Table 1. Baseline Characteristics of Patients in the Primary Analysis Population.
| Characteristics | Combination Therapy (n = 174) | Standard Therapy (n = 178) |
|---|---|---|
| Age, median (IQR), y | 65 (51-76) | 63 (47-79) |
| Sex, No. (%) | ||
| Male | 121 (70) | 110 (62) |
| Female | 53 (30) | 68 (38) |
| Maintenance dialysis before study enrollment, No. (%) | 25 (14) | 30 (17) |
| Country, No. (%) | ||
| Australia/New Zealand | 124 (71) | 128 (72) |
| Singapore | 28 (16) | 28 (16) |
| Israel | 22 (13) | 22 (12) |
| Acquisition, No. (%)a | ||
| Nosocomial acquisition | 56 (32) | 48 (27) |
| Health care–associated infection | 105 (60) | 120 (67) |
| Time from index blood culture to randomization, median (IQR), d | 2 (1-2) | 2 (1-2) |
| Charlson Comorbidity Index, median (IQR)b | 5 (2-7) | 5 (2-7) |
| Pitt bacteremia score, median (IQR)c | 2 (2-3) | 2 (2-3) |
| SOFA score, median (IQR)d | 2 (1-4) | 1 (0-4) |
| Indwelling vascular device, No. (%)e | 95 (55) | 97 (54) |
| Indwelling prosthetic valve or cardiac device, No. (%) | 20 (11) | 14 (8) |
| Other intravascular foreign material, No. (%)f | 7 (4) | 5 (3) |
| Injecting drug use in the last 30 d, No. (%) | 14 (8) | 16 (9) |
| Recognized infection foci at time of index blood culture, No. (%) | ||
| Skin and soft tissue infection | 40 (23) | 50 (28) |
| Primary blood stream infection | 34 (20) | 35 (20) |
| Native osteoarticular | 31 (18) | 27 (15) |
| Intravenous line related | 25 (14) | 22 (12) |
| Pleuropulmonary infection | 13 (7) | 11 (6) |
| Device related | 9 (5) | 9 (5) |
| Infective endocarditis | 9 (5) | 6 (3) |
| Other | 13 (7) | 18 (10) |
| Any antibiotic in 72 h preceding randomization, No. (%) | 170 (98) | 174 (98) |
| Any β-lactam in 72 h preceding randomization, No. (%) | 111 (64) | 104 (58) |
| Drugs affecting kidney function in 48 h preceding randomization, No. (%)g | 98 (56) | 108 (61) |
| Baseline creatinine level, median (IQR), mg/dLh | 1.13 (0.8-2.5) | 1.22 (0.8-2.7) |
| Baseline C-reactive protein level, median (IQR), mg/L | 174 (92-269) | 161 (77-248) |
| Multilocus ST, No./total (%)i | ||
| ST22 | 33/160 (21) | 34/161 (21) |
| ST93 | 23/160 (14) | 28/161 (17) |
| ST45 | 21/160 (13) | 26/161 (16) |
| ST5 | 24/160 (15) | 15/161 (9) |
| ST239 | 7/160 (4) | 10/161 (6) |
| ST1 | 7/160 (4) | 9/161 (6) |
| ST30 | 5/160 (3) | 8/161 (5) |
| Otherj | 40/160 (25) | 31/161 (19) |
| Vancomycin MIC, No./total (%)i,k | ||
| ≤1 μg/mL | 152/160 (95) | 153/161 (95) |
| 2 μg/mL | 8/160 (5) | 8/161 (5) |
Abbreviations: IQR, interquartile range; ST, sequence type.
Nosocomial acquisition was indicated if patients were inpatients for more than 48 hours at the time of index blood culture collection. A health care–associated infection was indicated if patients had any of the following: outpatient parenteral antibiotic therapy service in the past 30 days, more than 48 hours in the hospital in the past 90 days, outpatient chemotherapy in the past 30 days, or living in a residential care facility.
The Charlson Comorbidity Index provides a 10-year mortality risk based on weighted comorbid conditions, ranging from 0 (no comorbid conditions) to 29, with a score of 4 associated with an estimated 10-year survival of 53%.15
The Pitt bacteremia score provides a measure of in-hospital mortality risk in patients with bloodstream infections based on clinical variables, ranging from 0 to 14, with a Pitt score of 4 or greater associated with a risk of mortality of approximately 40%.16
The Sequential Organ Failure Assessment (SOFA) score provides a mortality prediction score based on the degree of dysfunction of 6 organ systems, ranging from 0 to 24, with a SOFA score of 6 to 7 associated with a risk of mortality of approximately 20%.17 The SOFA score was based on the worst recorded parameters in the 24 hours preceding randomization.
Indwelling vascular devices included peripheral intravenous cannulas, hemodialysis synthetic arteriovenous grafts, vascaths, peripherally inserted central catheters, central venous catheters, tunneled lines, portacaths, and arterial lines. The presence of any of these was noted without making a judgment as to whether methicillin-resistant Staphylococcus aureus bacteremia was attributable to the vascular device.
Data collected indicated the presence of “other intravascular foreign material” without further information (it was a tick-box only, without a further text field).
Drugs affecting kidney function included radiocontrast dye, amphotericin B, loop diuretics, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, nonsteroidal anti-inflammatory drugs, aminoglycosides, and calcineurin inhibitors.
To convert creatinine to μmol/L, multiply by 88.4. Baseline creatinine was defined as the highest creatinine measurement in the 24 hours preceding randomization.
There were 321 isolates recovered for in silico genotyping by whole genome sequencing and determination of vancomycin minimum inhibitory concentration (MIC) by broth microdilution.
Three of these had genotypes consistent with Staphylococcus argenteus, which is recommended to be clinically managed as for S aureus.
Vancomycin MIC was tested by broth microdilution that uses a vancomycin range of 1 to 128 μg/mL (in 2-fold increments). No isolates had an MIC greater than 2 μg/mL.