Table 3. Primary and Secondary Outcomes.
| Outcomes | No./Total No. (%) | Risk Difference, % (95% CI) | P Value | |
|---|---|---|---|---|
| Combination Therapy | Standard Therapy | |||
| Primary Outcomea,b | ||||
| Primary analysis population | 59/170 (35) | 68/175 (39) | −4.2 (−14.3 to 6.0) | .42 |
| Per protocol | 47/144 (33) | 68/175 (39) | −6.2 (−16.7 to 4.3) | .25 |
| Secondary Outcomesc | ||||
| All-cause mortalityd | ||||
| Day 14 | 13/170 (8) | 13/174 (7) | 0.2 (−5.4 to 5.8) | .95 |
| Day 42 | 25/170 (15) | 19/174 (11) | 3.8 (−3.3 to 10.8) | .29 |
| Day 90 | 35/170 (21) | 28/174 (16) | 4.5 (−3.7 to 12.7) | .28 |
| Persistent bacteremiae | ||||
| Day 2 | 50/167 (30) | 61/173 (35) | −5.3 (−15.3 to 4.6) | .29 |
| Day 5 | 19/166 (11) | 35/172 (20) | −8.9 (−16.6 to −1.2) | .02 |
| Microbiological relapsea | 14/169 (8) | 18/175 (10) | −2.0 (−8.1 to 4.1) | .52 |
| Microbiological treatment failurea | 16/170 (9) | 17/175 (10) | −0.3 (−6.5 to 5.9) | .92 |
| Acute kidney injuryf | 34/145 (23) | 9/145 (6) | 17.2 (9.3 to 25.2) | <.001 |
| Duration of intravenous antibiotics, mean (SD), d | 29.3 (19.5) | 28.1 (17.4) | .72 | |
The primary outcome was a composite of mortality at day 90, persistent bacteremia at day 5, microbiological relapse (a positive blood culture for methicillin-resistant Staphylococcus aureus [MRSA] at least 72 hours after a preceding negative culture), and microbiological treatment failure (a positive sterile-site culture for MRSA at least 14 days after randomization).
The primary analysis population consisted of all participants with data available for the primary end point, who were analyzed according to treatment randomization, regardless of treatment received. The per-protocol population was defined as (1) for the combination group, those who received at least 75% of study β-lactam doses; (2) for the standard treatment group, those who received no more than 1 defined daily dose of study β-lactam; and (3) for both groups, those with data available for the primary end point.
Results for secondary outcomes are reported for the primary analysis population. Results for secondary outcomes for the per-protocol population are found in eTables 1 and 3 in Supplement 3.
One patient did not have mortality data available but did meet the criteria for persistent bacteremia and so met the primary composite end point.
The median time from the date of first positive blood culture to study day 2 was 4 days and from date of first positive blood culture to study day 5 was 7 days.
Participants undergoing dialysis at randomization were excluded from the acute kidney injury (AKI) outcome. Acute kidney injury was defined as at least stage 1 modified RIFLE criteria (1.5-fold increase in serum creatinine) at any time within the first 7 days or new need for renal replacement at any time between day 1 and day 90. There were 5 participants in the combination therapy group and 11 in the standard therapy group who did not have baseline creatinine measurement data but could still qualify for AKI if they required renal replacement therapy. When these participants with missing baseline creatinine measurement data were excluded from the analysis, AKI occurred in 34 of 140 (24%) in the combination therapy group and 9 of 134 (7%) in the standard therapy group (risk difference, 18%; 95% CI, 9.3%-26%; P < .001).