This article systematically reviews the clinical reappraisal of temocillin for multidrug-resistant Gram-negative bacterial infections, focusing on its stability against ESBL- and AmpC-producing bacteria, pharmacokinetic characteristics, and therapeutic potential across different infection types. It highlights temocillin's role in carbapenem-sparing strategies, particularly for urinary tract, bloodstream, intra-abdominal, and central nervous system infections. Synergistic effects with certain antibiotics (e.g., fosfomycin) and its safety/efficacy profile in special populations (children, elderly, immunosuppressed patients) are also discussed.
Literature Overview
This article, 'Temocillin: A Narrative Review of Its Clinical Reappraisal', published in Antibiotics, summarizes temocillin's antimicrobial spectrum, pharmacokinetics, pharmacodynamic features, and clinical application potential. It analyzes temocillin's high stability against ESBL- and AmpC-producing Enterobacteriaceae, with partial activity against KPC-producing strains. Additionally, temocillin demonstrates low ecological impact and favorable safety profile, making it suitable for outpatient parenteral antimicrobial therapy (OPAT) and specific populations such as pediatrics, geriatrics, and immunosuppressed patients. The review notes that current evidence is primarily derived from retrospective and observational studies, necessitating further validation through prospective randomized controlled trials.
Background Knowledge
Temocillin is a narrow-spectrum β-lactam antibiotic initially introduced in the 1980s but recently re-emerging due to increasing multidrug-resistant Gram-negative pathogens. It exhibits high stability against ESBL (extended-spectrum β-lactamases) and AmpC-producing bacteria, though activity against metallo-β-lactamase producers (e.g., NDM, VIM) and certain KPC strains remains limited. Its mechanism involves binding to bacterial penicillin-binding proteins (PBPs), inhibiting cell wall synthesis, with primary activity against Enterobacteriaceae such as Escherichia coli, Klebsiella, and Proteus. The narrow spectrum minimizes resistance induction risks and microbiome disruption, making it ideal for urinary tract, bloodstream, intra-abdominal, and pulmonary infections. Subcutaneous administration stability positions temocillin as a viable OPAT candidate. While existing clinical trials support efficacy, global epidemiological data and standardized dosing regimens remain limited, warranting further prospective studies for optimal application.
Research Methods and Experiments
This study employed a narrative literature review approach, systematically searching PubMed for temocillin-related publications. Key areas investigated included microbiology, pharmacokinetics, pharmacodynamics, clinical efficacy, and safety. Multiple retrospective and prospective clinical studies were analyzed to evaluate temocillin's therapeutic performance across infection types, including urinary tract infections, bloodstream infections, intra-abdominal infections, pneumonia, and central nervous system infections. Special attention was given to its application in special populations (pediatric, geriatric, immunosuppressed) and synergistic interactions with other antibiotics. Subgroup analyses covered P. aeruginosa resistance mechanisms, pharmacokinetic differences between intravenous and subcutaneous administration routes, and tissue penetration characteristics in specific anatomical sites (e.g., prostate, bile).
Key Conclusions and Perspectives
Research Significance and Prospects
Temocillin represents a promising agent for antimicrobial stewardship due to its stability against β-lactamases, safety profile, and ecological advantages in carbapenem-sparing strategies. However, definitive evidence from prospective RCTs is required to validate efficacy in severe systemic infections and non-urinary indications. Future research priorities include dose optimization across populations, PK/PD modeling development, resistance mechanism surveillance, and global epidemiological studies. Ongoing trials like PITAGORE (comparing temocillin with piperacillin-tazobactam or carbapenems) will provide critical evidence for its ICU application.
Conclusion
Temocillin's high β-lactamase stability, low resistance induction potential, and excellent tissue penetration position it as a critical carbapenem-sparing antibiotic. Current clinical evidence supports its application in urinary tract, bloodstream, intra-abdominal, and selected pneumonia cases, particularly for ESBL/AmpC-producing pathogens. Limited pediatric and immunosuppressed patient data exist, though preliminary studies show high treatment success rates. Subcutaneous administration's stability and convenience make it ideal for OPAT programs. Future studies should focus on optimizing dosing strategies, expanding efficacy evaluations to diverse infection types, and validating its role in critical care settings. Continued investigation into synergistic combinations, resistance mechanisms, and global epidemiology is essential for maximizing its antimicrobial stewardship potential.
