Professional Documents
Culture Documents
REVIEW :
MICROBIAL MAPPING
2011-2012
No.
1.
%
22%
2.
Acinetobacter spp
3.
E coli
16,9%
4.
Klebsiella pneumoniae
11,8%
5.
Enterobacter aerogenes
10,1%
No
.
22%
1.
82,3
2.
Staphylococcus aureus
7,2
3.
Streptococcus spp
3,9
4.
Corynebacterium spp
3,9
5.
Enterococcus
2,6
Amikacin
100
Meropenem
88,8
Ceftazidime
88,8
Gentamycine
77,7
Cefotaxime
77,7
Imipenem
77,7
Piperacilline tazobactam
77,7
Ampi sulbactam
66,6
Tobramycin
66,6
Ceftriaxone
66,6
Cefoperazone sulbactam
55,5
Amoxyclav
55,5
Ciprofloxacin
55,5
Cotrimoxazole
55,5
Meropenem
100
Amikacin
100
Cefoperazone sulbactam
83,3
Ciprofloxacine
83,3
Levofloxacin
83,3
Imipenem
66,6
Cotrimoxazole
66,6
Ampicillin Sulbactam
66,6
Gentamycine
50
Ceftazidim
50
Piperacillin tazobactam
33,3
Cefotaxime
33,3
Amoxyclav
16,7
Ceftriaxone
16,7
Meropenem
100
Amikacin
83,3
Cotrimoxazole
83,3
Gentamycin
50,0
Ceftazidime
50,0
Cefoperazone sulbactam
33,3
Levofloxacin
33,3
Imipenem
33,3
Ampicillin Sulbactam
16,7
Piperacillin tazobactam
16,7
Cefotaxime
16,7
Ceftriaxone
Penicilli
ns
Cephal
osporins
Monobactam
s
Carbapenems
FOCU
S
PK/PD PARAMETERS
AFFECTING ANTIBIOTIC
EFFICACY IN VIVO
Concentration
Cmax:MIC
AUC:MIC
MIC
T>MIC
0
PAE
Time (hours)
Definition of PK/PD
Index
Examples of
Antibiotic
BETALACTAM
Aminoglycosides
Concentration- AUC
dependent
MIC
with timedependent
Fluoroquinolones
Glycopeptides
Tigecycline
0-24
Carbapenems
Lincosamides
Figure 1. Time-kill curves, ranging from one-fourth to 64 times the MIC, that
show the bactericidal pattern of activity of tobramycin, cipro floxacin, and
ticarcillin against Pseudomonas aeruginosa American Type Culture Collec
tion (ATCC) 27853.
Ambrose et al, Pharmacokinetics Pharmacodynamics of Antimicrobial Therapy:
Its Not Just for Mice Anymore. Clinical Infectious Diseases 2007; 44:7986
PHARMACOKINETIC /PHARMACODYNAM
IC BETA LACTAM
Optimization of Beta Lactam Therapy :
Manipulati
on of
Infusion
Time
CEPHALOSPORIN AGENTS
1st
Generation
Agents cefadroxil,
cefazolin,
cephalexin,
cephalothin,
cephapirin,
cephradine
2nd Generation
3rd
Generation
4th
Generation
cefaclor,
cefamandole,
cefonicid,
cefuroxime,
cefprozil,
cefoxitin,
cefmetazole,
cefotetan
cefoperazone cefepime
, cefotaxime,
ceftazidime,
ceftizoxime,
ceftriaxon
e, cefixime,
cefpodoxime,
cefdinir,
ceftibuten
FOCU
S
CEFOPERAZONE
CEFTRIAXONE
CEFTAZIDIME
PHARMACOKINETIC CHARACTERISTICS O
F THIRD GENERATION CEPHALOSPORIN
Drugs
Volum
e
distrib
ution
(Vd)
Prote T
in
norm
bindi al
ng
T
ESR
D
Excretion
CEFTRIAX
ONE
0,080,3
L/kg
85-95
%
5-9 hr
16 hr
Urine (33-67 % as
unchanged drug); Feces
(as inactive drug)
Cefoperazone
0,17
L/kg
8293%
1.5-3
hr
2,4
hr
Urine (20-30 % as
unchanged drug); Mainly in
the bile
Cefotaxime
0,25
L/kg
30-40
%
1-1.5
hr
15 hr
Ceftazidime
0,36
10 % 1-2 hr 21 hr Mainly in urine (80-90 % as
L/kg
Lacy et al, 2009. Drug
Information Handbook 17th Edition unchanged drug)
Sweetman, 2009. Martindale : The Complete Drug Reference 36 th Edition
Cunha, 2010. Antibiotic Essentials ninth edition
PHARMACOKINETIC /PHARMACODYNAM
IC
CEFTRIAXONE
PHARMACOKINETIC /PHARMACODYNAM
IC
CEFTRIAXONE
DOSAGE REGIMENTATION OF
EFTRIAXONE
Dosage
No
adjustment
range:
is generally necessary; if severe impairment, particular
No change
CrCl 10-50ml/min
No change
No change
Post HD dose
None
No change
Post PD dose
None
CVVH dose
No change
No change
No change
(max dose 2 g/day)
PROBLEM
Ceftriaxo
ne 2 x 1
g
Ceftriaxo
ne 1 x 2
g
CALCULATION
Ceftrixones PK characteristics :
Vd = 6-14 L
T = 5 9 hr
Do 1-2 g Cp = 0.5 300 mg/L
Formula : Css =
F x Do
Vd x 0.693 x
Do = 1 g ; = 12 hr Css = 77.30 mg/L (0.5 300
t
mg/L)
Do= 2 g; = 24 hr Css = 77.30 mg/L (0.5 300 m
g/L)
CALCULATION
% T > MIC = ln
Do
100
Vd x MIC
ln 2
CALCULATION
Ceftrixones PK characteristics :
Vd = 6-14 L
T = 5 9 hr
Protein binding = 95 % free drug = 5 %
Do = 1000 mg; = 12 jam
Co = Do x %free
Vd
= 3.57 mg/L
After the first-twelve hours ( t = 12 hr)
Cp = Co x e kt
= 1.42 mg/L
CALCULATION
Then , the second injection is administered
Cp = Co + Cp
Cp = 3.57 + 1.42 = 4, 99 mg
Plasma concetration at 24 hr (Cp ) is assumed as MIC.
e.g Ceftriaxones MIC = 1 g/ mL
Cp = Cp x e kt
t = 20.88 hr
Cefriaxone 2 x 1 g To reach its MIC, the time needed is :
(12 + 20.88) = 32.88 hr
CALCULATION
Do = 2000 mg; = 24 jam
Co = Do x % free
Vd
= 7.14 mg/L
Plasma concetration at 24 hr (Cp ) is assumed as MIC.
e.g Ceftriaxones MIC = 1 g/ mL
Cp = Co x e kt
t = 25.53 hr
Cefriaxone 1 x 2 g To reach its MIC, the time needed is : 25.
53 hr
CLINICAL CONSIDERATION
Hypoalbuminemia
Renal CL
Pea et al, 2005. Antimicrobial Therapy in Critically Ill Patients. Clin Pharmacokinet
page 1009-1030
Varghese et al, Antimicrobial Pharmacokinetic and Pharmacodynamic Issues in the
SUMMARY
Ceftriaxone is time-dependent antibiotic which can be
adminestered 1-2 g every 12-24 hours
Do = 1 g ; = 12 hr
Css = 77.30 mg/L (0.5 300 mg/L)
%T> MIC = 236.88 %
To reach its MIC, the time needed is 32.88 hr
Do= 2 g; = 24 hr
Css = 77.30 mg/L (0.5 300 mg/L)
%T> MIC = 155.94 %
To reach its MIC, the time needed is 25.53 hr
REFERENCES