Table 1.
Published Studies Describing Oral Antibiotic Therapy for S. aureus Bacteremia
| Author | Year | Study Type | Samplea | Study Question |
|---|---|---|---|---|
| Linezolid | ||||
| Stevens et al. [29] | 2002 | Randomized, open-label trial | 460 ITT patients, 242 with culture- confirmed S. aureus infections; 43 had confirmed MRSA bacteremia | Linezolid (IV→PO) vs IV vancomycin for MRSA; assessed clinical cure for those presenting for follow-up |
| Moise et al. [30] | 2002 | Open-label, nonrandomized, noncomparative study | 191 S. aureus infections in 183 adult and pediatric patients; 40 SAB episodes, 24 with MRSA episodes, 21 of which were evaluable | Compassionate use of linezolid (PO or IV) for vancomycin failure or intolerance in MRSA infections |
| Birmingham et al. [31] | 2003 | Open-label, nonrandomized, noncomparative study | 828 gram-positive infections in 796 adult or pediatric patients; 31 MRSA bacteremia | Compassionate use of linezolid (IV or PO) for gram-positive infections |
| Wilcox et al. [32] | 2004 | RCT | 430 adult (>13 years old) patients with gram-positive infections, 33 with SAB | Linezolid (IV or IV→PO) vs teicoplanin (IV→IM) for gram-positive infections |
| Shorr et al. [33] | 2005 | Pooled analysis of RCTsb | 5 RCTs, 3228 patients total, evaluating the use of linezolid (IV or IV→PO) vs vancomycin IV in 144 patients with primary or secondary SAB; 64 MRSA and 80 MSSA | Linezolid (IV or IV→PO) vs vancomycin IV for primary or secondary SAB |
| Wilcox et al. [34] | 2009 | Open-label, randomized noninferiority trial | 726 adults (>13 years old) ITT patients with suspected catheter-related infection, 526 with gram-positive infections, 157 with S. aureus, 145 with SAB | Evaluated linezolid (IV or PO) vs IV vancomycin for catheter-related SAB; no difference in microbiological cure |
| Usery et al. [35] | 2015 | Retrospective cohort | 122 SAB cases due to MRSA treated with linezolid, vancomycin, or daptomycin | Evaluated linezolid vs daptomycin vs vancomycin in MRSA bacteremia |
| Willekens et al. [36] | 2018 | Prospective matched cohort | 135 adult patients with SAB; 45 oral linezolid vs 90 SPT cases | Evaluated outcomes of linezolid (IV→PO) vs SPT propensity score–matched cohort for treatment of SAB |
| Fluoroquinolones | ||||
| Bouza et al. [37] | 1989 | Open-label noncomparative trial | 68 adult patients with bacteremia, 2 with SAB | Evaluated clinical cure for 2/2 (100%) patients with SAB who received ciprofloxacin |
| Dworkin et al. [8] | 1989 | Open-label noncomparative trial | 14 adult PWID complicated by S. aureus right-sided endocarditis with ciprofloxacin IV→PO + rifampicin PO | Evaluated 10 patients who were not withdrawn |
| Heldman et al. [9] | 1996 | Open-label randomized trial | 573 PWID, 93 sustained staphylococcal bacteremia concerning for right-sided endocarditis, 87 SAB; 5 of which were MRSA | Evaluated oral ciprofloxacin + rifampin vs IV oxacillin or vancomycin + gentamicin for clinically evaluable right-sided staphylococcal endocarditis patients vs patients who were microbiologically cured at 6–7 days post-treatment |
| Schrenzel et al. [38] | 2004 | RCT | 127 ITT adult patients with staphylococcal infection, 119 evaluable for clinical cure, 104 S. aureus infections, 98 were evaluable | Evaluated oral fleroxacin + rifampicin vs IV flucloxacillin or vancomycin for SAB; no difference in clinical cure between 44/56 (78.6%) fleroxacin + rifampicin patients vs 32/42 (76.2%) IV therapy patients |
| Beganovic et al. [39] | 2019 | Retrospective cohort | 428 cases of SAB due to MSSA; 103 (24.1%) received levofloxacin or moxifloxacin (IV or PO); 212 (49.5%) received IV oxacillin, cefazolin, or nafcillin | Evaluated MSSA bacteremia treatment in propensity-matched cohort of veterans treated with a single antibiotic |
| Trimethoprim/sulfamethoxazole | ||||
| Markowitz et al. [40]c | 1992 | RCT | 228 adult PWID with suspected S. aureus infections were randomized; 101 were evaluable; 67 had SAB, primary or secondary, and 11 had right-sided endocarditis | Evaluated TMP-SMX IV vs vancomycin IV for SAB |
| Goldberg et al. [41] | 2010 | Retrospective cohort | 1005 cases of SAB in 954 adult patients, 451 patients with MRSA | Evaluated oral or IV TMP-SMX vs IV vancomycin for MRSA bacteremia in a matched 1:2 ratio |
| Paul et al. [42] | 2015 | RCT | 252 patients with severe MRSA infections randomized, 91 patients with SAB | Evaluated oral TMP-SMX vs IV vancomycin for MRSA severe infections; excluded those with left-sided endocarditis or who had received study drugs previously |
| Harbarth et al. [43] | 2015 | Randomized, open-label noninferiority trial | 150 adult patients with MRSA infection randomized, 18 with MRSA SAB | Evaluated IV to oral switch linezolid vs IV to oral switch TMP-SMX + rifampin for MRSA infections; successful cure in 6/9 (66.7%) linezolid vs 7/9 (77.8%) TMP-SMX + rifampin patients |
| Tissot-Dupont et al. [44] | 2019 | Before/after intervention study | 341 patients with S. aureus endocarditis; 170 pre-intervention control patients and 171 postintervention patients | Compared 2 protocols for the treatment of S. aureus endocarditis |
| Clindamycin | ||||
| Martinez- Aguilar et al [45]. | 2003 | Retrospective cohort | 99 pediatric patients with invasive S. aureus infections, all of whom survived; 9 with SAB; 25 additional had secondary SAB and were not included in bacteremia analysis and not identified separately | Evaluated treatment of MRSA and MSSA invasive infection with clindamycin (IV or PO), IV nafcillin, IV vancomycin, other β-lactams, and TMP-SMX (only 1 case) |
| Other | ||||
| Carney et al. [14] | 1982 | Retrospective cohort | 45 episodes of SAB in 34 adult patients with cancer | Described the outcomes of oral step-down therapy in 21/45 episodes of SAB |
| Thwaites et al. [15] | 2010 | Prospective cohort | 630 patients with SAB in the UK and Vietnam with 1 Nepal patient included | Described treatment of SAB in the UK and Nepal; documented that >50% of patients received partial oral antibiotic therapy and 14 patients received only oral antibiotics; no information regarding outcomes |
| Jorgensen et al. [13] | 2019 | Retrospective cohort | 492 adult patients with MRSA SAB discharged with oral antibiotics only vs parenteral antibiotics | Evaluated the difference in 90-day clinical failure between patients who received oral step-down therapy compared with those who received OPAT for SAB |
| Iversen et al. [12] | 2019 | RCT | 400 adult patients with left-sided endocarditis, 87 with S. aureus as the causative pathogen | Evaluated patients with left-sided endocarditis due to Enterococcus faecalis, S. aureus, Streptococcus or coagulase-negative staphylococci comparing partial oral (after at least 10 days IV) vs total parenteral antibiotic therapy; primary outcomes were the difference in all-cause mortality, unplanned cardiac surgery, embolic events, or relapse of blood cultures |
Abbreviations: IM, intramuscular; ITT, intention-to-treat; IV, intravenous; MRSA, methicillin-resistant S. aureus; MSSA, methicillin-sensitive S. aureus; OPAT, outpatient parenteral antibiotic therapy; PO, per os (oral); RCT, randomized controlled trial; SAB, Staphylococcus aureus bacteremia; SPT, standard parenteral therapy; TMP-SMX, trimethoprim-sulfamethoxazole.
aDoes not include information regarding sex and age distribution as SAB patients were often a subgroup of a larger analysis and therefore the provided demographics are not reflective of the SAB cases.
bIncludes the 2002 Stevens et al. study reported above and 4 others not reported above due to explicit use of only IV linezolid or not well defined.
cIncluded because it was a landmark trial and curtailed further research evaluating oral TMP-SMX in the treatment of S. aureus bacteremia and/or endocarditis.