Scandinavian Journal of Primary Health Care, 2013; 31: 235–240 ORIGINAL ARTICLE Different recommendations for empiric fi rst-choice antibiotic treatment of uncomplicated urinary tract infections in Europe JOSEPHINE MCQUISTON HASLUND1 , MARIANNE ROSBORG DINESEN1 , ANNI BRIT STERNHAGEN NIELSEN1 , CARL LLOR2 & L ARS BJERRUM 1 1 Section and Research Unit of General Practice, Department of Public Health, University of Copenhagen, Denmark, and 2 University Rovira I Virgili, Tarragona, Spain Abstract Objective . Uncomplicated urinary tract infection (uUTI) is a common reason for antibiotic treatment in primary health care. Due to the increasing prevalence of antibiotic-resistant uropathogens it is crucial to use the most appropriate antibi- otics for fi rst-choice empiric treatment of uUTI. Particularly, it is important to avoid antibiotics associated with a high rate of antimicrobial resistance. This study compares national recommendations from six European countries, investigating recommendations for fi rst-choice antibiotic therapy of uUTI. S etting . General practice in six European countries. M ethod . Searches were undertaken on PubMed, the Cochrane Library databases, Google, and Google Scholar. Recommendations from different geographical regions in Europe were investigated: Northern Europe (Denmark, Sweden), Western Europe (Scotland), Central Europe (Germany), Southern Europe (Spain), and Eastern Europe (Croatia). R esults . The six countries recommended seven different antibiotics. Five countries recommended more than one antibiotic as fi rst-choice treatment. Half of the countries recommended antibiotics associated with a high rate ((cid:2) 10 – 20%) of resistant E . coli. All countries recommended at least one antibiotic associated with a low ((cid:3) 5%) resistance rate. D iscussion . The differences in fi rst-choice treatment of uUTI could not be explained by differences in local bacterial aetiology or by different patterns of antimicro- bial resistance. Despite resistance rates exceeding 10– 20%, sulphamethizole, trimethoprim. or fl uoroquinolones were rec- ommended in half of the countries. Conclusion . Within the European countries there are considerable differences in recommendations for empiric fi rst-choice antibiotic treatment of uUTI. In order to reduce the increasing antimicrobial resistance in Europe, it is important to agree on the most appropriate antibiotics for empiric treatment of uUTI. Key Words: Antibiotics , a ntimicrobial resistance , Denmark , general practice , primary health care , recommendations , u ncomplicated urinary tract infection Introduction and bacterial eradication within a few days, making Uncomplicated urinary tract infection (uUTI) is one antibiotic treatment relevant [4,5]. of the most common infections in primary care [1]. Due to the increasing prevalence of antibiotic- Some 10% of all women will experience an episode resistant bacteria, particularly the extended spectrum of uUTI within a year. About 20% of all antibiotic beta-lactamase (ESBL) producing gram-negative prescriptions issued by GPs are for patients with bacteria, it is crucial to avoid antibiotic overprescribing. uUTI. Patients with uUTI are often treated empiri- Particularly, it is important to avoid antibiotics that cally without preceding culture or susceptibility test- provoke the emergence of antimicrobial resistance, ing, and the GP ’ s choice of antibiotics typically such as the so-called critically important antibiotics depends on traditions and national treatment recom- [6]. The pattern of microbial resistance and the use mendations. Without treatment, the infection is often of antibiotics vary considerably between countries self-limiting over time and only seldom associated [7]. During the last decade the resistance rate of with serious complications [2,3]. However, in most E. coli to fl uoroquinolone has increased, particularly cases, antibiotic treatment leads to symptom relief in the Southern European countries. In the Nordic Correspondence: Josephine McQuiston Haslund, Section and Research Unit of General Practice, Department of Public Health, Ø ster Farimagsgade 5, DK- 1014 Copenhagen K, Denmark. Tel: (cid:4) 45 35 32 79 60. Fax: (cid:4) 45 (cid:4) 45 35 32 79 46. E-mail: [email protected] (Received 22 January 2013; accepted 5 August 2013) ISSN 0281-3432 print/ISSN 1502-7724 online © 2013 Informa Healthcare DOI: 10.3109/02813432.2013.844410 236 J. M. Haslund et al. and Google Scholar. The following search terms were The increasing antimicrobial resistance in used: urinary tract infection , treatment , clinical guide- Europe makes it important to agree on the line, recommendations , and antimicrobial resistance. most appropriate antibiotics for empiric fi rst- Recommendations were included if they met the choice treatment of uncomplicated urinary following criteria: tract infections. • Recommendations for empiric antibiotic • National recommendation for empiric antibi- treatment of uncomplicated urinary tract otic treatment of uUTI in primary health infection differ considerably between six care. European countries. • Agreement about the defi nition of uUTI: • Half of the countries recommend antibiotics Acute urinary tract infection in a premenopausal, for which the resistance rate of E . coli is more non-pregnant woman, with no anatomical and than 10– 20%. functional abnormalities of the urogenital tract, no • Use of antibiotics with resistance rates recent instrumentation of the urinary tract, and no exceeding 10– 20% is associated with an comorbidity. increased risk of treatment failure and selec- • Language restriction to: English, Spanish, tion of resistant strains. German, Norwegian, Swedish, and Danish. Recommendations for treatment of recurrent UTI, complicated UTI (men, children, and patients with countries an increasing resistance rate of E . coli to comorbidity), postmenopausal and post-surgery UTI sulphamethizole and ampicillin is emerging [8]. In were excluded. all European countries, E. coli is the most frequent Recommendations from six countries in fi ve aetiology of uUTI, accounting for 80 – 90% of all different geographical areas of Europe were included: cases [9]. • Northern Europe: Denmark [14 – 17], Sweden According to the European Survey of Antibiotic [18]; Consumption (ESAC), resistant strains are respon- • Western Europe: Scotland [19]; sible for an attribute mortality of about 25 000 Euro- • Eastern Europe: Croatia [20]; peans yearly. A considerable part of this increased • S outhern Europe: Spain [21]; mortality is caused by complications of urinary tract • Central Europe: Germany [22]. infections [10]. To reduce the selection of resistant bacteria, empiric prescribing of broad-spectrum antibiotics Results should be avoided in patients with trivial and uncom- plicated infections, such as uUTI. Furthermore, Recommendations for fi rst-choice empiric antibiotic critically important antibiotics, such as fl uoroquino- treatment of patients with uUTI are given in Table I. lones, should be restricted to the most severe infec- In total, seven preparations from six different groups tions and always be preceded by a susceptibility test. of antimicrobials were recommended [23]. Moreover, antibiotics where resistance rates of the most frequent uropathogens exceed 10– 20% should • beta-lactams; be avoided due to an increased risk of treatment • sulphonamide; failure and complications [11– 13]. • trimethoprim; In order to reduce the increased risk of complica- • fl uoroquinolone; tions related to infections with resistant bacteria it is • phosphonic acid derivative; crucial to choose the most appropriate antibiotic for • furan derivative. fi rst-choice empiric treatment for uUTI. The aim Most countries [15– 19,21,22] included more than of this study was to compare recommendations one antibiotic as fi rst-choice recommendation for for empiric fi rst-choice empiric antibiotic treatment uUTI, but none of the preparations was recom- of uUTI in a selected number of countries, from mended by all countries. Nitrofurantoin was included different geographical areas of Europe. as fi rst-choice antibiotic in fi ve countries and pivme- cillinam in three countries. Spain [21] was the only country including fl uoroquinolone and amoxicillin/ Material and methods clavulanic acid as fi rst-choice recommendation, We searched (September 2011) for literature in the and Denmark was the only country recommending PubMed and Cochrane Library Databases, Google, sulphamethizole [14– 17]. Treatment recommendations for uUTI in Europe 237 Table I. Recommendations for fi rst choice antibiotic treatment of uUTI in Europe. Fosfomycine/ Amoxicillin/ Nitrofurantoin Pivmecillinam Trimethoprim Sulphamethizole Fluoroquinolone trometamol clavulanic acid Croatiaa √ Denmark b √ √ √ Germanyc √ √ √ Scotlandd √ √ Spain e √ √ √ √ Sweden f √ √ a Skerk V, Andrasevic AT, Andrasevic S, Susic E, Dzepina AM, Madaric V et al. [ISKRA guidelines on antimicrobial treatment and prophylaxis of urinary tract infections—Croatian national guidelines]. Lijec Vjesn 2009;131(5– 6):105– 118. b IRF, Institut for Rationel Farmakoterapi [internet]. Antibiotika til systemisk brug (Institute for Rational Pharmacotherapy, Antibiotics for Systemic Use). 12-2-2009. [cited 1– 5-2012]. Available from: http://www.irf.dk/dk/rekommandationsliste/infektionssygdomme/ antibiotika_systemisk_brug/test_sulfonamider_og_trimethoprim_j01e.htm. Basislisten 2011 [internet]. Basislisten, læ gens væ rkt ø j til rationel medicinordination. (The Basic list, the doctor’s tool for rational drug prescribing). [cited 3-2-2012]. Available from: https://www.sundhed.dk/content/cms/15/4915_2012-basislisten.pdf Helweg-Larsen J, Frimodt-Moller N, Nielsen H, Dahl Knudsen J, Holme P. Antibiotika (systemisk brug), baggrundsnotat, 2009. (Antibiotics (systemic use), background notes, 2009). [internet]. [cited 12-9-2009]. Available from: http://www.irf.dk/dk/rekommandationsliste/ baggrundsnotater/infektionssygdomme/antibiotika_systemisk_brug.htm#Uro-genitale_infektioner. Gahrn-Hansen B, Kolmos HJJ. Antibiotikapolitik og behandling af hyppigt forekommende infektioner i almen praksis. (Policy of antibiotics and treatment of common infections in general practice). Institute for Rational Pharmacotherapy. Danish Medicines Agency. 2001;7. c Wagenlehner FM, Schmiemann G, Hoyme U, Funfstuck R, Hummers-Pradier E, Kaase M et al. Nationale S3-Leitlinie, unkomplizierte harnwegsinfektionen. Empfehlungen zu terapie und management unkomplizierter bakterieller ambulant erworbener harnwegsinfektionen bei erwachsenen patienten. (S3-guideline for uncomplicated urinary tract infections - treatment guidelines compliance). Med Monatsschr Pharm 2011;34(5):164– 168. d Scottish Intercollegiate Guideline Network. Management of suspected bacterial urinary tract infection in adults. A national clinical guideline. 2012; 7– 12. e Rabanaque G, Romera Á , Domingo C, Herrera C, Plana A, Sá nchez J. Infecciones del tracto urinario. (Urinary tract infections). Manual de enfermedades infecciones en atenció n primaria. (Handbook of infectious diseases in primary helth care). Barcelona: 2010:153– 181. f Andr é M, Ahlqvist-Rastad J, Beermann B. Nedre urinvä gsinfektion (UVI) hos kvinnor - Behandlingsrekommendation. (Lower urinary tract infection (UTI) in women - Treatment recommendation). Lä kemedelsverket 2007;2:8– 15. Discussion resistant strains during recent years. Furthermore, we did not include information on the availability of The national recommendations for fi rst-choice different kinds of antibiotics in the countries included. empiric antibiotic treatment of uUTI varied consid- Some antibiotics may not be available in all the coun- erably between the six European countries. Nitro- tries and therefore would not be included in the furantoin and pivmecillinam were the preparations guideline. For example, pivmecillinam is at the most agreed upon; they were recommended in fi ve moment not available in Spain. and three countries, respectively. Spain was the only The differences found between the six countries country recommending fl uoroquinolones and amox- are considered to be minimum estimates of the real icillin/clavulanic acid as fi rst-choice antibiotic for differences in recommendations for antibiotic treat- uUTI. Denmark was the only country recommend- ment of uUTI between the European countries. ing sulphamethizole. Inclusion of more European countries might have Before conclusion, some limitations have to be taken into account. We have no information about led to a higher number of different recommendations the adherence to the recommendations in the differ- for fi rst-choice treatment of uUTI. Antibiotic resis- ent countries, and we are not aware of potential tance rates differ considerably between the countries regional recommendations that may have overruled (Table II). In all six countries E . coli has a high resis- the national recommendations. Furthermore, we tance rate against sulphamethizole (22– 37%) and may have overlooked guidelines that were not pub- trimethoprim (15– 32%), and a low resistance rate lished in peer-reviewed journals or available on the against nitrofurantoin ((cid:3) 5%), mecillinam (1– 5%) internet. This is, however, not likely since two of the and fosfomycine ((cid:3) 2%) [14– 22,24]. The rate of authors (JMH, MRD) searched separately. For each resistance to fl uoroquinolones, in urine gathered of the included countries we tried to identify the from the primary care sector, varies considerably newest guideline available. However, two guidelines between the European countries with the lowest rate were more than fi ve years old. Older guidelines may in Scotland (1%) and the highest rate in Spain (24%) not have accounted for the increased prevalence of [9,21,24]. Results of the susceptibility pattern of 238 J. M. Haslund et al. Table II. Antimicrobial resistance (%) for E . coli in urine samples from patients with urinary tract infections, in six European countries. Amoxicillin/ Nitrofurantoin Pivmecillinam Fosfomycine Sulfamethizole Trimethroprim Ciprofl oxacin clavulanic acid (%) (%) (%) (%) (%) (%) (%) Croatiaa 2 – – 24 * 24* 10 4 (2009) Denmark b 0 – 5 4 – 5 – 35– 38 10 – 28 11 – (2009) Germanyc 1 – 2 1 – 2 (cid:3) 1 25 – 26 * 25– 26 * 3 – 4 1 – 2 (2006) Scotland d * * 0 1– 2 (cid:3) 1 36 16– 17 1– 2 3 – 4 (2000) Spain e 3 – 4 4 1 – 2 32 * 32 * 23.9 8 (2006) Swedenf 1 3 1 15 * 15 * 5 – 10 25 (2007) Notes: * (cid:5) resistance to trimethroprim/sulfamethizole. – (cid:5) no data. a Skerk V, Andrasevic AT, Andrasevic S, Susic E, Dzepina AM, Madaric V et al. [ISKRA guidelines on antimicrobial treatment and prophylaxis of urinary tract infections—Croatian national guidelines]. Lijec Vjesn 2009;131(5– 6):105– 118. b Danmap 2009 [internet]. Use of antimicrobial agents and occurrence of antimicrobial resistance from food animals, fruits and humans in Denmark. [cited 1– 6-2011.] Available from: www.danmap.org. 2009. IRF, Institut for Rationel Farmakoterapi [internet]. Antibiotika til systemisk brug (Institute for Rational Pharmacotherapy, Antibiotics for Systemic Use).12-2-2009. [cited 1– 5-2012]. Available from: http://www.irf.dk/dk/rekommandationsliste/infektionssygdomme/antibiotika_ systemisk_brug/test_sulfonamider_og_trimethoprim_j01e.htm. c Naber K, Schito G, Botto H, Palou J, Mazzei T. Surveillance study in Europe and Brazil on Clinical Aspects and antimicrobial Resistance Epidemiology in females with cystitis (ARESC): Implications for Empiric Therapy. European Urology 2008:54:1164– 1178. d Kahlmeter G. The ECO.SENS Project: a prospective, multinational, multicentre epidemiological survey of the prevalence and antimicrobial susceptibility of urinary tract pathogens—interim report. J Antimicrob Chemother 2000;46 Suppl 1:15– 22. e Rabanaque G, Romera Á , Domingo C, Herrera C, Plana A, Sá nchez J. Infecciones del tracto urinario. (Urinary tract infections). Manual de enfermedades infecciones en atenció n primaria. (Handbook of infectious diseases in primary helth care). Barcelona: 2010:153– 181. Naber K, Schito G, Botto H, Palou J, Mazzei T. Surveillance study in Europe and Brazil on Clinical Aspects and antimicrobial Resistance Epidemiology in females with cystitis (ARESC): Implications for Empiric Therapy. European Urology 2008:54:1164– 1178. f Andr é M, Ahlqvist-Rastad J, Beermann B. Nedre urinvä gsinfektion (UVI) hos kvinnor - Behandlingsrekommendation. (Lower urinary tract infection (UTI) in women - Treatment recommendation). Lä kemedelsverket 2007;2:8– 15. uropathogens from urine samples submitted from The reasons for the diverging recommenda- primary care to a microbiology department are, how- tions may be due to different price policies, differ- ever, highly dependent on the groups of patients ent availability, and/or different traditions. The from which the urine samples are collected. We have potential infl uence of such factors deserves further limited knowledge regarding the bacterial resistance investigation. pattern in patients with uncomplicated UTI because All six countries recommended one or more anti- these patients are most often treated without a pre- biotics with a low risk of E . coli resistance such as ceding urine culture and susceptibility test. However, nitrofurantoin, mecillinam, and fosfomycine as fi rst- in patients suspected to suffer from a complicated choice treatment of uUTI. However, three countries UTI the GP will often ask for a culture and suscep- (Denmark, Spain, and Scotland) also recommended tibility test before making a decision about antibiotic fi rst-choice antibiotics despite a high prevalence treatment. Therefore, results of the antimicrobial ( (cid:2) 10 – 20%) of resistant E . coli , such as sulphame- resistance pattern may be biased by a high number thizole (resistance rate in Denmark: 37%), trimethop- of uropathogenic bacteria from complicated UVI. rim (resistance rate in Scotland: 17%, and in The differences found in the recommendations Denmark: 10– 28%), and fl uoroquinolones (resis- for fi rst-choice treatment of uUTI cannot be sup- tance rate in Spain: 24%) [14– 17,19,21,24]. ported by different patterns of bacterial aetiology Use of antibiotics with resistance rates exceed- or a different resistance pattern for E . coli . In all ing 10– 20% is associated with an increased risk of countries, E . coli accounts for the majority (70 – treatment failure and selection of resistant strains 90%) of uUTI [14– 22] and S. saprophyticus is the [13,25]. Treatment failure is not common in patients second most common uropathogen, accounting for with uUTI, but selection of resistant strains may 2 – 11% of uUTI, and most frequent in young lead to an increased risk of treatment failures and women [4,9]. complications due to resistant bacteria. Despite a Treatment recommendations for uUTI in Europe 239 sulphamethizole resistance rate of 37% for E . coli, rates for the most frequent uropathogens exceeding this antibiotic is still recommended as fi rst-choice 10 – 20%. In order to reduce and control the increasing treatment for uUTI in Denmark. Antimicrobial antimicrobial resistance in Europe, it is important resistance to sulphamethizole has been associated to coordinate recommendations for empiric fi rst- with concurrent resistance to other antibiotics choice treatment of uUTI and choose the most appro- ( multidrug resistance), and it should therefore be priate antibiotic with the lowest risk of antibiotic considered to exclude sulphamethizole in the rec- resistance. ommendations for empiric treatment of uUTI [26]. Fluoroquinolones belong to the group of critically Declaration of interests important antibiotics [6] having an important role in the treatment of more severe infections, such as sep- The authors report no confl ict of interest. The ticaemia; therefore resistance to fl uoroquinolones authors alone are responsible for the content and can have serious clinical consequences. Resistance to writing of the paper. fl uoroquinolones emerges fast, and it should there- fore be used with caution and reserved for severe infections, and preceded by antimicrobial suscepti- References bility testing of the bacteria involved [25]. Susceptibility analyses for E . coli have shown [1] Nicolle L , Anderson PA , Conly J , Mainprize TC , Meuser J , Nickel JC , et al . Uncomplicated urinary tract infection in resistance rates against amoxicillin/clavulanic acid as women: Current practice and the effect of antibiotic resist- high as 29%, when including urine samples from ance on empiric treatment. Can Fam Physician 2006; 52 : both the primary and secondary healthcare sectors 612 – 18 . [27]. Furthermore, it has been shown that the [2] Christiaens TC , De MM , Verschraegen G , Peersman W , increase in resistance to amoxicillin/clavulanic acid is Heytens S , De Maeseneer JM . Randomised controlled trial of nitrofurantoin versus placebo in the treatment of uncom- closely related to the resistance to ciprofl oxacin, plicated urinary tract infection in adult women. Br J Gen which is as high as 24% in Spain [21,24,28]. Pract 2002; 52 : 729 – 34 . Before conclusion, it is important to mention [3] Ferry SA , Holm SE , Stenlund H , Lundholm R , Monsen TJ . other factors that may infl uence the increasing resis- The natural course of uncomplicated lower urinary tract tance to antibiotics. In some countries “ over the infection in women illustrated by a randomized placebo controlled study. Scand J Infect Dis 2004; 36 : 296 – 301 . counter ” antibiotics are available at pharmacies. In [4] Nicolle LE . Uncomplicated urinary tract infection in adults Spain, for example, Campos et al. found that up to including uncomplicated pyelonephritis. Urol Clin North 30% of all antibiotics purchased are “ over the coun- Am 2008; 35 : 1 – 12 . ter ” and thereby non-prescription [29]. According [5] Falagas ME , Kotsantis IK , Vouloumanou EK , Rafailidis PI . to a Spanish study carried out in 2008 nearly 80% Antibiotics vs. placebo in the treatment of women with uncomplicated cystitis: A meta-analysis of randomized con- of the female patients visiting a pharmacy could trolled trials. J Infect 2009; 58 : 91 – 102 . obtain antibiotics for their UTI without a prescrip- [6] Critically Important Antimicrobials for Human Medicine. tion [30]. Non-prescription antibiotics have been 2nd Revision – 2009. WHO Advisory Group on Integrated associated with an increase in resistant bacteria Surveillance of Antimicrobial Resistance (AGISAR). Geneva: in a worldwide study, underlining the need for treat- World Health Organization, Department of Food Safety and Zoonoses; 2009. ment guidelines, regarding both the diagnosis [7] Goossens H , Ferech M , Vander SR , Elseviers M . of infection and the treatment, which is the focus Outpatient antibiotic use in Europe and association with of this article [31]. resistance: S cross-national database study. Lancet 2005; Another factor affecting resistance is the use of 365 : 579 – 87 . antibiotics in agriculture. In general, resistance to [8] Danmap 2009 [internet]. Use of antimicrobial agents and occurrence of antimicrobial resistance from food animals, nitrofurantoin, mecillinam, and fosfomycine is low fruits and humans in Denmark. [cited 1– 6 – 2011.] Available in Europe. This may be due to the fact that these from: www.danmap.org. 2009 . antibiotics are not used in agriculture [32]. [9] Kahlmeter G . The ECO.SENS Project: A prospective, multinational, multicentre epidemiological survey of the prevalence and antimicrobial susceptibility of urinary tract Conclusion pathogens – interim report . J Antimicrob Chemother 2000; 46(Suppl 1): 15 – 22 . The comparison of different national recommenda- [10] ECDC/EMEA [internet]. Joint Technical Report. The bacte- tions for fi rst-choice empiric treatment of uUTI in rial challenge: Time to react. 2009 [cited 5– 12 – 2012]. different European countries showed considerable Available from: EMEA/576176/2009.www.ema.europa.eu/docs/ en_GB/document_library/Report/2009/11/WC500008770. differences between countries [14– 22]. Three coun- pdf.09.2009; vii. tries (Denmark, Scotland, and Spain) recommended [11] Le TP , Miller LG . Empirical therapy for uncomplicated empiric treatment with antibiotics despite resistance urinary tract infections in an era of increasing antimicrobial 240 J. M. Haslund et al. resistance: A decision and cost analysis. Clin Infect Dis primaria [Handbook of infectious diseases in primary helth 2001; 33 : 615 – 21 . care]. Barcelona: 2010. p. 153 – 81 . [12] Gupta K , Hooton TM , Naber KG , Wullt B , Colgan R , [22] Wagenlehner FM , Schmiemann G , Hoyme U , Funfstuck R , Miller LG , et al . International clinical practice guidelines for Hummers-Pradier E , Kaase M , et al . Nationale S3-Leitlinie, the treatment of acute uncomplicated cystitis and pyelone- unkomplizierte harnwegsinfektionen. Empfehlungen zu tera- phritis in women: A 2010 update by the Infectious Diseases pie und management unkomplizierter bakterieller ambulant Society of America and the European Society for Micro- erworbener harnwegsinfektionen bei erwachsenen patienten biology and Infectious Diseases. Clin Infect Dis 2011; 52 : [S3 guideline for uncomplicated urinary tract infections – e103 – e120 . treatment guidelines compliance]. Med Monatsschr Pharm [13] Raz R , Chazan B , Kennes Y , Colodner R , Rottensterich E , 2011; 34: 164 – 8 . Dan M , et al . Empiric use of trimethoprim-sulfamethoxazole [23] Gahrn-Hansen B , S ø gaard P . Midler mod bakterielle infek- (TMP-SMX) in the treatment of women with uncompli- tionssygdomme [Agents for treatment of bacterial infectious cated urinary tract infections, in a geographical area with a diseases] In: Kampmann JP, Brø sen K, Simonsen U, high prevalence of TMP-SMX-resistant uropathogens. Clin editors . Basal og klinisk farmakologi [Basic and clinical Infect Dis 2002; 34 : 1165– 9 . phamacology]. 3rd ed. Copenhagen: FADL‘ s forlag A/S; [14] IRF, Institut for Rationel Farmakoterapi [internet]. Antibi- 2007 . p. 601 – 21 . otika til systemisk brug [Institute for Rational Pharmaco- [24] Naber K , Schito G , Botto H , Palou J , Mazzei T . Surveillance therapy, Antibiotics for systemic use].12– 2 – 2009. [cited study in Europe and Brazil on clinical aspects and antimi- 1 – 5 – 2012]. Available from: http://www.irf.dk/dk/rekomman- crobial resistance epidemiology in females with cystitis dationsliste/infektionssygdomme/antibiotika_systemisk_ (ARESC): Implications for empiric therapy. Eur Urology brug/test_sulfonamider_og_trimethoprim_j01e.htm. 2008: 54 : 1164– 78 . [15] Basislisten 2011 [internet]. Basislisten, læ gens v æ rkt ø j til [25] Dalhoff A . Resistance surveillance studies: A multifaceted rationel medicinordination [The basic list, the doctor’ s tool problem – the fl uoroquinolone example. Infection 2012; 40 : for rational drug prescribing]. [cited 3– 2 – 2012]. Available 239 – 62 . from: https://www.sundhed.dk/content/cms/15/4915_2012- [26] Kerrn MB , Klemmensen T , Frimodt-Moller N , Espersen F . basislisten.pdf Susceptibility of Danish Escherichia coli strains isolated from [16] Helweg-Larsen J , F rimodt-Moller N , N ielsen H , urinary tract infections and bacteraemia, and distribution of Dahl Knudsen J , Holme P . Antibiotika (systemisk brug), bag- sul genes conferring sulphonamide resistance. J Antimicrob grundsnotat, 2009 [Antibiotics (systemic use), background Chemother 2002; 50 : 513 – 16 . notes, 2009]. [internet]. [ cited 12 – 9 – 2009]. Available from: [27] Llor C , Aspiroz C , Cano A , Barranco M . The use of amoxi- http://www.irf.dk/dk/rekommandationsliste/baggrundsno- cillin and clavulanic acid and quinolones as fi rst choice anti- tater/infektionssygdomme/antibiotika_systemisk_brug. biotics in uncomplicated urinary tract infections in Spain htm#Uro – genitale_infektioner. should be reviewed. Aten Primaria 2012; 44 : 443 – 4 . [17] Gahrn-Hansen B , Kolmos HJJ . Antibiotikapolitik og behan- [28] Cuevas O , Oteo J , Lazaro E , Aracil B , de AF , Garcia-Cobos S , dling af hyppigt forekommende infektioner i almen praksis et al . Signifi cant ecological impact on the progression of [Policy of antibiotics and treatment of common infections in fl uoroquinolone resistance in Escherichia coli with increased general practice]. Copenhagen: Institute for Rational Phar- community use of moxifl oxacin, levofl oxacin and amoxicillin/ macotherapy, Danish Medicines Agency; 2001. p. 7 . clavulanic acid. J Antimicrob Chemother 2011; 66 : 664 – 9 . [18] Andr é M , Ahlqvist-Rastad J , Beermann B . Nedre urinv ä gsin- [29] Campos J , Ferech M , Lazaro E , Abajo F , Oteo J , Stephens P , fektion (UVI) hos kvinnor – Behandlingsrekommendation et al . Surveillance of outpatient antibiotic consumption in [Lower urinary tract infection (UTI) in women – Treatment Spain according to sales data and reimbursement data . J recommendation]. L ä kemedelsverket 2007; 2 : 8 – 15 . Antimicrob Chemother 2007; 60 : 698 – 701 . [19] Scottish Intercollegiate Guideline Network. Management of [30] Llor C , Cots JM . The sale of antibiotics without prescription suspected bacterial urinary tract infection in adults: A in pharmacies in Catalonia, Spain. Clin Infect Dis 2009; 48 : national clinical guideline; 2012 . p. 7 – 12 . 1345– 9 . [20] Skerk V , Andrasevic AT , Andrasevic S , Susic E, Dzepina AM , [31] Morgan DJ , Okeke I , Laxminarayan R , Perencevich E , Madaric V , et al . [ISKRA guidelines on antimicrobial treat- Weisenberg S. Non-prescription antimicrobial use world- ment and prophylaxis of urinary tract infections – Croatian wide: A systematic review. Lancet Infect Dis 2011; 11 : national guidelines]. Lijec Vjesn 2009; 131 : 105 – 18 . 692 – 701 . [21] Rabanaque G , Romera Á , Domingo C , Herrera C , Plana A , [32] Grave K , Torren-Edo J , Mackay D . Comparison of the sales S á nchez J . Infecciones del tracto urinario [Urinary tract of veterinary antibacterial agents between 10 European infections]. Manual de enfermedades infecciones en atenció n countries . J Antimicrob Chemother 2010; 65 : 2037– 40 .