今日の臨床サポート

膀胱炎

著者: 濵砂良一 国家公務員共済組合連合会 新小倉病院 副院長 泌尿器科部長

監修: 中川昌之 公益財団法人 慈愛会 今村総合病院 泌尿器科顧問

著者校正/監修レビュー済:2022/11/09
参考ガイドライン:
  1. 日本感染症学会日本化学療法学会:JAID/JSC 感染症治療ガイドライン 2016 -尿路感染症・男性器感染症- (日本化学療法学会雑誌 64(1):1-30, 2016)
  1. 日本感染症学会日本化学療法学会:JAID/JSC 感染症治療ガイド 2019 XI 尿路感染症(JAID/JSC 感染症治療ガイド 2019, 202-220, ライフサイエンス出版株式会社 東京, 2018)
患者向け説明資料

概要・推奨   

  1. 急性単純性膀胱炎の原因菌の60-80%は大腸菌であり、このほかS. saprophyticus(8%程度)、Klebsiella属、Proteus属、Streptococcus属、Enterococcus属などが原因となる。急性単純性膀胱炎から分離される大腸菌の7-15%がキノロン耐性であるが、閉経前の女性では耐性率は7-10%程度で、閉経後の患者では約20%である。ESBL産生菌は我が国では4-10%で検出される。閉経前女性では、第1選択薬またはグラム陽性菌が検出される場合にはキノロン系抗菌薬を処方する。第2選択薬またはグラム陰性菌が検出される場合には経口セファロスポリン系抗菌薬を処方する。閉経後の女性では、第1選択薬またはグラム陰性菌が検出される場合には経口セファロスポリン系抗菌薬を処方する。第2選択薬またはグラム陽性菌が検出される場合にはキノロン系抗菌薬を処方する。
  1. 複雑性膀胱炎では、受診時に原因菌を想定することは困難である。キノロン系抗菌薬、オーグメンチン、ユナシンなどのBLI(βラクタマーゼ阻害薬)配合ペニシリン薬を7-14日間投与し、薬剤感受性試験の結果で、抗菌薬を変更する。
 
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、 著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※同効薬・小児・妊娠および授乳中の注意事項等は、海外の情報も掲載しており、日本の医療事情に適応しない場合があります。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適応の査定において保険適応及び保険適応外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適応の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
濵砂良一 : 特に申告事項無し[2022年]
監修:中川昌之 : 特に申告事項無し[2022年]

改訂のポイント:
  1. 日本感染症学会/日本化学療法学会からのガイドライン、治療ガイド、および尿路感染症の原因菌の新しい薬剤感受性試験結果をもとに、新たな治療ガイドを作成した。

病態・疫学・診察

疾患情報(疫学・病態)  
ポイント:
  1. 膀胱炎は尿路感染症の一病態である。尿路感染症は主に尿路における細菌または真菌による感染症であり、細菌が尿路の粘膜へ付着し、さらに粘膜下層へ浸潤、増殖し、炎症を起こす。
  1. 膀胱炎とは膀胱粘膜に炎症があり、排尿時痛、頻尿、尿意切迫感などの膀胱刺激症状を来す疾患の総称である。一般には細菌または真菌による感染性の膀胱炎を指す。
  1. 尿路感染症は感染部位により、上部尿路感染症と下部尿路感染症に分類され、膀胱炎は下部尿路感染症の代表的な疾患である。また病勢により急性膀胱炎と慢性膀胱炎に分類される。単純性膀胱炎は閉経前の女性と閉経後の女性とは別々に治療を考えるべきである。閉経前の女性では急性単純性膀胱炎が多く、閉経後の女性では慢性単純性膀胱炎と考えられる症例も含まれる。急性単純性膀胱炎が若い女性に発症する場合強い症状を呈することが多い。閉経後の女性では症状が軽いこともあり、時に慢性の経過をとる。慢性単純性膀胱炎は高齢者に多く、比較的緩徐に発症する。成人男子では、単純性膀胱炎を原則的には発症しない。
 
複雑性膀胱炎と単純性膀胱炎:
  1. 膀胱炎は基礎疾患の有無により、複雑性膀胱炎と単純性膀胱炎に分けられる。複雑性膀胱炎は、局所(尿路)または全身に基礎疾患を有する患者に発症する膀胱炎であり、明らかな原疾患を有さないものを単純性膀胱炎と呼ぶ。
  1. 女性は尿道が短いため男性と比較して膀胱炎に罹患しやすい。一方、成人以上の男性は尿道が長く基礎疾患がない限り膀胱炎を発症しにくい。したがって成人以上の男性に尿路感染症が発症した場合は、複雑性尿路感染症と判断してよい。
  1. 複雑性膀胱炎の基礎疾患は、成人では、前立腺肥大症、尿道狭窄などの男性の下部尿路閉塞疾患、神経因性膀胱、水腎症、尿路結石、尿路腫瘍、尿路カテーテルに合併するもの(カテーテル関連尿路感染症)、糖尿病などが挙げられる。小児では膀胱尿管逆流(VUR)、重複腎盂尿管、尿管狭窄、尿管瘤、尿道憩室などの先天疾患を含めた疾患を考慮する。
問診・診察のポイント  
問診のポイント:
  1. 膀胱炎の症状として、排尿時痛、頻尿、尿意切迫感などの膀胱刺激症状や尿混濁、膀胱部不快感などの症状を確認する。

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文献 

Stephen Bent, Brahmajee K Nallamothu, David L Simel, Stephan D Fihn, Sanjay Saint
Does this woman have an acute uncomplicated urinary tract infection?
JAMA. 2002 May 22-29;287(20):2701-10.
Abstract/Text CONTEXT: Symptoms suggestive of acute urinary tract infection (UTI) constitute one of the most common reasons for women to visit clinicians. Although the clinical encounter typically involves taking a history and performing a physical examination, the diagnostic accuracy of the clinical assessment for UTI remains uncertain.
OBJECTIVE: To review the accuracy and precision of history taking and physical examination for the diagnosis of UTI in women.
DATA SOURCES: We conducted a MEDLINE search for articles published from 1966 through September 2001 and manually reviewed bibliographies, 3 commonly used clinical skills textbooks, and contacted experts in the field.
STUDY SELECTION: Studies were included if they contained original data on the accuracy or precision of history or physical examination for diagnosing acute uncomplicated UTI in women. One author initially screened titles and abstracts found by our search. Nine of 464 identified studies met inclusion criteria.
DATA EXTRACTION: Two authors independently abstracted data from the included studies. Disagreements were resolved by discussion and consensus with a third author.
DATA SYNTHESIS: Four symptoms and 1 sign significantly increased the probability of UTI: dysuria (summary positive likelihood ratio [LR], 1.5; 95% confidence interval [CI], 1.2-2.0), frequency (LR, 1.8; 95% CI, 1.1-3.0), hematuria (LR, 2.0; 95% CI, 1.3-2.9), back pain (LR, 1.6; 95% CI, 1.2-2.1), and costovertebral angle tenderness (LR, 1.7; 95% CI, 1.1-2.5). Four symptoms and 1 sign significantly decreased the probability of UTI: absence of dysuria (summary negative LR, 0.5; 95% CI, 0.3-0.7), absence of back pain (LR, 0.8; 95% CI, 0.7-0.9), history of vaginal discharge (LR, 0.3; 95% CI, 0.1-0.9), history of vaginal irritation (LR, 0.2; 95% CI, 0.1-0.9), and vaginal discharge on examination (LR, 0.7; 95% CI, 0.5-0.9). Of all individual diagnostic signs and symptoms, the 2 most powerful were history of vaginal discharge and history of vaginal irritation, which significantly decreased the likelihood of UTI when present (LRs, 0.3 and 0.2, respectively). One study examined combinations of symptoms, and the resulting LRs were more powerful (24.6 for the combination of dysuria and frequency but no vaginal discharge or irritation). One study of patients with recurrent UTI found that self-diagnosis significantly increased the probability of UTI (LR, 4.0).
CONCLUSIONS: In women who present with 1 or more symptoms of UTI, the probability of infection is approximately 50%. Specific combinations of symptoms (eg, dysuria and frequency without vaginal discharge or irritation) raise the probability of UTI to more than 90%, effectively ruling in the diagnosis based on history alone. In contrast, history taking, physical examination, and dipstick urinalysis are not able to reliably lower the posttest probability of disease to a level where a UTI can be ruled out when a patient presents with 1 or more symptoms.

PMID 12020306
W E Stamm, G W Counts, K R Running, S Fihn, M Turck, K K Holmes
Diagnosis of coliform infection in acutely dysuric women.
N Engl J Med. 1982 Aug 19;307(8):463-8. doi: 10.1056/NEJM198208193070802.
Abstract/Text We reevaluated conventional criteria for diagnosing coliform infection of the lower urinary tract in symptomatic women by obtaining cultures of the urethra, vagina, midstream urine, and bladder urine. The traditional diagnostic criterion, greater than or equal to 10(5) bacteria per milliliter of midstream urine, identified only 51 per cent of women whose bladder urine contained coliformis. We found the best diagnostic criterion to be greater than or equal to 10(2) bacteria per milliliter (sensitivity, 0.95; specificity, 0.85). Although isolation of less than 10(5) coliforms per milliliter of midstream urine has had a low predictive value of previous studies of asymptomatic women, the predictive value of the criterion of greater than or equal to 10(2) per milliliter was high (0.88) among symptomatic women the prevalence of coliform infection exceeded 50 per cent. In view of these findings, clinicians and microbiologists should alter their approach to the diagnosis and treatment of women with acute symptomatic coliform infection of the lower urinary tract.

PMID 7099208
F Smaill, J C Vazquez
Antibiotics for asymptomatic bacteriuria in pregnancy.
Cochrane Database Syst Rev. 2007 Apr 18;(2):CD000490. doi: 10.1002/14651858.CD000490.pub2. Epub 2007 Apr 18.
Abstract/Text BACKGROUND: Asymptomatic bacteriuria occurs in 2% to 10% of pregnancies and, if not treated, up to 30% of mothers will develop acute pyelonephritis. Asymptomatic bacteriuria has been associated with low birthweight and preterm delivery.
OBJECTIVES: To assess the effect of antibiotic treatment for asymptomatic bacteriuria on persistent bacteriuria during pregnancy, the development of pyelonephritis and the risk of low birthweight and preterm delivery.
SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (January 2007).
SELECTION CRITERIA: Randomized trials comparing antibiotic treatment with placebo or no treatment in pregnant women with asymptomatic bacteriuria found on antenatal screening.
DATA COLLECTION AND ANALYSIS: We assessed trial quality.
MAIN RESULTS: Fourteen studies were included. Overall the study quality was poor. Antibiotic treatment compared to placebo or no treatment was effective in clearing asymptomatic bacteriuria (risk ratio (RR) 0.25, 95% confidence interval (CI) 0.14 to 0.48). The incidence of pyelonephritis was reduced (RR 0.23, 95% CI 0.13 to 0.41). Antibiotic treatment was also associated with a reduction in the incidence of low birthweight babies (RR 0.66, 95% CI 0.49 to 0.89) but a difference in preterm delivery was not seen.
AUTHORS' CONCLUSIONS: Antibiotic treatment is effective in reducing the risk of pyelonephritis in pregnancy. A reduction in low birthweight is consistent with current theories about the role of infection in adverse pregnancy outcomes, but this association should be interpreted with caution given the poor quality of the included studies.

PMID 17443502
Abstract/Text The study was undertaken to determine the causes of the more frequent pre-term deliveries, fetal and neonatal deaths associated with maternal urinary-tract infections during pregnancy. The combined perinatal mortality rate for eight common placental and fetal disorders was 42 per thousand births in the infected vs. 21 per thousand in the noninfected, owing to a greater mortality from noninfectious placental and fetal disorders in the gestations with the urinary-tract infections (P less than 0.001). All the mortality excess took place when the urinary-tract infections occurred within 15 days of delivery. Death rates were highest when the urinary-tract infections coexisted with maternal hypertension and acetonuria.Hydramnios, amniotic-fluid bacterial infections and abruptio placentae were responsible for two thirds of the more frequent preterm deliveries in the pregnancies complicated by urinary-tract infections.

PMID 370593
L K Millar, S M Cox
Urinary tract infections complicating pregnancy.
Infect Dis Clin North Am. 1997 Mar;11(1):13-26.
Abstract/Text Urinary tract infections (asymptomatic bacteriuria, cystitis, and pyelonephritis) are frequently encountered medical complications of pregnancy. The majority of infections in pregnancy are asymptomatic; however, even covert bacteriuria places the mother at risk for low birth weight and preterm birth. Pyelonephritis can result in significant maternal and fetal morbidity and mortality. Therefore, all pregnant women should be screened for asymptomatic bacteriuria, and urinary tract infections should be promptly treated to prevent adverse pregnancy outcome. This article reviews the diagnosis, etiology, treatment, and complications associated with urinary tract infections in pregnancy.

PMID 9067782
T F Patterson, V T Andriole
Detection, significance, and therapy of bacteriuria in pregnancy. Update in the managed health care era.
Infect Dis Clin North Am. 1997 Sep;11(3):593-608.
Abstract/Text Profound physiologic and anatomic changes of the urinary tract during pregnancy contribute to the increased risk for symptomatic urinary tract infection in women with bacteriuria. Asymptomatic bacteriuria is the major risk factor for developing symptomatic UTIs during pregnancy and may be associated with adverse effects on maternal and fetal health. Because most symptomatic UTIs develop in women with bacteriuria earlier in pregnancy, treatment of bacteriuria is undertaken to prevent symptomatic infections. All pregnant women should be screened at the first antenatal visit, which is reliably and inexpensively done with a dipstick culture. Short-course therapy should be given to women with bacteriuria and clearance of bacteriuria should be documented after therapy is complete. Failure to eliminate bacteriuria with repeated therapy or recurrence with the same organism is indicative of renal parenchymal infection or a structural abnormality. All women with persistent bacteriuria or recurrent infection should have follow-up cultures and a urologic evaluation after delivery.

PMID 9378925
J E Delzell, M L Lefevre
Urinary tract infections during pregnancy.
Am Fam Physician. 2000 Feb 1;61(3):713-21.
Abstract/Text Urinary tract infections are common during pregnancy, and the most common causative organism is Escherichia coli. Asymptomatic bacteriuria can lead to the development of cystitis or pyelonephritis. All pregnant women should be screened for bacteriuria and subsequently treated with antibiotics such as nitrofurantoin, sulfisoxazole or cephalexin. Ampicillin should no longer be used in the treatment of asymptomatic bacteriuria because of high rates of resistance. Pyelonephritis can be a life-threatening illness, with increased risk of perinatal and neonatal morbidity. Recurrent infections are common during pregnancy and require prophylactic treatment. Pregnant women with urinary group B streptococcal infection should be treated and should receive intrapartum prophylactic therapy.

PMID 10695584
P J WHALLEY, F G MARTIN, P C PETERS
SIGNIFICANCE OF ASYMPTOMATIC BACTERIURIA DETECTED DURING PREGNANCY.
JAMA. 1965 Sep 13;193:879-81.
Abstract/Text
PMID 14341129
D J Rouse, W W Andrews, R L Goldenberg, J Owen
Screening and treatment of asymptomatic bacteriuria of pregnancy to prevent pyelonephritis: a cost-effectiveness and cost-benefit analysis.
Obstet Gynecol. 1995 Jul;86(1):119-23. doi: 10.1016/0029-7844(95)00097-B.
Abstract/Text OBJECTIVE: To compare the effectiveness, benefits, and costs of two asymptomatic bacteriuria screening and treatment strategies to prevent pyelonephritis in pregnancy.
METHODS: A decision analytic model was created to compare strategies based on either 1) a leukocyte esterase-nitrite dipstick, or 2) on urine culture, with a policy of no screening or treatment. A literature search was conducted to generate probability estimates. Cost estimates were based on a local pharmacy and laboratory survey and supplemented by recent literature estimates. Sensitivity analyses were performed over wide ranges of probability and cost estimates.
RESULTS: Under baseline assumptions, no screening resulted in 23.2 cases of pyelonephritis per 1000 pregnancies, versus 16.2 cases with the dipstick strategy and 11.2 with the culture strategy. The cost of screening and treatment of asymptomatic bacteriuria per 1000 pregnancies was $1968 with dipstick and $19,264 with culture. The cost of treating pyelonephritis with no screening was $57,562, versus $40,257 with dipstick and $27,832 with culture. Therefore, both the dipstick strategy and the culture strategy were cost-beneficial (based on a pyelonephritis cost of $2485) when compared with no screening. However, because it cost $3492 to prevent each additional case of pyelonephritis with culture that was not prevented by dipstick, the culture strategy was not cost-beneficial compared with the dipstick strategy. These results were sensitive to varying estimates for the prevalence of asymptomatic bacteriuria, the rate of progression of asymptomatic bacteriuria to pyelonephritis, the sensitivity of the dipstick, culture costs, and the cost of a case of pyelonephritis.
CONCLUSION: When compared with a policy of no screening, screening for and treatment of asymptomatic bacteriuria to prevent pyelonephritis in pregnancy is cost-beneficial whether based on the leukocyte esterase-nitrite dipstick or on urine culture. However, the culture strategy is not cost-beneficial when compared with the dipstick strategy.

PMID 7784004
R Mittendorf, M A Williams, E H Kass
Prevention of preterm delivery and low birth weight associated with asymptomatic bacteriuria.
Clin Infect Dis. 1992 Apr;14(4):927-32.
Abstract/Text Since the first report of an association between asymptomatic bacteriuria and low birth weight (less than 2,500 g) in 1962, greater than 30 other studies on the same subject have been published. Some of these confirmed this association while others disputed it. Now, however, by using meta-analysis (a technique considered valid by many but not all statisticians) one may conclude with increased certainty that true associations between asymptomatic bacteriuria and preterm delivery (less than 37 weeks of gestation) and asymptomatic bacteriuria and low birth weight do exist. Because asymptomatic bacteriuria in pregnancy remains prevalent and preventable, a review of this important subject is relevant at this time.

PMID 1533541
E Gratacós, P J Torres, J Vila, P L Alonso, V Cararach
Screening and treatment of asymptomatic bacteriuria in pregnancy prevent pyelonephritis.
J Infect Dis. 1994 Jun;169(6):1390-2.
Abstract/Text Although asymptomatic bacteriuria during pregnancy is associated with an increased risk of developing pyelonephritis, the effectiveness of screening programs to reduce this risk is controversial. A sharp reduction in the annual incidence of pyelonephritis (1.8% to 0.6%, P < .001) occurred after the introduction of a program to screen and treat asymptomatic bacteriuria among pregnant women followed at a large teaching hospital. The data provide retrospective and prospective evidence that screening and treatment programs for asymptomatic bacteriuria during pregnancy reduce the risk of pyelonephritis in a population with a moderate to high prevalence of bacteriuria.

PMID 8195624
J Villar, A M Gülmezoglu, M de Onis
Nutritional and antimicrobial interventions to prevent preterm birth: an overview of randomized controlled trials.
Obstet Gynecol Surv. 1998 Sep;53(9):575-85.
Abstract/Text The study was conducted to assess the effectiveness of interventions for the prevention or treatment of nutritional and infectious disorders during pregnancy on preterm birth rates. Cochrane systematic reviews or any other more up-to-date systematic review of antimicrobial and nutritional interventions were sought. Electronic searches of the Cochrane Controlled Trials Register were carried out to identify any trials published since the most recent update of the systematic review. Also, authors of Cochrane systematic reviews, which have not been updated recently, were contacted regarding new information. Systematic reviews of nutritional and antimicrobial interventions during pregnancy, reporting preterm delivery rates (delivery before 37 weeks) and "prematurity" (including low birth weight) either as primary or secondary outcomes, were included. General interventions without a specific nutritional supplementation or antimicrobial component were not considered for inclusion. Interventions to stop labor or prolong pregnancy after a diagnosis of preterm labor were excluded. For each systematic review, data on preterm delivery rate by intervention group was obtained. The total number of trials in the review, number of trials reporting preterm birth as an outcome, number of participants and events have been systematically extracted. Eighteen systematic reviews (10 nutritional and 8 antimicrobial) were considered. Our results indicated that, overall, the treatment of asymptomatic bacteriuria reduces the incidence of preterm birth or low birth weight (< 2500 gm) (typical relative risk (RR): 0.67; 95 percent confidence interval (CI): 0.52-0.85). The protective effect of treating asymptomatic bacteriuria for preterm delivery persisted when only the three trials reporting preterm delivery (< 37 weeks) were included in the meta-analysis (typical RR: 0.53, 95 percent CI: 0.33-0.86). Routine iron supplementation prevents maternal anemia and one trial comparing routine versus selective iron supplementation showed a statistically nonsignificant reduction in preterm birth. Zinc, magnesium, and fish oil supplementations show promising results in reducing preterm birth, but the evidence is not strong. Calcium supplementation remains controversial, although there was a statistically significant reduction in preterm delivery in the subgroup of women at high risk of developing hypertension during pregnancy. Two trials with use of metronidazole (alone or with erythromycin) showed a reduction in preterm delivery in women who were at a high risk of preterm delivery and had bacterial vaginosis at screening. We have concluded that asymptomatic bacteriuria should be screened and treated in all settings that offer antenatal care. Single dose treatment seems to be as effective as longer (4-7 days) treatment, although this needs to be confirmed by a large, methodologically rigorous trial. There are a number of promising interventions such as calcium supplementation in women with low calcium intake, iron, zinc, magnesium, and fish oil supplementation, and treatment of bacterial vaginosis in women at high risk of preterm delivery that need additional research to determine a possible role for prevention of preterm delivery.

PMID 9751940
Matthew E Falagas, Ioannis K Kotsantis, Evridiki K Vouloumanou, Petros I Rafailidis
Antibiotics versus placebo in the treatment of women with uncomplicated cystitis: a meta-analysis of randomized controlled trials.
J Infect. 2009 Feb;58(2):91-102. doi: 10.1016/j.jinf.2008.12.009. Epub 2009 Feb 4.
Abstract/Text BACKGROUND: Acute uncomplicated cystitis is one of the most common bacterial infections in women and is conventionally treated with antibiotics. However, emergence of resistant uropathogens forces physicians to reconsider the prescription of antibiotics for acute uncomplicated cystitis in non-pregnant young women.
OBJECTIVE: To evaluate the effectiveness of antibiotics in the treatment of acute uncomplicated cystitis.
METHODS: We searched PubMed, the Cochrane Central Register of Controlled Trials and Scopus database.
RESULTS: Five randomized controlled trials (RCTs) involving non-pregnant, non-immunocompromised adult women with clinically and microbiologically documented acute uncomplicated cystitis were included. Clinical success was significantly more likely in women treated with antibiotics versus those treated with placebo [4 RCTs, 1062 patients, random effects model (REM), odds ratio (OR)=4.81, 95% confidence intervals (CI)=2.51-9.21]. Antibiotics were also superior to placebo, regarding cure (4 RCTs, 1062 patients, REM, OR=4.67, 95%CI=2.34-9.35); microbiological eradication at the end of treatment (3 RCTs, 967 patients, REM, OR=10.67, 95%CI=2.96-38.43); after the end of treatment (3 RCTs, 738 patients, REM, OR=5.38, 95%CI=1.63-17.77), and microbiological reinfection or relapse (5 RCTs, 843 patients, REM, OR=0.27, 95%CI=0.13-0.55). However, adverse events were more likely to occur in antibiotic-treated patients versus placebo-treated women (4 RCTs, 1068 patients, REM, OR=1.64, 95%CI=1.10-2.44). No difference was found between the compared treatment arms regarding study withdrawals from adverse events, the development of pyelonephritis and emergence of resistance.
CONCLUSION: Antibiotics are superior to placebo regarding both clinical and microbiological success in adult non-pregnant women with microbiologically confirmed acute uncomplicated cystitis. However, they are associated with more adverse events.

PMID 19195714
Florian M E Wagenlehner, Udo Hoyme, Martin Kaase, Reinhard Fünfstück, Kurt G Naber, Guido Schmiemann
Uncomplicated urinary tract infections.
Dtsch Arztebl Int. 2011 Jun;108(24):415-23. doi: 10.3238/arztebl.2011.0415. Epub 2011 Jun 17.
Abstract/Text BACKGROUND: Urinary tract infections (UTIs) are among the most common types of bacterial infection in outpatient medicine. Rising rates of antibiotic resistance and a better understanding of the ecological adverse effects (collateral damage) of antibiotics warrant a reevaluation of the treatment recommendations for uncomplicated UTI. The new S3 guideline contains updated recommendations.
METHODS: The new S3 guideline is based on a review of publications on uncomplicated UTI retrieved by a systematic search of the Medline and Cochrane Library databases. Guidelines from abroad were also considered in the review.
RESULTS: Uncomplicated UTI is classified as either uncomplicated cystitis (UC) or uncomplicated pyelonephritis (UP). The choice of a suitable antibiotic is determined by the following main criteria: the patient's individual risk profile and prior antibiotic treatment, if any; the spectrum of pathogens and antibiotic susceptibility; the proven efficacy of the antibiotic; the ecological adverse effects (collateral damage) of antimicrobial therapy; the side effects for the patient under treatment. On the basis of these criteria, co-trimoxazole/trimethoprim and fluoroquinolones can no longer be recommended as first-line empirical treatment for UC. Rather, the new recommended treatment of first choice consists of fosfomycin-trometamol, nitrofurantoin, or pivmecillinam. High-dose fluoroquinolones are still recommended, however, as first-line oral treatment for UP. Asymptomatic bacteriuria should only be treated in exceptional situations such as pregnancy or before urological procedures that will probably injure the mucosa of the urinary tract.
CONCLUSION: The new S3 guideline on uncomplicated UTI incorporates a forward-looking approach to the use of antibiotics in treating this common type of infection. It is intended to bring about a sustained improvement in the quality of care.

PMID 21776311
R Ikäheimo, A Siitonen, T Heiskanen, U Kärkkäinen, P Kuosmanen, P Lipponen, P H Mäkelä
Recurrence of urinary tract infection in a primary care setting: analysis of a 1-year follow-up of 179 women.
Clin Infect Dis. 1996 Jan;22(1):91-9. doi: 10.1093/clinids/22.1.91.
Abstract/Text In a prospective study, 179 adult women (age range, 17-82 years) were followed up for 12 months after an index episode of community-acquired cystitis caused by Escherichia coli. Episodes of symptomatic urinary tract infection (UTI) were recorded, and urinary isolates were compared with the index episode isolate; 147 UTI episodes were detected during the follow-up. Of these episodes, 131 were classified as recurrences occurring at least 1 month after the index episode; 44% of the patients had recurrences. A history of UTI increased the risk of recurrence; only 11.8% of the 17 patients without previous episodes of UTI had at least one recurrence, while 47.5% of those with previous episodes had at least one recurrence (OR, 6.8; univariate logistic regression). E. coli caused 78% of the recurrent episodes. Phenotypic and genotypic analysis of E. coli strains showed that one-third of the recurrences were caused by the index episode strain, which could persist and cause recurrences throughout the 1-year follow-up period. The prevalence of adhesins or other identified virulence factors for UTI among the recurrence strains was identical to that among the index episode strains. The presence of these factors did not affect the risk of recurrence but did increase the likelihood that the index episode strain would persist and cause recurrent episodes of UTI.

PMID 8824972
P Little, R Merriman, S Turner, K Rumsby, G Warner, J A Lowes, H Smith, C Hawke, G Leydon, M Mullee, M V Moore
Presentation, pattern, and natural course of severe symptoms, and role of antibiotics and antibiotic resistance among patients presenting with suspected uncomplicated urinary tract infection in primary care: observational study.
BMJ. 2010 Feb 5;340:b5633. Epub 2010 Feb 5.
Abstract/Text OBJECTIVE: To assess the natural course and the important predictors of severe symptoms in urinary tract infection and the effect of antibiotics and antibiotic resistance.
DESIGN: Observational study.
SETTING: Primary care.
PARTICIPANTS: 839 non-pregnant adult women aged 18-70 presenting with suspected urinary tract infection.
MAIN OUTCOME MEASURE: Duration and severity of symptoms.
RESULTS: 684 women provided some information on symptoms; 511 had both laboratory results and complete symptom diaries. For women with infections sensitive to antibiotics, severe symptoms, rated as a moderately bad problem or worse, lasted 3.32 days on average. After adjustment for other predictors, moderately bad symptoms lasted 56% longer (incidence rate ratio 1.56, 95% confidence interval 1.22 to 1.99, P<0.001) in women with resistant infections; 62% longer (1.62, 1.13 to 2.31, P=0.008) when no antibiotics prescribed; and 33% longer (1.33, 1.14 to 1.56, P<0.001) in women with urethral syndrome. The duration of symptoms was shorter if the doctor was perceived to be positive about diagnosis and prognosis (continuous 7 point scale: 0.91, 0.84 to 0.99; P=0.021) and longer when the woman had frequent somatic symptoms (1.03, 1.01 to 1.05, P=0.002; for each symptom), a history of cystitis, urinary frequency, and more severe symptoms at baseline.
CONCLUSION: Antibiotic resistance and not prescribing antibiotics are associated with a greater than 50% increase in the duration of more severe symptoms in women with uncomplicated urinary tract infection. Women with a history of cystitis, frequent somatic symptoms (high somatisation), and severe symptoms at baseline can be given realistic advice that they are likely to have severe symptoms lasting longer than three days.

PMID 20139213
S H Zinner, E H Kass
Long-term (10 to 14 years) follow-up of bacteriuria of pregnancy.
N Engl J Med. 1971 Oct 7;285(15):820-4. doi: 10.1056/NEJM197110072851502.
Abstract/Text
PMID 4936826
Lindsay E Nicolle, Suzanne Bradley, Richard Colgan, James C Rice, Anthony Schaeffer, Thomas M Hooton, Infectious Diseases Society of America, American Society of Nephrology, American Geriatric Society
Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults.
Clin Infect Dis. 2005 Mar 1;40(5):643-54. doi: 10.1086/427507. Epub 2005 Feb 4.
Abstract/Text
PMID 15714408
L M Vercaigne, G G Zhanel
Recommended treatment for urinary tract infection in pregnancy.
Ann Pharmacother. 1994 Feb;28(2):248-51.
Abstract/Text OBJECTIVE: To establish and recommend a therapeutic regimen for the treatment of urinary tract infection (UTI) in pregnancy based on the published studies.
DATA SOURCES: An English-language literature search employing MEDLINE, Index Medicus, and bibliographic reviews of the references obtained were searched (key terms: urinary tract infection, UTI, pregnancy, bacteriuria).
STUDY SELECTION AND DATA EXTRACTION: All identified human studies dealing with bacteriuria or UTI in pregnancy were analyzed.
DATA SYNTHESIS: Limited data are available regarding the appropriate antibiotic management of UTI in pregnancy. Single-dose cure rates with amoxicillin are approximately 80 percent. Trimethoprim/sulfamethoxazole provides cure rates of greater than 80 percent. Cephalosporins and nitrofurantoin produce variable results.
CONCLUSIONS: We recommend separating pregnant subjects with UTI into two groups. Those with asymptomatic bacteriuria can be treated with a single dose of an antimicrobial to which the organism is susceptible. For those with symptomatic UTI, we recommend amoxicillin 500 mg tid for three days. Urine cultures should be repeated seven days following therapy to assess cure or failure. Well-designed studies need to be performed, comparing single-dose and three-day therapy for UTI in pregnancy.

PMID 8173146
Ryoichi Hamasuna, Hironori Betsunoh, Tetsuya Sueyoshi, Kazumichi Yakushiji, Hiromasa Tsukino, Masafumi Nagano, Toshiyuki Takehara, Yukio Osada
Bacteria of preoperative urinary tract infections contaminate the surgical fields and develop surgical site infections in urological operations.
Int J Urol. 2004 Nov;11(11):941-7. doi: 10.1111/j.1442-2042.2004.00941.x.
Abstract/Text BACKGROUND: The risk factors for surgical site infection (SSI) following urological operations have not been clearly identified, although the presence of a preoperative urinary tract infection (UTI) is thought to be one risk factor. We studied potential risk factors to clarify when and how bacteria contaminate wounds and SSI develop.
METHODS: Objects of the present study were patients with SSI after open urological operations that were performed at the Department of Urology, Miyazaki Medical College Hospital, University of Miyazaki, Kiyotake, Miyazaki, Japan, during the period between June 1999 and December 2000. Endourological operations, operations on children and short operations of less than 2 h duration were excluded. Patients were screened for the presence of UTI before the operation and subcutaneous swabs for culture were collected at the end of the operation by brushing with a sterile cotton-swab just before skin closure.
RESULTS: Surgical site infections occurred in 20 of 134 patients. Bacteria from the subcutaneous swabs were detected in 15 (75.0%) of the patients with SSI. All patients received antimicrobial prophylaxis (AMP), but bacteria from the subcutaneous swabs of patients with SSI were less susceptible to the agents (20.0%). Preoperative UTI were observed in 11 (55.0%) of the patients with SSI. In these patients, four had the same species of bacteria detected from urine, swab and wound, three had the same species from swab and wound and one had the same species from urine and wound.
CONCLUSIONS: Preoperative UTI was the most important risk factor for SSI following urological operations. It is most likely that the bacteria in the urine contaminated the surgical fields and the AMP resistant strains produced SSI.

PMID 15509195
S Richter, R Lang, F Zur, I Nissenkorn
Infected urine as a risk factor for postprostatectomy wound infection.
Infect Control Hosp Epidemiol. 1991 Mar;12(3):147-9.
Abstract/Text OBJECTIVE: To study the relation of preoperative infected urine and postprostatectomy wound infection in patients with and without indwelling bladder catheters.
DESIGN: Patients undergoing prostatectomy were evaluated for the presence of infected urine prior to prostatectomy and postoperative wound infection. They were further divided into patients with indwelling urinary catheter and catheter-free patients. All had received antibiotic prophylaxis.
PATIENTS: One hundred fifty consecutive patients undergoing open prostatectomy--mean age was 67 years; 100 patients with an indwelling catheter for a mean period of 50 days; 50 catheter-free patients.
RESULTS: Wound infection was found in 19 of 81 (23.5%) and in 6 of 69 (8.7%) patients with infected and sterile urine, respectively (p = .028). In patients with indwelling catheters prior to operation, wound infection was 22.4% when urine was infected and 8.3% when it was not. In patients without catheters, infected urine was associated with 40% of wound infections, as compared with 8.9% of wound infections in patients with sterile urine. Organisms obtained from infected wound and urine were identical in 84% of cases. These results were obtained despite antibiotic prophylaxis.
CONCLUSIONS: Wound infection has been demonstrated to be a postprostatectomy complication directly related to the presence of urinary infection at surgery; thus, elective prostatectomy should be deferred until urine becomes sterile.

PMID 2022859
G K Harding, L E Nicolle, A R Ronald, J K Preiksaitis, K R Forward, D E Low, M Cheang
How long should catheter-acquired urinary tract infection in women be treated? A randomized controlled study.
Ann Intern Med. 1991 May 1;114(9):713-9.
Abstract/Text OBJECTIVE: To determine the optimal management of catheter-acquired bacteriuria after short-term catheter use in women.
PATIENTS: Asymptomatic patients (119) with catheter-acquired bacteriuria were randomly assigned to receive no therapy, a single dose (320-1600 mg) of therapy with trimethoprim-sulfamethoxazole, or 10 days (160-800 mg twice daily) of therapy. Thirty-two patients with lower tract symptoms alone received a single dose or 10 days of therapy, and 10 patients with upper tract symptoms or signs received 10 days of therapy.
MAIN RESULTS: The mean and median durations of catheter use were 6 and 4 days, respectively. Bacteriuria resolved within 14 days without therapy in 15 of 42 (36%; 95% CI, 21% to 51%) asymptomatic patients. Seven of the remaining patients developed symptoms. Single-dose therapy resolved infection in 30 of 37 patients (81%; CI, 68% to 94%); 10 days of therapy resolved infection in 26 of 33 (79%; CI, 65% to 93%). For patients with lower tract symptoms alone, resolution rates with single-dose therapy or 10 days of therapy were similar (11 of 14 [79%] and 13 of 16 [81%], respectively). Ten days of therapy resolved infection in 6 of 9 (67%) patients with upper tract symptoms. Infection was resolved more often in women who were less than or equal to 65 years than in older women (62 of 70 [89%] versus 24 of 39 [62%]; P less than 0.001). Bacteriuria resolved spontaneously more frequently in younger (14 of 19 [74%] compared with 1 of 23 older women [4%]; P less than 0.001). Single-dose therapy resolved infection in 31 of 33 (94%) patients who were less than or equal to 65 years.
CONCLUSIONS: Asymptomatic bacteriuria after short-term catheter use frequently becomes symptomatic and should be treated. For asymptomatic patients and patients with lower tract symptoms alone, single-dose therapy was as effective as 10 days of therapy; it was very effective in women who were less than or equal to 65 years. Bacteriuria resolved spontaneously within 14 days after catheter removal more commonly in women who were less than or equal to 65 years and both types of therapy were less effective in older women.

PMID 2012351
A Iravani, I Klimberg, C Briefer, C Munera, S F Kowalsky, R M Echols
A trial comparing low-dose, short-course ciprofloxacin and standard 7 day therapy with co-trimoxazole or nitrofurantoin in the treatment of uncomplicated urinary tract infection.
J Antimicrob Chemother. 1999 Mar;43 Suppl A:67-75.
Abstract/Text The study was undertaken to compare the safety and efficacy of twice-daily ciprofloxacin for 3 days with standard 7 day therapy with either co-trimoxazole or nitrofurantoin in the treatment of women with acute, uncomplicated urinary tract infections (UTI). This multicentre, prospective, randomized, double-blind trial compared oral ciprofloxacin (100 mg bd) for 3 days with co-trimoxazole (160/800 mg bd) or nitrofurantoin (100 mg bd) for 7 days. Bacteriological and clinical evaluations were performed at study entry, during therapy and 4-10 days and 4-6 weeks after the completion of therapy. The primary efficacy parameter was eradication of the causative organism 4-10 days following treatment. Of 713 women enrolled and evaluable for safety, 521 were evaluable for efficacy (168 ciprofloxacin, 174 co-trimoxazole, 179 nitrofurantoin). Escherichia coli (83%) was the most frequently isolated pathogen in all treatment groups. Bacteriological eradication was reported in 88% of ciprofloxacin patients, 93% of co-trimoxazole patients and 86% of nitrofurantoin patients. At the 4-6 week follow-up, ciprofloxacin had statistically significantly higher eradication rates (91%) than co-trimoxazole (79%; 95% confidence limit (CL) = -20.6%, -3.9%) and nitrofurantoin (82%; 95% CL = -17.1%, -0.9%). Clinical resolution 4-10 days after therapy and at the 4-6 week follow-up was similar among the three treatment groups. The overall incidence of treatment-emergent adverse events was not significantly different (P = 0.093) among the three drug regimens, although co-trimoxazole was associated with a greater number of adverse events than ciprofloxacin (P < or = 0.05). Ciprofloxacin also caused fewer episodes of nausea than either of the other agents (P < or = 0.01).

PMID 10225575
L E Nicolle, K S Madsen, G O Debeeck, E Blochlinger, N Borrild, J P Bru, C Mckinnon, B O'Doherty, W Spiegel, F A M Van Balen, P Menday
Three days of pivmecillinam or norfloxacin for treatment of acute uncomplicated urinary infection in women.
Scand J Infect Dis. 2002;34(7):487-92. doi: 10.1080/00365540110080728.
Abstract/Text Pivmecillinam is a unique beta-lactam antimicrobial that has been used for the treatment of acute uncomplicated urinary infection for > 20 y. Since this agent was introduced, the quinolone antimicrobials have become widely used for the same indication. This study compared the efficacy of a 3-d regimen of pivmecillinam 400 mg b.i.d. with norfloxacin 400 mg b.i.d. Women aged between 18 and 65 y presenting with symptoms of acute cystitis of < 7 d duration were eligible for enrollment; 483 were randomized to receive pivmecillinam and 471 to receive norfloxacin. In each group, 30% of women had negative urine cultures prior to therapy. Bacteriologic cure at early post-therapy follow-up was achieved in 222/298 (75%) pivmecillinam patients and 276/302 (91%) norfloxacin patients [p < 0.001; 95% confidence interval (CI) 12.0-21.8]. Clinical cure/improvement at Day 4 following initiation of therapy was observed in 434/457 (95%) women who received pivmecillinam and 425/442 (96%) who received norfloxacin (p = 0.39; 95% CI 1.5-3.9). Early post-therapy (11 +/- 2 d) clinical cure was achieved in 360/437 women (82%) who received pivmecillinam and 381/433 (88%) who received norfloxacin (p = 0.019; 95% CI 0.9-10.3). In women aged < or = 50 y, early clinical cure rates were 294/351 (84%) for pivmecillinam and 299/340 (88%) for norfloxacin (p = 0.11; 95% CI 1.0-9.4). Adverse effects were similar for both regimens, and there was no evidence of the emergence of organisms of increasing resistance with therapy. Short-course therapy with norfloxacin was superior to that with pivmecillinam in terms of bacteriologic outcome, although differences in clinical outcome were less marked. In conclusion, short-course therapy with pivmecillinam is an effective empirical treatment for pre-menopausal women.

PMID 12195873
D Henry, W Ellison, J Sullivan, D L Mansfield, D J Magner, M B Dorr, G H Talbot
Treatment of community-acquired acute uncomplicated urinary tract infection with sparfloxacin versus ofloxacin. The Sparfloxacin Multi Center UUTI Study Group.
Antimicrob Agents Chemother. 1998 Sep;42(9):2262-6.
Abstract/Text The efficacy and safety of a 3-day regimen of sparfloxacin were compared with those of a 3-day regimen of ofloxacin for the treatment of community-acquired acute uncomplicated urinary tract infections. Four hundred nineteen women were enrolled in a randomized, open-label, observer-blinded, multicenter study; 204 received sparfloxacin as a 400-mg loading dose on the first day and 200 mg once daily thereafter, and 215 received ofloxacin as 200 mg twice daily. A total of 383 patients met the criteria for clinical evaluability, and 174 were also bacteriologically evaluable; all treated patients were included in the safety analysis. Escherichia coli (86%) and Staphylococcus saprophyticus (4.6%) were the organisms most commonly isolated. Positive clinical responses were obtained 5 to 9 days after therapy in more than 92% of the patients in each group; sustained clinical cure rates 4 to 6 weeks after therapy were 78.3 and 76.9% in the sparfloxacin and ofloxacin groups, respectively. A positive bacteriologic response was observed in 98% of the bacteriologically evaluable patients in each treatment group at 5 to 9 days posttherapy and in 88.2 and 92.6% of the patients in the sparfloxacin and ofloxacin groups, respectively, 4 to 6 weeks after therapy. Almost 90% of all adverse events were of mild or moderate severity; the most frequent events at least possibly related to drug treatment were those common to the fluoroquinolones, namely, nausea, diarrhea, headache, insomnia, and photosensitivity. Photosensitivity was more frequent in the sparfloxacin group (6.9% versus 0.5% in the ofloxacin group); insomnia was more frequent in the ofloxacin group (3.7% versus 1.0% in the sparfloxacin group). These data suggest that a once-daily, 3-day regimen of sparfloxacin is effective and generally well tolerated in the treatment of acute uncomplicated urinary tract infections.

PMID 9736546
Abstract/Text OBJECTIVES: To compare the efficacy and safety of single-dose and 3-day fluoroquinolone treatment of uncomplicated urinary tract infection (UTI).
METHODS: Adult women with acute uncomplicated UTI were randomized to receive either a single dose of gatifloxacin (400 mg), 3 days of gatifloxacin (200 mg daily), or 3 days of ciprofloxacin (100 mg twice daily). Patients were assessed at four points during the study: before treatment (within 48 hours before the initiation of the study medication), at the end of treatment (by telephone contact on day 3), and twice after treatment completion (5 to 9 days after treatment [test-of-cure visit] and 29 to 42 days after treatment [only patients with a bacteriologic response of eradication at the test-of-cure visit]).
RESULTS: The bacterial eradication rate for the single-dose gatifloxacin, 3-day gatifloxacin, and 3-day ciprofloxacin groups was 90%, 95%, and 89%, respectively; the clinical efficacy rate was 93%, 95%, and 93%, respectively, for microbiologically assessable patients at the test-of-cure visit. Eradication of the most common uropathogens, including Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis, was achieved with gatifloxacin and ciprofloxacin. Single-dose gatifloxacin was equivalent to 3-day ciprofloxacin in both microbiologic and clinical efficacy.
CONCLUSIONS: Single-dose and 3-day gatifloxacin were microbiologically and clinically equivalent to 3-day ciprofloxacin for the treatment of acute UTI among women. Single-dose gatifloxacin may offer advantages over 3-day fluoroquinolone therapy for uncomplicated UTI by decreasing secondary use of medical resources and improving patient compliance.

PMID 11880065
Jean L Fourcroy, Bret Berner, Yu-Kun Chiang, Marilou Cramer, Lynne Rowe, Neal Shore
Efficacy and safety of a novel once-daily extended-release ciprofloxacin tablet formulation for treatment of uncomplicated urinary tract infection in women.
Antimicrob Agents Chemother. 2005 Oct;49(10):4137-43. doi: 10.1128/AAC.49.10.4137-4143.2005.
Abstract/Text The efficacy and safety of a novel once-daily extended-release ciprofloxacin (ciprofloxacin ER) 500-mg dose were compared with those of an immediate-release ciprofloxacin (ciprofloxacin IR) 250-mg twice-daily dose, each administered orally for 3 days in the treatment of acute uncomplicated urinary tract infection (uUTI) in women. Adult female outpatients (mean age, 39 years) with clinical signs and symptoms of acute uUTI and a positive pretreatment urine culture (> or =10(5) CFU/ml) were enrolled in a multicenter, randomized, double-blind, noninferiority trial. Patients were assessed at a test-of-cure visit (4 to 11 days posttreatment) and a late-posttreatment visit (4 to 6 weeks posttreatment) for microbiological and clinical outcomes and safety. The primary efficacy endpoint and microbiological eradication rate at the test-of-cure visit in the ciprofloxacin ER group (254/272; 93.4%) were noninferior to those in the ciprofloxacin IR group (225/251; 89.6%) (95% confidence interval [CI] of difference, -0.99%, 8.59%). Clinical-cure rates at the test-of-cure visit were 85.7% (233/272) for ciprofloxacin ER and 86.1% (216/251) for ciprofloxacin IR (95% CI of difference, -6.37%, 5.57%). At the late-posttreatment visit, microbiological and clinical outcomes were similar for the two treatments and consistent with test-of-cure results. Both treatments were well tolerated, but the frequencies of nausea and diarrhea were lower in the ciprofloxacin ER group than in the ciprofloxacin IR group (nausea, ER, 0.6%; IR, 2.2%; P = 0.033; diarrhea, ER, 0.2%; IR, 1.4%; P = 0.037). Once-daily ciprofloxacin ER was safe, effective, and noninferior to twice-daily ciprofloxacin IR in the treatment of acute uUTI. Additionally, ciprofloxacin ER was associated with significantly reduced frequencies of nausea and diarrhea.

PMID 16189090
Dan C Henry, Robert B Bettis, Ernie Riffer, Daniel C Haverstock, Steven F Kowalsky, Kathryn Manning, Kamal A Hamed, Deborah A Church
Comparison of once-daily extended-release ciprofloxacin and conventional twice-daily ciprofloxacin for the treatment of uncomplicated urinary tract infection in women.
Clin Ther. 2002 Dec;24(12):2088-104.
Abstract/Text BACKGROUND: Trimethoprim/sulfamethoxazole (TMP/SMX) is currently the first choice for empiric therapy of acute uncomplicated urinary tract infection (UTI) in women. In areas where resistance to TMP/SMX is known to be high, ciprofloxacin and other fluoroquinolones are recommended as first-line choices for the empiric therapy of UTI.
OBJECTIVE: This study compared the efficacy and safety profile of once-daily extended-release ciprofloxacin 500 mg (referred to hereafter as ciprofloxacin QD) with those of conventional ciprofloxacin 250 mg BID, each administered orally for 3 days, in the treatment of uncomplicated UTI in women.
METHODS: In this multicenter, prospective, randomized, double-blind, double-dummy, Phase III trial, adult women with clinical signs and symptoms of acute uncomplicated UTI, pyuria, and a positive pretherapy urine culture (>/=10(5) colony-forming units/mL) received ciprofloxacin QD or ciprofloxacin BID. Bacteriologic and clinical outcomes were assessed at the test-of-cure visit (4-11 days after completion of therapy) and the late follow-up visit (25-50 days after completion of therapy).
RESULTS: The intent-to-treat population consisted of 891 patients (444 ciprofloxacin QD, 447 ciprofloxacin BID); 422 patients were evaluable for efficacy (199 ciprofloxacin QD, 223 ciprofloxacin BID). At the test-of-cure visit, bacteriologic eradication was achieved in 94.5% (188/199) of the ciprofloxacin QD group and 93.7% (209/223) of the ciprofloxacin BID group (95% CI, -3.5 to 5.1). Clinical cure was achieved in 95.5% (189/198) of the ciprofloxacin QD group and 92.7% (204/220) of the ciprofloxacin BID group (95% CI, -1.6 to 7.1). Bacteriologic and clinical outcomes at the late follow-up visit were consistent with the test-of-cure findings. The rate of eradication of Escherichia coli, the most prevalent organism, was >97% in each treatment group. Rates of drug-related adverse events were similar with the once- and twice-daily ciprofloxacin regimens (10% and 9%, respectively).
CONCLUSION: Extended-release ciprofloxacin 500 mg given once daily for 3 days was as effective and well tolerated as conventional ciprofloxacin 250 mg given twice daily for 3 days in the treatment of acute uncomplicated UTI in women.

PMID 12581547
Thomas Vogel, René Verreault, Marie Gourdeau, Michèle Morin, Lise Grenier-Gosselin, Louis Rochette
Optimal duration of antibiotic therapy for uncomplicated urinary tract infection in older women: a double-blind randomized controlled trial.
CMAJ. 2004 Feb 17;170(4):469-73.
Abstract/Text BACKGROUND: The optimal duration of antibiotic therapy in older patients with uncomplicated urinary tract infection (UTI) is still a matter of debate. The aim of this randomized controlled double-blind noninferiority trial was to compare the efficacy and safety of 3-day and 7-day courses of oral ciprofloxacin for uncomplicated symptomatic UTI in older women.
METHODS: A total of 183 women at least 65 years of age with acute uncomplicated UTI were recruited from ambulatory clinics and hospital acute care units. Patients with pyelonephritis, contraindications to fluoroquinolones, recent use of antibiotics, urinary tract abnormalities and diabetes mellitus were excluded. Women were randomly assigned to receive either ciprofloxacin 250 mg twice daily orally for 3 days followed by placebo for 4 days (the 3-day group, 93 patients) or ciprofloxacin 250 mg twice daily orally for 7 days (the 7-day group, 90 patients). Bacterial eradication, clinical improvement and occurrence of adverse events were determined 2 days after completion of treatment, and occurrence of reinfection or relapse were determined 6 weeks after completion of treatment. Bacterial eradication and relapse were determined by urine culture. Double-blind procedures were maintained throughout data collection.
RESULTS: The proportion of patients with bacterial eradication at 2 days after treatment was 98% (91/93) in the 3-day group and 93% (83/89) in the 7-day group (p = 0.16). The frequency of adverse events, including drowsiness, headache, nausea or vomiting, and loss of appetite, was significantly lower in the 3-day group.
INTERPRETATION: These results suggest that a 3-day course of antibiotic therapy is not inferior to a 7-day course for treatment of uncomplicated symptomatic UTI in older women, and that the shorter course is better tolerated.

PMID 14970093
F Auquer, F Cordón, E Gorina, J C Caballero, C Adalid, J Batlle, Urinary Tract Infection Study Group
Single-dose ciprofloxacin versus 3 days of norfloxacin in uncomplicated urinary tract infections in women.
Clin Microbiol Infect. 2002 Jan;8(1):50-4.
Abstract/Text A double-blind, randomized controlled study to evaluate the efficacy and safety of a single dose of 500 mg of ciprofloxacin versus 3 days 400 mg twice-daily of norfloxacin in uncomplicated urinary tract infection in women was designed. Patients underwent four visits: baseline, and at 3, 7 and 28 days. The main efficacy variables were clinical and microbiological outcome at day 7. Analyses on both valid patients and intention-to-treat populations were performed. Two hundred and twenty-six patients (114 receiving ciprofloxacin and 112 receiving norfloxacin) were considered valid for efficacy evaluation. Bacteriologic cure was 91.2% in the ciprofloxacin group and 91.9% in the norfloxacin group. Clinical resolution was 91.2 and 93.8%, respectively. Both treatments were equally efficacious (P = 0.016).

PMID 11906502
Thomas M Hooton, Delia Scholes, Kalpana Gupta, Ann E Stapleton, Pacita L Roberts, Walter E Stamm
Amoxicillin-clavulanate vs ciprofloxacin for the treatment of uncomplicated cystitis in women: a randomized trial.
JAMA. 2005 Feb 23;293(8):949-55. doi: 10.1001/jama.293.8.949.
Abstract/Text CONTEXT: The high prevalence of resistance to trimethoprim-sulfamethoxazole and other antimicrobials among Escherichia coli causing acute cystitis in women has led to increased use of alternative antibiotics. One such antibiotic, amoxicillin-clavulanate, has not been well studied.
OBJECTIVE: To compare the efficacy of a 3-day regimen of amoxicillin-clavulanate to that of a 3-day regimen of ciprofloxacin in the treatment of acute cystitis in women. The primary study hypothesis was that the amoxicillin-clavulanate and ciprofloxacin treatment groups would differ in clinical cure.
DESIGN, SETTING, AND PATIENTS: Randomized, single-blind treatment trial of 370 women, aged 18 to 45 years, with symptoms of acute uncomplicated cystitis and a urine culture with at least 10(2) colony-forming units of uropathogens per milliliter from a university student health center or a health maintenance organization.
INTERVENTIONS: Women were randomly assigned to receive amoxicillin-clavulanate (500 mg/125 mg twice daily) or ciprofloxacin (250 mg twice daily) for 3 days and were followed up for 4 months.
MAIN OUTCOME MEASURES: The main outcome measure was clinical cure. Secondary study outcomes of interest were microbiological cure and vaginal E coli colonization at the 2-week follow-up visit.
RESULTS: Clinical cure was observed in 93 (58%) of 160 women treated with amoxicillin-clavulanate compared with 124 (77%) of 162 women treated with ciprofloxacin (P<.001). Amoxicillin-clavulanate was not as effective as ciprofloxacin even among women infected with strains susceptible to amoxicillin-clavulanate (65 [60%] of 109 women in the amoxicillin-clavulanate group vs 114 [77%] of 149 women in the ciprofloxacin group; P = .004). The difference in clinical cure rates occurred almost entirely within the first 2 weeks after therapy. Microbiological cure at 2 weeks was observed in 118 (76%) of 156 women treated with amoxicillin-clavulanate compared with 153 (95%) of 161 women treated with ciprofloxacin (P<.001). At this visit, 45% of women in the amoxicillin-clavulanate group compared with 10% in the ciprofloxacin group had vaginal colonization with E coli (P<.001).
CONCLUSIONS: A 3-day regimen of amoxicillin-clavulanate is not as effective as ciprofloxacin for the treatment of acute uncomplicated cystitis, even in women infected with susceptible strains. This difference may be due to the inferior ability of amoxicillin-clavulanate to eradicate vaginal E coli, facilitating early reinfection.

PMID 15728165
Monika Lutters, Nicole B Vogt-Ferrier
Antibiotic duration for treating uncomplicated, symptomatic lower urinary tract infections in elderly women.
Cochrane Database Syst Rev. 2008 Jul 16;(3):CD001535. doi: 10.1002/14651858.CD001535.pub2. Epub 2008 Jul 16.
Abstract/Text BACKGROUND: Urinary tract infections (UTI) are common in elderly patients. Authors of non systematic literature reviews often recommend longer treatment durations (7 to 14 days) for older women, but the evidence for such recommendations is unclear.
OBJECTIVES: To determine the optimal duration of antibiotic treatment for uncomplicated symptomatic lower UTI in elderly women.
SEARCH STRATEGY: We contacted known investigators and pharmaceutical companies, screened reference lists of identified articles, reviews and books, and searched MEDLINE, EMBASE, CINAHL, Healthstar, Popline, Gerolit, Bioethics Line, The Cochrane Library, Dissertation Abstracts International and Index to Scientific & Technical Proceedings without language restriction. Date of most recent search: 7 May 2008.
SELECTION CRITERIA: All randomised controlled trials (RCTs) comparing different treatment durations of oral antibiotics for uncomplicated symptomatic lower UTIs in elderly women were included. Whenever possible we obtained outcome data for older women included in studies with a broader age range. We excluded patients with fever, flank pain or complicating factors; studies with treatment durations longer than 14 days and prevention studies.
DATA COLLECTION AND ANALYSIS: The two authors independently assessed study quality and extracted data. Statistical analyses were performed using the random effects model and results expressed as risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes with 95% confidence intervals (CI).
MAIN RESULTS: Fifteen studies (1644 elderly women) were included. Three studies compared single dose with short-course treatment (3 to 6 days), six compared single dose with long-course treatment (7 to 14 days) and six compared short- with long-course treatment. Methodological quality of all studies was low except for a more recent geriatric study. There was a significant difference for persistent UTI between single dose and short-course treatment (RR 2.01, 95% CI 1.05 to 3.84) and single versus long-course treatment (RR 1.93, 1.01 to 3.70 95% CI), in the short-term (< 2 weeks post-treatment) but not at long-term follow-up or on clinical outcomes. Patients preferred single dose treatment (RR 0.73, 95% CI 0.60 to 0.88) to long-course treatments, but this was based on one study comparing different antibiotics. Short versus longer treatments showed no significant difference in efficacy. Rate of adverse drug reactions increased significantly with longer treatment durations in only one study.
AUTHORS' CONCLUSIONS: Short-course treatment (3 to 6 days) could be sufficient for treating uncomplicated UTIs in elderly women, although more studies on specific commonly prescribed antibiotics are needed.

PMID 18646074
Takuya Sadahira, Koichiro Wada, Motoo Araki, Ayano Ishii, Atsushi Takamoto, Yasuyuki Kobayashi, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu, Hiromi Kumon, Okayama Urological Research Group (OURG)
Efficacy and safety of 3 day versus 7 day cefditoren pivoxil regimens for acute uncomplicated cystitis: multicentre, randomized, open-label trial.
J Antimicrob Chemother. 2017 Feb;72(2):529-534. doi: 10.1093/jac/dkw424. Epub 2016 Oct 12.
Abstract/Text BACKGROUND: Fluoroquinolone-non-susceptible Escherichia coli isolated from patients with acute uncomplicated cystitis are a matter of increasing concern. Cefditoren pivoxil is an oral, β-lactamase-stable, extended-spectrum cephalosporin that is effective against fluoroquinolone-non-susceptible bacteria.
OBJECTIVES: To evaluate the clinical and microbiological efficacies of cefditoren pivoxil against acute uncomplicated cystitis and to determine the optimal duration of cefditoren pivoxil treatment.
METHODS: We compared 3 and 7 day regimens of cefditoren pivoxil in a multicentre, randomized, open-label study.
RESULTS: A total of 104 female patients with acute uncomplicated cystitis were enrolled and randomized into 3 day (n = 51) or 7 day (n = 53) treatment groups. At first visit, 94 bacterial strains were isolated from the 104 participants of which 81.7% (85/104) were E. coli. Clinical and microbiological efficacies were evaluated 5-9 days following administration of the final dose of cefditoren pivoxil. The clinical efficacies of the 3 and 7 day groups were 90.9% (40/44) and 93.2% (41/44), respectively (P = 1.000). The microbiological efficacies of the 3 and 7 day groups were 82.5% (33/40) and 90.2% (37/41), respectively (P = 0.349). There were no adverse events due to cefditoren pivoxil treatment, with the exception of a mild allergic reaction in one patient, after which the cefditoren pivoxil was exchanged for another antimicrobial.
CONCLUSIONS: Cefditoren pivoxil is safe and effective for uncomplicated cystitis, with no significant differences in clinical and microbiological efficacies between 3 and 7 day regimens.

© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
PMID 27733519
Hiroshi Hayami, Satoshi Takahashi, Kiyohito Ishikawa, Mitsuru Yasuda, Shingo Yamamoto, Koichiro Wada, Kanao Kobayashi, Ryoichi Hamasuna, Shinichi Minamitani, Tetsuya Matsumoto, Hiroshi Kiyota, Kazuhiro Tateda, Junko Sato, Hideaki Hanaki, Naoya Masumori, Hiroyuki Nishiyama, Jun Miyazaki, Kiyohide Fujimoto, Kazushi Tanaka, Shinya Uehara, Akio Matsubara, Kenji Ito, Kenji Hayashi, Yuichiro Kurimura, Shin Ito, Toshimi Takeuchi, Harunori Narita, Masanobu Izumitani, Hirofumi Nishimura, Motoshi Kawahara, Makoto Hara, Takahide Hosobe, Kenji Takashima, Hirofumi Chokyu, Masaru Matsumura, Hideari Ihara, Satoshi Uno, Koichi Monden, Toru Sumii, Shuichi Kawai, Satoru Kariya, Takashi Sato, Masaru Yoshioka, Hitoshi Kadena, Shinji Matsushita, Shohei Nishi, Yukinari Hosokawa, Takeshi Shirane, Mutsumasa Yoh, Syuji Watanabe, Shinichi Makinose, Tetsuji Uemura, Hirokazu Goto
Second nationwide surveillance of bacterial pathogens in patients with acute uncomplicated cystitis conducted by Japanese Surveillance Committee from 2015 to 2016: antimicrobial susceptibility of Escherichia coli, Klebsiella pneumoniae, and Staphylococcus saprophyticus.
J Infect Chemother. 2019 Jun;25(6):413-422. doi: 10.1016/j.jiac.2019.02.021. Epub 2019 Mar 21.
Abstract/Text The Japanese Surveillance Committee conducted a second nationwide surveillance of antimicrobial susceptibility patterns of uropathogens responsible for acute uncomplicated cystitis (AUC) in premenopausal patients aged 16-40 years old at 31 hospitals throughout Japan from March 2015 to February 2016. In this study, the susceptibility of causative bacteria (Escherichia coli, Klebsiella pneumoniae, Staphylococcus saprophyticus) for various antimicrobial agents was investigated by isolation and culturing of organisms obtained from urine samples. In total, 324 strains were isolated from 361 patients, including E. coli (n = 220, 67.9%), S. saprophyticus (n = 36, 11.1%), and K. pneumoniae (n = 7, 2.2%). The minimum inhibitory concentrations (MICs) of 20 antibacterial agents for these strains were determined according to the Clinical and Laboratory Standards Institute (CLSI) manual. At least 93% of the E. coli isolates showed susceptibility to fluoroquinolones and cephalosporins, whereas 100% of the S. saprophyticus isolates showed susceptibility to fluoroquinolones and aminoglycosides. The proportions of fluoroquinolone-resistant and extended-spectrum β-lactamase (ESBL)-producing E. coli strains were 6.4% (13/220) and 4.1% (9/220), respectively. The antimicrobial susceptibility of K. pneumoniae was retained during the surveillance period, while no multidrug-resistant strains were identified. In summary, antimicrobial susceptibility results of our second nationwide surveillance did not differ significantly from those of the first surveillance. Especially the numbers of fluoroquinolone-resistant and ESBL-producing E. coli strains were not increased in premenopausal patients with AUC in Japan.

Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
PMID 30905628
Koichiro Wada, Teruhiko Yokoyama, Satoshi Uno, Motoo Araki, Takuya Sadahira, Yuki Maruyama, Herik Acosta, Hirochika Nakajima, Yoshiki Hiyama, Yasuharu Kunishima, Yoshikazu Togo, Takuhisa Nukaya, Hiroki Yamada, Katsumi Shigemura, Shin Ito, Masanobu Tanimura, Kanao Kobayashi, Hiroyuki Kitano, Jun Teishima, Mitsuru Yasuda, Shinya Uehara, Ryoichi Hamasuna, Toyohiko Watanabe, Tohru Nakagawa, Hiroshi Hayami, Jun Miyazaki, Satoshi Takahashi, Naoya Masumori, Kiyohito Ishikawa, Hiroshi Kiyota, Masato Fujisawa, Soichi Arakawa, Yasutomo Nasu, Shingo Yamamoto
Nationwide surveillance of bacterial pathogens isolated from patients with acute uncomplicated cystitis in 2018: Conducted by the Japanese Research Group for Urinary Tract Infections (JRGU).
J Infect Chemother. 2021 Aug;27(8):1169-1180. doi: 10.1016/j.jiac.2021.03.012. Epub 2021 May 27.
Abstract/Text INTRODUCTION: The aim of this study was to monitor the development of drug-resistant bacteria isolated from acute uncomplicated cystitis (AUC) and to evaluate methodology of the survey conducted by collecting only clinical data.
METHODS: We enrolled female patients at least 16 years of age diagnosed with AUC in 2018. Patient information including age, menopausal status, and results of bacteriological examination were collected and analyzed regardless of bacterial identification, antimicrobial susceptibility testing or extended-spectrum β-lactamase (ESBL) detection method.
RESULTS: A total of 847 eligible cases were collected. Escherichia coli (E. coli) was the most frequently isolated bacterial species at about 70%, with proportions of fluoroquinolone-resistant E. coli (QREC) and ESBL-producing E. coli isolates at 15.6% and 9.5% of all E. coli isolates, respectively. The proportion of Staphylococcus saprophyticus (S. saprophyticus) was significantly higher in premenopausal women. Regarding the drug susceptibility of E. coli, isolates from Eastern Japan had significantly higher susceptibility to cefazolin, cefotiam and cefpodoxime and lower susceptibility to levofloxacin in postmenopausal women. ESBL-producing E. coli isolates had a high susceptibility to tazobactam-piperacillin, cefmetazole, carbapenems, aminoglycosides, and fosfomycin. In S. saprophyticus, the susceptibility to β-lactams including carbapenems was 40-60%.
CONCLUSIONS: The proportions of QREC and ESBL-producing E. coli were increasing trends and lower susceptibility to LVFX in postmenopausal women was observed. Such surveillance, consisting of the collecting only clinical data, could be conducted easily and inexpensively. It is expected to be continuously performed as an alternative survey to conventional one collecting bacterial strains.

Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
PMID 33863634
Ryoichi Hamasuna, Kazushi Tanaka, Hiroshi Hayami, Mitsuru Yasuda, Satoshi Takahashi, Kanao Kobayashi, Hiroshi Kiyota, Shingo Yamamoto, Soichi Arakawa, Tetsuro Matsumoto, Japanese Research Group for UTI (JRGU)
Treatment of acute uncomplicated cystitis with faropenem for 3 days versus 7 days: multicentre, randomized, open-label, controlled trial.
J Antimicrob Chemother. 2014 Jun;69(6):1675-80. doi: 10.1093/jac/dku014. Epub 2014 Feb 6.
Abstract/Text OBJECTIVES: The increasing prevalence of resistant bacteria such as fluoroquinolone-resistant or extended-spectrum β-lactamase-producing strains in pathogens causing acute uncomplicated cystitis has been of concern in Japan. Faropenem sodium is a penem antimicrobial that demonstrates a wide antimicrobial spectrum against both aerobic and anaerobic bacteria. It is stable against a number of β-lactamases.
METHODS: We compared 3 and 7 day administration regimens of faropenem in a multicentre, randomized, open-label, controlled study.
RESULTS: In total, 200 female patients with cystitis were enrolled and randomized into 3 day (N = 97) or 7 day (N = 103) treatment groups. At the first visit, 161 bacterial strains were isolated from 154 participants, and Escherichia coli accounted for 73.9% (119/161) of bacterial strains. At 5-9 days after the completion of treatment, 73 and 81 patients from the 3 day and 7 day groups, respectively, were evaluated by intention-to-treat analysis; the microbiological efficacies were 58.9% eradication (43/73), 20.5% persistence (15/73) and 8.2% replaced (6/73), and 66.7% eradication (54/81), 6.2% persistence (5/81) and 7.4% replaced (6/81), respectively (P = 0.048). The clinical efficacies were 76.7% (56/73) and 80.2% (65/81), respectively (P = 0.695). Adverse events due to faropenem were reported in 9.5% of participants (19/200), and the most common adverse event was diarrhoea.
CONCLUSIONS: The 7 day regimen showed a superior rate of microbiological response. E. coli strains were in general susceptible to faropenem, including fluoroquinolone- and cephalosporin-resistant strains.

© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
PMID 24508899
Tetsuro Matsumoto, Tetsuro Muratani, Chikara Nakahama, Kazunori Tomono
Clinical effects of 2 days of treatment by fosfomycin calcium for acute uncomplicated cystitis in women.
J Infect Chemother. 2011 Feb;17(1):80-6. doi: 10.1007/s10156-010-0092-2. Epub 2010 Aug 7.
Abstract/Text Fosfomycin calcium is a fosfomycin antimicrobial agent with a characteristic structure. After oral administration, the drug is absorbed and excreted via the kidneys in the unchanged form, without being metabolized in the body. It is, therefore, indicated for the treatment of urinary tract diseases, including cystitis and pyelonephritis. In the present study, the clinical usefulness of fosfomycin calcium (FOSMICIN® TABLETS 500) administered orally at the dosage of 1 g (two tablets) three times daily for 2 days was examined in female patients, who were at least 20 years of age, with acute uncomplicated cystitis of bacterial origin. Of the 48 patients enrolled between February 2008 and August 2008, 39 were evaluable for efficacy and safety. Overall evaluation of the cure revealed that microbiological eradication rate (microbiological outcome) and clinical efficacy rate (clinical outcome) at 5-9 days after drug administration (visit 2) were 94.9%. Determination of the microbiological and clinical outcomes for the evaluation of recurrence at 4-6 weeks after drug administration (visit 3) were 75.8 and 85.7%, respectively. Of the 48 patients, 40 (83.3%) returned to the clinic at visit 3. The causative bacterial species for cystitis was Escherichia coli in 31 (79.5%) of the 39 patients evaluable for efficacy and safety. Adverse drug reactions observed during the administration and follow-up periods included mild diarrhea and loose stools in 1 patient each, neither requiring any specific treatment. Evaluation of cure at visit 2 in patients in whom the causative bacterial species for the infection was E. coli revealed a microbiological outcome of 93.5%, and clinical outcome was 96.8%. Furthermore, evaluation for recurrence at visit 3 revealed a microbiological outcome of 74.1% and clinical outcome of 82.1%. When the patients were divided by age into an under 60 years of age group and an over 60 years of age group, the microbiological and clinical outcomes determined for evaluation of cure at visit 2 were 96.4 and 92.9%, respectively, and the corresponding rates determined for the evaluation of recurrence at visit 3 were 87.0 and 96.0%, respectively, in the under 60 years of age group. In the over 60 years of age group, the corresponding microbiological outcome and clinical outcome rates evaluated for cure were 90.9 and 100%, respectively, and those evaluated for recurrence were 50.0 and 60.0%, respectively. These results indicate the usefulness of fosfomycin calcium administered at 1 g three times daily for 2 days for acute uncomplicated cystitis.

PMID 20694571
Kanao Kobayashi, Shingo Yamamoto, Satoshi Takahashi, Kiyohito Ishikawa, Mitsuru Yasuda, Koichiro Wada, Ryoichi Hamasuna, Hiroshi Hayami, Shinichi Minamitani, Tetsuya Matsumoto, Hiroshi Kiyota, Kazuhiro Tateda, Junko Sato, Hideaki Hanaki, Naoya Masumori, Yoshiki Hiyama, Hiroki Yamada, Shin Egawa, Takahiro Kimura, Hiroyuki Nishiyama, Jun Miyazaki, Kazumasa Matsumoto, Yukio Homma, Jun Kamei, Kiyohide Fujimoto, Kazumasa Torimoto, Kazushi Tanaka, Yoshikazu Togo, Shinya Uehara, Akio Matsubara, Koichi Shoji, Hirokazu Goto, Hisao Komeda, Toru Ito, Katsuhisa Mori, Koji Mita, Masao Kato, Yoshinori Fujimoto, Takako Masue, Hisato Inatomi, Yoshito Takahashi, Satoshi Ishihara, Kazuo Nishimura, Kenji Mitsumori, Noriyuki Ito, Sojun Kanamaru, Daisuke Yamada, Maeda Hiroshi, Masuo Yamashita, Masaya Tsugawa, Tadasu Takenaka, Koichi Takahashi, Yasuhiko Oka, Tomihiko Yasufuku, Shuji Watanabe, Yoshitomo Chihara, Kazuhiro Okumura, Hiroaki Kawanishi, Masanori Matsukawa, Masanobu Shigeta, Shuntaro Koda
The third national Japanese antimicrobial susceptibility pattern surveillance program: Bacterial isolates from complicated urinary tract infection patients.
J Infect Chemother. 2020 May;26(5):418-428. doi: 10.1016/j.jiac.2020.01.004. Epub 2020 Feb 17.
Abstract/Text The antimicrobial susceptibility patterns of bacterial pathogens isolated from patients with complicated urinary tract infections were analyzed using national surveillance data. The data consisted of 881 bacterial strains from eight clinically relevant species. The data were collected for the third national surveillance project from January 2015 to March 2016 by the Japanese Society of Chemotherapy, the Japanese Association for Infectious Disease, and the Japanese Society of Clinical Microbiology. Surveillance was undertaken with the cooperation of 41 medical institutions throughout Japan. Fluoroquinolone required a MIC90 of 2-64 mg/L to inhibit the 325 Escherichia coli strains tested and the proportion of levofloxacin resistant E. coli strains increased to 38.5% from 29.6% in 2011 and 28.6% in 2008. The proportion of levofloxacin resistant strains of Pseudomonas aeruginosa and Enterococcus faecalis decreased from previous reports and the proportion of multidrug-resistant P. aeruginosa and carbapenem-resistant Enterobacteriaceae remained low. Among methicillin-resistant Staphylococcus aureus (MRSA) strains, strains with reduced susceptibility to vancomycin (minimum inhibitory concentration, 2 μg/mL) increased to 14.7% from 5.5%. Bacterial strains that produced extended-spectrum β-lactamase included E. coli (79 of 325 strains, 24.3%), Klebsiella pneumoniae (9 of 177 strains, 7.7%), and Proteus mirabilis (6 of 55 strains, 10.9%). The proportion of extended-spectrum β-lactamase producing E. coli and K. pneumoniae strains increased from previous surveillance reports.

Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
PMID 32081647
Delia Scholes, Thomas M Hooton, Pacita L Roberts, Kalpana Gupta, Ann E Stapleton, Walter E Stamm
Risk factors associated with acute pyelonephritis in healthy women.
Ann Intern Med. 2005 Jan 4;142(1):20-7.
Abstract/Text BACKGROUND: Although most cases of acute pyelonephritis occur in otherwise healthy women, data on risk factors for this condition are lacking.
OBJECTIVE: To evaluate infection characteristics, incidence, and risk factors associated with acute pyelonephritis in a sample of women.
DESIGN: Population-based case-control study.
SETTING: Group Health Cooperative, a prepaid health plan in Washington.
PARTICIPANTS: 788 nonpregnant women, 18 to 49 years of age. Case-patients (n = 242) were women with pyelonephritis who were identified from computerized databases. Controls were 546 similar-age women with no pyelonephritis diagnosis in the previous 5 years who were randomly selected from enrollment databases. Response rates for case-patients and controls were 73% and 64%, respectively.
MEASUREMENTS: Characteristics of infection and potential risk factors for pyelonephritis, ascertained through computer-assisted telephone interview and computerized databases.
RESULTS: 7% of case-patients were hospitalized. Escherichia coli was the infecting pathogen in 85% of cases. In multivariable models, factors associated with pyelonephritis risk were frequency of sexual intercourse in the previous 30 days (odds ratio, 5.6 [95% CI, 2.8 to 11.0] for > or =3 times per week), recent urinary tract infection (UTI) (odds ratio, 4.4 [CI, 2.8 to 7.1]), diabetes (odds ratio, 4.1 [CI, 1.6 to 10.9]), recent incontinence (odds ratio, 3.9 [CI. 2.6 to 5.9]), new sexual partner in the previous year (odds ratio, 2.2 [CI, 1.4 to 3.6]), recent spermicide use (odds ratio, 1.7 [CI, 1.1 to 2.8]), and UTI history in the participant's mother (odds ratio, 1.6 [CI, 1.1 to 2.5]). Risk factors for selected subgroups (patients < or = 30 years of age, patients > 30 years of age, patients with no UTI history, and inpatients) were also evaluated.
LIMITATIONS: Potential recall bias, reliance on automated case definition criteria, and limited data on diabetes and incontinence variables.
CONCLUSIONS: Few nonpregnant, community-dwelling women younger than 50 years of age with pyelonephritis are hospitalized. As with cystitis in reproductive-age women, sexual behaviors and patient and family history of UTI are associated with increased pyelonephritis risk. Diabetes and incontinence also seem to independently increase the risk for pyelonephritis.

PMID 15630106
L E Nicolle, A R Ronald
Recurrent urinary tract infection in adult women: diagnosis and treatment.
Infect Dis Clin North Am. 1987 Dec;1(4):793-806.
Abstract/Text Recurrent urinary infection may be either relapse or reinfection. The majority of women experiencing recurrent infection have normal genitourinary tracts. For recurrent cystitis, single-dose therapy is optimal and symptomatic episodes are effectively prevented with continuous low-dose antimicrobial prophylaxis. For upper tract infection, or relapse after single dose therapy, two-week therapy is generally adequate. Investigation for abnormalities of the genitourinary tract should be reserved for women who fail to respond to therapy or with relapsing or bacteremic infection.

PMID 3333659
L E Nicolle
Prophylaxis: recurrent urinary tract infection in women.
Infection. 1992;20 Suppl 3:S203-5; discussion S206-10.
Abstract/Text Long-term, low-dose antimicrobial prophylaxis is effective for the prevention of acute uncomplicated urinary tract infection in women. Selected new antimicrobials should be assessed to determine their efficacy for this clinical use. Recommended guidelines for future studies of prophylactic therapy need to address several issues. The study population must be limited to women with recurrent symptomatic uncomplicated urinary tract infection. Antimicrobials studied should be excreted in the urine, with an in vitro spectrum that includes the common uropathogens. An extended half-life may be beneficial. Monitoring during the study should include monthly urine cultures and vaginal, periurethral and rectal colonization studies. The primary outcome measurement is symptomatic urinary tract infection. Secondary outcomes would include asymptomatic bacteriuria, adverse antimicrobial effects, colonization with potential uropathogens, and development of resistance. The comparative regimen should be one of the current standard regimens, trimethoprim/sulphamethoxazole, nitrofurantoin, or trimethoprim.

PMID 1490746
L D Chew, S D Fihn
Recurrent cystitis in nonpregnant women.
West J Med. 1999 May;170(5):274-7.
Abstract/Text Consistent evidence from RCTs shows that antibiotic prophylaxis (either continuous or postcoital), using trimethoprim TMP-SMZ, nitrofurantoin, or a quinolone, reduces infection rates in women with high rates of recurrent cystitis (at least two per year). Limited evidence suggests that intermittent patient-administered treatment (taken at the onset of symptoms) is an effective alternative management strategy to continuous antibiotic prophylaxis in women with high rates of infection (at least two per year). Limited evidence suggests that long-term prophylaxis is likely to benefit women with a baseline rate of more than two infections per year over many years. However, long-term treatment has not yet been evaluated in RCTs. In women who experience recurrent, uncomplicated cystitis, there is no evidence to support routine investigation of the urinary tract with excretory urography, ultrasonography, cystoscopy, or voiding cystourethrography. No specific subgroups of women who would clearly benefit from investigation have yet been adequately defined.

PMID 10379218
X Albert, I Huertas, I I Pereiró, J Sanfélix, V Gosalbes, C Perrota
Antibiotics for preventing recurrent urinary tract infection in non-pregnant women.
Cochrane Database Syst Rev. 2004;(3):CD001209. doi: 10.1002/14651858.CD001209.pub2.
Abstract/Text BACKGROUND: Urinary tract infection (UTI) is a common health care problem. Recurrent UTI (RUTI) in healthy non-pregnant women is defined as three or more episodes of UTI during a twelve month period. Long-term antibiotics have been proposed as a prevention strategy for RUTI.
OBJECTIVES: To determine the efficacy (during and after) and safety of prophylactic antibiotics used to prevent uncomplicated RUTI in adult non-pregnant women.
SEARCH STRATEGY: We searched MEDLINE (1966-April 2004), EMBASE (1980-January 2003), Cochrane Central Register of Controlled Trials( in The Cochrane Library Issue 1, 2004) and reference lists of retrieved articles
SELECTION CRITERIA: Any published randomised controlled trial where antibiotics were used as prophylactic therapy in RUTI.
DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) with 95% confidence intervals (CI).
MAIN RESULTS: Nineteen studies involving 1120 women were eligible for inclusion. Antibiotic versus antibiotic (10 trials, 430 women): During active prophylaxis the rate range of microbiological recurrence patient-year (MRPY) was 0 to 0.9 person-year in the antibiotic group against 0.8 to 3.6 with placebo. The RR of having one microbiological recurrence (MR) was 0.21 (95% CI 0.13 to 0.34), favouring antibiotic and the NNT was 1.85. For clinical recurrences (CRPY) the RR was 0.15 (95% CI 0.08 to 0.28). The NNT was 1.85. The RR of having one MR after prophylaxis was 0.82 (95% CI 0.44 to 1.53). The RR for severe side effects was 1.58 (95% CI 0.47 to 5.28) and for other side effects the RR was 1.78 (CI 1.06 to 3.00) favouring placebo. Side effects included vaginal and oral candidiasis and gastrointestinal symptoms. Antibiotic versus antibiotic (eight trials, 513 women): These trials were not pooled. Weekly pefloxacin was more effective than monthly. The RR for MR was 0.31(95% CI 0.19 to 0.52). There was no significant difference in MR between continuous daily and postcoital ciprofloxacin.
REVIEWERS' CONCLUSIONS: Continuous antibiotic prophylaxis for 6-12 months reduced the rate of UTI during prophylaxis when compared to placebo. After prophylaxis two studies showed nodifference between groups. There were more adverse events in the antibiotic group. One RCT compared postcoital versus continuous daily ciprofloxacin and found no significant difference in rates of UTIs, suggesting that postcoital treatment could be offered to woman who have UTI associated with sexual intercourse.

PMID 15266443
R Raz, W E Stamm
A controlled trial of intravaginal estriol in postmenopausal women with recurrent urinary tract infections.
N Engl J Med. 1993 Sep 9;329(11):753-6. doi: 10.1056/NEJM199309093291102.
Abstract/Text BACKGROUND: Recurrent urinary tract infections are a problem for many postmenopausal women. Estrogen replacement restores atrophic mucosa, lowers vaginal pH, and may prevent urinary tract infections.
METHODS: We enrolled 93 postmenopausal women with a history of recurrent urinary tract infections in a randomized, double-blind, placebo-controlled trial of a topically applied intravaginal estriol cream. Midstream urine cultures were obtained at enrollment, monthly for eight months, and whenever urinary symptoms occurred. Vaginal cultures and pH measurements were obtained at entry and after one and eight months. The women were assigned to receive either estriol (n = 50) or placebo (n = 43), both administered intravaginally; 36 and 24, respectively, completed the eight months of follow-up.
RESULTS: The incidence of urinary tract infection in the group given estriol was significantly reduced as compared with that in the group given placebo (0.5 vs. 5.9 episodes per patient-year, P < 0.001). Survival analysis showed that more of the women in the estriol group than in the placebo group remained free of urinary tract infection (P < 0.001). Lactobacilli were absent in all vaginal cultures before treatment and reappeared after one month in 22 of 36 estriol-treated women (61 percent) but in none of the 24 placebo recipients (P < 0.001). With estriol the mean vaginal pH declined from 5.5 to 3.8 (P < 0.001), whereas there was no significant change with placebo. The rate of vaginal colonization with Enterobacteriaceae fell from 67 percent to 31 percent in estriol recipients but was virtually unchanged (from 67 to 63 percent) in the placebo recipients (P < 0.005). Side effects were minor, but caused 10 estriol recipients (28 percent) and 4 placebo recipients (17 percent) to discontinue treatment.
CONCLUSIONS: The intravaginal administration of estriol prevents recurrent urinary tract infection in postmenopausal women, probably by modifying the vaginal flora.

PMID 8350884
Cibele Barbosa-Cesnik, Morton B Brown, Miatta Buxton, Lixin Zhang, Joan DeBusscher, Betsy Foxman
Cranberry juice fails to prevent recurrent urinary tract infection: results from a randomized placebo-controlled trial.
Clin Infect Dis. 2011 Jan 1;52(1):23-30. doi: 10.1093/cid/ciq073.
Abstract/Text BACKGROUND: A number of observational studies and a few small or open randomized clinical trials suggest that the American cranberry may decrease incidence of recurring urinary tract infection (UTI).
METHODS: We conducted a double-blind, placebo-controlled trial of the effects of cranberry on risk of recurring UTI among 319 college women presenting with an acute UTI. Participants were followed up until a second UTI or for 6 months, whichever came first. A UTI was defined on the basis of the combination of symptoms and a urine culture positive for a known uropathogen. The study was designed to detect a 2-fold difference between treated and placebo groups, as was detected in unblinded trials. We assumed 30% of participants would experience a UTI during the follow-up period.
RESULTS: Overall, the recurrence rate was 16.9% (95% confidence interval, 12.8%-21.0%), and the distribution of the recurrences was similar between study groups, with the active cranberry group presenting a slightly higher recurrence rate (20.0% vs 14.0%). The presence of urinary symptoms at 3 days, 1-2 weeks, and at ≥ 1 month was similar between study groups, with overall no marked differences. CONCLUSIONS.: Among otherwise healthy college women with an acute UTI, those drinking 8 oz of 27% cranberry juice twice daily did not experience a decrease in the 6-month incidence of a second UTI, compared with those drinking a placebo.

PMID 21148516
Mariëlle A J Beerepoot, Gerben ter Riet, Sita Nys, Willem M van der Wal, Corianne A J M de Borgie, Theo M de Reijke, Jan M Prins, Jeanne Koeijers, Annelies Verbon, Ellen Stobberingh, Suzanne E Geerlings
Cranberries vs antibiotics to prevent urinary tract infections: a randomized double-blind noninferiority trial in premenopausal women.
Arch Intern Med. 2011 Jul 25;171(14):1270-8. doi: 10.1001/archinternmed.2011.306.
Abstract/Text BACKGROUND: The increasing prevalence of uropathogens resistant to antimicrobial agents has stimulated interest in cranberries to prevent recurrent urinary tract infections (UTIs).
METHODS: In a double-blind, double-dummy noninferiority trial, 221 premenopausal women with recurrent UTIs were randomized to 12-month prophylaxis use of trimethoprim-sulfamethoxazole (TMP-SMX), 480 mg once daily, or cranberry capsules, 500 mg twice daily. Primary end points were the mean number of symptomatic UTIs over 12 months, the proportion of patients with at least 1 symptomatic UTI, the median time to first UTI, and development of antibiotic resistance in indigenous Escherichia coli.
RESULTS: After 12 months, the mean number of patients with at least 1 symptomatic UTI was higher in the cranberry than in the TMP-SMX group (4.0 vs 1.8; P = .02), and the proportion of patients with at least 1 symptomatic UTI was higher in the cranberry than in the TMP-SMX group (78.2% vs 71.1%). Median time to the first symptomatic UTI was 4 months for the cranberry and 8 months for the TMP-SMX group. After 1 month, in the cranberry group, 23.7% of fecal and 28.1% of asymptomatic bacteriuria E coli isolates were TMP-SMX resistant, whereas in the TMP-SMX group, 86.3% of fecal and 90.5% of asymptomatic bacteriuria E coli isolates were TMP-SMX resistant. Similarly, we found increased resistance rates for trimethoprim, amoxicillin, and ciprofloxacin in these E coli isolates after 1 month in the TMP-SMX group. After discontinuation of TMP-SMX, resistance reached baseline levels after 3 months. Antibiotic resistance did not increase in the cranberry group. Cranberries and TMP-SMX were equally well tolerated.
CONCLUSION: In premenopausal women, TMP-SMX, 480 mg once daily, is more effective than cranberry capsules, 500 mg twice daily, to prevent recurrent UTIs, at the expense of emerging antibiotic resistance.
TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN50717094.

PMID 21788542
J Avorn, M Monane, J H Gurwitz, R J Glynn, I Choodnovskiy, L A Lipsitz
Reduction of bacteriuria and pyuria after ingestion of cranberry juice.
JAMA. 1994 Mar 9;271(10):751-4.
Abstract/Text OBJECTIVE: To determine the effect of regular intake of cranberry juice beverage on bacteriuria and pyuria in elderly women.
DESIGN: Randomized, double-blind, placebo-controlled trial.
SUBJECTS: Volunteer sample of 153 elderly women (mean age, 78.5 years).
INTERVENTION: Subjects were randomly assigned to consume 300 mL per day of a commercially available standard cranberry beverage or a specially prepared synthetic placebo drink that was indistinguishable in taste, appearance, and vitamin C content but lacked cranberry content.
OUTCOME MEASURES: A baseline urine sample and six clean-voided study urine samples were collected at approximately 1-month intervals and tested quantitatively for bacteriuria and the presence of white blood cells.
RESULTS: Subjects randomized to the cranberry beverage had odds of bacteriuria (defined as organisms numbering > or = 10(5)/mL) with pyuria that were only 42% of the odds in the control group (P = .004). Their odds of remaining bacteriuric-pyuric, given that they were bacteriuric-pyuric in the previous month, were only 27% of the odds in the control group (P = .006).
CONCLUSIONS: These findings suggest that use of a cranberry beverage reduces the frequency of bacteriuria with pyuria in older women. Prevalent beliefs about the effects of cranberry juice on the urinary tract may have microbiologic justification.

PMID 8093138
T Kontiokari, K Sundqvist, M Nuutinen, T Pokka, M Koskela, M Uhari
Randomised trial of cranberry-lingonberry juice and Lactobacillus GG drink for the prevention of urinary tract infections in women.
BMJ. 2001 Jun 30;322(7302):1571.
Abstract/Text OBJECTIVE: To determine whether recurrences of urinary tract infection can be prevented with cranberry-lingonberry juice or with Lactobacillus GG drink.
DESIGN: Open, randomised controlled 12 month follow up trial.
SETTING: Health centres for university students and staff of university hospital.
PARTICIPANTS: 150 women with urinary tract infection caused by Escherichia coli randomly allocated into three groups.
INTERVENTIONS: 50 ml of cranberry-lingonberry juice concentrate daily for six months or 100 ml of lactobacillus drink five days a week for one year, or no intervention.
MAIN OUTCOME MEASURE: First recurrence of symptomatic urinary tract infection, defined as bacterial growth >/=10(5 )colony forming units/ml in a clean voided midstream urine specimen.
RESULTS: The cumulative rate of first recurrence of urinary tract infection during the 12 month follow up differed significantly between the groups (P=0.048). At six months, eight (16%) women in the cranberry group, 19 (39%) in the lactobacillus group, and 18 (36%) in the control group had had at least one recurrence. This is a 20% reduction in absolute risk in the cranberry group compared with the control group (95% confidence interval 3% to 36%, P=0.023, number needed to treat=5, 95% confidence interval 3 to 34).
CONCLUSION: Regular drinking of cranberry juice but not lactobacillus seems to reduce the recurrence of urinary tract infection.

PMID 11431298
Chih-Hung Wang, Cheng-Chung Fang, Nai-Chuan Chen, Sot Shih-Hung Liu, Ping-Hsun Yu, Tao-Yu Wu, Wei-Ting Chen, Chien-Chang Lee, Shyr-Chyr Chen
Cranberry-containing products for prevention of urinary tract infections in susceptible populations: a systematic review and meta-analysis of randomized controlled trials.
Arch Intern Med. 2012 Jul 9;172(13):988-96. doi: 10.1001/archinternmed.2012.3004.
Abstract/Text BACKGROUND: Urinary tract infection (UTI) is one of the most commonly acquired bacterial infections. Cranberry-containing products have long been used as a folk remedy to prevent UTIs. The aims of this study were to evaluate cranberry-containing products for the prevention of UTI and to examine the factors influencing their effectiveness.
METHODS: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were systemically searched from inception to November 2011 for randomized controlled trials that compared prevention of UTIs in users of cranberry-containing products vs placebo or nonplacebo controls. There were no restrictions for language, population, or publication year.
RESULTS: Thirteen trials, including 1616 subjects, were identified for qualitative synthesis from 414 potentially relevant references; 10 of these trials, including a total of 1494 subjects, were further analyzed in quantitative synthesis. The random-effects pooled risk ratio (RR) for cranberry users vs nonusers was 0.62 (95% CI, 0.49-0.80), with a moderate degree of heterogeneity (I(2) = 43%) after the exclusion of 1 outlier study. On subgroup analysis, cranberry-containing products seemed to be more effective in several subgroups, including women with recurrent UTIs (RR, 0.53; 95% CI, 0.33-0.83) (I(2) = 0%), female populations (RR, 0.49; 95% CI, 0.34-0.73) (I(2) = 34%), children (RR, 0.33; 95% CI, 0.16-0.69) (I(2) = 0%), cranberry juice drinkers (RR, 0.47; 95% CI, 0.30-0.72) (I(2) = 2%), and subjects using cranberry-containing products more than twice daily (RR, 0.58; 95% CI, 0.40-0.84) (I(2) = 18%).
CONCLUSIONS: Our findings indicate that cranberry-containing products are associated with protective effect against UTIs. However, this result should be interpreted in the context of substantial heterogeneity across trials.

PMID 22777630
Ruth G Jepson, Gabrielle Williams, Jonathan C Craig
Cranberries for preventing urinary tract infections.
Cochrane Database Syst Rev. 2012 Oct 17;10:CD001321. doi: 10.1002/14651858.CD001321.pub5. Epub 2012 Oct 17.
Abstract/Text BACKGROUND: Cranberries have been used widely for several decades for the prevention and treatment of urinary tract infections (UTIs). This is the third update of our review first published in 1998 and updated in 2004 and 2008.
OBJECTIVES: To assess the effectiveness of cranberry products in preventing UTIs in susceptible populations.
SEARCH METHODS: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL in The Cochrane Library) and the Internet. We contacted companies involved with the promotion and distribution of cranberry preparations and checked reference lists of review articles and relevant studies.Date of search: July 2012
SELECTION CRITERIA: All randomised controlled trials (RCTs) or quasi-RCTs of cranberry products for the prevention of UTIs.
DATA COLLECTION AND ANALYSIS: Two authors independently assessed and extracted data. Information was collected on methods, participants, interventions and outcomes (incidence of symptomatic UTIs, positive culture results, side effects, adherence to therapy). Risk ratios (RR) were calculated where appropriate, otherwise a narrative synthesis was undertaken. Quality was assessed using the Cochrane risk of bias assessment tool.
MAIN RESULTS: This updated review includes a total of 24 studies (six cross-over studies, 11 parallel group studies with two arms; five with three arms, and two studies with a factorial design) with a total of 4473 participants. Ten studies were included in the 2008 update, and 14 studies have been added to this update. Thirteen studies (2380 participants) evaluated only cranberry juice/concentrate; nine studies (1032 participants) evaluated only cranberry tablets/capsules; one study compared cranberry juice and tablets; and one study compared cranberry capsules and tablets. The comparison/control arms were placebo, no treatment, water, methenamine hippurate, antibiotics, or lactobacillus. Eleven studies were not included in the meta-analyses because either the design was a cross-over study and data were not reported separately for the first phase, or there was a lack of relevant data. Data included in the meta-analyses showed that, compared with placebo, water or not treatment, cranberry products did not significantly reduce the occurrence of symptomatic UTI overall (RR 0.86, 95% CI 0.71 to 1.04) or for any the subgroups: women with recurrent UTIs (RR 0.74, 95% CI 0.42 to 1.31); older people (RR 0.75, 95% CI 0.39 to 1.44); pregnant women (RR 1.04, 95% CI 0.97 to 1.17); children with recurrent UTI (RR 0.48, 95% CI 0.19 to 1.22); cancer patients (RR 1.15 95% CI 0.75 to 1.77); or people with neuropathic bladder or spinal injury (RR 0.95, 95% CI: 0.75 to 1.20). Overall heterogeneity was moderate (I² = 55%). The effectiveness of cranberry was not significantly different to antibiotics for women (RR 1.31, 95% CI 0.85, 2.02) and children (RR 0.69 95% CI 0.32 to 1.51). There was no significant difference between gastrointestinal adverse effects from cranberry product compared to those of placebo/no treatment (RR 0.83, 95% CI 0.31 to 2.27). Many studies reported low compliance and high withdrawal/dropout problems which they attributed to palatability/acceptability of the products, primarily the cranberry juice. Most studies of other cranberry products (tablets and capsules) did not report how much of the 'active' ingredient the product contained, and therefore the products may not have had enough potency to be effective.
AUTHORS' CONCLUSIONS: Prior to the current update it appeared there was some evidence that cranberry juice may decrease the number of symptomatic UTIs over a 12 month period, particularly for women with recurrent UTIs. The addition of 14 further studies suggests that cranberry juice is less effective than previously indicated. Although some of small studies demonstrated a small benefit for women with recurrent UTIs, there were no statistically significant differences when the results of a much larger study were included. Cranberry products were not significantly different to antibiotics for preventing UTIs in three small studies. Given the large number of dropouts/withdrawals from studies (mainly attributed to the acceptability of consuming cranberry products particularly juice, over long periods), and the evidence that the benefit for preventing UTI is small, cranberry juice cannot currently be recommended for the prevention of UTIs. Other preparations (such as powders) need to be quantified using standardised methods to ensure the potency, and contain enough of the 'active' ingredient, before being evaluated in clinical studies or recommended for use.

PMID 23076891
Satoshi Takahashi, Ryoichi Hamasuna, Mitsuru Yasuda, Soichi Arakawa, Kazushi Tanaka, Kiyohito Ishikawa, Hiroshi Kiyota, Hiroshi Hayami, Shingo Yamamoto, Tatsuhiko Kubo, Tetsuro Matsumoto
A randomized clinical trial to evaluate the preventive effect of cranberry juice (UR65) for patients with recurrent urinary tract infection.
J Infect Chemother. 2013 Feb;19(1):112-7. doi: 10.1007/s10156-012-0467-7. Epub 2012 Sep 8.
Abstract/Text We examined the rate of relapse, as a variable index, in patients with urinary tract infection (UTI) who suffered from multiple relapses when using cranberry juice (UR65). A randomized, placebo-controlled, double-blind study was conducted from October 2007 to September 2009 in Japan. The subjects were outpatients aged 20 to 79 years who were randomly divided into two groups. One group received cranberry juice (group A) and the other a placebo beverage (group P). To keep the conditions blind, the color and taste of the beverages were adjusted. The subjects drank 1 bottle (125 mL) of cranberry juice or the placebo beverage once daily, before going to sleep, for 24 weeks. The primary endpoint was relapse of UTI. In the group of females aged 50 years or more, there was a significant difference in the rate of relapse of UTI between groups A and P (log-rank test; p = 0.0425). In this subgroup analysis, relapse of UTI was observed in 16 of 55 (29.1 %) patients in group A and 31 of 63 (49.2 %) in group P. In this study, cranberry juice prevented the recurrence of UTI in a limited female population with 24-week intake of the beverage.

PMID 22961092
Abstract/Text PURPOSE: We determined whether routine replacement of a chronic indwelling catheter before instituting antimicrobial therapy leads to an improved bacteriological or clinical outcome when treating symptomatic urinary tract infection in elderly nursing home residents.
MATERIALS AND METHODS: We performed a prospective randomized open clinical trial at 2 long-term care facilities. Patients were randomized to indwelling catheter replacement before initiating antimicrobial therapy or no replacement. Urine and blood cultures were done before antimicrobial therapy began. Clinical and microbiological outcomes were assessed after 3 days of therapy, and 7 and 28 days after therapy was complete.
RESULTS: Enrolled in our study were 21 male and 33 female nursing home residents with a mean age of 72.6 years, a chronic indwelling catheter and a clinical diagnosis of urinary tract infection. A total of 27 cases were randomized to either catheter replacement and no replacement before antimicrobial therapy. Polymicrobial bacteriuria significantly decreased 3 days after therapy was initiated, and 7 and 28 days after it was discontinued in 24 versus 8 (p = 0.002), 18 versus 9 (p = 0.01) and 13 versus 5 (p = 0.02) patients with and without catheter replacement, respectively. Catheter replacement was also associated with a shorter time to afebrile status, improved clinical status 72 hours after the initiation of therapy in 25 versus 11 patients (p <0.001) and a lower rate of symptomatic clinical relapse 28 days after therapy in 3 versus 11 (p = 0.015).
CONCLUSIONS: Clinical and bacteriological outcomes are improved when long-term indwelling catheters are replaced before initiating antimicrobial therapy for symptomatic urinary tract infection.

PMID 10992375
Thomas M Hooton, Suzanne F Bradley, Diana D Cardenas, Richard Colgan, Suzanne E Geerlings, James C Rice, Sanjay Saint, Anthony J Schaeffer, Paul A Tambayh, Peter Tenke, Lindsay E Nicolle, Infectious Diseases Society of America
Diagnosis, prevention, and treatment of catheter-associated urinary tract infection in adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America.
Clin Infect Dis. 2010 Mar 1;50(5):625-63.
Abstract/Text Guidelines for the diagnosis, prevention, and management of persons with catheter-associated urinary tract infection (CA-UTI), both symptomatic and asymptomatic, were prepared by an Expert Panel of the Infectious Diseases Society of America. The evidence-based guidelines encompass diagnostic criteria, strategies to reduce the risk of CA-UTIs, strategies that have not been found to reduce the incidence of urinary infections, and management strategies for patients with catheter-associated asymptomatic bacteriuria or symptomatic urinary tract infection. These guidelines are intended for use by physicians in all medical specialties who perform direct patient care, with an emphasis on the care of patients in hospitals and long-term care facilities.

PMID 20175247
Marc Leone, Anne-Sophie Perrin, Isabelle Granier, Pierre Visintini, Valery Blasco, François Antonini, Jacques Albanèse, Claude Martin
A randomized trial of catheter change and short course of antibiotics for asymptomatic bacteriuria in catheterized ICU patients.
Intensive Care Med. 2007 Apr;33(4):726-9. doi: 10.1007/s00134-007-0534-1. Epub 2007 Feb 9.
Abstract/Text OBJECTIVE: To determine the effect on the occurrence of urosepsis of a treatment with a short course of antibiotics and indwelling urethral catheter replacement in clinically asymptomatic intensive care unit (ICU) patients with a positive urine culture occurring at least 48 h after catheterization.
METHODS: A prospective randomized clinical trial was conducted in the medico-surgical ICU of a tertiary care centre. Sixty patients hospitalized in the ICU with an indwelling urethral catheter for longer than 48 h developing an asymptomatic positive urine culture were randomized to receive either a 3-day course of antibiotics associated with the replacement of the indwelling urethral catheter 4 h after first antibiotic administration or no antibiotics, no catheter replacement (standard of care).
RESULTS: Three patients in each group developed urosepsis (P=0.1). There were no significant differences in duration of mechanical ventilation between the study group and the standard of care group (9 [4-20] days vs 5 [2-15] days, P=0.2), in duration of urinary catheterization (22 [11-40] days vs 18 [14-33] days, P=0.8), or in length of ICU stay (28 [13-46] vs 19 [15-34], P=0.6). The recurrence of positive urine culture at days 7 and 15 was not affected by the randomization (P=0.1). The profile of bacterial resistance was similar in the two groups.
CONCLUSIONS: Treating a positive urine culture in an asymptomatic patient with an indwelling urethral catheter does not reduce the occurrence of urosepsis in the medico-surgical ICU.

PMID 17294169
J W Warren, W C Anthony, J M Hoopes, H L Muncie
Cephalexin for susceptible bacteriuria in afebrile, long-term catheterized patients.
JAMA. 1982 Jul 23;248(4):454-8.
Abstract/Text Patients with long-term indwelling urethral catheters are subject to acute and long-term complications of bacteriuria. To evaluate the common practice of short-course antibiotic therapy in such patients, we performed a randomized controlled trial of ten-day courses of cephalexin monohydrate repeated whenever a susceptible bacteriuria was present. We observed 17 cephalexin group patients for 545 patient-weeks (160 cephalexin courses) and 18 control group patients for 477 patient-weeks. Throughout the study, the groups were comparable in regard to incidence and prevalence of bacteriuria, number of bacterial strains per weekly urine specimen, incidence of febrile days, and incidence of obstructed catheters. In the cephalexin group, the frequency of fever during periods when antibiotics were being used was similar to that during periods when antibiotics were not being used. More cephalexin-resistant bacteria were isolated from cephalexin group patients. Routine treatment with cephalexin of asymptomatic long-term catheterized patients, even for susceptible organisms, does not seem to be warranted.

PMID 7045440

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