Antibiotic drug resistance pattern of uropathogens seen in the first episode of community-acquired pediatric urinary tract infections at a tertiary care hospital

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This study aims to analyze the antimicrobial resistance profile of uropathogens isolated from children with the first attack of community-acquired UTI. Materials and Methods This retrospective cohort study was conducted between January 2010-December 2016, with the patients aged one month to 18 years diagnosed with the first attack of community-acquired UTI at the pediatric outpatient clinic of a tertiary care hospital. Patients' age, sex, UTI history, clinical findings at admission, urine analysis, urine culture, and antibiogram results were recorded. Results A total of 1086 patients and 1086 cultures were included in the study. The male/female ratio was 1/5.3. The mean age of the children was 73.7±47.1 (0.4-215.9) months. 16.0% were aged 1-24 months. E. coli was the most common causative agent found to be 85.1% in frequency. The overall antimicrobial resistance was found to be highest for ampicillin, followed by piperacillin and trimethoprim-sulfamethoxazole (63.5, 41.6 and 38.1%, respectively). Imipenem, amikacin, and tobramycin had the least resistance (0.5, 0.5, and 7.6%, respectively). The overall antimicrobial resistance against amoxicillin-clavulanate, ampicillin-sulbactam, cefuroxime, ceftriaxone was 19.4, 24, 25.9 and 21.1%; respectively. Extended-spectrum beta-lactamase positivity was detected in 5.6% (n=61) of samples. Conclusion Our study showed significant increase in antimicrobial resistance to the most common antibiotics which are prescribed before urine culture results and antibiotic sensitivities are available. The resistance rates for amoxicillin-clavulanate, ampicillin-sulbactam, cefuroxime, ceftriaxone were almost 20% or above in children with the first UTI attack in an outpatient setting. Pediatrics Urology & Nephrology General Microbiology urinary tract infection uropathogen antimicrobial resistance antimicrobial susceptibility Figures Figure 1 Introduction Urinary tract infections (UTI) are among the most common bacterial infections in children. 1 Escherichia coli is the most common bacterial pathogen responsible for UTI. 1 , 2 One lingering effect of childhood UTI is that it can damage the growing kidney by forming kidney scarring associated with long-term complications, hypertension, and renal failure. 1 – 4 Clinical guidelines about UTI in children encourage rapid diagnosis and early treatment with an appropriate agent to prevent kidney scarring and long-term complications. 4 – 7 Antibiotic resistance is strikingly increasing among the uropathogens, and bacterial resistance causes problems for clinicians due to limited treatment options. 1 , 2 , 6 , 7 Data are available on the antimicrobial susceptibility patterns of endemic uropathogens in different countries of the world, but it is necessary to update the changing patterns of resistance to determine the appropriate treatment plans. 1,2,6−9 Since treatment to reduce UTI-related morbidity is usually started early before the results of urinary microbiology are obtained, current data on the most common uropathogens and local antibiotic resistance patterns will help to choose accurate empirical therapy. This study was conducted to determine the antimicrobial resistance patterns of uropathogens isolated from patients with the first episode of community-acquired urinary tract infections to choose appropriate empirical UTI treatment in children. To our knowledge, this is the only study examining antimicrobial resistance patterns in the first UTI episode in children. Materials And Methods This observational study was conducted between January 2010-December 2016, with children aged one month to 18 years diagnosed with their first episode of UTI at pediatric outpatient polyclinics at Dr. Sami Ulus Children's Health and Diseases Training and Research Hospital. Ankara Hematology-Oncology Hospital Ethics Committee approved the study. Urine samples for microbial examination were collected by midstream clean-catch method in the toilet-trained and urethral catheterization method in non-toilet-trained children. No samples in the study were collected by the bag or suprapubic aspiration. A positive urine culture was defined as the growth of a single pathogen of at least 10 5 colony forming units (CFU)/ml for midstream sampling, and 10 4 colonies/ml for catheter specimens. 10 Only a single positive culture per patient was included in the analysis. The diagnosis of UTI was then based on clinical findings and positive urine culture. Children with urinary tract abnormalities, recurrent UTIs, vesicoureteral reflux (VUR), urolithiasis, complicated urinary tract infections, known chronic or other medical disorders, polymicrobial culture results, culture results defined as contamination by medical microbiology expert and using antibiotics before admission or already on antibiotic treatment and hospitalized children were excluded from the study. All urine samples were tested using standard procedures and were cultivated into MacConkey agar and incubated at 37°C for 48 h. The VITEK 2 automated microbial identification system was used to identify uropathogens and antimicrobial "susceptible" or "resistant" status. Bacterial identification and the determination of sensitivity and resistance patterns of these microorganisms were assessed by the criteria established by the Clinical Laboratory Standards Institute (formerly National Committee for Clinical Laboratory Standards) guidelines. 11 Patients' sex, age, clinical findings, urine analysis (UA), urine culture and susceptibility rates of etiologic agents to different antimicrobials were recorded retrospectively. The patients' previous UTI history was asked to parents and checked by hospital records if they had applied to our hospital before. Patients were classified as E. Coli and non-E. Coli UTI, according to urine culture results. Statistical analysis was performed in SPSS for Windows 15.0 (SPSS Inc., Chicago, IL, USA). Descriptive statistics are given as mean, the standard deviation for continuous variables, and frequency, the percentage for categorical variables. Comparisons were performed using the t-test, Mann-Whitney u test, and chi-squares test, where p < 0.05 was considered as statistically significant. Results Clinical and demographic characteristics The 1086 cultures of 1086 patients with first UTI episodes were enrolled in the study. Of these patients; 15.8% ( n = 172) were male, 84.2% ( n = 914) were female. The male/female ratio was 1/5.3. The number of girls was significantly higher than boys ( P < 0.001). The mean age was 73.7 ± 47.1 (0.4-215.9) months. Of the 1086 positive UCs, 16.0% (n = 174) were from children aged 1–24 months. 82.4% of UCs were obtained by midstream clean catch. 17.6% were obtained by catheterization. Demographical and clinical characteristics were shown in Table 1 . UTI with non- E. Coli isolates were younger than patients with UTI with E. coli isolates, more seen in males, and had more normal urinalysis (Table 2 ). Table 1 Demographic characteristics of the patients The mean age 73.7 ± 47.1 (0.4-215.9) months Age groups < 2 years 2–5 years 6-10years 11–18 years % ( n) 16.0 (174) 27.3 (296) 43.0 (467) 13.7 (149) Sex Male Female % ( n) 15.8 (172) 84.2 (914) Symptoms Fever Urinary complaints Abdomen/flunk pain Vomiting Irritability Other (malnutrition, prolonged jaundice) % ( n) 72.7 (789) 27.0 (293) 6.1 (67) 3.4 (38) 4.4 (48) 3.2 (35) Urine analysis Positive nitrite Positive leukocyte esterase (LE) Nitrite and LE positivity Normal urine microscopy Normal results in urinalysis and microscopy % ( n) 52.0 (557) 77.6 (846) 42.2 (452) 12.5 (134) 7.8 (84) Table 2 Demographic and clinical characteristics of E. Coli and non- E. Coli groups Characteristics E. Coli Non-E. Coli P-value Mean age (years) 6.3 ± 3.7 4.7 ± 4.4 < 0.01 < 2 years of age (%) 13.1 32.3 < 0.01 Male sex (%) 9.8 49.3 < 0.01 Fever positive (%) 21.4 14.8 0.056 Normal urinanalysis 5.8 19.3 < 0.01 Isolated uropathogens E. coli (85.1%, n = 924) was the most common causative agent in all age groups followed by Proteus species (7.6%, n = 82), and Klebsiella species (6.5%, n = 71). Other isolates (M. morgagni, Enterobacter, Streptecocspp, S. aureus) were 0.9% (n = 9) in frequency ( Table 3 ). Table 3 Antibiotic resistance frequencies according to isolated uropathogens Antibiotics E. Coli % (n) Proteus % (n) Klebsiella % (n) Total UCs % (n) Ampicillin 62.7% (561) 41.8% (33) 95.8 (68) 63.5% (668) Piperacillin 44.5% (182) 9.1% (3) 39.4 (13) 41.6% (198) Amoxicillin-clavulanate 19.4 (173) 7.5 (6) 33.3 (23) 19.8% (208) Ampicillin-sulbactam 24.6 (216) 5.2 (4) 36.2 (25) 24% (248) Piperacillin-tazobactam 11.1 (67) 1.7 (1) 17.3 (9) 10.9% (78) Aztreonam 19.3 (107) 0 (0/37) 35.4 (17) 19.4% (124) Cephazolin 16.5 (94) 9.3 (5) 27.7 (13) 16.9% (114) Cephalotin 29.2 (142) 11.9 (5) 30 (12) 28.2% (161) Cefepime 12.3 (64) 0 (0/40) 13.5 (5) 11.4% (69) Cefuroxime 25.4 (156) 11.4 (5) 38.3 (18) 25.9% (184) Cefixime 18.9 (10) 0 (0/20) - 17.5% (10) Ceftriaxone 21.5 (37) 0 (0/46) 35.2 (19) 21.1% (157) Cefotaxime 10.7 (55) 0 (0/40) 30.8 (12) 11.3% (67) Ceftazidime 21.1 (128) 0 (0/46) 36.7 (18) 20.7% (146) Nitrofurantoin 5.5 (22) 94.3 (33) 33.3 (10) 14.4% (68) Trimethoprim-sulfamethoxazole 37.5 (336) 52.6 (41) 32.9 (23) 38.1% (400) Gentamicin 9.5 (86) 5.1 (4) 14.1 (10) 9.5% (100) Amikacin 0.5 (4) 2.4 (2) 1.4 (1) 0.5% (5) Tobramycin 7.7 (33) 2.6 (1) 11.4 (4) 7.6% (38) Imipenem 0.4 (2) 0 (0/39) 2.6 (1) 0.5% (3) Ciprofloxacin 9.1 (68) 1.5 (1) 8.1 (5) 8.4% (74) Antibacterial susceptibility Among all isolates, the overall antimicrobial resistance was found to be highest for ampicillin, followed by piperacillin and TMP-SMX (63.5, 41.6, and 38.1%, respectively). The overall antimicrobial resistance against amoxicillin-clavulanate, ampicillin-sulbactam, cefuroxime, ceftriaxone was 19.4, 24, 25.9, and 21.1%; respectively. Imipenem, amikacin, and tobramycin had the least resistance (0.5, 0.5, and 7.6%, respectively). The antimicrobial resistance patterns of the uropathogens were shown in Table 3 . E. coli demonstrated high resistance to ampicillin, piperacillin, and TMP/SMX (62.7, 44.5, and 37.5%, respectively). The least resistance was for imipenem and amikacin and nitrofurantoin (0.4, 0.5, 5.5%, respectively) (Table 3 ). Proteus spp represented high resistance to nitrofurantoin, TMP-SMX, and ampicillin (94.3, 52.6, and 41.8%, respectively). Proteus spp had no resistance against third-generation cephalosporins and imipenem (Table 3 ). Klebsiella spp had the highest resistance to ampicillin (95.8%). Cephalosporins other than cefepime and cephazolin had a resistance frequency of ≥ 30%. The least resistance was for amikacin, imipenem, and ciprofloxacin. (1.4, 2.6, 8.1%, respectively) (Table 3 ). The extended-spectrum beta-lactamase (ESBL) producer isolates were detected in 61 samples (5.6%, n = 61/1086). Of these, n = 55 were among E. coli isolates, n = 6 were among Klebsiella species. Extended-spectrum beta-lactamase positive strains showed high resistance to ampicillin (100%), ceftriaxone (96.5%), and nitrofurantoin (33.3%). They revealed the least resistance for amikacin (8.5%) and imipenem (7.1%). Discussion Uropathogens are showing a rising trend in the antimicrobial resistance throughout the world. 2,7,8,12−20 The most common oral antibiotics prescribed for UTI as empirical antimicrobial agents in outpatient settings in Turkey are amoxicillin/clavulanate, an oral third-generation cephalosporin 'cefixime.' The most common agents used for parenteral treatment are aminoglycosides and parenteral cephalosporins (ceftriaxone or cefotaxime) in the case of patients under three months of age, toxic, or could not have oral intake. For secondary prophylaxis cefixime, co-trimoxazole and nitrofurantoin are commonly prescribed. Our study showed a significant increase in antimicrobial resistance to the most common antibiotics prescribed for UTI in childhood with the first UTI attack even in an outpatient setting. The resistance rates for amoxicillin-clavulanate, ampicillin-sulbactam, cefuroxime, ceftriaxone were almost 20% or above in our study. This result is striking because the frequency of cephalosporin resistance was nearly half in the previous study conducted at our center between 2004–2008 years 19 , which included all positive UCs by not taking into consideration the comorbid factors, including urinary tract anomalies, recurrent UTI which assumed to increase the frequency of antimicrobial resistance. A comparison of antimicrobial resistance against uropathogens in consecutive (2004–2008, 2010–2016) periods in our center was shown in Fig. 1 . These results indicate that UTI treatment will be troublesome in the future, even in an outpatient setting. These results are important because of heralding the risk of UTI complication burden. The significant increase in resistance to third-generation cephalosporins also harbors significant risks not only in UTI but also in other childhood disease treatments. Ghadageet al. 21 reported increased resistance to commonly used empirical therapy -ampicillin and co-trimoxazole- for UTI in India. Kothari and Sagar 22 also reported low susceptibility to amoxicillin, amoxicillin/clavulanate, ciprofloxacin, co-trimoxazole in uropathogens. Prais et al. 23 reported that empirical treatment with co-trimoxazole or cephalexin as the initial drug is inadequate in approximately one-third of UTI cases, but that nitrofurantoin and nalidixic acid maintained their very high efficacy against urinary pathogens in Israel. The European Centre for Disease Prevention and Control reported the increasing resistance to antibiotic treatments, including carbapenems. 24 Imipenem-resistant E. coli rates were reported at 1.4–3.5% in Turkey. 8 , 25 In our study, while resistance to ampicillin, piperacillin, and TMP-SMX was high among all isolates, imipenem, amikacin, and tobramycin had the lowest resistance. All Klebsiella isolates are sensitive to imipenem and amikacin in our study, as in a study by Abuhandan et al. 26 However, Wang et al. reported resistance to imipenem and amikacin at a frequency of 21.12% and 6.83%, respectively. 6 These results may vary because of the different patient inclusion criteria in different studies. Proteus isolates also revealed no resistance to third-generation cephalosporins and imipenem in our study. The overall ESBL positivity has been reported to be 5% in Europe, 39% in Asia, and 30% -50% in Turkey. 27 , 28 . Kurt-Şükür et al. reported a prominently increase in overall ESBL positivity from 7.8–23.5% within ten years. 8 ESBL positivity in our study was 5.6% in frequency, which is lower than the reports of other studies. This may because all of our patients had the first UTI episode without comorbid conditions and frequent antibiotic usage for UTI treatment. The increase of resistant strains can be attributed to either availability of the drugs for unnecessary and improper use of many antimicrobials, or by empirical treatment. 29 , 30 Therefore, continuous surveillance, new strategies, and multidisciplinary actions should be developed against over consumption and unnecessary antibiotic treatments. Recently, in this context, the Turkish Ministry of Health restricted antibiotic intake without prescription and planned projects to improve rational antibiotic use, such as public education campaigns, to increase awareness about this topic. Studies in the future will show the results of these precautions. Our study has the following limitations. The major limitation was its retrospective nature. The history of previous UTI episodes was limited to the family expression and the investigations performed in our hospital. Another limitation relates to in vitro susceptibility testing, which may not be fully reflected in clinical outcomes, as in-vivo sensitivity may be different. Also, the results obtained from our study may not be valid for other patients in different regions. Conclusion The present study showed that initial empirical treatment with amoxicillin, trimethoprim-sulfamethoxazole, and first-generation cephalosporins are no longer appropriate, but fluoroquinolones, cefepime, imipenem, amikacin and nitrofurantoin (for E. Coli ) maintained their high efficacy against urinary pathogens in Turkey. Almost one in five children have antimicrobial resistance against antimicrobials which are the ones likely to be prescribed before culture results and antibiotic sensitivities are available to the clinician. This result reveals upcoming future challenges in the successful treatment of pediatric UTI, even in an outpatient setting. The present results may be of significant value to assist physicians in the appropriate choice of antibiotics, and to prevent the misuse or excessive use of antibiotics. Declarations Funding Source: No external funding for this manuscript Financial Disclosure: Authors have indicated that they have no financial relationships relevant to this article to disclose Conflict of interest: The authors declare no conflict of interest Contributors’ Statement Dr Sari conceptualized and designed the study, drafted the initial manuscript, and reviewed, and revised the manuscript. Drs Yazilitas, Oztek-Celebi, Akcaboy, and Akisoglu designed the data collection instruments, collected data, carried out the initial analyses, and reviewed and revised the manuscript. Prof. Senel conceptualized and designed the study, coordinated and supervised data collection, and critically reviewed the manuscript for important intellectual content. 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Ankara Dr Sami Ulus Kadin Dogum Cocuk Sagligi ve Hastaliklari Egitim ve Arastirma Hastanesi","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Fatma","middleName":"Zehra Oztek","lastName":"Celebi","suffix":""},{"id":14449666,"identity":"f51f4a7b-813e-445f-8e6f-b5b459f5a26a","order_by":3,"name":"Meltem Akcaboy","email":"","orcid":"","institution":"Doktor Sami Ulus Cocuk Hastanesi: SBU Ankara Dr Sami Ulus Kadin Dogum Cocuk Sagligi ve Hastaliklari Egitim ve Arastirma Hastanesi","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Meltem","middleName":"","lastName":"Akcaboy","suffix":""},{"id":14449667,"identity":"a351ee83-5fb3-490f-9b16-1b7351600bba","order_by":4,"name":"Ozlem Akisoglu","email":"","orcid":"","institution":"Doktor Sami Ulus Cocuk Hastanesi: SBU Ankara Dr Sami Ulus Kadin Dogum Cocuk Sagligi ve Hastaliklari Egitim ve Arastirma Hastanesi","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ozlem","middleName":"","lastName":"Akisoglu","suffix":""},{"id":14449668,"identity":"6cf024ff-deca-4130-b803-a41f3245f2ab","order_by":5,"name":"Saliha Senel","email":"","orcid":"","institution":"Doktor Sami Ulus Cocuk Hastanesi: SBU Ankara Dr Sami Ulus Kadin Dogum Cocuk Sagligi ve Hastaliklari Egitim ve Arastirma Hastanesi","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Saliha","middleName":"","lastName":"Senel","suffix":""}],"badges":[],"createdAt":"2021-02-23 08:26:53","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-269767/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-269767/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.12956/tchd.1071855","type":"published","date":"2022-03-09T20:05:21+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":6818710,"identity":"dd276450-94de-497f-84dd-cba91487a866","added_by":"auto","created_at":"2021-03-10 22:08:38","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":11983,"visible":true,"origin":"","legend":"Comparison of antimicrobial resistance against uropathogens in two consecutive period in the same center","description":"","filename":"OnlineFigure1.png","url":"https://assets-eu.researchsquare.com/files/rs-269767/v1/8a19105f067e671b89e088cf.png"},{"id":19703161,"identity":"dc660834-cda0-48c0-95a5-3b371d41e9b9","added_by":"auto","created_at":"2022-03-28 20:06:46","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":328122,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-269767/v1/5fbdd65c-d8e0-442c-8376-814b41fe2794.pdf"}],"financialInterests":"","formattedTitle":"Antibiotic drug resistance pattern of uropathogens seen in the first episode of community-acquired pediatric urinary tract infections at a tertiary care hospital","fulltext":[{"header":"Introduction","content":" \u003cp\u003eUrinary tract infections (UTI) are among the most common bacterial infections in children.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e \u003cem\u003eEscherichia coli\u003c/em\u003e is the most common bacterial pathogen responsible for UTI.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e One lingering effect of childhood UTI is that it can damage the growing kidney by forming kidney scarring associated with long-term complications, hypertension, and renal failure.\u003csup\u003e\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e Clinical guidelines about UTI in children encourage rapid diagnosis and early treatment with an appropriate agent to prevent kidney scarring and long-term complications.\u003csup\u003e\u003cspan additionalcitationids=\"CR5 CR6\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e Antibiotic resistance is strikingly increasing among the uropathogens, and bacterial resistance causes problems for clinicians due to limited treatment options.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e Data are available on the antimicrobial susceptibility patterns of endemic uropathogens in different countries of the world, but it is necessary to update the changing patterns of resistance to determine the appropriate treatment plans.\u003csup\u003e1,2,6\u0026minus;9\u003c/sup\u003e Since treatment to reduce UTI-related morbidity is usually started early before the results of urinary microbiology are obtained, current data on the most common uropathogens and local antibiotic resistance patterns will help to choose accurate empirical therapy.\u003c/p\u003e \u003cp\u003eThis study was conducted to determine the antimicrobial resistance patterns of uropathogens isolated from patients with the first episode of community-acquired urinary tract infections to choose appropriate empirical UTI treatment in children. To our knowledge, this is the only study examining antimicrobial resistance patterns in the first UTI episode in children.\u003c/p\u003e "},{"header":"Materials And Methods","content":"\u003cp\u003eThis observational study was conducted between January 2010-December 2016, with children aged one month to 18 years diagnosed with their first episode of UTI at pediatric outpatient polyclinics at Dr. Sami Ulus Children's Health and Diseases Training and Research Hospital. Ankara Hematology-Oncology Hospital Ethics Committee approved the study.\u003c/p\u003e\n\u003cp\u003eUrine samples for microbial examination were collected by midstream clean-catch method in the toilet-trained and urethral catheterization method in non-toilet-trained children. No samples in the study were collected by the bag or suprapubic aspiration. A positive urine culture was defined as the growth of a single pathogen of at least 10\u003csup\u003e5\u003c/sup\u003e colony forming units (CFU)/ml for midstream sampling, and 10\u003csup\u003e4\u003c/sup\u003e colonies/ml for catheter specimens.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eOnly a single positive culture per patient was included in the analysis. The diagnosis of UTI was then based on clinical findings and positive urine culture.\u003c/p\u003e\n\u003cp\u003eChildren with urinary tract abnormalities, recurrent UTIs, vesicoureteral reflux (VUR), urolithiasis, complicated urinary tract infections, known chronic or other medical disorders, polymicrobial culture results, culture results defined as contamination by medical microbiology expert and using antibiotics before admission or already on antibiotic treatment and hospitalized children were excluded from the study.\u003c/p\u003e\n\u003cp\u003eAll urine samples were tested using standard procedures and were cultivated into MacConkey agar and incubated at 37\u0026deg;C for 48 h. The VITEK 2 automated microbial identification system was used to identify uropathogens and antimicrobial \"susceptible\" or \"resistant\" status.\u003c/p\u003e\n\u003cp\u003eBacterial identification and the determination of sensitivity and resistance patterns of these microorganisms were assessed by the criteria established by the Clinical Laboratory Standards Institute (formerly National Committee for Clinical Laboratory Standards) guidelines.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e Patients' sex, age, clinical findings, urine analysis (UA), urine culture and susceptibility rates of etiologic agents to different antimicrobials were recorded retrospectively. The patients' previous UTI history was asked to parents and checked by hospital records if they had applied to our hospital before. Patients were classified as E. Coli and non-E. Coli UTI, according to urine culture results. Statistical analysis was performed in SPSS for Windows 15.0 (SPSS Inc., Chicago, IL, USA). Descriptive statistics are given as mean, the standard deviation for continuous variables, and frequency, the percentage for categorical variables. Comparisons were performed using the t-test, Mann-Whitney u test, and chi-squares test, where p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered as statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\n\u003ch2\u003eClinical and demographic characteristics\u003c/h2\u003e\n\u003cp\u003eThe 1086 cultures of 1086 patients with first UTI episodes were enrolled in the study. Of these patients; 15.8% (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;172) were male, 84.2% (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;914) were female. The male/female ratio was 1/5.3. The number of girls was significantly higher than boys (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The mean age was 73.7\u0026thinsp;\u0026plusmn;\u0026thinsp;47.1 (0.4-215.9) months. Of the 1086 positive UCs, 16.0% (n\u0026thinsp;=\u0026thinsp;174) were from children aged 1\u0026ndash;24 months. 82.4% of UCs were obtained by midstream clean catch. 17.6% were obtained by catheterization. Demographical and clinical characteristics were shown in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. UTI with non- \u003cem\u003eE. Coli\u003c/em\u003e isolates were younger than patients with UTI with E. coli isolates, more seen in males, and had more normal urinalysis (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eDemographic characteristics of the patients\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eThe mean age\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e73.7\u0026thinsp;\u0026plusmn;\u0026thinsp;47.1 (0.4-215.9) months\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eAge groups\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;2 years\u003c/p\u003e\n\u003cp\u003e2\u0026ndash;5 years\u003c/p\u003e\n\u003cp\u003e6-10years\u003c/p\u003e\n\u003cp\u003e11\u0026ndash;18 years\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e% ( n)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e16.0 (174)\u003c/p\u003e\n\u003cp\u003e27.3 (296)\u003c/p\u003e\n\u003cp\u003e43.0 (467)\u003c/p\u003e\n\u003cp\u003e13.7 (149)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMale\u003c/p\u003e\n\u003cp\u003eFemale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e% ( n)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e15.8 (172)\u003c/p\u003e\n\u003cp\u003e84.2 (914)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eSymptoms\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFever\u003c/p\u003e\n\u003cp\u003eUrinary complaints\u003c/p\u003e\n\u003cp\u003eAbdomen/flunk pain\u003c/p\u003e\n\u003cp\u003eVomiting\u003c/p\u003e\n\u003cp\u003eIrritability\u003c/p\u003e\n\u003cp\u003eOther (malnutrition, prolonged jaundice)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e% ( n)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e72.7 (789)\u003c/p\u003e\n\u003cp\u003e27.0 (293)\u003c/p\u003e\n\u003cp\u003e6.1 (67)\u003c/p\u003e\n\u003cp\u003e3.4 (38)\u003c/p\u003e\n\u003cp\u003e4.4 (48)\u003c/p\u003e\n\u003cp\u003e3.2 (35)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eUrine analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePositive nitrite\u003c/p\u003e\n\u003cp\u003ePositive leukocyte esterase (LE)\u003c/p\u003e\n\u003cp\u003eNitrite and LE positivity\u003c/p\u003e\n\u003cp\u003eNormal urine microscopy\u003c/p\u003e\n\u003cp\u003eNormal results in urinalysis and microscopy\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e% ( n)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e52.0 (557)\u003c/p\u003e\n\u003cp\u003e77.6 (846)\u003c/p\u003e\n\u003cp\u003e42.2 (452)\u003c/p\u003e\n\u003cp\u003e12.5 (134)\u003c/p\u003e\n\u003cp\u003e7.8 (84)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eDemographic and clinical characteristics of E. Coli and non- E. Coli groups\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eCharacteristics\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eE. Coli\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eNon-E. Coli\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eP-value\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMean age (years)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4.7\u0026thinsp;\u0026plusmn;\u0026thinsp;4.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;2 years of age (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e13.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e32.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMale sex (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9.8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e49.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFever positive (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14.8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.056\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNormal urinanalysis\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5.8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e19.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n\u003ch2\u003e\u0026nbsp;\u003c/h2\u003e\n\u003ch2\u003eIsolated uropathogens\u003c/h2\u003e\n\u003cp\u003e\u003cem\u003eE. coli\u003c/em\u003e (85.1%, n\u0026thinsp;=\u0026thinsp;924) was the most common causative agent in all age groups followed by Proteus species (7.6%, n\u0026thinsp;=\u0026thinsp;82), and Klebsiella species (6.5%, n\u0026thinsp;=\u0026thinsp;71). Other isolates (M. morgagni, Enterobacter, Streptecocspp, S. aureus) were 0.9% (n\u0026thinsp;=\u0026thinsp;9) in frequency ( Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab3\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eAntibiotic resistance frequencies according to isolated uropathogens\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eAntibiotics\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eE. Coli\u003c/p\u003e\n\u003cp\u003e% (n)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eProteus\u003c/p\u003e\n\u003cp\u003e% (n)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eKlebsiella\u003c/p\u003e\n\u003cp\u003e% (n)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eTotal UCs\u003c/p\u003e\n\u003cp\u003e% (n)\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAmpicillin\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e62.7% (561)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e41.8% (33)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e95.8 (68)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e63.5% (668)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePiperacillin\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e44.5% (182)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9.1% (3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e39.4 (13)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e41.6% (198)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAmoxicillin-clavulanate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e19.4 (173)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7.5 (6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e33.3 (23)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e19.8% (208)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAmpicillin-sulbactam\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e24.6 (216)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5.2 (4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e36.2 (25)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e24% (248)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePiperacillin-tazobactam\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e11.1 (67)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.7 (1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17.3 (9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10.9% (78)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAztreonam\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e19.3 (107)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0/37)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e35.4 (17)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e19.4% (124)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCephazolin\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e16.5 (94)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9.3 (5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e27.7 (13)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e16.9% (114)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCephalotin\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e29.2 (142)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11.9 (5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e30 (12)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e28.2% (161)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCefepime\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e12.3 (64)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0/40)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e13.5 (5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11.4% (69)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCefuroxime\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e25.4 (156)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11.4 (5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e38.3 (18)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e25.9% (184)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCefixime\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e18.9 (10)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0/20)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17.5% (10)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCeftriaxone\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e21.5 (37)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0/46)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e35.2 (19)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21.1% (157)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCefotaxime\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e10.7 (55)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0/40)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e30.8 (12)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11.3% (67)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCeftazidime\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e21.1 (128)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0/46)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e36.7 (18)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e20.7% (146)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNitrofurantoin\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e5.5 (22)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e94.3 (33)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e33.3 (10)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14.4% (68)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTrimethoprim-sulfamethoxazole\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e37.5 (336)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e52.6 (41)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e32.9 (23)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e38.1% (400)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGentamicin\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e9.5 (86)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5.1 (4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14.1 (10)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9.5% (100)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAmikacin\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.5 (4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.4 (2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.4 (1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.5% (5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTobramycin\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e7.7 (33)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.6 (1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11.4 (4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7.6% (38)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eImipenem\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.4 (2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0/39)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.6 (1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.5% (3)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCiprofloxacin\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e9.1 (68)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.5 (1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8.1 (5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8.4% (74)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\n\u003ch2\u003e\u0026nbsp;\u003c/h2\u003e\n\u003ch2\u003eAntibacterial susceptibility\u003c/h2\u003e\n\u003cp\u003eAmong all isolates, the overall antimicrobial resistance was found to be highest for ampicillin, followed by piperacillin and TMP-SMX (63.5, 41.6, and 38.1%, respectively). The overall antimicrobial resistance against amoxicillin-clavulanate, ampicillin-sulbactam, cefuroxime, ceftriaxone was 19.4, 24, 25.9, and 21.1%; respectively. Imipenem, amikacin, and tobramycin had the least resistance (0.5, 0.5, and 7.6%, respectively). The antimicrobial resistance patterns of the uropathogens were shown in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eE. coli\u003c/em\u003e demonstrated high resistance to ampicillin, piperacillin, and TMP/SMX (62.7, 44.5, and 37.5%, respectively). The least resistance was for imipenem and amikacin and nitrofurantoin (0.4, 0.5, 5.5%, respectively) (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eProteus spp represented high resistance to nitrofurantoin, TMP-SMX, and ampicillin (94.3, 52.6, and 41.8%, respectively). Proteus spp had no resistance against third-generation cephalosporins and imipenem (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eKlebsiella spp had the highest resistance to ampicillin (95.8%). Cephalosporins other than cefepime and cephazolin had a resistance frequency of \u0026ge;\u0026thinsp;30%. The least resistance was for amikacin, imipenem, and ciprofloxacin. (1.4, 2.6, 8.1%, respectively) (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). The extended-spectrum beta-lactamase (ESBL) producer isolates were detected in 61 samples (5.6%, n\u0026thinsp;=\u0026thinsp;61/1086). Of these, n\u0026thinsp;=\u0026thinsp;55 were among E. coli isolates, n\u0026thinsp;=\u0026thinsp;6 were among Klebsiella species. Extended-spectrum beta-lactamase positive strains showed high resistance to ampicillin (100%), ceftriaxone (96.5%), and nitrofurantoin (33.3%). They revealed the least resistance for amikacin (8.5%) and imipenem (7.1%).\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eUropathogens are showing a rising trend in the antimicrobial resistance throughout the world.\u003csup\u003e2,7,8,12\u0026minus;20\u003c/sup\u003e The most common oral antibiotics prescribed for UTI as empirical antimicrobial agents in outpatient settings in Turkey are amoxicillin/clavulanate, an oral third-generation cephalosporin 'cefixime.' The most common agents used for parenteral treatment are aminoglycosides and parenteral cephalosporins (ceftriaxone or cefotaxime) in the case of patients under three months of age, toxic, or could not have oral intake. For secondary prophylaxis cefixime, co-trimoxazole and nitrofurantoin are commonly prescribed. Our study showed a significant increase in antimicrobial resistance to the most common antibiotics prescribed for UTI in childhood with the first UTI attack even in an outpatient setting. The resistance rates for amoxicillin-clavulanate, ampicillin-sulbactam, cefuroxime, ceftriaxone were almost 20% or above in our study. This result is striking because the frequency of cephalosporin resistance was nearly half in the previous study conducted at our center between 2004\u0026ndash;2008 years \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e, which included all positive UCs by not taking into consideration the comorbid factors, including urinary tract anomalies, recurrent UTI which assumed to increase the frequency of antimicrobial resistance. A comparison of antimicrobial resistance against uropathogens in consecutive (2004\u0026ndash;2008, 2010\u0026ndash;2016) periods in our center was shown in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. These results indicate that UTI treatment will be troublesome in the future, even in an outpatient setting. These results are important because of heralding the risk of UTI complication burden. The significant increase in resistance to third-generation cephalosporins also harbors significant risks not only in UTI but also in other childhood disease treatments.\u003c/p\u003e\n\u003cp\u003eGhadageet al.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e reported increased resistance to commonly used empirical therapy -ampicillin and co-trimoxazole- for UTI in India. Kothari and Sagar\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e also reported low susceptibility to amoxicillin, amoxicillin/clavulanate, ciprofloxacin, co-trimoxazole in uropathogens. Prais et al.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e reported that empirical treatment with co-trimoxazole or cephalexin as the initial drug is inadequate in approximately one-third of UTI cases, but that nitrofurantoin and nalidixic acid maintained their very high efficacy against urinary pathogens in Israel. The European Centre for Disease Prevention and Control reported the increasing resistance to antibiotic treatments, including carbapenems.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e Imipenem-resistant E. coli rates were reported at 1.4\u0026ndash;3.5% in Turkey.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e In our study, while resistance to ampicillin, piperacillin, and TMP-SMX was high among all isolates, imipenem, amikacin, and tobramycin had the lowest resistance. All Klebsiella isolates are sensitive to imipenem and amikacin in our study, as in a study by Abuhandan et al.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e However, Wang et al. reported resistance to imipenem and amikacin at a frequency of 21.12% and 6.83%, respectively.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e These results may vary because of the different patient inclusion criteria in different studies. Proteus isolates also revealed no resistance to third-generation cephalosporins and imipenem in our study. The overall ESBL positivity has been reported to be 5% in Europe, 39% in Asia, and 30% -50% in Turkey.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e27\u003c/span\u003e,\u003cspan class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e. Kurt-Ş\u0026uuml;k\u0026uuml;r et al. reported a prominently increase in overall ESBL positivity from 7.8\u0026ndash;23.5% within ten years.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e ESBL positivity in our study was 5.6% in frequency, which is lower than the reports of other studies. This may because all of our patients had the first UTI episode without comorbid conditions and frequent antibiotic usage for UTI treatment. The increase of resistant strains can be attributed to either availability of the drugs for unnecessary and improper use of many antimicrobials, or by empirical treatment.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e29\u003c/span\u003e,\u003cspan class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e Therefore, continuous surveillance, new strategies, and multidisciplinary actions should be developed against over consumption and unnecessary antibiotic treatments. Recently, in this context, the Turkish Ministry of Health restricted antibiotic intake without prescription and planned projects to improve rational antibiotic use, such as public education campaigns, to increase awareness about this topic. Studies in the future will show the results of these precautions. Our study has the following limitations. The major limitation was its retrospective nature. The history of previous UTI episodes was limited to the family expression and the investigations performed in our hospital. Another limitation relates to in vitro susceptibility testing, which may not be fully reflected in clinical outcomes, as in-vivo sensitivity may be different. Also, the results obtained from our study may not be valid for other patients in different regions.\u003c/p\u003e"},{"header":"Conclusion","content":" \u003cp\u003eThe present study showed that initial empirical treatment with amoxicillin, trimethoprim-sulfamethoxazole, and first-generation cephalosporins are no longer appropriate, but fluoroquinolones, cefepime, imipenem, amikacin and nitrofurantoin (for \u003cem\u003eE. Coli\u003c/em\u003e) maintained their high efficacy against urinary pathogens in Turkey. Almost one in five children have antimicrobial resistance against antimicrobials which are the ones likely to be prescribed before culture results and antibiotic sensitivities are available to the clinician. This result reveals upcoming future challenges in the successful treatment of pediatric UTI, even in an outpatient setting. The present results may be of significant value to assist physicians in the appropriate choice of antibiotics, and to prevent the misuse or excessive use of antibiotics.\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding Source:\u003c/strong\u003e No external funding for this manuscript\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFinancial Disclosure:\u003c/strong\u003e Authors have indicated that they have no financial relationships relevant to this article to disclose\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest:\u003c/strong\u003e The authors declare no conflict of interest\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eContributors\u0026rsquo; Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDr Sari conceptualized and designed the study, drafted the initial manuscript, and reviewed, and revised the manuscript.\u003c/p\u003e\n\u003cp\u003eDrs Yazilitas, Oztek-Celebi, Akcaboy, and Akisoglu designed the data collection instruments, collected data, carried out the initial analyses, and reviewed and revised the manuscript. Prof. Senel conceptualized and designed the study, coordinated and supervised data collection, and critically reviewed the manuscript for important intellectual content.\u003cbr /\u003e All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKorbel L, Howell M, Spencer JD. The clinical diagnosis and management of urinary tract infections in children and adolescents. Paediatr Int Child Health. 2017;37:273\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKonca C, Tekin M, Uckardes F, Akgun S, Almis H, Bucak IH, et al. Antibacterial resistance patterns of pediatric community-acquired urinary infection: Overview. Pediatr Int. 2017;59:309\u0026ndash;15.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTullus K. Outcome of post-infectious renal scarring. Pediatr Nephrol. 2015;30:1375\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShaikh N, Mattoo TK, Keren R, Ivanova A, Cui G, Moxey-Mims M, et al. Early Antibiotic Treatment for Pediatric Febrile Urinary Tract Infection and Renal Scarring. JAMA Pediatr. 2016;170:848\u0026ndash;54.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKaravanaki KA, Soldatou A, Koufadaki AM, Tsentidis C, Haliotis FA, Stefanidis CJ. Delayed treatment of the first febrile urinary tract infection in early childhood increased the risk of renal scarring. Acta Paediatr. 2017;106:149\u0026ndash;54.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang J, He L, Sha J, Zhu H, Huang L, Zhu X, et al. Etiology and antimicrobial resistance patterns in pediatric urinary tract infection. Pediatr Int. 2018;60:418\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eErol B, Culpan M, Caskurlu H, Sari U, Cag Y, Vahaboglu H, et al. Changes in antimicrobial resistance and demographics of UTIs in pediatric patients in a single institution over a 6-year period. J Pediatr Urol. 2018;14:176.e1-176.e5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKurt-Ş\u0026uuml;k\u0026uuml;r ED, \u0026Ouml;z\u0026ccedil;akar ZB, Doğan \u0026Ouml;, \u0026Ouml;zt\u0026uuml;rk M, Karaman M, \u0026Ccedil;akar N, et al. The changing resistance patterns of bacterial uropathogens in children. Pediatr Int. 2020 Apr 29. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/ped.14270\u003c/span\u003e\u003c/span\u003e. Online ahead of print.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRaupach T, Held J, Prokosch HU, Rascher W, Zierk J. Resistance to antibacterial therapy in pediatric febrile urinary tract infections-a single-center analysis. J Pediatr Urol. 2020;16:71\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSubcommittee on urinary tract infection. Reaffirmation of AAP Clinical Practice Guideline: The Diagnosis and Management of the Initial Urinary Tract Infection in Febrile Infants and Young Children 2\u0026ndash;24 Months of Age. Pediatrics 2016;138 (6). pii: e20163026.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNational Committee for Clinical Laboratory Standards. Performance Standards for Antimicrobial Susceptibility Testing. Twelfth Informational Supplement. NCCLS document M100-S12. Wayne, National Committee for Clinical Laboratory Standards, 2002.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRasamiravaka T, Shaista Sheila HS, Rakotomavojaona T, Rokato-Alson AO. Rasamindrakotroka. Changing profile and increasing antimicrobial resistance of uropathogenic bacteria in Madagascar. Med Mal Infect. 2015;45:173\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWu CT, Lee HY, Chen CL, Pao-Lan T, Cheng-Hsun C. High prevalence and antimicrobial resistance of urinary tract infection isolates in febrile young children without localizing signs in Taiwan. J Microbiol Immunol Infect. 2016;49:243\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRobinson JL, Le Saux N. Management of urinary tract infections in children in an era of increasing antimicrobial resistance. Expert Rev Anti Infect Ther. 2016;14:809\u0026ndash;16.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRezaee MA, Abdinia B. Etiology and Antimicrobial Susceptibility Pattern of Pathogenic Bacteria in Children Subjected to UTI: A Referral Hospital-Based Study in Northwest of Iran. Med (Baltim). 2015;94:e1606.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMoore CE, Sona S, Poda S, Putchhat H, Kumar V, Sopheary S, et al. Antimicrobial susceptibility of uropathogens isolated from Cambodian children. Paediatr Int Child Health. 2016;36:113\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSharef SW, El-Naggari M, Al-Nabhani D, Al Sawai A, Al Muharrmi Z, Elnour I, et al. Incidence of antibiotics resistance among uropathogens in Omani children. presenting with a single episode of urinary tract infection. J Infect Public Health. 2015;8:458\u0026ndash;65.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAkhtar MS, Mohsin N, Zahak A, Ain MR, Pillai PK, Kapur P, et al. Antimicrobial sensitivity pattern of bacterial pathogens in urinary tract infections in South Delhi, India. Rev Recent Clin Trials. 2014;9:271\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSenel S, Karacan C, Erkek N, Gol N. A single-center experience of antimicrobial resistance patterns in pediatric urinary tract infection. Medical Principles Practice. 2010;19:359\u0026ndash;63.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKo\u0026ccedil;ak M, B\u0026uuml;y\u0026uuml;kkarag\u0026ouml;z B, \u0026Ccedil;elebi-Tayfur A, \u0026Ccedil;altik A, K\u0026ouml;ksoy AY, \u0026Ccedil;izmeci Z, et al. Causative pathogens and antibiotic resistance in children hospitalized for urinary tract infection. Pediatr Int. 2016;58:467\u0026ndash;71.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGhadage DP, Nale SS, Kamble DS, Muley VA, Wankhade AB, Mali RJ, Bhore AV. Study of Aetiology and Anti-biogram of Uropathogens in Children-A Retrospective Analysis. J Clin Diagn Res. 2014;8:20\u0026ndash;2.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKothari A, Sagar V. Antibiotic resistance in pathogens causing community-acquired urinary tract infections in India: A multicenter study. J Infect Dev Ctries. 2008;2:354\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePrais D, Straussberg R, Avitzur Y, Nussinovitch M, Harel L, Amir J. Bacterial susceptibility to oral antibiotics in community-acquired urinary tract infection. Arch Dis Child. 2003;88:215\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEuropean Centre for Disease Prevention and Control. Antimicrobial resistance surveillance in Europe in 2015. Annual Report of the European Antimicrobial Resistance Surveillance Network (EARS-Net). 2017, \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://ecdc.europa.eu/en/publications/Publications/antimicrobial-resistance-europe-2015.pdf\u003c/span\u003e\u003c/span\u003e (accessed May 2019).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDemir M, Kazanasmaz H. Uropathogens and antibiotic resistance in the community and hospital-induced urinary tract infected children. J Glob Antimicrob Resist. 2020;20:68\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAbuhandan M, G\u0026uuml;zel B, Oymak Y, \u0026Ccedil;ift\u0026ccedil;i H. Antibiotic sensitivity and resistance in children with urinary tract infection in Sanliurfa. Turk J Urol. 2013;39:106\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTseng MH, Lo WT, Lin WJ, Teng CS, Chu ML, Wang CC. Changing trend in antimicrobial resistance of pediatric uropathogens in Taiwan. Pediatr Int. 2008;50:797\u0026ndash;800.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFlammang A, Morello R, Vergnaud M, Brouard J, Eckart P. Profile of bacterial resistance in pediatric urinary tract infections in 2014. Arch Pediatr. 2017;24:215\u0026ndash;24.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMueller T, \u0026Ouml;stergren PO. The correlation between regulatory conditions and antibiotic consumption within the WHO European Region. Health Policy. 2016;120:882\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBryce A, Hay AD, Lane IF, Thornton HV, Wootton M, Costelloe C. Global prevalence of antibiotic resistance in paediatric urinary tract infections caused by Escherichia coli and association with routine use of antibiotics in primary care: systematic review and meta-analysis. BMJ. 2016;352:i939.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"urinary tract infection, uropathogen, antimicrobial resistance, antimicrobial susceptibility","lastPublishedDoi":"10.21203/rs.3.rs-269767/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-269767/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eIncreased antibiotic resistance is a significant problem associated with higher morbidity, mortality, and costs in managing urinary tract infections (UTI). This study aims to analyze the antimicrobial resistance profile of uropathogens isolated from children with the first attack of community-acquired UTI.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMaterials and Methods\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eThis retrospective cohort study was conducted between January 2010-December 2016, with the patients aged one month to 18 years diagnosed with the first attack of community-acquired UTI at the pediatric outpatient clinic of a tertiary care hospital. Patients' age, sex, UTI history, clinical findings at admission, urine analysis, urine culture, and antibiogram results were recorded.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eA total of 1086 patients and 1086 cultures were included in the study. The male/female ratio was 1/5.3. The mean age of the children was 73.7±47.1 (0.4-215.9) months. 16.0% were aged 1-24 months. \u003cem\u003eE. coli\u003c/em\u003e was the most common causative agent found to be 85.1% in frequency. The overall antimicrobial resistance was found to be highest for ampicillin, followed by piperacillin and trimethoprim-sulfamethoxazole (63.5, 41.6 and 38.1%, respectively). Imipenem, amikacin, and tobramycin had the least resistance (0.5, 0.5, and 7.6%, respectively). The overall antimicrobial resistance against amoxicillin-clavulanate, ampicillin-sulbactam, cefuroxime, ceftriaxone was 19.4, 24, 25.9 and 21.1%; respectively.\u003c/p\u003e\u003cp\u003eExtended-spectrum beta-lactamase positivity was detected in 5.6% (n=61) of samples.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eOur study showed significant increase in antimicrobial resistance to the most common antibiotics which are prescribed before urine culture results and antibiotic sensitivities are available. The resistance rates for amoxicillin-clavulanate, ampicillin-sulbactam, cefuroxime, ceftriaxone were almost 20% or above in children with the first UTI attack in an outpatient setting.\u003c/p\u003e","manuscriptTitle":"Antibiotic drug resistance pattern of uropathogens seen in the first episode of community-acquired pediatric urinary tract infections at a tertiary care hospital","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-03-10 22:05:37","doi":"10.21203/rs.3.rs-269767/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"cc6d9d81-2f26-4b7f-8622-d7aecce96019","owner":[],"postedDate":"March 10th, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":2894751,"name":"Pediatrics"},{"id":2894752,"name":"Urology \u0026 Nephrology"},{"id":2894753,"name":"General Microbiology"}],"tags":[],"updatedAt":"2022-03-28T20:05:21+00:00","versionOfRecord":{"articleIdentity":"rs-269767","link":"https://doi.org/10.12956/tchd.1071855","journal":{"identity":"turkish-journal-of-pediatric-disease","isVorOnly":true,"title":"Turkish Journal of Pediatric Disease"},"publishedOn":"2022-03-09 20:05:21","publishedOnDateReadable":"March 9th, 2022"},"versionCreatedAt":"2021-03-10 22:05:37","video":"","vorDoi":"10.12956/tchd.1071855","vorDoiUrl":"https://doi.org/10.12956/tchd.1071855","workflowStages":[]},"version":"v1","identity":"rs-269767","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-269767","identity":"rs-269767","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}