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6A CONCISE STUDY OF AMR MECHANISMS OF MICROORGANISMS INCLUDED IN THE CRITICAL GROUP OF WHO BACTERIAL PRIORITY PATHOGENS LIST 2024
DAHAIR ABDULRAHMAN NOOR BAKRI
General Medicine Second Year Student (Group 2011a), Karaganda Medical University,
Karaganda, Kazakhstan
CHAUDHARY SARANSH
General Medicine Fourth Year Student (Group 4018a), Karaganda Medical University,
Karaganda, Kazakhstan
KUMAR PUNIT
Department of Morphology, Karaganda Medical University, Karaganda, Kazakhstan
Abstract. Antibiotics are developed to control bacterial infections, but the emergence of antimicrobial resistance (AMR) in pathogens is creating challenges to control infectious diseases. Antimicrobial resistance is one of the biggest global health concerns for societies and hospital settings. Bacterial AMR is found directly responsible for millions of deaths every year. Furthermore, antimicrobial resistance is increasing the treatment cost as patients who have infections of antibiotic-resistant pathogens have longer treatment duration and use costly antibiotics. Including this, AMR is also increasing mortality and morbidity. Furthermore, a lack of effective treatment options may worsen the problem. The main cause of AMR is the overuse and misuse of antibiotics in humans, animals, and agriculture. It spreads faster than the identification of new antibiotics. Combating antimicrobial resistance requires a multidimensional approach including the understanding of resistance mechanisms, contributing factors, antimicrobial stewardship, the formation of policies, and the development of new antimicrobial agents effective against resistant pathogens. In this article, we have discussed the antibiotic-resistant mechanisms of pathogens mentioned in the critical group of the World Health Organization (WHO) bacterial priority pathogen list 2024.
Keywords: Antimicrobial resistance; Pathogens; World Health Organization; Antimicrobial stewardship; Horizontal Gene Transfer
Introduction
Antimicrobial resistance (AMR), especially bacterial AMR, has become an important global health threat definitely affecting the treatment of bacterial infections and the efficacy of antibiotic treatment (Ho et al., 2024). AMR is one most challenging health-related issues existing in almost all countries. It is estimated that bacterial AMR was directly associated with 1.27 million deaths, and contributed to 4.95 million deaths worldwide in 2019. Furthermore, according to estimates of the World Bank, AMR may be responsible for US$ 1 trillion additional healthcare expenditure by 2050 (WHO Fact Sheet, 2023). The financial burden may rise if proper measures are not taken and the current trend of antibiotic misuse continues. AMR, mainly due to multidrug-resistant organisms (MDROs), is considered a global health threat and it makes infections difficult to treat and develops negative impacts on patient morbidity and mortality rates, and economic burden (Fu et al., 2021).
AMR does not obey international bounders, and its effects are observed everywhere and at all income levels. There are many well-known drivers for the spread of antimicrobial resistance which are at the level of people, physicians, pathogens, and government. Some examples of these drivers are overuse and misuse of antimicrobials, lack of awareness of antibiotic resistance, transfer of antimicrobial resistance genes among pathogens, poor infection control, lack of adequate medical facilities, and lack of coordination between countries to frame policies to combat antimicrobial resistance at the global level.
Over the duration of 1990-2021, the trends in AMR mortality demonstrated variations by age and location. During this duration, the deaths due to AMR decreased among children younger than 5
years while such deaths increased among adults aged 70 years and more. The methicillin-resistant Staphylococcus aureus increased the most deaths (attributable deaths, and associated deaths to AMR) globally from 1990 to 2021. Furthermore, among the Gram-negative bacteria, resistance against carbapenems increased more deaths (attributable deaths, and associated deaths to AMR) globally from 1990 to 2021 than any other antibiotic class. It is also estimated that in 2050, AMR could cause about 191 million attributable deaths and 8 22 million associated deaths globally (Naghavi et al., 2024).
The COVID-19 pandemic also increased antibiotic consumption and increased the prevalence of AMR among COVID-19 patients (Kariyawasam et al., 2022). It was also observed that among the patients of COVID-19 admitted to the intensive care unit, an increased prevalence of infections caused by carbapenem-resistant A. baumannii, methicillin-resistant S. aureus, carbapenem-resistant Enterobacteriaceae, and C. auris was found (Segala et al., 2021). During the COVID-19 pandemic, the rate of multidrug-resistant gram-positive and gram-negative bacteria was increased, while the rate of extended-spectrum beta-lactamase inhibitor (ESBL) producing Enterobacteriaceae and carbapenem-resistant Pseudomonas aeruginosa (CRPA) was reduced (Abubakar et al., 2023).
To combat the issue of antimicrobial resistance, WHO has prepared a bacterial priority pathogens list (2024 WHO BPPL). This list was also prepared in 2017, and the list of 2024 is updated and refines the prioritization of pathogens to manage issues related to antibiotic resistance. This list categorized pathogens into three categories as; critical, high, and medium priority groups. The 2024 WHO BPPL covers 24 pathogens from 15 families of antibiotic-resistant bacterial pathogens. This list also covers their global impact and other issues like transmissibility, treatability, and prevention options (World Health Organization, 2024). Similarly, a distinct group of pathogens is described as ESKAPE pathogens including Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp. These pathogens were initially identified as critical MDR bacteria that require effective therapies (Miller and Arias, 2024).
This article covers the descriptions of critical group pathogens included in the 2024 WHO BPPL including the mechanism of antibiotic resistance, and strategies to combat antibiotic resistance.
DESCRIPTION OF PATHOGENS MENTIONED IN 2024, WHO BPPL
The 2024 WHO BPPL contains bacteria that are resistant to last-resort antibiotics, mainly comprising drug-resistant mycobacterium tuberculosis, and other pathogens such as Neisseria gonorrhoeae, Pseudomonas aeruginosa, Salmonella, Shigella and Staphylococcus aureus (World Health Organization, 2024). The study reflects the global effort to systematically prioritize the endemic pathogens on the basis of their role in regional and global health. In the critical priority list, Gram's negative bacteria are resistant to antibiotics like carbapenems, and cephalosporins, and tuberculosis bacteria are resistant to rifampicin. These pathogens pose a global threat due to their ability to develop resistance, and their ability to spread resistance to other pathogens, associated with high burden.
This list incorporates the lessons learned from the previous list of 2017, advancements in the surveillance, and new information about antimicrobial resistance. This list also covers the public health impact caused by these pathogens and also suggests novel products, measures to control infection, and access to antibiotics and vaccines (Jesudason, 2024).
Table 1: Priority groups of pathogens (WHO Bacterial Priority Pathogens List, 2024; Ho et al., 2024). __
Priority group of pathogen Pathogens
1 Critical Acinetobacter baumannii (Carbapenem-resistant) Enterobacterales (third-generation cephalosporin-resistant) (E. coli, Klebsiella pneumoniae, Enterobacter spp., Citrobacter spp., Proteus spp., Serratia spp., Morganella spp.) Enterobacterales (Carbapenem-resistant)
(Klebsiellapneumoniae, Enterobacter spp., E. coli) Mycobacterium tuberculosis (Rifampicin-resistant)
2 High Salmonella typhi (fluoroquinolone-resistant) Shigella spp. (fluoroquinolone-resistant) Enterococcus faecium (Vancomycin-resistant) Pseudomonas aeruginosa (Carbapenem-resistant) Non-typhoidal Salmonella (Fluoroquinolone-resistant) Neisseria gonorrhoeae (third-generation cephalosporin, and/or fluoroquinolone-resistant) Staphylococcus aureus (methicillin-resistant)
2 Medium Group A Streptococci (macrolide-resistant) Streptococcus pneumoniae (macrolide-resistant) Haemophilus influenzae (Ampicillin-resistant) Group B Streptococci (Penicillin-resistant)
Pathogens mentioned in the critical group are considered to pose the highest threat to public health as there are limited treatment options to control infections from these pathogens. These infections are highly transmissible and difficult to control.
Carbapenem-resistant Acinetobacter baumannii
Acinetobacter baumannii is a Gram-negative, oxidase-negative, catalase-positive, non-motile, non-fermenting coccobacilli (Howard et al., 2012; Nguyen and Joshi, 2021). These are recognized as opportunistic microbes associated with severe infections. A. baumannii also causes nosocomial health care-associated infections worldwide. This bacterium has a strong environmental adaptability nature and is capable of forming biofilms (Nocera et al., 2021). Indeed, strains showing fully resistant profiles represent a worrisome problem in clinical therapeutic treatment. Furthermore, A. baumannii-associated veterinary nosocomial infections have been reported in recent literature. Particularly, carbapenem-resistant A. baumannii can be considered an emerging opportunistic pathogen in human medicine as well as in veterinary medicine.
Carbapenems are broad-spectrum antibodies that are reserved for the treatment of pathogens expressing MDR. These antibiotics belong to P-lactams antibiotics that contain penicillins, monobactams, and cephalosporins, etc (Aurilio et al., 2022). However, the structure of carbapenems has some similarities with penicillins but possesses an additional pyrroline ring. This additional pyrroline ring provides protection to the beta-lactam ring from the degradation from bacterial lactamases. The resistance against carbapenem has severe implications for patients and hospital epidemiology (Smith et al., 2024).
Carbapenem-resistant Acinetobacter baumannii (CRAB) is assumed to be resistant to nearly all antibiotics (CDC, 2021). CRAB performs colonization and infection mainly among hospitalized patients (Bartal et al., 2022). Some CRAB expresses carbapenemase that inactivates carbapenem antibiotics. Antibiotic Resistance Laboratory Network (AR Lab Network) investigations during 2019 revealed that carbapenemase genes were present almost in 83% of tested CRAB isolates (CDC,
2021). These genes can disperse among bacteria, and increase the chances of spreading of multidrug resistance will spread. Resistance to carbapenems significantly decreases the treatment options for patients. It is found that two categories of carbapenemase gene-positive Acinetobacter baumannii (CP-CRAB). The more common type CP-CRAB has carbapenemase encoding gene which is also identified among Acinetobacter spp. More common gene encodes OXA-23-like, 0XA-24/40-like, and OXA-58-like oxacillinases. Some CP-CRAB (less common) are reported to have carbapenemase-encoding mobile genes (KPC, IMP, NDM, VIM, OXA-48-like) (CDC, 2021). There are very limited options for CRAB and combination therapies including high-dose ampicillin-sulbactam combined with high-dose tigecycline, polymyxins, etc. are suggested as good treatment options (Bartal et al.,
2022). One study suggested that carbapenem-hydrolysing class D beta-lactamases (CHDLs) are
common widespread beta-lactamases having carbapenemase properties in A. baumannii. These enzymes are related to clavulanic acid-resistant beta-lactamases, represented by OXA-23, OXA-24 and OXA-58, encoded by chromosome or plasmid. A. baumannii also has intrinsic carbapenem-hydrolysing oxacillinase which may contribute carbapenem resistance. Including this, porin or penicillin-binding protein modifications may also play a role in carbapenem resistance in A. baumannii (Poirel and Nordmann, 2006).
Third-generation cephalosporin-resistant Enterobacterales
The order Enterobacterales comprises the family Enterobacteriaceae and with more than 250 species. They are among the most common human pathogens responsible for many infections like urinary tract infections, gastroenteritis, bloodstream infections etc. (Doern, 2024). Enterobacterales include Enterobacter spp., Klebsiella spp., and E. coli (Ho et al., 2024). Mostly all Enterobacteriaceae (except Salmonella spp.,) synthesize intrinsic encoded beta-lactamases encoded by bacterial chromosome which play an important role in intrinsic resistance of individual species among Enterobacteriaceae. The production of broad-spectrum beta-lactamases has provided resistance against ampicillin, first-generation cephalosporins, ticarcillin, and piperacillin. The plasmid-encoded extended-spectrum ß-lactamases (ESBLs) hydrolyze oxymino-cephalosporins, penicillins, and other cephalosporins, except for cephamycin (cefoxitin and cefotetan). The chromosomal AmpC ß-lactamases are inducible and resistant to almost all penicillins and cephalosporins, to ß-lactamase inhibitors, and aztreonam. Plasmid-mediated AmpC ß-lactamases are uninducible and have a similar substrate profile as chromosomal (Susic, 2004). It is also suggested that resistance against third-generation cephalosporin in Enterobacterales is mainly due to plasmid-mediated extended-spectrum ß-lactamases (ESBLs), AmpC ß-lactamases, and OXA-type ß-lactamases (Logan et al., 2014; Balley et al., 2021). It is also assumed that Enterobacteriaceae infections, ESBL production causes high mortality and delay in effective therapy (Schwaber and Carmeli, 2007).
Dasgupta-Tsinikas et al. (2022) identified many risk factors for urinary tract infections due to third-generation cephalosporin-resistant Enterobacterales such as; prior acute healthcare utilization, underlying medical conditions, and prior antibiotic exposure. The suggested treatment options for third-generation cephalosporin-resistant Enterobacterales include targeted antibiotic therapy (Paul et al., 2022).
Carbapenem-resistant Enterobacterales
These Enterobacterales are resistant to Carbapenems (Imipenem, ertapenem, and meropenem). This group of microorganisms is associated with pneumonia, urinary tract infections, bloodstream infections, and other infections. It is estimated that in the USA about 13000, infections are caused by Carbapenem-resistant Enterobacterales every year, and out of them about 11,00 people die (Cleveland Clinic, 2023). Carbapenem-resistant Enterobacteriaceae (CRE) are considered a global public health threat. The mechanism causing Enterobacteriaceae resistant to carbapenems includes efflux pumps, carbapenemase enzyme production (main resistance mechanism), penicillin-binding protein alteration, porins, and biofilm production (Suay-García B, Pérez-Gracia, 2019; Ma et al., 2023). Enterobacterales produce three main groups of enzymes (Ambler class A, Ambler class B, and Ambler class D) for example Klebsiella pneumoniae carbapenemase (Ambler class A), Metallo-ß-Lactamases (Ambler class B), and OXA-48-like (Ambler class D). Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae cause endemic infections mainly in Argentina, Colombia, Greece, Italy, and the USA. Metallo-ß-Lactamases NDM-1 mainly cause carbapenem resistance in India, Pakistan, and Sri Lanka. OXA-48-like enzyme producers cause endemic mainly in Malta, North Africa, Turkey, and the Middle East. These enzymes are mainly encoded by plasmid and dispersed by horizontal gene transfer (Suay-García B, Pérez-Gracia, 2019).
The vast majority of Carbapenem-resistant Enterobacterales (CRE) research is focusing carbapenemase-producing Enterobacterales while noncarbapenemase-producing CRE (non-CP-CRE) are also increasingly recognized. However, little is known about the carbapenem resistance
mechanism of non-CP-CRE, but carbapenem nonsusceptibility determinants in Enterobacterales are considered to play an important role (Shropshire et al., 2022).
The emergence and spread of carbapenem-resistant bacteria are associated with the dissemination of carbapenemases encoding genes by horizontal gene transfer. This rapid dissemination causes host colonization and infections in humans or hospitalized patients who are exposed to hosts and environments having carbapenemase-producing bacteria (Caliskan-Aydogan and Alocilja, 2023). As there are limited antibiotic-based treatment options for CRE, the infections caused by CRE are challenging to manage. The treatment comprises single or combined use of antibiotics, and new antibiotics are under development (Ma et al., 2023).
Rifampicin-resistant Mycobacterium tuberculosis
Tuberculosis (TB) is caused by Mycobacterium tuberculosis bacteria that most commonly affects the lungs. It spreads through coughing, sneezing, or spitting from the infected patients. Mycobacterium tuberculosis is recognized as one of the most important infectious agents responsible for more than 1.5 million annual deaths (Jacobo-Delgado et al., 2023).
It is assumed that globally about 25% of the population has been infected with TB bacteria. Furthermore, about 5-10% of infected people get symptoms and develop TB disease. Infected people are treated with antibiotics and it can be fatal without treatment. In many countries, the Bacille Calmette-Guerin (BCG) vaccine is administered to children as an immunization program. Due to inappropriate treatment, poor-quality drugs, or patients stopping treatment prematurely drug resistance developed against TB bacteria. Multidrug-resistant (MDR) TB bacteria that do not respond to isoniazid and rifampicin. The WHO, factsheet of tuberculosis stated that in 2023, about 1.25 million people died due to tuberculosis (including HIV associated 161,000) (WHO, Tuberculosis, 2024).
Though, global efforts for TB treatment have saved about 79 million lives since 2000. Still, MDR-TB is a health security threat. Furthermore, ending the TB epidemic by 2030 is also a health target of the United Nations Sustainable Development Goals (WHO, Tuberculosis, 2024). Due to the development of antimicrobial resistance. It is assumed that it is easy to find TB patients virtually resistant to all antibiotics, and this alarming situation urgently requires a search for new antimicrobial molecules and effective therapies (Jacobo-Delgado et al., 2023). Globally it is estimated that in 2022, about 410,000 people acquired multidrug- or rifampicin-resistant tuberculosis (MDR/RR-TB). Although the success rate for MDR/RR-TB is improving, it is still low. The worldwide, success rate of treatment was 63%, in 2020, 60% in 2019, and 50% in 2012 (WHO, Newsroom, Tuberculosis, 2024).
Rifampicin is considered a first-line anti-tuberculosis medicine, and rifampicin resistance (RIF-R) is affecting the treatment regimen by forcing to use of toxic second-line drugs. It is found that RIF-R of Mycobacterium tuberculosis is caused by RIF resistance-related mutations in the rpoB gene. Including the mutations in rpoB gene, tuberculosis bacteria can reduce the entry of drugs into bacterial cells by changing the permeability of cell wall, and drug efflux enhancement by efflux pumps (Xu et al., 2021). It is also observed that patients infected with drug-resistant tuberculosis bacteria demonstrate changes in immune responses with limited activation of immune cells and more accumulation of immune regulatory cells (Bobba and Khader, 2023).
Conclusions
Antibiotics are used to treat infections caused by pathogens. Inappropriate prescriptions, self-treatment, lack of diagnostics, and use of antibiotics for improper duration, etc. are many factors that may cause the emergence of antimicrobial resistance among pathogens. While considering the consequences of antimicrobial resistance, WHO has prepared a list of critical pathogens to target as a priority. These pathogens are classified into three categories; critical, high, and medium. These common mechanisms conferring the resistance against cephalosporin and carbapenem are conferred by the synthesis of beta-lactamase (extended-spectrum P-lactamases, AmpC P-lactamases, and OXA-type P-lactamases) and carbapenemase from the pathogen. Furthermore, mutations in rpoB gene are found to play a key role in MDR tuberculosis bacteria. The patients infected with MDR TB also
display altered immune responses. In order to control and treatment of drug-resistant pathogens effectively, it is important to know the mechanism behind the resistance against the drug, rapid detection of pathogens, and design an effective treatment plan. Including this, a proper infection control plan should be implemented with other activities like antibiotic stewardship, and creating awareness of antibiotic resistance among the people. Antimicrobial resistance is also creating an economic burden on societies, and its quantification will help policymakers to set their priorities.
Acknowledgements
The authors are thankful to Karaganda Medical University for providing the necessary facilities to conduct this study.
REFERENCES
1. Abubakar U, Al-Anazi M, Alanazi Z, Rodríguez-Baño J. Impact of COVID-19 pandemic on multidrug resistant gram positive and gram negative pathogens: A systematic review. J Infect Public Health. 2023;16(3):320-331. DOI: 10.1016/j.jiph.2022.12.022.
2. Aurilio C, Sansone P, Barbarisi M, Pota V, Giaccari LG, Coppolino F, Barbarisi A, Passavanti MB, Pace MC. Mechanisms of Action of Carbapenem Resistance. Antibiotics (Basel). 2022;11(3):421. DOI: 10.3390/antibiotics11030421.
3. Bartal C, Rolston KVI, Nesher L. Carbapenem-resistant Acinetobacter baumannii: Colonization, Infection and Current Treatment Options. Infect Dis Ther. 2022;11(2):683-694. DOI: 10.1007/s40121 -022-00597-w.
4. Belley A, Morrissey I, Hawser S, Kothari N, Knechtle P. Third-generation cephalosporin resistance in clinical isolates of Enterobacterales collected between 2016-2018 from USA and Europe: genotypic analysis of P-lactamases and comparative in vitro activity of cefepime/enmetazobactam. Journal of Global Antimicrobial Resistance. 2021; 25:93-101. DOI: 10.1016/j.jgar.2021.02.031
5. Bobba S, Khader SA. Rifampicin drug resistance and host immunity in tuberculosis: more than meets the eye. Trends in immunology. 2023;44(9):712-23.
6. Caliskan-Aydogan O, Alocilja EC. A Review of Carbapenem Resistance in Enterobacterales and Its Detection Techniques. Microorganisms. 2023 3;11(6):1491. DOI: 10.3390/microorganisms11061491.
7. CDC. Carbapenem-resistant Acinetobacter baumannii (CRAB): An urgent public health threat in United States healthcare facilities. 2021. https://arpsp.cdc.gov/story/cra-urgent-public-health-threat. Accessed on Nov 12, 2024.
8. Cleveland Clinic, Carbapenem-Resistant Enterobacterales (CREs). 2023. https://my.clevelandclinic.org/health/diseases/cre-infection. Accessed on Nov 13, 2024.
9. Dasgupta-Tsinikas S, Zangwill KM, Nielsen K, Lee R, Friedlander S, Donovan SM, Van TT, Butler-Wu SM, Batra JS, Yeh SH; Resistant UTI in Children Study Team. Treatment and Epidemiology of Third-Generation Cephalosporin-Resistant Urinary Tract Infections. Pediatrics. 2022; 150(1):e2021051468. DOI: 10.1542/peds.2021-051468.
10. Doern CD. Chapter 2- Classification of medically important bacteria. In Molecular Medical Microbiology (Third Edition) 2024 (pp. 9-21). Academic Press. DOI: 10.1016/B978-0-12-818619-0.00029-0
11. Fu P, Xu H, Jing C, Deng J, Wang H, Hua C, Chen Y, Chen X, Zhang T, Zhang H, Chen Y, Yang J, Lin A, Wang S, Cao Q, Wang X, Deng H, Cao S, Hao J, Gao W, Huang Y, Yu H, Wang C. Bacterial Epidemiology and Antimicrobial Resistance Profiles in Children Reported by the ISPED Program in China, 2016 to 2020. Microbiol Spectr. 2021;9(3):e0028321. DOI: 10.1128/Spectrum.00283-21.
12. Ho CS, Wong CT, Aung TT, Lakshminarayanan R, Mehta JS, Rauz S, McNally A, Kintses B, Peacock SJ, de la Fuente-Nunez C, Hancock RE. Antimicrobial resistance: a concise update. The Lancet Microbe. 2024; 100947. DOI: 10.1016/j.lanmic.2024.07.010
13. Howard A, O'Donoghue M, Feeney A, Sleator RD. Acinetobacter baumannii: an emerging opportunistic pathogen. Virulence. 2012;3(3):243-50. DOI: 10.4161/viru.19700.
14. Jacobo-Delgado YM, Rodríguez-Carlos A, Serrano CJ, Rivas-Santiago B. Mycobacterium tuberculosis cell-wall and antimicrobial peptides: a mission impossible? Front Immunol. 2023; 14:1194923. DOI: 10.3389/fimmu.2023.1194923.
15. Jesudason T. WHO publishes updated list of bacterial priority pathogens. The Lancet Microbe. 2024;5(9):100940. DOI: 10.1016/j.lanmic.2024.07.003
16. Kariyawasam RM, Julien DA, Jelinski DC, Larose SL, Rennert-May E, Conly JM, Dingle TC, Chen JZ, Tyrrell GJ, Ronksley PE, Barkema HW. Antimicrobial resistance (AMR) in COVID-19 patients: a systematic review and meta-analysis (November 2019-June 2021). Antimicrob Resist Infect Control. 2022;11(1):45. DOI: 10.1186/s13756-022-01085-z.
17. Logan LK, Braykov NP, Weinstein RA, Laxminarayan R; CDC Epicenters Prevention Program. Extended-Spectrum ß-Lactamase-Producing and Third-Generation Cephalosporin-Resistant Enterobacteriaceae in Children: Trends in the United States, 1999-2011. J Pediatric Infect Dis Soc. 2014; 3(4):320-8. DOI: 10.1093/jpids/piu010.
18. Ma J, Song X, Li M, Yu Z, Cheng W, Yu Z, Zhang W, Zhang Y, Shen A, Sun H, Li L. Global spread of carbapenem-resistant Enterobacteriaceae: Epidemiological features, resistance mechanisms, detection and therapy. Microbiological Research. 2023; 266:127249. DOI: 10.1016/j .micres.2022.127249
19. Miller WR, Arias CA. ESKAPE pathogens: antimicrobial resistance, epidemiology, clinical impact and therapeutics. Nature Reviews Microbiology. 2024; 22: 598-616. DOI: 10.1038/s41579-024-01054-w
20. Naghavi M, Vollset SE, Ikuta KS, Swetschinski LR, Gray AP, Wool EE, Aguilar GR, Mestrovic T, Smith G, Han C, Hsu RL. Global burden of bacterial antimicrobial resistance 1990-2021: a systematic analysis with forecasts to 2050. The Lancet. 2024;404(10459):1199-1226. DOI: 10.1016/S0140-6736(24)01867-1
21. Nguyen M, Joshi SG. Carbapenem resistance in Acinetobacter baumannii, and their importance in hospital-acquired infections: a scientific review. Journal of AMicrobiology. 2021;131(6):2715-2738. DOI: 10.1111/jam.15130
22. Nocera FP, Attili AR, De Martino L. Acinetobacter baumannii: Its Clinical Significance in Human and Veterinary Medicine. Pathogens. 2021;10(2):127. DOI: 10.3390/pathogens10020127
23. Paul M, Carrara E, Retamar P, Tängdén T, Bitterman R, Bonomo RA, De Waele J, Daikos GL, Akova M, Harbarth S, Pulcini C. European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines for the treatment of infections caused by multidrug-resistant Gram-negative bacilli (endorsed by European society of intensive care medicine). Clinical Microbiology and Infection. 2022; 28(4):521-47. DOI: 10.1016/j.cmi.2021.11.025
24. Poirel L, Nordmann P. Carbapenem resistance in Acinetobacter baumannii: mechanisms and epidemiology. Clin Microbiol Infect. 2006;12(9):826-36. DOI: 10.1111/j.1469-0691.2006.01456.x.
25. Schwaber MJ, Carmeli Y. Mortality and delay in effective therapy associated with extended-spectrum beta-lactamase production in Enterobacteriaceae bacteraemia: a systematic review and meta-analysis. J Antimicrob Chemother. 2007;60(5):913-20. DOI: 10.1093/jac/dkm318.
26. Segala FV, Bavaro DF, Di Gennaro F, Salvati F, Marotta C, Saracino A, Murri R, Fantoni M. Impact of SARS-CoV-2 Epidemic on Antimicrobial Resistance: A Literature Review. Viruses. 2021;13(11):2110. DOI: 10.3390/v13112110.
27. Shropshire WC, Konovalova A, McDaneld P, Gohel M, Strope B, Sahasrabhojane P, Tran CN, Greenberg D, Kim J, Zhan X, Aitken S. Systematic analysis of mobile genetic elements mediating ß-lactamase gene amplification in noncarbapenemase-producing carbapenem-resistant Enterobacterales bloodstream infections. Msystems. 2022;7(5):e00476-22. DOI: 10.1128/msystems.00476-22
28. Smith HZ, Hollingshead CM, Kendall B. Carbapenem-Resistant Enterobacterales. 2024 Feb 2. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK551704/
29. Suay-García B, Pérez-Gracia MT. Present and Future of Carbapenem-resistant Enterobacteriaceae (CRE) Infections. Antibiotics (Basel). 2019;8(3):122. DOI: 10.3390/antibiotics8030122.
30. Susic E. Mehanizmi rezistencije enterobakterija prema beta-laktamskim antibioticima [Mechanisms of resistance in Enterobacteriaceae towards beta-lactamase antibiotics]. Acta Med Croatica. 2004;58(4):307-12.
31. WHO Bacterial Priority Pathogens List, 2024. https://iris.who.int/bitstream/handle/10665/376776/9789240093461-eng.pdf?sequence=1. Accessed on Nov 12, 2024.
32. WHO Fact Sheet. Antimicrobial resistance, 2023. https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance. Accessed on Nov 12, 2024.
33. WHO, Newsroom. Tuberculosis: Multidrug-resistant (MDR-TB) or rifampicin-resistant TB (RR-TB). 2024. https://www.who.int/news-room/questions-and-answers/item/tuberculosis-multidrug-resistant-tuberculosis-(mdr-tb). Accessed on Nov 13, 2024.
34. WHO, Tuberculosis. Key facts. 2024. https://www.who.int/news-room/fact-sheets/detail/tuberculosis. Accessed on Nov 13, 2024.
35. World Health Organization. WHO bacterial priority pathogens list, 2024: Bacterial pathogens of public health importance to guide research, development and strategies to prevent and control antimicrobial resistance. 2024. https://www.who.int/publications/i/item/9789240093461. Accessed on Nov 12, 2024.
36. Xu G, Liu H, Jia X, Wang X, Xu P. Mechanisms and detection methods of Mycobacterium tuberculosis rifampicin resistance: The phenomenon of drug resistance is complex. Tuberculosis. 2021;128:102083. DOI: 10.1016/j.tube.2021.102083
