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Urinary Tract Infections and Antibiotic Sensitivity Patterns Among Women Referred to Azadi Teaching Hospital, Duhok, Iraq

The Urinary tract infection (UTI) is a common acquired bacterial infection with an estimation of 150 million episodes worldwide annually (1,2). The communityacquired uncomplicated lower UTI is the most common form that is often handled in primary care units (3). UTIs are more common in female due to shorter urethra which allows microorganisms to travel more easily into the bladder and sexual activities that increase the inoculation of bacteria into the bladder; in addition, delayed postcoital urination with the use of a birth control measures such as diaphragm may further predispose female to recurrent UTI (3,4). It is worth mentioning that persistent symptoms for at least 7 days increases the risk of recurrent infection because of the occult kidney infection especially in females with lower socioeconomic status (3). It was previously revealed that the high resistance rate to the commonly used antimicrobial medications might also play a role in occurrence of complicated and recurrent UTI. Besides, variations in antibiotic resistance have been demonstrated in different geographical regions (2,3,5,6). Therefore, it is recommended that antibiotic resistance pattern for any infection be investigated in different countries since this plays a pivotal role for both correct management and antimicrobial resistance prevention. Furthermore, studying antimicrobial susceptibility patterns may help allocating UTI empirical treatment guidelines. In a previous study conducted in Iraq, recruiting 141 samples of both genders it was found that Escherichia coli was the most common infectious agents causing UTI (7). Amongst the gram positive microorganisms, staph species were the most common bacteria causing UTI and were resistant to the most commonly used antibiotics (7-9).


Patients and Methods
Sample Collection Urine samples were collected from 371 UTI afflicted subjects residing in residing in Duhok, Kurdistan, Iraq. Clean catch midstream urine was obtained from the patients to avoid contamination. The collected samples were inoculated on blood and MacConkey agars and then incubated at 37 о C for 24 hours. The presence of ≥10 5 identical colonies was considered as microbiological evidence of a UTI. Bacterial colonies were initially classified by gram staining and then determined depending upon standard culture and biochemical characteristics of isolates and identification was performed in accordance with local standards and guidelines.
Antimicrobial Susceptibility Test Phoenix system (Becton Dickinson) was used for identification of bacteria and antimicrobial susceptibility testing. The test was performed according to the manufacturer's instructions.
Ethics Statement Consent was obtained from patients recruited in the report. This research and method of attaining consent were approved by the scientific committee of the department of sciences, University of Zakho, Kurdistan, Iraq.

Patients Characteristics
In this study, 371 female patients were recruited; the majority of these patients were within the age range of 13-45 years. Sixty out of 371 (16.1%) and 70 out of 371 (18.9%) of the patients were older than 45 years old and within the age range of 19-30 years, respectively (Table 1).

Antibiotics Sensitivity Pattern
The vast majority of the isolates were gram negative and only 2 (0.5%) isolates were gram positive.  Table 2). It was found that 31% and 0% of isolated Klebsiella strains were resistant to ciprofloxacin and amikacin, respectively ( Table  2). Regarding the sensitivity pattern of pseudomonas, it was revealed that 42%, 75%, and 50% of the strains were resistant to ceftazidime, ertapenem, and ciprofloxacin, respectively. The sensitivity of Proteus to ciprofloxacin and ceftazidime was found to be 26% and 18.7%, respectively ( Table 2).

Discussion
The UTI is considered to be one of the most widespread infections worldwide. Although every individual is susceptible to UTI, some groups are more vulnerable. Women, in general, are more susceptible to such an infection due to anatomical and physiological features. The vast majority of national and international guidelines recommend empirical antibiotic therapy for UTI treatment. However, the effectiveness of such an empirical antibiotic treatment relies upon local antimicrobial resistance patterns. It is worth mentioning that the spectrum of microorganisms isolated from subjects suffering from UTI is almost stable and E. coli remains as the most prevalent causative agent. In a study conducted in Iran where 1513 patients participated, it was found that E. coli was the most common pathogen especially in women. In the same study, Klebsiella was observed as the second most common infection (10). In another study carried out in Turkey involving 429 women between the age of 18 to 65 years old, E. coli was found to be the most common causative agent of UTI (11). In agreement with this, it was revealed that E. coli strains were the most common causative microorganisms of UTI in our locality. It is important to notice that significant changes in bacterial susceptibility profile have been demonstrated over the last decades (12). For example, the average resistance for ampicillin is more than 50% in some countries (12). In a study conducted in Turkey, the resistance rates of E. coli for ampicillin, amoxicillin/ clavulanic acid, ceftriaxone, ciprofloxacin as well as sulfamethoxazole/trimethoprim were 55.1%, 32.7%, 15.9%, 25.2%, and 41.1%, respectively (11). In the present study, about 75% of the isolated E. coli strains were resistant to amoxicillin/clavulanic acid. Moreover, our results showed that around 65% of isolated E. coli were resistant to ceftriaxone, ceftazidime, and cefipime. Besides, it was found that 31% and 0% of isolated Klebsiella strains were resistant to ciprofloxacin and amikacin, respectively. The resistance pattern of Klebsiella to ciprofloxacin was similar to what was found in Africa. However, the sensitivity to amikacin in this study was much better that of found in Africa (0% comparing to 11%) (13). The sensitivity pattern of Pseudomonas was alarming as 42%, 75%, and 50% of the strains were resistant to ceftazidime, ertapenem, and ciprofloxacin, respectively. The sensitivity of Proteus to ciprofloxacin and ceftazidime was reported to be 26% and 18.7% in the current study which was less than what was found in a study in Taiwan (54% and 80%, respectively) (14). The association of Acinetobacter species and UTIs is well established. Risk factors predisposing to infection with such bacteria include prolonged hospital and intensive care unit admission, surgical intervention, and prolong antibiotics use (15). In this study, few causes of UTI resulted from Acinetobacter species showing 100% resistance to aztreonam and amoxicillin/clavulanic were reported. Unfortunately, due to missing data, it was not possible to determine whether or not those patients were exposed to above-mentioned risk factors.
In a previous study in Iraq, it was indicated that about 50% of the bacteria causing UTI were gram positive and the vast majority of them were staph species (7). Surprisingly, in this study, 2 cases of UTI caused by staph species were found. This is difficult to explain and more study is needed in this respect.
It was previously demonstrated that the distribution of microorganisms causing UTI was age dependent (3,16). A lower prevalence of E. coli isolates was found in patients younger than 13 years or older than 60 years. Unfortunately, such a comparison was not reliable in the present study as the majority (60%) of the patients were within the age range of 31-45 years old.

Conclusion
The current study makes a clear case that resistance of microorganisms causing UTI has reached alarming levels and immediate plan is required to cope with the issue. Another important finding of this study is that continuous surveillance of antibacterial resistance is required to monitor the changes taking place in the sensitivity pattern in any society. Strengthening local and global antibiotics resistance surveillance is critical since it provides essential information for global strategies, monitors the effectiveness of public health measures, and determines new trends and threats.