Professional Documents
Culture Documents
Disclosures
h
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
Necrotising
fasciitis
Cellulitis and
erysipelas
Pyomyositis
Furuncles
and
carbuncles
Impetigo
Cutaneous
abscess
1. May AK, et al. Surg Infect 2009;10:46799; 2. Arias CA, et al. N Engl J Med 2009; 360:43943
Indication
Infection Type
Infection Severity
Primary Endpoints
cSSSI
ABSSSI
Intermediate/Severe
Severe
Subjective
(Clinicians Assessment at 7-14
Days After EOT)
Objective
(20% reduction in lesion size at
4872 hours)
Secondary
Endpoints
Varied
** 2010
2010 FDA
FDA Guidance
Guidance primary
primary endpoint:
endpoint:
Cessation
of
lesion
spread
&
fever
Cessation of lesion spread & fever at
at 48-72
48-72 hrs
hrs was
was
updated
updated in
in 2013
2013
HOST
Systemic
BUG
Microbial
Local
Dynamic process
BUG
Microbial
Local
Dynamic process
BUG
Microbial
Local
Malnutrition1-3
Generalised sepsis5
Diabetes1-5
Obesity1-3,5
Chronic renal failure3,6
Malignancy1,4
Transplantation4
Immunosuppression 3,4
Older age1,3
Cardiovascular disease3-5
Smoking1-3
Dynamic process
1. Bandyk. Semin Vasc Surg 2008;21:119-23;
2. Moucha et al. J Bone Joint Surg Am 2011;93:398-404;
3. Tognetti et al. J Eur Acad Dermatol Venereol 2012;26:931-41;
4. Fish et al. Ther Clin Risk Manag 2006;2:401-15;
5. Eron et al. J Antimicrob Chemother 2003;52 Suppl 1:i3-17;
6. Pesanti. Infect Dis Clin North Am 2001;15:81332
BUG
Microbial
Resistance1
Synergistic infections2
Toxin production eg. PVL3
Local
Dynamic process
PVL, PantonValentine leukocidin
;
1. Itani et al. Am J Infect Control 2011; 39:42-49;
CAMPIONI DA EVITARE:
h
ascessi perirettali,
Se necessario usare
TAMPONI: usare Tamponi
floccati con terreno di
trasporto adeguato per
ANAEROBI
SSTI: Aetiology
MSSA
Impetigo
Erysipelas
Cellulitis
Abscesses
Furuncles
Fasciitis
Pyomyositis
Bites
DFI
Decubit Ulcers
MRSA
Gram+
Gram-
Anaer
Staphylococcus aureus
71%
77.5%
22.5%
59%%
19%
40%
Methicillin-resistant
S. aureus (MRSA)
Enterococcus spp.
-Hemolytic streptococci
Methicillin-susceptible
S aureus (MSSA)
Pseudomonas aeruginosa
Coagulase-negative
staphylococci
Other
30
Percentage (%)
25
20
* p<0.01
* p<0.01
15
10
5
S.
py
St
og
re
en
p.
es
no
nA
gr
ou
ps
P.
ae
ru
gi
no
En
sa
te
ro
ba
ct
er
ia
ce
ae
R
SA
*
M
R
SA
/N
O
M
SS
A
h
h
h
ICU admission6
Invasive procedures, such as dialysis3 and CVC5
1.Bandyk.SeminVascSurg2008;21:11923;
Parenteral drug use3
2.Yanoetal.ActaOrthop2009;80:48690;
3.Viallonetal.AmJEmergMed2007;25:8806;
4.Yamakawaetal.BMCInfectDis2011;11:303;
5.Harbarthetal.InfectControlHospEpidemiol2008;29:8903;
6.IbelingsandBruining.EurJSurg1998;164:4118
MRSAinItaly:2013
9
19
9
0
20
0
0
20
1
0
20
2
0
20
3
0
20
4
0
20
5
0
20
6
0
0
2
7
0
20
8
0
20
9
1
20
0
1
20
3
33%
17%
11%
1%
65%
25%
14%
22%
39%
36%
39%
30%
30%
8%
0%
92%
10,782(22.8%) patients
Increased mortality
(OR2.91;95%CI2.343.62)
Increased readmission /
death within 30 days among
patients with decubitis ulcersa
Glycopeptides
Agent
Dose
Route
Spectrum
Indications
Comments
Vancomycin
1-1.5gm bd
15mg/kg
IV
Gm+
MDR-Gm+
infections
Teicoplanin
400mg bd,od
6-10 mg/kg
IV
Gm+
MDR-Gm+
infections
Oritavancin
1200mg stat
IV
Gm+ in
VRE
ABSSI
IV
Gm+
Dalbavancin
Linezolid
600mg bd
IV/po
Gm+
ABSSI, CAP
Tedizolid
200mg od
IV/po
Gm+
ABSSI
Glycylcycline
Tigecycline
100mg, then
50mgbd
IV
Gm+,
Gm-
ABSSI, IAI
Lipopeptide
Daptomycin
4-6mg/kg
IV
Gm+
ABSSI, right
endocarditis
Fluoroquinolones
Moxifloxacin
400mg od
IV/po
Gm+,
Gm-
Ceftaroline
600mg bd
IV
Gm+,
Gm-
ABSSI, CAP
Oxazolidanones
Beta-lactams
BassettiMetal.ClinMicrobiolInfect2014;20(Suppl.4):318
Susceptibility of
Complicated dosing
S. aureus compromised?
Linezolid
337.351
104%7,a
Vancomycin
1485.742
10-30%8,b
Teicoplanin
1879.73
24-77%9,10,a
Daptomycin
1620.674
68%
11,a
Tigecycline
585.655
380%12,c
Ceftaroline
762.756
Not available
New options
ESTABLISH-1
Infection
ABSSSI
667
Evaluated
LIN
TED
LIN
Wound
85.6
83.7
84.5
89.8
Cellulitis
74.8
71.9
88.1
82.0
80
85.7
83.0
87.8
Major
cutaneous
abscess
TEAEs
Similar rates
Based on the
observed
minimum
inhibitory
concentrations,
tedizolid was
four-to eightfold more
active than
linezolid
against
Staphylococcus
spp including
MRSA, and
Streptococcuss
pp.
Early clinical evaluation or response endpoints occurred at 48-72 hours after treatment initiation
evaluation (PTE) occurred at 7-14 days after end of therapy .
1.. Prokocimer P et al. JAMA. 2013;309(6):559-69
a
Post therapy
Composite
endpoint at ECE
Early
48-72 h
Post Rx
7-14 d
20% reduction
in lesion size
Investigator
Assessed Clinical
Cure at PTE
Vancomycin
better
ICAAC 2013
Oritavancin
better
*Primary
endpoint
for
EMA;
CE=Clinically Evaluable; ITT =Intent to
Treat;
Secondary Endpoint: Clinical Status at End of Therapy (Day 14-15, EMA primary
endpoint).
Severity
of Infection
Switch Therapy
Hospital Discharge
IV
Therapy
PO
Therapy
Cure
20.6
14
Days
22.1
19.4
15.2
11.7
15
25
23.1
22.1
22
19.4
13.4
18.2 18.6
14.8
21.8
16.4
12.1
18.3
12.7
13.9
15.2
10.1
Literature review with expert validation formed the basis for 14 criteria used in the study;
inclusive of Desai & Parodi criteria
The key (essential) criteria were selected by KOLs, and were used to estimate ES/ED
hypothetical opportunities
Stable clinical
infection
Afebrile/Temp
<38o C for 24 hrs
No unexplained
tachycardia
Systolic BP
100 mm Hg
Patient tolerates
oral fluids/diet
ES
ED
No other reason to
stay in hospital
except infection
management
Nathwani D, et al. Clin Microbiol Infect. 2014 Mar 27. doi: 10.1111/1469-0691.12632..
Nathwani D, et al. Clin Microbiol Infect. 2014 Mar 27. doi: 10.1111/1469-0691.12632.