Molecular epidemiology of enterovirus 71, coxsackievirus A16 and A6 associated with hand,foot and mouth disease in Spain

Hand, foot and mouth disease (HFMD) is a childhood illness frequently caused by genotypes belonging to the enterovirus A species, including coxsackievirus (CV)-A16 and enterovirus (EV)-71. Between 2010 and 2012, several outbreaks and sporadic cases of HFMD occurred in different regions of Spain. The objective of the present study was to describe the enterovirus epidemiology associated with HFMD in the country. A total of 80 patients with HFMD or atypical rash were included. Detection and typing of the enteroviruses were performed directly in clinical samples using molecular methods. Enteroviruses were detected in 53 of the patients (66%). CV-A6 was the most frequent genotype, followed by CV-A16 and EV-71, but other minority types were also identified. Interestingly, during almost all of 2010, CV-A16 was the only causative agent of HFMD but by the end of the year and during 2011, CV-A6 became predominant, while CV-A16 was not detected. In 2012, however, both CV-A6 and CV-A16 circulated. EV-71 was associated with HFMD symptoms only in three cases during 2012. All Spanish CV-A6 sequences segregated into one major genetic cluster together with other European and Asian strains isolated between 2008 and 2011, most forming a particular clade. Spanish EV-71 strains belonged to subgenogroup C2, as did most of the European sequences circulated. In conclusion, the recent increase of HFMD cases in Spain and other European countries has been due to a larger incidence of circulating species A enteroviruses, mainly CV-A6 and CV-A16, and the emergence of new genetic variants of these viruses.     

Clinical features of severe cases of hand,foot and mouth disease with EV71 virus infection in China

Introduction

Hand, foot and mouth disease (HFMD) caused by EV71 infection has become one of the major public health issues in China, which deeply affects children''s health. The prevention and control of EV71 is a challenge currently because there is no safe and effective vaccine or antiviral medications available.

Material and methods

A case control study was conducted in a designated hospital to compare severe and mild cases of patients infected with the EV71 virus. Demographic information along with clinical features of HFMD was collected through a standardized questionnaire. Multi-factorial logistic regression was used to analyze independent associations between potential risk factors and severe HFMD.

Results

There were 120 cases (60 cases and 60 controls) collected. The male-to-female ratio was 1.3: 1 in the case group and 1.7: 1 in the control group. Multi-factorial logistic regression revealed that the main risk factors for severe cases were highest body temperature being ≥ 38.5°C (OR = 9.45, 95% CI: 2.07–43.11, p < 0.05), first visited a village level clinic (OR = 4.72, 95% CI: 1.15–19.45, p < 0.05), etc.

Conclusions

Close surveillance combined with laboratory testing should be in place during the epidemic period of HFMD. Grass root level medical facilities and training of clinical and laboratory staff should be reinforced so that the diagnostic and treatment capacity can be improved.     

Ongoing change of severe hand,foot, and mouth disease pathogens in Yunnan,China, 2012 to 2016

Hand, foot, and mouth disease (HFMD) is a common infectious disease caused by enteroviruses (EVs). In this study, a total of 341 children with serious HFMD were admitted to a pediatric hospital in Yunnan, China in 2012 to 2016. EVs were detected in 283 specimens (83.0%) and were assigned to 17 EV types. Enterovirus A71 (EV-A71) was predominant, accounting for 41.6%, and was followed by coxsackievirus A16 (CV-A16; 18.8%), CV-A6 (9.1%), CV-A10 and E-9 (2.9%), CV-B5 (1.8%), CV-A9 (1.2%), E-30 (0.9%), E-18, CV-A4, C-B3, and CV-A2 (0.6%) and other EV types such as CV-A8, CV-A14, E-14, E-11, and CV-B4 (0.3%). All of the EV-A71 isolates belonged to C4a; the CV-A16 belonged to B1b or B1a, although the B1b strains were predominant; and CV-A6 belonged to D3. In 2012 to 2014, E-9 was the third most frequent serotype (8.2%, 5.0%, and 6.5%, respectively). E-9 was not detected in 2015 and 2016. CV-A6 was not detected in 2012 but was the second most frequent serotype (25.3%) in 2015. Active etiological surveillance of HFMD makes it necessary to be aware of these emerging pathogens.     

Association of gene polymorphisms of CD55 with susceptibility to and severity of hand,foot, and mouth disease caused by enterovirus 71 in the Han Chinese population

Hand, foot, and mouth disease (HFMD) caused by enterovirus 71 (EV71) can lead to high morbidity and mortality, and genetic background plays an important role during the disease process. We investigated the association between the single-nucleotide polymorphism (SNP) rs2564978 of the CD55 gene and susceptibility to and severity of HFMD using the SNPs can multiple SNP typing methods. Soluble CD55 (sCD55) expression was significantly lower in the EV71 HFMD group than in the control group and lower in severe cases than in mild cases (P < .001). Moreover, CD55 rs2564978 (C vs T OR = 1.300, 95% CI, 1.120-1.509) was associated with the risk of EV71 infection, and genotype TC was related to the severity of the infection (TC vs TT OR = 4.523, 95% CI, 2.033-10.066). Our results suggest that sCD55 expression and the CD55 polymorphism rs2564978 may influence the susceptibility to and severity of EV71 infection.     

Association of polymorphisms in the vitamin D receptor gene with severity of hand,foot, and mouth disease caused by enterovirus 71

Severe hand, foot, and mouth disease (HFMD) is sometimes associated with critical complications that can cause substantial child mortality. Activity of the vitamin D receptor (VDR) may influence the outcomes of enterovirus 71 (EV71) infection. This case-control study aimed to assess the association of single-nucleotide polymorphisms (SNPs) in the gene encoding the VDR with the severity of EV71-associated HFMD. We selected four VDR SNPs based on linkage disequilibrium and functional prediction, and we tested them using the SNPscan multiple SNP typing method for potential association with severity of EV71-associated HFMD. We found a significant association in the case of rs11574129 (G vs A: odds ratio (OR), 0.3439; 95% confidence intervals (CI), 0.1778-0.6653) and rs739837 (T vs G: OR, 0.5580; 95%CI, 0.3352-0.9291). Our results suggest that these two SNPs may influence the severity of EV71-associated HFMD.     

Association of Interleukin-17F Gene Polymorphism with Enterovirus 71 Encephalitis in Patients with Hand, Foot, and Mouth Disease

Enterovirus 71 (EV71) is one of the common pathogenic agents of hand, foot, and mouth disease (HFMD) and is associated with severe complications including encephalitis. Interleukin (IL)-17F plays an important role in tissue inflammation by inducing release of proinflammatory cytokines and chemokines. We investigated the association between EV71 encephalitis and of IL-17F 7488T/C (rs763780) gene polymorphism, which is known to cause a His-to-Arg substitution at amino acid 161. The study was performed in 58 Chinese patients with EV71 encephalitis and 127 Chinese patients with EV71-related HFMD without complications. Genotyping was determined by the polymerase chain reaction–restriction fragment length polymorphism technique. The patients with EV71 encephalitis had a significantly lower frequency of the IL-17F 7488TC+CC genotypes (10.3 %) as compared to the patients with EV71-related HFMD without complications (27.6 %, p?=?0.008). The frequency of IL-17F 7488C alleles was also significantly lower among the patients with EV71 encephalitis (5.2 %) as compared to that of the patients with EV71-related HFMD without complications (15 %, OR?=?0.310, 95 % CI?=?0.127–0.756, p?=?0.006). Furthermore, homozygotes with the T allele had significantly higher levels of C-reactive protein, white blood cell count, and neutrophil count as compared to the patients with CC+CT genotypes (p?=?0.004, 0.001, and 0.000, respectively). These findings suggested that the IL-17F 7488C allele could be significantly associated with protection against encephalitis in Chinese patients with EV71-related HFMD.     

Co-detection in the pathogenesis of severe hand-foot-mouth disease

It still needs to be elucidated whether co-detection of EV71 with other intestinal tract viruses plays a role in the pathogenesis of severe hand-foot-mouth disease (HFMD). A total of 680 stool specimens collected from clinically diagnosed mild and severe-HFMD patients were tested for EV71, CA16, norovirus, bocavirus and rotavirus. The results showed that EV71 was significantly associated with severe-HFMD patients. Co-detection of EV71 with norovirus and rotavirus was also significantly associated with severe-HFMD patients: The OR (95?% CI) value was 6.466 (2.735, 15.283) and 7.561 (3.560, 16.057), p?<?0.001, respectively. Co-detection of EV71 with rotavirus or norovirus is probably associated with severe HFMD.     

Enterovirus spectrum from the active surveillance of hand foot and mouth disease patients under the clinical trial of inactivated Enterovirus A71 vaccine in Jiangsu,China, 2012‐2013

Epidemiological data from active surveillance on human enterovirus, which could cause hand, foot, and mouth disease, were limited. An active surveillance system was used to investigate the enterovirus spectrum and the incidence of different enteroviruses in infants aged 6–35 months in Jiangsu Province from 2012 to 2013. Fifty‐nine infants were randomly selected from 522 non‐EV‐A71/CV‐A16 HFMD patients. We collected 173 throat swabs and 174 rectal swabs from these infants. RT‐PCR was used to amplify 5'‐UTR and VP1 regions of enteroviruses and the serotypes were determined by the sequence comparison using BLAST. Twenty‐one non‐EV‐A71/CA16 enterovirus serotypes were detected in those infants. E16, E18 were firstly reported in HFMD patients. The four top common non‐EV‐A71/CV‐A enteroviruses among infants were CV‐B3, CV‐A10, CV‐A6, and E9 with the HFMD incidence rates at 1.4%, 0.84%, 0.56%, and 0.47%, respectively. Over 20.8% patients were co‐infected with multiple enteroviruses. Neither the course of sickness nor clinical symptoms of the co‐infected patients was more severe than those infected with single enterovirus. Two patients were infected different enterovirus successively within 2 months. Several new enterovirus serotypes and multiple models of infection associated with HFMD were discovered through the active surveillance system. These data provide a better understanding of the viral etiology of HFMD. J. Med. Virol. 87:2009–2017, 2015. © 2015 Wiley Periodicals, Inc.

     

Cost-effectiveness of bivalent versus monovalent vaccines against hand,foot and mouth disease

ObjectivesEnterovirus 71 (EV71) and coxsackievirus A16 (CA16) were responsible for 43.3% (235 123/543 243) and 24.8% (134 607/543 243) of all laboratory-confirmed hand, foot and mouth disease (HFMD) cases during 2010–2015 in China. Three monovalent EV71 vaccines have been licensed in China while bivalent EV71/CA16 vaccines are under development. A comparative cost-effectiveness analysis of bivalent EV71/CA16 versus monovalent EV71 vaccination would be useful for informing the additional value of bivalent HFMD vaccines in China.MethodsWe used a static model parameterized with the national HFMD surveillance data during 2010–2013, virological HFMD surveillance records from all 31 provinces in mainland China during 2010–2013 and caregiver survey data of costs and health quality of life during 2012–2013. We estimated the threshold vaccine cost (TVC), defined as the maximum additional cost that could be paid for a cost-effective bivalent EV71/CA16 vaccine over a monovalent EV71 vaccine, as the outcome. The base case analysis was performed from a societal perspective. Several sensitivity analyses were conducted by varying assumptions governing HFMD risk, costs, discounting and vaccine efficacy.ResultsIn the base case, choosing the bivalent EV71/CA16 over monovalent EV71 vaccination would be cost-effective only if the additional cost of the bivalent EV71/CA16 compared with the monovalent EV71 vaccine is less than €4.7 (95% CI 4.2–5.2). Compared with the TVC in the base case, TVC increased by up to €8.9 if all the test-negative cases were CA16-HFMD; decreased by €1.1 with an annual discount rate of 6% and exclusion of the productivity loss; and increased by €0.14 and €0.3 with every 1% increase in bivalent vaccine efficacy against CA16-HFMD and differential vaccine efficacy against EV71-HFMD, respectively.ConclusionsBivalent EV71/CA16 vaccines can be cost-effective compared with monovalent EV71 vaccines, if suitably priced. Our study provides further evidence for determining the optimal use of HFMD vaccines in routine paediatric vaccination programme in China.     

A review and meta‐analysis of the epidemiology and clinical presentation of coxsackievirus A6 causing hand‐foot‐mouth disease in China and global implications

Coxsackievirus A6 (CV‐A6) has been associated with increasingly occurred sporadic hand‐foot‐mouth disease (HFMD) cases and outbreak events in many countries. In order to understand epidemiological characteristics of CV‐A6, we collected the information describing HFMD caused by CV‐A6 to describe the detection rate, severe rate and onychomadesis rate, which is defined as one or more nails defluvium, caused by CV‐A6 from 2007 to 2017. The results showed that there was an outbreak of CV‐A6 every other year, and overall trend of the epidemic of CA6‐associated HFMD was increasing in China. The detection rate of CV‐A6 in other countries was 32.0% (95% CI: 25.0%~40.0%) before 2013 and 28.0% (95% CI: 20.0%~36.0%) after 2013, respectively. Although the severe rate of HFMD caused by CV‐A6 was low (0.10%, 95% CI: 0.01%~0.20%), CV‐A6 can cause a high incidence of onychomadesis (28.0%, 95%CI: 21.9%‐34.3%). Thus, it would be worthwhile to research and develop an effective multivalent vaccine for CV‐A6 to achieve a more powerful prevention of HMFD.     

From conduct disorder to severe mental illness: associations with aggressive behaviour, crime and victimization

BACKGROUND: Conduct disorder (CD) prior to age 15 has been associated with an increased risk of aggressive behaviour and crime among men with schizophrenia. The present study aimed to replicate and extend this finding in a clinical sample of severely mentally ill men and women. METHOD: We examined a cohort of in-patients with severe mental illness in one mental health trust. A total of 205 men and women participated, average age 38.5 years. CD was diagnosed using a structured diagnostic tool. Alcohol and illicit drug use, aggressive behaviour and victimization were self-reported. Information on convictions was extracted from official criminal records. Analyses controlled for age and sex. RESULTS: CD prior to age 15 was associated with an increased risk of assault over the lifespan [odds ratio (OR) 3.98, 95% confidence interval (CI) 1.87-8.44)], aggressive behaviour in the 6 months prior to interview (OR 2.66, 95% CI 1.24-5.68), and convictions for violent crimes (OR 3.19, 95% CI 1.46-6.97) after controlling for alcohol and illicit drug use. The number of CD symptoms present prior to age 15 significantly increased the risk of serious assaults over the lifespan, aggressive behaviour in the past 6 months, and violent crime after controlling for alcohol and illicit drug use. CONCLUSIONS: Men and women with severe mental illness who have a history of CD by mid-adolescence are at increased risk for aggressive behaviour and violent crime. These patients are easily identifiable and may benefit from learning-based treatments aimed at reducing antisocial behaviour. Longitudinal, prospective investigations are needed to understand why CD is more common among people with than without schizophrenia.     

基于飞行时间质谱技术研究手足口病人群IL-22／IL-22RA1基因单核苷酸多态性

目的探讨Th22细胞相关性细胞因子IL-22／IL-22RA1基因单核苷酸多态性（SNP）与手足口病易感性及其转归的关系。方法采用病例-对照研究方法,选取2012年4月至9月深圳市第三人民医院收治并确诊的手足口病住院患者296例为病例组,其中轻症手足口病患者178例,重症患者118例,对照组为同期在该医院健康体检儿童155例。应用飞行时间质谱（timeoffightmassspectrum,TOF—MS）生物芯片技术,检测IL-22／IL-22RAl基因共4个SNP位点基因型（rs2227473、rs2227483、rs3795299、rs34379702）,对SNP进行Hardy．Weiberg平衡检测,并计算各SNP位点在不同人群中等位基因频率,筛选与手足口病易感性、预后相关的SNP位点。结果纳入研究的4个SNP位点的基因型分布均处于遗传平衡状态。人组人群中IL-22的基因rs2227473位点存在GG、GA和AA基因型,重症手足口病组rs222743位点A等位基因频率（13．14％,31／236）显著高于轻症组（6．18％,22／356）,差异有统计学意义（x^2=8．424,P〈0．001,A=2．296,95％CI=1．294—4．074）。对于EV71相关性手足口病而言,重症组A等位基因频率（19．64％,22／112）显著高于轻症组（7．41％,4／54）,差异有统计学意义（x^2=4．129,P=0．042,A=3．056,95％CI=0．997—9．368）。结论IL-22基因rs2227473位点多态性与手足口病转归密切相关,尤其是EV71相关性手足口病。     

CREB1 gene polymorphisms combined with environmental risk factors increase susceptibility to major depressive disorder (MDD)

Major depressive disorder (MDD) is one of the most severe psychiatric disorders. The objective of this study was to explore the effects of CREB1 gene polymorphisms on risk of developing MDD and the joint effects of gene-environment interactions. Genotyping was performed by Taqman allelic discrimination assay among 586 patients and 586 healthy controls. A significant impact on rs6740584 genotype distribution was found for childhood trauma (P = 0.015). We did not find an association of CREB1 polymorphisms with MDD susceptibility. However, we found a significantly increased risk associated with the interactions of CREB1 polymorphisms and drinking (OR = 11.67, 95% CI = 2.52-54.18; OR = 11.52, 95% CI = 2.55-51.95 for rs11904814; OR = 4.18, 95% CI = 1.87-9.38; OR = 5.02, 95% CI = 2.27-11.14 for rs6740584; OR = 7.58, 95% CI = 2.05-27.98; OR = 7.59, 95% CI = 2.12-27.14 for rs2553206; OR = 8.37, 95% CI = 3.02-23.23; OR = 7.84, 95% CI = 2.93-20.98 for rs2551941). We also noted that CREB polymorphisms combined with family harmony and childhood trauma conferred increased susceptibility for MDD. In conclusion, polymorphisms in the CREB gene may not be independently associated with MDD risk, but they are likely to confer increased susceptibility by interacting with environmental risk factors in the Chinese population.     

Klotho gene polymorphisms are related to colorectal cancer susceptibility

Aim: The purpose of this study was to investigate the relationship of Klotho gene G-395A and C1818T polymorphisms with colorectal cancer (CRC) susceptibility. Methods: 125 CRC patients and 125 controls were enrolled in the study. G-395A and C1818T polymorphisms were genotyped with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technology. Haploview software was utilized to conduct linkage disequilibrium and haplotype analysis. Odds ratio (OR) and 95% confidence interval (95% CI) were used to analyze the correlation of genotypes and haplotypes with CRC susceptibility. Results: AA and GA genotypes of G-395A polymorphisms were related with CRC risk (AA: OR = 4.161, 95% CI = 1.437-12.053; GA: OR = 1.958, 95% CI = 1.133-3.385). The frequency of A allele was much higher in case group, compared with controls (31.2% vs.17.6%) and the value of OR AND 95% CI suggested that A allele served as a risk factor for CRC (OR = 2.123, 95% CI = 1.393-3.236). Haplotypes analysis indicated that A-C and A-T haplotypes were significantly associated with risk of CRC (OR = 1.822, 95% CI = 1.124-2.954; OR = 2.877, 95% CI = 1.340-6.176). Conclusion: G-395A polymorphism of Klotho gene could increase the risk of CRC.     

A polymorphism in melanoma differentiation-associated gene 5 may be a risk factor for enterovirus 71 infection

Enterovirus 71 (EV71) infection has a wide variety of clinical manifestations, from no symptoms to fatal disease. Host immune response may be a determinant of disease severity. We investigated the association of polymorphisms in three pattern recognition receptor (PRR) genes—toll-like receptor 3 (TLR3) (rs3775291), retinoic acid-inducible gene I (RIG-I) (rs10813831) and melanoma differentiation-associated gene 5 (MDA5) (rs1990760)—with the severity of EV71 infection. Polymorphisms of candidate genes in 87 EV71-infected patients and 57 asymptomatic controls were detected. Binary logistic regression analysis revealed statistically significant differences in polymorphism of MDA5 (rs1990760) between patients with severe EV71 infection and asymptomatic controls in an additive model (OR 0.424, 95% CI 0.213-0.845, p 0.015) and a dominant model (OR 0.256, 95% CI 0.103-0.635, p 0.003). Polymorphism of MDA5 (rs1990760) (OR 0.399, 95% CI 0.199-0.798, p 0.009) was found to be associated with the severity of EV71 infection with the analysis of ordinal logistic regression. These results indicated the association between MDA5 (rs1990760) polymorphism and an increased risk of a severe EV71 infection in Chinese children, which offers potential for investigating the innate immune mechanism of EV71 infection and identifying at-risk infants, for whom a preventive strategy may reduce the severity of EV71 infection.     

Association analysis of polymorphisms in OAS1 with susceptibility and severity of hand,foot and mouth disease

Hand, foot and mouth disease (HFMD) is a common childhood illness that mainly affects Asian children under the age of 5 years. Human enterovirus 71 (EV71) and coxsackievirus A16 (CA16) are the most common pathogens of HFMD. It is imperative that the susceptible population is screened early and that the severe illness population can be identified via genetic variation detection in children. Four single‐nucleotide polymorphisms (SNP) [2′‐5′‐oligoadenylate synthetase1 (OAS1) rs10774671, selectin P ligand (SELPLG) rs2228315, scavenger receptor class B member 2 (SCARB2) rs41284767 and interleukin 28B (IL28B) rs12979860] were determined by Taqman assays in 333 HFMD samples and 163 control samples. The rs2228315, rs41284767 and rs12979860 polymorphisms did not differ significantly between HFMD patients and the controls, but the prevalence of the rs10774671 polymorphism was significantly different between the control children and children infected with CA16 (GG genotype vs. AA + AG genotype, P < 0.05). Children with the GG genotype were more susceptible to CA16‐type HFMD. Furthermore, the rs10774671 genotype distribution was clearly different between children with severe HFMD and those with mild HFMD [P < 0.05, OR 0.240, 95% CI (0.071–0.809)]. HFMD children with the AA+AG genotype were more likely to progress to encephalitis than were those with the GG genotype. Plasma γ‐interferon (IFN) expression levels among control children and the mild and severe HFMD children were detected by ELISA. Those with mild HFMD had higher γ‐IFN expression levels compared with those with severe HFMD (P < 0.05). In addition, there is a significant correlation between γ‐IFN levels and OAS1 rs10774671 SNP, as analysed by linear correlation assay. The GG genotype correlated with higher γ‐IFN levels (P < 0.05). In short, the OAS1 rs10774671 SNP GG genotype contributed to CA16 susceptibility and was associated with the development of mild HFMD.     

柯萨奇病毒A组天津分离株的分型鉴定及分子特征分析

目的 鉴定天津市手足口病病原体柯萨奇病毒A组2、4、5、6和10型,并分析其VP1区基因及分子流行病学特征.方法 提取45株非EV71非CV-A16肠道病毒分离株核酸,利用RT-PCR法扩增其VP1基因并测序,然后根据VP1区基因核酸序列,进行肠道病毒型别鉴定和同源性分析,构建种系发生树.结果 45株非EV71非CV-A16肠道病毒天津分离株分别为6株柯萨奇病毒A组2型(Coxsackie virus A2,CV-A2),14株CV-A4,3株CV-A5,8株CV-A6和14株CV-A10.柯萨奇病毒各型的株间核酸序列同源性均在80％以上,各型分离株与原型株的同源性均在71.2％ ～ 85.8％之间.天津各型分离株在种系发生树上均聚集于各自相对独立的分支,与国内流行株处在同一分支内,而与国外原型株处于不同的进化分支.结论柯萨奇病毒A组2、4、5、6和10型成为天津市手足口病的流行病原体,各型天津分离株株间核酸序列同源性较高,呈现一定的区域聚集性.     

Risk Factors for Antimicrobial Resistance Among the Escherichia coli Strains Isolated from Korean Patients with Acute Uncomplicated Cystitis: A Prospective and Nationwide Study

We investigated the risk factors for resistance to ciprofloxacin, cefazolin, ampicillin and co-trimoxazole in Escherichia coli isolates from urine of Korean female patients with acute uncomplicated cystitis (AUC). A total of 225 patients and their E. coli isolates were prospectively and nationwidely enrolled between May and October, 2006. All the antimicrobials did not show any differences according to the age group. A higher rate of ciprofloxacin resistance was observed in the south (OR: 3.04, 95% CI: 1.19-7.80 for Chungcheong-do & Jeolla-do; OR: 3.04, 95% CI: 1.22-7.58 for Gyeongsang-do) compared to Gyeonggi-do. Two recurrences of AUC in the past year was an important risk factor for antimicrobial resistance (ciprofloxacin; OR: 6.71, 95% CI: 1.86-24.11 and cefazolin; OR: 5.72, 95% CI: 1.20-27.25). However, the resistance to co-trimoxazole and ampicillin was not associated with any of the risk factors. This study also revealed the pattern of multi-drugs resistance in ciprofloxacin resistant E. coli strains. In conclusion, for Korean patients with two more recurrences of AUC in the past year, it is strongly recommended to perform an antimicrobial sensitivity test with a urine sample before empirical treatment.