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November 3, 2021

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Can Short-Duration Antibiotic Therapy for Uncomplicated Gram-Negative Bloodstream Infection Be Safely Incorporated into Treatment Algorithms?

By A. Krishna Rao, MD, MS

Recent evidence has emerged that 7-day antimicrobial regimens for uncomplicated gram-negative bloodstream infection (uGNBSI) have similar efficacy and safety compared to 14-day regimens. Real-world effectiveness research is an important step in deploying insights from trials that demonstrate efficacy. In a study conducted at Johns Hopkins Hospital and published in Infection Control & Hospital Epidemiology, Bae et al. sought to determine if a treatment algorithm could identify candidate patients and safely reduce the duration of antimicrobial therapy for uGNBSI.

As part of a quasi-experimental study, the investigators implemented a treatment algorithm that identified patients with uGNBSI defined as meeting all of the following by day 5 of therapy: no current or expected neutropenia; no hematopoietic stem-cell transplantation in the previous 12 months; no ongoing therapy for graft-versus-host disease; no solid-organ transplant; adequate source control; no evidence of metastatic infection; no evidence or risk of endovascular infection (e.g., prosthetic valve or vascular graft); no ongoing fevers or need for fluid resuscitation or vasopressors; and no persistently positive blood cultures. If eligible, an infectious diseases pharmacist contacted the patient’s clinical team to recommend 7-day treatment. The primary outcome was total duration of antibiotic therapy, and secondary outcomes included duration of intravenous therapy and length of stay. The comparator group was patients with GNBSIs during the same period in the previous year. Patients in hospice or who died within 7 days of the initial culture were excluded, as were those with non-fermenting GNBSIs (e.g., Pseudomonas).

There were 142 and 203 patients included in the baseline and intervention periods, with 55 (39%) and 59 (29%) meeting criteria for 7-day therapy, respectively. There were no notable differences in age, Pitt bacteremia score, or intensive care unit status. There were slightly more biliary and fewer catheter-associated infections during the intervention period. The most common organisms in both periods were E. coli and Klebsiella species, and multidrug resistance was noted in < 15% of cases. Both total median duration (8 vs. 10 days; P = .04) and intravenous antibiotic duration (4 vs. 7 days; P = .004) were shorter during the interventional period, as was length of stay (4 vs. 7 days; P = .029). There were no differences in recurrence of GNBSI or mortality, though fewer than five patients developed these outcomes during both periods.

The investigators demonstrate how a treatment algorithm based on clinical trial data can be used in their hospital to identify patients eligible for safe reduction in therapy for uGNBSI. Limitations include the single-center design, use of historical controls, and small sample size resulting in low power for detecting an increase in adverse outcomes.  Additionally, the results cannot be generalized to patients with non-fermenting GNBSIs—the authors excluded such patients from the intervention because they were underrepresented in the original clinical trial data. Furthermore, for many providers moving to short courses for uGNBSIs is hardly a settled issue and would constitute a major shift in clinical practice. However, this research does support the position that deployment of shorter treatment durations for uGNBSI in real-world settings can be done safely and results in an overall reduction in antibiotic exposure and length of stay. Whether the findings of Bae et al. will be replicated in other centers remains to be seen, but their algorithm could serve as a template for deployment and assessment at other centers that seek to reduce antimicrobial exposure in the inpatient setting.

(Bae et al. Infect Control Hosp Epidemiol. 2021;42(9):1136-1138.)

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