The Rise Of Pan-Resistant Diseases: How Often Do They Occur?

The emergence of pan-resistant infections is a major public health concern. Antimicrobial resistance (AMR) occurs when bacteria, viruses, fungi and parasites no longer respond to antimicrobial medicines, making infections harder to treat and increasing the risk of disease spread, severe illness, disability and death. The misuse and overuse of antimicrobials in humans, animals and plants are the main drivers in the development of drug-resistant pathogens. AMR is a complex problem that requires a coordinated global approach. Pan-resistant bacteria have emerged globally, and clinicians face a dilemma in how to treat multidrug-resistant strains. Polyarteritis Nodosa (PAN) is a rare condition of inflamed blood vessels that can affect people of all ages but usually occurs in those aged 45 to 65. It is caused by an unknown factor, but immune mechanisms appear to be involved.

Pan-drug-resistant organisms (MDROs)

MDROs, including MRSA, VRE, and GNB, deserve special attention in healthcare facilities. In addition to MRSA and VRE, certain GNB, including those producing extended-spectrum beta-lactamases (ESBLs) and those resistant to multiple classes of antimicrobial agents, are of particular concern. Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa are examples of MDROs that have been reported in multiple countries. These organisms have become resistant to all commercially available antimicrobial agents, leaving limited treatment options.

The clinical manifestations of MDRO infections are similar to those caused by susceptible pathogens. However, the options for treating patients with these infections are often very limited. For example, vancomycin was once the only effective therapy for potentially life-threatening MRSA infections, and there were virtually no antimicrobial agents available to treat VRE infections. While antimicrobials are now available for MRSA and VRE, resistance to each new agent has already emerged. Similarly, therapeutic options are limited for ESBL-producing isolates of gram-negative bacilli and strains of A. baumannii resistant to all antimicrobial agents except imipenem.

The emergence of pan-resistant bacteria poses a significant challenge to clinicians, as they must determine how to treat multidrug-resistant strains. Susceptibility testing methods need to be up-to-date and capable of detecting these strains to prevent inappropriate therapy. Rapid genomic analysis is also necessary to identify resistance mechanisms and monitor resistance patterns through reporting and surveillance.

The impact of MDROs is significant, with increased lengths of stay, costs, and mortality associated with these infections. Studies have documented increased mortality, hospital lengths of stay, and hospital charges associated with multidrug-resistant gram-negative bacilli, including outbreaks in healthcare settings. MDROs, such as vancomycin-resistant enterococci (VRE), have been linked to increased mortality, length of hospital stay, admission to the ICU, surgical procedures, and costs.

Antimicrobial resistance

The World Health Organization (WHO) has declared AMR as one of the top global public health and development threats. It is estimated that AMR was directly responsible for 1.27 million deaths in 2019 and contributed to 4.95 million deaths globally. By 2050, it is projected that 10 million people could die annually from drug-resistant infections, with Africa alone accounting for 4.5 million deaths.

The emergence of pan-resistant infections, where bacteria are resistant to all known antimicrobials, further exacerbates the AMR crisis. Clinicians are faced with limited therapeutic options as pan-resistant bacteria become a growing reality. The first case of pan-resistant bacteria in the US was reported by McGann et al., who identified an Escherichia coli strain resistant to both colistin and β-lactamase. Subsequently, a case of pan-resistant Klebsiella pneumoniae was documented in a patient from India, who died from septic shock within a month despite limited therapeutic options.

The lack of effective treatments for pan-resistant infections highlights the urgent need for innovation and investment in AMR research and development. The clinical pipeline for new antimicrobials is sparse, and the challenge of creating profitable treatments due to the short-term nature of antibiotic use further exacerbates the issue. To address this, several countries are exploring innovative financial models, such as the UK's "subscription model," to incentivize the development of novel antimicrobials.

The impact of AMR is felt most severely in low- and middle-income countries, and it poses a significant barrier to sustainable development. The Africa CDC reports that the continent faces the highest mortality rate from AMR, with 27.3 deaths per 100,000 people, exceeding the combined death toll from HIV-AIDS, tuberculosis, and malaria. Additionally, millions in Africa lack access to essential antibiotics, with only 1.3% of microbiology labs in member states capable of testing for key AMR pathogens.

The emergence of pan-resistant bacteria

The most common PDR bacteria include Gram-negative bacteria such as Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, and Escherichia coli. These bacteria are significant because they are widespread in clinical settings, have a high colonisation incidence rate, and pose a severe threat to human health due to their strong stability and resistance to antibacterial substances.

The treatment of PDR infections is challenging and often requires the use of synergistic combinations of multiple antimicrobial agents. For example, the treatment of PDR A. baumannii may include the use of tigecycline in combination with colestimethate, imipenem, amikacin, and ampicillin-sulbactam. The PDR K. pneumoniae has been treated with tigecycline and colistin, but more effective agents such as nitrofurantoin, fosfomycin, and pivmecillinam are now being used. The treatment of PDR P. aeruginosa typically involves the use of conventional antipseudomonal β-lactam antibacterial drugs, such as cefepime and carbapenems, in combination with another antibiotic class. The treatment of PDR E. coli focuses on urinary tract infections (UTIs) and includes the use of nitrofurantoin, fosfomycin tromethamine, or pivmecillinam as first-line treatments.

The emergence of PDR bacteria has led to increased hospitalisation, healthcare costs, and mortality rates. It has also limited the effectiveness of common antibiotics, making it difficult to treat bacterial infections. The lack of effective treatments for PDR bacteria has prompted the need for new medicines and methods to combat antimicrobial resistance.

The impact of pan-resistant infections on healthcare

Pan-resistant infections, or antimicrobial resistance (AMR), pose a significant threat to healthcare systems worldwide. AMR occurs when bacteria, viruses, fungi, and parasites no longer respond to antimicrobial medicines, rendering them ineffective and leaving infections untreated or difficult to treat. This leads to severe illness, disability, and death, causing approximately 1.27 million deaths globally in 2019.

The emergence of AMR is accelerated by the misuse and overuse of antimicrobials in humans, animals, and plants. The rise of AMR has made common infections harder to treat and has made other medical procedures, such as surgeries, caesarean sections, and cancer chemotherapy, much riskier. It also impacts the health of animals and plants, reducing productivity in farms and threatening food security.

AMR has significant economic implications for healthcare systems. It increases the need for more expensive and intensive care, prolongs hospital stays, and affects patient and caregiver productivity. The World Bank estimates that AMR could result in additional healthcare costs of up to $3.4 trillion per year by 2030.

To address AMR, it is crucial to prevent infections, ensure universal access to quality diagnosis and appropriate treatment, and enhance surveillance and research for novel solutions. The development and spread of AMR do not recognize country borders, and it is essential to have a coordinated global response to tackle this issue effectively.

Preventing pan-resistant infections

The emergence of pan-resistant infections poses a significant threat to global health, as these infections are resistant to all known antimicrobial compounds. The development of drug-resistant pathogens is largely driven by the overuse and misuse of antimicrobials in humans, animals, and plants. To prevent the spread of pan-resistant infections, a range of measures must be implemented across various sectors, including human health, food production, animal health, and the environment.

Preventing Infections

One key strategy to address pan-resistant infections is to prevent all infections that may lead to the inappropriate use of antimicrobials. This includes improving access to clean water, sanitation, and hygiene (WASH) for both humans and animals, as well as enhancing infection prevention and control practices in homes, healthcare facilities, and farms.

Surveillance and Monitoring

Surveillance and monitoring of antimicrobial resistance (AMR) and antimicrobial consumption are crucial to track the spread of pan-resistant infections. The World Health Organization (WHO) has established the Global Antimicrobial Resistance and Use Surveillance System (GLASS) to fill knowledge gaps and inform strategies at all levels. Participating countries are required to complete the Tracking AMR Country Self-Assessment Survey (TrACSS) to monitor their progress in implementing AMR national action plans.

Access to Quality Diagnosis and Treatment

Ensuring universal access to quality diagnosis and appropriate treatment of infections is essential. This includes improving access to quality and affordable vaccines, diagnostics, and medicines, especially in low- and middle-income countries. Antimicrobial stewardship programs should be implemented to educate and support healthcare professionals in following evidence-based guidelines for prescribing and administering antimicrobials.

Innovation and Research

There is an urgent need for innovation and research to address the threat of pan-resistant infections. This includes the development of new antimicrobials, diagnostics, and vaccines, as well as enhancing epidemiological and operational research to inform public health actions.

Global Coordination and Collaboration

Pan-resistant infections do not respect country borders, and a coordinated global response is necessary. The WHO's Global Action Plan (GAP) on AMR, adopted by countries during the 2015 World Health Assembly, provides a framework for countries to develop and implement multisectoral national action plans. The One Health approach brings together stakeholders from various sectors to communicate and collaborate in designing, implementing, and monitoring programs, policies, legislation, and research to mitigate AMR.

Public Awareness and Education

Raising public awareness about the dangers of pan-resistant infections and educating communities about proper antimicrobial use can help prevent the overuse and misuse of these medications. Campaigns such as World AMR Awareness Week play a crucial role in increasing understanding and promoting best practices among the public, stakeholders, and policymakers.

By implementing these comprehensive strategies, we can work towards preventing pan-resistant infections and safeguarding the effectiveness of antimicrobial treatments.

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