Open research questions in Antibiotic Resistance in Bacteria

What the literature leaves open

• The development of phage therapy is challenged by the need for a better understanding of host-phage immune interactions. The paper identifies the challenge of translating phage therapy from in vitro and in vivo studies to clinical applications. There is a need to address the potential for phage-resistant bacterial populations to emerge.

  Phage therapy against Klebsiella pneumoniae infections: integrating host–phage immune interactions, therapeutic strategies, and clinical translation · 2026 · DOI

• investigating the efficacy of phage-antibiotic combinations, - exploring the use of phage-derived enzymes and biofilm-targeting agents, - examining the potential of immunomodulatory strategies to enhance bacterial clearance

  Phage therapy against Klebsiella pneumoniae infections: integrating host–phage immune interactions, therapeutic strategies, and clinical translation · 2026 · DOI

• The small sample size of the study is a limitation. The lack of a control group is a challenge. The need for further studies to determine the most suitable patient population for cefepime/enmetazobactam is a challenge.

  Cefepime/enmetazobactam for invasive infections caused by extended-spectrum beta-lactamase-producing Enterobacterales: a real-world case series · 2026 · DOI

• Further studies are needed to specify the most suitable patient population, - Research to determine the appropriate patient populations for BL/BLI as carbapenem-sparing agents

  Cefepime/enmetazobactam for invasive infections caused by extended-spectrum beta-lactamase-producing Enterobacterales: a real-world case series · 2026 · DOI

• Small sample size of 12 isolates, - Limited geographic scope to Niger, - No comparison to a control group

  NDM‑mediated cefiderocol resistance among a series of carbapenem‑resistant Gram‑negative bacilli isolates in Niger · 2026 · DOI

• Further studies are needed to investigate the dissemination of NDM-producing isolates, - Research on the molecular mechanisms of cefiderocol resistance is necessary, - Larger, multicenter studies are required to determine the prevalence of cefiderocol resistance

  NDM‑mediated cefiderocol resistance among a series of carbapenem‑resistant Gram‑negative bacilli isolates in Niger · 2026 · DOI

• the PK/PD profile of tigecycline in critically ill patients should be revisited, - further studies are needed to confirm the findings, - the relationship between clinical outcome and exposure should be further analyzed

  Clinical outcomes and their relationship with tigecycline exposure in critically ill patients with drug resistant infections · 2026 · DOI

• The paper identifies the challenge of class imbalance in datasets. The authors highlight the need for careful selection of metrics and cross-validation techniques. The paper discusses the challenge of interpreting metrics, such as the F1 score and MCC score.

  Response to comment on “Using genomic data and machine learning to predict antibiotic resistance: A tutorial paper” · 2026 · DOI

• The paper identifies the limitation of using accuracy as a metric, particularly in imbalanced datasets. The authors highlight the need for alternative metrics and cross-validation techniques.

  Response to comment on “Using genomic data and machine learning to predict antibiotic resistance: A tutorial paper” · 2026 · DOI

• Limited understanding of the risk factors for Enterobacterales carriage in humans and companion animals. Need for further research on the One Health implications of antimicrobial resistance.

  Survey-based risk factors and genomic characterization of oral and oropharyngeal Enterobacterales carriage in humans and companion animals: a One Health study · 2026 · DOI

• Investigation of overexpression of intrinsic RND-family efflux systems, - Investigation of altered membrane permeability

  Antimicrobial resistance phenotypes, disinfectant susceptibility, and resistance-associated gene detection in carbapenem-resistant Pseudomonas aeruginosa from two tertiary hospitals in Urumqi, China · 2026 · DOI

• The study identifies a gap in the understanding of antimicrobial resistance phenotypes and disinfectant susceptibility in CRPA isolates. The study highlights the need for local surveillance evidence to inform antimicrobial stewardship and infection prevention and control.

  Antimicrobial resistance phenotypes, disinfectant susceptibility, and resistance-associated gene detection in carbapenem-resistant Pseudomonas aeruginosa from two tertiary hospitals in Urumqi, China · 2026 · DOI

• Detailed local data integrating genomic, clinical, and therapeutic information on OXA-48-producing K. pneumoniae remain scarce. The epidemiology of OXA-48-producing K. pneumoniae remains heterogeneous, driven by both plasmid dissemination and the spread of high-risk clones.

  Clinical, Microbiological and Genomic Characterization of OXA-48-Producing Klebsiella pneumoniae ST395 Circulating in a Secondary-Care Hospital in North-Eastern Italy, 2024–2025 · 2026 · DOI

• High levels of antimicrobial resistance among certain bacterial pathogens. Variability in resistance patterns across different clinical specimens and hospital wards. Need for effective antimicrobial strategies and drug development to address the growing threat of antimicrobial resistance.

  Antimicrobial susceptibility patterns in Jalisco, Mexico: a snapshot of regional resistance (2021-2023) · 2026 · DOI

• Investigate the molecular mechanisms of resistance, - Conduct a prospective study to validate the findings, - Expand the study to include more hospitals and regions, - Investigate the economic burden of antimicrobial resistance, - Develop and implement effective strategies to combat antimicrobial resistance

  Antimicrobial susceptibility patterns in Jalisco, Mexico: a snapshot of regional resistance (2021-2023) · 2026 · DOI

• further studies are needed to confirm the findings, - research on the mechanisms of resistance in CRPA is needed, - studies on the optimal treatment regimens for CRPA are needed

  The efficacy and safety of ceftazidime/avibactam or polymyxin B based regimens for carbapenem-resistant Pseudomonas aeruginosa infection: a multicenter real-world and propensity score-matched study · 2025 · DOI

• The comparative effectiveness of ceftazidime/avibactam and polymyxin B based regimens for carbapenem-resistant Pseudomonas aeruginosa infection is poorly characterized. There is a need for a multicenter real-world study to evaluate the efficacy and safety of the two regimens.

  The efficacy and safety of ceftazidime/avibactam or polymyxin B based regimens for carbapenem-resistant Pseudomonas aeruginosa infection: a multicenter real-world and propensity score-matched study · 2025 · DOI

• The difficulty in distinguishing between closely related species of Acinetobacter. The challenge of analyzing large datasets of antimicrobial resistance surveillance data. The need to develop effective methods for detecting and preventing the spread of antimicrobial-resistant Acinetobacter species.

  Epidemiology and antimicrobial resistance trends of Acinetobacter species in the United Arab Emirates: a retrospective analysis of 12 years of national AMR surveillance data · 2024 · DOI

• further studies are needed to understand the epidemiology of Acinetobacter spp. in other regions, - research on the molecular mechanisms of antibiotic resistance is necessary, - studies on the effectiveness of different treatment strategies for CRAB and non-CRAB patients are needed

  Epidemiology and antimicrobial resistance trends of Acinetobacter species in the United Arab Emirates: a retrospective analysis of 12 years of national AMR surveillance data · 2024 · DOI

• Limited understanding of the genomics and virulence of hvKp clinical strains. Lack of research on the genetic relatedness of hvKp isolates. Need for further investigation of the resistance of hvKp strains to human serum killing.

  Hypervirulent Capsular Serotypes K1 and K2 Klebsiella pneumoniae Strains Demonstrate Resistance to Serum Bactericidal Activity and Galleria mellonella Lethality · 2024 · DOI

• There is limited data support for the pharmacokinetic/pharmacodynamic target of tigecycline. The relationship between tigecycline exposure and clinical outcome in critically ill patients is not well understood.

  Clinical outcomes and their relationship with tigecycline exposure in critically ill patients with drug resistant infections · 2026 · DOI

• OXA-48-like {beta}-lactamases, such as OXA-163, OXA-181, OXA-405, OXA-505, among others, are class D carbapenem-hydrolyzing enzymes increasingly reported worldwide, yet some variants remain poorly characterized at the phenotypic levels.

  Phenotypic Characterization of OXA-439, an OXA-163 variant, isolated from uropathogenic Escherichia coli · 2026 · DOI

• However, the impact of these mutations on bacterial gene expression has not been explored extensively, particularly among P.

  Diverse transcriptomic effects of evolved imipenem-relebactam resistance in Pseudomonas aeruginosa · 2026 · DOI

• Although the mechanistic basis of NDM1 inhibition by bicyclic boronate inhibitors remains incompletely elucidated, this study systematically characterizes the binding profiles and intermolecular interaction landscapes between NDM1 and four cyclic boronic acid based inhibitors, vaborbactam (RPX7009), taniborbactam (VNRX 5133), xeruborbactam (QPX7728), and ledaborbactam (VNRX-5236).

  Insight into the mechanism of molecular interactions of the NDM metallo-beta-lactamase and cyclic boronate inhibition by molecular docking and molecular dynamics simulations · 2026 · DOI

• IMPORTANCE GES-type carbapenemases represent an important but underrecognized diagnostic challenge due to their low global prevalence, heterogeneous hydrolytic activity, and the limited performance data available for routine phenotypic detection methods.

  Evaluation of carbapenem inactivation method-based phenotypic assays for the detection of GES-type carbapenemases in Enterobacterales, Pseudomonas aeruginosa , and Acinetobacter baumannii · 2026 · DOI

Most-cited papers in Antibiotic Resistance in Bacteria

• The Crisis in Antibiotic Resistance · Science · 1992 · 2,123 citations
• Assessment of global health risk of antibiotic resistance genes · Nature Communications · 2022 · 846 citations
• Efflux-Mediated Drug Resistance in Bacteria · Drugs · 2009 · 805 citations
• Mechanisms of drug resistance: quinolone resistance · Annals of the New York Academy of Sciences · 2015 · 620 citations
• Progress in Alternative Strategies to Combat Antimicrobial Resistance: Focus on Antibiotics · Antibiotics · 2022 · 516 citations
• ResFinder – an open online resource for identification of antimicrobial resistance genes in next-generation sequencing data and prediction of phenotypes from genotypes · Microbial Genomics · 2022 · 499 citations
• Metallo‐β‐lactamase structure and function · Annals of the New York Academy of Sciences · 2012 · 467 citations
• Antimicrobial resistance: One Health approach · Veterinary World · 2022 · 466 citations
• Rapid Spread of Carbapenem-Resistant Klebsiella pneumoniae in New York City · Archives of Internal Medicine · 2005 · 462 citations
• Multidrug Resistance (MDR): A Widespread Phenomenon in Pharmacological Therapies · Molecules · 2022 · 429 citations

Most recent work

• Breaking the outer membrane barrier: structure, targets, and antimicrobial strategies for Gram-negative bacteria · Frontiers in Microbiology · 2026
• Molecular resistance mechanisms to newly approved antibiotics (2017–2025) in WHO priority pathogens · Frontiers in Microbiology · 2026
• Fluoroquinolone resistance in ESKAPE pathogens: evolutionary pathways, one health transmission, and clinical surveillance · Frontiers in Microbiology · 2026
• Development and validation of an interpretable machine learning–based model for predicting carbapenem-resistant Acinetobacter baumannii infection in postoperative ICU patients: a retrospective cohort study · Frontiers in Cellular and Infection Microbiology · 2026
• The type VI secretion system of Acinetobacter: mechanisms, biology and therapeutic potential · Communications Biology · 2026
• Emergence and spread of multidrug-resistant pathogens: A global health challenge · Mass Gathering Medicine · 2026
• Risk factors, and outcomes of patients with carbapenem-resistant Enterobacterales bloodstream infection: an eight-year case-case-control study · Frontiers in Cellular and Infection Microbiology · 2026
• Real-world effectiveness and predictors of treatment failure for eravacycline in patients with Acinetobacter baumannii or Klebsiella pneumoniae infections: a multicenter retrospective analysis · Frontiers in Cellular and Infection Microbiology · 2026
• Indian Society of Critical Care Medicine Guidelines on Evidence-based Recommendations for the Treatment of Carbapenem-resistant Enterobacterales, Carbapenem-resistant Acinetobacter baumannii, and Carbapenem-resistant Pseudomonas aeruginosa in Critically Ill Patients: A GRADE-guided Approach · Indian Journal of Critical Care Medicine · 2026
• Bloodstream infection with NDM-1/5 Enterobacter cloacae complex in China: diverse STs, multi-virulence systems and carbapenem resistance · Frontiers in Cellular and Infection Microbiology · 2026

Related topics in Biochemistry, Genetics and Molecular Biology