Bloodstream Infections: When Can Oral Antibiotics

Why does the pandemic's resistance legacy matter for antibiotic treatment?

The CDC's COVID-19 and antimicrobial resistance overview describes a substantial setback: resistant infections beginning in hospitals and associated deaths each increased by at least 15% between 2019 and 2020 across seven pathogens. Staffing shortages, longer hospital stays and difficulties maintaining infection prevention contributed to the conditions in which resistant organisms could spread. These are historical surveillance findings, rather than measurements of infections occurring this October. [CDC overview](https://www.cdc.gov/antimicrobial-resistance/data-research/threats/covid-19.html)

A subsequent CDC analysis found that six categories of resistant bacterial infections beginning in hospitals increased by a combined 20% during the pandemic compared with the period before it. Their combined burden peaked in 2021 and remained elevated in 2022. These findings provide context for efforts to improve treatment, but they do not establish which antibiotic regimen is best for an individual patient. [CDC surveillance update](https://www.cdc.gov/antimicrobial-resistance/data-research/threats/update-2022.html)

What does the clinical trial show about switching to oral antibiotics?

The trial, published in Clinical Microbiology and Infection in 2024, evaluated switching after three to five days of effective intravenous antibiotics. Participants needed an organism susceptible to an oral option, at least 48 hours without fever or circulatory instability, and a controlled infection source. The main analysis included 165 adults. Pregnancy, heart-valve infection and neurological infection were excluded. [Randomized trial](https://doi.org/10.1016/j.cmi.2023.10.014)

Treatment failure within 90 days occurred in 21.7% of the oral group and 25.6% of the intravenous group. This composite outcome included death, additional antibiotic treatment, microbiological relapse or infection-related readmission. The study met its prespecified 10-percentage-point noninferiority margin; it did not demonstrate that oral treatment was superior. Its small size and selected population limit extrapolation to more complicated or highly resistant infections. [Trial results](https://doi.org/10.1016/j.cmi.2023.10.014)

A separate observational study in JAMA Network Open also estimated comparable 90-day mortality with early oral switching for uncomplicated Gram-negative bloodstream infections. Because clinicians selected treatments in routine care, remaining differences between patient groups could influence those findings. Together, these studies support considering an oral switch after appropriate assessment; they do not show that changing the route alone reduces antimicrobial resistance. [Observational study](https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2814214)

Which oral antibiotics can be considered for resistant bloodstream infections?

Extended-spectrum beta-lactamases, or ESBLs, are bacterial enzymes that disable many penicillins and cephalosporins. Some affected bacteria remain susceptible to trimethoprim-sulfamethoxazole, ciprofloxacin or levofloxacin. IDSA's July 2026 guidance supports considering these oral options when laboratory testing confirms activity, circulation is stable and intestinal absorption is reliable. Their ability to achieve adequate bloodstream concentrations matters. [IDSA treatment guidance](https://www.idsociety.org/practice-guideline/amr-guidance/)

A drug's usefulness for a bladder infection does not establish its suitability for a bloodstream infection. IDSA advises against oral nitrofurantoin or fosfomycin as follow-on treatment for ESBL bloodstream infections because adequate blood concentrations are a concern. The practical implication is that an oral switch requires a suitable drug and clinical assessment, rather than simply replacing an infusion with any available tablet. [IDSA recommendations](https://www.idsociety.org/practice-guideline/amr-guidance/)