Table 1.
General features of nine Food and Drug Administration (FDA)- or European Medicines Agency (EMA)- approved antibiotic drugs with Gram-positive activity discussed in this paper.
| Cephalosporins | Lipopeptides | Lipoglycopeptides | Oxazolidinones | Fluoroquinolones | Tetracyclines | ||||
|---|---|---|---|---|---|---|---|---|---|
| Ceftaroline | Daptomycin | Telavancin | Dalbavancin | Oritavancin | Linezolid | Tedizolid | Delafloxacin | Omadacycline | |
| In vitro activity | MSSA, MRSA, CoNS, streptococci, some Enterococcus faecalis isolates | MSSA, MRSA, CoNS, streptococci, enterococci including VRE vanA, vanB | MSSA, MRSA, CoNS, streptococci, enterococci including VRE vanB | MSSA, MRSA, CoNS, streptococci, enterococci including VRE vanB | MSSA, MRSA, CoNS, streptococci, enterococci including VRE vanA, vanB | MSSA, MRSA, CoNS, streptococci, enterococci including VRE vanA, vanB | MSSA, MRSA, CoNS, streptococci, enterococci including VRE vanA, vanB | MSSA, MRSA, CoNS, streptococci, E. faecalis | MSSA, MRSA, CoNS, streptococci, enterococci including VRE vanA, vanB |
| No activity | Enterococcus faecium, VRE vanA, vanB | VRE vanA | VRE vanA | E. faecium, VRE vanA, vanB | |||||
| Drug target | Cell wall synthesis | Cell wall synthesis | Cell wall synthesis | Cell wall synthesis | Cell wall synthesis | Protein synthesis | Protein synthesis | DNA replication | Protein synthesis |
| FDA/EMA approved dosing regimen (for ABSSSI, unless otherwise mentioned) | 600 mg b.i.d. IV | ABSSSI 4 mg/kg/day IVBSI/IE 6 mg/kg/day IV |
10 mg/kg/day IV | 1500 mg IV single doseAlternative: 1000 mg IV single dose at day 1, followed by 500 mg IV single dose at day 8 | 1200 mg IV single dose | 600 mg b.i.d. IV / PO | 200 mg q.d. IV / PO | 300 mg b.i.d. IV OR450 mg b.i.d. PO | Loading dose: - IV: 200 mg q.d. on day 1 OR 100 mg b.i.d on day 1- PO (for ABSSSI only): 450 mg q.d. on day 1 and 2. Maintenance: - IV: 100 mg q.d. OR- PO: 300 mg q.d. |
| Recommended dosing regimen for IE and OSM/PJI | 600 mg b.i.d. - t.i.d. IV (15-18) | 6-12 mg/kg/day IV (34, 37, 46) | No data | No data | No data | No data | No data | No data | No data |
| Dose adjustments | Creatinine clearance: - 30-50 mL/min: 400 mg b.i.d. IV; - 15-30 mL/min 300 mg b.i.d.; - ESRD/HD: 200 mg b.i.d. |
Creatinine clearance <30 mL/min, HD, CAPD: 6 mg/kg IV every 48 h |
Creatinine clearance:- 30-50 mL/min 7.5 mg/kg/day - < 30 mL/min 10 mg/kg every 48 h | Creatinine clearance < 30 mL/min: 750 mg IV single dose at day 1, followed by 375 mg IV at day 8 |
Not recommended in mild or moderate impairment, pharmacokinetics in patients with severe renal impairment has not been evaluated | None | None | Creatinine clearance 15-29 mL/min: 200 mg b.i.d. IV. No dose adjustment PO. |
None |
| Points of interest | Only approved cephalosporin active against MRSA | Not indicated for pneumoniaMonitor CPK and renal function once weekly | Renal dysfunction observed more often compared with vancomycin | Single dose therapy | Single dose therapy | Oral formulation available with 100% oral bioavailabilityRisk of myelosuppression after prolonged use >14 days, monitoring recommended | Oral formulation available with 91% oral bioavailability | Oral formulation available with 58.8% oral bioavailability | Oral formulation availableAdequate oral bioavailability only in fasted state (≥4 h before and 2 h after dose) |
| FDA approval (year, brand name, and indications) | 2010, Teflaro®, ABSSSI, CAP |
2003, Cubicin®, ABSSSI, right-sided infective endocarditis SA, bacteremia SA | 2009, Vibativ®, ABSSSI, HAP, VAP | 2014, Xydalba®, ABSSSI | 2014, Orbactiv®, ABSSSI | 2000, Zyvox®, - ABSSSI (including diabetic foot infection, without osteomyelitis) caused by MSSA, MRSA, Streptococcus pyogenes, Streptococcus agalactiae= HAP caused by MSSA, MRSA, Streptococcus pneumoniae- CAP caused by S. pneumoniae (incl. BSI), MSSA- VRE infections incl. BSI | 2014, Sivextro®, ABSSSI | 2017 and 2019, Baxdela® ABSSSI (2017), CAP (2019) |
2018, Nuzyra®, ABSSSI, CAP |
| EMA approval (year, brand name, and indications) |
2012, Zinforo®, ABSSSI, CAP | 2006, Cubicin®, ABSSI, right-sided infective endocarditis SA, bacteremia SA | Not EMA approved | 2015, Xydalba®, ABSSSI | 2015, Orbactiv®, ABSSSI | 2001, Zyvox®, ABSSSI, HAP, CAP | 2015, Sivextro®, ABSSSI | 2019, Quofenix®, ABSSSI | Not EMA approved |
Abbreviations: MSSA, methicillin-sensitive Staphylococcus aureus; MRSA, methicillin-resistant S. aureus; CoNS, coagulase-negative staphylococci; VRE, vancomycin-resistant E. faecium; ABSSSI, acute bacterial skin and skin structure infections; BSI, bloodstream infections; IE, infective endocarditis; CAP, community-acquired pneumonia; HAP, hospital-acquired pneumonia; VAP, ventilator-assisted pneumonia. IV, intravenous; PO, per os; OSM; osteomyelitis; PJI, prosthetic joint infection; q.d., quaque die/once daily; b.i.d., bis in die/twice daily; t.i.d., ter in die/three times daily; CAPD, continuous ambulatory peritoneal dialysis; ESRD, end-stage renal disease; HD, hemodialysis; CPK, creatinine phosphokinase; FDA, Food and Drug Administration; EMA, European Medicines Agency; SA, S. aureus.