Ella Walter
Antimicrobial resistance (AMR) occurs when microorganisms such as bacteria, viruses, fungi, and parasites are no longer responsive to antimicrobial medicines. AMR is a global public health threat, causing 1.27 million deaths in 2019 and contributing to 4.95 million deaths. The misuse and overuse of antimicrobials in humans, animals, and plants are the main drivers of AMR. As AMR spreads, infections become harder to treat, and medical procedures such as surgery and chemotherapy become riskier. Pan-resistant bacteria are those that cannot be eliminated by currently approved therapies. The emergence of pan-resistant bacteria, such as the first US case reported in Nevada, highlights the critical need for domestic and international programs to address this issue.
| Characteristics | Values |
|---|---|
| Definition | Antibiotic resistance occurs when microorganisms resist the drugs used to treat the infection they cause. |
| Types of Bacteria | Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli, Carbapenem-resistant Enterobacteriaceae (CRE), Staphylococcus aureus, Mycobacterium tuberculosis, etc. |
| Global Deaths | Bacterial AMR was directly responsible for 1.27 million global deaths in 2019 and contributed to 4.95 million deaths. |
| Treatment | Antimicrobial medicines |
| Prevention | CDC recommends screening for patients travelling to areas with a higher incidence of CRE. |
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What You'll Learn
Antimicrobial resistance (AMR)
AMR is a problem worldwide, affecting countries at all income levels. However, low- and middle-income countries are the most impacted due to poverty, inequality, and a lack of access to clean water, sanitation, and hygiene (WASH) for both humans and animals. The misuse and overuse of antimicrobials in humans, animals, and plants are the primary drivers of AMR, and it is exacerbated by a lack of access to quality and affordable vaccines, diagnostics, and medicines.
The emergence of drug-resistant pathogens threatens our ability to treat common infections and perform life-saving procedures. For example, the first case of pan-resistant bacteria in the US was reported by McGann et al., who identified an Escherichia coli strain isolated from a urine culture that was resistant to both colistin and β-lactamase. Additionally, Klebsiella pneumoniae, a common intestinal bacterium, has shown elevated resistance levels against critical antibiotics, leading to the potential over-utilization of last-resort drugs like carbapenems.
The increasing rate of antimicrobial resistance poses a significant threat to modern medicine. It diminishes the efficacy of common antibiotics against widespread bacterial infections and endangers human health worldwide. As resistance levels rise, the world faces an antibiotics pipeline and access crisis, with an inadequate research and development response.
To address AMR, it is crucial to improve the use of antibiotics and antifungals to slow the development of resistance. Additionally, there is a need for robust antimicrobial stewardship practices and enhanced surveillance coverage worldwide. Preventing infections in the first place is also essential, as well as stopping the spread of AMR when it does occur.
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Antibiotic resistance
Bacteria can also acquire resistance by exchanging genetic material, such as through plasmids—pieces of bacterial DNA that can be transferred between bacteria. Plasmids can encode for enzymes that make antibiotics ineffective, and their transfer between bacteria facilitates the spread of resistance. Additionally, spontaneous mutations in bacterial genetic material can lead to the development of resistance. Over time, bacteria can become resistant to multiple antibiotic classes, resulting in "superbugs" that are challenging to treat.
The emergence of antibiotic-resistant bacteria has endangered human health worldwide. Without effective antibiotics, common infections such as bacterial pneumonia could become life-threatening, and complex medical procedures would be far more dangerous. According to the CDC, 2 million people in the US develop antibiotic-resistant infections annually, with at least 23,000 deaths attributed to these infections.
Several bacterial species are associated with pan-drug resistance or resistance to multiple drugs. For example, Acinetobacter baumannii, a Gram-negative coccobacillus, exhibits various drug resistance mechanisms and causes infections such as pneumonia, wound infections, and urinary tract infections. The prevalence of A. baumannii with resistance patterns to carbapenems has increased over the years, leading to high mortality rates in hospital settings. Another example is Klebsiella pneumoniae, which has become a significant public health concern due to its resistance to carbapenems and other drugs, making the treatment of infections challenging.
To combat antibiotic resistance, it is crucial to use antibiotics judiciously and follow instructions when taking them. Healthcare practitioners play a vital role in selecting appropriate antibiotics based on the type of infection, a patient's medical history, and laboratory tests. By optimizing antibiotic use, we can help slow the development of antibiotic resistance and preserve the effectiveness of these crucial medications.
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Multidrug-resistant tuberculosis (MDR-TB)
Antimicrobial resistance (AMR) is a significant global health threat, and the misuse and overuse of antimicrobials in humans, animals, and plants are the primary drivers of AMR development. AMR occurs when bacteria, viruses, fungi, and parasites develop resistance to antimicrobial medicines, rendering them ineffective and making infections harder to treat.
Tuberculosis (TB) is a major contributor to AMR. Multidrug-resistant tuberculosis (MDR-TB) is a form of TB caused by Mycobacterium bacteria that have become resistant to the two most effective first-line anti-TB drugs, isoniazid (INH) and rifampicin (RIF). MDR-TB results from improper treatment regimens, non-compliance with therapy, and spontaneous mutations in the Mycobacterium. It is defined as resistance to at least isoniazid and rifampicin, and it is treatable and curable using second-line drugs. However, these second-line treatments are more expensive, toxic, and difficult to administer, and extensive drug resistance can still develop.
The latest World Health Organization (WHO) survey estimated approximately 450,000 cases of MDR-TB worldwide in 2005, with the majority found in China, India, Eastern European, and Central Asian countries. MDR-TB is seen mainly in people with HIV/AIDS and in Africans. The emergence of MDR-TB threatens to make TB a potentially untreatable infectious disease, and it is a significant concern for TB control programs.
The recommended treatment for MDR-TB combines all first-line drugs to which the strain is still sensitive, a fluoroquinolone, an injectable drug, and one of the several approved second-line drugs. Treatment can last up to two years and is often accompanied by severe side effects. Additionally, MDR-TB poses a substantial financial burden, costing 10 to 100 times more than typical TB treatment, which can endanger the management of other cases if resources are limited.
To address the challenge posed by MDR-TB, it is crucial to prescribe the correct drugs from the beginning and provide supervised treatment. This increases the chances of a cure and reduces the risk of symptom recurrence. Detecting and treating MDR-TB early with appropriate drug combinations is essential, along with managing side effects and supporting patients throughout their treatment journey.
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Pan-resistant Klebsiella pneumoniae
Antimicrobial resistance (AMR) is a significant threat to public health worldwide. AMR occurs when bacteria, viruses, fungi, and parasites no longer respond to antimicrobial medicines, rendering antibiotics and other antimicrobial medicines ineffective. This problem is exacerbated by the overuse and misuse of antimicrobials, which are used to treat, prevent, and control infections in humans, animals, and plants.
One of the bacteria that have become resistant to antimicrobials is Klebsiella pneumoniae (K. pneumoniae). K. pneumoniae is a Gram-negative bacterium that has become the second most prevalent clinically isolated Gram-negative bacilli after E. coli. The emergence of carbapenem-resistant K. pneumoniae is particularly concerning due to the lack of effective therapeutic options. Carbapenem-resistant K. pneumoniae, also known as PDR bacteria or super bacteria, has been isolated in health centers worldwide and has shown resistance to drugs such as tigecycline and colistin.
In 2016, a case of pan-resistant K. pneumoniae was documented in the US in a woman who had recently arrived from India and was admitted to a Nevada hospital. The K. pneumoniae strain isolated from her hip abscess was resistant to all 26 antimicrobials tested, including B-lactams, colistin, and aminoglycosides. The isolate was also found to be resistant to tigecycline, a drug developed in response to emerging antibiotic resistance. This case highlighted the importance of current and effective susceptibility testing methods to prevent inappropriate therapy.
The emergence of pan-resistant K. pneumoniae poses a significant threat to public health due to the high mortality rate and lack of valid treatment options. The development of new antibiotics and combination drugs, such as plazomicin, ceftazidime-avibactam, and meropenem-vaborbactam, has been spurred by the increasing resistance of K. pneumoniae. However, resistance to these drugs has also been reported, emphasizing the need for ongoing research and development to combat AMR.
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Pan-resistant Escherichia coli
Antibiotic resistance occurs when microorganisms can resist the drugs used to treat the infection they cause, neutralizing their effects. This resistance can be developed through various mechanisms, including preventing drug absorption and changing drug targets. The emergence of antibiotic resistance in bacteria has endangered human health worldwide, and the problem is observed in both Gram-positive and Gram-negative bacteria.
Escherichia coli, or E. coli, is one of the most common causes of sepsis, contributing to over 15% of sepsis cases. Multidrug resistance in E. coli has become a significant concern in human and veterinary medicine globally. While E. coli is typically susceptible to almost all clinically relevant antimicrobial agents, it has a remarkable ability to accumulate resistance genes, primarily through horizontal gene transfer.
The most problematic resistance mechanisms in E. coli are related to the acquisition of specific genes. These include genes coding for extended-spectrum β-lactamases, which confer resistance to broad-spectrum cephalosporins, and carbapenemases, which provide resistance to carbapenems. Additionally, E. coli may possess 16S rRNA methylases, resulting in pan-resistance to aminoglycosides, and plasmid-mediated quinolone resistance (PMQR) genes, conferring resistance to fluoroquinolones.
The first reported case of pan-resistant E. coli in the United States was identified by researchers at Johns Hopkins University School of Medicine. They encountered a 66-year-old male patient who had travelled to India for a kidney transplant and subsequently developed cystitis (bladder inflammation). The patient was then treated for pyelonephritis (kidney infection) caused by New Delhi metallo-beta-lactamase (NDM)-producing E. coli. Despite antimicrobial susceptibility testing indicating resistance to preferred treatment regimens, the patient was continued on the same treatment and experienced a relapse.
The emergence of pan-resistant bacteria, including E. coli, poses a significant threat to global health. Modelling the impact of a single hypothetical pan-resistant E. coli strain in the United States suggested that sepsis deaths could increase drastically within five years of its emergence. This underscores the importance of preventing the spread of antimicrobial resistance and developing effective treatments for pan-resistant infections.
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Frequently asked questions
Pan-resistant bacteria are bacteria that are resistant to all currently approved therapies and antibiotics.
Antimicrobial Resistance (AMR) occurs when bacteria, viruses, fungi, and parasites no longer respond to antimicrobial medicines. This is a natural process that happens over time through genetic changes in pathogens. The emergence and spread of AMR are accelerated by human activity, such as the misuse and overuse of antimicrobials.
Pan-resistant bacteria pose a significant threat to global health and development. Infections become harder or even impossible to treat, increasing the risk of severe illness, disability, and death. AMR also puts the gains of modern medicine at risk, making medical procedures such as surgery and cancer chemotherapy much riskier.
While pan-resistant bacteria are uncommon, they have been reported in the United States and around the world. The first US case of pan-resistant bacteria was reported by McGann et al., who identified an Escherichia coli strain resistant to both colistin and β-lactamase. Another notable case occurred in 2016, where a woman in Nevada with Klebsiella pneumoniae was resistant to all 26 antimicrobials tested.
