Current Death Toll and Future Projections

In a study published in 2022, it was estimated that 4.95 million (95% CI 3.62-6.57 million) deaths were associated with antimicrobial resistance (AMR) in 2019, with 1.27 million of them attributed to bacterial AMR [2]. These figures indicate that deaths due to AMR represent a major global health concern, comparable in scale to leading causes of mortality such as ischaemic heart disease, stroke, and chronic obstructive pulmonary disease [3]. 

Out of the 4.95 million AMR-associated deaths, a staggering 4.3 million are occurring in low- and middle-income countries (LMICs) [4]. This stark disparity underscores the urgent need to enhance infection prevention and control and to improve access to affordable diagnoses in these regions. The Lancet Series on Antimicrobial Resistance suggests that aligning infection prevention and control standards in LMICs' healthcare settings with those in high-income countries could prevent up to 337,000 AMR-associated deaths annually [4].

Leading Causes of AMR

The rise of antibiotic resistance is primarily fuelled by the high selective pressure caused by the increasing use and misuse of antibiotics over the years. In the past two decades, global antimicrobial use has increased by 46% [3]. The overuse of antibiotics provides an advantage for resistant bacteria, causing them to proliferate since they survive better in the environment than their susceptible competitors [3]. 

In nature, horizontal gene transfer occurs among species of bacteria. This process enables bacteria to exchange their genetic material, including antibiotic resistance genes (ARGs), often across multiple species, greatly facilitating collaboration among bacterial populations in the development of multidrug resistance (MDR) [5]. Obviously, MDR leads to escalations in the severity of the problem, the most evident of which being superbugs, which are strains of bacteria resistant to several types of antibiotics. This phenomenon dramatically challenges the treatment process of a bacterial infection. 

Concerning Implications

In a broader scope, AMR causes problems beyond the increased challenge of treating bacterial infection. It also complicates the treatment of chronic kidney disease, diabetes and associated urinary tract and foot infections, chronic obstructive pulmonary disease, liver cirrhosis, as well as surgical care due to the risk of exposure to resistant infections [3]. In addition, AMR impedes progress towards the global childhood survival rate targeted by Sustainable Development Goal 3: Good Health and Well-being. This is because one-third of newborn deaths are caused by infections, with half of these infection-related deaths attributed explicitly to sepsis [3]. Worryingly, the pathogens driving these deadly infections are becoming increasingly resistant to the most widely used antibiotic treatments [3]. 

Furthermore, the rise of antimicrobial resistance has diminished the effectiveness of previously useful antimicrobial drugs, causing access to antimicrobials previously considered second-line to become increasingly crucial [3]. The Organisation for Economic Cooperation and Development (OECD) projects a twofold surge in resistance to last-resort antibiotics from 2005 to 2035 based on current trends [6].

Future Outlook

In addressing the problems of antibiotic resistance, the Lancet series, in 2024, proposed three goals to be achieved globally by 2030: a 10% decrease in deaths from AMR, a 20% reduction in inappropriate human antibiotic use, and a 30% reduction of that in animals [7]. These goals can only be achieved with optimised global surveillance, including fast and accurate diagnoses to prevent the misuse of ineffective antibiotics, which only furthers resistance prevalence.

However, current technologies for diagnosing antibiotic resistance, such as minimum inhibitory concentration (MIC), require lengthy culturing, while genetic tests like PCR necessitate trained personnel. Additionally, routine bacteriological culture testing is available in only 1.3% of laboratories in sub-Saharan Africa [8]. To counteract the rising trend of antibiotic resistance and to provide better access to diagnostic kits in low-resource settings, a cheaper, faster, and simpler technology is needed.

Antibiotic Resistance in Klebsiella pneumoniae

Klebsiella pneumoniae is often cited as a common cause of pneumonia [9]. It is a gram-negative, encapsulated, and non-motile bacterium found in the environment, mainly colonising human mucosal surfaces of the oropharynx and gastrointestinal (GI) tract [9]. Klebsiella pneumoniae infection is best treated with third- and fourth-generation cephalosporins, quinolones, or carbapenems [10]. However, over the years, Klebsiella pneumoniae has been shown to produce extended-spectrum beta-lactamase (ESBL) that breaks down and deactivates beta-lactam antibiotics, including cephalosporin, rendering third-generation cephalosporin drugs ineffective for treating Klebsiella pneumoniae infections. 

Additionally, cases of carbapenem-resistant Klebsiella pneumoniae have also been discovered. This thus classifies Klebsiella pneumoniae as one of the carbapenemase-producing Enterobacteriaceae (CPE). Similar to beta-lactamase, carbapenem resistance is conferred by producing carbapenemase capable of hydrolysing and neutralising the drug molecule [11], [12]. Notably, carbapenemases are encoded on plasmids such as blaKPC and blaNDM-1 [13]. This means it can be easily transferred between bacteria through horizontal gene transfer, resulting in a more vigorous spread of the resistance [14]. 

Urgency for Detection

In terms of its resistant variants, resistant Klebsiella pneumoniae commonly causes community-acquired urinary tract infections along with resistant Escherichia coli, Proteus mirabilis, and Staphylococcus saprophyticus [3]. According to the World Health Organisation, Klebsiella pneumoniae showed elevated resistance levels against major antibiotics, compromising the effectiveness of these last-resort drugs and increasing the risk of untreatable infections [6]. This indicates that Klebsiella pneumoniae is one of the most significant pathogens regarding antibiotic resistance. Additionally, the 2024 Lancet series emphasised the need for novel strategies to address the burden of ESKAPE pathogens, which includes Klebsiella pneumoniae [4], [13].

Low-Resource Settings

Among the estimated 1.27 million deaths caused by AMR, Klebsiella pneumoniae was one of the six leading contributing pathogens [2]. In sub-Saharan Africa, Klebsiella pneumoniae contributed to 19.9% of deaths caused by AMR and 17.5% of AMR-associated mortality [2]. Other than that, Klebsiella pneumoniae is one of the most common causes of neonatal sepsis in low-resource settings, such as in sub-Saharan Africa [3], [15]. Although it is estimated that only 3-5% of all community-acquired pneumonia in Western culture is related to Klebsiella pneumoniae infection, in developing countries such as African countries, for example, community-acquired Klebsiella pneumoniae accounts for roughly 15% of all pneumonia cases [9].

With this regard, we consider Klebsiella pneumoniae as our starting focus in developing our diagnosis method. With its level of urgency, especially in low-resource settings, performing diagnosis of resistant Klebsiella pneumoniae in a simple and low-cost manner will benefit the community for more effective usage of antibiotics and enhanced surveillance.