PO Antibiotic Stepdown for Gram Negative Bacteremia

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Tamma PD, Conley AT, Cosgrove SE, et al. Association of 30-Day Mortality With Oral Step-Down vs Continued Intravenous Therapy in Patients Hospitalized With Enterobacteriaceae Bacteremia. JAMA Intern Med. 2019;179(3):316–323. doi:10.1001/jamainternmed.2018.6226

This is a multicenter retrospective cohort on patients with monomicrobial Enterobacteriacae blood stream infections (Citrobacter spp, Enterobacter spp, E.coli, Klebsiella spp, Proteus mirabilis, or Serratia marcecens) comparing the clinical outcomes of PO stepdown vs ongoing IV therapy. The “exposed” group were those who had their antibiotics switched to PO by day 5 (chosen given the evidence that 7d of antibiotics in uncomplicated cases may be sufficient). They excluded those who received PO from day 1 or transitioned after day 5. Of note, the IV group had to have met criteria for step down to PO at day 5, including source control within first 5 days, been able to take PO, able to use PO based on cultures, and Pitt bacteremia score <5. Exclusion criteria included >16 days of antibiotics as this may reflect uncontrolled sources. Primary outcome was 30d all cause mortality, 30d recurrent bloodstream infection, and duration of hospitalization.

Big table coming your way, but those who received IV therapy were more likely to be neutropenic, had received a SCT, had received combination therapy, had GI or line as the source, and had been in the ICU on day 1:

Of course, this makes sense. Sicker or higher risk = IV. They used one to one propensity matched cohort in their analysis. There was no difference in the number of deaths between either group (97 deaths, 13.1% in the PO step down vs 99 deaths, 13.4% in the IV group, HR 1.03; 95% CI 0.82-1.30. Kaplan-Meier curve:

They also note 6 episodes of recurrent bacteremia within 30d in the PO therapy group vs 4 in the IV therapy (HR 0.82; 95% CI 0.33-2.01) Notably, the IV therapy group had a longer hospitalization, median of 5 days in the PO group vs 7d in the IV group (HR 0.98; 95% CI 0.97-1, p-value <0.001). Most of the patients who received PO therapy had either a FQ or TMP-SMX, which were considered to be the “highly bioavailable” antibiotics:

I am not surprised there was no difference in outcomes here. There have been narrative reviews (Al-Hasan MN, Rac H, Transition from intravenous to oral antimicrobial therapy in patients with uncomplicated and

complicated bloodstream infections, Clinical Microbiology and Infection,) and some retrospective studies (https://doi.org/10.1016/j.ijantimicag.2017.12.007) as well as meta-analysis (DOI: 10.1093/ofid/ofz364) suggesting this is a fairly safe practice, provided there is source control. In general, bacteremia (outside of Staph and Candida) shouldn’t really alter the duration of therapy so long as you have a clear course (lack of source, that is another issue). A few days of IV and then finish off with PO (even beta lactams) in cases of uncomplicated bacteremia (i.e. no plastic or device left in) should be a fairly safe practice, that is supported by the literature.

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