ISSN 2465-8243(Print) / ISSN: 2465-8510(Online) https://doi.org/10.14777/uti.2017.12.2.55 Review Urogenit Tract Infect 2017;12(2):55-64

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The Clinical Guidelines for Acute Uncomplicated Cystitis and Acute Uncomplicated Pyelonephritis

Ki Ho Kim, Jae Heon Kim1, Seung-Ju Lee2, Hong Chung3, Jae Min Chung4, Jae Hung Jung5, Hyun Sop Choe2, Hun Choi6, Sun-Ju Lee7; The Committee of The Korean Association of Urogenital Track Infection and Inflammation

Department of Urology, Dongguk University College of Medicine, Gyeongju, 1Department of Urology, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, 2Department of Urology, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon, 3Department of Urology, Konkuk University Chungju Hospital, Konkuk University School of Medicine, Chungju, 4Department of Urology, Pusan National University Yangsan Hospital, Yangsan, 5Department of Urology, Yonsei University Wonju College of Medicine, Wonju, 6Department of Urology, Korea University Ansan Hospital, Ansan,7Department of Urology, Kyung Hee University School of Medicine, Seoul, Korea

To date, there has not been an establishment of guidelines for urinary tract Received: 10 April, 2017 infections, due to limited domestic data in Korea, unlike other North American and Revised: 25 April, 2017 Accepted: 25 April, 2017 European countries. The clinical characteristics, etiology, and antimicrobial susceptibility of urinary tract infections vary from country to country. Moreover, despite the same disease, necessary to treat it may vary from country to country. Therefore, it is necessary to establish a guideline that is relevant to a specific country. However, in Korea, domestic data have been limited, and thus, guidelines

considering the epidemiological characteristics pertaining specifically to Korea do Correspondence to: Ki Ho Kim not exist. Herein, describe a guideline that was developed by the committee of The http://orcid.org/0000-0001-8532-6517 Korean Association of Urogenital Tract Infection and Inflammation, which covers Department of Urology, Dongguk University College of Medicine, 87 Dongdae-ro, Gyeongju 38067, Korea only the uncomplicated urinary tract infections, as covering all parts in the first Tel: +82-54-770-8525, Fax: +82-54-770-8503 production is difficult. E-mail: [email protected]

Keywords: Cystitis; Pyelonephritis; Urinary tract infections; Guideline This guideline is a reference for all patients; it may not be uniformly applicable to all patients. The clinical judgment should be made on a case-by-case Copyright 2017, Korean Association of Urogenital Tract Infection and Inflammation. All rights reserved. basis. This is an open access article distributed under the terms of the Creative Commons Attribution This guideline can be used for personal medical and Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits educational purposes, but it cannot be used for unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is commercial purposes or medical examination properly cited. purposes.

INTRODUCTION from the most recently published Asian Association of UTI & STI (2016), Asian European Association of Urology (2014), 1. Background and Purpose Infectious Diseases Society of America (2011), and AMMI Urinary tract infections (UTIs) are one of the most Canada Guidelines Committee (2005). Major literature common infectious diseases. They are divided according published in Korea was searched using MEDLINE (January to the site of infection, presence or absence of symptoms, 1976 to September 2014), Embase (January 1985 to anatomical or functional abnormalities, and the presence September 2014), Cochrane Library (January 1987 to or absence of underlying diseases. The aim of this study September 2014), and KoreaMed (January 1958 to September was to develop a guideline for uncomplicated UTIs. 2014). We used the following keywords to search these databases: “cystitis,” “pyelonephritis,” “urinary tract 2. Methodology infections,” “necrotizing pyelonephritis,” “pyelonephritides,” The guideline presented here is based on the guidelines “Korea.”

55 56 Ki Ho Kim, et al. Clinical Guideline for Uncomplicated UTIs

3. Level of Evidence and Grade of the 1) Definition Recommendation Acute cystitis is a symptom characterized by lower urinary The level of evidence (LE) and the grade (GR) of tract symptoms, such as discomfort in the pubic area, as recommendation were accepted and used in accordance well as storage symptoms, such as pain during urination with the recent guidelines of the Oxford Center for without vaginal discharge, urinary frequency, urgency, and Evidence-Based Medicine. nocturia (LE: 2a, GR: B). There must be no risk factors that can cause complicated UTIs. 1) Level of evidence I: Evidence from at least one randomized controlled trial 2) Diagnosis II: Evidence obtained from at least one well-designed Urine dipstick test and urinary microscopy are widely controlled study without randomization used basic diagnostic methods [1]. Although urinalysis is III: Evidence obtained from well-designed non-experi- not mandatory, it is advised to perform a culture test, if mental studies, such as comparative studies, correla- acute pyelonephritis suspicion persists for 2-4 weeks or tion studies, and case reports there is recurrent cystitis symptoms (LE: 4, GR: B). In Korea, IV: Evidence obtained from expert committee reports, UTIs have a high rate of resistance to . Acute opinions, or clinical experience of respected authorities cystitis is diagnosed when the urine (microscopy, more than 10 leukocytes) is observed or the colony is more than 2) Grade of recommendation 10,000 cfu/ml [2,3]. Additional diagnostic studies should A: Good evidence to support the recommendation for be considered when there is atypical symptoms, fever or against use without costovertebral angle tenderness, or no response B: Moderate evidence to support the recommendation to treatment (LE: 4, GR: B) [4,5]. for or against use C: Poor evidence to support the recommendation 3) Treatment Antibiotic treatment is recommended for patients with CLINICAL PRACTICE GUIDELINES BY acute cystitis because antibiotics have a significant DISEASE therapeutic benefit compared with placebos [6]. Since the resistance rate of E. coli to fluoroquinolone has already 1. Acute Uncomplicated Cystitis been reported to be greater than 20% in Korea, Acute uncomplicated cystitis is the most common UTI fluoroquinolone should be used carefully to empirically occurring mainly in adult women, especially sexually active treat simple UTIs [7,8]. Therefore, in the selection of young women and postmenopausal women. It is the most empirical antibiotics, it is important to consider the risk frequently encountered disease in primary medical factors of antibiotic resistance in patients, as well as the institutions, including urology, obstetrics, and gynecology. tendency to susceptibility of the area. Moreover, antibiotics More than half of healthy adult women visit the hospital should be altered in accordance with clinical features, and with acute uncomplicated cystitis at least once in their the duration of treatment should be adjusted in accordance lifetime. Escherichia coli is the most common organism with clinical features and persistence of symptoms. responsible for acute uncomplicated cystitis, followed by The criteria for determining empirical antibiotics are as Staphylococcus saprophyticus, Klebsiella pneumoniae, and follows: Proteus mirabilis. trimethoprim-sulfamethoxazole (TMP-SMX) • Clinical examination (no clinical symptoms of or fluoroquinolone was used as an empirical antibiotic. pyelonephritis such as high fever and flank pain, the However, fluoroquinolone-resistant strains and extended history of complicated UTIs such as diabetes) spectrum beta-lactamase (ESBL)-bacteria have increased, • Spectrum and susceptibility pattern of pathogenic requiring regional antibiotic resistance information and bacteria antibiotic guidelines. • Therapeutic patterns and antibiotic resistance rates in the community

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• Availability, tolerability, history of hypersensitivity to clavulanate 500 mg/125 mg oral twice a day, 250 drugs, and side effects mg oral three times a day, 100 mg oral three times • Cost a day, cefcapene pivoxil 100 mg oral three times a day, • Compliance to treatment and proxetil 100 mg oral twice a day is A 3-day fluoroquinolone therapy has been widely used recommended (LE: 1, GR: A). and recommended as an empirical antibiotic treatment for In regions where the resistance rate of E. coli to TMP-SMX acute cystitis (LE: 1, GR: A). Ciprofloxacin 500 mg oral is less than 20%, it is possible to administer TMP-SMX bid (twice a day) for 3 days, ciprofloxacin SR 500 mg qd 160/800 mg twice daily for 5 days [12-14] (LE: 1b, GR: (once a day) for 3 days, and tosufloxacin 150 mg oral B). However, according to a recent multicenter antibiotic bid are recommended [9] (LE: 1b, GR: B). In Korea, resistance study for UTIs, 30% or more of E. coli identified fluoroquinolone is not approved to treat acute cystitis, which in patients with acute uncomplicated cystitis is resistant can lead to insurance-related problems. Due to increased to TMP/SMX, and thus, have limited role as an empirical resistance to fluoroquinolone, it is important to identify antibiotic (Table 1) [7]. patients with suspected resistance through history taking. Risk factors for fluoroquinolone resistance is recent history 4) Follow-up of antibiotic treatment, recent hospitalization history, recent Urinalysis or urine culture in asymptomatic patients is experience in nursing home care, and chronic respiratory not recommended [12] (LE: 2b, GR: B). Even if urine culture disease. In any of these cases, it is desirable to select an shows bacteriuria, asymptomatic bacteriuria is not antibiotic other than fluoroquinolone. Recently, antibiotic recommended for treatment. Exceptionally, antibiotic therapy that is recommended in many countries, mainly treatment of asymptomatic bacteriuria is recommended only Europe, instead of fluoroquinolone, is trome- when planning an operation for the urologic urinary tract tamol 3 g oral single dose therapy, 400 mg or only in pregnant women. In general, if there is recurrence oral tid for 3 days, or nitrofurantoin macrocrystal 100 mg within 2 weeks or if symptoms persist for 2 weeks, urine oral bid for 5-7 days [10,11] (LE: 1a, GR: A). However, culture and antibiotic susceptibility are indispensable. pivmecillinam and nitrofurantoin are not produced and Moreover, it is recommended to follow the results of the cannot be used in Korea. antibiotic susceptibility or retreat for more than 7 days with As a beta-lactam antibiotic, - a different antibiotic (LE: 4, GR: C) (Fig. 1). 250 mg/125 mg oral three times a day or amoxicillin- An increase in ESBL-producing bacteria has also been observed with increased resistance to fluoroquinolone in Korea. ESBL production is mainly seen in E. coli and Table 1. Empirical antibiotic therapy for acute uncomplicated cystitis Klebsiella strains, and most of them are resistant to Daily dose Duration of antibiotics, except antibiotics, making the Antibiotic (oral) therapy (d) treatment of acute cystitis difficult. Fosfomycin, an oral Fosfomycin trometamol 3 g qd 1 Pivmecillinama) 400 mg tid 3 antibiotic, should be used when ESBL-producing bacteria Nitrofurantoin macrocrystala) 100 mg bid 5-7 are observed on the urine culture and when empirical -Lactams antibiotic therapy fails. In such case, 3 g of fosfomycin Amoxicillin-clavulanic acid 250/125 mg tid 7 500/125 mg bid trometamol is recommended to be administered three times Cefaclor 250 mg tid 7 at 48-hour intervals. Amoxicillin-clavulanate can be used Cefdinir 100 mg tid 5-7 Cefcapene pivoxil 100 mg tid 5-7 in patients where the use of fostomycin is difficult; Cefpodoxime prexetil 100 mg bid 5-7 additionally, ciprofloxacin or TMP-SMX may also be effective Fluoroquinolones if it is susceptible to urine culture (Fig. 2). Ciprofloxacinb) 500 mg bid 3 500 mg SR qd b) Tosufloxacin 150 mg bid 3 2. Acute Uncomplicated Pyelonephritis qd: once a day, tid: three times a day, bid: twice a day, SR: In Korea, amoxicillin, TMP-SMX, and have sustained-release. a)April 2016, not available in Korea, b)not available for pregnant women. all been used as the primary treatment antibiotics for UTIs.

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Fig. 1. Algorithm for clinical treatment of acute uncomplicated pyelonephritis. TMP-SMX: trimethoprim-sulfamethoxazole.

However, resistance to these antibiotics has been increasing increase in prevalence among patients aged 15 to 25 years, as of late; therefore prescribing fluoroquinolone antibiotics, while remaining stable in those aged 25 to 80 years; in which have a relatively low resistance rate and can be men, this prevalence seems to increase with age [18]. used orally, has been on the rise [15-17]. However, resistance According to a report in 2007, acute pyelonephritis was to fluoroquinolone antibiotics has also been increasing; thus, reported in 38.1% of males in their 60s or older and 38.6% it is necessary to evaluate and prepare for this as well. of females in their 20s and 30s [19]. Despite limited data, recurrence of acute pyelonephritis is 7 per 10,000 1) Epidemiology population. The mean treatment duration was 8.4 days. The annual prevalence rate of acute pyelonephritis in And the mean treatment duration was 7.2 days in outpatients Korea was reported to be 35.7 persons per 10,000 population and 14.1 days in hospitalized patients, with an average between January 1, 1997 and August 30, 1999, according hospital stay of 7.9 days. The mortality rate was 1.2 persons to the National Health Insurance data, with 59.0 in women in 1,000 population; 2.0 males and 1.0 females [18]. In and 12.6 in men. It was reported that 9.96 women and the case of acute uncomplicated pyelonephritis between 1.18 men were hospitalized for every 10,000 people. Acute 2010 and 2011, according to a multicenter study in Korea, pyelonephritis in women has been associated with a sudden the mean age was 43 years, with a male to female ratio

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Fig. 2. Algorithm for clinical management of acute uncomplicated cystitis (AUC). UTI: urinary tract infection, ESBL: extended spectrum beta-lactamase, TMP-SMX: trimethoprim-sulfamethoxazole.

of 1:14.4 [20]. Table 2. Factors that suggest a potential acute complicated pyelonephritis [23] 2) Diagnosis The presence of an indwelling catheter, stent or splint (urethral, ureteral, renal) or the use of intermittent bladder catheterisation (1) Clinical diagnosis: Acute pyelonephritis is a UTI caused Post-void residual urine of ＞100 ml An obstructive uropathy of any aetiology, e.g., bladder outlet obstruc- by acute bacterial infection of the renal pelvis and renal tion (including neurogenic urinary bladder), stones and tumor parenchyma, with clinical symptoms of flank pain, nausea, Vesicoureteric reflux or other functional abnormalities Urinary tract modifications, such as an ileal loop or pouch vomiting, fever of 38 degrees or more, and urinary Chemical or radiation injuries of the uroepithelium symptoms, such as urinary frequency, dysuria, residual urine Peri- and postoperative urinary tract infection Renal insufficiency and transplantation, diabetes mellitus and immu- sense, and gross hematuria. However, physical examination nodeficiency may show costovertebral angle tenderness with fever without urinary symptoms [21]. For this reason, it is difficult to diagnose acute pyelonephritis only with high fever and pyelonephritis are shown in Table 2 [23]. flank pain, requiring further examinations [22]. All patients (2) Laboratory diagnosis: A urinalysis (dipstick method) suspected of acute pyelonephritis should be evaluated for is recommended as a basic test (LE: 4, GR: C). A colony multiple factors associated with complicated acute count of ＞103 cfu/ml of uropathogens is considered to be pyelonephritis, and one of the most important methods clinically significant, indicating bacteriuria (LE: 2b, GR: C). is history taking. Making a distinction between uncom- The major causative organism of acute pyelonephritis plicated and complicated acute pyelonephritis requires is E. coli, and from 2000 to 2005, 79% of the 2,910 multicenter careful history taking at the initial diagnosis of pyelonephritis studies in Korea reported E. coli-induced pyelonephritis since the choice and duration of antibiotics as well as the [24]. The most common causative organism for acute need for other treatments are different. However, it is often pyelonephritis was determined to be E. coli in other difficult to distinguish between uncomplicated and domestic studies. K. pneumoniae, Proteus mirabilis, complicated acute pyelonephritis with only the initial clinical Enterococcus strain, and S. saprophyticus have also been symptoms. Factors that may cause complicated acute identified [7,17,24-26]. These causative organisms differ in

Urogenit Tract Infect Vol. 12, No. 2, August 2017 60 Ki Ho Kim, et al. Clinical Guideline for Uncomplicated UTIs distribution, especially according to age. Urine cultures and is complaint of persistent fever even after 72 hours of susceptibility tests should be performed to promote the treatment, unenhanced helical computed tomography, use of antibiotics in a cost effective manner because the excretory urography, or dimercaptosuccinic acid renal scans use of inappropriate antibiotics can have serious should be considered as additional tests (LE: 4, GR: C). consequences (Grade B). However, blood culture tests are Recently, it has been reported that computed tomography not mandatory and should be performed according to the may be more useful than ultrasonography. Especially, the circumstances (Grade D). If two or more of the following classification according to the degree of parenchymal conditions are present, blood culture should be performed invasion of the contrast enhancement computed more than two times: body temperature above 38oC, white tomography image is associated with the severity and blood cells below 4,000 or above 12,000, heart rate of prognosis of pyelonephritis [30-33]. less than 90/min, respiratory rate of more than 20/min,

PaCO2 below 32 mmHg, systolic blood pressure below 90 3) Treatment mmHg (Grade C). Due to the lack of well-designed systematic studies, The detection of bacteria in the urine culture under clinical treatment for acute uncomplicated pyelonephritis can be diagnosis of acute pyelonephritis is 46.3-78.8% [24,26]. If empirical therapy based on the results of UTI pathogens causative organisms are not detected, it can be considered and antibiotic susceptibility that lead to acute uncomplicated as one of two things: the infection cannot be cultured after cystitis (LE: 4, GR: B) [34]. S. saprophyticus, a causative inoculation on blood agar medium and MacConkey agar organism of acute uncomplicated pyelonephritis, is seen medium, or the antibiotics has been taken from primary less frequently than acute cystitis (LE: 4, GR: B) (Table 3). medical institutions or pharmacies. Blood tests may result (1) Mild and moderate acute uncomplicated pyelonephritis: in increased neutrophil leukocytosis, elevated erythrocyte For patients with mild-to-moderate acute pyelonephritis, sedimentation rate, increased C-reactive protein (CRP), and 10 to 14 days of oral antibiotic therapy is recommended elevated serum creatinine levels associated with renal failure (LE: 1b, GR: B) (Table 4). , TMP-SMX, and decreased creatinine clearance. Recently, procalcitonin first-generation cephalosporin, and etc., are recommended levels in the blood have been reported to be a good predictor as first-line antibiotics for E. coli, which is a major cause of mortality and sepsis in acute pyelonephritis compared of acute pyelonephritis with high resistance in Korea (Table with the traditional blood markers, such as CRP [27,28]. 5). The resistance rates to E. coli are high with ampicillin In women with acute pyelonephritis, blood culture is not (62.3%), TMP-SMX (36.7-37.2%), and first-generation recommended; however, it should be considered if the cephalosporin (33.9-58.3%). It is not appropriate as a complicated acute pyelonephritis is suspected [29]. If there primary antibiotic for patients with acute uncomplicated is persistent fever or flank pain even after 72 hours of pyelonephritis [24,26]. Fluoroquinolone can be used as a treatment, aggravated acute pyelonephritis or complicated primary treatment in areas with its resistance rate of around acute pyelonephritis should be considered. At this time, 10% (LE: 1b, GR: A) [35]. In Korea, the resistance rate blood cultures may be positive. of fluoroquinolone (6.9-12.9%) and third-generation (3) Imaging test: Ultrasonography must be performed cephalosporin (ex, cefotaxim: 0.8-10.2%) antibiotics is to evaluate upper urinary tract disorders, such as obstruction reported to be around 10% [24,26]. If the dose of of the urinary tract or renal stone (LE: 4, GR: C). If there fluoroquinolone is increased, the treatment period may be

Table 3. Initial therapy recommended for severe acute uncomplicated pyelonephritis Initial therapy LE GR A parenteral fluoroquinolone, in communities with Escherichia coli fluoroquinolone-resistance rates ＜10%. 1b B A third-generation cephalosporin, in communities with ESBL-producing E. coli resistance rates ＜10%. 1b B An plus a -lactamase-inhibitor in cases of known susceptible Gram-positive pathogens. 4 B An aminoglycoside or carbapenem in communities with fluoroquinolone and/or ESBLs-producing E. coli resistance rates ＞10%. 1b B LE: level of evidence, GR: grade, ESBL: extended spectrum beta-lactamase.

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Table 4. Initial empirical antimicrobial therapy in acute uncomplicated pyelonephritis in premenopausal women (oral therapy: mild and moderate acute uncomplicated pyelonephritis) Antibiotics Daily dose Duration of therapy (d) Reference Ciprofloxacina) 500-750 mg bid 7-10 Talan et al. [35] Levofloxacina) 250-500 mg qd 7-10 Richard et al. [41] Levofloxacin 750 mg qd 5 Klausner et al. [36] Peterson et al. [37] Alternative (clinically equivalent to fluoroquinolone but not equivalent to bacteriological effect) Cefpodoxime proxetil 200 mg bid 10 Cronberg et al. [38] 400 mg bid 10 Peterson et al. [37] If an antibiotic susceptibility test is performed (not appropriate for primary treatment) Trimethoprim-sulphamethoxazole 160/800 mg bid 14 Rubin et al. [42] Co-amoxiclavb),c) 0.5/0.125 g tid 14 Bid: twice a day, qd: once a day, tid: three times a day, Co-amoxiclav: amoxicillin-clavulanic acid. a)Lower dose studied, but higher dose recommended by experts, b)not studied as monotherapy in acute uncomplicated pyelonephritis, c)mainly for Gram-positive pathogens.

Table 5. Antibiotic susceptibility (%) AP SAM AK GM TOB CIP LFX SPT Antibiotic sensitivity of Escherichia coli and Klebsiella pneumoniae E. coli 27.2 77.1 92.1 75.5 83.7 79.0 67.4 44.7 K. pneumoniae 43.2 63.5 98.1 97.2 97.3 88.3 66.7 85.6 Antibiotic sensitivity of Gram(-) organisms between 2000 and 2004 2000 year 38.5 79.3 91.7 83.1 85.3 80.2 67.5 59.0 2004 year 18.9 74.4 95.4 72.1 79.1 76.7 65.5 38.1 Adapted from the article of Lee et al. J Korean Med Sci 2009;24:296-301 [19]. Comparison between E. coli and K. pneumoniae (p＜0.05). Comparison between 2000 and 2004 yr (p＜0.05). AP: ampicillin, SAM: ampicillin/, AK: amikacin, GM: gentamycin, TOB: tobramycin, CIP: ciprofloxacin, LFX: levofloxacin, SPT: trimetoprim/sulfamethoxazole. shortened to 5 days (LE: 1b, GR: B) [36,37]. But, considering rate of ESBL exceeds 10%, aminoglycosides or the global expression pattern of fluoroquinolone-resistant can be used as a primary treatment until antibiotic E. coli, the use of an initial high dose of fluoroquinolone susceptibility test results are reported (LE: 4, GR: B). should be limited. (2) Severe acute uncomplicated pyelonephritis: In Third generation , such as cefpodoxime patients with severe acute pyelonephritis, without the proxetil, , and ceftibuten, can be used as an possibility of oral administration due to systemic symptoms, alternative drug (LE: 1b, GR: B) [36,38,39]. However, such as nausea and vomiting, parenteral antibiotics should according to the reports to date, there have been clinically be considered as the initial treatment (Table 4) [35-38,41,42]. equivalent effects with ciprofloxacin, but bacteriological Hospital admission should be considered if complicating and efficacious aspects have not been proven. Considering factors cannot be ruled out in diagnostic procedures or that the community resistance rate for Cotrimoxazole is if patients have clinical signs and symptoms of sepsis (LE: greater than 10% in most areas, it may not be appropriate 4, GR: B). After improvement, patients can be switched as an empirical therapy; however, it may be considered to oral therapy, and the treatment should continue for at if there no resistance as shown on the antimicrobial least 1-2 weeks (LE: 1b, GR: B). susceptibility test (LE: 1b, GR: B) [40]. Amoxicillin-clavulanic After improvement, the patient can be switched to an acid is not recommended as a primary treatment agent oral therapy (Table 4) and continue treatment for 1-2 weeks. (LE: 4, GR: B), but may be selected as a therapeutic agent Table 6 shows daily dose only [35,36,41,43-47]. if Gram-positive bacteria are cultured in an antimicrobial susceptibility test (LE: 4, GR: C). In regions where the 4) Follow-up resistance rate of fluoroquinolone is high and the resistance Urinalysis or urine culture for follow-up in asymptomatic

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Table 6. Initial empirical antimicrobial therapy in acute uncomplicated additional guidelines for UTIs, including recurrent UTIs and pyelonephritis in premenopausal women (parenteral therapy: severe complicated UTIs, are needed. acute uncomplicated pyelonephritis) Antibiotic Daily dose Reference Ciprofloxacin 400 mg bid Talan et al. [35] CONFLICT OF INTEREST Levofloxacina) 250-500 mg qd Richard et al. [41] Levofloxacin 750 mg qd Klausner et al. [36] No potential conflict of interest relevant to this article Alternative Cefotaximeb) 2 g tid was reported. Ceftriaxonea),d) 1-2 g qd Wells et al. [43] Ceftazidimeb) 1-2 g tid Mouton and Beuscart [44] Cefepimea),d) 1-2 g bid Giamarellou [45] REFERENCES Co-amoxiclavb),c) 1.5 g tid / 2.5-4.5 g tid Naber et al. [46] tazobactama),d) 1. Stamm WE, Hooton TM. Management of urinary tract Gentamicinb) 5 mg/kg qd infections in adults. N Engl J Med 1993;329:1328-34. b) Amikacin 15 mg/kg qd 2. Bradbury SM. Collection of urine specimens in general d) 1 g qd Wells et al. [43] practice: to clean or not to clean? J R Coll Gen Pract 1988;38: /cilastatind) 0.5/0.5 g tid Naber et al. [46] d) 363-5. 1 g tid Mouton and Beuscart [44] Doripenemd) 0.5 g tid Naber et al. [47] 3. Lifshitz E, Kramer L. Outpatient urine culture: does collection Bid: twice a day, qd: once a day, tid: three times a day, Co-amoxiclav: technique matter? Arch Intern Med 2000;160:2537-40. amoxicillin-clavulanic acid. 4. Foxman B, Brown P. Epidemiology of urinary tract infections: a) b) Lower dose studied, but higher dose recommended by experts, not transmission and risk factors, incidence, and costs. Infect Dis studied as monotherapy in acute uncomplicated pyelonephritis, c)mainly for Gram-positive pathogens, d)same protocol for acute Clin North Am 2003;17:227-41. uncomplicated pyelonephritis and complicated urinary tract infection. 5. Fihn SD. Clinical practice. Acute uncomplicated urinary tract infection in women. N Engl J Med 2003;349:259-66. patients is not recommended (LE: 4, GR: C). Acute 6. Gupta K, Hooton TM, Naber KG, Wullt B, Colgan R, Miller LG, et al. International clinical practice guidelines for the treatment uncomplicated pyelonephritis can be followed-up if risk of acute uncomplicated cystitis and pyelonephritis in women: factors for complicated UTI (Table 2) is suspected. If a 2010 update by the Infectious Diseases Society of America symptoms do not improve within 3 days after diagnosis, and the European Society for Microbiology and Infectious or if there is no symptom loss or recurrence within 2 week, Diseases. Clin Infect Dis 2011;52:e103-20. urine culture and antibiotic susceptibility test, as well as 7. Kim ME, Ha US, Cho YH. Prevalence of antimicrobial resistance kidney ultrasonography, computed tomography, and renal among uropathogens causing acute uncomplicated cystitis in female outpatients in South Korea: a multicentre study in 2006. scintigraphy should be performed (LE: 4, GR: B). In patients Int J Antimicrob Agents 2008;31 Suppl 1:S15-8. without functional structural abnormalities of the urinary 8. Lee SJ, Lee DS, Choe HS, Shim BS, Kim CS, Kim ME, et al. tract, and if an antibiotic-resistant bacterium is initially Antimicrobial resistance in community-acquired urinary tract suspected, an alternative antibiotic should be administered infections: results from the Korean Antimicrobial Resistance based on urine cultures (LE: 4, GR: B). A recurrence of Monitoring System. J Infect Chemother 2011;17:440-6. acute uncomplicated pyelonephritis by the same pathogen 9. Rafalsky V, Andreeva I, Rjabkova E. Quinolones for uncom- should be reevaluated for factors that may cause recurrent plicated acute cystitis in women. Cochrane Database Syst Rev 2006;(3):CD003597. pyelonephritis (LE: 4, GR: C). 10. Nicolle LE. Pivmecillinam in the treatment of urinary tract infections. J Antimicrob Chemother 2000;46 Suppl 1:35-9; CONCLUSIONS discussion 63-5. 11. Gupta K, Hooton TM, Roberts PL, Stamm WE. Short-course 1. Limitations nitrofurantoin for the treatment of acute uncomplicated cystitis The authors attempted to develop a guideline for UTIs in women. Arch Intern Med 2007;167:2207-12. 12. Warren JW, Abrutyn E, Hebel JR, Johnson JR, Schaeffer AJ, considering domestic characteristics; however, domestic Stamm WE. Guidelines for antimicrobial treatment of literature regarding this is severely lacking. It is necessary uncomplicated acute bacterial cystitis and acute pyelonephritis to provide guidelines that adheres to the domestic in women. Infectious Diseases Society of America (IDSA) Clin characteristics through continuous research. In addition, Infect Dis 1999;29:745-58.

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