nuovi antibiotici per i gram-positivi · matteo bassetti, md, phd infectious diseases division...
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Matteo Bassetti, MD, PhD
Infectious Diseases Division
Santa Maria Misericordia University
Hospital
Udine, Italy
Nuovi antibiotici per i Gram-positivi
Disclosures
Research grants
- Astellas, Pfizer, MSD, Gilead
Advisor/consultant
- Angelini, Astellas, AstraZeneca, Bayer, Basilea, Cubist,
Gilead, MSD, Pfizer, Novartis, Shionogi, Vifor,
Medicines company, Tetraphase
Speaker/chairman
- Astellas, AstraZeneca, Pfizer, MSD, Gilead, Angelini,
Vifor, Novartis, Bayer, Cubist
Unmet needs
Broad and narrow spectrum drugs active aganist MDR
Gram-negative rods (enterobacteriaceae, pseudomonas,
and acinetobacter)
- Including those that produce carbapenemase where the only
active agents are tigecycline and colistin (anticipated to increase
over the next decade)
- Oral formulation in addition to IV is a plus
Gram-positive drugs active against MRSA and Coag neg
Staph show improved efficacy in more difficult to treat
infections like osteo, endocarditis and PJI, particularly
drugs taht are more effective, safer and /or more
convenient than current drugs
Drugs for MDR TB; MDR gonorrhea
GRAM + GRAM -
DRUGS HERE AND THOSE COMING Staphylococcus aureus
Drug Here Drug On The Way
Agent Route Agent Class Route
Ceftaroline IV BC-3781 pleuromutilin IV-PO
Ceftobiprole IV Ceftobiprole ceph IV
Daptomycin IV Dalbavancin glycopeptide IV
Linezolid IV-PO Delafloxacin FQ IV-PO
Rifampin IV-PO JNJ-Q2 FQ IV-PO
SMX/TMP IV-PO Oritavancin Glycopeptide IV
Telavancin IV Omedacycline
Tetracycline IV-PO
Tigecycline IV Brilacidin defensin-mimetics IV
Vancomycin IV Tedizolid oxazolidinone IV-PO
Teicoplanin IV, IM Eravacycline Tetracycline IV/PO
Antibiotics approved in
2014-2015
Source CDDEP 2015; WHO 2014 and PAHO
Dalbavancin - Bactericidal in vitro* at plasmatic
concentrations and proposed posology and administration
profile
Dalbavancin
Initial Dose 1000 mg
Dalbavancin
Second Dose 500 mg
Pla
sm
a C
on
ce
ntr
ati
on
(m
g/L
)
(+-
Sta
nd
ard
Devia
tio
n)
Time (Days)
Leighton et al. ANTIMICROB AGENTS CHEMOTHER 2004; 940-945
• Pharmacokinetic
parameters after a single
1000 mg dose
• Effective half-life is
approximately 8.5 days
• Terminal elimination half-
life is 14.4 days
*Pri
ma
ry
en
dp
oin
t fo
r E
MA
;
CE
=C
lin
ica
lly E
va
lua
ble
; IT
T =
Inte
nt
to
Tre
at;
Primary Endpoint: early response at 48-72 hours post initiation of therapy
cessation of spread of the erythema of the lesion, and resolution of fever.
Secondary Endpoint: Clinical Status at End of Therapy (Day 14-15, EMA primary
endpoint).
Dalbavancin - Phase 3 study design
Boucher et al. (2014) N Engl J Med 370:2169
Boucher et al. N Engl J Med 2014; 370:2169
Dalbavancin for infections of the skin compared
to Vancomycin/Linezolid
Dalbavancin - Outcomes by specific Pathogens
Proportion of Patients Achieving ≥ 20% Reduction in Lesion Size at 48-72 Hours by Pathogen, Studies DUR001-301/302 (pooled)
Dalbavancin single dose vs
double doses
Dunne MW et al. Clin Infect Dis. 2016 Mar 1;62(5):545-51
Dalbavancin tolerability in pts treated
more than 10 days
Dunne MW et al. Drug Saf 2016; 39:147–157
BSI: Dalbavancin
Raad. I. CID. 2005
A phase 2, open-label, randomized, controlled, multicenter study
75 adults CR-BSIs
Dalbavancin
1000 500
Vancomycin
1000 bid 14 d
Dalbavancin 33
Dalbavancin: Once a week
Vancomycin 34
67 patients
Dalba Vanco
Overall success at EOT 21/23 (91.3%) 18/28 (64.3%)
Clinical success 20/23 (87%) 14/28 (50%)
Microbiological success 22/23 (95.7%) 22/28 (78.6%)
Adverse events Similar Similar
Revolutionary drugs
Ceftriaxone
- Long half life ( 8h)
- Once a day
- Protein binding (85%)
- Only IV ( IM)
- Milestone of OPAT
- Well telerated
- Many indications
(SSTI, CAP, UTI, etc.)
- Cost
Dalbavancin - Long half life ( 5-7 days)
- Weekly drug
- Protein binding (dalba 93%)
- Only IV
- Potential for OPAT
- Well tolerated
- Potential for many indications
- Cost
80s 2016
Potential indications
Label:
- cSSTIs: one-two shots!
- Erysipelas, cellulitis, abscess, skin ulcers,
nosocomial cellulitis
Not-label:
- CBSIs: empiric and targeted use
- Bone and joint infections
- Mediastinitis
- Endocarditis
- CDAD
Potency Against Important Gram Positive
Organisms
US and European isolates collected between 2010-2012
MIC90 (µg/mL)
Pathogen (n) Oritavancin Vancomycin Daptomycin Linezolid
S. aureus (13,336) 0.06 1 0.5 2
MSSA (7,800) 0.06 1 0.5 2
MRSA (5,536) 0.06 1 0.5 1
β streptococci (2,281) 0.12 0.5 0.25 1
E. faecalis (2,132) 0.06 2 1 2
E. faecium (1,237) 0.06 >16 2 2
Randomized double blind trial design with 60 day safety follow
up
PTE Secondary endpoint
EMA
Safety Evaluation
60-day Safety
ECE (48-72 hrs)
Primary endpoint
FDA
Da
y 1
Da
y 7
Da
y 1
0
Oritavancin 1 x 1200mg
Vancomycin 7-10 days
(1g or 15mg/kg BID)
n=1959 Post-Treatment Evaluations
Active drug Placebo
Note: Infusions on days 7-10 were administered at the investigators’ discretion
Legend:
IV
IV IV IV IV IV IV IV
IV IV IV IV IV IV IV
IV IV IV IV IV IV IV
IV IV IV IV IV IV
IV IV
IV
IV
IV IV
IV IV
IV IV IV
IV IV IV
Oritavancin Phase III Clinical Studies
Gram-Positive Therapeutics: Latest Data on IV
Antibiotics Awaiting Approval for ABSSSI
Early Clinical Response (%)a,c PTE Clinical Cure (%)b
ORI VAN ORI VAN
Wound 88.0 85.1 83.4 78.3
Cellulitis 76.0 75.5 76.0 78.8
Major cutaneous abscess
81.5 84.3 85.7 84
Similar safety profile
Oritavancin (ORI)
Phase 3 Study SOLO 1 and 2 pooled analysis
Infection ABSSSI
N 1959
Evaluated IV dose of ORI or vancomycin (VAN) for 7-10 days
Corey GR et al. 24th ECCMID Barcelona, Spain 10-13 May 2014. poster_113642
Wilcox M et al. ICAAC 2013. Denver, Colorado. 10-13 September 2013. Poster L-202
Telavancin is a novel lipoglycopeptide
antibacterial agent
O
O O
O
Me
Me OH
OH OH
OH CI
O O
CI O
HO
O
NH
HO2C
HO OH OH
H N
H
N
H
O
O
H
N
O
N
H
O
OH O
Me
Me
H
N
H2N Me H
N
H N
H
N
H
O
HN OH
OH
P
Lipophilic side-chain
Membrane anchoring
• Improved potency
• Rapid cidality
Hydrophilic side-chain
Favourable PK-ADME properties
• Long half-life
• Renal clearance
Leadbetter et al. J Antibiot 2004
Unique dual mechanism of action
– Bacterial cell wall inhibition:
preventing polymerisation and
crosslinking
– Bacterial cell membrane
disruption
Telavancin: microbiologic
profile
Dual mechanism of action
Broad Gram-positive spectrum
Active against VISA, daptomycin-NS and
linezolid-NS organisms
Potent bactericidal activity
Low potential for emergence of resistance
Telavancin – activity against S. aureus
Pathogen* Agent MIC µg/ml†
CLSI %
Susceptible
EUCAST %
Susceptible 50% 90%
MRSA
(n=5,000)
Telavancin 0.03 0.06 100‡ 100
Vancomycin 1 1 99.9 99.9
Teicoplanin ≤2 ≤2 >99.9 98.7
Daptomycin 0.25 0.5 99.9 99.9
Linezolid 1 2 >99.9 >99.9
MSSA
(n=5,000)
Telavancin 0.03 0.06 100‡ 100
Vancomycin 1 1 100 100
Teicoplanin ≤2 ≤2 100 99.9
Daptomycin 0.25 0.5 100 100
Linezolid 2 2 100 100
Mendes et al. Antimicrob Agents Chemother, 2010
Mendes et al. Diagnostic Microbiology and Infectious
Disease, 2015
*Global (N America, EU, Latin America, Asia-West Pacific) isolates; †MICs determined using CLSI microdilution methodology;
‡Based upon FDA approved breakpoint of ≤1 µg/mL for S. aureus
MRSA, methicillin-resistant S. aureus; MSSA, methicillin-susceptible S. aureus
23
Telavancin in Uncomplicated S. aureus
Bacteremia ASSURE Trial
• Comparators:
Telavancin 10 mg/kg IV q24h
Vancomycin 1 g IV q12h or
Nafcillin 2 g IV q6h or
Oxacillin 2 g IV q6h, or
Cloxacillin 2 g IV q6h
• Treatment duration: 14 days
Double-blind, randomized comparison of telavancin vs standard therapy for treatment of “uncomplicated” S. aureus blood stream infection
• Primary Endpoint: Clinical Cure at 84 days
• Continuation criteria used to identify complicated cases (deep-seated infection [eg, endocarditis, osteomyelitis] requiring > 2 weeks treatment)
• 60 patients enrolled in this exploratory study at ~30 sites in 8 countries
• 3,000 patients screened over 3+ years
1. Stryjewski ME, BMC Infect Dis. 2014 May 23;14(1):289.
24
Cure Rates ATT and CE Populations
Analysis Population Telavancin
(n=30) Standard
Therapy (n=30)
All-treated population (AT) 29 (97%) 29 (97%)
Ineligible patients 14 (47%) 13 (43%)
All-treated target population (ATT) 15 (50%) 16 (53%)
Clinically evaluable population (CE) 8 (27%) 9 (30%)
1. Stryjewski ME, BMC Infect Dis. 2014 May 23;14(1):289.
Corey RG et al. Clin Infect Dis 2015; DOI: 10.1093/cid/ciu971
Cure Rates in Patients With Bacteremia in
Clinical Studies With Telavancin
Corey RG et al. Clin Infect Dis 2015; DOI: 10.1093/cid/ciu971
Locke et al. CID 2014
Prokocimer et al. AAC 2012
Pharmacokinetic and relative penetration ratios for
single doses of tedizolid and linezolid in the murine
pneumonia model under various conditions
Drug Model Blood fAUCb ELF AUC
ELF
penetration
ratio
Tedizolid Immunocomp
etent 4.7 (0.1)c 43.9 (2.8)c 9.34
Neutropenic 3.35 (0.1)c 35.6 (0.2)c 10.63
Uninfected 2.77 (0.1)c 17.0 (0.1)c 6.14
Linezolid Immunocomp
etent 115.9 (44.0)d 155.8 (14.2)d 1.34
Neutropenic 53.4 (4.7) 61.4 (17.9) 1.15
Uninfected 36.3 (0.9) 62.5 (17.7) 1.72
Keel RA et al. Antimicrob. Agents Chemother 2012; 56: 3420-3422
Tedizolid: Novel Oxazolidinone
NDA=new drug application; IV=intravenous; HAP=hospital-acquired pneumonia; VAP=ventilator-associated pneumonia.
1. www.Cubist.com ; assessed December 17, 2013.
• Proposed indication: treatment of acute
bacterial skin and skin structure infections
(ABSSSI)
• Clinical development program – ABSSSI
• Under regulatory review
– Hospital-acquired/ventilator associated bacterial
pneumonia (HABP/VABP) • Late stage development
Gram-Positive Therapeutics: Latest Data on
Oral Antibiotics Awaiting Approval for ABSSSI
Based on the observed minimum inhibitory concentrations, tedizolid was four-to eight-fold more active than linezolid against Staphylococcus spp including MRSA, and Streptococcus spp.
Early Clinical Responsea (%)
PTEb Clinical Success (%)
TED LIN TED LIN
Wound 85.6 83.7 84.5 89.8
Cellulitis 74.8 71.9 88.1 82.0
Major cutaneous abscess
80 85.7 83.0 87.8
TEAEs Similar rates
Tedizolid (TED)1
Phase 3 Study ESTABLISH-1
Infection ABSSSI
N 667
Evaluated 6-day oral tedizolid vs 10-day oral linezolid therapy
a Early clinical evaluation or response endpoints occurred at 48-72 hours after treatment initiation b Post therapy evaluation (PTE) occurred at 7-14 days after end of therapy . 1.Prokocimer P et al. JAMA. 2013;309(6):559-69
Platelet Counts– Pooled Phase 3
Studies
TEAE=treatment-emergent adverse events; GI=gastrointestinal; LLN=lower limit of normal; TZP=tedizolid; LZD=linezolid.
aPlatelet counts were collected on Study Day 7-9, Study Day 11-13, and after the last dose of study drug.
1. DeAnda C, et al. Integrated results from 2 phase 3 studies comparing tedizolid phosphate 6 days vs. linezolid 10 days in patients with ABSSSI. Poster presented at: 53rd Interscience
Congress on Antimicrobial Agents and Chemotherapy (ICAAC); September 10-13, 2013; Denver, CO. (L-203).
At any post-baseline assessment through last dose of study druga
6.4
2.1
12.6
4.5
0
10
15
20
Below LLN Substantially Abnormal (<75% of LLN)
Pa
tie
nts
Wit
h T
EA
Es (
%)
6-Day TZP 200 mg once daily 10-Day LZD 600 mg twice daily
P=.0002
P=.0175
5
Omadacycline
SPA-Approved Phase 3 Trial Design for ABSI -
1108 (OASIS)
[1] 655 Randomized Subjects, 10 subjects were randomized, but never treated [2] Early Clinical Response = primary end point for FDA. [3] PTE end point = Co-primary end points confirmed through EMA scientific advice.
d2-3
FDA - Early Clinical
Response[2]
d7 to d14
End of Treatment
d1
Omadacycline
IV
Omadacycline
IV or Oral
Linezolid
IV
Linezolid
IV or Oral
ABSS
SI 645 treated
subjects[1]
7-14d after last treatment day
EMA - Post-Treatment
Evaluation[3]
3
Primary Endpoints Achieved for Both FDA and
EMA
84,8 86,1
96,3
85,5 83,6 93,5
0
10
20
30
40
50
60
70
80
90
100
Early Clinical Response
mITT PTE - Clinical Success
CE-PTE - Clinical Success
Early C
linic
al S
uccess, %
Omadacycline
EMA Co-Primary Endpoints
Delta (95% CI)
-0.7 (-6.9, 4.9) Delta (95% CI)
+2.5 (-3.2, 8.2)
Delta (95% CI)
+2.8 (-1.0, 6.9)
FDA Primary Endpoint
Plasma and Intrapulmonary
Concentrations of Eravacycline
Connors KP, et al. Antimicrob Agents Chemother 2014;58:2113-2118
Sample Site AUC0-12
(ug-h/mL)
Site:Unbound Plasma Ratio
Plasma (total) 4.56
Plasma (unbound) 0.77
ELF 4.59 6.44
AM 39.53 51.63
Eravacycline 1.0 mg/kg IV q12h
for a total of seven doses
Eravacycline
Pros
Broad spectrum (Gram+
[MRSA], Gram- [including
P. aeruginosa, ESBLs,
KPC, NDMs], anaerobes)
Favorable safety and
tolerability profile expected
Q12-Q24 interval
Oral dosing
Good lung penetration
Con
Contraindicated in
pregnancy and in children
Failed in cUTI P3 trial
Oral formulation: low
avialability
Relative to tigecycline:
2-4× more potent; 2× higher AUC AUC, area under the plasma drug concentration-time curve; NDM, New Delhi metallo-β-lactamase
Ceftaroline in vitro & in animal models
Active & bactericidal vs.
- Staphylococci, including MRSA
- Streptococci including penR pneumococci
- H. influenzae and M. catarrhalis including ß-lactamase-producers
- Enterobacteriaceae EXCEPT if ESBL, high level AmpC or carbapenemase
- Not active vs non-fermenters, Bacteroides
High affinity for PBP2a in S. aureus; PBP2x/2a/2b in S. pneumoniae
Hard to select resistance in MRSA1,2
In vivo efficacy vs.
- MRSA & VISA in lung, endocarditis and other models1,2
- Penicillin-resistant S. pneumoniae (PRSP) in a rabbit pneumonia3
1. Zhanel G et al. Drugs. 2009;69:809–831. 2. Kanafini ZA. Future Microbiol. 2011;6:9–18. 3. Croisier-Bertin D et al. Antimicrob Agents Chemother. 2011;55:3557–3563.
Ceftaroline penetration
CSF penetration: 14% +/- 5%
Lung penetration: 42.0 +/- 11.2%
Cottanoud et al. 50th ICAAC Boston 2010- Abstract B702
Jacqueline C et al. 46th ICAAC San Francisco 2006 Abstract A-1938
Garrison et al. Expt Rev Anti Infect Ther 2012
CANVAS 1 & 2: Evidence of an early
treatment effect with Ceftaroline may help
subsequent treatment decisions
Friedland HD et al. Antimicrob Agents Chemother. 2012;56:2231–2236.
Ceftaroline
Use off licensed indications
CNS
Orthopaedic
Endocarditis
• Ceftobiprole medocaril is the prodrug of the active moiety ceftobiprole.
• Ceftobiprole shows predictable and linear pharmacokinetics across the dose range of 125–1000 mg, with low variability (< 30%) and no accumulation.
• Distribution restricted to the extracellular water compartment (Vss = 18 L).
• Half-life of 3–4 hours.
• Eliminated primarily unchanged by renal excretion (glomerular filtration), with minimal metabolism to an open-ring metabolite.
• No relevant hepatic metabolism.
• Dose adjustment in renal impairment (CLCR < 50 mL/min), no dose adjustment in hepatic impairment.
• Low plasma protein binding of ~16%.
• Low potential for drug–drug interactions.
Zevtera Summary of Product Characteristics; MHRA Zevtera Public Assessment Report 2013
Clinical pharmacology of ceftobiprole
43
Ceftobiprole Activity vs Gram-positive pathogens Europe, Turkey & Israel 2005-2010
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
E. faecium (2,222)
E. faecalis (3,968)
VGS (1,264)
BHS (2,981)
Ceftriaxone RSP (20)
Ceftriaxone NSP (202)
PRSP (11)
PISP (209)
PNSP (217)
PSSP (4,223)
S. pneumoniae (4,443)
MR-CoNS (4,246)
MS-CoNS (1,317)
CoNS (5,563)
MRSA (4,147)
MSSA (11,279)
S. aureus (15,426)
% Susceptible % Resistant Adapted from Farrell et al. AAC. 2014; 58(7):3882-8
2 mg/L
% strains inhibited
99.5
100
98.3
93.1
100
91.0
99.3
99.8
90.0
92.8
36.4
85.6
15.0
100
94.1
95.9
6.8
CoN
S
S. pn
eum
on
iae
44
S. au
reu
s O
ther
4 mg/L
2 mg/L
0.5 mg/L
MIC
0.25 mg/L
0.5 mg/L
Activity against clinical isolates of Staphylococcus aureus
including MRSA from European surveillance
SENTRY study: N=15426, EU: 2005-
2010
27% of isolates are MRSA as defined by oxacillin resistance
Adapted from Farrell et al. AAC 2014; 58(7):3882-8 45
Potency against MSSA is similar to that of oxacillin and
superior to other extended-spectrum cephalosporins
0
10
20
30
40
50
60
70
80
90
100
Cu
mu
lativ
e %
in
hib
ite
d
MIC mg/L
SENTRY, EU, 2010 (CLSI broth microdilution), N=1974
Ceftobiprole
Oxacillin
Cefepime
Ceftriaxone
Ceftazidime
Basilea Pharmaceutica International Ltd.: Data on file 46
Activity against S. aureus with reduced
susceptibility or resistance to the major anti-
MRSA agents
Adapted from Farrell et al. Int J Antimicrob Agents 2014; 43(4):323-7 47
MIC (mg/L) %Susc. / %Resistant
Resistant subset (no. tested) / antimicrobial agent
50% 90% Range EUCAST
All MRSA (216)
Ceftobiprole 1 2 0.12 – 4 97.3 / 2.7
Vancomycin 1 2 ≤0.12 – >16 91.2 / 8.8
Daptomycin 0.5 2 0.12 – 4 81.0 / 19.0
Linezolid 1 2 0.25 – >8 90.7 / 9.3
Teicoplanin ≤2 4 ≤2 – >8 89.8 / 10.2
Ceftobiprole
Linezolid non-susceptible (21)c 1 2 0.25 – 2 100.0 / 0.0
Daptomycin-non-susceptible (32) 0.5 2 0.25 – 2 100.0 / 0.0
VISA (12) 2 2 1 – 2 100.0 / 0.0
hVISA (32) 2 2 0.5 – 2 100.0 / 0.0
VRSA (10) 0.5 1 0.12 – 2 100.0 / 0.0
SCCmec type I (21) 2 4 2 – 4 71.4 / 28.6
SCCmec type II (22) 1 2 0.25 – 2 100.0 / 0.0
SCCmec type III (22) 2 2 1 – 2 100.0 / 0.0
SCCmec type IV (44) 1 1 0.5 – 1 100.0 / 0.0
c. LZD=linezolid. One S. aureus isolate (MIC at 4 mg/L) was positive for cfr rRNA methyltransferase. MIC Source: Adapted from Farrel et al. [Farrel 2014].
Clinical cure at TOC (CE)
69%
78%
38%
71% 76%
56%
0%
20%
40%
60%
80%
100%
% p
ati
en
ts w
ith
c
lin
ica
l c
ure
at
the T
OC
vis
it (
CE
)
Ceftobiprole Ceftazidime/Linezolid
N=251 N=244 N=198 N=185 N=53 N=59
All patients VAP HAP (excl. VAP)
48
Ceftobiprole vs Ceftazidime/Linezolid:
Difference (95% CI): -2.0% (-10.0; 6.1) 1.6% (-6.9; 10.4) -18.2% (-36.4; 0.0)
Awad et al. Clin Infect Dis 2014; 59(1):51-61
HAP (excl. VAP):
Post-hoc analysis of early improvement at Day 4
(CE)
87% 87% 95%
78% 74%
53%
0%
20%
40%
60%
80%
100%
% p
ati
en
ts w
ith
cli
nic
al c
ure
at
the
TO
C v
isit
Ceftobiprole Ceftazidime/Linezolid
N=198 N=185 N=61 N=69 N=19 N=19
All patients MRSA at baseline Gram-positive at baseline
Adapted from Scheeren et al., DIVI 2014; Poster P/06/06 49
:
Difference (95% CI): 8.5% (0.9; 16.1) 13.0% (−0.4; 26.4) 42.1% (17.5; 66.7)
HAP (excl. VAP):
Outcomes in patients with baseline bacteraemia
(ITT)
Welte et al., ERS 2014; Presentation 4643
29%25%
21%17%
30%
24%
37%41%
0%
10%
20%
30%
40%
50%
60%
%withoutcome
Ce obiprole Ce azidime/Linezolid
24
Allpa ents AllICUpa ents
Number 12171227 2724 17AllICUpa ents
Allpa ents
Clinical cure (TOC visit) 30-day all-cause
mortality
50
Pros and cons of new antimicrobials for cSSTI
Drug Pros Cons
Daptomycin Rapid bactericidal activity
Antibiotic film
Good tolerability profile
Only intravenous
Spectrum limited to Gram positives
Tigecycline Broad spectrum of activity Only intravenous
Bacteriostatic
Linezolid Oral formulation allows treatment of outpatients and early
oral-switch
Bacteriostatic
Spectrum limited to Gram positives
Drug-Drug interactions
Important adverse effects
Tedizolid Oral formulation allows treatment of outpatients and early
oral-switch
Once-daily administration
Low drug interactions
Low myelotoxicity
Bacteriostatic
Spectrum limited to Gram positives
Dalbavancin Once-weekly administration
Good penetration into cortical bone and auricular tissues
Good tolerability profile
Spectrum limited to Gram positives
Only intravenous
Oritavancin Single-dose treatment
Good tolerability profile
Spectrum limited to Gram positives
Only intravenous
Ceftaroline Broad-spectrum activity
Good tolerability profile
Only intravenous
Bassetti M, et al. Curr Opin Infect Dis 2016;29(2):99-108.