Bacterial Profile, Antimicrobial Susceptibility Pattern, and Associated Factors of Community- and Hospital-Acquired Urinary Tract Infection at Dessie Referral Hospital, Dessie, Northeast Ethiopia

Background Bacterial urinary tract infection is among the most common community and hospital-acquired infections. Therefore, to know the status of the community and hospital-acquired urinary tract infection, antimicrobial susceptibility patterns, and associated factors among urinary tract infection profiles are essential to physicians and health workers to implement appropriate intervention. Methods An institution-based cross-sectional study was conducted among 422 urinary tract infection suspected patients. All isolates were identified by standard microbiological techniques, and their antibiotic susceptibility was done by the Kirby–Bauer disc diffusion method. Data were entered using EpiData version 3.1 and analyzed by SPSS software version 20. P value < 0.05 at 95% CI was considered statistically significant. Result Of 422 urine samples processed, 100 (23.7%) yielded bacterial isolates. About 50(30.7%) and 50(19.3%) were bacterial isolates from the community and hospitalized patients, respectively. E. coli 44/103(42.7%) predominated across the two groups, followed by S. aureus 25/103(24.3%), CONs, 14/103(13.5%), Klebsiella spp. 7/103(6.78), Proteus spp. 3/103(2.91), and Enterococcus spp. 3/103 (2.91%). Pseudomonas spp. 3/103 (2.91), Citrobacter spp. 2/103(1.94%), and Acinetobacter spp. 1/103(0.999), which were isolated from only the hospitalized patients. Meropenem susceptibly was 100% in both study groups and Ampicillin resistance was documented as 83.3% to 100% and 76.9% to 100% in hospitalized and community-acquired samples, respectively. Conclusion This study found a high prevalence of bacterial urinary tract infection in the study area and a high rate of bacterial resistance was observed to most antimicrobial drugs tested. Meropenem and nitrofurantoin were the most active drugs for urinary tract infections. Therefore, expanding routine bacterial culture and identification with antimicrobial susceptibility testing and strengthening regular surveillance systems are essential for appropriate patient care.


Introduction
Urinary tract infections (UTI) constitute a significant public health problem and present an important cause of morbidity and mortality worldwide [1,2]. Bacterial pathogens are the commonest etiological agent to cause UTI. It affects both lower and upper urinary tracts with different clinical symptoms, including fever, dysuria, urgency, burning sensation, and intermittent urination.
Suprapubic tenderness [3] is the second most common infection after respiratory tract infections and accounts for a great proportion of prescriptions of antibiotics. e major causative organisms for UTI are bacteria organisms. ey account for more than 95% of cases [4,5], which may be Gram-negative and Gram-positive bacteria that account for 80-85% and 15-20%, respectively [6,7]. Urinary tract infection starts with contamination of the periurethral by uropathies residing in the bowel flora colonization. e urethra ascends to the bladder and migrates to the kidney or prostate. e result of host-pathogen complex interactions ultimately determines whether uropathogens are successful in colonization or eliminated [8]. Community-acquired UTI (CAUTI) is the member of intestinal microbial flora. e most common are E. coli and Klebsiella spp. In communityacquired urinary tract infection, E. coli and S. saprophyticus accounts for 80% and 5% to 15% of outpatients, respectively, across the various regions of the world, and the remaining 5% to 10% of cases are aerobic Gram-negative rods such as Klebsiella spp. and Proteus spp. and other Enterobacter spp. [9][10][11].
Hospital-acquired urinary tract (HAUTI) infections are mostly healthcare-related infections because these are the ones that occur more frequently and are commonly related to the use of a medical device such as catheterization [10,12,13].
Urinary tract infections are an important cause of septicemia, resulting in high mortality rates, prolonged hospital stays, and increased healthcare costs [14]. e death of hospitalized patients among the victims of hospital-acquired urinary tract infections are 2 to 3-times higher than those among nonbacteriuric patients [15]. Catheter-associated urinary tract infections occur with high incidence if healthcare safety is not maintained. Studies reveal that 79.3% of UTI can be prevented if catheterization is not performed in hospitals [16]. Multiple risk factors can affect the occurrence of urinary tract infections. ese include age, sex, catheterization and hospitalization, previous exposure to antibiotics, recurrent UTI, duration of catheterization, and care of catheter [12,[17][18][19][20].
In developing countries, including Ethiopia, where there is a high level of poverty and poor hygiene practices, there is also a high prevalence of fake and spurious drugs of questionable quality in circulation [21,22]. Besides this, the easy availability in the community without clinician order and low cost makes the drugs subject to abuse. ese make increasing drug resistance [23]. erefore, the current study aims to assess the prevalence and antimicrobial susceptibility pattern and associated factors among urinary tract infection profiles and provides updated information to regulatory bodies and those who would like to use the findings for the development of intervention strategies as appropriate.

Study Design and Setting.
A hospital-based cross-sectional study was conducted at Dessie Referral Hospital from March 2019-April 2019. e hospital was found in Dessie town with a distance of 401 km from the capital city of Ethiopia, Addis Ababa, and 471 km far from Bahir Dar, which is the capital city of Amhara Regional State. e hospital provides health services for more than 6 million people. is large number of people from the surrounding zones and nearby regions visits the hospital for different medical services. Dessie Referral Hospital provides emergency, ART services, chronic care, surgical, dental, medical, pediatric, gynecologic, obstetric, and other services.

Sample Size and Sampling Technique.
A single population proportion formula was used to determine the sample size, 50% prevalence (anticipated proportion). By considering a 5% margin of error, 95% confidence level, and 10% nonresponse rate, a total of 422 participants were proposed and systematically recruited. e completeness and clarity of the collected data were checked every day. A pretested structured questionnaire was used for the data collection on sociodemographic characteristics and associated risk factors. e questionnaire was initially prepared in English and translated into the local language, Amharic.

Laboratory Quality Control.
e sterility of culture media was checked by incubating about 5% a batch of the media at 35-37OC overnight and evaluated for possible contamination. Standard reference strains of S. typhimurium (ATCC-14028) and E. coli (ATCC-25922) were used as quality control throughout the study for culture [26]. Data quality was ensured at various activities of the study by following the prepared standard operating procedure (SOP) of the laboratory.

Data Analysis and Interpretation.
Collected data were entered into Epi-data 3.1 and exported to SPSS version 20 statistical software for analysis. During analysis, Descriptive statistics including mean, frequency, and percentage were used to summarize the data as appropriate. en the findings of this study were presented in the form of texts, tables, and graphs as appropriate. A P value of <0.05 was considered statistically significant.

Operational Definition.
Community-acquired UTI is an infection if an individual with UTI is suspected before hospital admission and specimens are collected from the outpatient or within less than 48 hours of hospital admission.

Hospital-Acquired UTI.
ose individuals are not present or incubating at the time of the hospital admission and developing 48-72 hours after hospital admission. is manuscript presents in the <research square> as a preprint. https://www.researchsquare.com/article/rs-157817/v1.
International Journal of Microbiology e frequency of isolated bacteria increases the duration of catheterization. E. coli, S. aureus, CONs, Pseudomonas spp., Klebsiella, and Enterococcus spp. were increased after one week of catheterization. However, Proteus spp., Citrobacter spp., and Acinetobacter spp. were found only for more than one week of catheterization ( Figure 2).   ose individuals who were inpatient were 1.753 times more likely exposed to develop HAUTIas compared to outpatient individuals. In addition, being female of sex was 8.925 times more likely to have increased urinary tract infection as compared with being male (AOR � 8.925; CI: 1.790-44.48, P � 0.008), and ages of 15-29 years and 30-45 years old were 0.126 and 0.057 less likely to have developed urinary tract infection when compared with ages of individuals whose age were >60 years old (AOR � 0.126; CI,0.020-0.792, P � 0.027) and (AOR � 0.057; CI,0.057-0.480, P � 0.008), respectively [ Table 4].

Risk Factors of Community and Hospital-Acquired
In addition, individuals with the diabetic disease were 6.702 times more likely to have increased developing UTI as compared with individuals who were not diabetic (AOR � 6.702; CI,1.994-22.528, P � 0.002) [ Table 4].
Besides these, previous usage of prolonged antibiotics was 5.689 times more likely to have developed urinary tract infection when compared with nonusers of antibiotics (AOR � 5.689; CI.1.840-17.590, P � 0.003). Moreover, those patients who used catheters were 3.886 times more likely to have increased developing UTI as compared with those patients who have not used catheters (AOR � 3.886; CI,1.323-11.47, P � 0.014) ( Table 4).
However, there was no association among other characteristics like ages 0-14 years and 45-59 years, recurrent urinary tract infection, history of urinary tract obstruction, history of renal calculi, waiting for time in hospital, and duration of catheterization (P value >0.05) ( Table 4).

Antimicrobial Susceptibility of Community and Hospital-Acquired Urinary Tract Infection.
In this study, the highest degree of resistance among the 15 antimicrobial drugs was observed indifferent bacterial isolates. Klebsiella spp. was resistant to 100% for Ampicillin and 80% Augmentin in hospital-acquired and Tetracycline in community-acquired    Multidrug resistance (MDR) was detected in 18 (69.2%) and 11(61.1%) of E. coli isolates in both community and hospital-acquired urinary tract infections, respectively. e resistance patterns of 103 bacterial uropathogens isolated were tested against 15 antimicrobial agents. e predominant profile of E. coli MDR was observed in AMP, AMOX-CLAV, TET, and SXT with 4 (3.85%) among hospital-acquired and AMP, AUG, TET, CPR, SXT, and CTR with 2 (5.56%) among community-acquired UTI. Among the total numbers, Proetus spp. isolates were 100% MDR, three of them in hospital-acquired and the rest community-acquired.
e scenario was also observed in Klebsiella spp. Moreover, S. aureus MDR was a higher proportion in hospital-acquired cases than community-acquired cases. In this study, antibiotic profile, except Penicillin, one S. aureus isolate resists all antimicrobials in hospital-acquired urinary tract infections (Table 7).
Pseudomonas spp.  According to our study, E. coli was the predominant uropathogen and no significant change has occurred in terms of pattern or position, of 26/50 (52%) and 18/53 (33.96%) in community and hospital-acquired UTI, respectively. is report is comparable with Nigeria [5], Saudi Arabia (38), and Kuwait [33]. It might be due to several virulent factors specific for colonization and invasion of the urinary epithelium, such as P-fimbria and S-fimbria adhesion. However, the frequency of isolation of E. coli in urine samples varies in different study areas. It may be due to the high variation of different species of bacteria in the study and differ in the laboratory method of isolation. is makes it difficult to compare. e frequency of CAUTI caused by E. coli is higher than that of HAUTI in this study. is is because most of the bacterial organisms causing UTI originate from the fecal flora and are dominated by various virulence factors that facilitate the ascent of bacteria from the perianal area to the urethra into the bladder and less frequently allow the organisms to reach the kidneys to induce symptomatic inflammation [38]. e second most frequent bacteria isolated were S. aureus at isolation rates of (24% vs. 24.5%) in CAUT and HAUTI, respectively. is result was a similar pattern with the study in Arbaminch, Ethiopia [29], and Southwestern Nigeria [39] in CAUTI and HAUTI, respectively. is study was at variance with other studies that reported a higher prevalence of other Gram-negative enteric bacilli Congo [21] K. pneumoniae, Saudi Arabia [32] Enterobacter spp., and Bangladesh [33] Pseudomonas spp. compared to as S. aureus.
In our study, coagulase-negative staphylococcus was the third position 8/50(16%) and 6/53 (11.3%) for CAUTI and HAUTI, respectively. However, our result was not correlated with other reports in Saudi Arabia [32], Bangladesh [33], and Abuja Nigeria [5] Pseudomonas spp. and is a retrospective study in Dessie regional lab, the second and third isolates were Klebsiella spp. and Proteus spp., respectively [40]. e possible reason for this variance was most Gram-positive bacteria survived commensally and it has been shifting with the environmental conditions such as temperature, humidity and resistance patterns. On the other hand, an increase in Staphylococcal UTI in the hospital setup may increase the use of instrumentation such as a catheter [41].
In our study, the prevalence of Klebsiella spp. was higher in hospital-acquired setting 5/53 (9.4%) than in community-acquired setting 2/50 (4%). In this study, it can be justified by its ability for adaptation to the hospital environment, and it can survive longer than other bacteria, enabling cross-infection within hospitals [42]. is report is correlated with the study in Bangladesh [33]. Citrobacter spp., Pseudomonas spp., and Acinetobacter spp. were International Journal of Microbiology 9 isolated from hospitalized patients only. Similar results were found in Yemen [34]. Pseudomonas spp. is enabled to survive and thrive well in soaps and disinfectants used for urethral catheterization [35]. Antimicrobial resistance has been recognized as an emerging worldwide problem in both ideveloped and developing countries. In hospital-acquired urinary tract infections, the resistance rate of Gram-negative isolates was 86.6% and 75% for Ampicillin and Amoxclav, respectively. In Gram-positive isolates, 76% and 68.4% were resistant to Tetracycline and SXT, respectively, except Enterococcus spp. is result was comparable with Yemen [37].
In community-acquired urinary tract infections, resistance for Ampicillin and Tetracycline was 79.3% and 68.9% to Gram-negative isolates and 61.9% and 36% for Tetracycline and SXT to Gram-positive isolates, respectively. is report is in agreement with Jordan (73%) [43] and Yemen (tetracycline (68.7%)) [34]. e high proportion of resistance found in ampicillin, tetracycline, amox-clav, and SXT in both settings could be explained by the long period for which these drugs have been available and in use for UTI and in our study area, people having easy access to antibiotics in drug shops and therefore greater intake that contributes to increased the proportion of resistance.  However, meropenem and nitrofurantoin were the most active drugs for both types of UTI because they are not easily accessible. is report was similar to Northwestern India for Nitrofurantoin [31]. In this study, the overall prevalence of multidrug resistance was 55.3% (57/103) (95%CI:10.0-16.8), in which 72.2% (21/29) of Gram-negative and 20% (4/20) of Grampositive isolates in CAUTI and 75% (21/28) of Gram-negative and 57% (11/19) of Gram-positive isolates in HAUTI were observed; this finding showed that Gram-negative isolates were almost equally distributed. In both settings, this may be due to multidrug resistance bacteria circulating from hospital setting to community setting and vice versa. On the other hand, almost twofold Gram-positive MDR isolates were seen in hospital setup; most probably due to instrumentation or unsafe healthcare practice.
is report was lower than the study in Gondar [44]. e possible reason for this result was geographical variation. Different demographic characteristics in various studies have been described to be associated with an increase in community and hospital-acquired UTI. In our study on CAUTI, previous use of antibiotics was significantly associated (P � 0.024) with the prevalence of CAUTI. Of 39.4% of the study subjects who had previously used antibiotics for UTI or other than UTI, 36.3% were culture-positive. is finding was consistent with other studies, India [45] in Gondar, Ethiopia [46]. e possible reason for this finding is that the common source of pathogens causing UTI is intestinal flora exposed to too many antibiotic classes for UTI and other than UTI bacterial diseases, and hence damaging intestinal flora, then allowing uropathogens to colonize and subsequently infect the urinary tract [47]. In the previous retrospective study, Dessie regional lab, being female, and age were risk factors of developing CAUTI as compared to males. But in this study, none of them were associated with these infections. e differences observed in this study might be because of characteristics of the population studied (immunological status, urological disorder), and most isolates from the community that is tested in the regional lab may be predominantly from referral patients for whose previous antimicrobial treatment failed.
In HAUTI, patient setting, sex, age, diabetic mellitus, catheterization, and previous use of antibiotics have a statistically significant relationship with significant bacteriuria. Similar studies were found in Gondar-Ethiopia [46], Harar-Ethiopia [36], and Uganda [48]. e high prevalence of bacteriuria among inpatients 53/103(51.5%) as compared to the outpatients, 50/103 (48.5%) was that increased risk of infection due to indwelling catheter that contributed to 64.4% of the inpatients UTIs. (X2 � 6.537, P � 0.011). is study is comparable with the study conducted in Uganda (49) and India [45] because infections could have been acquired through unsafe healthcare practices such as catheterization.
is indicates that females have stronger predictions for HAUTI compared to males. e possible reason for this finding is females are more catheterized than males due to obstetric and gynecological causes (urinary tract abnormalities or obstruction) and shorter length of female urethra, its proximity to the anal canal, and absence of prostatic secretions. is report is similar to the study in Bangladesh [33].
In this study, the age range of 15-29 years, the isolation rate of CAUTI and HAUTI were 91% in females and 8.7% in males and 0% male, and 100% in females, respectively. is high frequency is due to the sexually active stage in females or probably pregnant women. On the other hand, old age (>60 years) 50% female and 50% male and 29.2% in male and 70.8% in female in CAUTI and HAUTI were found, respectively. e high isolation rate of UTI among the old age group could be due to Genito-urinary atrophy and vaginal prolapse after menopause which increasing vaginal pH and decreasing vaginal Lactobacillus that allows Gram-negative bacteria to grow and act asuropathogens [33]. Moreover, it is the possible reason for males' prostatic gland enlargement and decrease of bacteriostatic prostatic secretions might account for such infections [33]. is finding is comparable with Bangladesh [33], Nigeria [49], and Shashemenie in Ethiopia [28].
In hospital-acquired urinary tract infections, previous use of antibiotics was significantly associated (P � 0.003) with the prevalence of hospital-acquired urinary tract infections. Of the total of 31.9% of previous antibiotic users for UTI or other than UTI, 52% of them were culture-positive. Our studies reflected that the prior and continuous use of antibiotics correlates with the UTI because the widespread use of antibiotics may cause multiple drug resistance microorganisms, this finding correlated with the study conducted in India [50] and Bangladesh [33].
In this study, urinary catheterization was the leading one among the causes of UTI due to instrumentation. From this study, 31.2% of UTI symptomatic study subjects used catheters in the hospital settings, 64.4% of those study participants were culture-positive. is reflects the greater proportion of HAUTI was significantly associated (P � 0.014) with catheterization. is finding is comparable with the study in Bangladesh [33], India [45], and Bahir Dar-Ethiopia [48]. e statistically significant association between HAUTI and diabetes (P � 0.002) could be due to altered immunity in diabetic patients, which includes depressed polymorphonuclear leukocyte functions, altered leukocyte adherence, chemotaxis, phagocytosis, the impaired bactericidal activity of the antioxidant system [51], and neuropathic complications, such as impaired bladder emptying. Moreover, a higher glucose concentration in the urine may create a culture medium for pathogenic microorganisms in diabetic patients that may result in this UTI. Similar reports are shown in Harar-Ethiopia [36], Nepal [52] India [45], and Uganda [48].

Conclusion and Recommendations
Findings of this study revealed that the overall prevalence rate of UTI was slightly high, and the hospital-acquired UTI International Journal of Microbiology group of patients has a higher rate of infection than community-acquired infection. E. coli is still the leading cause of community and hospital-acquired UTI, along with its increasing resistance pattern to different antibiotics, and is going to be an alarming health hazard. is study has shown that the alarming level of resistance (Ampicillin) achieved by bacteria is involved in causing UTI. E. coli and various isolates were more sensitive to meropenem and nitrofurantoin compared to other antibiotics tested. e healthcare policy should be discouraging inappropriate use of antibiotics and prevent further development of resistant strains among bacteria. A continual audit of antimicrobial susceptibility patterns among the community and hospital-acquired UTI as a cause of morbidity should be performed and the findings should be reviewed periodically. Awareness should be created among the community members to prevent risk factors associated with the infection. Nitrofurantoin should be the first choice for empirical treatment of UTI in this study area. Further research should be focused on the effectiveness of risk factor reducing strategies and the changes to economic costs and healthcare benefits.

Limitation of the Study
is study did not consider anaerobic bacteria and few bacterial isolates were not identified at the species level that causes UTI due to lack of facility. Our study limitation was using only the antibiotics disks diffusion method to perform antimicrobial susceptibility instead of the microdilution method.

Data Availability
Data used to support the finding of this study are available from the corresponding author upon request.

Ethical Approval
Ethical clearance was obtained from the School of Biomedical and Laboratory Sciences, University of Gondar ethical review committee, and a letter informing Dessie Referral Hospital Dessie about the purpose of the study and permission was obtained from Dessie Referral Hospital to access data from the study population.

Consent
Consent was obtained from study participants after explaining the purpose and objective of the study. If study participants are children (under 16 years of age), consent to participate was collected from the parents/guardians in written form. Study participants who were not willing to participate in the study were not forced to participate. Study participants were informed that all data and samples obtained from them were kept confidential by using codes instead of any personal identifiers and are meant only for the study. For those study participants who were positive, we advised going to the health institution to consult the clinicians for medical treatment and treated with the respective antibiotics;

Conflicts of Interest
e authors declare that they have no conflicts of interest.