BioMed Research International
Volume 2018 (2018), Article ID 4536905, 13 pages
https://doi.org/10.1155/2018/4536905

Review Article

Drug Resistance Patterns of Escherichia coli in Ethiopia: A Meta-Analysis

Kald Beshir Tuem,¹ Abadi Kahsu Gebre,¹ Tesfay Mehari Atey,² Helen Bitew,³ Ebrahim M. Yimer,¹ and Derbew Fikadu Berhe¹

¹Department of Pharmacology and Toxicology, School of Pharmacy, College of Health Sciences, Mekelle University, Mekelle, Ethiopia
²Clinical Pharmacy Unit, School of Pharmacy, College of Health Sciences, Mekelle University, Mekelle, Ethiopia
³Department of Pharmacognosy, School of Pharmacy, College of Health Sciences, Mekelle University, Mekelle, Ethiopia

Correspondence should be addressed to Kald Beshir Tuem; kalizad2003@gmail.com

Received 20 December 2017; Revised 14 March 2018; Accepted 20 March 2018; Published 6 May 2018

Academic Editor: Giovanni Mariscalco

Copyright © 2018 Kald Beshir Tuem et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract.

Background. Antimicrobial drug resistance is a global threat for treatment of infectious diseases and costs life and money and threatens health delivery system’s effectiveness. The resistance of E. coli to frequently utilized antimicrobial drugs is becoming a major challenge in Ethiopia. However, there is no inclusive countrywide study. Therefore, this study intended to assess the prevalence of E. coli resistance and antimicrobial-specific resistance pattern among E. coli clinical isolates in Ethiopia. Methods. Articles were retrieved from PubMed, Embase, and grey literature from 2007 to 2017. The main outcome measures were overall E. coli and drug-specific resistance patterns. A random-effects model was used to determine pooled prevalence with 95% confidence interval (CI), using DerSimonian and Laird method. In addition, subgroup analysis was conducted to improve the outcome. The study bias was assessed by Begg’s funnel plot. This study was registered in PROSPERO as follows: PROSPERO 2017: CRD42017070106. Results. Of 164 articles retrieved, 35 articles were included. A total of 19,235 study samples participated in the studies and 2,635 E. coli strains were isolated. Overall, E. coli antibacterial resistance was 45.38% (95% confidence interval (CI): 33.50 to 57.27). The resistance pattern ranges from 62.55% in Addis Ababa to 27.51% in Tigray region. The highest resistance of E. coli reported was to ampicillin (83.81%) and amoxicillin (75.79%), whereas only 13.55% of E. coli isolates showed resistance to nitrofurantoin. Conclusion. E. coli antimicrobial resistance remains high with disparities observed among regions. The bacterium was found to be highly resistant to aminopenicillins. The finding implies the need for effective prevention strategies for the E. coli drug resistance and calls for multifaceted approaches with full involvement of all stakeholders.

1. Background

Escherichia coli (E. coli) is one of the most widespread bacteria throughout the world. Some strains of E. coli can cause serious illness for humankind [1] including urinary tract infections [2–4], bloodstream infections [5], skin infection, otitis media [6, 7], and diarrhea [8].

E. coli resistance to antimicrobials is creating trouble to the healthcare system worldwide [9, 10]. This complicates treatment outcomes, increases the cost of treatment, and limits the therapeutic options that contribute to the global spectra of a postantimicrobial age in which some of the most effective drugs lose their efficiency [11]. The bacterium is becoming highly resistant to conventionally used antibiotics (to both the newer and older medicines) as evidenced by many previous studies [12–16]. Adaptive resistance was supposed to be the main mechanism for the development of resistance including that to lethal doses of the antimicrobials [17].

Antimicrobial resistance of E. coli in developing countries including Ethiopia is reported to be one major reason for failure of treatment of infectious diseases [18]. A number of studies conducted in Ethiopia from various clinical settings show increments in the prevalence of antimicrobial resistance patterns of E. coli [6, 19, 20]. However, there is no comprehensive and aggregated nationwide study to show the pattern of antimicrobial resistance in E. coli. Hence, the purpose of this meta-analysis was to sum up the available data and to establish the pooled prevalence and antimicrobial resistance of E. coli in Ethiopia.

2. Methods

This study was conducted in a similar approach to Eshetie et al. (2016) [21] and according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Checklist [22] (additional S1 file).

2.1. Study Selection

A systematic literature search was conducted in PubMed and Embase, and also manual search for articles potentially relevant to our study was identified. We built our search strategy by combining the three main arms (Table 1): E. coli, drugs-related terms, and Ethiopia.

Table 1: Searching strategies including search arm and terms used in the study.

Search arm
Search terms

1
E. coli
“Escherichia coli” OR “E. coli”

2
Drug and/or resistance
“antibiotic resistance” OR “drug resistance” OR “drug resistance, microbial” OR “drug resistance, microbial” OR “antibacterial resistance” OR “antibiotic resistance” OR “antimicrobial resistance”

3
Ethiopia
“Ethiopia”

The word “OR” was used to combine search terms within each arm and the word “AND” was used to connect the three search arms (#1 AND #2 AND #3).

Among the citations extracted, abstracts were reviewed to retrieve the clinical studies on E. coli colonization. Articles that were relevant, by title and abstract, were accessed in full text to determine those that provided sufficient information to be included in our meta-analysis. Finally, the references cited by each eligible study were screened to identify additional articles.

2.2. Inclusion and Exclusion Criteria

Studies included in this meta-analysis were those that had extractable data on the prevalence of drug resistance of E. coli on a human in Ethiopian hospitals or research centers and were only published from 2007 to 2017 and were only in English language.

2.3. Outcome of Interest

The main outcome of interest was the prevalence of drug resistance or antimicrobial susceptibility of E. coli among the total E. coli clinical isolates. The prevalence was calculated by dividing the numbers of resistant E. coli isolates by the total number of clinically isolated E. coli. As a secondary outcome of interest, we had also calculated the pooled resistance pattern of E. coli isolates to specific antibiotics.

2.4. Data Extraction and Assessment of Quality of Study

Screening by title, abstract, and full text and data extraction were done independently by two authors (Kald Beshir Tuem and Abadi Kahsu Gebre) at each step and Derbew Fikadu Berhe was involved in consensus for discrepancies (if any) between the two authors (Kald Beshir Tuem and Abadi Kahsu Gebre). In cases of insufficient data, the authors reviewed the full text of the article for further information and clarification. The extracted data from each article were summarized into a spreadsheet. References and data for each study were carefully cross-checked to ensure that no overlapping data were present and to maintain the integrity of the meta-analysis. Information extracted from each paper was region, study area, study design, study population, culture specimens, number of E. coli isolated, the average percentage of resistant E. coli, antimicrobial resistance rate of E. coli, and references. With all the articles used in this study being cross-sectional, the score for the quality of the study was assessed using the modified Newcastle-Ottawa scale for the representativeness of sample, appropriateness of sample size, response rate, validity of method, strategy to control confounding factors, reliability of outcome determination, and appropriate statistical analyses. The quality score (Table 2) disagreements were resolved by consensus and a final agreed-upon rating was assigned to each study (S2 file) [58].

Table 2: Summary of 35 studies reporting the prevalence and resistance pattern of E. coli in different parts of Ethiopia.

References
Region
Study area
Study period
Study design
Study population
Culture specimens
Study samples
Number of E. coli isolated
Average %resistant E. coli
NOS quality score out of 7

Abejew et al., 2014 [23]
Amhara
Dessie
January to March 2012
RCS
Test results of patients diagnosed with UTI
Urine
2486
410
51.8
6

Kibret and Abera, 2014 [24]
Dessie
—
R
Patients
Mid-stream morning urine
1404
203
53.2
6

Kibret and Abera, 2011 [25]
Dessie
—
R
Patients
Urine, ear discharge, pus swab from wounds, and eye discharge
3,149
446
44.2
6

Azene and Beyene, 2011 [26]
Dessie
—
R
Patents with wound infections
Wound swab
599
82
49.8
6

Alebachew et al., 2016 [27]
Gondar
March 1 to May 2, 2013
CS
HIV patients
Blood
100
01
44.4
7

Alemu et al., 2012 [28]
Gondar
March 22 to April 30, 2011
CS
Pregnant women attending ANC
Urine
385
19
29.2
7

Wondimeneh et al., 2014 [29]
Gondar
January to May 2013
CS
Fistula patients
“Clean-catch” mid-stream urine specimen
53
6
59.3
6

Wondimu et al., 2013 [30]
Gondar
December 2011 to June 2012
CS
Blood donated from donors at blood bank
blood
137
2
0.7
7

Eshetie et al., 2015 [31]
Gondar
February to May 2014
CS
UTI-suspected patients
Urine
442
112
48.0
4

Tiruneh et al., 2014 [32]
Gondar
September 1, 2011, to June 30, 2012
CS
UTI-suspected patients
Urine
284
120
68.0
4

Eshetie et al., 2016 [33]
Gondar
February to June 2014
CS
Patients with UTI
Urine
446
112
38.8
6

Mulu et al., 2017 [34]
Debre Markos
January 2015
R
Patients
Pus/swab from wound, urine, ear discharge, blood, stool, urethral or cervical discharge, nasal or throat swab, and CSF
575
39
31.5
6

Abera and Kibret, 2014 [35]
West Gojjam
November 2009 to February 2010
CS
Adult patients who underwent trachomatous trichiasis surgery
Conjunctival swabs
1413
20
26.5
5

Adugna et al., 2015 [36]
Bahir Dar
December 2011 to February 2012
CS
Children below five years of age with acute diarrhea
Stool sample
422
204
42.8
7

Demilie et al., 2012 [37]
Bahir Dar
October 2010 to January 2011
CS
Pregnant women
Clean-catch urine
367
16
41.7
4

Derbie et al., 2017 [38]
Bahir Dar
January 2015
R
Patients
Urine
446
72
55.3
5

Melaku et al., 2012 [39]
Bahir Dar
April to August 2010
CS
Patients
Urine
1254
33
87.8
6

Mulu et al., 2012 [40]
Bahir Dar
October 2010 to January 2011
CS
Patients
Wound swab and venous blood samples
294
8
53.1
6

Wondemagegn et al., 2015 [41]
Bahir Dar
May to November 2013
CS
Women of reproductive age
Vaginal swab
409
105
50.5
7

Dereje et al., 2017 [42]
Central Ethiopia
Addis Ababa
February to May 2015
CS
Fistula patients
Clean-catch mid-stream urine
210
65
38.2
7

Dessie et al., 2016 [43]
Addis Ababa
October 2013 and March 2014
CS
Surgical site infected patients
Wound swab
107
24
68.4
6

Desta et al., 2016 [44]
Addis Ababa
December 2012
CS
All age groups patients
Fecal samples/swabs
267
235
83.0
7

Mamuye, 2016 [45]
Addis Ababa
August 2013 to January 2014
CS
Outpatient and inpatient and pregnant women
Mid-urine samples
424
53
52.2
5

Legese et al., 2017 [46]
Addis Ababa
January to March 2014
CS
Septicemia and UTI-suspected patients
Blood and urine
322
6
72.9
6

Ramos et al., 2014 [47]
Oromia
West Arsi
July to December 2013
CS
Leprosy patients
Pus produced by ulcer
68
17
35.8
5

Derese et al., 2016 [48]
Dire Dawa
February 18, 2015, to March 25, 2015
CS
Pregnant women
Urine specimens
186
9
34.4
6

Beyene and Tsegaye, 2011 [49]
Jimma
April to June 2010
CS
UTI cases patients
Urine
228
7
27.1
5

Debalke et al., 2014 [50]
Jimma
September to December 2012
CS
HIV/AIDS patients
Urine
481
31
36.6
7

Mama et al., 2014 [51]
Jimma
May to September 2013
CS
Patients with wound infection
Wound swab
150
29
61.6
6

Mulualem, 2012 [52]
Jimma
February to March 2007
CS
Inpatients and outpatients
Urine, sputum, stool, and wound
359
67
45.7
6

Zenebe et al., 2011 [53]
Jimma
October 27, 2009, to March 26, 2010
CS
Febrile patients
Venous blood
260
4
25.0
6

Nigussie and Amsalu, 2017 [54]
SNNP
Hawassa
June to October 2014
CS
Diabetic patients
Mid-stream urine
240
11
47.7
7

Amsalu et al., 2016 [55]
Hawassa
January 2012 to December 2014
RCS
Patients registered at microbiology lab book
Pus, ear discharge, nasal swab, urine, genital swab, CSF, and stool
510
35
64.0
7

Tadesse et al., 2014 [56]
Hawassa
March to September 2012
CS
Pregnant women attending ANC
Mid-stream urine
244
16
56.3
6

Wasihun et al., 2015 [57]
Tigray
Mekelle
March to October 2014
PCS
Febrile patients
Venous blood
514
16
27.5
6

Total
19,235
2,635

ANC: antenatal clinic, CSF: cerebrospinal fluid, CS: cross-sectional, PCS: prospective cross-sectional, R: retrospective review of culture, RCS: retrospective cross-sectional, SNNP: Southern Nations, Nationalities, and Peoples, UTI: urinary tract infection, —: no data.

2.5. Quality Control

The quality of eligible studies was checked independently by two authors (Kald Beshir Tuem and Abadi Kahsu Gebre) using a set of predetermined criteria such as research design quality of paper, completeness of extractable information, and employed methods for E. coli isolation. The study bias was measured by Begg’s funnel plot [59]. This study was registered in PROSPERO as follows: PROSPERO 2017: CRD42017070106.

2.6. Data Analysis

A random-effects model was used to determine pooled prevalence, subgroup analysis, and 95% confidence interval (CI) by employing the approach of DerSimonian and Laird [60]. Variances and CIs were stabilized using Freeman-Tukey arc-sine methodology [61]; the reason is that using the standard approach of inverse variance method to calculate pooled prevalence does not work well in meta-analysis of single-arm study because, for studies with small or large prevalence, the inverse variance method causes the variance to become small and the calculated CI may be outside of the range [62]. Heterogeneity of study results was assessed using test and significant heterogeneity was considered at and [60, 63]. Statistical analyses were performed using Open Meta-Analyst (version 3.13) and Comprehensive Meta-Analysis (version 3.1). In addition, we performed subgroup analyses according to the region of the country and the mechanism of action of the tested drugs to improve the specificity of the assessment.

3. Results

From Embase, PubMed, and manual searching, we found 164 potentially relevant studies, of which 35 were included for analysis (Figure 1).

Figure 1: Flowchart shows selected articles for meta-analysis.

The study design of all included articles (35) was cross-sectional study. In these studies, a total of 19,235 study samples participated, from which 2,635 E. coli strains were isolated. The published studies were from four regions in Ethiopia (Table 2) which include the federal capital city of Ethiopia, Addis Ababa. No report was obtained from other regions in the country (Afar, Benishangul-Gumuz, Gambella, and Somali). Most of the studies indicated that various specimens had been utilized for screening of E. coli; particularly multisite swabbing was performed from different parts of the body, including skin, nasal, eye, ear, urethra, throat, vagina, or genital area (Table 2), and other biological fluids like blood, urine, pus, stool, and cerebrospinal fluid (CSF) were taken for test. A total of 2,635 E. coli strains were isolated from these various sites. The lowest and highest proportions of E. coli resistance were reported, respectively, from Bahir Dar (55.20%) and Mekelle (27.50%) cities. The average prevalence of E. coli resistance was also noted in different regions of Ethiopia; Addis Ababa region was ranked first (62.55%, 95% CI: 38.28–6.83%), followed by Southern Nations, Nationalities, and Peoples of Ethiopia (58.14%, 95% CI: 48.69–67.58%), Amhara (47.83%, 95% CI: 39.77–55.89%), and Oromia (42.86%, 95% CI: 32.77–52.95%), whereas relatively low magnitude of E. coli resistance was reported from Tigray region (27.51%, 95% CI: 16.14–38.88%) (Figures 2 and 3).

Figure 2: Proportion of E. coli resistance in different regions of Ethiopia, 2007–2017. Values in parenthesis indicated 95% CI of E. coli resistance in different regions of Ethiopia.

Figure 3: Subgroup analysis of E. coli antibacterial resistance according to regions of Ethiopia.

Subgroup analyses (Figure 3) were carried out based on the region (Addis Ababa, Amhara, Oromia, SNNP, and Tigray) and the mechanism of action of the drugs (cell wall synthesis inhibitors, protein synthesis inhibitors, DNA synthesis inhibitors, and antimetabolites). A paper-based analysis in our study showed that the overall E. coli resistance in Ethiopia was 48.87% (95% CI: 42.17–55.57%) with highest prevalence in the capital city, Addis Ababa, 62.55% (95% CI: 38.28–86.83%) (Figure 3).

As presented in Figure 4 and Table 3, the pooled prevalence of E. coli resistance was 45.38% (95% CI: 33.50–57.27%), and high resistance rates were observed to ampicillin, 83.81% (95% CI: 76.95–90.67%), amoxicillin, 75.79% (95% CI: 64.26–87.32%), tetracycline, 67.18% (95% CI: 58.89–75.47%), trimethoprim-sulfamethoxazole, 57.47% (95% CI: 58.89–75.47%), and cephalothin, 56.69% (95% CI: 33.74–79.64%). A relatively low level of nitrofurantoin resistance was observed, 13.55% (95% CI: 5.83–21.27%).

Table 3: Percentage of pooled antibacterial resistance rates of E. coli in Ethiopia, 2007–2017.

Studies
Antibacterial

AML
AMP
AMC
KF
CRO
TE
DO
C
E
CN
K
CIP
NA
F
NOR
SXT

Abejew et al., 2014 [23]
84.6
80.0
---
42.3
46.9
82.2
64.5
49.0
94.4
34.0
20.0
28.3
13.3
10.4
---
75.8

Abera and Kibret, 2014 [35]
---
---
---
---
40
25
---
35
---
40
---
4
---
---
---
15

Adugna et al., 2015 [36]
---
86.8
47.5
---
---
76
---
36.2
---
37.2
---
6.9
---
---
9.3
---

Alebachew et al., 2016 [27]
---
100
100
---
0
100
---
0
---
0
---
0
---
0
---
100

Alemu et al., 2012 [28]
100
100
36.8
---
0
52.6
---
0
---
5.3
---
0
---
---
0
26.3

Beyene and Tsegaye, 2011 [49]
100
100
---
---
0
28.6
---
0
---
0
---
14.3
0
0
---
28.6

Debalke et al., 2014 [50]
---
88
---
---
4
---
---
0
---
---
---
---
52
0
16
96

Demilie et al., 2012 [37]
75
81.7
37.5
---
---
68.8
---
37.5
---
31.2
18.8
18.8
43.8
6.3
25
56.2

Derbie et al., 2017 [38]
---
89.1
78.6
---
---
66.1
---
---
---
27.6
---
64.4
---
25
27
64.5

Dereje et al., 2017 [42]
---
---
21.6
---
24.6
---
---
32.2
---
53.8
---
56.9
---
40
---
---

Derese et al., 2016 [48]
77.8
77.8
---
---
0
66.7
---
11.1
---
0
---
11.1
44.4
44.4
---
11.1

Dessie et al., 2016 [43]
---
95.8
70.8
---
83.3
83.3
---
25
---
54.2
---
66.7
---
---
---
---

Desta et al., 2016 [44]
---
---
93
98
---
---
---
---
---
63
---
78
---
---
---
---

Eshetie et al., 2015 [31]
---
92.9
60.7
---
17.9
53.6
---
64.3
---
57.1
---
10.7
25
---
---
50

Kibret and Abera, 2014 [24]
87.3
---
---
56.9
33.9
80.1
61
37.4
93.7
24.5
---
34.1
---
3.8
---
72.1

Kibret and Abera, 2011 [25]
86
---
---
59.5
37.4
72.4
---
35.3
89.4
13
---
19.9
---
3.6
6.5
62.9

Azene and Beyene, 2011 [26]
85.0
---
---
64.7
66.7
71.4
33.3
36.1
51.9
14.4
---
7.7
---
---
---
67.1

Mama et al., 2014 [51]
---
100
---
100
62
79
44.8
65.5
---
51.7
---
34
41
---
44.8
55

Mamuye, 2016 [45]
75.5
79.2
---
32.1
45.3
83.0
71.7
30.2
---
22.6
---
54.7
73.6
20.8
67.9
22.6

Melaku et al., 2012 [39]
85.7
100
---
---
---
81.6
---
83.7
---
---
---
---
---
---
---
---

Mulu et al., 2017 [34]
25
33.3
---
---
3.3
75
75
13
0
69.6
---
18.2
---
---
23.1
11.1

Mulualem et al., 2012 [52]
86
86
70.1
---
9
73.1
---
35.8
---
3
---
20.9
---
---
16.4
56.7

Mulu et al., 2012 [40]
90
78
---
---
55.6
66.7
66.7
0
---
44.4
44.4
44.4
66.7
22.2
44.4
67

Nigussie and Amsalu, 2017 [54]
---
100
36.4
---
63.6
---
---
---
---
72.7
---
18.2
---
0
9.1
81.8

Ramos et al., 2014 [47]
64.7
70.6
5.9
---
5.9
41.2
29.4
35.3
41.2
11.8
---
29.4
---
---
---
58.8

Wasihun et al.2015 [57]
---
---
6.7
---
60
---
40
---
---
13.3
---
6.7
---
26.7
60
6.7

Wondimeneh et al., 2014 [29]
50
66.7
---
---
50
100
---
16.7
---
66.7
---
50
---
---
66.7
66.7

Wondimu et al., 2013 [30]
---
33.3
0
---
0
0
0
0
0
0
---
33.3
---
---
---
0

Zenebe et al., 2011 [53]
0
100
---
0
0
75
---
100
---
75
---
0
0
---
---
100

Amsalu1 et al., 2016 [54]
---
100
26.1
---
45.7
---
---
64.3
---
60.6
---
56.2
---
---
68.8
90

Tadesse et al., 2014 [56]
---
68.8
---
---
---
---
---
---
---
43.8
---
---
---
---
18.8
81.2

Tiruneh et al., 2014 [32]
87.5
83.3
---
---
---
79.2
---
58.3
---
44.2
---
46.7
---
---
---
76.7

Legese et al., 2017 [46]
100
---
100
---
---
83.3
---
66.7
---
66.7
---
---
---
0
66.7
100

Eshetie et al., 2016 [33]
---
98.2
42
---
---
43.8
---
54.5
---
52.7
---
0.9
17
---
---
64.3

Wondemagegn et al., 2015 [41]
80
73.3
---
---
---
73.3
---
---
---
26.7
---
20
---
---
20
60

AMC: amoxicillin-clavulanic acid, AML: amoxicillin, AMP: ampicillin, C: chloramphenicol, CIP: ciprofloxacin, CN: gentamicin, CRO: ceftriaxone, DO: doxycycline, E: erythromycin, F: nitrofurantoin, K: kanamycin, KF: cephalothin, NA: nalidixic acid, NOR: norfloxacin, SXT: trimethoprim/sulfamethoxazole, TE: tetracycline, ---: not done.

Figure 4: Forest plot of the pooled percentage and confidence interval of E. coli resistance to antibacterial drugs in Ethiopia from 2007 to 2017.

Comparing the prevalence of E. coli resistance among the antibacterial drugs, subgroup analysis (Figure 5) revealed that the cell wall synthesis inhibitors account for the greatest resistance percentage, 59.37% (95% CI: 36.21–82.53%), and DNA synthesis inhibitors account for the lowest resistance percentage, 26.14% (95% CI: 33.50–57.27%).

Figure 5: Subgroup analysis of pooled percentage and confidence interval of E. coli resistance to antibacterial drugs according to drug mechanism of action.

There was a high level of heterogeneity by random model methods (; ). Hence, the included studies have been conducted in different study settings, study periods, and study populations, which could have an effect on the heterogeneity of the included studies. The symmetry of funnel plot showed small study bias, which yielded insignificant effect.

4. Discussion

Antibiotic resistance continues to be a major global challenge in the management of bacterial infection. The trouble behind antibiotic resistance is highly marked in undeveloped or developing countries, including Ethiopia, where infectious diseases are highly prevalent [64]. Factors responsible for an increase in rates of antimicrobial resistance include misuse/overuse of antibiotics by healthcare professionals and general public and inadequate surveillance systems due to lack of reliable microbiological techniques leading to the inappropriate prescription of antibiotics [33]. Antimicrobial resistance in E. coli has increased worldwide and its susceptibility patterns show substantial variation in different geographical locations [5]. To date, the overall epidemiology and burden of multidrug resistance (MDR) bacteria have not been fully understood, especially in resource-limited countries including Ethiopia [64, 65]. To the best of our knowledge, this is the first meta-analysis study conducted to determine the pooled prevalence of E. coli prevalence and resistance in Ethiopia. Our result revealed that E. coli strains displayed diverse resistance patterns, with percentages varying slightly based on sample type and geographical distribution. Based on the tested antimicrobials, the overall E. coli resistance in Ethiopia was nearly 50% (45.38% (95% CI: 33.50–57.27%)).

Developing countries have comparatively higher risk factors associated with MDR strains than the developed ones [64, 66]. Resistance to antibacterial agents is a normal evolutionary process for microorganisms, but it is highly aggravated by continuous deployment of antimicrobial drugs in treating infections [67, 68]. It is claimed that more than half of drugs are prescribed, sold, or dispensed without following standard protocols, and the situation is more pronounced in developing countries including Ethiopia [69]. Sosa et al. (2010) reported that antibiotic usage in most of the low-income countries is generally unregulated, which is a prime factor for the occurrence of resistant bacterial strains [64]. This implies that antibiotics are being used widely and inappropriately in resource-limited countries including Ethiopia. This may lead to an increase in the occurrence of drug-resistive bacterial strains such as E. coli.

In our study, the regional prevalence of E. coli resistance was estimated, and the subgroup analysis showed that the highest prevalence of E. coli resistance (62.55%) was noted in Addis Ababa city, which was almost two times higher than Tigray region (27.51%). The observed variation might be due to differences in study location, hospital setup, and antimicrobial utilization.

Subgroup analysis also showed that E. coli strains exhibited higher resistance with cell wall inhibitors, specifically aminopenicillins (ampicillin and amoxicillin), followed by protein synthesis inhibitors, mainly to tetracycline, and lesser resistance prevalence to nitrofurantoin. In line with our data, globally, E. coli strains were reported to be highly resistant to the above-mentioned antibiotics, mainly to aminopenicillins [70, 71]. Săndulescu (2016) reported that E. coli showed low resistance to nitrofurantoin, which is in line with the present finding.

Moreover, our finding indicated the higher magnitude of E. coli resistance. This may imply the need for intervention in prescribing and using antibacterial against E. coli infections. Interventional strategies may include creating public awareness, maintaining hand hygiene, applying infection prevention protocols, and maintaining environmental sanitation, which are encouraged for preventing infection. In addition to these, promoting health education, maintaining continuous professional educations, and advocating rational prescribing habits are evidently effective in the minimization of the unwanted use of antibiotics, which in turn decrease selective pressure of resistant strains.

5. Conclusion

In this meta-analysis, the pooled E. coli resistance is considerably high. E. coli strains were highly resistant to ampicillin but showed lesser resistance to nitrofurantoin. Adopting safety protocols and implementing proper antibiotic prescription policies could be potential interventional strategies to address the emerging resistance of E. coli.

Abbreviation

ANC: | Antenatal clinic
AMC: | Amoxicillin-clavulanic acid
AML: | Amoxicillin
AMP: | Ampicillin
C: | Chloramphenicol
CI: | Confidence interval
CIP: | Ciprofloxacin
CN: | Gentamicin
CRO: | Ceftriaxone
CS: | Cross-sectional
CSF: | Cerebrospinal fluid
DO: | Doxycycline
E: | Erythromycin
E. coli: | Escherichia coli
F: | Nitrofurantoin
K: | Kanamycin
KF: | Cephalothin
MDR: | Multidrug resistance
NA: | Nalidixic acid
NOR: | Norfloxacin
PCS: | Prospective cross-sectional
R: | Retrospective review of culture
RCS: | Retrospective cross-sectional
SNNP: | Southern Nations, Nationalities, and Peoples
SXT: | Trimethoprim/sulfamethoxazole
TE: | Tetracycline
UTI: | Urinary tract infection.

Ethical Approval

Ethical clearance was not required and was not necessary for this study.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

Authors’ Contributions

Kald Beshir Tuem contributed to conception of the research protocol and study design. Kald Beshir Tuem, Abadi Kahsu Gebre, Tesfay Mehari Atey, and Derbew Fikadu Berhe contributed to literature review, data collection, data extraction, data analysis and interpretation, and drafting the manuscript. Kald Beshir Tuem, Abadi Kahsu Gebre, Tesfay Mehari Atey, Helen Bitew, Ebrahim M. Yimer, and Derbew Fikadu Berhe contributed to drafting and reviewing the manuscript. All authors have read and approved the manuscript.

Supplementary Materials

Supplementary 1. S1 file: PRISMA 2009 Checklist. We have conducted the meta-analysis according to Moher et al. (2009), “Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement.” We included all the criteria on the checklist, except in the discussion part; we did not include the limitations of the study related to incomplete retrieval of articles, as we did not face such a problem.

Supplementary 2. S2 file: Modified Newcastle-Ottawa Scale. This scale had been adapted from Wells et al. (2009), “The Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Nonrandomized Studies in Meta-Analyses.” We considered the comparability to be controlled if the standard laboratory procedure is described in the articles. Since the outcome of the bacterial sensitivity test is obtained after full growth of the bacterial strains, we assigned one star for the assessment outcomes of all studies.

References

M. M. Levine, “Escherichia coli that cause diarrhea: enterotoxigenic, enteropathogenic, enteroinvasive, enterohemorrhagic, and enteroadherent,” The Journal of Infectious Diseases, vol. 155, no. 3, pp. 377–389, 1987.

F. M. Wagenlehner, K. G. Naber, and W. Weidner, “Rational antibiotic therapy of urinary tract infections,” Medizinische Monatsschrift für Pharmazeuten, vol. 31, no. 10, pp. 385–90, 2008.

M. A. De Francesco, R. Giuseppe, P. Laura, N. Riccardo, and M. Nin, “Urinary tract infections inBrescia, Italy: Etiology of uropathogens and antimicrobial resistance of common Uropathogens,” Medical Science Moniit, vol. 13, no. 6, pp. 136–144, 2007.

N. Kashef, G. E. Djavid, and S. Shahbazi, “Antimicrobial susceptibility patterns of community-acquired uropathogens in Tehran, Iran,” The Journal of Infection in Developing Countries, vol. 4, no. 4, pp. 202–206, 2010.

D. J. Biedenbach, G. J. Moet, and R. N. Jones, “Occurrence and antimicrobial resistance pattern comparisons among bloodstream infection isolates from the SENTRY Antimicrobial Surveillance Program (1997-2002),” Diagnostic Microbiology Infection Disease, vol. 50, no. 1, pp. 59–69, 2004.

S. Gebre-Sellassie, “Antimicrobial resistance patterns of clinical bacterial isolates in southern Ethiopia,” Ethiopian Medial Journal, vol. 45, no. 4, pp. 363–370, 2007.

N. A. Khan, N. Saba, A. S. Abdus, and A. A. Ali, “Incidence and Antibiogram Patterns of Escherichia coli Isolated from Various Clinical Samples from Patients at NIH Islamabad,” Pakistan Journal of Biological Sciences, vol. 5, no. 1, pp. 111–113, 2002.

S. M. Turner, A. Scott-Tucker, L. M. Cooper, and I. R. Henderson, “Weapons of mass destruction: Virulence factors of the global killer enterotoxigenic Escherichia coli,” FEMS Microbiology Letters, vol. 263, no. 1, pp. 10–20, 2006.

J. M. Bell, J. D. Turnidge, A. C. Gales, M. A. Pfaller, and R. N. Jones, “Prevalence of extended spectrum β-lactamase (ESBL)-producing clinical isolates in the Asia-Pacific region and South Africa: regional results from SENTRY Antimicrobial Surveillance Program (1998–99),” Diagnostic Microbiology Infection Disease, vol. 42, no. 3, pp. 193–198, 2002.

A. El Kholy, H. Baseem, G. S. Hall, G. W. Procop, and D. L. Longworth, “Antimicrobial resistance in Cairo, Egypt 1999–2000: a survey of five hospitals,” Journal of Antimicrobial Chemotherapy, vol. 51, no. 3, pp. 625–630, 2003.

J. A. Dromigny, P. Nabeth, A. Juergens-Behr, and J. D. Perrier-Gros-Claude, “Risk factors for antibiotic-resistant Escherichia coli isolated from community-acquired urinary tract infections in Dakar, Senegal,” Journal of Antimicrobial Chemotherapy, vol. 56, no. 1, pp. 236–239, 2005.

D. A. Tadesse, S. Zhao, and E. Tong, “Antimicrobial drug resistance in Escherichia coli from humans and food animals, United States, 1950–2002,” Emerging Infectious Diseases, vol. 18, no. 5, pp. 741–749, 2012.

US Food and Drug Administration, “National antimicrobial resistance monitoring system –enteric bacteria (NARMS): 2008 executive report. Rockville (MD); 2010,” http://www.fda.gov/AnimalVeterinary/SafetyHealth/AntimicrobialResistance/NationalAntimicrobialResistanceMonitoringSystem/default.htm.

B. A. Atkinson and V. Lorian, “Antimicrobial agent susceptibility patterns of bacteria in hospitals from 1971 to 1982,” Journal of Clinical Microbiology, vol. 20, pp. 791–796, 1984.

L. Blaettler, D. Mertz, R. Frei et al., “Secular trend and risk factors for antimicrobial resistance in escherichia coli isolates in Switzerland 1997-2007,” Infection, vol. 37, no. 6, pp. 534–539, 2009.

G. Kronvall, “Antimicrobial resistance 1979-2009 at Karolinska hospital, Sweden: Normalized resistance interpretation during a 30-year follow-up on Staphylococcus aureus and Escherichia coli resistance development,” APMIS-Acta Pathologica, Microbiologica et Immunologica Scandinavica, vol. 118, no. 9, pp. 621–639, 2010.

T. Patel and A. Levitin, “Escherichia Coli Adaptive Resistance to Clinical Antibiotics,” JSM Microbiology, vol. 2, no. 1, 2014.

A. Erb, T. Stürmer, R. Marre, and H. Brenner, “Prevalence of antibiotic resistance in Escherichia coli: Overview of geographical, temporal, and methodological variations,” European Journal of Clinical Microbiology & Infectious Diseases, vol. 26, no. 2, pp. 83–90, 2007.

N. Endalafer, S. Gebre-Selassie, and B. Kotiso, “Nosocomial bacterial infections in a tertiary hospital in Ethiopia,” Journal of Infection Prevention, vol. 12, no. 1, pp. 38–43, 2011.

G. Yismaw, S. Abay, D. Asrat, S. Yifru, and A. Kassu, “Bacteriological profile and resistant pattern of clinical isolates from pediatric patients, Gondar University Teaching Hospital, Gondar, Northwest Ethiopia,” Ethiopian Medical Journal, vol. 48, no. 4, pp. 293–300, 2010.

S. Eshetie, F. Tarekegn, F. Moges, A. Amsalu, W. Birhan, and K. Huruy, “Methicillin resistant Staphylococcus aureus in Ethiopia: A meta-analysis,” BMC Infectious Diseases, vol. 16, no. 1, article no. 689, 2016.

D. Moher, A. Liberati, J. Tetzlaff, and D. G. Altman, “Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement,” British Medical Journal, vol. 339, article b2535, 2009.

A. A. Abejew, A. A. Denboba, and A. G. Mekonnen, “Prevalence and antibiotic resistance pattern of urinary tract bacterial infections in Dessie area, Northeast Ethiopia,” BMC Research Notes, vol. 7, no. 1, article 687, 2014.

M. Kibret and B. Abera, “Prevalence and antibiogram of bacterial isolates from urinary tract infections at Dessie Health Research Laboratory, Ethiopia,” Asian Pacific Journal of Tropical Biomedicine, vol. 4, no. 2, pp. 164–168, 2014.

M. Kibret and B. Abera, “Antimicrobial susceptibility patterns of E. coli from clinical sources in northeast Ethiopia,” African Health Sciences, vol. 11, pp. S40–S45, 2011.

M. K. Azene and B. A. Beyene, “Bacteriology and antibiogram of pathogens from wound infections at Dessie Laboratory, North-east Ethiopia,” Tanzania Journal of Health Research, vol. 13, no. 4, pp. 68–74, 2011.

G. Alebachew, B. Teka, M. Endris, Y. Shiferaw, and B. Tessema, “Etiologic Agents of Bacterial Sepsis and Their Antibiotic Susceptibility Patterns among Patients Living with Human Immunodeficiency Virus at Gondar University Teaching Hospital, Northwest Ethiopia,” BioMed Research International, vol. 2016, Article ID 5371875, 2016.

A. Alemu, F. Moges, Y. Shiferaw et al., “Bacterial profile and drug susceptibility pattern of urinary tract infection in pregnant women at University of Gondar Teaching Hospital, Northwest Ethiopia,” BMC Research Notes, vol. 5, article no. 197, 2012.

Y. Wondimeneh, D. Muluye, A. Alemu et al., “Urinary tract infection among obstetric fistula patients at Gondar University Hospital, Northwest Ethiopia,” BMC Women's Health, vol. 14, no. 1, article no. 12, 2014.

H. Wondimu, Z. Addis, F. Moges, and Y. Shiferaw, “Bacteriological Safety of Blood Collected for Transfusion at University of Gondar Hospital Blood Bank, Northwest Ethiopia,” ISRN Hematology, vol. 2013, Article ID 308204, pp. 1–7, 2013.

S. Eshetie, C. Unakal, A. Gelaw, B. Ayelign, M. Endris, and F. Moges, “Multidrug resistant and carbapenemase producing Enterobacteriaceae among patients with urinary tract infection at referral Hospital, Northwest Ethiopia,” Antimicrobial Resistance and Infection Control, vol. 4, no. 1, article no. 12, 2015.

M. Tiruneh, S. Yifru, M. Gizachew et al., “Changing Trends in Prevalence and Antibiotics Resistance of Uropathogens in Patients Attending the Gondar University Hospital, Northwest Ethiopia,” International Journal of Bacteriology, vol. 2014, pp. 1–7, 2014.

S. Eshetie, F. Tarekegn, G. Kumera, and F. Mekonnen, “Multidrug resistant Escherichia coli strains isolated from urine sample, University of Gondar Hospital, Northwest Ethiopia,” Journal of Coastal Life Medicine, vol. 4, no. 2, pp. 140–142, 2016.

W. Mulu, B. Abera, M. Yimer, T. Hailu, H. Ayele, and D. Abate, “Bacterial agents and antibiotic resistance profiles of infections from different sites that occurred among patients at Debre Markos Referral Hospital, Ethiopia: A cross-sectional study,” BMC Research Notes, vol. 10, no. 1, article no. 254, 2017.

B. Abera and M. Kibret, “Azithromycin, fluoroquinolone and chloramphenicol resistance of non-chlamydia conjunctival bacteria in rural community of Ethiopia,” Indian Journal of Ophthalmology, vol. 62, no. 2, pp. 236–239, 2014.

A. Adugna, M. Kibret, B. Abera, E. Nibret, and M. Adal, “Antibiogram of e. Coli serotypes isolated from children aged under five with acute diarrhea in bahir dar town,” African Health Sciences, vol. 15, no. 2, pp. 656–664, 2015.

T. Demilie, G. Beyene, S. Melaku, and W. Tsegaye, “Urinary bacterial profile and antibiotic susceptibility pattern among pregnant women in north west Ethiopia,” Ethiopian Journal of Health Sciences, vol. 22, no. 2, pp. 121–128, 2012.

A. Derbie, D. Hailu, D. Mekonnen, B. Abera, and G. Yitayew, “Antibiogram profile of uropathogens isolated at bahir dar regional health research laboratory centre, northwest ethiopia,” Pan African Medical Journal, vol. 26, article no. 134, 2017.

S. Melaku, M. Kibret, B. Abera, and S. Gebre-Sellassie, “Antibiogram of nosocomial urinary tract infections in Felege Hiwot referral hospital, Ethiopia,” African Health Sciences, vol. 12, no. 2, pp. 134–139, 2012.

W. Mulu, G. Kibru, G. Beyene, and M. Damtie, “Postoperative nosocomial infections and antimicrobial resistance pattern of bacteria isolates among patients admitted at Felege Hiwot Referral Hospital, Bahirdar, Ethiopia,” Ethiopian Journal of Health Sciences, vol. 22, no. 1, pp. 7–18, 2012.

M. Wondemagegn, M. Yimer, Y. Zenebe, and B. Abera, “Common causes of vaginal infections and antibiotic susceptibility of aerobic bacterial isolates in women of reproductive age attending at Felegehiwot referral Hospital, Ethiopia: a cross sectional study,” BMC Women's Health, vol. 15, no. 42, pp. 1–9, 2015.

M. Dereje, Y. Woldeamanuel, D. Asrat, and F. Ayenachew, “Urinary tract infection among fistula patients admitted at Hamlin fistula hospital, Addis Ababa, Ethiopia,” BMC Infectious Diseases, vol. 17, no. 1, article no. 150, 2017.

W. Dessie, G. Mulugeta, S. Fentaw, A. Mihret, M. Hassen, and E. Abebe, “Pattern of bacterial pathogens and their susceptibility isolated from surgical site infections at selected referral hospitals, Addis Ababa, Ethiopia,” International Journal of Microbiology, vol. 2016, Article ID 2418902, 8 pages, 2016.

K. Desta, Y. Woldeamanuel, A. Azazh et al., “High gastrointestinal colonization rate with extended-spectrum β-lactamase-producing Enterobacteriaceae in hospitalized patients: Emergence of carbapenemase-producing K. Pneumoniae in Ethiopia,” PLoS ONE, vol. 11, no. 8, Article ID e0161685, 2016.

Y. Mamuye, “Antibiotic Resistance Patterns of Common Gram-negative Uropathogens in St. Paul's Hospital Millennium Medical College,” Ethiopian Journal of Health Sciences, vol. 26, no. 2, pp. 93–100, 2016.

M. H. Legese, G. M. Weldearegay, and D. Asrat, “Extended-spectrum beta-lactamase- and carbapenemase-producing Enterobacteriaceae among ethiopian children,” Infection and Drug Resistance, vol. 10, pp. 27–34, 2017.

J. M. Ramos, R. Pérez-Tanoira, C. García-García et al., “Leprosy ulcers in a rural hospital of Ethiopia: Pattern of aerobic bacterial isolates and drug sensitivities,” Annals of Clinical Microbiology and Antimicrobials, vol. 13, no. 1, article no. 47, 2014.

B. Derese, H. Kedir, Z. Teklemariam, F. Weldegebreal, and S. Balakrishnan, “Bacterial profile of urinary tract infection and antimicrobial susceptibility pattern among pregnant women attending at Antenatal Clinic in Dil Chora Referral Hospital, Dire Dawa, Eastern Ethiopia,” Therapeutics and Clinical Risk Management, vol. 12, pp. 251–260, 2016.

G. Beyene and W. Tsegaye, “Bacterial Uropathogens in Urinary Tract Infection and Antibiotic Susceptibility Pattern in Jimma University Specialized Hospital, Southwest Ethiopia,” Ethiopian Journal of Health Sciences, vol. 21, no. 2, 2011.

S. Debalke, W. Cheneke, H. Tassew, and M. Awol, “Urinary tract infection among antiretroviral therapy users and nonusers in jimma university specialized hospital, Jimma, Ethiopia,” International Journal of Microbiology, vol. 2014, Article ID 968716, 2014.

M. Mama, A. Abdissa, and T. Sewunet, “Antimicrobial susceptibility pattern of bacterial isolates from wound infection and their sensitivity to alternative topical agents at Jimma University Specialized Hospital, South-West Ethiopia,” Annals of Clinical Microbiology and Antimicrobials, vol. 13, article 14, 2014.

Y. Mulualem, T. Kasa, Z. Mekonnen, and S. Suleman, “Occurrence of extended spectrum beta (b)-lactamases in multi-drug resistant Escherichia coli isolated from a clinical setting in Jimma University Specialized Hospital, Jimma, southwest Ethiopia.,” East African Journal of Public Health, vol. 9, no. 2, pp. 58–61, 2012.

T. Zenebe, S. Kannan, D. Yilma, and G. Beyene, “Invasive Bacterial Pathogens and their Antibiotic Susceptibility Patterns in Jimma University Specialized Hospital, Jimma, Southwest Ethiopia,” Ethiopian Journal of Health Sciences, vol. 21, no. 1, 2011.

D. Nigussie and A. Amsalu, “Prevalence of uropathogen and their antibiotic resistance pattern among diabetic patients,” Turk Uroloji Dergisi, vol. 43, no. 1, pp. 85–92, 2017.

A. Amsalu, Z. Geto, D. Asegu, and S. Eshetie, “Antimicrobial resistance pattern of bacterial isolates from different clinical specimens in Southern Ethiopia: A three-year retrospective study,” African Journal of Bacteriology Research, vol. 9, no. 1, pp. 1–8, 2017.

E. Tadesse, M. Teshome, Y. Merid, B. Kibret, and T. Shimelis, “Asymptomatic urinary tract infection among pregnant women attending the antenatal clinic of Hawassa Referral Hospital, Southern Ethiopia,” BMC Research Notes, vol. 7, no. 1, article no. 155, 2014.

A. G. Wasihun, L. N. Wlekidan, S. A. Gebremariam et al., “Bacteriological profile and antimicrobial susceptibility patterns of blood culture isolates among febrile patients in mekelle hospital, Northern Ethiopia,” SpringerPlus, vol. 4, no. 1, 2015.

G. Wells, B. Shea, and D. O'Connell, The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses, Ottawa Hospital Research Institute, Ottawa, Canada, 2009, http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.

J. P. A. Ioannidis, “Interpretation of tests of heterogeneity and bias in meta-analysis,” Journal of Evaluation in Clinical Practice, vol. 14, no. 5, pp. 951–957, 2008.

R. DerSimonian and N. Laird, “Meta-analysis in clinical trials,” Controlled Clinical Trials, vol. 7, no. 3, pp. 177–188, 1986.

S. Fazel, V. Khosla, H. Doll, and J. Geddes, “The prevalence of mental disorders among the homeless in Western countries: Systematic review and meta-regression analysis,” PLoS Medicine, vol. 5, no. 12, pp. 1670–1681, 2008.

J. J. Barendregt, S. A. Doi, Y. Y. Lee, R. E. Norman, and T. Vos, “Meta-analysis of prevalence,” Journal of Epidemiology and Community Health, vol. 67, no. 11, pp. 974–978, 2013.

G. Rücker, G. Schwarzer, J. R. Carpenter, and M. Schumacher, “Undue reliance on I2 in assessing heterogeneity may mislead,” BMC Medical Research Methodology, vol. 8, article no. 79, 2008.

A. D. J. Sosa, C. F. Amábile-Cuevas, D. K. Byarugaba, -R. Hsueh, S. Kariuki, and I. N. Okeke, Antimicrobial resistance in developing countries, Springer, New York, Dordrecht Heidelberg, London, 2010.

World Health Organization, “Antimicrobial resistance: global report on surveillance. World Health Organization; 2014,” http://www.who.int/drugresistance/documents/surveillancereport/en/.

N. Nelson, M. Joshi, and R. Kirika, “Antimicrobial Resistance: The Need for Action in the East, Central and Southern Africa Region. Submitted to the US Agency for International Development by the Strengthening Pharmaceutical Systems (SPS) Program. Arlington, VA: Management Sciences for Health. 2009,” http://apps.who.int/medicinedocs/documents/s18415en/s18415en.pdf.

R. Laxminarayan, A. Duse, and C. Wattal, “Antibiotic resistance—the need for global solutions,” The Lancet Infectious Diseases, vol. 13, no. 12, pp. 1057–1098, 2013.

T. F. O'Brien, “Emergence, spread, and environmental effect of antimicrobial resistance: how use of an antimicrobial anywhere can increase resistance to any antimicrobial anywhere else,” Clinical Infectious Diseases, vol. 34, supplement 3, pp. S78–S84, 2002.

World Health Organization, “Promoting rational use of medicines: core components. Geneva: WHO Press, 2002,” http://apps.who.int/medicinedocs/pdf/h3011e/h3011e.pdf.

O. Săndulescu, “Global distribution of antimicrobial resistance in E. coli,” Journal of Contemporary Clinical Practice, vol. 2, no. 2, pp. 69–74, 2012.

A. Bryce, C. Costelloe, C. Hawcroft, M. Wootton, and A. D. Hay, “Faecal carriage of antibiotic resistant Escherichia coli in asymptomatic children and associations with primary care antibiotic prescribing: A systematic review and meta-analysis,” BMC Infectious Diseases, vol. 16, no. 1, article no. 359, 2016.