Prevalence of uropathogens and antimicrobial susceptibility profile in outpatient from Jataí-GO

First submission on 24/03/14; last submission on 05/05/14; accepted for publication on 05/05/14; published on 20/06/14 1. Master of Applied Health Science at Universidade Federal de Goiás (UFG)-regional Jataí. 2. PhD in Clinical Analysis at Universidade Estadual Paulista (UNESP)-campus Araraquara; associated professor at UFG-regional Jataí. 3. Biotechnology Specialist at Universidade Estadual de Maringá (UEM); master of Health Science at UEM. 4. Master in Pharmacology at Universidade de São Paulo (USP), Ribeirão Preto. ABStrACt

introDuCtion Urinary tract infection (UTI) ranks second in incidence of bacterial disease, second only to respiratory tract infections (12,25) .UTI is defined as an invasion and multiplication of microorganisms in tissue within the urinary tract from the urethra to the kidney.Pathogens can reach the urinary tract in three pathways: ascending, hematogenous, or lymphatic (20) .These may results in bacteriuria, cystitis, pyelonephritis, or even acute urethral syndrome (21) .They affect individuals at any age, but the groups most affected are male newborns, preschoolers girls, sexually active young woman, men with prostatic obstruction, and elderly (5) .
UTIs are, usually, caused by Gram-negative aerobic bacteria, present in the intestinal flora.In acute symptomatic urinary tract infections, Escherichia coli is prevalent, whereas a higher incidence of other enterobacteria with high prevalence of infections caused by Klebsiella sp., Proteus sp., Pseudomonas sp., Enterobacter sp., and Gram-positive from genera Enterococcus sp., and Staphylococcus sp., is observed in chronic infections, or acquired in hospital environment, or related to structural abnormalities of the urinary tract (10,21,23) .
The occurrence of pathogens causing UTI varies geographically, and susceptibility profile requires monitoring in order to provide information for therapeutic orientation, especially 10.5935/1676-2444.20140015regarding the empirical antimicrobial therapy.The increase in bacterial resistance to antimicrobial drugs is evident and brings difficulties in controlling urinary tract infections (8,14,24) .
Most of studies on isolation and identification of multiresistant bacterial strains is focused on hospitalized patients; however, it is believed that resistant microorganisms can be isolated from individuals in community, due to indiscriminate use of antimicrobials (24) .The empirical treatment of UTI is a routine that should be based on regional epidemiologic data, in order to be familiar with the main pathogens and their antimicrobial susceptibility profile.The Infectious Diseases Society of America recommends that therapeutic practice must be based on local epidemiologic data, as a way to periodically reevaluate the empirical therapies employed in that community, as well as to detect possible changes in the susceptibility profile (16,28) .Thus, this study aims to help doctors in southwest Goiás, and also provide information that may contribute to the knowledge of UTIs in the country.

oBJECtivES
This study aimed to describe the pathogens causing urinary tract infection in outpatients of clinical analysis laboratory at Jataí, in the state of Goiás, and analyze the antimicrobial susceptibility profile of the bacterial species.

MEthoD
This is a retrospective cross-sectional study.The study was performed by collecting data in records of microbiological cultures and susceptibility tests on three clinical analysis laboratories, in Jataí, state of Goiás.Data on urine cultures performed from March 2010 to June 2012 were analyzed.Authorize access to records was warranted by technical experts of the laboratories, and the Project was approved by Research Ethics Committee-Universidade Federal de Goiás (UFG) (protocol 238/11).
Urine cultures were performed in dip slide, according to the laboratory routine, and bacterial identification was performed by conventional biochemical tests.
Susceptibility testing was performed according to antibiotic disk diffusion method.The antimicrobials tested differed among the laboratories participants in the study.Thus, the results for evaluating the susceptibility profile correspond to those antimicrobials tested in all laboratories.The results were expressed as simple percentages.

rESuLtS
In this study, we analyzed the results of 2,181 urine cultures from outpatients in Jataí-GO; patients were 1,791 (82.1%) female, and 390 (17.9%) male.From the total urine cultures performed, 510 (23.4%) showed colony counts equal or greater than 10 5 UFC/ml of urine.Patients with positive urine culture were mostly female (81.4%).The age of the patients who underwent urine microbiological test varied from 0 to 97 years, and was prevalent in the age group 21-64 years (59.7%).Analyzing only patients whose urine culture was positive, there were also a prevalence of individuals in this age group (59.2%), as can be observed in Table 1.The UTIs frequency, according to patient's gender was not statistically significant in individuals under 12 years of age.Above this age, all age groups showed statistically significant difference between genders.
From 510 clinical samples with bacterial growth consistent to infection, E. coli was the most prevalent specie, representing 61% of bacteria strain.As shown in Table 2, Proteus sp. and Staphylococcus saprophyticus showed the second highest prevalence (9.4%).Analyzing the uropathogens prevalence, according to patient gender, it is possible to observe significant differences in the E. coli, S. saprophyticus, Proteus sp., Klebsiella sp. e Enterobacter sp.results.

DiSCuSSion
Urinary tract infection is a very common disorder that affects millions of people each year.It is one of the main reason that leads people to seek medical aid (2) .
According to the literature, UTIs affect mainly women (2) ; this study also meet this result.The high prevalence in female is justified due to hormonal effects, behavioral factors, and woman anatomic characteristics, since their urethra is short and the anus is near to the vaginal vestibule, which favor urinary tract infections (13,20,21) .
Escherichia coli is a microorganism belonging to normal human intestinal flora, and may cause extra intestinal infections (9) .The higher prevalence of E. coli as community urinary tract infection agent is expected and reported in epidemiologic studies worldwide.This microorganism was reported in 65.9% (6) and 75% (4) studies carried out in the State of São Paulo.In Santa Catarina and Minas Gerais, the prevalence found was 79.9% (23) and 72% (25) , respectively.The increased E. coli prevalence found as an UTI agent is used to orientate/guide the empiric treatment, in which the recommendation is especially based on the susceptibility profile of Gram-negative bacteria, mainly E. coli (19) .However, despite the higher prevalence of this microorganism, rates can change dramatically; consequently, they will interfere in the therapeutic used.A study published in 2010, performed in Campina Grande -PB, a significant lower percentage of E. coli (48,2%) was found (9) .
In other countries this variation in the major uropathogens prevalence can also be observed.An Indian study (26) showed E. coli prevalence of 48.3%; other studies showed prevalence of 71.3% in Turkey (1) and 77.5% in Belgium (3) .In the literature, data on other pathogens prevalence show large variation, while in this study, the most prevalent uropathogens, excepting E. coli, were S. saprophyticus (9.4%) and Proteus sp.(9.4%); other studies suggest Klebsiella sp. as the second most prevalent (7,27) .Otherwise, Beraldo-Massoli et al. (4) found prevalence of 11% to Enterobacter sp., while Queiroz and Felício (25) found similar results to those here observed.
In addition to data regarding the causative agent to UTI, for establishing an efficient empiric therapy, it is important to consider patient the age and sex, as regards to antimicrobials pharmacological properties and patient clinical history, but also to the prevalence differences of microbial agents in each region.In a study conducted by den Heijer et al., E. coli prevalence as UTI causative agent was significantly different between men (51%) and women (72%) (11) .Otherwise, these authors found Prevalence of uropathogens and antimicrobial susceptibility profile in outpatient from Jataí-GO of 41.1% to fluoroquinolones strains resistant, in a study carried out in Turkey (1) .Guajardo-Lara et al., in a study performed in Mexico, found 24.7% of resistance to ciprofloxacin (15) .Similar resistance percentage (23.5%)was also reported in India (26) .
In Brazil, this situation is not different.Silveira et al., in a study performed in Uberaba-MG, found trimethoprimsulfamethoxazole (48%) and ciprofloxacin (25%) resistance rates similar to those here observed (27) .Otherwise, in other regions of the country, fluoroquinolones resistance does not reach such high rates.In a study carried out in Campina Grande-PB (9) , trimethoprim-sulfamethoxazole resistance rate (41.9%) was similar to that found here, but the E. coli isolated strains showed low resistance to ciprofloxacin and norfloxacin (8.2% for both).Thus, these drugs represent an excellent therapeutic choice in that region.

ConCLuSion
Due to high levels of resistance found to first choice drugs, empirical therapy became a difficult clinical decision.Therefore, it is important to know the epidemiologic and resistance aspects of main pathogens in each region, in order to help in use of appropriate therapy to regional circumstances.significant differences in susceptibility profile of isolated strains between male and female patients, demonstrating that empirical treatment should consider this aspect.Another study demonstrates significant differences in UTI etiology, according to patient sex and age.Thus, Proteus sp.showed significant higher prevalence among men, and E. coli prevalence among infants was significantly lower (18) .These last two antimicrobials are extensively used in UTI empirical treatment, but data demonstrated that significant number of E. coli are resistant.These data should be used to discourage the administration of these drugs for empirical treatment.Naber suggest that in regions which the rate of resistance to a given antimicrobial is greater than 10% to 20%, this drug should not be used empirically (22) .Quinolones are widely used drugs in UTI treatment, and its administration is indicated for treatment when ther is a high resistant rate to trimethoprimsulfamethoxazole (16,28) , but data here obtained, also reveal high resistance rate to this antimicrobial group: 48.6% to nalidixic acid, and 30.2% to ciprofloxacin.This finding indicates that the use of these drugs should be careful, and the empirical use should be discouraged, since its use easily select resistant strains (17) .

tABLE 1 -
Positivity of urine culture according to patient's sex *p < 0.05.

tABLE 2 -
Frequency of microorganisms isolated at clinical analysis laboratories in Jataí, from March 2010 to June 2012 *p < 0.05.

tABLE 3 -
Resistance profile of major uropathogens isolated in outpatients samples in Jataí, from March 2010 to June 2012 NT: not tested.