Gram-negative infections: Gradual oral treatment is safe from the first days

Patients with a Gram-negative bacterial infection would benefit from switching from intravenous antibiotics to oral antibiotics from day four of infection. In addition to avoiding certain complications, the risk of mortality remains similar, according to the results of a study carried out by Danish researchers.A target trial emulation was carried out in four hospitals in Copenhagen. To be eligible, patients had to be hospitalized, aged 18 or older and a blood culture had to show the presence of Gram-negative bacteria. Treatment with IV antibiotics was initiated within 24 hours following blood culture. If patients were stable after four days, they were eligible for the clinical study. Of the 914 patients enrolled, 433 transitioned to oral treatment on day four, and 481 received extended intravenous treatment for a minimum of an additional 24 hours. About 10% of participants died during the study, with a significantly higher proportion in the group that received prolonged IV antibiotics. In the intention-to-treat analysis, the 90-day all-cause mortality risk was 9.1% (95% CI, 6.7%-11.6%) for the oral progressive treatment group and 11.7% (95% CI, 9.6%-13.8%) for the group that continued IV treatment.Read: What's working: How this made-in-Canada solution helps more than 400 hospitals worldwide improve prescribing for infections and reduce antibiotic resistanceHowever, the researchers point out that individuals who transitioned to oral therapy were generally younger, had fewer comorbidities and were more likely to have acquired the infection in the community. Their infections mainly came from the urinary tract. To obtain more representative estimates, they then carried out a per-protocol analysis excluding all patients who had deviated from the treatment plan (for example, if the total duration of antibiotic treatment was less than seven days or exceeded 14 days).This time, the 90-day all-cause mortality risk was virtually identical between the group that transferred to oral therapy and the group that continued IV therapy (9.6% vs. 9.7%). For exploratory purposes, a small group of 77 immunosuppressed individuals was divided into two groups (35 assigned to oral step-up therapy and 42 to IV therapy). Both treatment protocols generated results comparable to those of the group without immunosuppression.The researchers mention that there would be many benefits in finding the ideal timing and eligibility criteria for progressive oral treatment: “A rapid transition could reduce the length of hospital stay, reduce associated costs and improve the quality-of-life of the patient. In addition, transferring to oral therapy would mitigate the risks associated with IV catheters while facilitating the resumption of daily activities for the patient.” Read: Preventive use of amikacin can reduce cases of ventilator-acquired pneumonia

Gram-negative infections: Gradual oral treatment is safe from the first days

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