Antibiotics Resistance & The Epidemic of Superbugs

Antimicrobial resistance (AMR) is an emerging global public health threat. Antimicrobial drugs, which include antibiotics, antivirals, antifungals, and antiparasitic agents, are designed to treat infections caused by bacteria, fungi, viruses, protozoa, and parasites. The term antimicrobial resistance (AMR) refers to the ability of microorganisms to thrive despite the presence of these drugs meant to eradicate them i.e. these microorganisms thrive, even in the presence of drugs that are designed to kill them! The rising prevalence of AMR challenges modern medicine by limiting life-saving therapeutic options. Left unaddressed, previously manageable surgeries could become insurmountable, and once treatable infections could now pose life-threatening risks.

Historically, the emergence of penicillin resistance in the 1950s marked a significant clinical challenge, threatening decades of medical progress. The subsequent discovery of beta-lactam antibiotics in the 1960s briefly restored confidence in antibiotic treatment. However, this was quickly undermined by the appearance of Methicillin-resistant Staphylococcus aureus (MRSA) in the United Kingdom in 1962 and in the United States in 1968, followed by reports of vancomycin resistance in 1979 and 1983. Studies have indicated persistent resistance in pathogens like Pseudomonas aeruginosa and Klebsiella pneumoniae, particularly in hospital environments. The 2022 Global Antimicrobial Resistance and Use Surveillance System (GLASS) report highlights alarming resistance rates among prevalent bacterial pathogens, with median reported rates in 76 countries of 42% for third-generation cephalosporin-resistant E. coli and 35% for MRSA, further complicating the treatment of infections.

The World Health Organization (WHO) identifies several factors contributing to the development of AMR, including overprescription, inadequate diagnostics, substandard drug quality, and extensive agricultural antibiotic use. Additional drivers include the over-the-counter availability of antimicrobials, inadequate hygiene, lack of clean water, poor infection control in healthcare and agricultural settings, limited access to quality medications, and insufficient awareness and enforcement of antimicrobial use regulations. This problem is exacerbated by the limited introduction of novel drugs and inappropriate food handling. AMR affects countries at all income levels, but its drivers and consequences are exacerbated by poverty and inequality, with low- and middle-income countries (LMICs) most affected.

A study conducted in one of Pakistan’s major tertiary care hospitals revealed a high prevalence (75%) of antibiotic use, primarily involving third-generation cephalosporins, often for surgical prophylaxis. It also underscored the absence of antimicrobial guidelines in 61.9% of cases, emphasizing the urgent need for national interventions to curtail excessive and empirical antimicrobial use.

Additionally, a mortality rate as high as 50% was discovered by the Situation Analysis Report on Antimicrobial Resistance published in 2018. Enhanced stewardship programs and targeted policy initiatives are crucial for rationalizing antibiotic use and combating AMR effectively. Another BMC Infectious Diseases article presented a detailed analysis of AMR rates in Pakistan from 2006 to 2018, focusing on pathogens identified by the Global Antimicrobial Surveillance

System (GLASS). Significant findings include:

• Resistance rates exceeding 50% for third-generation cephalosporins, fluoroquinolones, and cotrimoxazole in both Klebsiella pneumoniae and Escherichia coli from hospital settings.
• Carbapenem resistance remained below 30% in these bacteria.
• Resistance rates for Acinetobacter species to aminoglycosides and carbapenems exceeded 50% in hospital environments.
• There was a notable rise in methicillin-resistant Staphylococcus aureus

(MRSA) in hospital settings, from below 30% in 2008 to over 50% by 2010.

• High resistance rates to fluoroquinolones were reported in Neisseria gonorrhoeae, and there was an emergence of ceftriaxone-resistant Salmonella Typhi.

AMR poses a severe threat by enabling antimicrobial-resistant organisms to eliminate beneficial microbes, allowing resistant traits to spread among pathogens. This issue is particularly acute in low- and middle-income countries (LMICs), where inadequate healthcare infrastructure and high infectious disease burdens intensify the challenge, leading to longer hospital stays, increased medical costs, and higher mortality rates. AMR was directly responsible for 1.27 million global deaths in 2019 and contributed to 4.95 million deaths, as reported by WHO.

AMR compromises the immune system by allowing resistant infections to persist and spread, reducing the effectiveness of standard treatments and necessitating more complex and costly alternatives. The term “post-antibiotic era” describes a potential future where common infections could become lethal again due to ineffective antimicrobial treatments, jeopardizing the advances insurgeries and chronic disease management. Effective countermeasures against AMR encompass improved infection prevention, judicious antimicrobial use, and investment in new drugs, diagnostic tools, and vaccines. These strategies require global, national, and local coordination to be effective.

Preventing antibiotic resistance involves using antibiotics only when necessary, adhering strictly to prescribed treatments, avoiding self-medication, and ensuring proper hygiene and infection control measures. Additionally, reducing antibiotic use in livestock and maintaining rigorous hygiene in healthcare settings are crucial. The economic impact of AMR is also significant, with the World Bank estimating up to US$ 3.4 trillion in GDP losses per year by 2030 due to increased healthcare costs.

Recent innovations, such as genomic surveillance and antimicrobial peptides, alongside research into natural substances like honey, offer new avenues to combat AMR. However, common misconceptions, such as the belief that individuals can become resistant to antibiotics or that frequent antibiotic use prevents illness, exacerbate the crisis.

In conclusion, AMR remains a critical global and local public health emergency. It demands comprehensive, coordinated actions to mitigate its effects, ensuring the continued efficacy of antimicrobial drugs and protecting public health. This global challenge requires an integrated, One Health approach, uniting efforts across human, animal, and environmental health to prevent and control AMR effectively. In the post-COVID era, the challenge of AMR is heightened by the increased use of antibiotics during the pandemic, which may accelerate resistance patterns globally. Responses have varied; globally, there are concerted efforts through WHO initiatives, but local responses in many regions lack coordination and funding, affecting effectiveness.

 

This article is written by Prof. Dr. Nadeem A. Rizvi, Consultant Pulmonologist, holding degrees of MBBS, MRCP (UK), MCPS, FRCP (Edinburgh), and CESR (Pulmonary Medicine & Internal Medicine) UK. Dr. Rizvi has previously served as the Head of Chest Medicines at JPMC and as the President of the Pakistan Chest Society.
Co-authored by:
Dr. Khalid Shafi, Associate Professor in the Community Medicine Department at Dow Medical College, and General Secretary of PPA.