Table 2.
Details of Study Arms, Outcomes, and Antibiotic Administration for Published Studies Describing Oral Antibiotic Therapy for S. aureus Bacteremia
| Author & Year | Study Arm | Study Arm Outcome | Standard Therapy Arm | Standard Therapy Outcome | Outcome Analysis | Days IV Before PO Switch |
|---|---|---|---|---|---|---|
| Linezolid | ||||||
| Stevens et al. [29] 2002 | Linezolid 600 mg IV twice daily → change to linezolid 600 mg PO twice daily at investigator discretion, at least 7 days | 9/15 (60.0%) of evaluable MRSA bacteremia achieved clinical cure | Vancomycin 1 g IV twice daily | 7/10 (70.0%) of evaluable MRSA bacteremia achieved clinical cure | — | Specific information about linezolid route of administration or duration was not given for SAB patients |
| Moise et al. [30] 2002 | Linezolid oral or IV 600 mg twice daily (adult); 10 mg/ kg oral or IV (pediatric or <40 kg) | 18/21 (85.7%) clinically evaluable bacteremic patients achieved clinical cure | — | — | — | 58/191 (30.4%) received IV and oral linezolid; days of each not given; 76/191 (39.8%) received oral linezolid |
| Birmingham et al. [31] 2003 | Linezolid oral or IV 600 mg twice daily (adult); 10 mg/ kg oral or IV (pediatric or <40 kg) | 16/31 evaluable; 12/16 (63.2%) achieved clinical cure; 10/14 (71.4%) microbiological cure | — | — | — | Specific information about linezolid route of administration or duration was not given for SAB patients |
| Wilcox et al. [32] 2004 | Linezolid (IV→PO) 600 mg twice daily | 13/15 (86.7%) SAB patients achieved clinical cure with linezolid | Teicoplanin (IV→IM) | 9/18 (50%) SAB patients achieved clinical cure with teicoplanin | — | Specific information about linezolid route of administration or duration was not given for SAB patients |
| Shorr et al. [33] 2005 | Linezolid IV or IV→PO 600 mg twice daily | 28/74 (36%) of ITT SAB achieved clinical cure; 14/25 (56%) of evaluable MRSA bacteremia achieved clinical cure; 41/59 (69%) achieved microbiological cure | Vancomycin 1 g IV twice daily | 25/70 (36%) of ITT SAB achieved clinical cure; 13/28 (46%) MRSA bacteremia achieved clinical cure; 41/56 (73%) achieved microbiological cure | Odds ratio for linezolid vs vancomycin clinical cure was 1.47 (95% CI, 0.50 to 2.65) | Specific information about linezolid route of administration or duration was not given for SAB patients |
| Wilcox et al. [34] 2009 | Linezolid 600 mg (route not specified) | 38/52 (75.0%) SAB and 22/25 (88.0%) MRSA bacteremia achieved clinical cure; 46/56 (82.1%) SAB; 21/26 (80.8%) MRSA bacteremia achieved microbiological cure | Vancomycin 1 g twice daily with option to change to oxacillin 2 g IV or dicloxacillin 500 mg oral every 6 hours for MSSA | 29/42(69.0%) SAB and 16/21 (76.2%) MRSA bacteremia achieved clinical cure; 35/42 (83.3%) SAB; 18/21 (85.7%) MRSA bacteremia achieved microbiological cure | 95% CI for SAB clinical cure was –12.3 to 24.2 for MRSA bacteremia, –10.4 to 34.0 for SAB, –16.3 to 13.9 for MRSA bacteremia, –26.2 to 16.4 for microbiological cure; P values for these analyses not provided | Specific information about linezolid route of administration or duration was not given for SAB patients |
| Usery et al. [35] 2015 | Linezolid 600 mg twice daily (IV or PO not specified) | 12/15 (80%) had complicated bacteremia; 9/15 (60%) achieved clinical cure; 14/14 linezolid (100%) achieved microbiological cure; 6/15 (40%) linezolid died | Vancomycin IV | 48/54 (88.9%) of vancomycin and 51/53 (96.2%) daptomycin patients had complicated bacteremia; 31/53 (58.5%) daptomycin and 33/54 (61.1%) vancomycin achieved clinical cure; 44/47 (93.56%) daptomycin and 45/50 (90%) vancomycin achieved microbiological cure; 10/53 (18.9%) daptomycin and 5/54 (9.3%) vancomycin died | P = .9624 for clinical cure; P = .6777 for microbiological cure; P = .0186 for mortality | — |
| Willekens et al. [36] 2018 | Linezolid IV→PO 600 mg twice daily | 1/45 (2.2%) 90-day relapse, 0/45 (0.0%) 14-day mortality, and 1/45 (2.2%) 30-day mortality | SPT included: cloxacillin, cefazolin, extended β-lactams, carbapenems, daptomycin, cefepime and teicoplanin for MSSA and daptomycin, vancomycin and linezolid IV for MRSA | Propensity score-matched cohort had 4/90 (4.4%) 90-day relapse; 6/90 (6.7%) 14-day mortality and 12/90 (13.3%) 30-day mortality | P values: .87 for 90-day relapse, .18 for 14-day mortality, .08 for 30-day mortality | IV to PO linezolid switch performed after 3–9 days of IV therapy |
| Fluoroquinolones | ||||||
| Bouza et al. [37] 1989 | Ciprofloxacin IV, IV→ PO or PO; for IV, doses ranged from 200 to 400 mg daily; for PO, doses ranged from 1000 to 1500 mg daily | 2/2 (100%) achieved clinical cure | — | — | — | Specific information about ciprofloxacin route of administration or duration was not given for SAB patients |
| Dworkin et al. [8] 1989 | Ciprofloxacin 300 mg IV + rifampicin 300 mg PO twice daily for 7 days changed to ciprofloxacin 750 mg PO + rifampicin 300 mg PO twice daily for 21 days | 5 patients were lost to follow-up without record of readmission; 5 patients readmitted with other infections or re-infection | — | — | 95% CI for clinical cure was 76%–100% | Mean duration of IV ciprofloxacin was 6–7 days, followed by mean duration of 21 days of oral ciprofloxacin |
| Heldman et al. [9] 1996 | Ciprofloxacin 750 mg PO + rifampin 300 mg PO twice daily | 18/19 (94.7%) achieved microbiological cure | Oxacillin 2 g IV every 4 hours or vancomycin 1 g IV twice daily + gentamicin IV for first 5 days | 22/25 (80.0%) achieved microbiological cure | Odds ratio for microbiological treatment failure (oral vs SPT) was 0.4 (95% CI, 0.01 to 5.5; P = .6) | Oral ciprofloxacin + rifampin began on admission |
| Schrenzel et al. [38] 2004 | Fleroxacin 400 mg PO daily + rifampicin 600 mg PO daily | 15/19 (79%) catheter-related SAB; 10/11 (91%) primary SAB achieved clinical cure; 15/19 (79%) catheter-related SAB and 10/10 (100%) primary SAB achieved microbiological cure | Flucloxacillin 2 g IV every 6 hours or vancomycin 1 g IV twice daily | 10/11 (91%) catheter-related SAB, 4/5 (80%) primary SAB achieved clinical cure; 9/10 (90%) catheter- related SAB and 5/5 (100%) primary SAB achieved microbiological cure | Relative risk was 0.8 (95% CI, 0.4 to 1.3; P = .81), 1.4 (95% CI, 0.3 to 5.9; P = .54), 0.8 (95% CI, 0.5 to 1.3; P = .63), and undefined (P = .33) | Fleroxacin + rifampicin oral therapy was started on admission or after up to 24 hours of IV fleroxacin + rifampin therapy |
| Beganovic et al. [39] 2019 | Levofloxacin or moxifloxacin (administration route and dose unknown) | Of 32 patients for whom patient characteristics were balanced, there was no difference in time to mortality | Nafcillin, oxacillin, or cefazolin IV (dose unknown) | Of 32 patients for which patient characteristics were balanced, there was no difference in time to mortality | Hazard ratio of 1.33, with 95% CI of 0.30 to 5.96 | Specific information about levofloxacin or moxifloxacin route of administration or duration was not given |
| Trimethoprim/sulfamethoxazole | ||||||
| Markowitz et al. [40] 1992 | TMP-SMX 320 mg/1600 mg IV twice daily | Overall cure rate for all infections was 37/43 (86.0%); no subanalyses of bacteremia | Vancomycin 1 g IV twice daily | Overall cure rate for all infections was 57/58 (98.3%), no subanalyses of bacteremia | All infection P = .014 | Oral therapy was not evaluated in this study |
| Goldberg et al. [41] 2010 | TMP-SMX oral or IV, dose not given | 13/38 (34.2%) 30-day mortality; 3/38 (7.9%) relapse or persistent bacteremia | Vancomycin IV, dose not given | 31/76 (40.8%) 30-day mortality; 13/67 (11.8%) relapse or persistent bacteremia | Odds ratio of 30-day mortality TMP-SMX vs vancomycin was 0.76 (95% CI, 0.34 to 1.7) and for relapse or persistent bacteremia 0.42 (95% CI, 0.11 to 1.56) | No specific information given about duration or route of TMP-SMX administration |
| Paul et al. [42] 2015 | TMP-SMX 320 mg/1600 mg IV with potential to change to PO at physician discretion | Failed to meet noninferiority standards for all infections; demonstrated a trend toward higher all-cause 30-day mortality in the ITT bacteremia patients 14/41 (34%) | Vancomycin 1 g IV twice daily | 9/50 (18%) 30-day all-cause mortality | Multivariate adjusted 7-day treatment failure for all infections was 2.00 (95% CI, 1.09 to 3.65); odds ratio for bacteremia- specific 30-day all-cause mortality in the ITT analysis was 1.90 (95% CI, 0.92 to 3.93) | No specific information given about duration or route of TMP-SMX administration |
| Harbarth et al. [43] 2015 | TMP-SMX (IV→PO) 160 mg/800 mg 3 times daily + rifampin IV or PO 600 mg daily | 6/9 (66.7%) clinical cure in ITT bacteremia patients | Linezolid (IV→PO) 600 mg | 7/9 (77.8%) clinical cure in ITT bacteremia patients | Risk difference of 11.1 (95% CI, –31.2 to 50.0) for bacteremia | For all infections, TMP- SMX IV therapy was given in 18 (24.0%) patients for a median of 6 days before oral switch; linezolid was given IV in 11 (14.7%) patients for a median of 1 day before oral switch |
| Tissot-Dupont et al. [44] 2019 | TMP-SMX 960 mg/4800 mg IV every 4 hours + clindamycin 1800 mg IV 3 times daily for 7 days → TMP-SMX 160 mg/800 mg PO (6 tablets per day) | 7/171 (4.1%) had relapse; 6/171 (3.5%) had recurrence | Oxacillin 12 g IV daily for MSSA or vancomycin 30 mg/kg/ d IV for MRSA | 10/170 (5.9%) had relapse; 12/170 (7.06%) had recurrence | P = .046 for relapse and P = .15 for recurrence | Defined in intervention, patients received 7 days of IV TMP- SMX + clindamycin before oral switch to TMP-SMX PO; there were significant caveats with the design of this studya |
| Clindamycin | ||||||
| Martinez-Aguilar et al. [45] 2003 | Clindamycin 40 mg/kg/d IV or PO | 20/46 (43.5%) MRSA and 18/52 (34.6%) MSSA invasive infections were treated with clindamycin only (39/46 patients with MRSA invasive infection and 24/52 patients with MSSA received clindamycin as their final antibiotic) | Nafcillin, vancomycin, other β-lactam | 18/46 (39.1%) with MRSA and 15/52 (28.8%) with MSSA invasive infections were treated with vancomycin IV, of whom 6/18 (33.3%) with MRSA and 0/52 (0%) with MSSA completed therapy with vancomycin IV | — | Although oral clindamycin was given as a therapeutic choice, the authors note that most received predominantly IV clindamycin; specific numbers not given |
| Other | ||||||
| Carney et al. [14] 1982 | 21/45 (46.7%) treated with dicloxacillin, cephalexin, or erythromycin | 0/21 (0%) died from S. aureus; only 1/21 (4.8%) (received erythromycin) had SAB relapse | Multiple IV therapy regimens | 6/17 (35%) died from S. aureus | — | 2–16 days of IV therapy were given before oral switch |
| Thwaites et al. [15] 2010 | UK SAB patients | 25% of included UK patients received oral antibiotic exclusively for >50% of their treatment duration | Vietnam/Nepal SAB patients | 4% of included patients received oral antibiotics exclusively for >50% of their treatment duration | — | 98% of patients were given IV antibiotic for some or all of their treatment; 14/630 (2.2%) received oral antibiotics only, of whom all had MSSA and 11/14 (78.6%) received flucloxacillin |
| Jorgensen et al. [13] 2019 | Oral linezolid, TMP-SMX, clindamycin, or doxycycline +/- adjuvant rifampin | 5/70 (7.1%) had 90-day clinical failure; overall, 35/70 (50.0%) received linezolid, 24/70 (34.3%) TMP-SMX, 11/70 (15.7%) clindamycin, 2/70 (2.9%) doxycycline, and 2/70 (2.9%) adjuvant rifampin | OPAT with IV daptomycin, vancomycin, or ceftaroline | 63/422 (14.9%) had 90-day clinical failure; overall, 194/422 (46.0%) received vancomycin, 194/422 (46.0%) daptomycin, 50/422 (11.8%) ceftaroline, and 16/422 (3.8%) adjuvant rifampicin | The adjusted hazard ratio for 90-day clinical failure with OPAT as the reference was 0.379 (95% CI, 0.131 to 1.101; P = .0747) | The median duration of inpatient IV therapy was 8 days in the outpatient oral antibiotic group and 10 days in the OPAT group |
| Iversen et al. [12] 2019 | Oral regimens for the 87 S. aureus patients were based on penicillin and methicillin sensitivity; there were 13 combinations, of which the 3 most common were 15/45 (33%) dicloxacillin + rifampicin, 13/45 (29%) amoxicillin + rifampicin, and 3/45 (7%) moxifloxacin + rifampicin | 3/47 (6.4%) had a primary outcome | IV antibiotics chosen based on European Society of Cardiology guidelines | 3/40 (7.5%) had a primary outcome | Odds ratio was 0.84 (95% CI, 0.15 to 4.78; P = .94) for evaluation of all bacterial sources | Per protocol, 10 or more days and at least 7 days of IV treatment after valve surgery were given before transition to oral antibiotics |
Abbreviations: CI, confidence interval; ITT, intention-to-treat; IM, intramuscular; IV, intravenous; MRSA, methicillin-resistant S. aureus; MSSA, methicillin-sensitive S. aureus; OPAT, outpatient parenteral antibiotic therapy; PO, per os (oral); SAB, Staphylococcus aureus bacteremia; SPT, standard parenteral therapy; TMP-SMX, trimethoprim-sulfamethoxazole.
aThe TMP-SMX + clindamycin group had significantly lower rates of fever, heart murmur, mycotic aneurysm, and vegetations at baseline; only 40% of the TMP-SMX/clindamycin group received the protocol drugs from the start of treatment, and 19% had their protocol treatment interrupted.