Table 2.
Primary and secondary endpoints in the intention-to-treat and per-protocol populations
| Intention-to-treat population | Cloxacillin plus fosfomycin (n = 104) | Cloxacillin alone (n = 110) | Risk difference % (95% CI) | P value* |
|---|---|---|---|---|
| Primary endpoint | ||||
| Treatment success at day 7 | 83 (79.8%) | 82 (74.5%) | 5.3 (−5.95–16.48) | 0.360 |
| Secondary endpoints | ||||
| All-cause mortality at day 7 | 4 (3.8%) | 1 (0.9%) | 2.9 (−2.1–7.97) | 0.333 |
| All-cause mortality at end of therapya | 10 (9.6%) | 14 (12.7%) | −3.1 (−11.53–5.31) | 0.453 |
| All-cause mortality at TOCb | 10 (9.6%) | 17 (15.5%) | −5.9 (−14.66–2.98) | 0.196 |
| Persistent bacteremia at day 3c | 4/95 (4.2%) | 18/102 (17.6%) | −13.4 (−22.88–−3.99) | 0.006 |
| Persistent bacteremia at day 7d | 2/90 (2.2%) | 4/97 (4.1%) | −1.9 (−7.97–4.16) | 0.748 |
| Microbiological treatment failure at 14 dayse | 0 (%) | 0 (%) | – | – |
| Relapsing bacteremia at TOCf | 0/93 (0%) | 1/102 (1%) | −0.9 (−3.87–1.91) | 1 |
| Complicated bacteremia at TOCg | 21/95 (22.1%) | 35/105 (33.3%) | −11.2 (−23.51–1.06) | 0.077 |
| Emergence of fosfomycin-resistant strains at TOC | 0 (0%) | 0 (0%) | – | – |
| Length of intensive care unit stay, median (IQR), days | 8.0 (3.0–17.0) | 4.0 (3.25–8.50) | – | 0.355 |
| Duration of intravenous antibiotic treatment, median (IQR), days | 14.0 (11.0–22.0) | 15.5 (11.0–26.0) | – | 0.245 |
| Serious adverse events leading to discontinuation of therapyh | 11 (10.6%) | 9 (8.2%) | 2.40 (−5.43–10.22) | 0.547 |
| Per-protocol population | Cloxacillin plus fosfomycin (n = 101) | Cloxacillin alone (n = 106) | Risk difference % (95% CI) | P value* |
|---|---|---|---|---|
| Primary endpoint | ||||
| Treatment success at day 7 | 81 (80.2%) | 81 (76.4%) | 3.8 (−7.43–15) | 0.51 |
| Secondary endpoints | ||||
| All-cause mortality at day 7 | 2 (2%) | 0 (0%) | 2 (−1.7–5.66) | 0.145 |
| All-cause mortality at end of therapya | 10 (9.9%) | 11 (10.4%) | −0.5 (−8.7–7.75) | 0.91 |
| All-cause mortality at TOCb | 10 (9.9%) | 14 (13.2%) | −3.3 (−11.99–5.38) | 0.458 |
| Persistent bacteremia at day 3c | 4/94 (4.3%) | 17/99 (17.2%) | −12.9 (−22.43–−3.4) | 0.005 |
| Persistent bacteremia at day 7d | 2/88 (2.3%) | 4/95 (4.2%) | −1.9 (−8.13–4.26) | 0.684 |
| Microbiological treatment failure at 14 dayse | 0 (%) | 0 (%) | – | – |
| Relapsing bacteremia at TOCf | 0/91 (0%) | 1/99 (1%) | −1 (−3.99–1.97) | 1 |
| Complicated bacteremia at TOCg | 20/93 (21.5%) | 34/102 (33.3%) | −11.8 (−24.21–0.56) | 0.078 |
| Emergence of fosfomycin-resistant strains at TOC | 0 (0%) | 0 (0%) | – | – |
| Length of intensive care unit stay, median (IQR), days | 9.0 (4.75–15.8) | 4.0 (3.25–8.50) | – | 0.168 |
| Duration of intravenous antibiotic treatment, median (IQR), days | 14.0 (11.0–22.0) | 16.0 (11.0–26.0) | – | 0.181 |
| Serious adverse events leading to discontinuation of therapyh | 10 (9.9%) | 6 (5.7%) | 4.2 (−4.03–12.51) | 0.304 |
*The P values were obtained from a two-sided test for differences in proportions.
aEnd of therapy visit 48 h after the last dose of antibiotic treatment.
bTOC visit 12 weeks after randomization.
cAt least one positive blood culture for MSSA at day 3.
dAt least one positive blood culture for MSSA at day 7.
eDefined as a positive sterile site culture for MSSA at least 14 days after randomization.
fAt least one positive blood culture for MSSA at least 72 h after a preceding negative culture at TOC.
gDefined as persistent bacteremia, endocarditis, metastatic emboli or the presence of prosthetic devices at TOC.
hDuring the first 7 days after randomization.