Bacterial profile, antimicrobial susceptibility pattern and associated factors of community and hospital acquired urinary tract infection at Dessie referral hospital, Dessie, Northeast Ethiopia

doi:10.21203/rs.3.rs-157817/v1

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Bacterial profile, antimicrobial susceptibility pattern and associated factors of community and hospital acquired urinary tract infection at Dessie referral hospital, Dessie, Northeast Ethiopia

https://doi.org/10.21203/rs.3.rs-157817/v1

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Back ground:

Urinary tract infection are one of the most common bacterial infections in the community and in the hospital. Nowadays, little is known about the status of community and hospital acquired urinary tract infection, antimicrobial susceptibility pattern and associated factors among urinary tract infection patients in Ethiopia, particularly in our study area.

Methods

A hospital based cross sectional study was carried out in Dessie referral hospital. A total of 422 urine samples were enrolled using systematic random sampling technique. All isolates were identified by standard microbiological techniques and their antibiotic susceptibility was done by Kirby Bauer disc diffusion method. Data was entered using Epi data version 3.1 and analyzed by SPSS software version 20. P- Value < 0.05 at 95% CI was considered as statistically significant.

Result

Of 422 urine samples processed 100 (23.7%) yielded bacterial isolates. About50(30.7%) and 50(19.3%) samples from hospitalized and community showed significant bacteriuria 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 spps 7/103(6.78), proteus spps 3/103(2.91), and Entrococcus spps 3/103 (2.91%). Pseudomonas spps 3/103 (2.91), Citrobacter spps 2/103(1.94%) and Acinetobacter Spp 1/103(0.999), which were isolated from only the hospitalized samples. Meropenem susceptibly was 100% in both study groups and Ampicillin resistance was documented as 83.3–100% and 76.9–100% in hospitalized and community acquired respectively. Among risk factors previous use of antibiotics, female gender, Age, Diabetics, catheterization were associated with the infection.

Conclusion

The present study revealed that slightly high prevalence of urinary tract infection. High antimicrobial resistance was observed to most antimicrobial drugs tested. Meropenem and Nitrofurantoin were the most active drugs for urinary tract infection. Empirical selection of antimicrobial agents should be based on antibiotic sensitivity pattern of uropathogens that prevalent in that area. Female sex, age, previous use of antibiotics, catheterization and diabetics were at risk of urinary tract infection.

General Microbiology

Urinary tract infection

Antimicrobial susceptibility tests

Urinary tract infection (UTI) are one of the commonest diseases mainly caused by bacterial pathogens in human worldwide (1, 2). It affects both lower and upper urinary tracts with different clinical symptoms including fever, dysuria, urgency, burning sensation and intermittent suprapubic tenderness (3). It is the second most common infections after the respiratory tract infections and accounts a great proportion of prescription of antibiotics. The major causative organisms for UTI are bacteria ,they accounts for more than 95% of cases (4, 5), which may be Gram-negative and Gram-positive bacteria, that accounts 80–85% and 15–20% respectively (6, 7).

Urinary tract infection starts with contamination of peri-urethral by uropathies residing in the bowel flora colonization the urethra ascends to the bladder and migrate to the kidney or prostate. The result of host–pathogen complex interactions ultimately determine whether uropathogens are successful in colonization or eliminated (8). UTI are very common infection both in the community and hospital settings. Community acquired UTI (CAUTI) are members of intestinal microbial flora, the most common are E.coli and Klebisiella spp. In community acquired urinary tract infection, E.coli and S.saprophyticus accounts 80% and 5–15% of outpatients respectively across the various regions of the world, and the remaining 5–10% of cases are aerobic gram-negative rods such as Klebsiella spps and Proteus spps and other Enterobacteria spps (9–11).

Hospital acquired urinary tract (HAUTI) infections are mostly health care related infection and stand out from all hospital acquired infections, because these are the ones that occur more frequently and are commonly related to the use of a medical device such as catheterization. Hospitalized patients who acquired UTI have more comorbidities, recurrent, and have previously received antibiotics more often than patients with CAUTI (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).The death of hospitalized patients among the victims of hospital acquired urinary tract infection are 2 to 3-times higher than that among the non-bacteriuric patients (15). Catheter associated urinary tract infections occur with high incidence if health care safety were not maintained. Studies reveal that 79.3% of UTI can be prevented, if catheterization was not performed in hospitals (16). Multiple risk factors can affect the occurrence of urinary tract infections, these includes age ,sex, catherization and hospitalization, previous exposure of the antibiotics, recurrent UTI, duration of catheterization and care of catheter are included (12, 17–20).

In developing countries, including Ethiopia, where 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, these make increasing of drug resistance (23). Therefore, it is important for clinicians to have a working knowledge of etiologic agents and their susceptibility patterns of UTI pathogens in their population based on local community and hospital settings.

Study design and area

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

Study population and sample size

During the Two-month study period, a total of 422 UTI suspected patients from both inpatient and outpatient department who attended at Dessie referral hospital laboratory during the study period were included.

Data collection tools and procedure

Socio-demographic and clinical data collection

After taking informed consent, Socio-demographic characteristics, clinical data and associated factors were collected by professional nurse using pretested structured and standardized questionnaire guided interview. The questionnaire was translated to local language (Amharic) and re- translated back to English to make the reliability of data collection. Data was collected from their places of the study participants from outpatient departments or inpatient wards.

Sample collection and transportation

Urine samples were collected from Dessie referral hospital laboratory, where the study participants came from various outpatient (OPDs) and Inpatient Departments (IPDs) of Dessie referral Hospital.10-15 ml mid-stream urine, catheterized urine samples were collected using sterile container with screw cap tops. Urine samples were examined chemically and microscopically. Then, they were delivered to Amhara public health microbiology laboratory and process within 1-2 hours for analysis in case of delay the samples were refrigerated at 2-8ºC for up to 6 h.

Culture and identification

Urine specimens collected from different departments were directly inoculated on cystine lactose electrolyte deficient agar (CLED) (Oxoid, Ltd, England) media using calibrated inoculating wire loop (0.001 mL). Culture plates were incubated in the aerobic environment at 37⁰C for 24 hrs. After incubation, all suspected colonies were sub-cultured on to MacConkey agar (Oxoid, England) and 5% sheep blood agar (Oxoid, England) for further identification. Identification of bacterial isolates were done using colony characteristics on blood agar, MacConkey agar and gram reaction of the bacteria and biochemical tests in accordance with standard procedure (24).

Identification of the organisms

All isolates were subjected to gram staining for initial identification of organism according to their gram reaction, colony morphology and finally by biochemical test. Gram positive bacteria will be identified by catalase test, coagulase test.

Antimicrobial Susceptibility testing

Pure colonies were taken from plates with fresh, pure culture using sterile wire loops, and transferred to a tube containing 5ml of 0.85% normal saline and mixed gently until it forms a homogeneous suspension. The turbidity of the suspension was then adjusted to the density of a McFarland standard 0.5 in order to standardize the inoculums size. A sterile cotton swab was dipped into the adjusted suspension and excess was removed by gentle rotation of the swab against the inside wall of the tube. The swab was inoculated evenly over the entire surface of Mueller–Hinton agar (Oxoid) and then the inoculated plates were allowed to air dry for 3minuts and then the following disks was placed aseptically on the plate using sterile forceps.

Ampicillin (AMP,10µg), Amoxclavunic (20/10), Tetracycline (TE,30µg), Ciprofloxacin (CIP,5µg), Trimethoprim+sulphamethozol (SXT,1.25/23.75), Gentamicin (CN,10µg), Ceftriaxone (CRO,30µg), Cefixime(CXM,5µg), Nalidixicacid (NA,30µg), Nitrofurantoin (F,300µg),piperacillin (PIP,100µg), Vancomycin(VAN,10 µg), Penicillin (PEN,10µg), Meropenem (MER,10µg) and Tobramycin (TOB,10µg) then plates were incubated at 37^oC for 24.On the next day, plates were read by taking measurement of zone of inhibition. The antimicrobial agents were selected based on the CLSI guide line. Finally, inhibition zone diameters were measured to the nearest millimetres using a ruler. The results were interpreted by comparing to cut off points in the Clinical and Laboratory Standard Institute (CLSI) result interpretive standards (25).

Data quality control

Pre-tested structured questionnaire guided interview was used for data collection on socio-demographic characteristics, clinical data and associated risk factors. Training was given for five diploma professional nurses about research objectives, data collection tools and interview techniques for one day. The principal investigator supervised the data collection and checking completeness the returned questionnaire on daily basis.

Laboratory quality control

The sterility of culture media was checked by incubating 5% of the batch at 35-37^OC overnight and was evaluated for possible contamination. The reference strains also used as control E. coli (ATCC 25922), S. aureus (ATCC25923) were tested weekly as controls on CLED blood agar plates, MacConkey Agar, including Mueller Hinton agar and with antimicrobial discs to assure testing performance of the potency of antimicrobial discs. To standardize the inoculums density of bacterial suspension for the susceptibility test, 0.5 McFarland standard was used (26). Moreover, the whole procedures and result interpretation was done following standard operating procedure of the Amhara public Health Research Institute (SOP).

Data organization, processing and analysis

Data was entered using Epi-data3.1 version and analyzed using SPSS Version 20. Bacteria profile of community and hospital acquired UTI, antimicrobial susceptibility and associated factors were determined and frequency distributions of the socio-demographic characteristics were described. Inferential statistics: chi-square, odds ratio, confidence interval/p-value was used to determine association between variables. To determine factors associated with urinary tract infection, Bivariate logistic regression analyses was done and factors with a p-value of ≤ 0.2 was subjected to multivariable logistic regression analysis. Crude and adjusted odds ratios were calculated to quantify the strength of association between UTI and risk factors. The 95% confidence interval was determined and risk factors with p-value of less than 0.05 was considered as significant. Data was presented on tables.

Results

Socio Demographic and clinical characteristics of study participants

A total of 422 participants of all age group clinically diagnosed as Urinary Tract Infection
were studied to isolate bacteria from urine, of which 259 (61.4%) were from community acquired cases and 163(38.6%) from hospital acquired cases. The age range of study participants 5-90 years with a median age of 32 years. Among the total number of participants 55.2% (234/422) were from urban part of Dessie and surrounding areas, whereas 44.8% (188/422) of the patients were from rural part of Dessie as well as the surrounding areas. In the two study groups, majority of females 66.4% (172/259) and 33.6% (87/259) of male in the community acquired UTI and 66.9% (109/163) and 33.1% (54/163) in hospital acquired UTI suspected patients were visiting the hospital. Patients of ages 15-29 years of 22.2% (57/259) and 25.8% (42/163) and patients of ages >60 years 10.4% (27/259) and 20.8% (34/163) were presented in the study area with CAUTI and HAUTI cases respectively. Moreover, one hundred two (39.4%) and fifty-four (33.1%) of study subjects were history of previous exposure of antibiotics in community and hospital acquired UTI. Besides this, patients of fifty-two (31.9%) in hospital acquired UTI were history of catheterization and twenty-eight (10.8 %) and forty-two (25.7%) in community and hospital acquired urinary tract infection were history of diabetes respectively (Table1 & 2).

Prevalence of urinary tract infections

The overall prevalence of urinary tract infection was 23.7 % (100/422) (95% CI: 19.3-27.5). Out of 259 community acquired UTI symptomatic patients 19.7% (50/259) (95% CI:16.0-24.7) were culture positive and 30.7% (50/163) (95%CI:23.3-38) were culture positive for hospitalized patients (Table-3). Of the total 422 urine specimens processed 74.17% (313/422) showed no significant bacteriuria growth and 2.13% (9/422) showed insignificant bacterial growth. Significant growth was present in 23.7% (100/422) samples with 22.99 % (97/422) single growth and 0.71% (3/422) in mixed growth with two organisms in hospitalized patients. Three out of four hundred twenty-two (0.71%) of samples with two bacteria each were isolated making the number of bacteria isolated to be 103 with the isolation rate of (24.4%). From a total of 103 different uropathies bacterial isolated, 53(51.46%) were hospital acquired setting isolates and 50(48.54% were community acquired setting isolates. Sixty-one (59.22%) were Gram-negative bacilli and 42(40.78%) were Gram-positive cocci (Table 4 & 5).

Table 1. Bivariate and multivariate analyses of risk factors associated with community acquired UTI among Dessie referral hospital UTI suspected patients in Dessie.

Characteristics (n=422)	Negative N (%)	Positive N (%)	COR (95% CI)	P-Value	AOR (95%CI)	P-Value
Sex
Male	77(80.5)	10(19.5)	1
Female	132(76.7)	40(23.3)	2.333(1.105-4.939)	0.026	0.385(0.072-2.065)	0.266
Age
0-14	39(86.7)	6(13.3)	0.846(0.215-3.326)	0.811
15-29	45(66.2)	23(33.8)	2.811(0.866-9.129)	0.085	3.028(0.476-19.243)	0.240
30-44	61(81.3)	14(18.7)	1.262(0.375-4.248)	0.707
45-59	42(93.3)	3(6.7)	0.393(0.081-1.914)	0.247
>60	22(84.6)	4(15.4)	1
Education background
Illiterate	62(75.6)	20(24.4)	1.463(0.442-4.820)	0.553
Read and write only	66(86.8)	10(13.2)	0.644(0.180-2.307)	0.499
Up to grades 8 complete	51(82.3)	11(17.7)	0.917(0.258-3.262)	0.893
Up to grade 12complete	13(72.2)	5(27.8)	1.635(0.3657.360)	0.521
University/college &above	17(980.9)	4(19.1)	1
Residence
Urban	118(81.9)	26(18.1)	1
Rural	91(79.1)	24(20.9)	1.26(0.862-2.329)	0.459
Monthly income
Lower(<500EBR)	94(75.2)	31(24.8)	1.484(0.645-3.413)	0.353
Medium (5001-1000EBR)	69(85.2)	12(14.8)	1.111(0.449-2.751)	0.820
Higher(>1001EBE)	46(86.8)	7(13.2)	1
Pregnancy Status
Yes	6(50)	6(50)	3.72(1.104-12.533)	0.034	3.340 (0.786-14.109)	0.102
No	93(78.8)	25(21.2)	1
Diabetics (CDs)
yes	14(50)	14(50)	5.243(2.309-11.9)	0.000	1.751(0.472-6.494)	0.402
No	195((84.4)	36(15.6)	1
History of urinary tract obstruction
Yes	5(71.4)	2(28.6)	1.650(.312-8.756)	0.553
No	204(80.9)	48(19.1)	1
Previous exposure of antibiotics
Yes	65(63.72)	37(36.3)	5.814(2.9442-11.5)	0.000	4.427(1.214-16.146)	0.024
No	144(91.7)	13(8.3)	1
Recurrence urinary tract infection
yes	87(71.3)	35(28.7)	3.405(1.755-6.604)	0.000	1.023(0.311-3.363)	0.970
No	122(89.1)	15(10.9)	1
History of Renal calculi
Yes	16(72.7)	6(27.3)	1.651(0.611-0.226)	0.331
No	192(81.4)	44(18.6)	1
Use of Contraceptive Method
Yes	12(80)	3(20)	0.903(0.24-3.402)	0.880
No	112(78.3)	31(21.7)	1

Note: COR=Crude odd ratio, AOR=Adjusted odd ratio, CI=confidence interval, EBR=Ethiopian Birr.

Table 2. Bivariate and multivariate analyses of risk factors associated with Hospital acquired UTI among Dessie referral hospital UTI suspected patients in Dessie

Characteristics (n=422)	Negative N (%)	Positive N (%)	COR (95% CI)	P-Value	AOR (95%CI)	P-Value
Sex
Male	45(83.3)	9(16.7)	1
Female	68(62.4)	41(37.6)	3.015(1.336-6.803)	0.008	8.925(1.79-44.48)	0.008
Age
0-14	16(76.2)	5(23.8)	0.170(0.05-0.581)	0.005	0.332(0.045-2.456)	0.280
15-29	32(76.2)	10(23.8)	0.170(0.063-0.463)	0.001	0.126(0.020--0.792)	0.027
30-44	35(89.7)	4(10.3)	0.062(0.018- 0.218)	0.000	0.057(0.057-0.480)	0.008
45-59	18(66.7)	9(33.3)	0.273(0.094-0.791)	0.017	0.263(0.037-1.855)	0.180
>60	12(35.3)	22(64.7)	1
Education background
Illiterate	27(64.3)	15(35.70	1.29(0.291-5.766)	0.733
Read and write only	40(65.6)	21934.4)	1.225(0.287-5.233)	0.784
Up to grades 8 complete	35(79.5)	9(20.5)	0.600(0.129-2.794)	0.515
Up to grade 12complete	4(66.7)	2(33.3)	1.167(0.133-10.22)	0.889
University/college &above	7(70)	3(30)	1
Residence
Urban	67(71.3)	27(28.7)	1
Rural	46(63.0)	27(37)	1.710(0.874-3.374)	0.117	2.934(0.969-8.884)	0.057
Monthly income
Lower(<500EBR)	56(62.9)	33(37.1)	1.473(0.584-3.719)	0.412
Medium (5001-1000EBR)	37(80.4)	9(19.6)	0.608(0.203-1.821)	0.374
Higher(>1001EBE)	20 (71.4)	8(28.6)	1
Pregnancy Status
Yes	4 (50)	4(50)	2.39(0.538-10.612)	0.252
No	43 (70.5)	18(29.5)	1
Diabetics (CDs)
yes	15(34)	29(66)	9.002(4.130-19.71)	0.000	6.702(1.994-22.528)	0.002
No	98(82.4)	21(17.6)	1
History of urinary tract obstruction
Yes	12(36.3)	21(63.7)	6.095(2.082-13.85)	0.000	2.693(0.712-10.180)	0.144
No	101(77.7)	29(22.3)	1
Previous exposure of antibiotics
Yes	25(48.1)	27(51.9)	4.132(2.028-8.420)	0.000	5.689(1.840-17.590)	0.003
No	88(79.3)	23(20.7)	1
Recurrence urinary tract infection
yes	20(44.4)	25(55.6)	4.650(2.229-9.701)	0.000	1.616(0.499-5.226)	0.423
No	93(78.8)	25(21.2)	1
History of Renal calculi
Yes	22(28.3)	5(71.7)	6.167(1.154-32.956)	0.033	9.466(0.585-153.28)	0.114
No	111(71.2)	45(28.8)	1
Use of Contraceptive Method
Yes	4(100)	0(0)	0.000(0.000---)	0.999
No	66(70.2)	28(29.8)	1
Waiting time in hospital
48-72hours	458(0.4)	11(19.6)
>72 hours	68(63.6)	39(36.4)	2.346(1.089-5.056)	0.029	2.345(0.767-7.175)	0.135
History of catheterization
Yes	21(41.2)	30(58.8)	6.917(3.284-14.570)	0.000	3.886(1.323-11.47)	0.014
No	92(82.1)	20(17.9)	1
Duration of catheterization
<one week	8(53.3)	7(46.7)	1
>one week	13(34.2)	25(65.8)	2.198(0.652-7.413)	0.204

Note: COR=Crude odd ratio, AOR=Adjusted odd ratio, CI=confidence interval, EBR=Ethiopian Birr

The predominant bacteria isolates in both community and hospital acquired UTI were E. coli 52% (26/50) versus 33.96% (18/53) followed by S. aureus 24% ( 12/50) Vs 24.5 % (13/53), CONs 16% (8/53) Vs11.32% (6/53), klebsiella spp 4%(2/50) Vs 9.43% (5/53), Proetus spps 2% (1/50) Vs 5.7%(3/53),and Enterococcus spps 2%(1/50) Vs 3.8%(2/53) were isolated in both study groups whereas Pseudomonas spp 5.7%(3/53),Citrobacter spp 3.8%(2/53) and Acinetobacter spps 1.79% (1/53) were isolated only hospitalized patients (Table-5).

Table 3. Distribution of culture among community versus hospital- acquired UTI groups of patients at Dessie referral hospital Dessie.

UTI Types	Urine cultured	Cultured Positive cases	Percentage	X²	P
CAUTI	259	50	19.3	6.537	0.011
HAUTI	163	50	30.7
Total	422	100	23.7

Note: (by chi-squire, X ²=6.537, df=1, P=0.011), HAUTI= Hospital Acquired UTI, CAUTI= Community acquired UTI

In the two study groups, females were more affected than a male to female ratio of 0.505:1 and 0.495:1 and the rate of isolation was highest in patients >60 years and those between 15 and 29 among HAUTI patients and CAUTI patients respectively. Among hospital acquired UTI patients and community acquired UTI patients, significant bacteriuria was detected in 64.7% (22/36) Vs 15.4% (4/26) of patients > 60 years and 33.8% (23/68) Vs 23.8% of patients between 15 and 29 years (Table-6).

Table 4. Results of growth in culture among in study cases at Dessie referral hospital, Dessie.

Growth	Number	%
Single growth	97	22.99
Mixed growth	3	0.71
Total growth	100	23.7
Insignificant growth	9	2.13
No growth	313	74.17

Key: 3 mixed growth yield total 6 bacteria

Table 5. Distribution of bacterial isolated among CAUTI and HAUTI at Dessie referral hospital Dessie.

Isolated Organism	Type of UTI
	CAUTI(n=50)		HAUTI (n=53)		Total
	Male	Female	Male	Female
Escherichia coli	5(19.2)	21(80.8)	4(22.2)	14((77.8)	44(42.72)
S. aureus	3(25)	9(75)	3(23)	10(77)	25((24.27)
CONS	1(12.5)	7(87.5)	1(16.7)	5(83.3)	14(13.6)
Klebsiella Spps	1(50)	1(50)	1(20)	4(80)	7(6.78)
Proteus Spps	0(0)	1(100)	0(0)	3(100)	4(3.88)
Enterococcus Spps	0(0)	1(100)	0(0)	2(100)	3(2.91)
Pseudomonas Spps	0(0)	0(0)	0(0)	3(100)	3(2.91)
Citrobacter Spps	0(0)	0(0)	0(0)	2(100)	2(1.94)
Acinetobacter Spps	0(0)	0(0)	0(0)	1(100)	1(0.99)
Total	10(20)	40(80)	9(17)	44((83)	103(100)

Note: CONs= Coagulase negative staphylococcus, HAUTI= Hospital Acquired UTI, CAUTI= Community acquired UTI

Table 6. Showing age and sex distribution among the culture positive isolates of both study group at Dessie referral hospital, Dessie.

Age	CAUTI			HAUTI
Age	Male	Female	Total	Male	Female	Total
0-14	3	3	6	1	4	5
15-29	2	21	23	0	11	11
30-44	1	13	14	0	4	4
45-59	2	1	3	1	8	9
>60	2	2	4	7	17	24
Total	10	40	50	9	44	53

Note: HAUTI= Hospital Acquired UTI, CAUTI= Community acquired UTI

Frequency of isolated bacteria increases duration of catheterization E. coli, S. aureus, CONs, Pseudomonas spps, Klebsiella spps and Enterococcus spps were increased after one-week catheterization, However, Proteus spps, Citrobacter spps and Acinetobacter spps were found only more than one-week catheterization (Table-7).

Table 7. Distribution of isolates varies in the duration of Catheterization at Dessie referral hospital, Dessie.

Type of Isolate	Duration of Catheterization
Type of Isolate	<one week n (%)	>one week n (%)	Total n (%)
Escherichia coli	1(10)	9(90)	10(100)
Staphylococcus aureus	2(25)	6(75)	8(100)
CONS	1(33.3)	2(66.7)	3(100)
Pseudomonas spps	1(33.3)	2(66.7)	3(100)
Proteus spps	0(0)	2(100)	2(100)
Klebsiella spps	1(33.3)	2(66.7)	3(100)
Enterococcus spp	1(50)	1(50)	2(100)
Citrobacter spps	0(0)	2(100)	2(100)
Acinetobacter spps	0(0)	1(100)	1(100)
Total	7(20.58)	2(79.42)	34(100)

Note: CONs- Coagulase Negative staphylococcus

Risk factors of community and hospital acquired urinary tract infection

In Bivariate and multivariate analysis of CAUTI study subject, previous usage of antibiotics were 4.427 times more likely to have developed urinary tract infection when compared with non-user antibiotics (AOR=4.427; CI,1.214-16.146, P=0.024). However, there was no association among other characteristics like sex, age, pregnancy, chronic disease and recurrence urinary tract infection (P value >0.05).

The prevalence of bacteria significantly differs from inpatient 53/163(30.7%) to outpatient, 50/259(19.3%) UTIs. (X²=6.537, OR=1.753, CI:1.175-2.912, P=0.011). Those individuals who were inpatient were 1.753 times more likely exposed to develop HAUTI as 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:1.790-44.480,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. In addition, Individuals with diabetic disease were 6.702 times more likely to have increased developing UTI as compared with individuals who were not with Diabetic (AOR= 6.702; CI,1.994-22.528, P=0.002).

Besides these, usage of prolonged antibiotics were 5.689 times more likely to have developed urinary tract infection when compared with non-user antibiotics (AOR=5.689; CI.1.840-17.590, P=0.003). Moreover, those patients who used catheter were 3.886 times more likely to have increased developing UTI as compared with those patients who were not used catheter, (AOR= 3.886; CI,1.323-11.47, P=0.014). However, there was no association among other characteristics like ages 0-14 years and 45-59 years, recurrence urinary tract infection, history of urinary tract obstruction, history of renal calculi, waiting time in hospital and duration of catheterization (P value >0.05) (Table1 & 2).

Antimicrobial susceptibility of community and hospital acquired urinary tract infection

The resistance patterns of 103 bacterial uropathogens isolated were tested against 15 antimicrobial agents (Table 10). In this study, the highest degree of resistance among the 15 antimicrobials were observed in different bacterial isolates. klebsiella spps was resistance to 100% for Ampicillin and 80% Augmentin in hospital acquired and Tetracycline in community acquired UTI. Ampicillin, Tetracycline and cotrimoxazole were resisted 100% by Proetus spps in both study groups and Augmentin was 100% resisted in community acquired UTI as well. Citrobacter spps was 100% resistance to Augmentin, Tetracycline, Cotrimoxazole and ceftriaxone. Acinetobacter spps was 100% resistance to Tetracycline in hospital acquired UTI. Penicillin and Ampicillin were 100% resisted by Entrococcus spps in Community Acquired urinary tract infections.

(83.3%) and (76.9%) of E. coli isolates were resist for ampicillin in hospital and community acquired urinary tract infection respectively. 83.3% Vs 37.5, 83.3 Vs 37.5 and 83.3% Vs 50% of CONs isolates in hospital and community acquired urinary tract infection resist for Penicillin, cotrimoxazole and tetracycline respectively. 80% Vs 50% and 80% Vs 100% Augmentin and tetracycline were resisted by Klebsiella spps in hospital and community acquired urinary tract infections respectively (Table 8 &9).

E. coli, Proetus spps and Klebsiella spps were susceptible to 100% for meropenem in both community and hospital acquired urinary tract infections and Citrobacter spps, Pseudomonas Spps and Acinetobacter spps were susceptible to 100% for meropenem in hospital acquired urinary tract infection. Even though the sample size is too small, Proteus spps, Klebsella spps, Citrobacter spps and Entrococcus spps were susceptible to 100% for Nitrofurantoin. Meropenem was the most sensitive drug 100% for both types of urinary tract infection (Table-8&9).

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 infection respectively. The 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. All 4 isolates of Proetus Spp were 100% MDR three of them in hospital acquired and the rest community acquired the scenario was observed also in Klebsiella spps. Moreover, S. aureus MDR was higher proportion in hospital acquired cases than community acquired cases. In this study antibiotic profile, Except Penicillin, one S. aureus isolate resist all antimicrobials in hospital acquired urinary tract infections (Table -10).

Table 8. Antimicrobial susceptibility pattern of Hospital acquired urinary tract infection at Dessie Referral Hospital, Dessie.

Antibiotic	*E. coli* (n=18)	*Proteus* Spp (n=03)	*Klebsella* spps (n=5)	*Citrobacter* spps (n=2)	*Pseudomonas* spps (n=3)	*Enterococcus* spps (n=2)	*Acetobacter* spps (n=1)	*S.aureus* (n=13)	CONS (n=6)	Total N (%)
Ampicillin (n=30)
S	1(5.6)	0(0)	0(0)	0(0)	NA	1(50)	NA	NA	NA	2(6.7)
I	2(11.1)	0(0)	0(0)	0(0)	NA	0(0)	NA	NA	NA	2(6.7)
R	15(83.3)	3(100)	5(100)	2(100)	NA	1(50)	NA	NA	NA	26(87)
Augmentin (n=28)
S	5(27.8)	1(33.3)	0(0)	0(0)	NA	NA	NA	NA	NA	6(21.4)
I	0(0)	0(0)	1(20)	0(0)	NA	NA	NA	NA	NA	1(3.6)
R	13(72.2)	2(66.7)	4(80)	2(100)	NA	NA	NA	NA	NA	21(75)
Nalidixic acid (n=28)
S	15(83.3)	3(100)	4(80)	1(50)	NA	NA	NA	NA	NA	23(82.1)
I	0(0)	0(0)	1(20)	1(50)	NA	NA	NA	NA	NA	2(7.1)
R	3(16.7)	0(0)	0(0)	0(0)	NA	NA	NA	NA	Na	3(10.8)
Tetracycline (n=50)
S	5(28.8)	0(0)	0(0)	0(0)	NA	0(0)	0(0)	2(15.4)	1(16.7)	8/50(16)
I	2(11.1)	0(0)	1(20)	0(0)	NA	0(0)	1(100)	2(15.4)	0(0)	6/50(12)
R	11(61.1)	3(100)	4(80)	2(100)	NA	2(100)	0(0)	9(69.2)	5(83.3)	36/50(72)
Meropenem (n=32)
S	18(100)	3(100)	5(100)	2(100)	3(100)	NA	1(100)	NA	NA	32(100)
I	0(0)	0(0)	0(0)	0(0)	0(0)	NA	0(0)	NA	NA	0(0)
R	0(0)	0(0)	0(0)	0(0)	0(0)	NA	0(0)	NA	NA	0(0)
Ciprofloxacillin (n=53)
S	12(66.7)	3(100)	3(60)	1(50)	0(0)	1(50)	1(100)	9(69.2)	3(50)	33(62.3)
I	0(0)	0(0)	1(20)	1(50)	1(33.3)	0(0)	0(0)	0(0)	1(16.7)	4(7.5)
R	6(33.7)	0(0)	1(20)	0(0)	2(66.7)	1(50)	0(0)	4(30.8)	2(33.3)	16(30.2)
Cotrimoxazole (n=48)
S	8(44.4)	0(0)	2(40)	0(0)	NA	NA	0(0)	5(38.5)	1(16.7)	16(33.3)
I	0(0)	0(0)	0(0)	0(0)	NA	NA	0(0)	0(0)	0(0)	0(0)
R	10(55.6)	3(100)	3(60)	2(100)	NA	NA	1(100)	8(61.5)	5(83.3)	32(66.7)
Gentamycin (n=51)
S	12(66.7)	1(33.3)	3(60)	1(50)	2(66.7)	NA	0(0)	10(76.9)	4(66.7)	33(64.7)
I	1(5.6)	0(0)	0(0)	1(50)	0(0)	NA	1(100)	1(7.7)	0(0)	4(7.8)
R	5(27.7)	2(66.7)	2(40)	0(0)	1(33.3)	NA	0(0)	2(15.4)	2(33.3)	14(27.5)
Ceftriaxone (n=29)
S	15(83.3)	2(66.7)	2(40)	0(0)	NA	NA	0(0)	NA	NA	19(65.5)
I	0(0)	0(0)	0(0)	0(0)	NA	NA	0(0)	NA	NA	0(0)
R	3(16.7)	1(33.3)	3(60)	2(100)	NA	NA	1(100)	NA	NA	10(34.5)
Cefixime (n=29)
S	12(66.7)	2(66.7)	4(80)	1(50)	NA	NA	0(0)	NA	NA	19(65.5)
I	0(0)	0(0)	0(0)	0(0)	NA	NA	1(100)	NA	NA	1(3.4)
R	6(33.3)	1(33.3)	1(20)	1(50)	NA	NA	0(0)	NA	NA	9(31.1)
Nitrofurantoin (n=49)
S	16(88.9)	3(100)	5(100)	2(100)	NA	2(100)	NA	9(69.2)	4(66.7)	41(83.7)
I	1(5.6)	0(0)	0(0)	0(0)	NA	0(0)	NA	0(0)	0(0)	1(2.0)
R	1(5.6)	0(0)	0(0)	0(0)	NA	0(0)	NA	4(30.8)	2(33.3)	7(14.3)
Tobramycin (n=4)
S	NA	NA	NA	NA	3(100)	NA	1(100)	NA	NA	4(100)
I	NA	NA	NA	NA	0(0)	NA	0(0)	NA	NA	0(0)
R	NA	NA	NA	NA	0(0)	NA	0(0)	NA	NA	0(0)
Piperacillin (n=3)
S	NA	NA	NA	NA	2(66.7)	NA	NA	NA	NA	2(66.7)
I	NA	NA	NA	NA	1(33.3)	NA	NA	NA	NA	1(33.3)
R	NA	NA	NA	NA	0(0)	NA	NA	NA	NA	0(0)
Penicillin (n=23)
S	NA	NA	NA	NA	2(66.7)	1(50)	NA	4(33.3)	1(16.7)	8(34.5)
I	NA	NA	NA	NA	1(33.3)	0(0)	NA	1(8.3)	0(0)	2(8.7)
R	NA	NA	NA	NA	0(0)	1(50)	NA	7(58.3)	5(83.3)	13(56.8)
Vancomycin (n=2)
S	NA	NA	NA	NA	NA	2(100)	NA	NA	NA	2(100)
I	NA	NA	NA	NA	NA	0(0)	NA	NA	NA	0(0)
R	NA	NA	NA	NA		0(0)	NA	NA	NA	0(0)

KEY: NA= Not Applicable

Table 9. Antimicrobial susceptibility pattern of Community acquired urinary tract infection at Dessie Referral Hospital, Dessie.

Antibiotic	E.coli (n=26)	Proteus Spp (n=1)	Klebsella Spp (n=2)	Enterococcus Spps (n= 1)	S. aureus (n=12)	CONS (n=8)	Total N (%)
Ampicillin
S	5(19.2)	0(0)	0(0)	0(0)	NA	NA	5(16.7)
I	1(3.8)	0(0)	0(0)	0(0)	NA	NA	1(3.3)
R	20(76.9)	1(100)	2(100)	1(100)	NA	NA	24(80)
Amox-clavunic acid
S	11(42.3)	0(0)	1(50)	NA	NA	NA	12(41.4)
I	1(3.8)	0(0)	0(0)	NA	NA	NA	1(3.4)
R	14(53.8)	1(100)	1(50)	NA	NA	NA	16(55.5)
Nalidixic acid
S	18(69.2)	1(100)	1(50)	NA	NA	NA	20(68.9)
I	0(0)	0(0)	0(0)	NA	NA	NA	0(0)
R	8(30.8)	0(0)	1(50)	NA	NA	NA	9(31)
Tetracycline
S	9(34.5)	0(0)	0(0)	0(0)	1(8.3)	3(37.5)	13(26)
I	0(0)	0(0)	0(0)	0(0)	3(25)	1(12.5)	4(8)
R	17(65.4)	1(100)	2(100)	1(100)	8(66.7)	4(50)	33(66)
Meropenem
S	26(100)	1(100)	1(100)	NA	NA	NA	28(100)
I	0(0)	0(0)	0(0)	NA	NA	NA	0(0)
R	0(0)	0(0)	0(0)	NA	NA	NA	0(0)
Ciprofloxacillin
S	24(92.3)	1(100)	1(50)	1(100)	8(66.7)	6(75)	41(82)
I	1(3.8)	0(0)	NA	0(0)	0(0)	1(12.5)	2(4)
R	1(3.8)	0(0)	1(50)	0(0)	4(33.4)	1(12.5)	7(14)
Cotrimoxazole
S	12(46.2)	0(0)	1(50)	NA	5(41.7)	5(62.5)	23(46.9)
I	0(0)	0(0)	0	NA	1(8.3)	0(0)	1(2.0)
R	14(53.8)	1(100)	1(50)	NA	6(50)	3(37.5)	25(51.1)
Gentamycin
S	21(80.8)	0(0)	1(50)	NA	9(75)	7(87.5)	38(77.5)
I	1(3.8)	1(100)	0	NA	0(0)	0(0)	2(4.1)
R	4(15.4)	0(0)	1(50)	NA	3(25)	1(12.5)	9(18.4)
Ceftriaxone
S	21(80.8)	1(100)	1(50)	NA	NA	NA	23(79.2)
I	2(7.7)	0(0)	()	NA	NA	NA	2(6.9)
R	3(11.5)	0(0)	1(50)	NA	NA	NA	4(13.9)
Cefixime
S	22(84.6)	1(100)	1(50)	NA	NA	NA	24(82.8)
I	1(3.8)	0(0)	0	NA	NA	NA	1(3.4)
R	3(11.5)	0(0)	1(50)	NA	NA	NA	4(13.8)
Nitrofurantoin
S	25(96.2)	1(100)	2(100)	1(100)	12(100)	7(87.5)	48(96)
I	1(3.8)	0(0)	0(0)	0(0)	0(0)	1(12.5)	2(4)
R	0(0)	0(0)	0(0)	0(0)	0(0)	0(0)	0(0)
Penicillin
S	NA	NA	NA	0(0)	7(58.3)	5(62.5)	12(60)
I	NA	NA	NA	0(0)	1(8.3)	0(0)	1(8.3)
R	NA	NA	NA	1(100)	4(33.3)	3(37.5)	7(31.7)
Vancomycin
S	NA	NA	NA	0(0)	NA	NA	0(0)
I	NA	NA	NA	1(100)	NA	NA	1(100)
R	NA	NA	NA	0(0)	NA	NA	0(0)

KEY: NA= Not Applicable

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 infection respectively. The 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. All 4 isolates of Proetus Spp were 100% MDR three of them in hospital acquired and the rest community acquired the scenario was observed also in Klebsiella spps. Moreover, S. aureus MDR was higher proportion in hospital acquired cases than community acquired cases in this study antibiotic profile, Except Penicillin, one S. aureus isolate resist all antimicrobials in hospital acquired urinary tract infections (Table -10).

Table 10. Multi drug resistance pattern of community and hospital acquired bacterial isolates among Dessie referral hospital UTI suspected patients at Dessie, March-April, 2019

Isolates	Community Acquired Isolates		Hospital Acquired Isolates (n=53)
Isolates	Antimicrobial Agents	N (%)	Antimicrobial agents	N (%)
E. coli (18)-IPD E. coli (26)-OPD	AMOX-CLAV, SXT, CXM	1(3.85)	AMP, AMOX-CLA, GEN	1(5.56)
	AMP, AMOX-CLAV, SXT, CTR	1(3.85)	AMP, AMOX-CLAV, TET, SXT, CXM	1(5.56
	NAL, SXT, CTR	1(3.85)	AMOX-CLAV, SXT, CXM	1(5.56)
	AMP, AMOX-CLAV, TET	2(3.85)	AMP, AMOX-CLAV, TET CPRSXT, CXM	1(5.56)
	AMP, AMOX-CLAV, TET, SXT	4(3.85)	AMP AMOX-CLAV CPR GEN, NIT	1(5.56)
	TET, SXT, GEN	1(3.85)	AMP, TET, CPR	1(5.56)
	AMP, AMOX-CLAV NAL, TET, GEN	1(3.85)	AMP, NAL, TET	1(5.56)
	AMP, NAL, TET	1(3.85)	AMP, TET, CPR, SXT, CTR	2(5.56)
	AMP, AMOX-CLA, NAL TET, SXT	2(3.85)	AMP, AMOX-CLAV, CPR	1(5.56)
	AMP, AMOX-CLAV NAL, SXT	1(3.85)	AMP AMOX-CLAV, SXT	1(5.56)
	AMP, TET, SXT	1(3.85)
	AMP, TET, SXT, GEN	1(3.85)
	AMOX-CLAV, SXT	1(3.85)
Total		18(69.2)		11(61.1)
Proetus Spp (3)-IPD Proteus spps(1)-OPD	AMP, AMOX-CLAV, TET, SXT	1(100)	AMP, TET, SXT, GEN	1(33.3)
			AMP, AMOX-CLAV, TET SXT	1(33.33)
			AMP, AMOX-CLAV, TET, SXT, GEN, CTR	1(33.33)
Total		1(100)		3(100)
Klebsiella Spp (5)-IPD Klebsiella Spp (2)- OPD	AMP, NAL, TET, SXT, GEN, CTR	1(50)	AMP, AMOX-CLAV, TET	1(20)
	AMP, AMOX-CLAV NAL, TET, CPR	1(50)	AMP, AMOX-CLV SXT, GEN, CTR	1(20)
			AMP, AMOX-CLAV, TET, CTR	1(20)
			AMP, NAL, TET, CPR, SXT, CTR	1(20)
			AMP, AMOX-CLAV, SXT	1(20)
Total		2(100)		5(100)
Citrobacter Spp (2)			AMOX-CLAV, AMP, NAL, SXT, GEN, CTR	1(50)
Citrobacter Spp (2)			AMP, AMOX-CLAV, TET, SXT, CTR	1(50)
Total				2(100)
S. aureus (13)-IPD S. aureus (12)-OPD			TET, SXT, PEN	3(7.7)
S. aureus (13)-IPD S. aureus (12)-OPD	TET, CPR, PEN, GEN	1(8.3)	TET, CPR, SXT, GEN, NIT	1(7.7)
	TET, CPR, SXT, PEN	1(8.3)	TET, CPR, SXT, PEN	1(7.7)
			CPR, SXT, PEN	1(7.7)
			TET, PEN, NIT	1(7.7)
Total		2(16.6)		7(53.9)
CONS (6)-IPD CONS (8)-OPD	TET, CPR, SXT	1(12.5)	TET, PEN, GEN, CPR	1(16.6)
	TET, PEN, GEN	1(12.5)	TET, SXT, PEN	1(16.6)
			TET SXT, GEN	1(16.6)
			TET, CPR, SXT, PEN, GEN	1(16.6)
Total		2(25)		4(66.7)

Note: IPD= inpatient, OPD= outpatient Department, CONs= Coagulase negative staphylococcus, AMP=Ampicillin, TET=Tetracycline, PEN=Penicillin, GEN=Gentamycin, CPR=Ciprofloxacillin, SXT=Ssulphamethoxazole-trimethoprime, NIT =Nitrofurantoin=CTR=Ceftriaxone, CXM=Cefixime,

Urinary tract infection is the most common problem throughout the world, both in developed and developing countries. Findings of this study revealed that, overall prevalence rate of UTI was slightly high, and hospital acquired UTI 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. This study has showed that the alarming level of resistance (Ampicillin) achieved by bacteria involved in causing UTI. E. coli and Various isolates were more sensitive to meropenem and nitrofurantoin compared to other antibiotics tested. The presence of catheter in the urinary tract, Diabetic mellitus, previous use of antibiotics, female gender, age, patient setting, were identified as risk factors for acquired UTI.

Keeping the emerging antimicrobial resistance in mind, antibiotics should be used after doing a routine microscopy and microbiology culture of urine in order to inhibit acquisition and spread of drug resistance by the bacteria. By knowing the resistance rate differences in both settings, clinicians should be considered while treating patients who present with urinary tract symptoms and awaiting culture reports. The health care police should be discouraging inappropriate use of antibiotics and prevent further development of resistant strains among bacteria. A continual audit of antimicrobial susceptibility patterns among 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 community members in order to prevent risk factors associated with the infection. Anaerobic bacteria need to be isolated to know the responsibility of causing UTI. 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 health care benefits.

This study did not consider anaerobic bacteria and few bacterial isolates were not identified at a species level that cause of UTI due to lack of facility. Our study limitation was using only antibiotics disks diffusion method to perform antimicrobial susceptibility instead of micro-dilution method, which makes more sensitive.

ATCC

American Type Culture Collection, CAUTI:Community Acquired Urinary Tract Infection. CFU:Colony Forming Unit, CLSI:Clinical and Laboratory Standard Institute, CONS:Coagulase- Negative Staphylococci, HAUTI:Hospital Acquired Urinary Tract Infection, HCWs:Health Care Workers, HPF:High Power Field, IPD:Inpatient Department, OPD:Out Patient Department, SOP:Standard Operating Procedure, SPSS:Statistical Package For Social Sciences, UTI:Urinary Tract Infection, WHO:World Health Organization.

Ethical considerations

Ethical clearance was obtained from School of Biomedical and Laboratory Sciences, University of Gondar ethical review committee and a letter informing to Dessie Referral Hospital Dessie about the purpose of the study and permission was obtained from Dessie Referral Hospital to access data from study population. 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 as 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 sample obtained from them was kept confidential by using codes instead of any personal identifiers and is meant only for the purpose of the study. For those study participants who were positive, we advised to go to the health institution to consult the clinicians for medical treatment and treated with the respective antibiotics.

Consent for publication

All authors read the manuscript and have provided their consent to publish. All authors declare no conflict of interests

Availability of data and materials

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

Competing interests

The authors declare that they have no competing interests.

Funding Statement

This study was fully granted by University of Gondar.

Authors' contributions

BA: conceptualized the study, contributed to the format of the data collection instruments, contributed to the study protocol, development of the data collection tools field data collection and analysis. MJ and BS: participated in the pre-test, supervised the actual data collection process, enter the data significantly contribute in the analysis part. All authors participated in the data analysis, interpretation, and development of the manuscript. All authors read and approved the final manuscript.

Acknowledgements

Authors of this article would like to acknowledge University of Gondar Department of Medical Laboratory Sciences, Amhara Regional Health Bureau. Further, all study participants, data collectors, and Amhara public health institute and Dessie referral hospital are highly acknowledged.

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Bacterial profile, antimicrobial susceptibility pattern and associated factors of community and hospital acquired urinary tract infection at Dessie referral hospital, Dessie, Northeast Ethiopia

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