Urinary tract infections in the emergency department: which antibiotics are most appropriate?
The types of urinary tract infections (UTIs) presented to the emergency department (ED) in a clinic vary from simple cystitis to urosepsis (1).
The diagnosis of a UTI is done via urinary culture analysis, which can reveal a significant reproduction of bacteria (2). UTIs are classified by localization (upper/lower), clinical properties (complicated/ uncomplicated), or source (community acquired/nosocomial) (3). The foremost pathogen in community-acquired UTIs is E. coli, followed by Klebsiella spp., Proteus mirabilis, Enterococcus spp., and Pseudomonas aeruginosa; however, for nosocomial infections, the expected pathogen is generally related to the urinary catheter, and the patient's own flora is the culprit (4, 5). These classifications are used in order to choose the treatment method and duration (6).
In the guidelines of Infectious Diseases Society of America (IDSA) published in 2011, because of increasing antibiotic resistance, greater emphasis has been put on choosing the proper antibiotic; therefore, it becomes more important to understand changes in regional antibiotic resistances (3, 7).
The aim of this study is to analyze the urine cultures performed at our ED and define the antimicrobial resistance rates for our region.
Materials and Methods
Study design and setting
This study was a retrospective review of adult patients with a positive urine culture between January 1, 2010 and December 31, 2014, in the ED of the Tepecik Training and Research Hospital-a tertiary hospital. Local ethics committee approval was obtained.
Selection of participants
By tracing the electronic health record, the urinary cultures received from predetermined patients above 18 years old were carefully studied. Among these patients, the ones whose culture and anti-biogram results could not be obtained were excluded.
Methods and measurements
The demographic data of patients, their urinalysis, microorganisms which reproduced in their urine cultures, antibiogram results, accompanying diseases, history of urinary catheterization, method how the sample was obtained (catheter or mid-flow urine), and the outcomes were recorded.
Complete urine analysis was semi-quantitatively obtained using the H800 analyzer (Dirui Industrial Co. Ltd., China) and H10-800 strips (Dirui Industrial Co. Ltd., China). Test results that were negative (-) and trace (+/-) for leukocyte esterase (LE) were accepted as negative.
When bacteria >[10.sup.5] cfu/mL were reproduced in the urine culture, the result was considered positive. Isolated bacteria forms were conventionally defined. Isolates that were not conventionally identified were then defined by using a fully automated identification and antibiogram device (ViTEK 2 compact, bioMerieux, France). The presence of more than two isolates at a concentration [greater than or equal to] [10.sup.4] cfu/mL was considered as contamination.
For data analysis, Statistical Package for the Social Sciences (IBM SPSS Statistics Armonk, NY, USA) version 22 was used. Qualitative data were defined as the number of observations and percentage, while quantitative ones were represented as interquartile range (IQR) and minimum-maximum values. To compare the qualitative data, the chi-square test was used. For understanding the effect of LE and nitrite positivity on reproduction, the odds ratio (multinominal logistic regression) was considered for analyzing the mean modality. Values of p<0.05 were accepted to be statistically significant for a confidence interval of 95%.
During the 5-year period under consideration, 882,997 adult patients were admitted to the ED, and 4,493 patients were asked to provide a urine sample for culture. Because of getting no results, 80 samples were excluded; therefore, the research was carried out with 4,413 urine cultures.
Among the group who was asked to give a urine culture, 51.9% were female. The general median age was 66 years (IQR=32; min: 18; max: 114): the median age of men was 68 years (IQR: 26; min: 18; max: 97), whereas women had a median age of 63 years (IQR: 40; min: 18; max: 114). For all the cases, concomitant diseases were listed (Table 1).
In 2,585 urinary culture samples, bacteria reproduction was observed, but 11.3% (n=497) samples were considered as contamination. This contamination was more frequent in women (n=301, 13.1%) than men (n=196, 9.2%). As a result, 2,088 (47.3%) cases were accepted as culture-positive UTIs.
In our study, 91% microorganisms that reproduced in the culture were gram-negative bacilli; 7.5%, gram-positive cocci; and 0.7%, yeasts. Microorganism identities and their antimicrobial resistance frequencies are listed in Table 2 and 3.
Four of the top frequently prescribed antibiotics and their resistance rates are shown in Figure 1.
Here, 1,311 (29.7%) urine samples were obtained by employing urinary catheterization in the ED, and 1.8% samples were obtained from urine catheters, which were already present. The frequency of contamination was almost the same with the patients who did not have a urinary catheter.
Further, 23.7% patients who had been asked to give a urine culture were hospitalized, and 19.8% were ICU admissions.
The resistance ratio of the antibiotics, which are mostly empirically chosen, are listed in Table 4.
The relationship between urinary LE levels, nitrite positivity levels, and their relationship with respect to reproduction in urine cultures are listed in Table 5.
The resistance rates of E. coli strains against antimicrobial agents are listed in Table 6.
In this research that is based on investigating the urinary cultures that were requested from the ED, we found that 47.3% samples were positive for microorganism reproduction, and the most frequent species was E. coli. Nitrite positivity in urine has a more powerful effect on the positivity of LE.
Urinalysis is one of the most popularly used tests in the ED. Dipstick tests have taken the place of urinary microscopy because the use of the former is very easy and is cheaply available (8, 9). LE and nitrite positivity are stated to be good predictors in UTI diagnosis (10-12). In our study, the relationship between nitrite positivity and reproduction in cultures was found to be stronger than that with LE positivity. The +2/+3 LE positivity in the odds ratios of urinalysis were 1.5 and 1.9 by the order of value, while nitrite positivity was noted as 3.6. However, urinary culture is still the primary standard for proving the existence of UTIs (2).
In the study by Arman al. (13), it was determined that the average age was 39.4 [+ or -] 16.26 years (16-82 years) among 400 patients who applied to first-grade health farms. In this research, the most frequent uropathogens were gram-negative microorganisms [E. coli (62.8%), Enterococcus spp. (3.2%), Klebsiella pneumoniae (3.4%), Pseudomonas aeruginosa (4%), Proteus mirabilis (1.1%), and Eneterobacter cloacae (0.5%)], followed by coagulase-negative staphylococcus (24.5%) (13). In our study, the majority of the isolated uropathogens were gram-negative bacilli (91.8%). In agreement with the literature, the most frequent species was E. coli (66.7%), followed by Klebsiella pneumoniae (7.2%), coagulase-negative staphylococcus (6.4%), Pseudomonas aeruginosa (4%), Proteus mirabilis (3.4%), and Enterococcus faecalis (3.2%) in the order of frequency (4, 6).
The study by Bekeris et al. (14) was performed in 127 laboratories located in USA and Canada in which 14,739 urinary culture samples were collected, and the average contamination rate was noted as 15%. In our study, the contamination rate was 11.3%, which was notably excessive among women. Even though no disclosure form was present in our ED, the reason for the reduced contamination rate might be because the microbiology laboratory is located very close to the ED, so the samples reach the laboratory quickly, thereby reducing the risk of contamination.
In our study, it has been reported that even though having a downward trend from 2010 to 2014 (from 53.8% to 39.1% and from 51.5% to 33.1%, respectively), TMP-SMX and ciprofloxacin resistance levels are still found to be high. Nitrofurantoin and fosfomycin are noted to have lower resistance levels, namely, 13.3% and 7.6%, respectively.
In a retrospective research done by Guneysel et al. (15), among 274 patients who were diagnosed as having complicated UTI, the resistance rate of TMP-SMX was 34.4%. In 2013, a meta-analysis was carried out by detecting the resistance of TMP-SMX for E. coli variables; the resistance percentage was determined as 47.8% between 2008 and 2012 (16). In our study, the TMP-SMX resistance was found to be 44.8%, with a slight reduction during the intervening period. There are other studies that have revealed a similar resistance ratio (7, 17-19).
Karlowsky et al. (20) showed the resistance ratio for ciprofloxacin as 2.5% in 1999. Sanchez et al. (21) used the data from 2000 to 2010 and showed that the resistance ratio of ciprofloxacin increased from 3% to 17%. In the research by Arslan et al. (22), which was made throughout Turkey, ciprofloxacin resistance ratio with respect to E. coli isolates was found to be 17% in uncomplicated UTI patients, whilst it was 38% in complicated ones. In our study, we found that ciprofloxacin resistance reduced from 51% to 35%, implying that ciprofloxacin resistance is still too high for our region.
Because of having a very low resistance ratio, fosfomycin is one of the most appropriate agents for treating uncomplicated cystitis (23). In our study, we determined that fosfomycin resistance among women was 5.8%.
Nitrofurantoin resistance has been found to range between 2% and 28% in different studies. In our research, we found the resistance of nitrofurantoin to be 13.3%. Because of this low resistance ratio, the use of nitrofurantoin seems to effectively fit for our region (7, 17-20, 24).
Our study was limited due to its retrospective nature. Even though the presentations to the ED were mostly outpatients, the discrimination of infections (community-acquired or nosocomial) was not done. Because this study consisted of ED patients, it did not involve all the UTI cases. Also, some patients may have been discharged without being asked for a urine culture. In our study, the urine samples obtained from urinary catheters comprised 29.7% of the total; therefore, our research shows that the old with general debility may have been considered in a larger number as compared to other studies. For this reason, resistance ratios may be higher than expected.
In our study, we found that even though there is a slight reduction over the years, TMP-SMX and ciprofloxacin resistance ratios are still high. Because of lower resistance, fosfomycin and nitrofurantoin must be considered as the first choice for the treatment of lower UTIs.
Ethics Committee Approval: Ethics committee approval was received for this study from the ethics committee of Tepecik Training and Research Hospital (25.06.2014).
Informed Consent: In this retrospective study, informed consent form was not obtained, due to data abstracted from medical records.
Peer-review: Externally peer-reviewed.
Conflict of Interest: No conflict of interest was declared by the authors.
Financial Disclosure: The authors declared that this study has received no financial support.
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Ibrahim Toker , Turgay Yilmaz Kilic , Sukran Kose , Murat Yesilaras , Orkun Unek , Serkan Hacar , Aysin Kilinc Toker 
 Department of Emergency Medicine, Tepecik Training and Education Hospital, Izmir, Turkey
 Department of Infectious Diseases and Clinical Microbiology, Tepecik Training and Education Hospital, Izmir, Turkey
Correspondence to: Ibrahim Toker e-mail: email@example.com
Received: 09.06.2016 Accepted: 22.07.2016
Table 1. Concomitant diseases Concomittant diseases n (%) Malignancy 765 (17.3) Diabetes 572 (13) Acute Renal Failure 380 (8.6) Chronic renal failure 356 (8.1) Cerebrovascular Diseases 245 (5.6) Alzheimer's Disease 223 (5.1) Urolithiasis, nephrolithiasis 191 (4.3) Benign Prostate Hypertrophy 162 (3.7) Epilepsy 111 (2.5) Kidney Transplantation 57 (1.3) Parkinson's disease 41 (0.9) Immobile patients 15 (0.3) Hypertension 649 (14.7) Chronic obstructive pulmonary disease 132 (3) Heart failure 184 (4.2) Liver Cirrhosis 40 (0.9) AIDS 3 (0.1) Table 2. Uropathogen microorganisms reproduced in urine cultures Uropathogen microorganism n (%) Escherichia coli 1392 (66.7) Klebsiella pneumoniae 150 (7.2) Coagulase-negative staphylococcus 138 (6.6) Pseudomonas aeruginosa 84 (4) Proteus mirabilis 70 (3.4) Enterococcus faecalis 66 (3.2) Staphylococcus aureus 43 (2.1) Klebsiella oxytoca 26 (1.2) Candida spp. 17 (0.8) Acinetobacter baumannii 8 (0.4) Enterobacter aerogenes 7 (0.3) Others * 87 (4.2) Total 2088 (100) * Citrobacter freundii, Enterobacter cloacae, Stenotrophomonas maltophilia, Proteus vulgaris, Morganella morganiii Streptococus pyogenes, Enterecoccus faecium, Providencia rettgeri, Serratia marcescens, Citrobacter koseri, Salmonella spp., Streptococus viridans, Streptococcus spp., Providencia stuartii, Enterobacter spp., Enterococcus gallinarum, Corynebacterium spp., Streptococcus mitis Table 3. Resistance ratios of uropathogen microorganisms to antimicrobial agents Antimicrobial Agents Total % (n) Female % Male % Levofloxacin 45.7 (127) 32.3 58.5 Trimethoprim-sulfamethoxazole 44.8 (1743) 40.6 50.5 Cefuroxime 37.9 (596) 33 44.7 Ciprofloxacin 36.8 (1694) 30.7 44.9 Amoxicillin-clavulanate 36.2 (1207) 29.2 46.1 Cefixime 35.6 (402) 28.5 45.5 Ceftriaxone 32.6 (1397) 26.3 41.6 Extended-spectrum beta-lactamases 14.3 (1916) 12.2 17.1 Nitrofurantoin 13.3 (1135) 11.0 16.6 Piperacillin-tazobactam 11.8 (1684) 10.7 13.3 Fosfomycin 7.6 (1344) 5.8 10.1 Imipenem 3.4 (1160) 2.1 5.0 Vancomycin 1.9 (52) 5.3 0 Ertapenem 1.6 (980) 1.4 1.9 Table 4. Antimicrobial agents' resistance ratios among gender Gender p * Female, Male, n (%) n (%) Nitrofurantoin Susceptible 591 (89%) 393 (83.4%) 0.007 (n=1135) Resistant 73 (11%) 78 (16.6) TMP-SMX Susceptible 597 (59.4%) 365 (49.5%) <0.001 (n=1743) Resistant 408 (40.6%) 373 (50.5%) Ciprofloxacin Susceptible 669 (69.3%) 401 (55.1%) <0.001 (n=1694) Resistant 297 (30.7%) 327 (44.9%) Fosfomycin Susceptible 742 (94.2%) 500 (89.9%) 0.004 (n=1344) Resistant 46 (5.8%) 56 (10.1%) Resistant 214 (26.3%) 242 (41.6%) * Chi-square Table 5. Relationship of leukocyte esterase and nitrite positivity with reproduction in urine culture Reproduction in urine OR culture (95% CI) Negative Positive (n) (n) Leukocyte esterase Negative 1370 1090 1+ 215 175 1.0 (0.8-1.3) 2+ 229 265 1.5 (1.2-1.8) 3+ 258 397 1.9 (1.6-2.3) Nitrite positivity Negative 1574 906 Positive 496 1021 3.6 (3.1-4.1) Infrction sign Negative 1117 529 Positive 954 1398 3.1 (2.7-3.5) * Leukocyte esterase is least +1 or nitrite positivity, OR: odds ratio; CI: confidence interval Table 6. Resistance rates of E. coli strains against antimicrobial agents Antimicrobial agents Resistance ratio % (n) Levofloxacin 52.7 (55) Trimethoprim-sulfamethoxazole 44.6 (1277) Cefuroxime 35.3 (431) Ciprofloxacin 38.6 (1231) Amoxicillin-clavulanate 33.6 (923) Cefixime 34.4 (314) Ceftriaxone 30.5 (1032) Extended-spectrum beta-lactamases 11.3 (1916) Nitrofurantoin 6.7 (913) Piperacillin-tazobactam 8.7 (1224) Fosfomycin 4.8 (1061) Imipenem 0.25 (804) Vancomycin 0 (0) Ertapenem 0.82 (732) Figure 1. Resistance ratios for nitrofurantoin, trimethoprim-sulfamethoxazole, ciprofloxacin, and fosfomycin over several years 2010 2011 2012 2013 2014 nitrofurantoin 13,16 11,61 15,84 12,13 trimethoprim- sulfamethoxazole 53,85 47,22 16,55 46,72 39,11 ciprofloxacin 51,52 38,16 39,72 36,44 33,09 fosfomycin 7,32 4,35 5,48 4,17 13,68 Note: Table made from line graph.
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|Title Annotation:||Original Article|
|Author:||Toker, Ibrahim; Kilic, Turgay Yilmaz; Kose, Sukran; Yesilaras, Murat; Unek, Orkun; Hacar, Serkan; To|
|Publication:||Eurasian Journal of Emergency Medicine|
|Date:||Sep 1, 2016|
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