What is the treatment for Gram-negative (GN) bacteremia?

From the Guidelines

The treatment for gram-negative bacteremia from a urinary source should be 7 days of optimized antibiotic therapy, with the choice of drug and dose tailored to the patient and the urinary focus of infection, as supported by recent guidelines 1. When managing gram-negative bacteremia, it is crucial to consider the source of the infection, with urinary sources being a common origin. The guidelines from the Wikiguidelines Group Consensus Statement, published in JAMA Network Open in 2024 1, provide a clear recommendation for the treatment duration of gram-negative bacteremia from a urinary source.

• Key points to consider in the treatment include:
  • The duration of treatment: 7 days is recommended for gram-negative bacteremia from a urinary source when source control has been addressed, as evidenced by multiple RCTs showing noninferiority compared to 14 days of treatment for patient-oriented outcomes such as clinical cure, clinical failure, relapse, and all-cause mortality 1.
  • Choice of antibiotic: While no specific class of medications can be recommended based on the trials, which tested duration as a strategy and not specific drugs, it is reasonable to ensure that the choice of drug and the doses used are optimized for the patient and a urinary focus of infection.
  • Importance of source control: Addressing the source of infection, if applicable, is crucial in the management of gram-negative bacteremia.
  • Consideration of patient-oriented outcomes: The recommendation is based on evidence showing noninferiority of 7 days compared to 14 days of treatment for outcomes such as clinical cure, clinical failure, relapse, and all-cause mortality, emphasizing the importance of considering these outcomes in treatment decisions 1.

From the FDA Drug Label

The primary objective of the study was to evaluate the safety and tolerability of AVYCAZ and it was not powered for a statistical analysis of efficacy A total of 870 hospitalized adults with HABP/VABP were randomized and received trial medications in a multinational, multi-center, double-blind trial comparing AVYCAZ 2.5 grams (ceftazidime 2 grams and avibactam 0. 5 grams) intravenously every 8 hours to meropenem 1 gram intravenously every 8 hours for 7 to 14 days of therapy. Bacteremia at baseline was present in 4. 8% of patients.

The treatment for gram-negative bacteremia is AVYCAZ (ceftazidime-avibactam), which can be administered intravenously every 8 hours for 7 to 14 days of therapy 2.

• Key points:
  • The study compared AVYCAZ to meropenem in hospitalized adults with HABP/VABP.
  • Bacteremia was present in 4.8% of patients at baseline.
  • AVYCAZ was non-inferior to meropenem with regard to the primary endpoint (28-day all-cause mortality in the ITT population) 2.

From the Research

Treatment Options for Gram-Negative Bacteremia

• The treatment for gram-negative bacteremia can involve various antibiotic regimens, including the use of beta-lactams, aminoglycosides, and carbapenems 3, 4, 5.
• A study found that the addition of a single-dose aminoglycoside to a beta-lactam was not significantly associated with reduced mortality or increased time to recovery from acute kidney injury in patients with gram-negative bacteremia 3.
• Another study suggested that short-course antibiotic treatment may be non-inferior to long-course treatment for patients with uncomplicated gram-negative bacteremia, considering the drug-related side effects and cost-effectiveness 4.
• Meropenem, a broad-spectrum carbapenem antibiotic, has been shown to be effective in the treatment of serious bacterial infections, including gram-negative bacteremia, and has a similar efficacy to comparator antibacterial agents 5.

Antibiotic Selection and Stewardship

• The selection of empiric antibiotics for gram-negative bacteremia can be challenging due to rising resistance rates, and individualized clinical prediction models may help reduce broad-spectrum antibiotic use and preserve/improve adequacy of treatment 6.
• A study found that an antimicrobial stewardship intervention based on individualized predictive models for resistance can influence empiric antibiotic selections for gram-negative bacteremia and facilitate early de-escalation of therapy without compromising adequacy of antibiotic coverage 6.
• Local epidemiology should be taken into account when selecting empiric antibiotics for community-acquired gram-negative bacteremia, as the prevalence of resistant strains can vary depending on the region and other factors 7.

Considerations for Treatment

• The choice of antibiotic regimen should be based on the severity of the infection, the susceptibility of the causative organism, and the patient's clinical condition 3, 4, 5.
• The use of broad-spectrum antibiotics should be balanced with the need to minimize the development of antibiotic resistance and reduce the risk of adverse effects 4, 6.
• Further studies are needed to determine the optimal duration and choice of antibiotic treatment for gram-negative bacteremia, particularly in more severely ill patient populations 3, 4.