Urinary Tract Infections in the Kingdom of Saudi Arabia, a Review

Urinary tract infections (UTIs) are among the most common infections and are associated with an increased rate of antimicrobial resistance in Saudi Arabia. Better knowledge of the most common pathogens and their antimicrobial resistance patterns will be useful for creating new treatment guidelines. PubMed, Web of Science, Scopus, and Google Scholar were searched using suitable keywords to identify UTI publications until November 2022. Eligible studies were selected and analyzed. A total of 110 records were found, but only 58 articles were analyzed. Most studies were retrospective, and just a few were cross-sectional or prospective. The majority of the studies were conducted in the central region followed by the Eastern region. Escherichia coli and Klebsiella spp. were the most common pathogens. There was a significant resistance rate against co-trimoxazole and ciprofloxacin. On the other hand, amikacin was one of the most effective antibiotics. Overall, only a few studies have been published on UTIs in Saudi Arabia. Moreover, not all regions have been represented, so the full scope of the issue is unknown. UTIs are still a major problem, and resistance has developed against commonly used antibiotics. Thus, large epidemiological studies are needed to battle the rapid emergence of antimicrobial resistance.


Introduction
Urinary tract infections (UTIs) are one of the most common types of infections [1]. They tend to be much more common in women; around 60% of women can expect to experience at least one UTI in their lifetime [2,3]. UTIs remain a burden for the healthcare system in the Kingdom of Saudi Arabia (KSA); they account for 10% of all infections in the country, and they stand as the second most common reason for emergency department admissions [2,3]. Around 4% of UTI patients are admitted to the hospital for further treatment. Another issue is readmission; around 10% are readmitted within one week of their discharge, and one of the main reasons is ineffective treatment [3]. Similar problems are faced around the world, as has been reported by several studies [4,5].
UTIs have usually been treated with broad-spectrum antibiotics. However, the treatment is often started without taking into consideration the bacterial culture or antimicrobial sensitivity patterns, which has led to the development of antimicrobial resistance worldwide. Nowadays, there is an alarming rate of antimicrobial resistance, leading to multidrug-resistant (MDR) bacteria [6]. Antimicrobial susceptibility patterns of the same bacteria can vary according to geographic location [5]. The Infectious Diseases Society of America recommends that regional surveillance should be conducted to monitor changes in the susceptibility of uropathogens in specific regions [7].

Search Outcomes
A total of 110 records were found. These produced 95 unique records after 28 duplicate articles were removed through a careful read of the study titles. Manuscripts were screened carefully, and only 40 met the inclusion criteria. An additional 18 articles were found while scanning eligible articles and their references, bringing the total to 58 articles for analysis ( Figure 1). not included (i.e., exclusion criteria). All the studies were full-text and published in English.

Search Outcomes
A total of 110 records were found. These produced 95 unique records after 28 duplicate articles were removed through a careful read of the study titles. Manuscripts were screened carefully, and only 40 met the inclusion criteria. An additional 18 articles were found while scanning eligible articles and their references, bringing the total to 58 articles for analysis ( Figure 1).

Data Extraction Process and Analysis
From each included study, the following data were abstracted: (1) authors' names, (2) publication year, (3) study design, (4) sample age and size, (5) study population, (6) location, and (7) main findings. Initially, the data of the included studies were charted by one co-author and then reviewed independently by the lead and senior authors. The main findings of the eligible articles were categorized under broad themes.

General Description of the Studies
The majority of the studies were retrospective studies, and just a few were crosssectional or prospective. The first study was published in 1988, and the following decades (i.e., 1991-2000 and 2001-2010) saw an approximately equal proportion of publications, whereas the last decade (i.e., 2011-2021) saw the most publications. Most studies were conducted in the central region, which includes Riyadh and other nearby cities, followed by the eastern region, Jeddah, and the Al Qassim region. Other regions had one or two publications per region. All age groups were included, from neonates to older adults (aged from 0 to +90 years). The sample sizes ranged from 82 [22] to 49,779 [27] participants (Table 1). Mupirocin (80%), tigecycline (80%) and ceftriaxone (47%).

Not mentioned
It is recommended that a smaller-size catheter be used to provide better drainage.

UTI in Diabetic Patients
Different comorbidities such as diabetes and pregnancy are associated with complications such as urinary tract infections [69]. Five studies specifically mentioned the UTI prevalence in diabetic patients [13,14,25,46,65]. A study conducted in Riyadh found that diabetes was one of the main causes of complicated UTIs, which extends beyond the bladder to the upper urinary system [13]. In another study, it was reported that 25.3% of the general diabetic population experienced UTIs [13]. Female patients were at much higher risk compared to men, even among patients who did not have diabetes or other chronic conditions [13,25]. There were other risk factors that were associated with an increased risk for developing UTI among diabetic patients, such as hypertension (p = 0.006), microalbuminuria (p = 0.031), insulin therapy (p < 0.001), and a body mass index (BMI) greater than 30 kg/m 2 (p < 0.001), all of which are complications of diabetes [14,46]. Other factors such as age, diabetes type, duration of diabetes, and HbA1C levels did not significantly increase the risk of developing a UTI [46]. Diabetic patients are at high risk of asymptomatic pyuria, bacteriuria, and upper urinary tract infections. One of the main factors is glucosuria, as glucose is used as a source of energy for bacteria, thus creating a suitable environment for bacteria to replicate at a high rate; it is also related to neutrophil dysfunction [13,25].
The most common isolated pathogens were Escherichia coli, Pseudomonas, and Staphylococcus hominis. Only one study reported Staphylococcus hominis as the most common pathogen [64]. All groups showed a high resistance rate to ampicillin and clindamycin. A lower resistance was reported to imipenem, meropenem, and amikacin. Imipenem is one of the alternative drugs advised by the Saudi National Antimicrobial Therapy Guidelines [11]. There were high rates of sensitivity to aminoglycoside, tigecycline, gentamycin, and ciprofloxacin. Most of the isolated pathogens were reported to have been multidrug resistant [13,25,64]. Ciprofloxacin was suggested as the drug of choice for empirical therapy in 2001, and, still in 2022, another study reported high bacterial sensitivity to it, indicating that it is a safe choice for many clinicians. The rate of resistance to ciprofloxacin was reported as high as 34% [13,25].

UTI in Older Adults
UTIs associated with asymptomatic bacteriuria are a common challenge in older patients. This is due to the lack of localized genitourinary symptoms [70]. There were three papers in which older adults were specifically studied [32,33,65]. One of the studies reported that older patients were more prone to UTIs; 37.5% of urine cultures from older patients were positive for growth as compared to 24.34% and 32.29% in adults and children, respectively [33]. UTIs accounted for 14.6% of emergency department visits by older patients in 2018 and 11% in 2001 [32,65]. The prevalence of UTI was reported to be more common among female patients, but it tended to decrease with age. On the other hand, the prevalence among males tended to increase with age, especially among older men [33].
E. coli, Klebsiella species, and Enterobacter species accounted for most infections. There was a high resistance rate to ampicillin and trimoxazole commonly found among isolates [33,65]. UTI pathogens showed a higher resistance rate to antibiotics such as amoxicillin-clavulanic acid, ciprofloxacin, and nitrofurantoin among patients older than 65 years of age. Moreover, 47.2% of older patients experienced inappropriate antibiotic prescriptions, with inappropriate duration of treatment being the most common error (p < 0.05) [33]. Multidrug resistance was much more common among older people (50%) compared to other age groups (<20%), as was extended-spectrum β-lactamases (ESBL)-producing E. coli (8% in older people vs. 5% in other age groups) [32]. This high rate of resistance suggests the need to reevaluate and have an updated empiric therapy to combat the emergence of new resistant strains [32,33].

UTI in Cancer Patients
Two papers studied UTI prevalence in cancer patients. UTIs were the second most common infection after bloodstream infections [34,35]. The most common malignancies among the study groups were non-Hodgkin's lymphoma and AML (acute myeloid leukemia), followed by colorectal cancer and other types of malignancies. Patients who undergo chemotherapy have a high risk of developing febrile neutropenia, characterized by a fever of more than 38 • C and a decreased neutrophil count (less than 500 cells/mm 3 ), which is also associated with an increased risk for infection and mortality. Bacterial infections are among the major causes of mortality in neutropenic cancer patients [34,35].
In the past decades, there has been a shift in the prevalence of bacterial infections, from Gram-positive to Gram-negative being the most common. Studies conducted in the last decade reported E. coli and Klebsiella spp. as the most common Gram-negative bacteria pathogens [34,35]. Both pathogens were susceptible to imipenem-cilastatin, amikacin, piperacillin-tazobactam, and ceftriaxone. The ESBL production rate for E. coli and Klebsiella spp. were 38% and 22%, respectively [34,35].

UTI in Emergency Department Patients
UTIs are among the most common causes of emergency department (ED) visits, and the most common medical condition for which antibiotics are prescribed in many places around the world [71]. Four papers were found that included cases with UTI from emergency department [2,3,32,33]. UTI cases accounted for around 10% of total visits to the ED, with a higher prevalence of 13.3% in the month of January. Regarding age groups, 14.6% of older adults visited EDs due to UTI symptoms [3,32].
The male-to-female ratio was reported as 1:2 [3,32]. Women were most commonly affected by UTIs, except among older adults, where female patients were less than 50% of total older patients presenting with a UTI [3,33]. The average hospital stay of a patient with a UTI was around 3.5 days, and the longest stay was 23 days. Around 24% of patients required isolation, and 3% required admission to the ICU (intensive care unit).
E. coli was the most frequently isolated pathogen, followed by Enterobacter spp., Klebsiella spp., and Acinetobacter spp. E. coli showed resistance to ampicillin and co-trimoxazole and showed sensitivity to nitrofurantoin, followed by ciprofloxacin, amoxicillin-clavulanic acid, and cefazolin. ESBL-producing E. coli was detected in approximately 7% of the isolates [2,32,33].
Most of the patients (around 80%) were initially treated with broad-spectrum antibiotics. Cephalosporin and penicillin were the most common classes. Cefuroxime and norfloxacin were the most commonly prescribed antibiotics among adult and older adult patients, whereas in pediatric patients, the most common choice was amoxicillin-clavulanic acid followed by cefprozil [2,32,33].
UTIs account for a high economic cost for emergency departments. Only one study reported the economic impact of UTIs on EDs [32]. The cost of hospital treatment for a UTI in the ED of King Abdulaziz Medical City in 2018 ranged from USD 90.19 to USD 328.65 per patient, and an estimated yearly cost of USD 838,375. Another factor that contributes to the high cost is inappropriate prescription of antibiotics, which accounted for 47% of the overall cost (p < 0.05).
To some extent, we can say that there was an overestimation of UTIs among patients who visited EDs with UTI-like symptoms. This was confirmed with a 60% prevalence of positive cultures [3], and in some other cases only 30% of total ordered urine cultures from the ED were positive [32,33].
Another problem that was noted was the burden of readmissions. Around 10% to 15% of patients were found to be readmitted to the ED within 30 days after discharge, and the median time for readmission was around 7 days. Patients who required isolation were more likely to get readmitted. Readmission was more common in patients having underlying diseases [3]. Unplanned readmission is a huge burden on the hospital facilities, especially for emergency departments, as it increases the cost and overloads the setting.

Inappropriate Antibiotic Prescriptions
The overuse and inappropriate use of antibiotics are two of the most important causes of antimicrobial resistance [72]. According to a report from the WHO, around 20% to 50% of antibiotics are inappropriately prescribed [2,6]. Only two papers identified this issue in KSA [2,32]. Inappropriate use of antibiotics includes dose errors, duration errors, frequency errors, and inappropriate selection of antibiotic class [2,32]. Around 47.3% of prescribed antibiotics in EDs were inappropriate. Pediatric patients were the most vulnerable group (p < 0.001); 57.8% were prescribed inappropriate antibiotics as compared to a rate of 37.8% among adult patients. Pediatric patients were more prone to errors such as dosage (p < 0.001) and duration errors (p < 0.001), while adult patients were more prone to errors such as inappropriate selection of antibiotic class (p < 0.001). However, neither study reported a significant association between age and frequency of selection error (p = 0.74) [2,32].
Inappropriate antimicrobial prescription for a UTI is more common in the ED as EDs often prescribe antibiotics. Using a lower concentration of antibiotic or for a shorter duration will cause antibacterial resistance, and overuse will result in toxicity, an increased antimicrobial resistance rate, or other side effects. Inappropriate prescription is also associated with several clinical manifestations such as allergies, gastrointestinal disturbances, renal/liver distress, etc. Assessing the weight of an infant before prescribing a dosage of any antibiotic is quite important. Studies show that even though the weight of the infant was measured, there were still errors in dosage calculation, with overdose being the most common calculation error [2,32].
Inappropriate selection of antibiotics is related to an increased antibiotic resistance rate, along with several complications and an increased chance for readmission. It will also affect the healthcare system as it will increase the cost of treatment and make the battle against antimicrobial resistance more difficult. There was an interesting correlation between diagnostic tests, prescription inappropriateness, and cost. Patients who had undergone diagnostic tests had a higher incidence of being prescribed expensive antibiotics. On the other hand, patients who did not undergo diagnostic tests initially had a lower cost, but they were inappropriately prescribed antibiotics, causing many later complications [2,32].
Cephalosporin was 3.31 times more likely to be inappropriately prescribed to adult patients, compared to penicillin prescriptions. On the other hand, penicillin was more likely to be inappropriately prescribed to pediatric patients (33.6%) compared to other antibiotics (p < 0.05). Cephalosporin was the most inappropriately prescribed antibiotic (more than 90%). Most of the patients who were administered or prescribed antibiotics were not screened for antibiotic allergy; only 7% of patients were screened for antibiotic allergy prior to its administration or prescription.

UTI in Children
Twelve papers reported UTIs in children (0-12 years old) [2,15,17,[19][20][21][22]32,33,50,59,62]. UTIs account for 4% to 15% of total ED visits by pediatric patients [2,32]. UTIs and related complications account for around 5% of ED visits by children, compared to 15% of ED visits by other age groups. UTIs in children are common but difficult to diagnose due to their ambiguous nature. On the other hand, they have a very good prognosis [15,50]. Girls are at higher risk for infection. Up to the age of 6 years, the incidence rate is similar for both sexes, and this could be due to hygiene or other causes, but later the incidence among boys starts to decrease [15,21,50]. Circumcision is significantly associated with the development of UTIs among young boys. Uncircumcised boys are more prone to UTI than circumcised boys [20].
Some studies performed renal ultrasound on pediatric patients with a confirmed UTI. The most commonly reported abnormalities were hydronephrosis, uretric dilatation, dilatation of the renal calices and dilatation of the collecting system. Patients with abnormal ultrasound findings were associated with repeated episodes of UTI as compared to patients with normal findings who had only a single episode (p < 0.05). Moreover, abnormal ultrasound findings were significantly more common in non-E. coli UTIs [20][21][22].
As UTIs are common among children, they can be severe and have serious complications. A common complication is vesicoureteral reflux. Renal ultrasound is a good method to detect this complication [20][21][22]. Vesicoureteral reflux can be found in around 30% of children affected by UTI and bilateral reflux was very common as well. Patients who had vesicoureteral reflux had a high risk of developing pyelonephritis and scarring. In addition, renal parenchymal scarring was reported as a common complication of delayed treatment [20][21][22].
E. faecalis was not a commonly isolated pathogen. It was found to be highly sensitive to cephalothin, ciprofloxacin, linezolid, nitrofurantoin, teicoplanin, and vancomycin, but it was highly resistant to cefepime and tetracycline, followed by clindamycin and erythromycin, cefoxitin, gentamicin, and ampicillin [17].
Inappropriate antibiotic prescriptions were most common among pediatric patients, accounting for 51.3% of all prescriptions [16]. Some recent studies suggest the use of third-generation cephalosporin as a broad spectrum for community-acquired UTI because the majority of uropathogens were sensitive to it (96%) [17,19].

UTI in Adults
Urinary tract infections are among the most common infections worldwide, and they affect people from all age groups, especially women. The WHO has reported that an estimated 50% of women experience a UTI at some point in their lives [18]. We found 18 papers that studied UTIs in adults, especially in women, as they experienced more infections than men [2,13,18,24,[26][27][28][29][30]32,33,36,40,43,49,55,58,60]. Adult patients were the most represented in all the studies. In KSA, UTIs were reported to be the second leading cause of infection (predominantly in women) at EDs. Adult patients account for the most visits to an ED presenting with symptoms of UTI [2]. The vast majority of healthy adults who have a UTI will present with mild symptoms and can recover from the infection with a simple medication plan. The problem is reoccurrence, and using ineffective antibiotics will lead to an increased rate of resistance and urinary tract-related complications. On a large scale, many of the studies reported female patients as more likely to present with recurring UTIs [2,36,55].
Klebsiella spp. was the second most common pathogen, and it showed the highest resistance rate to ampicillin co-trimoxazole, followed by cefuroxime, aztreonam, cefepime, ceftriaxone, cefuroxime, cephalothin, ceftazidime, and amoxicillin. Additionally, Klebsiella spp. showed a high susceptibility rate to meropenem, imipenem, colistin, ertapenem, amikacin, and levofloxacin. The antimicrobial resistance patterns of other less common pathogens were similar to E. coli and Klebsiella spp. Ertapenem and imipenem are the first line of defense against ESBL-producing Enterobacter according to the Saudi National Antimicrobial Therapy Guidelines [11].

UTI in Pregnant Women
UTIs are very often encountered among women, especially pregnant women [73]. Three papers reported on UTIs in pregnant women [13,44,52]. The first one was published in 1991 [44], a second in 2013 [52], and the most recent in 2018 [13].
In the 1991 study [44], the prevalence of UTI among pregnant women was 16%. However, in the study that was conducted in the last decade, the prevalence of UTI was as high as 20% [52]. In both studies, around half of the patients who tested positive for UTI were asymptomatic. Patients with symptomatic UTI were significantly more likely to have a premature birth as compared to the asymptomatic group [44]. Asymptomatic UTIs can spread to the upper renal system and cause pyelonephritis, which is a major cause of septic shock among pregnant women [44,52].
UTIs during pregnancy were reported to be a common problem and they were commonly associated with several disorders [44,52]. Pre-eclampsia (a high blood pressure disorder that can occur during pregnancy) tended to be more common among patients with UTI. There was also a significant relationship between the presence of bacteriuria and development of conditions such as anemia and hypertension [44]. The incidence rate was similar between symptomatic and asymptomatic women [44,52].
The most common causative agents of UTI among pregnant women were E. coli, Staphylococcus, and Candida species, which is an indication of fecal contamination and poor personal hygiene [44,52].
Amoxicillin, cefoxitin, ceftazidime, norfloxacin, penicillin, and fusidic acid were the most useful antibiotics for treating UTIs as they showed the least resistance frequency. On the other hand, ampicillin and tetracycline had the highest resistance [13,44,52].

Catheter-Associated UTIs
Catheter-associated urinary tract infections (CAUTIs) are among the most frequent hospital-acquired infections. There were around eleven publications on CAUTIs [45,47,48,54,56,57,61,62,66,67,74]. CAUTIs are the most common nosocomial infections in KSA, where they account for 7% [54], 20% [61] 22% [66], 24.4% [45], 28.5% [57], and 42% [48] of hospitalacquired infections. There are several risk factors for the occurrence of CAUTI among ICU patients, such as prolonged hospitalization, prolonged catheter usage, poor aseptic technique, inappropriate use of antibiotics, gender, extremes of age, immunosuppressive drugs, etc. Sixty to seventy percent of CAUTIs can be prevented by proper infection control and by implementing preventive bundles [67]. Another risk factor related not only to CAUTIs but also to nosocomial infections in general is that they are caused by pathogens with very strong resistance rates and are a huge challenge to treat, especially for immunocompromised patients [45,54,61].
CAUTIs were more common in older patients (60 to 80 years old) [66,74]. The main causative pathogens were Klebsiella spp., followed by E. coli and Proteus, with a high sensitivity to amikacin, gentamicin, and carbapenem [54,66]. However, most of the articles did not report the main pathogens or their antimicrobial resistance patterns.
Some studies reported on interventions over a long period of time and tried to reduce the rate of nosocomial infections. Before the intervention, the rate of CAUTIs among patients admitted to ICU was 2.3 per 1000 days. After initial screening of the catheter and patients who were catheterized in ICU and with proper documentation and discouragement of routine replacement, the infection rate dropped to 1.9 per 1000 days in a short period [45]. In another intervention that lasted 2 years, the CAUTI rate dropped from 3.5 per 1000 days before the intervention to 2.9 per 1000 days after 1 year, to 2.2 in the beginning of the second year, and to 1.7 at the end of the last year [56]. In a 7-year surveillance and intervention, the CAUTI rate dropped from 6.75 per 1000 days to 3.41 per 1000 days [48]. The CAUTI rate dropped significantly after the intervention, but there is another noticeable fact. The early 2000s study [48] reported an incidence rate of around 10 per 1000 days, and the most recent study reported an incidence rate as low as 0.3 per 1000 days [56]. This is an indication that the standard of healthcare facilities and the adherence to infection control guidelines has improved.

Inpatient vs. Outpatient Studies
Most of the studies were retrospective in nature and took into consideration only cases with positive urine cultures; they did not categorize inpatients or outpatients or specify which clinic was visited. Some studies focused only on the patients who visited EDs, as mentioned in Section 3.5 [2,3,32,33]. However, some studies focused only on inpatients and mostly on CAUTIs; as mentioned in Section 3.11, they did not report causative pathogens or their antimicrobial resistance patterns [31,45,48,56,57,61,62]. Throughout this review, E.coli was found to be the most common uropathogen, except in some studies that reported inpatient data where Klebsiella spp. was the main causative pathogen [35,54,66]. There was a higher MDR rate among inpatient samples [54]. Additionally, when the hospital stay was prolonged (>8 days), the risk for acquiring a UTI was significantly higher [45]. Two studies specifically reported on outpatients from nephrology clinics, and E.coli was reported as the main causative pathogen, but neither of those two studies reported the antimicrobial resistance pattern for those uropathogens [14,50].

Discussion
There were 58 publications published in KSA about UTIs, UTI prevalence, and the main UTI pathogens. UTIs were much more common among women than men. However, the prevalence was approximately equal between the sexes among inpatient CAUTI cases and among children under the age of 5 years [4,63,75]. Among the reasons why UTIs are more frequent among women is the anatomical structure of their urogenital system. Children under 5 years have a similar infection rate for hygiene reasons, but, as they mature, they tend to become more aware of hygiene and eventually decrease the risk. Another factor in the incidence of UTI among children is circumcision as uncircumcised boys tend to have a higher prevalence of UTI [9,21].
In our review, the Enterobacteriaceae family was the main cause for UTI. E. coli and Klebsiella spp. were the most common isolated organisms, and in some studies, they were the only reported organisms. They tended to have a strong antimicrobial resistance pattern; those isolated from inpatients were more likely to present with MDR and a high ESBL production rate [51,64,76]. Another major problem contributing to the high resistance rate seems to be inappropriate antibiotic prescription. There was a high prevalence of inappropriate antibiotic prescriptions, especially in emergency rooms, which affected mostly children and older adult patients. This might be among the reasons why patients with UTI are admitted to ED very frequently. It was also reported that there was a high readmission rate among patients with inappropriate antimicrobial prescriptions. This issue was addressed only by two papers, and they revealed major inappropriateness and recommended more focus be given to this issue [2,32].
Hospital-acquired UTIs, especially CAUTIs, are a major challenge, and investigation, the measures taken, and incentives given seem to have had a good effect because these infections have significantly decreased in the last two decades [56,66,77]. The CAUTI incidence was similar between males and females; this could be due to immunosuppression, catheter usage, and/or other factors related to nosocomial infections [56].
Women in general are at high risk for developing UTIs, and pregnancy tends to increase the risk. The presence of a UTI seems to be related to other conditions during pregnancy, such as anemia, hypertension and even premature birth [69,73]. A similar risk of UTI was found among patients with diabetes; infection tended to be associated with uncontrolled diabetes [14,31,46]. These associations might be due to immunosuppression that pregnant women and diabetic patients experience.
All the included studies had adequate sample sizes. All studies enrolled more than 100 cases; only five had a sample of less than 100, and a few had more than 1000 cases. Many of the papers assessed other medical conditions (e.g., pregnancy, cancer, diabetes, and intensive care unit) and their correlation with UTI prevalence.
Most of the papers were descriptive papers and did not have any significant statistical analysis. Moreover, apart from a few papers, most studies were retrospective, included only UTI-positive samples, and were not compared to a control group to assess the risk factors for developing a UTI, and resulted in a 100% prevalence rate [12,13,15,16,18-21, 24-30,32,36,37,41,43,50-52,55,58-60,67]. Most of the publications were retrospective and lacked data on patients' course of treatment and the prevalence of UTI reoccurrence and complications. Additionally, not all regions were equally represented. As mentioned above, some regions were continuously studied, while some others were represented in only one or two studies.
Antimicrobial resistance is growing at a concerning rate. A continuous, more extensive, and inclusive study is needed to understand the full antimicrobial sensitivity pattern both locally and nationally in KSA and to plan an updated treatment regimen.
Improper antibiotic prescription is another factor that leads to complicated UTI and an increased rate of antimicrobial resistance, but, unfortunately, only a few papers highlighted this issue. The nature of most studies was retrospective, and there was no patient follow-up until the end of the treatment and recovery from the infection. Thus, data were limited on the appropriateness of the treatments. Moreover, the data of prescribed empirical therapy and its appropriateness for the microbiology report were not reported. Future studies should focus on these matters. This review paper was the outcome of a comprehensive search of multiple databases with specific keywords and careful examination of the titles and manuscripts of found publications. Therefore, it is unlikely that we missed any relevant English studies. However, any publication in Arabic only or nonpublished data on UTIs in KSA may have been missed. Additionally, some papers may have been excluded due to a lack of clearly specified samples/populations.

Conclusions
UTIs remain a major challenge for the healthcare system. Women and patients with underlying conditions tend to be at a higher risk, and E. coli remains the major causative pathogen. The current major concern is the rising antimicrobial resistance rate which requires rigorous scientific inquiry into antimicrobial resistance. Large epidemiological studies at the regional and national levels are needed to battle the rapid emergence of antimicrobial resistance. On the other hand, prospective and longitudinal studies are needed to assess the effectiveness of initially prescribed antibiotics. The data that can be obtained from these future studies will be valuable in developing new guidelines for the use of empiric therapies and controlling the increased rate of antimicrobial resistance.