Editor’s Note: Bloodstream infection (BSI) is a severe systemic infection, especially with multidrug-resistant bacteria such as carbapenem-resistant Gram-negative organisms (CRO), posing a significant threat to patient safety. Clinical management of BSI faces numerous challenges, with early diagnosis and precise treatment being crucial for improving patient outcomes. At the recent 34th European Congress of Clinical Microbiology and Infectious Diseases (ESCMID Global 2024), V. Anton-Vazquez and colleagues from St. George’s University Hospital NHS Foundation Trust in the UK presented a study titled “Clinical Outcomes and Factors Associated with Optimal Antibiotic Therapy in Gram-Negative BSI: A Post Hoc Analysis of a Comparative Study between Rapid and Conventional Antimicrobial Susceptibility Testing.” Infection Medicine has invited Professor Chongjie Pang from Tianjin Medical University General Hospital to provide an in-depth commentary on this study, asking him to further elucidate its clinical significance and value based on his clinical experience.
Introduction
Clinical Outcomes and Factors Associated with Optimal Antibiotic Therapy in Gram-Negative Bloodstream Infection (BSI): A Post Hoc Analysis of a Comparative Study between Rapid and Conventional Antimicrobial Susceptibility Testing (Abstract No: O1172)
Methods
A post hoc analysis was conducted on Gram-negative BSI patients from published prospective observational studies. The primary endpoint was to describe the clinical characteristics and outcomes of patients receiving optimal versus suboptimal antibiotic therapy. Optimal antibiotic therapy required two criteria: (1) in vitro sensitivity of the pathogen to the antibiotic and (2) the antibiotic with the narrowest spectrum based on previously published rankings of antimicrobial agents. Suboptimal antibiotics were effective in vitro but did not have the narrowest spectrum. Univariate and multivariate analyses were performed to explore factors influencing the 28-day mortality rate of patients receiving optimal antibiotic therapy and those receiving it.
Results
Among 191 Gram-negative BSI patients, 129 received optimal antibiotic therapy, while 62 received suboptimal antibiotic therapy. The median age was 69 years, with females accounting for 48%. Community-acquired BSI (37% vs. 21%, P=0.031), Escherichia coli BSI (66% vs. 50%, P=0.040), and urinary source BSI (61% vs. 29%, P<0.001) were more common in the optimal group. Conversely, intravascular source (19% vs. 4%, P<0.001), Pitt score >4 (85% vs. 71%, P<0.001), and ICU admission (34% vs. 18%, P=0.017) were more common in the suboptimal group. Factors influencing optimal therapy included Pitt score <4 (OR 3.15, 95%CI: 1.00–9.89, P=0.050) and non-Enterobacteriaceae (OR 12.92, 95%CI: 2.43–68.85, P=0.003). Compared to optimal therapy, patients receiving suboptimal therapy had higher 28-day mortality (21% vs. 9%, P=0.015) and longer hospital stays (17 vs. 9 days, P=0.018). Factors influencing 28-day mortality with optimal therapy included Charlson index >2 (OR 13.2, 95%CI: 1.30–134.29, P=0.029), CRP >100 mg/L (OR 6.70, 95%CI: 1.12–40.12, P=0.037), non-Escherichia coli (OR 0.19, 95%CI: 0.04–0.98, P=0.047), and results of conventional antimicrobial susceptibility testing (AST) (OR 7.89, 95%CI: 1.05–59.51, P=0.045).
Conclusion
Early pathogen identification, rapid AST, and timely initiation of optimal antibiotic therapy may positively impact patient prognosis. Prospective studies are needed to validate and explore additional factors influencing optimal antibiotic therapy in Gram-negative BSI.
Expert Commentary
Bloodstream infection (BSI) is a clinically severe systemic infectious disease, particularly BSI caused by multidrug-resistant bacteria such as carbapenem-resistant Gram-negative organisms (CRO), which can increase patient mortality and pose a serious threat to patient safety. For a long time, clinical diagnosis and treatment of BSI have faced many challenges, requiring continuous improvement in the early diagnosis and precise treatment of BSI. In recent years, rapid pathogen detection and microbial susceptibility testing have greatly aided in the early diagnosis of BSI, such as pathogen microbial metagenomics sequencing (mNGS), direct identification by MALDI-TOF MS after positive blood culture, and direct rapid antimicrobial susceptibility testing (RAST), as well as multiple lateral flow immunoassay (LFA) methods for rapid detection of CTX-M Gram-negative bacteria in blood culture. At the same time, direct communication between microbiology experts and clinicians is essential for enhancing BSI diagnosis. Empirical treatment of BSI should comprehensively consider whether it is community-acquired or hospital-acquired, the route of pathogen invasion, possible primary or migratory lesions, thereby ascertaining the infectious pathogen or resistance as much as possible, and combining patient pathophysiological conditions and pharmacokinetic/pharmacodynamic characteristics of antimicrobial agents to promptly administer effective antimicrobial therapy and actively manage infectious foci.
Professor Chongjie Pang
Department of Infectious Diseases, Tianjin Medical University General Hospital
Director of the Department of Infectious Diseases, Tianjin Medical University General Hospital; Deputy Director of the Department of Internal Medicine, Tianjin Medical University General Hospital; Chief Physician; Master’s Supervisor
Also serves as a member of the Chinese Society of Microbiology and Infection and Drug Resistance Prevention, a member of the Hospital Infection Control Branch of the Chinese Preventive Medicine Association, Executive Member of the Infectious Diseases Evidence-based and Translational Committee of the Chinese Research Hospital Association, Chairman of the Hospital Infection Control Branch of the Tianjin Medical Association, Vice Chairman of the Infectious Diseases Branch of the Tianjin Medical Association, Vice Chairman of the Infection Department Physician Branch of the Tianjin Medical Association, Deputy Director of the Second Committee of the Infection Department Physician Branch of the Tianjin Medical Association, Deputy Editor-in-Chief of the Microbiology and Infection Special Issue of Medical Reference News, and other positions. Also a member of the Expert Committee of the National Health Commission’s Clinical Application of Antibacterial Drugs and Bacterial Resistance Evaluation, the Expert Committee of the Fungal Disease Monitoring Network, and the Infection Control Expert Group.
Engaged in the diagnosis and treatment of fever of unknown origin, infectious diseases, antibiotic-resistant bacteria, fungal infections, consultation and management of clinical use of antimicrobial drugs, hospital infection control for a long time.&
