The Burden of Multidrug-Resistant Escherichia coli in Uganda

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By Patrick Vuzara

For correspondence: vuxarapatrice@gmail.com

Escherichia coli (E. coli) is a rod-shaped Gram-negative facultative anaerobe that is a commensal microbiota in the intestinal tract of humans, fish, and poultry.[1] It is considered an indicator and potentially opportunistic microbe,[2] and is a common cause of community- and hospital-acquired infections worldwide, including diarrhea, urinary tract infections, meningitis, and septicemia.[3] [4] Pathogenic strains of E. coli in poultry harbor many virulence genes and may carry antimicrobial resistance (AMR) mechanisms that influence disease presentation and treatment outcomes.[5]

AMR occurs when bacteria evolve to become resistant to the drugs used to treat infections and make those drugs less effective. The rise and spread of drug-resistant bacteria has developed into one of the leading public health fears of the 21st century.[6] Resistance to commonly used antibiotics is ascribed to the inappropriate use of these drugs by clinicians without evidence of a causative agent and antibiogram, and to self-treatment with readily available and cheap over-the-counter antibiotics.[7] Additionally, agricultural practices have been implicated in the emergence and spread of AMR, owing to the fact that antimicrobial agents are used as growth promoters and for prophylaxis in livestock production.[8] Transmission of resistant bacteria from animals to humans may occur via the food chain, environment or by direct interaction with animals.[9]

Because E. coli is the most common Gram-negative pathogen in humans, growing resistance to common antibiotics like cephalosporins and quinolones, as well as multidrug resistance (MDR), have been recognized as a global problem.[10] In 2019, it was reported that 1.27 million deaths were attributable to AMR and 4.95 million deaths were associated with AMR globally, and E. coli was one of the six leading pathogens linked to those deaths: 23.4% of deaths attributable to AMR and 24.3% of deaths associated with AMR were due to E. coli.[11]

Uganda, which has a structured national AMR surveillance program in alignment with the World Health Organization Global Antimicrobial Resistance and Use Surveillance System (GLASS), is one of many low- and middle-income countries where AMR poses a significant health threat. It has been reported to have a high burden of infectious diseases and high rates of antibiotic use and is consequently vulnerable to AMR.[12] Research has shown that 40% of the individuals who visit a healthcare facility in Uganda are treated with antibiotics.[13]

Although data on drug-resistant infections in low- and middle-income countries like Uganda is scant, drug resistance has been reported to be prevalent in healthcare settings in Uganda.[14] In Uganda, E. coli has been identified as one of the most prevalent (45.62%) GLASS priority pathogens, with high resistance noted in ceftriaxone (52.7%), and imipenem (18.8%), and ciprofloxacin (52%).[15] E. coli were reported to have caused 9.68% of surgical site infections in Southwestern Uganda, with 55.5% of these isolates highly resistant to commonly used antibiotics.[16]

Additionally, a 22.8% prevalence of phenotypic carbapenem resistance of E. coli was reported in a study conducted in four referral hospitals (Mbale Regional, Mbarara Regional, Mulago National, and Kampala International University-Teaching Hospital), with the highest prevalence (53.9%) obtained from Mbale regional.[17] Martin et al. also reported a high prevalence of non-typeable strains of MDR E. coli isolates from the urinary tracts of patients in Bushenyi, Uganda that were resistant to erythromycin, co-trimoxazole, and ampicillin.[18]E. coli was also the most common uropathogen (71.9%) isolated among HIV-infected patients in Uganda, whose isolates were completely resistant to cotrimoxazole and ampicillin.[19] Cotrimoxazole is being used as prophylaxis for opportunistic infections in this group of patients.

Based on another study, patients with  MDR E. coli infections had significantly higher odds of dying within 30 days of the onset of their infection as compared to patients with non-MDR E. coli infections.[20] Fluroquinolone resistance among E. coli isolated from the urinary tract has also been reported from Bushenyi Uganda, with ofloxacin being the most resistant (34.9%), followed by moxifloxacin (32.5%), levofloxacin (27.9%) and ciprofloxacin (26.7%).[21] Urinary tract infections are one of the most common infectious diseases, and they can damage different parts of the urinary system such as the urethra, bladder, ureters, and kidney. It is estimated that nearly 150 million people annually are diagnosed with UTIs, costing greater than $6 billion US dollars used for healthcare.[22]

In a study conducted in two hospitals in eastern Uganda, high rates of resistance in E. coli were reported for many other antimicrobial agents, including amoxicillin/ clavulanate (83.5%), cefotaxime (74.2%), ciprofloxacin (92.1%), gentamicin (51.8%), imipenem (3.2%), tetracycline (98%) and trimethoprim-sulfamethoxazole (74.1%).[23]

In addition, E. coli is widely distributed not only in humans in Uganda but also in domestic animals and other primates, as reported by Weiss et al.; in a study of E. coli isolates from rural Uganda, they found the frequency of resistant E. coli was 57.4% in people, 19.5% in domestic animals, and 16.3% in wild nonhuman primates.[24] Another study found an 88.4% prevalence of multidrug-resistant E. coli isolates in poultry in Uganda.[25] A study conducted in northern Uganda reported that 47.5% E. coli isolates obtained from pigs were resistant to sulfamethoxazole (88%), tetracycline (54%), and trimethoprim (17%).[26] Oreochromis niloticus (Nile Tilapia), a commonly consumed fish species in Uganda, were reported to be reservoirs of E. coli that were 72.7% resistant to ampicillin and erythromycin.[27]

In a low-resource country like Uganda, many factors are likely to contribute to the transmission of resistant E. coli strains, including poor hygienic practices and environmental hygiene that is potentiated by low levels of funding and supervision of sewage systems.[28] Uganda’s structured national AMR surveillance program could play role in monitoring transmission and estimating the effects of resistant E. coli on incidence, deaths, hospital length of stay, and healthcare costs.

Limiting the spread of resistant E. coli can be achieved at all levels of society, such as individuals, policymakers, health professionals, healthcare industries, and agricultural sectors. These measures include; avoiding the use of leftover antibiotic prescriptions, ensuring taking full prescriptions of prescribed antibiotics, use of antibiotics only when prescribed by a doctor, avoiding antibiotics as growth promoters in animals, vaccinating animals to reduce the need for antibiotics, investing in research and development of new antibiotics, reporting antibiotic-resistant infections to surveillance team, preventing infections by regular hand washing, hygienic food preparations, following doctor’s advice on antibiotic use and keeping vaccinations up to date.

References


[1] K. Ikwap et al., “The Presence of Antibiotic-Resistant Staphylococcus Spp. and Escherichia Coli in Smallholder Pig Farms in Uganda.” BMC Veterinary Research 17, no. 1 (December 18, 2021): 31, https://doi.org/10.1186/s12917-020-02727-3.

[2] Hamiisi Kikomeko, S.P Wamala, and K.K Mugimba, “Antimicrobial Resistance of Escherichia Coli Found in Intestinal Tract of Oreochromis Niloticus,” Uganda Journal of Agricultural Sciences 17, no. 2 (September 1, 2016): 157, https://doi.org/10.4314/ujas.v17i2.3

[3] M. C. MacKinnon et al., “Evaluation of the Health and Healthcare System Burden Due to Antimicrobial-Resistant Escherichia Coli Infections in Humans: A Systematic Review and Meta-Analysis,” Antimicrobial Resistance & Infection Control 9, no. 1 (December 10, 2020): 200, https://doi.org/10.1186/s13756-020-00863-x

[4] Kenneth Ssekatawa et al., “Carbapenem Resistance Profiles of Pathogenic Escherichia Coli in Uganda,” European Journal of Biology and Biotechnology 2, no. 2 (April 7, 2021): 63–73, https://doi.org/10.24018/ejbio.2021.2.2.171.

[5] Steven Kakooza et al., “A Retrospective Analysis of Antimicrobial Resistance in Pathogenic Escherichia Coli and Salmonella Spp. Isolates from Poultry in Uganda,” International Journal of Veterinary Science and Medicine 9, no. 1 (January 1, 2021): 11–21, https://doi.org/10.1080/23144599.2021.1926056.

[6] Christopher JL Murray et al., “Global Burden of Bacterial Antimicrobial Resistance in 2019: A Systematic Analysis,” The Lancet 399, no. 10325 (February 2022): 629–55, https://doi.org/10.1016/S0140-6736(21)02724-0.

[7] Derick Hope et al., “Antimicrobial Resistance in Pathogenic Aerobic Bacteria Causing Surgical Site Infections in Mbarara Regional Referral Hospital, Southwestern Uganda,” Scientific Reports 9, no. 1 (December 21, 2019): 17299, https://doi.org/10.1038/s41598-019-53712-2.

[8]  Kikomeko et al., “Escherichia Coli Found in Intestinal Tract of Oreochromis Niloticus.” 157

[9] Iramiot Jacob Stanley et al., “Multidrug Resistance among Escherichia Coli and Klebsiella Pneumoniae Carried in the Gut of Out-Patients from Pastoralist Communities of Kasese District, Uganda,” ed. Zhi Ruan, PLOS ONE 13, no. 7 (July 17, 2018): e0200093, https://doi.org/10.1371/journal.pone.0200093.

[10] MacKinnon et al., “Health and Healthcare System Burden Due to AMR E coli.”200

[11] Murray et al., “Global Burden of Bacterial Antimicrobial Resistance in 2019: A Systematic Analysis.”629-55

[12] George Abongomera et al., “Spectrum of Antibiotic Resistance in UTI Caused by Escherichia Coli among HIV-Infected Patients in Uganda: A Cross-Sectional Study,” BMC Infectious Diseases 21, no. 1 (December 23, 2021): 1179, https://doi.org/10.1186/s12879-021-06865-3.

[13] Stanley et al., “Escherichia Coli and Klebsiella Pneumoniae Carried in the Gut of Out-Patients.” e0200093

[14] Susan Nabadda et al., “Implementation of the World Health Organization Global Antimicrobial Resistance Surveillance System in Uganda, 2015-2020: Mixed-Methods Study Using National Surveillance Data,” JMIR Public Health and Surveillance 7, no. 10 (October 21, 2021): e29954, https://doi.org/10.2196/29954.

[15] Nabadda et al., “WHO GLASS in Uganda, 2015-2020.” e29954.

[16] Hope et al., “AMR in Pathogenic Aerobic Bacteria Causing Surgical Site Infections.” 17299

[17] Ssekatawa et al., “Carbapenem Resistance Profiles of Pathogenic Escherichia Coli in Uganda.”

[18] Martin et al., “Phylogenetic Analysis of Multidrug Resistant E. Coli Isolates from the Urinary Tract in Bushenyi District, Uganda Using the New Clermont Phylotyping Method.” African Journal of Microbiology Research 14, no. 2 (February 29, 2020): 51–64. https://doi.org/10.5897/AJMR2019.9221.

[19] Abongomera et al., “Antibiotic Resistance in UTI Caused by Escherichia Coli among HIV-Infected Patients.” 1179

[20] MacKinnon et al., “Health and Healthcare System Burden Due to AMR E coli.”200

[21] Martin Odoki et al., “Fluoroquinolone Resistant Bacterial Isolates from the Urinary Tract among Patients Attending Hospitals in Bushenyi District, Uganda,” Pan African Medical Journal 36 (2020): 1–12, https://doi.org/10.11604/pamj.2020.36.60.18832.

[22] Martin et al., “Phylogenetic Analysis of Multidrug Resistant E. Coli Isolates from the Urinary Tract.” 51–64.

[23] Samuel Baker Obakiro et al., “Prevalence of Antibiotic-Resistant Bacteria among Patients in Two Tertiary Hospitals in Eastern Uganda,” Journal of Global Antimicrobial Resistance 25 (June 2021): 82–86, https://doi.org/10.1016/j.jgar.2021.02.021

[24] Weiss et al., “Antibiotic-Resistant Escherichia Coli and Class 1 Integrons in Humans, Domestic Animals, and Wild Primates in Rural Uganda.” Edited by Edward G. Dudley. Applied and Environmental Microbiology 84, no. 21 (November 2018). https://doi.org/10.1128/AEM.01632-18.

[25] Kakooza et al., “AMR in Pathogenic Escherichia Coli and Salmonella Spp. Isolates from Poultry in Uganda.”11-21

[26] Ikwap et al., “The Presence of Antibiotic-Resistant Escherichia Coli in Smallholder Pig Farms in Uganda.” 63-73

[27] Kikomeko et al., “Escherichia Coli Found in Intestinal Tract of Oreochromis Niloticus.” 157

[28] Christine F Najjuka et al., “Antimicrobial Susceptibility Profiles of Escherichia Coli and Klebsiella Pneumoniae Isolated from Outpatients in Urban and Rural Districts of Uganda,” BMC Research Notes 9, no. 1 (December 25, 2016): 235, https://doi.org/10.1186/s13104-016-2049-8.

About the Author: Patrick Vuzara is a finalist pharmacy student at Kampala International University in Uganda. He is also an active member of the International Pharmaceutical Students Federation, Uganda Pharmaceutical Students Association, and Kampala International University Pharmacy Students Association

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