Long Way Education

By Mariam Mohammad

Mariam is a pharmacy student. She likes sharing her ideas with others.

This article discusses the types of antibiotic resistance, how bacteria resist antibiotics, the UAE’s efforts to decrease the susceptibility of common bacterial pathogens to key antibiotics, and the emergence of new resistance or resistance patterns.

Introduction

Since the development of antimicrobial medications, millions of lives have been saved due to their remarkable effectiveness in preventing bacterial infections. The development of resistance to many of the first effective drugs, even those newly produced, soon after their release, quickly demonstrated that bacterial pathogens are unlikely to succumb completely. It is important to recognize the different manifestations of resistance that an organism may exhibit. Antibiotic resistance may be intrinsic or acquired.

Antibiotics Definition

According to an article written on the NHS website, antibiotics are used to treat or prevent some types of bacterial infections. They work to kill bacteria or stop them from spreading. But they don’t work for all mild bacterial infections. Many mild bacterial infections get better on their own without antibiotics. Antibiotics don’t work for viral infections such as colds and coughs.

Intrinsic Resistance:

Intrinsic resistance to an antimicrobial agent characterizes resistance that is inherently or naturally possessed by bacteria. These organisms may lack the necessary drug-susceptible targets or have natural defenses that prevent the agent from reaching the target, like in the case of streptomyces, which have some genes that make them resistant to their antibiotic. Gram-negative bacteria have an outer membrane that establishes a permeability barrier against antibiotics. An organism may lack a transport system, a target, or a receptor for the antibiotic.

Acquired Resistance:

Acquired resistance is developed due to the changes in the genetic composition of a bacterium so that a drug that once was effective fails to be active. Even though the organisms are still sensitive to the medications, developed resistance is also thought to include tolerance to the previously fatal bactericidal effects. The ability of bacteria to endure antibiotics while ceasing cell development, or the antibiotic’s activity changing from bactericidal to bacteriostatic, is known as tolerance. On the other side, resistance is the continuance of bacterial survival and reproduction in the presence of antibiotics. Microorganisms have gained resistance to most antibiotics through a variety of biochemical mechanisms, which may be classified as follows: 

• Limiting the intracellular concentration of the antimicrobial agent by decreased influx or increased efflux.
• Enzymatic inactivation of antimicrobial agents.
• Decreased conversion of drugs to active growth inhibitory compounds.
• Increased concentration of metabolites antagonizing the drug.
• Altered amount of drug receptor.
• The decreased affinity of the receptor for the drug.
• Decreased activity of an enzyme required to express the drug effect.

Mechanisms of Resistance in Bacteria

Bacteria acquire resistance through two genetic processes:

1. Vertical evolution or vertical gene transfer.
2. Horizontal evolution, or horizontal gene transfer.

1. Vertical Gene Transfer

In vertical genetic exchange, genetic information is passed down to daughter cells through cell division. This resistance may be acquired by mutation and selection.

2. Horizontal Gene Transfer

The acquisition of resistance genes from one organism by another is known as horizontal evolution. The main mechanism behind the emergence of antibiotic resistance is horizontal genetic exchange. One type of bacterial genetic exchange is where one bacterium, which has evolved genetic resistance via mutation and selection, transmits its genes to another bacterial species, i.e., through conjugation, transduction, or transformation.

Antimicrobial Resistance

Antimicrobial resistance emergence is a natural phenomenon accelerated by the misuse and overuse of antimicrobials. Because bacteria are found in several ecosystems—human, animal, and environmental—and can exchange AMR genes between them, understanding AMR dynamics is paramount in mitigating its impact on human health and controlling its spread. The World Health Organization (WHO) released a study in 2015 detailing the findings of a global national situation analysis, which showed inadequacies in addressing antibiotic resistance globally, especially in the Eastern Mediterranean (WHO-EMRO), to which the UAE belongs. A national action plan for AMR, which is regarded as a priority and an outcome indicator for control measures, was specifically not reported as existing in any of the EMRO countries. There was poor awareness of antimicrobial resistance in all sectors, and only fragmented information on the safe use of antimicrobial medicines was available, although this is crucial. Only eight of the 21 countries reported monitoring of resistant microorganisms, indicating a lack of investment in antimicrobial resistance surveillance. Antimicrobial testing laboratories frequently lacked the resources necessary for precise, thorough testing.

In the Gulf Cooperation Council (GCC) region and for the United Arab Emirates, several reports from health authorities, universities, and healthcare facilities have demonstrated a decreasing susceptibility of common bacterial pathogens to key antibiotics and the emergence of new resistance or resistance patterns.

Situation Analysis and Assessment

1. GLASS and the role of surveillance in tackling AMR:

Surveillance is the cornerstone of assessing the spread of AMR and informing and monitoring the impact of local, national, and global strategies. WHO launched Glass in October 2015. GLASS offers a standardized method for countries to gather, analyze, and share AMR data. It also aims to record the current state of any newly created or existing national AMR monitoring systems. GLASS also encourages a change in monitoring strategies from those that just use laboratory data to ones that use epidemiological, clinical, and population-level data.

• Strengths of AMR surveillance: In 2017, the UAE started reporting AMR surveillance implementation data to the WHO and reported in 2018 the first AMR resistance data to the Global Antimicrobial Resistance Surveillance System (GLASS), and the number of hospitals included in the GLASS report reached 52 hospitals in 2018. A subnational Communicable Disease Bulletin has been issued (for Abu Dhabi Emirate), where AMR trends are described and antibiotic susceptibility of some invasive organisms is compared to those in Europe as per the European Antimicrobial Resistance Surveillance Network (EARS-Net), the European Centre for Disease Prevention and Control (ECDC), and annual surveillance reports on antimicrobial resistance. Most of the work has been achieved by a champion (Dr. Jens Thomsen), supported by the Ministry of Health. Food items are being tested for pathogenic organisms (not AMR), and imported meat is being tested for antimicrobial residues. More than 60% of facilities are internationally accredited, which mandates IPC and ASP.
• Weakness of AMR surveillance: The capacity and performance of the microbiology laboratories reporting to GLASS are not checked by the compilation system, whereby data is taken as reported. On the other hand, most reporting hospitals come from Abu Dhabi and Dubai, and the sample may not be epidemiologically representative of the whole country.
  

2. Infection and prevention control:

• Strengths: IPC programs, as part of accreditation standards, exist in most hospitals and are part of the organization of these hospitals; a standard hospital mandate with an infection control program has been issued and implemented in all facilities in the UAE.
  
• Weakness: IPC work is significant in hospitals, but national coordination is weak, and there is no national IPC office and no national minimum IPC for healthcare facilities.

3. Antimicrobial Use and ASP:

• Strength: There is a strong Medicines Office in the Department of Health and Prevention and the National Essential Medicines List, which includes antimicrobials. There is a policy not to dispense antimicrobials in community pharmacies without a prescription, and this policy is applied.
• Weakness: ASP is created in only a few hospitals, and it is difficult to get a new program into the charts of hospitals. Even stakeholders view ASP as part of the IPC programs, while the two programs should be recognized as independent programs with specific staff, terms of reference, and budget. During the workshop discussions, representatives of the Ministry of Commerce, Industry, and Environment described the use of antimicrobials in animals and agriculture as 100% compliant with international laws and biosafety rules, such as the absence of antimicrobials in animal feed, in addition to the absence of 17 of their misuses in this sector. These observations require field visits and reviews of local and international legislation. “One Health” thinking remains poor in the scientific community, as there are no efforts to integrate human and animal health, agriculture, and the environment.

Implemented strategies to Contain Antimicrobial-Resistant Spread

1. For AMR Surveillance

• Developing the rationale, strategies, and action plans for national AMR surveillance.
• AMR monitoring and surveillance techniques and capabilities, situational analysis.
• Review of international AMR surveillance guidelines, best practice examples, and global trends for AMR surveillance.
• Activities for AMR surveillance capacity building, education, and awareness.

2. For IPC in the Healthcare Sector

• Developing the rationale, strategies, action plans, standards, and policies for national antimicrobial stewardship programs.
• Conduct situational and gap analysis on capacities and practices for ASP in the UAE.
• Coordinate, standardize, and streamline efforts among stakeholders and within them.
• The national antibiotic stewardship program should be promoted and supported.

Sources

• Kaye, K.S., Engemann, J.J., Fraimow, H.S., Abrutyn, E. Pathogens resistant to antimicrobial agents: epidemiology, molecular mechanisms, and clinical management. Infect. Dis. Clin. N. Am., 2004; 18: 467-511.
• Mechanisms of Bacterial Resistance.
• Todar, K. Bacterial resistance to antibiotics. In: Todar’s Online Textbook of Bacteriology, University of Wisconsin, Department of Bacteriology. http://www.textbookofbacteriology.net, 2008. 
• Arora, D.R. Textbook of Microbiology, 2nd ed., CBS Publishers and Distributors, 2003; pp. 1-13, 67-94.
• O’Neill J. Tackling drug-resistant infections globally: final report and recommendations. 2016.
• WHO. Antimicrobial Resistance Factsheet 2016.
• (WHO, National Strategy and Action Plan for Combating Antimicrobials, 2019) 1, page 11.
• WHO. Global monitoring of antiviral resistance in currently circulating human influenza viruses (2011).
• WHO, National Strategy and Action Plan for Combating Antimicrobials, 2019.

©Mariam Mohammad, 2024

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