd their results significntly contributed to the dignostic decision, with GPs relying more on leucocytes thn the nitrite test. Additionlly, severl symptoms nd erlier UTI episodes were tken into considertion. However, this mixed pproch resulted in poorer positive predictive vlue thn dipsticks lone, nd the negtive predictive vlues were similrly low. Culture-confirmed UTI ws significntly predicted by positive nitrite test, nd to lesser degree by the symptom dysuri nd older ge. Leucocytes on dipstick re not helpful. Due to low sensitivity nd negtive predictive vlues, dipsticks cn confirm dignosis in symptomtic ptients, but re not very relible in excluding UTI. 24 It is somewht surprising tht neither reported fever nor flnk pin were significntly ssocited with bcteriuri. In line with current recommendtions, GPs hd ssocited both symptoms with pyelonephritis, but decided ginst this dignosis in few ptients. Possibly, GPs were wre tht co-existing common conditions like virl infections or low bck pin could blur the picture. Only bout one third of ll ptients in our study were dequtely treted, nd in hlf of ll ptients either the decision to prescribe n ntibiotic or the ntibiotic chosen ws inpproprite. Our cross-sectionl survey did not llow us to determine clinicl effectiveness of tretment or evolution of symptoms in untreted ptients with UTI or ptients receiving ntibiotics to which their pthogens were resistnt. As sometimes clinicl results hve shown to be better thn in vitro susceptibility would predict, 7,25 it is possible tht some of our indequtely treted ptients hd fvourble clinicl outcome. Additionlly to the pprent difficulty in trgeting ntibiotic prescriptions, tretment durtion ws shorter thn recommended 1,2,4,14 in one qurter of ptients with dditionl risk fctors, nd longer thn necessry in most young women with uncomplicted UTI. 26 In our comprison of different tretment pproches to the ptients in this study, empiricl tretment with either nitrofurntoin or fluoroquinolones proved superior, nd empiricl tretment with trimethoprim ws equivlent to the individulized pproch preferred by the study GPs. Tretment of ll symptomtic ptients hs been shown to be the most cost-effective option, 27 but costs of rising resistnce levels were not considered. 28 However, this would result in indequte tretment for one qurter to one third of ll ptients, including unnecessry ntibiotic exposure of ptients who did not hve UTI (22% in our study). This should be reson for concern in presence of high resistnce levels for ll common ntibiotics. 29,30,31 In our study, pthogens proved resistnt to the ntibiotic the ptient hd received in lmost qurter of ll cses. GPs seemed to be wre of resistnce problems nd choose to prescribe fluoroquinolones in one third of cses. Though still highly effective t the time of our study, the high prevlence of intermedite susceptibility indictes dropping susceptibility level: in Germny, the level of resistnce ginst ciprofloxcin in E.coli incresed from 7.7% in 1998 to 14.5 % in nd similr tendencies hve been observed in other countries. 7,33 One possibility to reduce unnecessry ntibiotic use is to tret only ptients with positive nitrite test. This would hve reduced the number of indequtely treted ptients in our study (s dipsticks were performed for only 90% of the ptients, however, dequcy could not be judged in mny cses). Due to the low negtive predictive vlue of dipsticks, cultures should then be considered for symptomtic ptients with negtive nitrite test. Ordering cultures for ll ptients nd delying ntibiotic tretment until results re vilble could limit over-tretment. 8 However this would increse direct costs, nd often cultures would hve no impct on mngement. In mny ptients without dditionl risk fctors, UTI seems to be self-limiting condition: A survey in British prctice hs shown tht few women with urinry symptoms ctully consult doctor; 34 one tril in Belgium hs shown tht hlf of the ptients were free of symptoms fter 3 dys of plcebo. 35 Symptomtic tretment of uncomplicted UTI my be n option which merits further reserch. Acknowledgements We thnk ll prticipting GPs for their efforts nd co-opertion. We re grteful to Dr Thoms Fischer, Göttingen, for his comments on the mnuscript.

7 Declrtion Funding: the medicl lbortory prtnership Wgner, Stibbe, Kst, Bispink & Prtners sponsored the urine cultures nd susceptibility testing. Ethicl pprovl: the locl ethics review bord hd no objections to the study. Conflicts of interest: none. References 1 Hummers-Prdier E, Kochen MM. Dysuri. DEGAM-guideline No. 1. [in Germn] Z Allg Med 2000; 76: Timmermns AE, Bselier PJAM, Winkens RAG et l. NHG stndrd: urinry trct infection. [in Dutch] Huisrts Wet 1999; 42: Flottorp S, Oxmn AD, Cooper JG, Hjortdhl P, Sndberg S, Vorlnd LH. Guidelines for dignosis nd tretment of cute urinry trct problems in women [in Norwegin]. Tidsskr Nor Legeforen 2000; 120: Prodigy guidnce. Urinry trct infections (lower) women, %20-%20women (ccessed on June 14, 2004.) 5 University of Michign Helth System. UMHS urinry trct infection guideline. Ann Arbor (MI): University of Michign Helth System; summry.spx?ss=15&doc_id=2284&nbr=1510&string=urinry %20AND%20trct%20AND%20infection%20AND%20women (ccessed on June 14, 2004.) 6 Institute for Clinicl Systems Improvement (ICSI). Uncomplicted urinry trct infection in women. Bloomington (MN): Institute for Clinicl Systems Improvement (ICSI); guideline.gov/summry/summry.spx?ss=15&doc_id=3675& nbr=2901&string=urinry%20and%20trct%20and%20 infection%20and%20women (ccessed on June 14, 2004.) 7 Gupt K, Hooton TM, Stmm WE. Incresing ntimicrobil resistnce nd the mngement of uncomplicted communitycquired urinry trct infections. Ann Intern Med 2001; 135: Dvey P, Steinke D, McDonld T, Phillips G, Sullivn F. Not so simple cystitis: how should prescribers be supported to mke informed decisions bout the incresing prevlence of infections cused by drug-resistnt bcteri? Br J Gen Prct 2000; 50: Stmm WE. An epidemic of urinry trct infections? 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