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Open research questions in Antibiotics Pharmacokinetics and Efficacy

142 gap statements mined from Antibiotics Pharmacokinetics and Efficacy papers in our 4.5M-paper local library, which holds 863 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • Although significant pharmacokinetic variability was observed among the 10, 20, and 40 mg/kg dosages— most notably a reduction in ClT and Vdss at the highest dose—these variations do not strictly confirm non-linear kinetics, and their direct clinical relevance remains to be fully elucidated.

    Pharmacokinetic Profiles of Pentoxifylline and Its 5-Hydroxyhexyl Metabolite Administered by Different Doses in Goats · 2026 · DOI

  • Although current guideline recommendations regarding target trough concentrations are inconsistent and supported by limited evidence, they provide a practical framework for clinical decision-making. Further prospective studies are warranted to strengthen the evidence base, directly compare simplified monitoring strategies, and refine dosing and monitoring approaches to optimize the clinical use of amikacin.

    Clinical Considerations of Amikacin Pharmacotherapy in Adults—A Narrative Review with Focus on Safety and TDM · 2026 · DOI

  • Current guidelines vary in their recommended target trough levels for safety (with the IDSA and Polish national guidelines suggesting < 5 mg/L, versus the more conservative threshold of <1 mg/L proposed by the Sanford Guide), yet these thresholds are based on limited evidence. Particular uncertainty exists in patients with intermediate trough concentrations, for whom clear evidence-based guidance is lacking.

    Clinical Considerations of Amikacin Pharmacotherapy in Adults—A Narrative Review with Focus on Safety and TDM · 2026 · DOI

  • Further studies are needed to evaluate the effectiveness and safety of Fosfomycin in treating CNS infections in different populations and settings. The study's results highlight the need for continued research into the treatment of CNS infections, particularly in cases where other antibiotics are not effective.

    Real-World Data on the Use of Intravenous Fosfomycin for the Treatment of Central Nervous System Infections: a Subgroup Analysis from the FORTRESS Study · 2026 · DOI

  • Fosfomycin-containing combination therapy may be a viable option for MDR/XDR/PDR Gram-negative infections; however, in-vivo evidence remains limited.

    The Efficacy of Antibiotic Combination Therapies with Fosfomycin For Multi-Drug Resistant Gram-Negative Bacterial Infections · 2026 · DOI

  • There is currently no standardized approach for determining which antimicrobial classes or groups should be used to define MDR, XDR, and PDR. In recent years, growing attention has been directed toward the synergistic potential of fosfomycin in combination with other antimicrobial agents, particularly against resistant strains for which therapeutic alternatives are scarce.

    The Efficacy of Antibiotic Combination Therapies with Fosfomycin For Multi-Drug Resistant Gram-Negative Bacterial Infections · 2026 · DOI

  • There is a lack of information on the safety of levofloxacin use during pregnancy. The study aims to fill this gap by examining the embryotoxic effects of levofloxacin exposure.

    Determination of Embryotoxic Effects of Levofloxacin Exposure by the In Ovo Method · 2026 · DOI

  • Also lacking information about the oral bioavailability of the drug in snails, we used a higher dose in the PO groups to compensate for potential low haemolymph concentrations resulting from unpredictable low PO bioavailability.

    Pharmacokinetics and residue depletion of enrofloxacin and its metabolite ciprofloxacin in land snails (Cornu aspersum maxima) · 2026 · DOI

  • The need to evaluate DDIs between RIF, CLR, and ETI. The lack of understanding of the effect of concomitant RIF and CLR on ETI plasma exposures.

    Effect of concomitant rifampin and clarithromycin on elexacaftor-tezacaftor-ivacaftor using a physiologically based pharmacokinetic (PBPK) modeling approach · 2026 · DOI

  • Further studies can investigate the implementation of sustainable protocols for other types of antibiotics. The study of the environmental impact of antibiotic administration can be extended to other healthcare settings.

    Optimizing β-lactam antibiotics with the highest concentration–for continuous infusion reduce carbon footprint in intensive care · 2026 · DOI

  • The environmental impact of antibiotic administration is a concern. There is a need to evaluate the environmental benefit of implementing the most sustainable protocol for antibiotic administration.

    Optimizing β-lactam antibiotics with the highest concentration–for continuous infusion reduce carbon footprint in intensive care · 2026 · DOI

  • The study faced challenges in terms of the retrospective design and the lack of a preliminary assessment of the number of subjects needed for inclusion. The study had to consider the impact of secular trends on the results. The study had to account for uncertainty in PK measurements and variability in PK/PD targets.

    Evaluation of Model-Informed Precision Dosing of Cefepime in Critically Ill Patients: A French Before–After Study · 2026 · DOI

  • The study did not perform a preliminary assessment of the number of subjects needed for inclusion. The study used a retrospective design. The study did not upload the statistical analysis plan on an external repository.

    Evaluation of Model-Informed Precision Dosing of Cefepime in Critically Ill Patients: A French Before–After Study · 2026 · DOI

  • Antimicrobial resistance remains one of the most formidable challenges to global public health. The -lactam ring inherent to both structures is highly susceptible to hydrolysis. The combination of cefixime trihydrate and potassium clavulanate requires reliable analytical methods for quality control and routine analysis.

    AN OVERVIEW OF CEFIXIME TRIHYDRATE & POTASSIUM CLAVULANATE FIXED-DOSE COMBINATION AND ITS DIFFERENT ANALYTICAL METHOD · 2026 · DOI

  • There is a limited number of analytical methods reported for the simultaneous estimation of cefixime trihydrate and potassium clavulanate. No validated UV spectrophotometric method has been published for this combination.

    AN OVERVIEW OF CEFIXIME TRIHYDRATE & POTASSIUM CLAVULANATE FIXED-DOSE COMBINATION AND ITS DIFFERENT ANALYTICAL METHOD · 2026 · DOI

  • Dosing guidelines of piperacillin are well defined in healthy pediatric and adult populations but have not been extensively studied in critically ill pediatric patients who often have significant alterations in antibiotic pharmacokinetics (PK) and pharmacodynamics (PD).

    Are We Dosing Correctly? Population Pharmacokinetics of Piperacillin in Critically Ill Pediatric Patients · 2026 · DOI

  • There is a lack of prospective multicenter pediatric studies using standardized dosing, outcome, and safety definitions. The incidence and complexity of multidrug-resistant infections in children are increasing, making it essential to establish the efficacy and safety of intravenous polymyxin-containing therapy.

    Clinical outcomes and adverse events associated with intravenous polymyxin-containing therapy in hospitalized children with resistant Gram-negative infections: a systematic review and meta-analysis · 2026 · DOI

  • Aminoglycoside antibiotics such as amikacin are indispensable for treating severe Gram-negative infections, but their clinical use is limited by a well-documented toxicity profile that has focused overwhelmingly on ototoxicity and nephrotoxicity, leaving their action on the peripheral nervous system comparatively unexplored.

    Ultrastructural Signatures of Amikacin Neurotoxicity and the Protective Modulation of Memantine in Peripheral Nerves: A Transmission Electron Microscopy Exploration in Wistar Rats · 2026 · DOI

  • The development of a chromatographic method is a challenging and complicated process due to multiple interacting parameters. The traditional univariate approach for developing a chromatographic method has numerous drawbacks.

    Emerging quality-by-design optimized HPLC method for the concurrent determination of cefixime and ornidazole: a multi-criteria green and blue environmental footprinting · 2026 · DOI

  • CNS infections are a major cause of morbidity and mortality worldwide. The epidemiology of bacterial meningitis varies considerably across geographic regions and healthcare environments. The treatment of CNS infections is challenging due to the complexity of the infections and the limited effectiveness of current treatment options.

    Real-World Data on the Use of Intravenous Fosfomycin for the Treatment of Central Nervous System Infections: a Subgroup Analysis from the FORTRESS Study · 2026 · DOI

  • In Türkiye, no standardized OPAT framework exists; patients continue therapy through emergency departments, primary care facilities, or privately funded nursing services.

    Multicentre insights into OPAT: a comprehensive analysis of Türkiye’s unstructured system · 2026 · DOI

  • Limited availability of data on nephrotoxicity and neurotoxicity.

    Clinical outcomes and adverse events associated with intravenous polymyxin-containing therapy in hospitalized children with resistant Gram-negative infections: a systematic review and meta-analysis · 2026 · DOI

  • Further studies on delafloxacin for skin and soft tissue infections, - Investigation of delafloxacin's efficacy in different patient populations, - Comparison of delafloxacin with other…

    Delafloxacin as a new therapeutic tool for the treatment of skin and soft tissue infections: experience in a single center · 2026 · DOI

  • Amikacin exerts a distinct, previously under-recognized ultrastructural neurotoxicity on peripheral nerves, and concurrent memantine confers substantial neuroprotection, supporting a potential adjunctive role for NMDA-receptor antagonism during aminoglycoside therapy.

    Ultrastructural Signatures of Amikacin Neurotoxicity and the Protective Modulation of Memantine in Peripheral Nerves: A Transmission Electron Microscopy Exploration in Wistar Rats · 2026 · DOI

  • A subsequent adequately powered confirmatory study, - Investigation of the ecological implications of imipenem-cilastatin, - Further evaluation of the efficacy and safety of imipenem-cilastatin…

    Toward More Predictable Musculoskeletal Embolization: A Translational Evaluation of Imipenem–Cilastatin Performance and Safety in a Porcine Model of Tendon Neovascularization · 2026 · DOI

Most-cited papers in Antibiotics Pharmacokinetics and Efficacy

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Open questions raised by papers listed on this page include: (1) Further prospective studies are warranted to strengthen the evidence base, directly compare simplified monitoring strategies, and refine dosing and monitoring approaches to optimize the clinical use of amikacin (“Clinical Considerations of Amikacin Pharmacotherapy in Adults—A Narrative…”, 2026); (2) Further studies are needed to evaluate the effectiveness and safety of Fosfomycin in treating CNS infections in different populations and settings (“Real-World Data on the Use of Intravenous Fosfomycin for the Treatment of…”, 2026); (3) Fosfomycin-containing combination therapy may be a viable option for MDR/XDR/PDR Gram-negative infections; however, in-vivo evidence remains limited (“The Efficacy of Antibiotic Combination Therapies with Fosfomycin For Multi-Drug…”, 2026); (4) There is a lack of information on the safety of levofloxacin use during pregnancy (“Determination of Embryotoxic Effects of Levofloxacin Exposure by the In Ovo…”, 2026); (5) The lack of understanding of the effect of concomitant RIF and CLR on ETI plasma exposures (“Effect of concomitant rifampin and clarithromycin on…”, 2026). 142 gap statements have been mined from Antibiotics Pharmacokinetics and Efficacy papers in our 4.5M-paper local library, which holds 863 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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