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Open research questions in Antibiotic Resistance in Bacteria

78 unresolved questions extracted from the limitations and future-work sections of 780 Antibiotic Resistance in Bacteria papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Future research should focus on genomic sequencing of resistance determinants, in vivo validation of protein efficacy, and formulation of protein-based antimicrobial agents. Moreover, the molecular mechanisms underlying protein–bacteria interactions and the specific resistance genes on the identified plasmids were not fully characterized.

    Plasmid-mediated multidrug resistance and the antibacterial potential of plant seed proteins · 2026 · DOI

  • Therefore, their contribution to resistance to ATM-based combinations in these isolates remains unclear. This finding aligns with the limited data available to date: four ATM-AVI-resistant NDM-producing E.

    In vitro activity of β-lactamase inhibitors avibactam, relebactam and vaborbactam in combination with aztreonam against metallo-β-lactamase producing Escherichia coli clinical isolates · 2026 · DOI

  • Overall, current evidence suggests that fosfomycin may provide additional benefit when incorporated into selected combination regimens for CRAB infections, although its independent contribution remains uncertain.

    Fosfomycin as an adjunctive agent against carbapenem-resistant Acinetobacter baumannii: an updated narrative review · 2026 · DOI

  • However, longitudinal studies investigating the population dynamics of environmental MDR-GNB and links between patients and the environment are lacking, especially in non-outbreak settings.

    Interconnected reservoirs of multidrug-resistant bacteria and plasmids within the hospital built environment · 2026 · DOI

  • gonorrhoeae infections in temporary residents will likely be underreported in this audit, as the notifications are grouped by permanent address, and the Pilbara has a large number of fly-in-fly-out temporary workers who do not have a Pilbara permanent address and therefore are not included within the dataset reviewed for this audit.

    Neisseria gonorrhoeae notifications, resistance and management in the Pilbara Region, Western Australia, July 2023 – June 2024 · 2026 · DOI

  • The nucleoside analogue zidovudine (azidothymidine, AZT) has emerged as a promising conjugation inhibitor, yet the consequences of AZT resistance for subsequent plasmid transfer remain poorly understood.

    Resistance to the conjugation inhibitor AZT reveals mating partner incompatibility during plasmid transfer · 2026 · DOI

  • Fosfomycin-resistant E. coli infections are on the rise, which emphasizes the necessity of ongoing research and the creation of practical solutions to maintain fosfomycin’s clinical usefulness. The molecular epidemiology of resistance genes, particularly plasmid-mediated determinants like fosA3, and their function in the spread of MDR strains should be the main focus of future research. In both hospital and community settings, WGS and advanced genomic surveillance may aid in the early identification and tracking of resistant clones [16]. Accurate diagnosis of fosfomycin resistance and prompt therapeutic decision-making depend on the development of quick molecular diagnostic approaches and uniform susceptibility testing procedures. Affordable molecular assays for rapid detection of fosA3 and other transferable resistance determinants remain limited in many resource-constrained settings and should be prioritized to improve early detection and surveillance of fosfomycin resistance. Additionally, investigating fosfomycin-based combination therapies against carbapenem-resistant and ESBL-producing E. coli may enhance treatment results and lessen the emergence of resistance during therapy [7]. Future goals should include bolstering antimicrobial stewardship initiatives, encouraging sensible antibiotic usage, and carrying out multicentric surveillance investigations, especially in emerging nations like India. To maximize fosfomycin’s therapeutic function against resistant Gram-negative organisms, more clinical trials assessing the drug’s effectiveness and safety in severe systemic infections are required [5].

    Fosfomycin Resistance in Escherichia coli: Mechanisms, Trends, and Clinical Challenges · 2026 · DOI

  • Current empirical antimicrobial guidance derives almost entirely from Western cohorts dominated by Streptococcus pyogenes and aerobic-anaerobic consortia, yet whether this microbial paradigm applies to tropical, high-antimicrobial-pressure settings has not been tested with culture-independent methods.

    Gram-negative-dominated polymicrobial microbiome of necrotizing soft tissue infections from North India: an integrated culture and 16S rRNA metagenomics prospective cohort study · 2026 · DOI

  • In scenarios like this, ATM alone is rendered ineffective due to degradation by ESBL and AmpC enzymes, while CZA alone is insufficient because avibactam lacks activity against MBLs.

    Hope Against Resistance: In Vitro Activity of the Ceftazidime-Avibactam and Aztreonam Combination Against Colistin-Resistant Klebsiella pneumoniae · 2026 · DOI

  • Such modifications would facilitate the use of the IC99 assay applications, such as further investigation of the β-lactam + DAP approach (as opposed to VAN or DAP monotherapy) for endovascular infections, particularly endocarditis.

    Restoration of daptomycin sensitivity with adjunctive cefazolin is associated with C-terminal MprF mutations in MRSA bacteremia isolates · 2026 · DOI

  • Although some ESBL-producing isolates may appear susceptible to piperacillin-tazobactam based on CLSI breakpoints, its use remains controversial due to the potential risk of 2026 Biradar et al.

    An Overview of Virulence, Resistance, and Clinical Significance of Klebsiella Infections · 2026 · DOI

  • pneumoniae in the WHO priority pathogen list highlights the importance of characterizing not only clinical reservoirs but also non-clinical sources, including food, which may act as underrecognized vehicle for human exposure.

    Whole-genome sequencing-based characterization of resistome and virulome in Klebsiella pneumoniae isolated from ready-to-eat foods · 2026 · DOI

  • Despite its unique iron-dependent entry mechanism, CFDC resistance has emerged in Klebsiella pneumoniae , primarily driven by alterations in siderophore transport and β-lactamase evolution; however, the broader intrinsic resistome that supports CFDC tolerance remains incompletely defined.

    Intrinsic resistance networks shape cefiderocol susceptibility in ST258 <i>Klebsiella pneumoniae</i> · 2026 · DOI

  • The IPS may offer a clinically interpretable framework for distinguishing infection from colonization in this underexplored setting, but its performance requires confirmation in larger, prospectively designed multicenter studies.

    Genomic and clinical insights into multidrug-resistant Corynebacterium striatum in a psychiatric hospital: development of an exploratory infection probability score · 2026 · DOI

  • Background Corynebacterium striatum is increasingly recognized as a multidrug-resistant (MDR) opportunistic pathogen, yet its role in psychiatric hospitals remains poorly characterized.

    Genomic and clinical insights into multidrug-resistant Corynebacterium striatum in a psychiatric hospital: development of an exploratory infection probability score · 2026 · DOI

  • ABSTRACT The global rise of convergent carbapenem-resistant and hypervirulent Klebsiella pneumoniae (CR-hvKp) represents a major clinical challenge, yet the role of virulence plasmids (pVirs) in shaping bacterial physiology and pathogenicity remains incompletely understood.

    Distinct and shared impacts of virulence plasmids on the phenotype and transcriptome in convergent carbapenem-resistant and hypervirulent <i>Klebsiella pneumoniae</i> · 2026 · DOI

  • 9% and relatively modest microbiologic eradication rates underscore the complexity of such infections and emphasize the pressing need for pharmacokinetic data to refine dosing in younger children, where evidence remains sparse.

    Clinical and Microbiologic Outcomes of Tigecycline in Pediatric Patients With Multidrug-resistant Gram-negative Infections · 2026 · DOI

  • While active-site residues are well characterised, the contributions of conserved non-active-site residues in exerting enzymatic activity remain unexplored, limiting our understanding about the roles of these residues in the overall OXA-232 function.

    Deciphering the role of the non-active site ancillary residues in maintaining the activity and substrate specificity of OXA-232 beta-lactamase · 2026 · DOI

  • Given the lack of data regarding the co-occurrence of plasmid-mediated quinolone resistance (PMQR) among ESBL-E responsible for infectious diseases in Cameroon, this study aims at determining the prevalence, phenotypic and genotypic characterization of PMQR among ESBL-Enterobacterales isolated from clinical samples in two healthcare facilities in Douala, Cameroon.

    Phenotypic and genotypic characterization of clinical plasmid-mediated quinolone resistance (PMQR) and extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales in two healthcare facilities in Douala, Cameroon · 2026 · DOI

  • Our investigation is limited to the carbapenem group only; however, it is suggested to evaluate the broader classes of antibiotic panel in relevance with all three classes of integrons (class 1,2 and 3), and multicenter designs for an extensive understanding of its molecular and clinical relevance.

    Dissemination of Class 1 Integron-Associated Meropenem and Imipenem Resistancein Pseudomonas Aeruginosa-related Infections · 2026 · DOI

  • However, a limitation of this study is the relatively small number of isolates included in the checkerboard and MBIC assays, which may affect the generalizability of the find- ings. Another limitation of this study is the lack of chemical characterization of the CFS, which may contribute to the observed variability in antimicrobial interactions.

    Synergistic and antagonistic interactions between colistin and cell-free supernatants of Lactobacillus species against clinical isolates of Acinetobacter baumannii · 2026 · DOI

  • Shiva Yadav M.Sc. Microbiology Amity University Lucknow Campus, Uttar Pradesh, India Abstract: Escherichia coli and Klebsiella pneumoniae are responsible for the majority of urinary tract infections (UTIs). UTIs are among the most prevalent infections in humans globally and therefore pose a significant public health problem (1,2). As a result of its nocturnal position as one of the most important Uropathogen responsible for either community-acquired or hospital-acquired UTIs, Klebsiella pneumoniae is now regarded as a significant medical threat (1). The increasing number of ESBLproducing Klebsiella pneumoniae, especially within the last two decades, has made it increasingly difficult to treat these infections; the number of effective treatment options has diminished due to the emergence of this pathogen, which is resistant to multiple antibiotic classes (2,3). As a result of the resistance exhibited by ESBL-producing Klebsiella pneumoniae to many β-lactam antibiotics in particular, the option of using extended-spectrum cephalosporins and monobactams as treatment options for these infections is significantly reduced (2). Therefore, the increased incidence of morbidity, mortality, and healthcare costs associated with the use of antibiotics to treat UTIs caused by ESBLproducing Klebsiella pneumoniae is due to the fact that ESBLs hydrolyze extended-spectrum cephalosporins and monobactams (3,4). This review will examine the epidemiology, pathogenesis, virulence factors, and mechanisms of ESBL production in Klebsiella pneumoniae UTI infections, discuss patterns of antimicrobial resistance, and summarize the diagnostic and treatment methods and emerging therapeutic alternatives associated with this pathogen(5). The review will also highlight some of the challenges associated with multidrug-resistant strains of Klebsiella pneumoniae causing UTIs and will provide a future perspective on infection control, antibiotic stewardship, and novel therapeutic interventions. An understanding of the evolving resistance of Klebsiella pneumoniae to antibiotics, especially ESBL-producing strains, will be important for the development of appropriate therapeutic strategies to reduce the global impact of antimicrobial resistance and the occurrence of UTIs (4,5). Keywords: ESBL, Klebsiella pneumoniae, Urinary Tract Infection, Antimicrobial Resistance, Multidrug Resistance, Antibiotic Stewardship. I. INTRODUCTION The prevalence of urinary tract infections (UTIs) globally is high with millions experiencing UTIs yearly. UTIs may affect all areas of the urinary tract such as urethra, bladder, ureters, and kidneys (6,7). Women have a higher propensity to develop UTIs due to their anatomy and physiology (7). Escherichia coli continues to be the most common cause of UTIs; however, Klebsiella pneumoniae has emerged as another important cause of community-acquired and nosocomial infections (1). The emergence of antimicrobial resistance has established K. pneumoniae as a major clinical threat (4,5).

    Extended-Spectrum Beta-Lactamase (ESBL)-Producing Klebsiella pneumoniae in Urinary Tract Infections: Current Challenges and Future Perspectives · 2026 · DOI

  • While our 15-year data set provides robust longitudi- nal insights, limitations include reliance on phenotypic 318 Anand Acharya, et al. methods and the absence of MIC breakpoints or molecular confirmation of resistance mechanisms. Inclusion of such data in future studies would offer a more granular under- standing of resistance drivers. Moreover, investigation into infection outcomes, ICU-specific dynamics, and environ- mental reservoirs would enrich the clinical interpretability of resistance trends. Future research should also explore the translational potential of emerging strategies, such as phage therapy, quorum-sensing inhibitors, iron chelators, and nanoparticle-based drug delivery-many of which are still in preclinical phases, as detailed by Pang et al. (2019) and Elfadadny et al. (2024) (1,2). However, this study did not have access to strain-level typing/outbreak analytics across the full 15-year period; therefore, we cannot exclude clonal expansion/endemic MDR circulation as contributors to observed temporal shifts. Given the longitudinal, retro- spective design and reliance on conventional phenotypic identification without routine molecular or MALDI-TOF confirmation across the entire study period, some degree of species misclassification cannot be fully excluded and may have introduced measurement variability in the year-wise susceptibility estimates.

    Fifteen-Year Trends in Antimicrobial Resistance of Pseudomonas aeruginosa at a South Indian Tertiary Care Centre: A Retrospective Analysis. · 2026 · DOI

  • transfer and The rapid plasmid-mediated horizontal recurrence of colistin-resistant chromosome-mediated infections pose a serious global threat. The continuous evolution of plasmid-mediated and chromosomal resistance contributes to treatment failures, prolonged hospital stays, high mortality and increased healthcare costs. Addressing this challenge requires sustained research and well-structured policy planning focused on key priorities. Specifically, it is necessary to restrict colistin use in agriculture and veterinary practice to reduce selective pressure, enhance rapid and accurate genomic and epidemiological surveillance for mcr genes and chromosomal mutations, and continue research into the molecular and evolutionary mechanisms underlying emerging resistance. To prevent transmission between animals, humans, and the environment, there is an urgent need to develop rapid, cost-effective, and accurate phenotypic and molecular detection methods, coupled with comprehensive surveillance strategies covering both clinical and non-clinical settings. Policies promoting antimicrobial stewardship to ensure judicious colistin use, along with effective surveillance strategies, are essential to curb the spread of colistin resistance. Future research should focus on affordable, field-deployable molecular assays and global genomic surveillance to track resistance evolution within a One Health framework, enabling effective management at both social and economic levels. For African countries, a number of priority actions stand out. First, laboratory capacity for BMD testing needs to be built through training programmes, equipment provision, and the development of regional reference laboratories. Second, national and regional surveillance systems should be established for mcr gene variants covering clinical, veterinary, and environmental isolates. Third, human and animal health data should be integrated under One Health frameworks that draw on the structures of Africa CDC and AU-IBAR. Fourth, African laboratories and health ministries should be supported (Global Antimicrobial Resistance and Use Surveillance System). Fifth, the development of diagnostic tools that are affordable and deployable outside centralised laboratory settings in WHO GLASS in participating investment. These are not deserves targeted research aspirational goals in the distant future; they are achievable with the right partnerships and commitment. Implementing robust strategies will support the development of a comprehensive framework for surveillance, management, treatment, and prevention of colistin-resistant infections, addressing treatment failures and reducing the threat to human, animal, and environmental health, ultimately improving public health outcomes.

    The colistin resistance pandemic: A dual threat from plasmid-encoded mobilised colistin resistance genes and chromosomal mutations · 2026 · DOI

  • should be acknowledged. The study has a retrospective, singlecenter design with a relatively small sample size in the CRO group (n = 43), limiting statistical power for subgroup analyses. Despite propensity score matching on key variables, residual confounding cannot be fully excluded, particularly due to the lack of data on acute and chronic GVHD, HCT-CI, Disease Risk Index (DRI), cumulative immunosuppression, steroid exposure, and detailed prior antibiotic history. We defined peri-transplant CRO infection within a broad 12-month window around alloHCT, which combines biologically distinct phases including pre-engraftment neutropenia, early post-engraftment, and late GVHD-related infections. Molecular genotyping for carbapenemase genes was not performed due to resource constraints, with resistance determined phenotypically only. Future research should prioritize prospective, multicenter studies to better define the epidemiology of CRO infections in trials transplant recipients across diverse regions.

    Outcomes of allogeneic hematopoietic cell transplantation in patients with carbapenem-resistant organisms infection: a propensity score-matched analysis · 2026 · DOI

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