Bugs in the Blood: Updates on Gram-negative BSI management

Reviewed by Cynthia T. Nguyen, PharmD, University of Chicago Medicine and James “Brad” Cutrell, MD, FIDSA, UT Southwestern Medical Center

An increasing body of literature has been published exploring the antibiotic management of uncomplicated gram-negative bloodstream infections (GN BSIs). Opportunities for stewardship include reducing durations of antibiotic therapy, transitioning to oral therapy, and guiding the need for repeat blood cultures. Much of the literature has focused on Enterobacterales BSI, but there is also opportunity for non-fermenting gram-negative rods, specifically Pseudomonas spp.

Bae and colleagues add to the evidence surrounding shorter versus longer durations of therapy for uncomplicated pseudomonal BSI with a 10-year, single-center, retrospective study. Uncomplicated BSI was defined as exclusion of metastatic infection or deep-seated infection (e.g. endovascular infection, osteoarticular infection or CNS infection) and negative follow-up blood cultures drawn within 48h of the initial set. The primary outcome was a composite of the rate of recurrent P. aeruginosa infection and 30-day mortality. A propensity score analysis with inverse probability of treatment weighting (IPTW) was used. 290 patients were included, including 97 (33%) who received short-course therapy (median of 9 days) and 193 (67%) who received prolonged-course therapy (median of 15 days). Approximately 10% of patients required an ICU stay and the most common source of infection was biliary, followed by primary BSI and pulmonary sources. Adequate source control was achieved in approximately 95% of patients in both treatment groups. There was no significant difference in the risk of recurrence or 30-day mortality (16% versus 11%; IPTW-adjusted HR = 0.68, 95% CI = 0.34-1.36). Limitations included a high percentage of excluded patients (80%) and bias given the retrospective study design, some of which was mitigated by the propensity score analysis. Ultimately, this study found that short-course antimicrobial therapy may be as effective as prolonged-course therapy for uncomplicated P. aeruginosa BSI.

Heil and colleagues recently published expert consensus guidance on management of uncomplicated GN BSIs created using a modified Delphi panel. A group of 7 ID physicians and 6 pharmacists from across the US with expertise in ASP developed a definition of uncomplicated GN BSIs which included: a) confirmed source from urinary, intra-abdominal/biliary, pneumonia, skin and soft tissue or catheter-related BSI; b) effective source control; c) immunocompetent patients; and d) clinical improvement within 72 hours of effective therapy. Then, they identified consensus management principles for these uncomplicated GN BSIs including a) appropriate duration of 7 days of effective therapy; b) repeat blood cultures for clearance not generally required; c) criteria for safe transition to oral antibiotics with agents that have adequate PK/PD target attainment. These core principles provide useful expert consensus guidance for ASP programs seeking to optimize GN BSI management in their healthcare facilities.


Bae M, Jeong Y, Bae S, et al. Short versus prolonged courses of antimicrobial therapy for patients with uncomplicated Pseudomonas aeruginosa bloodstream infection: a retrospective study. J Antimicrob Chemother. 2021 Sep 30:dkab358. https://doi.org/10.1093/jac/dkab358

Heil EL, Bork JT, Abbo LM, et al. Optimizing the management of uncomplicated Gram negative bloodstream infections: consensus guidance using a modified Delphi process. Open Forum Infectious Diseases, Volume 8, Issue 10, October 2021, ofab434. https://doi.org/10.1093/ofid/ofab434

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