Table 1.

Summary of novel antibiotics against Gram-positive bacteria approved by FDA and/or EMA during the last decade.

Drug	Approval Time	Antibiotic Class	Company	Spectrum Against Organisms	Indication	Dose 1	Comments/Warnings 2
Ceftaroline (Teflaro/Zinforo)	FDA: October 2010 EMA: August 2012	Cephalosporin	Allergan Pharmaceutical Industries Ltd. (US/Canada); Takeda Pharmaceutical Company Ltd. (Japan); Pfizer (globally except US/Canada/Japan)	ABSSSI: MRSA, MSSA, S. pyogenes, S. agalactiae CABP: MSSA, S. pneumoniae, H. influenzae	FDA: CABP and ABSSSI EMA: CABP and cSSSI	3 IV: 600 mg over 5 to 60 min every 12 h [13]	Serious anaphylactic reactions have been reported with beta-lactam antibiotics Direct Coombs’ test seroconversion has been reported; if anaemia develops during or after therapy, consider drug-induced haemolytic anaemia and ceftaroline
Ceftobiprole (Zevtera/Mabelio)	EMA: October 2013	Cephalosporin	Basilea Pharmaceutica Ltd.	MRSA, ampicillin-susceptible enterococci and penicillin-resistant pneumococci	EMA: HAP (excluding VAP) and CABP	IV: 500 mg over 2 h every 8 h [14]	Serious anaphylactic reactions have been reported in patients receiving beta-lactam antibiotics
Telavancin (Vibativ)	FDA: September 2009	Lipoglycopeptide	Theravance Biopharma Antibiotics, Inc.,	MRSA, vancomycin-intermediate S. aureus and penicillin-resistant S. pneumoniae	FDA: cSSSI, HAP (including VAP)	IV: 10 mg/kg over 60 min every 24 h for 7–14 days (cSSSI) and 7–21 days (HAP/VAP) [15]	Decreased efficacy with moderate/severe pre-existing renal impairment Interferes with some coagulation tests e.g., prothrombin time, international normalised ratio QTc prolongation Serious and potentially fatal hypersensitivity reactions Infusion-related reactions
Dalbavancin (Dalvance/ Xydalba)	FDA: May 2014	Lipoglycopeptide	Durata Therapeutics (acquired by Actavis in 2014)	MRSA, S. pyogenes, S. agalactiae and E. faecalis strains susceptible to vancomycin	FDA: ABSSSI	IV: 1000 mg over 30 min followed one week later by 500 mg over 30 min [16]	Serious anaphylactic and skin reactions have been reported with glycopeptides Rapid IV glycopeptide infusion can cause upper body flushing, urticaria, pruritis and/or rash ALT elevations have been reported
Oritavancin (Orbactiv)	FDA: August 2014 EMA: March 2015	Glycopeptide	Melinta Therapeutics Inc.	MSSA, MRSA, VRE and vancomycin-intermediate and vancomycin-resistant staphylococci	FDA: ABSSSI EMA: ABSSSI	IV: 1200 mg single dose over 3 h [17]	Co-administration with warfarin may increase warfarin exposure and increase bleeding risk Oritavancin administration may artificially prolong aPTT for up to 48 h and prolong PT/INR for up to 24 h Hypersensitivity and infusion related reactions including pruritus, urticaria and flushing have been reported 4 A higher incidence of osteomyelitis reported in the oritavancin treated ABSSSI arm than vancomycin-treated arm
Tedizolid Phosphate (Sivextro)	FDA: June 2014 EMA: March 2015	Oxazolidinone	Cubist Pharmaceuticals	MRSA, vancomycin-intermediate Enterococcus spp.	FDA: ABSSSI EMA: ABSSSI	IV: 200 mg single dose over 1 h for 6 days 5 PO: 200 mg once daily [18]	Safety and efficacy not adequately evaluated in neutropenic patients
Besifloxacin (Besivance)	FDA: June 2009	Fluoroquinolone	SSP Co. Ltd.	MRSA, S. epidermidis, S. pneumoniae, and H. influenzae	FDA: bacterial conjunctivitis	Instill one drop in the affected eye(s) 3 times a day, four to 12 h apart for 7 days [19]	Not for injection into the eye Prolonged use may result in the overgrowth of non-susceptible organisms resulting in a super-infection Avoid contact lens wear during course of therapy
Delafloxacin (Baxdela)	FDA: June 2017	Fluoroquinolone	Melinta Therapeutics Inc.	S. aureus (including MRSA), S. pneumoniae, other fluoroquinolone resistant strains (Ineffective against Fluoroquinolone-resistant enterococci)	FDA: ABSSSI	IV: 300 mg over 1 h every 12 h PO: 450 mg tablet every 12 h for 5 to 14 days [20]	Hypersensitivity reactions may occur after first or subsequent doses
Ozenoxacin (Ozaenex/Xepi)	FDA: December 2017	Non-fluorinated quinolone	Ferrer Internacional S.A.	MRSA, MSSA, MRSE and S. pyogenes	FDA: impetigo	Topical: apply a thin layer to the affected area twice daily for 5 days [21	Prolonged use of ozenoxacin may result in the overgrowth of non-susceptible organisms resulting in a super-infection
Omadacycline (Nuzyra)	FDA: October 2018	Tetracycline	Paratek Pharmaceuticals	MRSA, penicillin-resistant and multidrug-resistant S. pneumoniae, and vancomycin-resistant Enterococcus spp.	FDA: CABP, ABSSSI	Duration: 7–14 days Loading IV Day1: 200 mg over 1 h once daily or 100 mg over 30 min twice daily Maintainance: 100 mg over 30 min or 300 mg po once daily 6 Loading PO (ABSSSI) Day 1&2: 450 mg once daily Maintainance PO (ABSSSI) 300 mg once daily [22]	Commonest adverse reactions: Nausea, vomiting, hypertension, headache, diarrhea, insomnia and constipation Mortality imbalance observed in the CABP clinical trial: 8 deaths in the omadacycline group vs. 4 in the moxifloxacin group Omadacycline use during tooth development (last half of pregnancy, infancy and childhood >8 years) may cause permanent teeth discoloration and enamel hypoplasia Omadacycline use during the 2nd and 3rd trimester of pregnancy, infancy and childhood >8 years may cause reversible bone growth inhibition

Notes: ¹ All dosing regimens are indicated in adult patients >18 years old with no renal or hepatic impairment. See individual drug label for dosing regimens in other populations. ² C. difficile-associated diarrhea has been reported with nearly all systemic antibacterial agents; ³ 600 mg every 8 h should be considered as it is safe and is expected to be a better dosing scheme for critically ill patients with normal or augmented renal clearance [23]. ⁴ Patients with ABSSSIs treated with oritavancin should be monitored closely for symptoms and signs of osteomyelitis and in case of osteomyelitis diagnosis, appropriate treatment should be initiated promptly ⁵ Tedizolid has excellent oral bioavailability (more than 90%) and thus there is no need for dosage adjustment when switching from intravenous to oral administration [24]. ⁶ Omadacycline per os should be administered after at a fasted state and certain foods (e.g., dairy products, to be avoided for at least 4 h after dosing [25].