Antimicrobial Efficacy and Coagulation in Gram-Negative Infections

Gram-negative infections remain a formidable global health challenge owing to rising antimicrobial resistance and the risk of drug‐induced coagulation disorders. The outer membrane of Gram-negative bacteria impedes many antibiotics, necessitating novel agents and combination therapies to restore clinical efficacy. Concurrently, certain β-lactam antibiotics and their formulations can interfere with vitamin K metabolism or directly prolong prothrombin time, leading to hypoprothrombinemia and bleeding. Understanding the balance between potent microbial clearance and minimising haemostatic disturbance has become critical, especially in vulnerable populations such as critically ill or elderly patients. Advances in pharmacokinetic/pharmacodynamic modelling, machine learning risk stratification and meta-analytical evaluation of adverse coagulation signals now inform individualised dosing strategies and stewardship interventions. These developments aim to optimise bacterial eradication while reducing haemorrhagic complications, with implications for intensive care protocols, antibiotic development and global antimicrobial policy.

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Antimicrobial Efficacy and Coagulation in Gram-Negative Infections publication trend

The graph below shows the total number of articles in antimicrobial efficacy and coagulation in gram-negative infections across all publications each year (not limited to Nature Index journals).

Technical terms

Gram-negative bacteria: Microorganisms characterised by an outer membrane containing lipopolysaccharide, conferring intrinsic resistance to many antibiotics.

Beta-lactam antibiotics: A class of bactericidal agents that inhibit cell-wall synthesis by targeting penicillin‐binding proteins.

Hypoprothrombinemia: A reduction in prothrombin levels leading to impaired clot formation and increased bleeding risk.

Prothrombin time: A laboratory measure of the extrinsic coagulation pathway, expressed in seconds or as an international normalised ratio.

Minimum inhibitory concentration (MIC): The lowest antibiotic concentration that prevents visible growth of a microorganism in vitro.

Area under the receiver operating characteristic curve (AUC): A performance metric for diagnostic or predictive models, reflecting the trade‐off between sensitivity and specificity.

N-methylthiotetrazole (NMTT) side chain: A chemical moiety in certain cephalosporins known to interfere with vitamin K-dependent coagulation factors.

References

1. Machine learning models for coagulation dysfunction risk in inpatients administered β-lactam antibiotics. Frontiers in Pharmacology (2024).
2. The Association Between Cephalosporin and Hypoprothrombinemia: A Systematic Review and Meta-Analysis. International Journal of Environmental Research and Public Health (2019).
3. Model-Informed Drug Development of New Cefoperazone Sodium and Sulbactam Sodium Combination (3:1): Pharmacokinetic/Pharmacodynamic Analysis and Antibacterial Efficacy Against Enterobacteriaceae. Frontiers in Pharmacology (2022).
4. Serum trough concentration threshold and risk factors of cefoperazone-induced coagulopathy in critically ill patients: A retrospective case-control study. European Journal of Clinical Pharmacology (2024).