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Gram Negative BSIs
The Burden of Gram-negative Bloodstream Infections and Value of Rapid Antimicrobial Susceptibility Testing

Released: October 01, 2025

Jasmine R. Marcelin
Jasmine R. Marcelin, MD, FACP, FIDSA
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Key Takeaways
  • Gram-negative bloodstream infections are common and can be difficult to treat due to the rising incidence of antimicrobial resistance.
  • Rapid antimicrobial susceptibility testing combined with antimicrobial stewardship interventions may reduce the time to appropriate antibiotics and improve patient outcomes.

The Burden of Gram-negative Bloodstream Infections
Gram-negative bacteria are responsible for as many as half of all bloodstream infections (BSIs), depending on region and patient population. These infections are often linked to respiratory, urinary, or intra-abdominal sources. BSIs caused by gram-negative organisms are associated with significant morbidity, prolonged hospital stays, and increased inpatient antibiotic use.

Some patients require specialized testing and evaluations to identify and eliminate the source of infection. The mortality rates for gram-negative sepsis are also high, especially when patients present with shock and appropriate treatment is delayed.

Antimicrobial Resistance
When we think about antimicrobial resistance (AMR), we often highlight gram-negative bacteria, particularly those that are multidrug resistant (MDR). Resistance patterns vary regionally and globally. For example, the prevalence of ESBL E. coli isolates ranges from approximately 19% in North America to approximately 54% in Asia, where there may be more restriction in available empiric antibiotics. Globally, bacterial AMR is associated with an estimated 4.7 million deaths annually, with 1.14 million of those directly attributable. The burden of carbapenem-resistant gram-negative BSIs is highest in low- and middle-income countries.

Appropriate empiric antibiotics are critical, especially in patients presenting with sepsis. However, the rise of MDR gram-negative organisms makes this process increasingly complex. For example, although E. coli is a common cause of urinary-source sepsis, ESBL production may render ceftriaxone ineffective. By contrast, empirically choosing a carbapenem like meropenem may be unnecessarily broad spectrum if resistance is not present, contributing to AMR and adverse outcomes. This dilemma highlights the need for earlier diagnostic clarity, and this is precisely where rapid antimicrobial susceptibility testing (AST) can be beneficial.

Understanding AST
AST is an essential part of the diagnostic process as it helps with making decisions on appropriate antibiotics to treat an infection.

  • Rapid genotypic AST detects the presence of known resistance genes (eg, CTX-M, KPC, NDM) using molecular methods such as PCR or sequencing. These tests can be performed directly from blood culture specimens and typically return results within 1-3 hours. Genotypic AST is especially useful for early escalation decisions when resistance markers are present.
  • Rapid phenotypic AST, on the other hand, assesses actual bacterial growth inhibition in the presence of antibiotics. It determines whether the organism is susceptible or resistant based on its behavior, not just genetic potential. Rapid phenotypic AST platforms can return results in 4.5-7 hours, much faster than traditional culture-based methods, which may take 24-72 hours. However, it requires full organism identification before susceptibility testing to determine appropriate breakpoints.
  • Traditional AST relies on several 16- to 24-hour incubations and manual interpretation, delaying optimal therapy decisions. It also requires full organism identification before susceptibility testing can begin .

Rapid vs Traditional AST
Rapid AST offers several advantages over traditional methods. Most notably, it significantly shortens the time to actionable results, often by 24-48 hours, allowing healthcare professionals to make earlier decisions about escalation or de-escalation of therapy based on resistance profiles. This speed can translate into improved patient outcomes, including reduced hospital length of stay, shorter duration of IV antibiotic therapy, and lower risk of catheter-related infections.

In addition, rapid AST supports antimicrobial stewardship by enabling timely interventions and more precise antibiotic use.

However, implementing rapid AST comes with challenges. Not all institutions have the resources to support these platforms, and a careful cost–benefit analysis is essential. Interpretation of results requires clear communication and clinical expertise to avoid misapplication.

Genotypic AST is limited to detecting known resistance genes, meaning other resistance mechanisms may be missed. For example, genetic markers are often unreliable for nonfermenting bacteria like Pseudomonas aeruginosa, and carbapenemase genes are not present in many carbapenemase-resistant bacteria, making phenotypic AST critical in these cases.

Laboratories must also determine whether to apply AST universally or selectively, and ensure results are reported promptly.

Stewardship Integration
When people are very sick and there is diagnostic uncertainty, we tend to treat as broadly as possible because we do not want a poor outcome. Having rapid AST data can help us to be more confident in making both escalation and de-escalation choices to the right antibiotic. This rapid AST must be linked with antimicrobial stewardship interventions where members of the stewardship team call healthcare professionals to recommend antibiotic changes based on the results. This combined strategy facilitates faster de-escalation and makes diagnostic data more actionable. In the long term, the goal is to reduce the impact of unnecessary broad-spectrum antibiotics, thereby minimizing antibiotic resistance and adverse effects.

Conclusions
Gram-negative infections are important clinical syndromes that require us to act quickly to choose the right antibiotics to achieve better outcomes for our patients. Rapid AST may help us decrease the time to antibiotic de-escalation and potentially decrease the time on IV antibiotics, decrease the time in the hospital, and improve survival.

To learn more about this next frontier, check out my presentation, with Dr Jose Alexander and Dr Michael P. Veve at CCO’s upcoming IDWeek satellite symposium, The Next Frontier: Rapid AST to Optimize Care of Patients With Bloodstream Infections. You can join  in person and online on October 19, 2025.

Your Thoughts
What are your greatest challenges in treating patients with BSIs? Leave a comment to join the discussion.

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