About the Author(s)


Abera A. Kitaba Email symbol
National Clinical Bacteriology and Mycology Reference Laboratory, Ethiopian Public Health Institute, Addis Ababa, Ethiopia

Zelalem T. Bonger symbol
National Clinical Bacteriology and Mycology Reference Laboratory, Ethiopian Public Health Institute, Addis Ababa, Ethiopia

Degefu Beyene symbol
National Clinical Bacteriology and Mycology Reference Laboratory, Ethiopian Public Health Institute, Addis Ababa, Ethiopia

Zeleke Ayenew symbol
National Clinical Bacteriology and Mycology Reference Laboratory, Ethiopian Public Health Institute, Addis Ababa, Ethiopia

Estifanos Tsige symbol
National Clinical Bacteriology and Mycology Reference Laboratory, Ethiopian Public Health Institute, Addis Ababa, Ethiopia

Tesfa Addis Kefale symbol
National Clinical Bacteriology and Mycology Reference Laboratory, Ethiopian Public Health Institute, Addis Ababa, Ethiopia

Yonas Mekonnen symbol
National Clinical Bacteriology and Mycology Reference Laboratory, Ethiopian Public Health Institute, Addis Ababa, Ethiopia

Dejenie S. Teklu symbol
National Clinical Bacteriology and Mycology Reference Laboratory, Ethiopian Public Health Institute, Addis Ababa, Ethiopia

Elias Seyoum symbol
National Clinical Bacteriology and Mycology Reference Laboratory, Ethiopian Public Health Institute, Addis Ababa, Ethiopia

Abebe A. Negeri symbol
National Clinical Bacteriology and Mycology Reference Laboratory, Ethiopian Public Health Institute, Addis Ababa, Ethiopia

Citation


Kitaba AA, Bonger ZT, Beyene D, et al. Antimicrobial resistance trends in clinical Escherichia coli and Klebsiella pneumoniae in Ethiopia. Afr J Lab Med. 2024;13(1), a2268. https://doi.org/10.4102/ajlm.v13i1.2268

Original Research

Antimicrobial resistance trends in clinical Escherichia coli and Klebsiella pneumoniae in Ethiopia

Abera A. Kitaba, Zelalem T. Bonger, Degefu Beyene, Zeleke Ayenew, Estifanos Tsige, Tesfa Addis Kefale, Yonas Mekonnen, Dejenie S. Teklu, Elias Seyoum, Abebe A. Negeri

Received: 17 July 2023; Accepted: 11 Jan. 2024; Published: 27 Mar. 2024

Copyright: © 2024. The Author(s). Licensee: AOSIS.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background: Clinicians rely on local antimicrobial resistance pattern data to guide empiric treatment for seriously ill patients when culture and antimicrobial susceptibility testing results are not immediately available.

Objective: This study aimed to analyse 5-year trends in antimicrobial resistance profiles of Escherichia coli and Klebsiella pneumoniae isolates.

Methods: Bacteriology reports from 2017 to 2021 at the Ethiopian Public Health Institute were analysed retrospectively. Isolates were identified using either the VITEK 2 Compact system, the BD Phoenix M50 instrument, or conventional biochemical tests. Antimicrobial susceptibility testing was conducted using either the Kirby-Bauer disk diffusion method or the VITEK 2 Compact system and BD Phoenix M50 systems available at the time of testing. The Cochran Armitage trend test was employed to test the significance of antimicrobial resistance trends over time. P-values less than 0.05 were considered statistically significant.

Results: Of the 5382 bacteriology reports examined, 458 (9%) were on E. coli and 266 (5%) were on K. pneumoniae. Both K. pneumoniae (88%) and E. coli (65%) demonstrated high resistance to extended-spectrum cephalosporins. However, both K. pneumoniae (14%) and E. coli (5%) showed lower rates of resistance to carbapenems compared to other antimicrobials. In K. pneumoniae, resistance to carbapenems (from 0% to 38%; p < 0.001) and ciprofloxacin (from 41% to 90%; p < 0.001) increased significantly between 2017 and 2021.

Conclusion: Both organisms showed very high resistance to broad-spectrum antibiotics. Additionally, K. pneumoniae demonstrated a statistically significant rise in ciprofloxacin and carbapenem resistance.

What this study adds: This study emphasises the significance of regular reporting of local antimicrobial resistance patterns as this information can guide appropriate empiric therapy and efforts to address antimicrobial resistance issues.

Keywords: antimicrobial resistance; retrospective analysis; trend analysis; Escherichia coli; Klebsiella pneumoniae; Ethiopian Public Health Institute; Ethiopia.

Introduction

The emergence and spread of antimicrobial-resistant Enterobacteriaceae, particularly Escherichia coli and Klebsiella pneumoniae, is a critical health problem and threatens the effective prevention and treatment of serious infections.1 Antimicrobial-resistant E. coli and K. pneumoniae are responsible for a high proportion of serious nosocomial infections, including urinary tract, bloodstream, abdominal, and respiratory tract infections, and are a serious concern for global health and development.2,3 E. coli and K. pneumoniae develop resistance to beta-lactam antibiotics primarily by producing carbapenemase and extended-spectrum beta-lactamase enzymes.4,5,6,7

Klebsiella pneumoniae tends to be significantly more resistant than E. coli, with carbapenem resistance rates exceeding 25% reported in several southern European countries.7 Infections caused by carbapenem-resistant, extended-spectrum beta-lactamase-producing, and multidrug-resistant E. coli and K. pneumoniae are more difficult to treat and occur at higher frequencies.2,3,7 The United States Centers for Disease Control and Prevention has classified carbapenem-resistant E. coli and K. pneumoniae, as urgent threats and extended-spectrum beta-lactamase-producing E. coli and K. pneumoniae, as serious threats, whereas the World Health Organization classified them as critical priority pathogens requiring the development of new active antimicrobial agents.2,3

Globally, several studies and antimicrobial resistance surveillance systems have reported increasing rates of antimicrobial resistance among E. coli and K. pneumoniae.8,9,10,11,12,13 For example, a 10-year retrospective study in China found that the rate of carbapenem-resistant K. pneumoniae increased significantly, from 6.7% in 2010 to 56.7% in 2019.12 Similarly, a surveillance report from a hospital in Malawi revealed a substantial increase in ciprofloxacin-resistant E. coli (from 0.0% in 1998 to 31.1% in 2016) and ciprofloxacin-resistant Klebsiella species (from 1.7% in 1998 to 70.2% in 2016).14 Several scientific reports out of Africa have emphasised the fast-growing threat of antimicrobial resistance.8,11,14,15,16,17,18 The threat appears to be receiving more attention in the region than ever before, as evidenced by an increase in the number of publications on the subject, as well as the initiatives by the African Society for Laboratory Medicine and the African Centers for Disease Control and Prevention.19

Even though studies in Ethiopia have reported a high burden of antimicrobial resistance among E. coli and K. pneumoniae,8,17,18 there is limited information on the trends of antimicrobial resistance among these pathogens in Ethiopia. Therefore, the current study was designed to analyse 5-year antimicrobial resistance trends among E. coli and K. pneumoniae recovered from specimens referred to the Ethiopian Public Health Institute. The findings of our study may provide local antimicrobial resistance patterns of E. coli and K. pneumoniae to clinicians to guide empiric treatment for seriously ill patients when culture and antimicrobial susceptibility testing results are not immediately available. Moreover, the findings may provide information for initiatives aimed at combating the problem of antimicrobial resistance, including infection prevention and control practices and antimicrobial stewardship.

Methods

Ethical considerations

Due to the retrospective nature of this study, we were unable to obtain consent from the patients who provided specimens. Therefore, a waiver of informed consent to conduct the study was requested and approved by the institutional review board of the Ethiopian Public Health Institute with approval number EPHI-IRB-413-2021. To maintain confidentiality, patient names and other personal identifiers were encrypted, and unique identification numbers were utilised to identify data. Therefore, the study was conducted in accordance with Helsinki Declaration as revised in 2013.

Data collection

This retrospective study included routine bacteriology culture reports of E. coli and K. pneumoniae isolates obtained from various clinical specimens at the Ethiopian Public Health Institute between January 2017 and December 2021. The laboratory provides diagnostic services as well as a range of research activities. It was accredited by the Ethiopian Accreditation Service following the requirements of the International Organization for Standardization 15189:2012.

Isolate identification and antimicrobial susceptibility testing

Isolation and identification of the bacteria were achieved by culturing the specimens onto appropriate culture media and incubating them at 35 °C – 37 °C following laboratory standard operating procedures. The isolated bacteria were identified using one of the following laboratory methods available at the time of testing: VITEK 2 Compact system (bioMérieux, Marcy-l’Étoile, France), BD Phoenix M50 (Becton, Dickinson and Company, Franklin Lakes, New Jersey, United States), and standard biochemical tests. For standard biochemical tests, the following biochemical tests were used along with Gram staining for isolate identification: triple sugar iron agar (Oxoid Ltd., Basingstoke, Hampshire, England), lysine iron agar (Biomark, Pune, Maharashtra, India), sulfide indole motility (HIMEDIA, Mumbai, Maharashtra, India), Simmons citrate agar (Biomark, Pune, Maharashtra, India), urea agar (HIMEDIA, Mumbai, Maharashtra, India), and oxidase (Liofilchem, Roseto degli Abruzzi, Italy). Antimicrobial susceptibility testing was carried out using either the Kirby-Bauer disk diffusion method on Muller Hinton agar (Oxoid Ltd., Basingstoke, Hampshire, England), the VITEK 2 Compact system, or the BD Phoenix M50 system. The results of antimicrobial susceptibility tests (susceptible, intermediate, and resistant) were interpreted using the latest Clinical and Laboratory Standards Institute M100 criteria available at the time of testing.20

Quality control for antimicrobial susceptibility testing and biochemical tests and culture was carried out as per the Clinical and Laboratory Standards Institute guidelines20,21, manufacturer instructions, and laboratory standard operating procedures using different American-type culture collection strains. E. coli American-type culture collection 25922, Staphylococcus aureus American-type culture collection 25923, and Pseudomonas aeruginosa American-type culture collection 27853 strains were used for quality control during antimicrobial susceptibility testing.

Grouping antimicrobial agents for trend analysis

For trend analysis, we grouped related antimicrobials according to drug classes using the Clinical and Laboratory Standards Institute M02 guidelines.21 Antimicrobial agents were categorised as extended-spectrum cephalosporins, aminoglycosides, first- and second-generation cephalosporins, carbapenems, β-lactam-combination agents, ciprofloxacin, and trimethoprim/sulfamethoxazole. Resistance to at least one of the several agents within each antimicrobial class was used to define resistance at the antimicrobial class level. Isolates were considered extended-spectrum cephalosporin-resistant if they were resistant to at least one of the extended-spectrum cephalosporins: ceftazidime, cefepime, and ceftriaxone. Aminoglycoside-resistant isolates were those that were resistant to at least one of the following aminoglycosides: amikacin, tobramycin, and gentamycin. Strains that were resistant to amoxicillin/clavulanic acid or piperacillin/tazobactam were deemed resistant to a β-lactam-combination agent. Carbapenem resistance was defined as resistance to meropenem or imipenem. Strains resistant to cefazolin or cefuroxime were considered resistant to first- and second-generation cephalosporins.

Data extraction

The bacteriology records from the laboratory logbook were entered into WHONET software (WHO Collaborating Centre for Surveillance of Antimicrobial Resistance; https://whonet.org/software.html). The following information was obtained: type of specimen, final culture results, identity of the organism (for positive cultures), susceptibility testing results, date of specimen collection and receipt at the laboratory, and patients’ demographics (age and gender). To avoid bias from repetitive culture, only data on the first isolate from each patient were included.

Statistical analysis

The WHONET software was used to analyse resistance rates.22 For each species, the resistance rates were calculated by dividing the number of resistant isolates by the total number of isolates tested. This was calculated for each year, and the yearly trends over the 5 years were assessed. We also determined the distribution of pathogens according to the age and gender of patients, as well as specimen types and year of isolation. Statistical analysis was performed using R software,23 and the Cochran Armitage trend test was employed to test the statistical significance of antimicrobial resistance trends over time. P-values less than 0.05 were considered statistically significant.

Results

A total of 7199 clinical specimens were collected from 2017 to 2021 (Figure 1). Specimens other than blood, urine, and pus (n = 1745) were excluded from this study; isolates from stool, throat swabs, nasal swabs, and other specimens were not considered pathogens. Additionally, specimens with missing information on patient age and gender (n = 72) were excluded from this study. In total, 5382 records of blood, pus, and urine specimens with complete information were obtained, from which 458 (9%) E. coli and 266 (5%) K. pneumoniae isolates were recovered. The combined prevalence of E. coli and K. pneumoniae was 13% (724/5382).

FIGURE 1: Flow diagram of applied criteria for selection of bacteriology culture data for this study. Ethiopian Public Health Institute, Addis Ababa, Ethiopia, January 2017 – December 2021.

Distribution of E. coli and K. pneumoniae by age, gender, and specimen type

There were more male patients (n = 2890; 54%) than female patients (n = 2492; 46%) (Table 1). The majority of the patients (n = 2459; 46%) were aged between 19 and 45 years. Of the 5382 specimens, 42% were urine specimens, 40% were blood samples, and 18% were pus samples. Out of the 724 isolates, 458 (63%) were E. coli, the majority (n = 356; 78%) of which were recovered from urine. The remaining 266 (37%) isolates were K. pneumoniae, of which 129 (50%) were recovered from blood specimens. About 82% of all E. coli and K. pneumoniae isolates were recovered from blood and urine specimens. E. coli (n = 261; 57%) was more prevalent among female patients, while K. pneumoniae (n = 153, 58%) was more common in male patients.

TABLE 1: Distribution of Escherichia coli and Klebsiella pneumoniae by age, gender, and specimen types. Ethiopian Public Health Institute, Addis Ababa, Ethiopia, January 2017 – December 2021.
Five-year resistance patterns of E. coli and K. pneumoniae isolates

Among the E. coli isolates, the highest rates of resistance were recorded against ampicillin (88%), piperacillin (84%), and tetracycline (80%), and the lowest resistance rates were recorded against amikacin (2%), meropenem (3%), and imipenem (5%) (Figure 2). Among the K. pneumoniae isolates, the highest resistance rates were observed against cefazolin (91%), cefuroxime (91%), ceftriaxone (92%), and piperacillin (97%), while the lowest resistance rates were recorded against nitrofurantoin (9%), amikacin (13%), meropenem (13%), and imipenem (17%).

FIGURE 2: Resistance rates of Escherichia coli and Klebsiella pneumoniae to tested antimicrobials at the Ethiopian Public Health Institute, Addis Ababa, Ethiopia, January 2017 – December 2021.

Antimicrobial resistance trends of E. coli

Despite the observed high rates of resistance to common antimicrobial agents among the E. coli isolates in this study, we found no statistically significant increasing trends in resistance to any of the tested antimicrobials (Figure 3). The resistance rates of E. coli to ciprofloxacin ranged from 60% to 82% and from 71% to 80% for trimethoprim/sulfamethoxazole between 2017 and 2021. The proportion of ciprofloxacin-resistant E. coli was 70% in 2017 but fell to 68% in 2018 and 60% in 2019, before rising to 72% in 2020 and 80% in 2021.

FIGURE 3: Antimicrobial resistance trends among Escherichia coli at the Ethiopian Public Health Institute, Addis Ababa, Ethiopia, January 2017 – December 2021.

Carbapenem resistance trends in E. coli fluctuated during the study period. In 2017, the proportion of carbapenem-resistant E. coli was 4%. This proportion rose to 10% in 2018, then fell to 2% in 2019 and 0% in 2020 before rising again to 9% in 2021. Resistance rates to the extended-spectrum cephalosporins (range: 57% – 71%) and first- and second-generation cephalosporins (range: 54% – 72%) were continuously high throughout the study period. In 2017, the proportion of extended-spectrum cephalosporin-resistant E. coli was 71%. This proportion dropped slightly to 65% in 2018, 63% in 2019, and 57% in 2020 before rising again to 69% in 2021. For the aminoglycosides, the proportion of resistant E. coli isolates ranged from 23% to 31% between 2017 and 2021, while for the β-lactam combinations, the proportion of resistant E. coli isolates dropped from 41% to 20%.

Antimicrobial resistance trends of K. pneumoniae

Overall, K. pneumoniae exhibited high levels of antimicrobial resistance, with 88% of the isolates resistant to extended-spectrum cephalosporins, 51% resistant to aminoglycosides, 44% resistant to ciprofloxacin, and 14% resistant to carbapenems (Figure 4). There was a statistically significant increase in ciprofloxacin resistance and carbapenem resistance rates among the K. pneumoniae isolates (p < 0.0001). Over the 5 years, the proportion of carbapenem-resistant K. pneumoniae increased significantly from 0% in 2017 to 8% in 2018 and 2019, and from 19% in 2020 to 39% in 2021 (p < 0.001). From 2017 to 2018, the proportion of ciprofloxacin-resistant K. pneumoniae decreased from 41% to 24%. However, by 2019, this proportion increased to 39%, before surging to 71% in 2020 and 90% in 2021 (p < 0.001). Over the first 3 years of the study period, the prevalence of trimethoprim/sulfamethoxazole-resistant K. pneumoniae ranged between 81% and 85%. However, this proportion rose to 100% in 2020 before decreasing to 91% in 2021.

FIGURE 4: Antimicrobial resistance trends among Klebsiella pneumoniae at the Ethiopian Public Health Institute, Addis Ababa, Ethiopia, January 2017 – December 2021.

Among the K. pneumoniae isolates, resistance rates to the extended-spectrum cephalosporins remained above 80% throughout the study period. In 2017, 57% of K. pneumoniae isolates were resistant to aminoglycosides. However, the resistance rate decreased to 46% in 2018 and 42% in 2019, before rising to 71% in 2020 and 67% in 2021. The proportion of K. pneumoniae isolates that were resistant to the β-lactam combinations ranged from 33% to 79% between 2017 and 2021. In the first 2 years of the study period, the proportion of K. pneumoniae isolates resistant to the β-lactam combinations increased from 50% to 79%, before decreasing to 54% in 2019. Subsequently, in both 2020 and 2021, the resistance levels dropped below 50%, reaching 33% in 2020 and 42% in 2021.

Discussion

In this study, E. coli displayed high rates of resistance against ampicillin, piperacillin, and tetracycline, and low rates of resistance against amikacin and meropenem. K. pneumoniae exhibited high rates of resistance to cefazolin, cefuroxime, ceftazidime, trimethoprim-sulphamethoxazole, ceftriaxone, and piperacillin, and low rates of resistance against amikacin and meropenem. Regarding the trends in resistance observed over 5 years, our findings indicate that there were no statistically significant increases in resistance to the tested antimicrobials among E. coli isolates. However, we did observe a statistically significant rise in the rates of ciprofloxacin and carbapenem resistance among the K. pneumoniae isolates.

The Ethiopian Standard Treatment Guidelines for general hospitals provide comprehensive recommendations on the use of various antibiotics for empiric treatment.24 These guidelines consider the anatomical location and severity of different infections. For instance, in the case of sepsis, the guidelines recommend a combination of ampicillin and gentamicin, penicillin G, or a combination of an aminoglycoside or ciprofloxacin with ceftazidime.24 The guidelines suggest various medications, such as amoxicillin, cephalexin, ciprofloxacin, nitrofurantoin, ampicillin, gentamicin, trimethoprim-sulphamethoxazole, cefuroxime, ceftriaxone, and additional options, for the treatment of urinary tract infections.24 In the case of wound infections, the guidelines recommend piperacillin-tazobactam, ampicillin-sulbactam, cefazolin, amoxicillin-clavulanate, doxycycline, trimethoprim-sulphamethoxazole, and cefuroxime. These guidelines aim to ensure the effective and responsible use of antibiotics in Ethiopian hospitals.24

Regarding local prescribing practices, a study conducted in 2021 at Dilchora Referral Hospital in Ethiopia revealed that ciprofloxacin was the most frequently prescribed antibiotic for treating patients with urinary tract infections, followed by norfloxacin and amoxicillin/clavulanic acid.25 Another study at Ambo University Referral Hospital, Ethiopia, from 2019, reported that ceftriaxone was the most commonly prescribed single antibiotic, accounting for 21.7% of prescriptions.26 In that study, the combination of ceftriaxone and azithromycin was the most popular choice for empiric treatment of community-acquired pneumonia, accounting for 50.7% of prescriptions. The authors also highlighted a non-adherence rate of 36.4% to the national guidelines for antibiotic use. Furthermore, a study conducted at four governmental hospitals in eastern Ethiopia in 2017 identified amoxicillin, ceftriaxone, and ciprofloxacin as the top three prescribed antibacterial drugs.27 Lastly, research from Addis Ababa, Ethiopia, from 2016, revealed that amoxicillin was the most frequently prescribed antibiotic, accounting for 44.8% of prescriptions, followed by ciprofloxacin at 13.6%, and trimethoprim-sulphamethoxazole at 11.2%.28 The observed high resistance patterns of both E. coli and K. pneumoniae isolates to commonly used antibiotics may be attributed to these factors. Given that these pathogens have demonstrated high resistance to the antibiotics recommended in the Ethiopian Standard Treatment Guidelines, it is necessary to regularly revise the guidelines in accordance with local antimicrobial resistance levels.

In this study, we observed a significant increase in carbapenem resistance rates among K. pneumoniae, reaching 38% by the end of 2021. In agreement with our findings, China’s antimicrobial surveillance network reported a significant rise in the prevalence of meropenem-resistant K. pneumoniae from 2.9% in 2005 to 26.3% in 2018 (p < 0.001).29 Furthermore, a 20-year (1997–2016) report from the SENTRY Antimicrobial Surveillance Program revealed a significant increase in carbapenem resistance among K. pneumoniae, rising from 0.7% in 1997 to 14.2% in 2016 in Europe (p < 0.001).30 This increase in carbapenem resistance might be explained by poor hospital infection control and prevention practices and inappropriate prescription practices.31 Inappropriate prescription practices, in turn, may be related to the scarcity of bacteriology laboratories capable of promptly detecting resistant bacteria and providing antibiograms to clinicians in health facilities in developing countries.31 In contrast to our findings, however, earlier studies at 14 New York City hospitals reported a decline in carbapenem-resistant K. pneumoniae at 6 of the 14 hospitals (carbapenem-resistant K. pneumoniae decreased from 38% in 2006 to 29% in 2009; p < 0.001).32 Another study from the United States reported that the occurrence of carbapenem-resistant K. pneumoniae isolates declined significantly in a public health system in New York, United States, from 2016 to 2020, but increased between January 2021 and June 2022.33 These differences in observed trends could be attributed to strong infection control and prevention efforts done to decrease and prevent carbapenem-resistant K. pneumoniae infections in both hospital and community settings in New York City.32

Ciprofloxacin resistance rates increased significantly among K. pneumoniae from 2017 (41%) to 2021 (90%), consistent with findings of a study conducted in Sichuan, China, from 2017 to 2020 that reported increasing resistance of K. pneumoniae to ciprofloxacin from 14.7% in 2017 to 26.5% in 2020.34 Similarly, the SENTRY Antimicrobial Surveillance Program reported increasing rates of ciprofloxacin resistance among K. pneumoniae from 7.3% in 1997 to 27.9% in 2016 in Europe.30 Furthermore, the Taiwan Surveillance of Antimicrobial Resistance programme (2002–2012)35 reported a significant decrease in the proportion of ciprofloxacin-susceptible K. pneumoniae (average of 89.9% from 2002 to 2006 to an average of 81.6% from 2008 to 2012). Conversely, however, the Korean Antimicrobial Resistance Monitoring System reported an almost constant trend for ciprofloxacin-resistant K. pneumoniae from 2013 to 2015.13 Geographical variations may explain these observed differences.

High resistance rates to both first-line and last-resort antibiotics were observed in our study among E. coli and K. pneumoniae isolates. Overall, the rates of resistance to trimethoprim/sulfamethoxazole (E. coli 75% and K. pneumoniae 85%), ciprofloxacin (E. coli 69% and K. pneumoniae 44%), the first-generation to fourth-generation cephalosporins (E. coli 65% and K. pneumoniae 88%), and aminoglycosides (E. coli 28% and K. pneumoniae 51%) among both species during the 5-year study period were very high. This is consistent with the findings of previous studies in Ethiopia,8,17,18 Kenya,36 and Uganda.37 These high rates of resistance could be related to the high prevalence of irrational antibiotic use and self-prescription practices in Ethiopia.38,39,40,41,42 As a result, these antimicrobials may no longer be considered effective treatment options for infections caused by E. coli and K. pneumoniae. This, in turn, underlines the importance of developing bacteriology laboratory capacity in healthcare facilities to ensure that isolate identification and antimicrobial susceptibility testing results are made available for clinicians. Furthermore, antimicrobial stewardship programmes are required to monitor and regulate antibiotic use. Our findings are inconsistent with those of a retrospective analysis of data from a national surveillance network in Switzerland over 8 years (2009–2016) that showed lower resistance among E. coli and K. pneumoniae to commonly used antibiotics such as third- and fourth-generation cephalosporins (E. coli < 6%, K. pneumoniae < 5%), ciprofloxacin (E. coli > 14%, K. pneumoniae > 12%), and trimethoprim/sulfamethoxazole (E. coli < 23%, K. pneumoniae < 11%).43 This may be explained by the low use of antibiotics in both community and hospital settings in Switzerland.43

Limitations

The lack of molecular identification for K. pneumoniae could have led to the misidentification of various species within the K. pneumoniae species complex. Due to the retrospective nature of this study, we were unable to confirm resistance genes using polymerase chain reaction. This would have provided valuable additional information regarding the presence or absence of specific resistance genes in the organisms studied, enhanced our understanding of the mechanisms underlying antibiotic resistance, and potentially allowed a more comprehensive analysis of the genetic determinants contributing to resistance patterns.

Conclusion

Based on the findings of this study, both K. pneumoniae and E. coli showed very high resistance to both first-line and last-resort antibiotics recommended in the Ethiopian Standard Treatment Guidelines. However, the antimicrobial resistance trends for the majority of the antimicrobial agents fluctuated throughout the study period. Furthermore, K. pneumoniae showed a statistically significant increasing trend of resistance to carbapenems and ciprofloxacin. This is concerning, since it may compromise the treatment of critically ill patients. This necessitates continued infection control efforts, together with diagnostic and antimicrobial stewardship programmes in healthcare facilities. Additionally, it is necessary to regularly revise the guidelines in accordance with local antimicrobial resistance levels.

Acknowledgements

We would like to thank the Ethiopian Public Health Institute for allowing us to extract antimicrobial resistance data and conduct this research. We also extend our appreciation to Ms Mulushewa G/Egziabeher for her contribution in preparing the required culture media for this study. In addition,we would also express our gratitude Ms Shishig Masresha and Tigist Basheda for their valuable assistance in cleaning and sterilising the required Petri dishes and other equipment essential for the study.

Competing interests

The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article.

Authors’ contributions

A.A.K. played a substantial role in the study conception, WHONET software configuration, data curation and analysis, writing the original draft, review and editing. Z.T.B. participated in study WHONET software configuration and data curation and analysis. D.B., Z.A., E.T., T.A.K., D.S.T., Y.M., and E.S. participated in writing the original draft, review and editing. A.A.N. participated in supervising and writing, reviewing and editing. All authors read and approved the final manuscript.

Sources of support

The authors received no financial support for the research, authorship, and/or publication of this article.

Data availability

Raw data were extracted from the Ethiopian Public Health Institute antimicrobial resistance surveillance data storage. Raw data are available upon reasonable request from the corresponding author, A.A.K.

Disclaimer

The views and opinions expressed in this article are those of the authors and are the product of professional research. It does not necessarily reflect the official policy or position of any affiliated institution, funder, agency, or that of the publisher. The authors are responsible for this article’s results, findings, and content.

References

  1. Paterson DL. Resistance in gram-negative bacteria: Enterobacteriaceae. Am J Infect Control. 2006;34(5 SUPPL.):20–28. https://doi.org/10.1016/j.ajic.2006.05.238
  2. World Health Organization. New report calls for urgent action to avert antimicrobial resistance crisis [homepage on the Internet]. Jt News Release. 2019, p. 1–4. [cited 2023 February 25]. Available from: https://www.who.int/news/item/29-04-2019-new-report-calls-for-urgent-action-to-avert-antimicrobial-resistance-crisis
  3. United States Centers for Disease Control and Prevention. Antibiotic resistance threats in the United States, 2019. Atlanta, GA: CDC; 2019.
  4. Shaikh S, Fatima J, Shakil S, Rizvi SMD, Kamal MA. Antibiotic resistance and extended spectrum beta-lactamases: Types, epidemiology and treatment. Saudi J Biol Sci. 2015;22(1):90–101. https://doi.org/10.1016/j.sjbs.2014.08.002
  5. Sader HS, Farrell DJ, Flamm RK, Jones RN. Antimicrobial susceptibility of Gram-negative organisms isolated from patients hospitalised with pneumonia in US and European hospitals: Results from the SENTRY Antimicrobial Surveillance Program, 2009–2012. Int J Antimicrob Agents. 2014;43(4):328–334. https://doi.org/10.1016/j.ijantimicag.2014.01.007
  6. Rosenthal VD, Bijie H, Maki DG, Mehta Y, et al. International Nosocomial Infection Control Consortium (INICC) report, data summary of 36 countries, for 2004–2009. Am J Infect Control. 2012;40(5):396–407. https://doi.org/10.1016/j.ajic.2011.05.020
  7. Report S. Antimicrobial resistance in the EU in 2012. Vet Rec. 2014;174(14):341. https://doi.org/10.1136/vr.g2500
  8. Beyene D, Bitaw A, Evans M. Multidrug-resistant profile and prevalence of extended spectrum β -lactamase and carbapenemase production in fermentative Gram-negative bacilli recovered from patients and specimens referred to National Reference. PLoS ONE. 2019;14(9):e0222911. https://doi.org/10.1371/journal.pone.0222911
  9. Javaid N, Sultana Q, Rasool K, et al. Trends in antimicrobial resistance amongst pathogens isolated from blood and cerebrospinal fluid cultures in Pakistan (2011–2015): A retrospective cross-sectional study. PLoS One. 2021;16(4):e0250226. https://doi.org/10.1371/journal.pone.0250226
  10. Zellweger RM, Basnyat B, Shrestha P, et al. Changing antimicrobial resistance trends in Kathmandu, Nepal: A 23-year retrospective analysis of bacteraemia. Front Med. 2018;5(SEP):1–8. https://doi.org/10.3389/fmed.2018.00262
  11. Carroll M, Rangaiahagari A, Musabeyezu E, Singer D, Ogbuagu O. Five-year antimicrobial susceptibility trends among bacterial isolates from a tertiary health-care facility in Kigali, Rwanda. Am J Trop Med Hyg. 2016;95(6):1277–1283. https://doi.org/10.4269/ajtmh.16-0392
  12. Liu C, Xu M, Li X, Dong H, Ming L. Trends in antimicrobial resistance in bloodstream infections at a large tertiary-care hospital in China: A 10-year retrospective study (2010–2019). J Glob Antimicrob Resist. 2022;29:413–419. https://doi.org/10.1016/j.jgar.2021.09.018
  13. Kim D, Ahn JY, Lee CH, et al. Increasing resistance to extended-spectrum cephalosporins, fluoroquinolone, and carbapenem in gram-negative bacilli and the emergence of carbapenem non-susceptibility in klebsiella pneumoniae: Analysis of Korean Antimicrobial Resistance Monitoring System. Ann Lab Med. 2017;37(3):231–239. https://doi.org/10.3343/alm.2017.37.3.231
  14. Musicha P, Cornick JE, Bar-Zeev N, et al. Trends in antimicrobial resistance in bloodstream infection isolates at a large urban hospital in Malawi (1998–2016): A surveillance study. Lancet Infect Dis. 2017;17(10):1042–1052. https://doi.org/10.1016/S1473-3099(17)30394-8
  15. Massongo M, Ngando L, Pefura Yone EW, et al. Trends of antibacterial resistance at the national reference laboratory in Cameroon: Comparison of the situation between 2010 and 2017. Biomed Res Int. 2021;2021:9957112. https://doi.org/10.1155/2021/9957112
  16. Mhondoro M, Ndlovu N, Bangure D, et al. Trends in antimicrobial resistance of bacterial pathogens in Harare, Zimbabwe, 2012–2017: A secondary dataset analysis. BMC Infect Dis. 2019;19(1):1–9. https://doi.org/10.1186/s12879-019-4295-6
  17. Teklu DS, Negeri AA, Legese MH, Bedada TL, Woldemariam HK, Tullu KD. Production and multi-drug resistance among Enterobacteriaceae isolated in Addis. Antimicrob Resist Infect Control. 2019;8:39. https://doi.org/10.1186/s13756-019-0488-4
  18. Tufa TB, Mackenzie CR, Orth HM, et al. Prevalence and characterization of antimicrobial resistance among gram-negative bacteria isolated from febrile hospitalized patients in central Ethiopia. Antimicrob Resist Infect Control. 2022;11(1):1–12. https://doi.org/10.1186/s13756-022-01053-7
  19. Africa Centres for Disease Control and Prevention. Antimicrobial resistance control [homepage on the Internet]. [cited 2022 Aug 20]. p. 1–14. Available from: https://africacdc.org/programme/surveillance-disease-intelligence/antimicrobial-resistance-control/
  20. CLSI. Performance Standards for Antimicrobial Susceptibility Testing. 29th ed. CLSI supplement M100. Wayne, PA: Clinical and Laboratory Standards Institute; 2019.
  21. CLSI. Performance Standards for Antimicrobial Disk Susceptibility Tests. 13th ed. CLSI standard M02. Wayne, PA: Clinical and Laboratory Standards Institute; 2018.
  22. World Health Organization. WHONET Software [homepage on the Internet]. Geneva; 2021 [cited 2023 Nov 25]. Available from: https://whonet.org/software.html
  23. R Core Team: R: A Language and environment for statistical computing [homepage on the Internet]. Vienna: R Foundation for Statistical Computing; 2021 [cited 2023 Nov 26]. Available from: https://www.r-project.org/
  24. Food, Medicine and Health Care Administration and Control Authority. Standard treatment guidelines for general hospitals. 3rd ed. 2014. Addis Ababa: FMHACA. Available from: http://www.fmhaca.gov.et/wp-content/uploads/2019/03/STG-General-Hospital.pdf
  25. Sahilu T, Kano Z. Antibiotics prescribing practice among patients with urinary tract infection at outpatient department, the case of Dilchora referral hospital, Eastern Ethiopia: An institutional retrospective cross-sectional study. J Pharm Policy Pract. 2023;16(1):1–9. https://doi.org/10.1186/s40545-023-00539-y
  26. Mekonnen Eticha E, Gemechu WD. Adherence to guidelines for assessment and empiric antibiotics recommendations for community-acquired pneumonia at Ambo University Referral Hospital: Prospective observational study. Patient Prefer Adherence. 2021;15:467–473. https://doi.org/10.2147/PPA.S295118
  27. Sisay M, Gashaw T, Amare F, Tesfa T, Baye Y. Hospital-level antibacterial prescribing and its completeness in Ethiopia: Did it adhere to good prescribing practice? Int J Gen Med. 2020;13:1025–1034. https://doi.org/10.2147/IJGM.S280696
  28. Worku F, Tewahido D. Retrospective assessment of antibiotics prescribing at public primary healthcare facilities in Addis Ababa, Ethiopia. Interdiscip Perspect Infect Dis. 2018;2018: 4323769. https://doi.org/10.1155/2018/4323769
  29. Hu F, Guo Y, Yang Y, et al. Resistance reported from China antimicrobial surveillance network (CHINET) in 2018. Eur J Clin Microbiol Infect Dis. 2019;38(12):2275–2281. https://doi.org/10.1007/s10096-019-03673-1
  30. Sader HS, Castanheira M, Arends SJR, Goossens H, Flamm RK. Geographical and temporal variation in the frequency and antimicrobial susceptibility of bacteria isolated from patients hospitalized with bacterial pneumonia: Results from 20 years of the SENTRY Antimicrobial Surveillance Program (1997–2016). J Antimicrob Chemother. 2019;74(6):1595–1606. https://doi.org/10.1093/jac/dkz074
  31. Ayukekbong JA, Ntemgwa M, Atabe AN. The threat of antimicrobial resistance in developing countries: Causes and control strategies. Antimicrob Resist Infect Control. 2017;6(1):1–8. https://doi.org/10.1186/s13756-017-0208-x
  32. Landman D, Babu E, Shah N, et al. Transmission of carbapenem-resistant pathogens in New York City hospitals: Progress and frustration. J Antimicrob Chemother. 2012;67(6):1427–1431. https://doi.org/10.1093/jac/dks063
  33. Lee J, Sunny S, Nazarian E, et al. Carbapenem-resistant Klebsiella Pneumoniae in large public acute-care healthcare system, New York, New York, USA, 2016–2022. Emerg Infect Dis. 2023;29(10):1973–1978. https://doi.org/10.3201/eid2910.230153
  34. Zhang J, Li D, Huang X, Long S, Yu H. The distribution of K. pneumoniae in different specimen sources and its antibiotic resistance trends in Sichuan, China From 2017 to 2020. Front Med. 2022;9(February):1–7. https://doi.org/10.3389/fmed.2022.759214
  35. Lin WP, Wang JT, Chang SC, et al. The antimicrobial susceptibility of Klebsiella pneumoniae from community settings in Taiwan, a trend analysis. Sci Rep. 2016;6(May):1–11. https://doi.org/10.1038/srep36280
  36. Wangai FK, Masika MM, Lule GN, et al. Bridging antimicrobial resistance knowledge gaps: The East African perspective on a global problem. PLoS One. 2019;14(2):1–12. https://doi.org/10.1371/journal.pone.0212131
  37. Obakiro SB, Kiyimba K, Paasi G, et al. Prevalence of antibiotic-resistant bacteria among patients in two tertiary hospitals in Eastern Uganda. J Glob Antimicrob Resist. 2021;25:82–86. https://doi.org/10.1016/j.jgar.2021.02.021
  38. Bonomo RA, Szabo D. Mechanisms of multidrug resistance in Acinetobacter species and Pseudomonas aeruginosa. Clin Infect Dis. 2006;43(SUPPL. 2):49–56. https://doi.org/10.1086/504477
  39. Fentie AM, Degefaw Y, Asfaw G, et al. Multicentre point-prevalence survey of antibiotic use and healthcare-associated infections in Ethiopian hospitals. BMJ Open. 2022;12(2):1–10. https://doi.org/10.1136/bmjopen-2021-054541
  40. Gutema G, Håkonsen H, Engidawork E, Toverud EL. Multiple challenges of antibiotic use in a large hospital in Ethiopia – A ward-specific study showing high rates of hospital-acquired infections and ineffective prophylaxis. BMC Health Serv Res. 2018;18(1):1–7. https://doi.org/10.1186/s12913-018-3107-9
  41. Dache A, Dona A, Ejeso A. Inappropriate use of antibiotics, its reasons and contributing factors among communities of Yirgalem Town, Sidama regional state, Ethiopia: A cross-sectional study. SAGE Open Med. 2021;9:205031212110424. https://doi.org/10.1177/20503121211042461
  42. Gutema G, Ali S, Suleman S. Trends of community-based systemic antibiotic consumption: Comparative analyses of data from Ethiopia and Norway calls for public health policy actions. PLoS One. 2021;16(5 May):1–15. https://doi.org/10.1371/journal.pone.0251400
  43. Zanichelli V, Huttner A, Harbarth S, Kronenberg A, Huttner B, Swiss Centre For Antibiotic Resistance Anresis. Antimicrobial resistance trends in Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis urinary isolates from Switzerland: Retrospective analysis of data from a national surveillance network over an 8-year period (2009–2016). Swiss Med Wkly. 2019;149(July):w20110. https://doi.org/10.4414/smw.2019.20110


Crossref Citations

No related citations found.