Antimicrobial resistance (AMR) and Antibacterial Resistance (ABR)

The emergence of antimicrobial resistance (AMR) in pathogenic microorganisms poses a significant public health concern, leading to exacerbated illnesses, increased mortality rates, and elevated treatment expenses, often with restricted therapeutic options. Without effective interventions, the projected death toll by 2050 could surpass the alarming estimate of over 10 million deaths per year outlined in the 2014 AMR Review. Urgent and coordinated efforts are imperative to address this escalating threat to global health.

Antimicrobial resistance (AMR) refers to the capacity of microorganisms to withstand the effects of antimicrobials that were previously effective in eradicating or inhibiting their growth. The emergence of antimicrobial resistance enables microorganisms to persist and proliferate even following exposure to antimicrobial agents. In the context of pathogens, the development of resistance can prolong the recovery period from infections, exacerbate the severity of infections, necessitate higher medication dosages, and elevate the potential mortality rate.

Antimicrobial resistance is predominantly studied in bacteria and fungi, with a limited number of parasites exhibiting resistance to their respective treatment options. When bacteria resist the effects of antibiotics, it is termed “antibacterial resistance (ABR),” while fungi demonstrating resistance to antifungals are referred to as having “antifungal resistance (AFR).” Similarly, viruses and helminths developing resistance to their treatment options are termed “antiviral resistance” and “anthelmintic resistance,” respectively. This escalating challenge demands vigilant research and intervention strategies to preserve the efficacy of antimicrobial treatments.

Among antimicrobial resistance (AMR), antibacterial resistance (ABR) stands out as a paramount concern due to the widespread development of resistance among various pathogenic bacterial species, resulting in severe infections. While resistance in fungi, viruses, and parasites is currently less prevalent than bacterial resistance, reports of resistance in these microorganisms are on the rise. Vigilant monitoring and concerted efforts are essential to address the escalating issue of antimicrobial resistance across diverse pathogens.

AMR is Developed generally due to four AMR mechanisms

Antimicrobial resistance (AMR) commonly arises through four primary mechanisms:

1. Modification or inactivation of the drug.
2. Reduction in absorption or decreased affinity to the drug.
3. Increased efflux of the drug.
4. Modification of cellular components that serve as the target site for the drug.

These mechanisms can result from either genetic mutations or the insertion of genes governing these processes. Microbial resistance may be specific to a particular class of antimicrobials or extend across multiple types. In the case of resistance to a single class of structurally and mechanistically similar antimicrobials, it is termed “resistance to that particular class.” For instance, if bacteria are resistant to penicillin and its derivatives, they are referred to as “penicillin-resistant bacteria.”

On the other hand, if resistance encompasses different types of antimicrobials with distinct structures and modes of action, it is categorized as “multi-drug resistance (MDR).” MDR pathogens are commonly known as “SUPER BUGS.” MDR is further classified into “Extensively Drug-Resistant (XDR),” where organisms remain susceptible to antimicrobials in at most two structurally unrelated antimicrobial classes, and “Pan Drug-Resistant (PDR),” where organisms exhibit resistance to all available antimicrobials.

Recognizing the severity of AMR, the World Health Organization (WHO) has identified it as one of the top 10 global public health threats. In 2017, the WHO released a list of antibiotic-resistant bacteria in a report titled “Global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics.” Furthermore, the US Center for Disease Control and Prevention (CDC) published a list of resistant bacteria and fungi in its 2019 AR Threat Report, including additional pathogens of concern in the United States beyond those listed by the WHO in 2017. Addressing AMR remains a critical global health priority.

WHO 2017; Global Priority Pathogens List of antibiotic-resistant bacteria

The World Health Organization (WHO) released the Global Priority List of antibiotic-resistant bacteria in 2017. This list includes bacteria that pose the greatest threat to human health due to their high levels of resistance to existing antibiotics and their potential to cause severe infections. The list is divided into three priority categories: Critical, High, and Medium. Here are the bacteria included in each category:

Critical Priority:

1. Acinetobacter baumannii, carbapenem-resistant
2. Pseudomonas aeruginosa, carbapenem-resistant
3. Enterobacteriaceae (e.g., Klebsiella, Escherichia coli, Serratia, and Proteus species) producing extended-spectrum beta-lactamases (ESBLs)
   • Escherichia coli
   • Klebsiella pneumoniae
   • Klebsiella oxytoca
   • Proteus mirabilis
   • Others

High Priority:

1. Enterococcus faecium, vancomycin-resistant
2. Staphylococcus aureus, methicillin-resistant, vancomycin-intermediate, and resistant
3. Helicobacter pylori, clarithromycin-resistant
4. Campylobacter spp., fluoroquinolone-resistant
5. Salmonella spp., fluoroquinolone-resistant
6. Neisseria gonorrhoeae, cephalosporin-resistant, fluoroquinolone-resistant

Medium Priority:

1. Streptococcus pneumoniae, penicillin-non-susceptible
2. Haemophilus influenzae, ampicillin-resistant
3. Shigella spp., fluoroquinolone-resistant

CDC 2019; Antibiotic Resistance Threat List

The Centers for Disease Control and Prevention (CDC) in the United States regularly publishes the Antibiotic Resistance Threat List, which highlights the most urgent antibiotic-resistant threats to public health. The 2019 Antibiotic Resistance Threat Report categorizes pathogens based on their level of concern and impact on human health.

Urgent Threats:

1. Clostridioides difficile (C. difficile): This bacterium causes life-threatening diarrhea and is often associated with healthcare settings.
2. Carbapenem-resistant Acinetobacter: A bacterium that can cause severe respiratory and urinary tract infections, especially in healthcare settings.
3. Drug-resistant Neisseria gonorrhoeae: The bacteria responsible for gonorrhea, a sexually transmitted infection.

Serious Threats:

1. Multidrug-resistant Enterobacteriaceae (including Escherichia coli, Klebsiella pneumoniae, and others): These bacteria cause a range of infections and are becoming increasingly resistant to multiple antibiotics.
2. Methicillin-resistant Staphylococcus aureus (MRSA): A bacterium responsible for various infections, including skin infections and pneumonia.
3. Drug-resistant Streptococcus pneumoniae: This bacterium can cause pneumonia, meningitis, and other serious infections.

Concerning Threats:

1. Vancomycin-resistant Staphylococcus aureus (VRSA): A strain of MRSA that is also resistant to the antibiotic vancomycin.
2. Erythromycin-resistant Group A Streptococcus: This bacterium can cause various infections, including strep throat.

The CDC’s report emphasizes the need for coordinated efforts to combat antibiotic resistance through surveillance, prevention, and the development of new antibiotics. It serves as a resource for healthcare professionals, researchers, and policymakers to address the growing threat of antibiotic-resistant infections in the United States.

Key Differences between Antimicrobial resistance (AMR) and Antibacterial Resistance (ABR)