National guidelines for pneumonia (PNA), urinary tract infection (UTI), and acute bacterial skin and skin structure infection (ABSSSI) do not address treatment duration for infections associated with bacteremia. We evaluated clinical outcomes of patients receiving shorter (5-9 days) versus longer (10-15 days) duration of antibiotics.
This was a multicenter retrospective cohort study of inpatients with uncomplicated PNA, UTI, or ABSSSI and associated bacteremia. The primary outcome was clinical failure, a composite of rehospitalization, reinitiation of antibiotics, or all-cause mortality within 30 days of antibiotic completion. Secondary outcomes included individual components of the primary outcome, Clostridioides difficile infection, and antibiotic-related adverse effects necessitating change in therapy. A propensity score-weighted logistic regression model was used to mitigate potential bias associated with nonrandom assignment of treatment duration.
Of 408 patients included, 123 received a shorter treatment duration (median 8 days) and 285 received a longer duration (median 13 days). In the propensity-weighted analysis, the probability of the primary outcome was 13.5% in the shorter group and 11.1% in the longer group (average treatment effect, 2.4%; odds ratio [OR], 1.25; 95% confidence interval [CI], .65-2.40; P = .505). However, shorter courses were associated with higher probability of restarting antibiotics (OR, 1.62; 95% CI, 1.01-2.61; P = .046) and C. difficile infection (OR, 4.01; 95% CI, 2.21-7.59; P < .0001).
Shorter courses of antibiotic treatment for PNA, UTI, and ABSSSI with bacteremia were not associated with increased overall risk of clinical failure; however, prospective studies are needed to further evaluate the effectiveness of shorter treatment durations.

BACKGROUND: Admissions for acute bacterial skin and skin structure infections (ABSSSI) are often prolonged because of intravenous (IV) antibiotics. Use of a long-acting IV antibiotic may reduce length of stay (LOS) on a hospitalist service. The ENHANCE ABSSSI trial sought to determine the impact on LOS and work productivity in patients treated with a long-acting IV antibiotic, dalbavancin, vs. usual care at an urban tertiary-care center.
METHODS: A single-center, pre- vs. post-period pragmatic trial at Weill-Cornell Medical Center assessed usual care for consecutively enrolled admitted ABSSSI patients during an observational period (pre-period). Identification and treatment of eligible admitted ABSSSI patients with dalbavancin were implemented in the post-period. Those with life-threatening infections, requiring multiple antibiotics/intensive care, or with unstable comorbidities were excluded. Outcomes were assessed over a 44-day follow-up period.
RESULTS: Of 48 and 43 patients enrolled, respectively, in the pre- and post-periods, mean infection-related LOS was reduced in the post-period (3.2 days vs. 4.8 days; P = 0.003). Similar results were found in an adjusted LOS analysis. Work productivity and activity impairment outcomes significantly improved in the post-period (P ≤ 0.01). Complete response rates were similar: 50% (pre-period) and 57% (post-period). Among AEs identified, 17% (n = 7) were found to have possible causal relation to dalbavancin in the post-period. Few AEs were serious (n = 3; 7% post-period versus n = 1; 2% pre-period).
CONCLUSIONS: After implementing the ENHANCE ABSSSI pathway, LOS was significantly reduced by almost 2 days, with potential improvements in work productivity and ability to complete daily activities.
BACKGROUND: ClinicalTrials.gov identifier, NCT03233438.
BACKGROUND: Allergan plc.

Tedizolid phosphate is approved for the treatment of acute bacterial skin and skin structure infection (ABSSSI) caused by Gram-positive bacteria in the United States, Europe, and other countries. In this multicenter, double-blind, phase 3 study, 598 adult ABSSSI patients in China, Taiwan, the Philippines, and the United States were randomized to receive 200 mg of tedizolid, intravenously (i.v.)/orally (p.o.), once daily for 6 days or 600 mg of linezolid, i.v./p.o. twice daily for 10 days. The primary endpoint was early clinical response rate at 48 to 72 h. Secondary endpoints included programmatic and investigator-assessed outcomes at end-of-therapy (EOT) and posttherapy evaluation (PTE) visits. Safety was also evaluated. In the intent-to-treat (ITT) population, 75.3% of tedizolid-treated patients and 79.9% of linezolid-treated patients were early responders (treatment difference, -4.6%; 95% confidence interval [CI], -11.2, 2.2). After exclusion of patients who never received the study drug (tedizolid, n = 8; linezolid, n = 1; modified ITT), comparable early response rates were observed (tedizolid, 77.4%; linezolid, 80.1%; treatment difference, -2.7%; 95% CI, -9.4, 3.9). Secondary endpoints showed high and similar clinical success rates in the ITT and clinically evaluable (CE) populations at EOT and PTE visits (e.g., CE-PTE for tedizolid, 90.4%; for linezolid, 93.5%). Both drugs were well tolerated, and no death occurred. Eight patients experienced phlebitis with tedizolid while none did with linezolid; hence, drug-related treatment-emergent adverse events were reported in a slightly higher proportion in the tedizolid (20.9%) arm than in the linezolid arm (15.8%). The study demonstrated that tedizolid in a primarily Asian population was an efficacious and well-tolerated treatment option for ABSSSI patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT02066402.).

BACKGROUND: Acute bacterial skin and skin structure infections (ABSSSIs) remain among the most common infectious processes seen in the clinical setting. For patients with complicated ABSSSIs deemed to require intravenous antibiotics, vancomycin remains the mainstay therapy. Ceftaroline has been shown to be non-inferior to vancomycin and may result in faster resolution of signs of infection.
METHODS: Multicenter, prospective, open-label, randomized trial of ceftaroline versus vancomycin for the treatment of adult patients admitted for management of ABSSSIs from April 2012 to May 2016; 166 patients in the clinically evaluable (CE) group were needed to determine a 20% difference in primary outcome of clinical response at day 2 or 3 of antibiotics. Clinical response was defined as cessation of spread of lesion and improvement in systemic signs/symptoms of infection. A secondary outcome was a ≥ 20% reduction in lesion size at day 2 or 3 of antibiotics.
RESULTS: One hundred seventy-four patients were enrolled in the intention-to-treat (ITT) group and 108 were CE. Among CE patients, 54 were randomized to ceftaroline and 54 to vancomycin. Baseline characteristics were similar except patients in the ceftaroline arm were older and had a non-significantly higher degree of comorbidities (median Charlson score 2 vs. 4, respectively). Cellulitis was the most common type of ABSSSI (85.2% vs. 79.6%, respectively). Rapid diagnostic testing of available cultures (n = 55) demonstrated high agreement with clinical microbiology for identification of Staphylococcus aureus (100%) and MRSA (100%). There was no significant difference in primary outcome of day 2 or 3 clinical response (50.0% vs. 51.9%).
CONCLUSIONS: Early clinical response between vancomycin- and ceftaroline-treated ABSSSIs was similar. Patients with ABSSSIs rarely remained hospitalized for > 2-3 days, thus limiting our ability to critically assess clinical outcomes.
BACKGROUND: ClinicalTrials.gov identifier, NCT02582203.
BACKGROUND: Allergan plc.