A study led by researchers from Johns Hopkins University School of Medicine suggests that patients with Enterobacteriaceae bloodstream infections who've shown clinical improvement can be transitioned from intravenous (IV) to oral antibiotic therapy without compromising patient outcomes. The findings appeared yesterday in JAMA Internal Medicine.
In the retrospective cohort study involving nearly 1,500 patients with Enterobacteriaceae bacteremia, the researchers found no difference in 30-day mortality or recurrence of bacteremia between patients who received oral step-down antibiotic therapy within the first 5 days of IV treatment and those who continued to receive IV antibiotics. In addition, the patients who were transitioned to oral therapy were able to leave the hospital 2 days sooner.
Comparable outcomes but shorter stays
The multicenter study included patients at three hospitals—the Johns Hopkins Hospital, the Hospital of the University of Pennsylvania, and the University of Maryland Medical Center—who were treated for monomicrobial Enterobacteriaceae bloodstream infections from 2008 through 2014. Study participants had at least one positive blood culture for Enterobacteriaceae commonly recovered from bloodstream infections, including Citrobacter species, Enterobacter species, Escherichia coli, Klebsiella species, Proteus mirabilis, or Serratia marcescens.
To be eligible for the study, patients had to have the source of the infection controlled within the first 5 days, appropriate clinical response by day 5, active antibiotic therapy from day 1 until discontinuation, availability of an in vitro active oral antibiotic agent, and ability to consume other oral medications by day 5. In addition, patients had to have a Pitt bacteremia score—a measure of severity of illness—of 1 or lower by day 5.
Patients who were transitioned to oral therapy were less likely to be severely ill at the onset of their infection and more likely to have complex underlying conditions.
Outcomes included 30-day all-cause mortality, 30-day recurrent bloodstream infection with the same organism, and duration of hospitalization from day 1 of bacteremia until hospital discharge.
Using propensity-score matching to account for patient differences, the researchers grouped 1,478 patients on a 1:1 basis into the study's two arms, with 739 patients in the oral step-down group and 739 in the IV group. Patients in the oral step-down group received a median of 3 days of IV therapy, while patients in the IV group received a median of 14 day of IV therapy.
Sources of bacteremia in the patients included urine (594 patients [40.2%]), gastrointestinal tract (297 [20.1%]), central line-associated (272 [18.4%]), pulmonary (58 [3.9%]), and skin and other soft-tissue infections (41 [2.8%]).
Analysis of the outcomes demonstrated 97 deaths (13.1%) in the oral step-down group within 30 days, compared with 99 (13.4%) in the IV group (hazard ratio [HR], 1.03; 95% confidence interval [CI], 0.82 to 1.30), and 6 episodes (0.8%) of recurrent bacteremia within 30 days in the oral therapy group versus 4 (0.5%) in the IV group (HR, 0.82; 95% CI, 0.33 to 2.01). The median time from day 1 of bacteremia to hospital discharge was 5 days in the oral step-down group versus 7 days in the IV group (HR, 0.98; 95% CI, 0.97-1.00; P < .001).
Benefits of oral therapy
Although the researchers did not evaluate why the patients who continued on IV therapy remained in the hospital for 2 days longer than those who transitioned to oral therapy, they suggest the extra days could reflect the reluctance of clinicians to send patients home with peripherally inserted central catheters, difficulties associated with arranging outpatient parenteral antibiotic therapy, and the challenges of placing patients in post-acute care facilities.
But that finding is in line with previous research, which has shown that transitioning patients to oral antibiotics can improve patient quality of life by reducing length of hospital stays and eliminating the discomfort associated with IV catheters. Oral therapy is also associated with decreased risk for catheter-associated adverse events and reduced healthcare costs.
The authors of the study conclude, "Until a clinical trial is performed, our findings suggest that oral step-down therapy is not associated with inferior clinical outcomes for patients with Enterobacteriaceae bacteremia who have received appropriate source control and demonstrated an appropriate clinical response compared with patients who continue to receive IV therapy for the duration of their treatment course."
Jan 22 JAMA Internal Med study