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A review of current antibiotic resistance and promising antibiotics with novel modes of action to combat antibiotic resistance

Chen L, Kumar S, Wu H

Arch Microbiol, 2023 Oct 20;205(11):356.
PMID: 37863957 DOI: 10.1007/s00203-023-03699-2

The emergence and transmission of antibiotic resistance is a global public health crisis with significant burden on healthcare systems, resulting in high mortality and economic costs. In 2019, almost five million deaths were associated with drug-resistant infections, and if left unchecked, the global economy could lose $100 trillion by 2050. To effectively combat this crisis, it is essential for all countries to understand the current situation of antibiotic resistance. In this review, we examine the current driving factors leading to the crisis, impact of critical superbugs in three regions, and identify novel mechanisms of antibiotic resistance. It is crucial to monitor the phenotypic characteristics of drug-resistant pathogens and describe the mechanisms involved in preventing the emergence of cross-resistance to novel antimicrobials. Additionally, maintaining an active pipeline of new antibiotics is essential for fighting against diverse antibiotic-resistant pathogens. Developing antibacterial agents with novel mechanisms of action is a promising way to combat increasing antibiotic-resistant pathogens.

Matched MeSH terms: Drug Resistance, Microbial
Adaptive therapy to circumvent drug resistance to tyrosine kinase inhibitors in cancer: is it clinically relevant?

Faisal Hamdi AI, How SH, Islam MK, Lim JCW, Stanslas J

Expert Rev Anticancer Ther, 2022 Dec;22(12):1309-1323.
PMID: 36376248 DOI: 10.1080/14737140.2022.2147671

INTRODUCTION: Cancer is highly adaptable and is constantly evolving against current targeted therapies such as tyrosine kinase inhibitors. Despite advances in recent decades, the emergence of drug resistance to tyrosine kinase inhibitors constantly hampers therapeutic efficacy of cancer treatment. Continuous therapy versus intermittent clinical regimen has been a debate in drug administration of cancer patients. An ecologically-inspired shift in cancer treatment known as 'adaptive therapy' intends to improve the drug administration of drugs to cancer patients that can delay emergence of drug resistance.
AREAS COVERED: We discuss improved understanding of the concept of drug resistance, the basis of continuous therapy, intermittent clinical regimens, and adaptive therapy will be reviewed. In addition, we discuss how adaptive therapy provides guidance for future cancer treatment.
EXPERT OPINION: The current understanding of drug resistance in cancer leads to poor prognosis and limited treatment options in patients. Fighting drug resistance mutants is constantly followed by new forms of resistance. In most reported cases, continuous therapy leads to drug resistance and an intermittent clinical regimen vaguely delays it. However, adaptive therapy, conceptually, exploits multiple parameters that can suppress the growth of drug resistance and provides safe treatment for cancer patients in the future.

Matched MeSH terms: Drug Resistance
Emerging threat of antimicrobial resistance in Neisseria gonorrhoeae: pathogenesis, treatment challenges, and potential for vaccine development

Omeershffudin UNM, Kumar S

Arch Microbiol, 2023 Sep 09;205(10):330.
PMID: 37688619 DOI: 10.1007/s00203-023-03663-0

The continuous rise of antimicrobial resistance (AMR) is a serious concern as it endangers the effectiveness of healthcare interventions that rely on antibiotics in the long run. The increasing resistance of Neisseria gonorrhoeae, the bacteria responsible for causing gonorrhea, to commonly used antimicrobial drugs, is a major concern. This has now become a critical global health crisis. In the coming years, there is a risk of a hidden epidemic caused by the emergence of gonococcal AMR. This will worsen the global situation. Infections caused by N. gonorrhoeae were once considered easily treatable. However, over time, they have become increasingly resistant to commonly used therapeutic medications, such as penicillin, ciprofloxacin, and azithromycin. As a result, this pathogen is developing into a true "superbug," which means that ceftriaxone is now the only available option for initial empirical treatment. Effective management strategies are urgently needed to prevent severe consequences, such as infertility and pelvic inflammatory disease, which can result from delayed intervention. This review provides a thorough analysis of the escalating problem of N. gonorrhoeae, including its pathogenesis, current treatment options, the emergence of drug-resistant mechanisms, and the potential for vaccine development. We aim to provide valuable insights for healthcare practitioners, policymakers, and researchers in their efforts to combat N. gonorrhoeae antibiotic resistance by elucidating the multifaceted aspects of this global challenge.

Matched MeSH terms: Drug Resistance, Bacterial
Fulltext Antimicrobial resistance in 6 Malaysian general hospitals

Cheong YM, Lim VK, Jegathesan M, Suleiman AB

Med J Malaysia, 1994 Dec;49(4):317-26.
PMID: 7674966

Knowledge of local antimicrobial resistance patterns of bacteria is a valuable guide to empirical antimicrobial therapy. This paper reports the resistance patterns of more than 36,000 bacteria isolated between August 1991 and July 1992 in six Malaysian hospitals and discusses the implications of the results. A customized menu driven software programme was developed to analyse the results. Generally, resistance to the commonly used antibiotics like ampicillin, cloxacillin, cephalosporins, gentamicin, cotrimoxazole and tetracycline was high. Some differences in resistance rate amongst the six hospitals were also noted. Continuous surveillance of antimicrobial resistance in hospitals is encouraged for the effective control of the emergence of antimicrobial resistance.

Matched MeSH terms: Drug Resistance, Microbial*
Pakistan's national action plan for antimicrobial resistance: translating ideas into reality

Saleem Z, Hassali MA, Hashmi FK

Lancet Infect Dis, 2018 10;18(10):1066-1067.
PMID: 30303099 DOI: 10.1016/S1473-3099(18)30516-4
Matched MeSH terms: Drug Resistance, Microbial*
Fulltext Acinetobacter spp. infections in Malaysia: a review of antimicrobial resistance trends, mechanisms and epidemiology

Mohd Rani F, A Rahman NI, Ismail S, Alattraqchi AG, Cleary DW, Clarke SC, et al.

Front Microbiol, 2017;8:2479.
PMID: 29312188 DOI: 10.3389/fmicb.2017.02479

Acinetobacter spp. are important nosocomial pathogens, in particular the Acinetobacter baumannii-calcoaceticus complex, which have become a global public health threat due to increasing resistance to carbapenems and almost all other antimicrobial compounds. High rates of resistance have been reported among countries in Southeast Asia, including Malaysia. In this review, we examine the antimicrobial resistance profiles of Acinetobacter spp. hospital isolates from Malaysia over a period of nearly three decades (1987-2016) with data obtained from various peer-reviewed publications as well as the Malaysian National Surveillance on Antibiotic Resistance (NSAR). NSAR data indicated that for most antimicrobial compounds, including carbapenems, the peak resistance rates were reached around 2008-2009 and thereafter, rates have remained fairly constant (e.g., 50-60% for carbapenems). Individual reports from various hospitals in Peninsular Malaysia do not always reflect the nationwide resistance rates and often showed higher rates of resistance. We also reviewed the epidemiology and mechanisms of resistance that have been investigated in Malaysian Acinetobacter spp. isolates, particularly carbapenem resistance and found that blaOXA-23 is the most prevalent acquired carbapenemase-encoding gene. From the very few published reports and whole genome sequences that are available, most of the Acinetobacter spp. isolates from Malaysia belonged to the Global Clone 2 (GC2) CC92 group with ST195 being the predominant sequence type. The quality of data and analysis in the national surveillance reports could be improved and more molecular epidemiology and genomics studies need to be carried out for further in-depth understanding of Malaysian Acinetobacter spp. isolates.

Matched MeSH terms: Drug Resistance, Bacterial*
Fulltext Point-of-Care for Evaluating Antimicrobial Resistance through the Adoption of Functional Materials

Singh S, Numan A, Cinti S

Anal Chem, 2022 Jan 11;94(1):26-40.
PMID: 34802244 DOI: 10.1021/acs.analchem.1c03856
Matched MeSH terms: Drug Resistance, Bacterial*
Fulltext Educational resource for antimicrobial resistance and stewardship for dentistry programmes: a research protocol

Ang CY, Dhaliwal JS, Muharram SH, Akkawi ME, Hussain Z, Rahman H, et al.

BMJ Open, 2021 07 07;11(7):e048609.
PMID: 34233993 DOI: 10.1136/bmjopen-2021-048609

INTRODUCTION: Antimicrobial resistance (AMR) is a global public and patient safety issue. With the high AMR risk, ensuring that the next generation of dentists that have optimal knowledge and confidence in the area of AMR is crucial. A systematic approach is vital to design an AMR content that is comprehensive and clinically relevant. The primary objective of this research study will be to implement a consensus-based approach to elucidate AMR content and curriculum priorities for professional dentistry programmes. This research aims to establish consensus along with eliciting opinion on appropriate AMR topics to be covered in the Bachelor of Dental Surgery syllabus.
METHODS AND ANALYSIS: A three-phase approach to validate content for curriculum guidelines on AMR will be adopted. First, literature review and content analysis were conducted to find out the available pertinent literature in dentistry programmes. A total of 23 potential literature have been chosen for inclusion within this study following literature review and analysis in phase 1. The materials found will be used to draft curriculum on antimicrobials for dentistry programmes. The next phase involves the validation of the drafted curriculum content by recruiting local and foreign experts via a survey questionnaire. Finally, Delphi technique will be conducted to obtain consensus on the important or controversial modifications to the revised curriculum.
ETHICS AND DISSEMINATION: An ethics application is currently under review with the Institute of Health Science Research Ethics Committee, Universiti Brunei Darussalam. All participants are required to provide a written consent form. Findings will be used to identify significant knowledge gaps on AMR aspect in a way that results in lasting change in clinical practice. Moreover, AMR content priorities related to dentistry clinical practice will be determined in order to develop need-based educational resource on microbes, hygiene and prudent antimicrobial use for dentistry programmes.

Matched MeSH terms: Drug Resistance, Bacterial
CHLOROQUINE RESISTANT FALCIPARUM MALARIA IN MALAYA

MONTGOMERY R, EYLES DE

Trans R Soc Trop Med Hyg, 1963 Nov;57:409-16.
PMID: 14081295
Matched MeSH terms: Drug Resistance*; Drug Resistance, Microbial*
Fulltext Antibiotic stewardship

Lim V

International e-Journal of Science, Medicine & Education, 2012;6(Suppl 1):75-79.
MyJurnal

The discovery of antibiotics had been one of the most significant events in the history of medicine. Antibiotics had saved countless number of lives and had contributed significantly to the health of mankind.The emergence of resistance is however a major threat to the continued usefulness of antibiotics. There are now strains of bacteria which are resistant to virtually all available antibiotics and these strains are increasingly being encountered in clinical practice. The development of new agents had not kept pace with resistance and it is unlikely that there will be major breakthroughs in the near future. The world needs to conserve and prolong the useful lives of the existing agents. This can only be achieved through good antibiotic stewardship programmes. As antibiotic resistance is a global threat all major stakeholders have to work together to meet this challenge.

Matched MeSH terms: Drug Resistance, Microbial
SOME SEVERE ANTIBIOTIC RESISTANT STAPHYLOCOCCAL INFECTIONS IN SINGAPORE WITH SPECIAL REFERENCE TO THE USE OF AMINOSIDINE (GABBROMYCINA)

KHOOOON TEIK, LEEGUAT SIEW

Med J Malaysia, 1964 Sep;19:8-14.
PMID: 14244225
Matched MeSH terms: Drug Resistance*; Drug Resistance, Microbial*
STAPHYLOCOCCI AND INFANTILE GASTRO--ENTERITIS

CHAN KE, LUCAS JK

Med J Malaysia, 1964 Dec;19:150-3.
PMID: 14279239
Matched MeSH terms: Drug Resistance*; Drug Resistance, Microbial*
Characterization and Comparative Overview of Complete Sequences of the First Plasmids of Pandoraea across Clinical and Non-clinical Strains

Yong D, Tee KK, Yin WF, Chan KG

Front Microbiol, 2016;7:1606.
PMID: 27790203

To date, information on plasmid analysis in Pandoraea spp. is scarce. To address the gap of knowledge on this, the complete sequences of eight plasmids from Pandoraea spp. namely Pandoraea faecigallinarum DSM 23572(T) (pPF72-1, pPF72-2), Pandoraea oxalativorans DSM 23570(T) (pPO70-1, pPO70-2, pPO70-3, pPO70-4), Pandoraea vervacti NS15 (pPV15) and Pandoraea apista DSM 16535(T) (pPA35) were studied for the first time in this study. The information on plasmid sequences in Pandoraea spp. is useful as the sequences did not match any known plasmid sequence deposited in public databases. Replication genes were not identified in some plasmids, a situation that has led to the possibility of host interaction involvement. Some plasmids were also void of par genes and intriguingly, repA gene was also not discovered in these plasmids. This further leads to the hypothesis of host-plasmid interaction. Plasmid stabilization/stability protein-encoding genes were observed in some plasmids but were not established for participating in plasmid segregation. Toxin-antitoxin systems MazEF, VapBC, RelBE, YgiT-MqsR, HigBA, and ParDE were identified across the plasmids and their presence would improve plasmid maintenance. Conjugation genes were identified portraying the conjugation ability amongst Pandoraea plasmids. Additionally, we found a shared region amongst some of the plasmids that consists of conjugation genes. The identification of genes involved in replication, segregation, toxin-antitoxin systems and conjugation, would aid the design of drugs to prevent the survival or transmission of plasmids carrying pathogenic properties. Additionally, genes conferring virulence and antibiotic resistance were identified amongst the plasmids. The observed features in the plasmids shed light on the Pandoraea spp. as opportunistic pathogens.

Matched MeSH terms: Drug Resistance, Microbial
MDRO Beijing Consensus Meeting Report: Global burden of multidrug-resistant organisms' current antimicrobial resistance problems in Asia-Pacific

Gould IM, Wang GQ, Wu JJ, Lim VK, Hutchinson J, Walsh T, et al.

J Glob Antimicrob Resist, 2014 Mar;2(1):7-9.
PMID: 27873642 DOI: 10.1016/j.jgar.2013.10.005

The International Society of Chemotherapy's Working Groups on Antibiotic Resistance and Antibiotic Stewardship convened a half-day workshop on the burden of multidrug-resistant organisms in the Asia-Pacific. This short review is a summary of their discussion and conclusions.

Matched MeSH terms: Drug Resistance, Microbial
Fulltext Chloroquine-resistant falciparum malaria in Malaya

Sandosham AA

Singapore Med J, 1963 Mar;4(1):3-5.
PMID: 14162703
Matched MeSH terms: Drug Resistance*; Drug Resistance, Microbial*
Modern vaccine development via reverse vaccinology to combat antimicrobial resistance

Tobuse AJ, Ang CW, Yeong KY

Life Sci, 2022 Aug 01;302:120660.
PMID: 35642852 DOI: 10.1016/j.lfs.2022.120660

With the continuous evolution of bacteria, the global antimicrobial resistance health threat is causing millions of deaths yearly. While depending on antibiotics as a primary treatment has its merits, there are no effective alternatives thus far in the pharmaceutical market against some drug-resistant bacteria. In recent years, vaccinology has become a key topic in scientific research. Combining with the growth of technology, vaccine research is seeing a new light where the process is made faster and more efficient. Although less discussed, bacterial vaccine is a feasible strategy to combat antimicrobial resistance. Some vaccines have shown promising results with good efficacy against numerous multidrug-resistant strains of bacteria. In this review, we aim to discuss the findings from studies utilizing reverse vaccinology for vaccine development against some multidrug-resistant bacteria, as well as provide a summary of multi-year bacterial vaccine studies in clinical trials. The advantages of reverse vaccinology in the generation of new bacterial vaccines are also highlighted. Meanwhile, the limitations and future prospects of bacterial vaccine concludes this review.

Matched MeSH terms: Drug Resistance, Bacterial
Fulltext Bacterial Persister Cells and Development of Antibiotic Resistance in Chronic Infections: An Update

Kunnath AP, Suodha Suoodh M, Chellappan DK, Chellian J, Palaniveloo K

Br J Biomed Sci, 2024;81:12958.
PMID: 39170669 DOI: 10.3389/bjbs.2024.12958

The global issue of antimicrobial resistance poses significant challenges to public health. The World Health Organization (WHO) has highlighted it as a major global health threat, causing an estimated 700,000 deaths worldwide. Understanding the multifaceted nature of antibiotic resistance is crucial for developing effective strategies. Several physiological and biochemical mechanisms are involved in the development of antibiotic resistance. Bacterial cells may escape the bactericidal actions of the drugs by entering a physiologically dormant state known as bacterial persistence. Recent findings in this field suggest that bacterial persistence can be one of the main sources of chronic infections. The antibiotic tolerance developed by the persister cells could tolerate high levels of antibiotics and may give rise to persister offspring. These persister offspring could be attributed to antibiotic resistance mechanisms, especially in chronic infections. This review attempts to shed light on persister-induced antibiotic resistance and the current therapeutic strategies.

Matched MeSH terms: Drug Resistance, Bacterial
Emerging problems of antibiotic resistance in community medicine

Parasakthi N

Malays J Pathol, 1996 Jun;18(1):9-13.
PMID: 10879217

Emergence of antimicrobial resistance in bacteria associated with community acquired infections has made the choice of empirical therapy more difficult and more expensive. The problems due to possible spread of MRSA to the community, emergence of penicillin resistance in S. pneumoniae, ampicillin resistance in H. influenzae, and multiresistance among common enteric pathogens are highlighted. Bacteria have a remarkable ability to develop resistance to many of the newly synthesized antimicrobial agents but the appropriate use of antibiotics will delay and in many cases prevent the emergence of resistance.

Matched MeSH terms: Drug Resistance, Microbial*
Scope and applicability of social-ecological resilience to antimicrobial resistance

Wernli D, Søgaard Jørgensen P, Parmley EJ, Majowicz SE, Lambraki I, Carson CA, et al.

Lancet Planet Health, 2023 Jul;7(7):e630-e637.
PMID: 37438004 DOI: 10.1016/S2542-5196(23)00128-6

Social-ecological systems conceptualise how social human systems and ecological natural systems are intertwined. In this Personal View, we define the scope and applicability of social-ecological resilience to antimicrobial resistance. Resilience to antimicrobial resistance corresponds to the capacity to maintain the societal benefits of antimicrobial use and One Health systems' performance in the face of the evolutionary behaviour of microorganisms in response to antimicrobial use. Social-ecological resilience provides an appropriate framework to make sense of the disruptive impacts resulting from the emergence and spread of antimicrobial resistance; capture the diversity of strategies needed to tackle antimicrobial resistance and to live with it; understand the conditions that underpin the success or failure of interventions; and appreciate the need for adaptive and coevolutionary governance. Overall, resilience thinking is essential to improve understanding of how human societies dynamically can cope with, adapt, and transform to the growing global challenge of antimicrobial resistance.

Matched MeSH terms: Drug Resistance, Bacterial*
Typhoid fever and other salmonellosis: a continuing challenge

Pang T, Bhutta ZA, Finlay BB, Altwegg M

Trends Microbiol, 1995 Jul;3(7):253-5.
PMID: 7551636
Matched MeSH terms: Drug Resistance, Microbial; Drug Resistance, Multiple

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