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March 20, 2019

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Journal Club

In this feature, a panel of IDSA members identifies and critiques important new studies in the current literature that have a significant impact on the practice of infectious diseases medicine.


Click here for the previous edition of Journal Club. For a review of other recent research in the infectious diseases literature, see “In the Literature,”  by Stanley Deresinski, MD, FIDSA, in each issue of Clinical Infectious Diseases.

Michael T. Melia, MD

Oral Step-Down Therapy for Enterobacteriaceae Bacteremia

Reviewed by Michael T. Melia, MD

Transitioning from intravenous (IV) to oral antibiotic therapy is a hot infectious diseases topic. While there are data supporting this practice for Gram-negative bacteremia of genitourinary (GU) tract origin, a recent analysis in JAMA Internal Medicine provides further evidence in support of this practice for bacteremia from more heterogeneous sources.

Investigators performed a retrospective cohort study of 2,161 patients with monomicrobial Enterobacteriaceae bacteremia at three academic medical centers. All patients received at least 1 day of IV therapy; patients in the exposed group (876, 40.5 percent) were transitioned to oral therapy by day 5. Additional eligibility criteria included adequate source control, an available oral antibiotic, expected clinical improvement by day 5, and a Pitt bacteremia score ≤ 1 by day 5. One-to-one propensity-score matching yielded 1,478 patients (739 in each arm). The main outcome measure was 30-day mortality.

Most bacteremia stemmed from the GU (594 patients, 40.2 percent) or gastrointestinal tract (297, 20.1 percent), or was central line-associated (272, 18.4 percent). All patients received at least 7 days of treatment (range 7-15), but patients in the exposed group received a median of 3 days (interquartile range [IQR], 2-4 days) of IV therapy versus 14 days (IQR, 11-15 days) in the IV group. In the propensity-matched cohort, there were 97 (13.1 percent) deaths in the oral step-down group and 99 (13.4 percent) in the IV group within 30 days (hazard ratio 1.03, 95 percent confidence interval, 0.82-1.30). Recurrent bacteremia was rare (10 episodes total) without differences in rates between the two groups. Patients transitioned to oral step-down therapy were discharged from the hospital a mean of 2 days earlier than patients who remained on IV therapy (5 days [IQR 3-8 days] vs 7 days [IQR 4-14 days]; P < 0.001).

These data suggest that oral step-down therapy is appropriate for some patients with Enterobacteriaceae bacteremia with adequate source control and an appropriate clinical response to initial IV antibiotic therapy. Importantly and not surprisingly, transitioning to oral therapy was associated with shorter length of hospital stay. Of particular interest to the ID clinician, there were no differences in 30-day mortality whether patients in the exposed group were transitioned to an oral β-lactam agent or trimethoprim-sulfamethoxazole or a fluoroquinolone, although the authors noted they had insufficient power to detect a difference if one existed. Another intriguing consideration is whether the duration of therapy for Gram-negative bacteremia is longer than needed.

(Tamma et al. JAMA Intern Med. 2019;179(3):316-323.)



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Daniel Mendoza, MD, PhDOral Antibiotics for Bone and Joint Infections

Reviewed by Daniel Mendoza, MD, PhD

The treatment of bone and joint infections includes prolonged courses of intravenous (IV) antibiotics. A recent study from the United Kingdom published in the New England Journal of Medicine investigated whether oral antibiotics were non-inferior to IV antibiotics for these infections.

The multicenter, open-label, randomized clinical trial enrolled individuals with bone or joint infections within 7 days after surgery or within 7 days after the start of antibiotic treatment if the infection was being managed without surgery. Participants were randomized to IV or oral antibiotics to complete the first 6 weeks of therapy. The primary endpoint was treatment failure within one year, defined as the presence of at least one clinical criterion (e.g., presence of pus adjacent to bone), microbiologic criterion (e.g., phenotypically indistinguishable bacteria isolated from deep-tissue samples), or histologic criterion (presence of inflammatory infiltrate or bacteria). Subjects with S. aureus bacteremia or bacterial endocarditis were excluded, while patients with vertebral osteomyelitis or prosthetic joint infections were not excluded.

The authors randomized 1,054 participants (527 in each group). S. aureus or coagulase-negative staphylococcus were identified in 64.8 percent of participants. The most commonly used antibiotics were glycopeptides (41.1 percent) and cephalosporins (33.2 percent) in the IV group and quinolones (36.5 percent) and combination therapy (16.6 percent) in the oral group. One hundred twenty participants (22.9 percent) in the IV group and 165 patients (31.4 percent) in the oral group received rifampin for at least 6 weeks.

The primary endpoint occurred in 14.6 percent of IV patients and in 13.2 percent of the oral group. The intention-to-treat analysis showed a difference in the risk of treatment failure of −1.4 percentage points (95 percent confidence interval [CI], −5.6 to 2.9), meeting non-inferiority. There were 10 and six deaths in the IV and oral groups, respectively. Serious adverse events occurred in 27.7 percent of IV patients and in 26.2 percent of oral participants (P = 0.58). Catheter complications were more common in the IV group (9.4 percent vs 1.0 percent, P < 0.001), and median hospital stay was also longer (14 days vs 11 days, P < 0.001).

In conclusion, oral antibiotic therapy was non-inferior to IV therapy when used during the first 6 weeks for bone and joint infections, as assessed by treatment failure at one year. Close follow up is needed with either therapy, as serious adverse events are common. Oral antibiotic therapy should be considered for bone and joint infections.

(Li et al. New Engl J Med. 2019;380:425-436.)

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For a review of other recent research in the infectious diseases literature, see “In the Literature,” by Stanley Deresinski, MD, FIDSA, in each issue of Clinical Infectious Diseases

April 1

  • Coxiella burnetii Infections—the Usual and the Unusual
  • Isavuconazole Minimum Inhibitory Concentration and Treatment of Invasive Aspergillosis
  • Case Vignette: Protothecosis in Transplant Recipients

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