+ Antibiotics, used for over a century to treat bacterial infections, are one of the most successful medical
+ interventions. However, antibiotic resistance has increased due to overuse, causing previously manageable
+ diseases
+ to resurface. Many infectious diseases, which were wiped out by antibiotics, have become a more severe problem
+ in
+ recent years.
+
+ In a study published in 2022, it was estimated that 4.95 millions (95% CI 3.62-6.57 millions) of deaths were
+ associated with bacterial antimicrobial resistance (AMR) in 2019, and 1.27 millions of it were caused by
+ 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 ischemic heart disease, stroke, and chronic obstructive pulmonary disease
+ [3].
+
+
+ Out of the 4.95 millions of bacterial AMR-associated deaths, 4.3 millions are occurring in low-income and
+ middle-income countries (LMICs) [4]. This indicates a necessary step up in LMICs’ infection prevention and
+ control,
+ as well as access to affordable diagnosis. According to the Lancet Series on Antimicrobial Resistance, if
+ interventions are implemented to align infection prevention and control standards in LMICs’ healthcare settings
+ with
+ the standards in high-income countries, we will be able to prevent up to 337,000 AMR-associated deaths annually
+ [4].
+
+
+
+ The rise of antibiotic resistant trends is mainly driven by the high selection pressure caused by the increasing
+ use
+ and misuse of antibiotics over the years. Over the past two decades, global antimicrobial use has increased by
+ 46%
+ [3]. The usage of antibiotics to cure infections has actually provided advantages for those bacteria that have
+ resistance, causing the further spread of resistant bacteria since they survive better in the environment
+ compared
+ to the susceptible ones [3].
+
+
+
+ In the natural process, horizontal gene transfer might also occur among species of bacteria. This process
+ enables
+ bacteria to exchange their genetic material, including antibiotic resistance genes (ARGs), across diverse
+ species,
+ which greatly facilitates collaboration among bacterial populations in the development of multidrug resistance
+ (MDR)
+ [5]. Moreover, MDR leads to the escalation in severity of the problem. The most evident instance is Superbugs, a
+ strain of bacteria that are resistant to several types of antibiotics, which greatly challenges the treatment
+ process of a bacterial infection.
+
+
+ On a larger scope, the problem of AMR causes larger problems than just increased challenge in 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 the Sustainable Development Goal 3. This is because one third of newborn deaths are
+ caused by infections, and half of these infection-related deaths are specifically attributed to sepsis [3].
+ Concerningly, 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 that were previously considered second-line treatments has
+ become increasingly crucial [3]. The Organization for Economic Cooperation and Development (OECD) projects a
+ twofold surge in resistance to last-resort antibiotics by 2035 compared to 2005 levels [6].
+
+
+
+ In addressing the problems of antibiotic resistance, the Lancet series in 2024 proposed three goals to be
+ achieved globally by 2030; 10% decrease in deaths from AMR, 20% reduction in inappropriate human antibiotic use,
+ and 30% reduction in inappropriate animal antibiotic use [7]. These goals can only be achieved with optimised
+ surveillance, including diagnosis to prevent the misuse of ineffective antibiotics which only further drive
+ resistance. 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.
+
+
+
+ Klebsiella pneumoniae
+
+
Klebsiella pneumoniae has often been linked to causing pneumonia [9]. It is a
+ gram-negative, encapsulated, and non-motile type of 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 inactivates 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 pneumonia as one of the Carbapenemase-producing Enterobacteriaceae
+ (CPE). Similar to beta-lactamase, carbapenem resistance is conferred by the production of the carbapenemase
+ enzyme which is capable of hydrolyzing and disabling the drug molecule [11], [12]. More concerningly,
+ carbapenemases are encoded on plasmids, for instance, as bla
KPC and bla
NDM-1 [13]. This means that it can be easily transferred between
+ bacteria through horizontal gene transfer, resulting in a more vigorous spread of the resistance [14].
+
+
+ In the estimated 1.27 million deaths caused by AMR,
Klebsiella pneumoniae was one of
+ the six leading pathogens [2]. In sub-Saharan Africa,
Klebsiella pneumoniae
+ contributed to 19.9% 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].
+
+
+ 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 Organization,
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
+ when it comes to antibiotic resistance. Additionally, the 2024 Lancet series emphasised on the needs for novel
+ strategies to address the burden of ESKAPE pathogens, which includes
Klebsiella pneumoniae [4], [13].
+
+
+ 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 a more effective usage of antibiotics as well as for enhanced surveillance.
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