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Antibiotic treatment choices for SBP
P. Angeli
Dept. of Clinical and
Experimental Medicine
University of Padova
Treviso 8 Giugno 2009
Infections in cirrhosis
Treatment of spontaneous bacterial peritonitis (SBP)
•
•
Empirical antibiotic therapy must be initiated immediately
after the diagnosis of the infection is made.
Several antibiotics can be used for the initial therapy of SBP:
cefotaxime or other third-generation cephalosporins, or
amoxicillin-clavulanic acid or quinolones. The optimal costeffective dosage has only been investigated for cefotaxime. For
this antibiotic, a minimum dose of 2 g/12 hr i.v. should be
administered in patients with normal renal function. In
addition a minimum duration of 5 days of cefotaxime therapy
is recommended.
A. Rimola, et al. J. Hepatol. 2000 ; 32 : 142-153.
Infections in cirrhosis
Treatment of spontaneous bacterial peritonitis
In 1990s cefotaxime or other third generation cephalosporins were
investigated more extensively in the treatment of SBP on the basis of
two factors:
•
Gram negative aerobic bacteria from the family of
Enterobacteriaceae were the most common causative
microrganisms.
•
A favourable pharmacokinetic property (i.e antibiotic
concentration in the ascitic fluid > MIC90 for causative
microrganisms.
A. Rimola, et al. J. Hepatol. 2000 ; 32 : 142-153.
Infections in cirrhosis
Prevalence of multiresistance to cefotaxime or
amoxicillin/clavulanic acid in 224 patients with cirrhosis and
bacterial infections
(%)
100
80
P < 0.001
P < 0.001
P < 0.05
P = N.S.
60
40
20
0
SPB
UTI
nosocomial
Cellulitis
Pneumoniae
community-acquired
J.G. Acevedo et. al. 2009 EASL Meeting
Infections in cirrhosis
Main multiresistant bacteria isolated in 224 patients
with cirrhosis and bacterial infections
(number of cases)
50
P < 0.001
40
30
20
10
0
Enterobacteria producing
betalactamase
Pseudomonas aeruginosa
Meticillin-resistant Staphylococcus
aureus
J.G. Acevedo et. al. 2009 EASL Meeting
Enterococcus faecium
Infections in cirrhosis
Risk factors for SBP due to extended-spectrum β-lactamase- producing
Escherichia Coli and Klebsiella species (ESBL-EK)
Risk factor
ESBL-EK
(n=26)
Non ESBl-EK
(n=78)
OR (95% CI)
Hospital stay  2
weeks
13 (50%)
3 (4%)
35.11 (4.57 to 269.72)
Previous history of
SBP
19 (73%)
23 (30%)
12.91 (2.88 to 57.96)
Prior use of
antibiotics within
30 days
21 (81%)
13 (17%)
15.13 (4.44 to 51.52)
ICU care
5 (19%)
7 (9%)
2.53 (0.70 to 9.12)
Presentation of
septic shock
11 (42%)
22 (28%)
2.21 (0.78 to 6.31)
Kyoung-Ho Song et al. BMC Infect. Dis. 2009 ; 9 : 41 (Epub ahead of print)
Infections in cirrhosis
Resolution of bacterial infections with cefotaxime or
amoxicillin/clavulanic acid in 224 patients with cirrhosis and
bacterial infections
(%)
100
P < 0.001
P < 0.001
P < 0.005
P = 0.05
80
60
40
20
0
SPB
UTI
nosocomial
Cellulitis
Pneumoniae
community-acquired
J.G. Acevedo et. al. 2009 EASL Meeting
Infections in cirrhosis
Mortality rate of spontaneous bacterial peritonitis and
bacteremia by types of bacteria
(%)
100
P < 0.001
75
50
25
0
MSSA
Meticcillin-resistant
Staphyl. Aureus
Coagulase negative
Staphylococci sp.
Enterobacteriaceae
B. Campillo et al. Clin. Infect. Dis. 2002 ; 35 : 1-10.
Infections in cirrhosis
Resistances to antibiotic therapy in in 169 inpatients
with cirrhosis and bacterial infections
50
40
30
20
10
Preliminary unpublished data of an Italian multicenter study
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Infections in cirrhosis
Thirty day-mortality rate of spontaneous bacterial
peritonitis by types of bacteria
100
80
P < 0.05
60
SBP due to non ESBL-EK
40
SBP due to ESBL-EK
20
0
5
10
15
20
25
days
Kyoung-Ho Song et al. BMC Infect. Dis. 2009 ; 9 : 41 (Epub ahead of print)
Infections in cirrhosis
Mortality in cirrhotic patients with ascites and SBP who
failed to respond to the common first line therapies
(%)
100
80
P < 0.001
60
40
20
0
No need to change therapy
Need to change of therapy
A. Umgelter, et al. Infection 2009 ; (Epub ahead of print)
Infections in cirrhosis
Thirty day mortality in cirrhotic patients with SBP
according to the efficacy of initial antibiotic therapy
(%)
100
80
P < 0.001
60
40
20
0
Uneffective therapy
Effective therapy
Kyoung-Ho Song et al. BMC Infect. Dis. 2009 ; 9 : 41 (Epub ahead of print)
Infections in cirrhosis
Treatment of nosocomial spontaneous bacterial peritonitis:
proposal for consensus (1)
Nosocomial bacterial infections including SBP are frequently caused
by multiresistant bacteria in patients with cirrhosis.
Third generation cephalosporins or amoxicillin-clavulanic acid are
uneffective in a high percent of these patients and should not be used
longer as first line empiric antibiotic treatment.
A more effective empirical antibiotic therapy in these patients should
include a combination of antibiotics with a broader spectrum such as
carbapenems and glycopeptides or lipopeptides.
In order to establish the best empirical antibiotic treatment of
nosocomial infections in patients with cirrhosis further large
multicenter studies are needed.
De-escalation of the initially broad antimicrobial regimen should be
undertaken only once definitive culture results are available.
Infections in cirrhosis
Factors in the selection of antibiotics for enpirical therapy
• Expected antimicrobial susceptibility of infecting
bacteria
• Potential risk to induce/select resistant bacteria
• Overall safety of the agents
• Their penetration in the site of infection
• Detrimental interactions with other drugs
• Costs
Infections in cirrhosis
Pharmacokinetics and pahrmacodynamics of
carbapenemes in peritoneal fluid
K. Ikawa, et al. J. Infect. Chemother. 2008 ; 14 : 330-332.
Infections in cirrhosis
Pharmacokinetics of teicoplanin in patients udergoing
continuous ambulatory peritoneal dialysis
D. Stamadiatis, et al. Perit. Dial. Int. 2003 ; 23 : 127-131.
Infections in cirrhosis
Pharmacokinetics of daptomycin in patients udergoing
continuous ambulatory peritoneal dialysis
D. Stamadiatis, et al. Perit. Dial. Int. 2003 ; 23 : 127-131.
Infections in cirrhosis
Failure of antibiotic treatment of spontaneous bacterial peritonitis (SBP)
FAILURE
I.V. CEFTAZIDIME
(n°=55)
Switch therapy with
CIPROFLOXACIN
(n°=61)
P
No positive response
9.09%
11.47%
N.S.
Adverse effects
1.82%
3.28%
N.S.
Recurrence of
infection
1.82%
3.28%
N.S.
Superinfections
3.64%
1.64%
N.S.
TOTAL
16.36%
19.67%
N.S.
P. Angeli, et al. Aliment. Pharmacol. Ther. 2006 ; 23 : 75-84.
Infections in cirrhosis
Mean cost of treatment per patient with spontaneous
bacterial peritonitis
(€)
5000
* = P < 0.001
4000
3000
*
*
2000
1000
*
0
Ceftazidime
Cost of antibiotic
Ciprofloxacin
Cost of hospital stay
Total
P. Angeli, et al. Aliment. Pharmacol. Ther. 2006 ; 23 : 75-84.
Infections in cirrhosis
Main multiresistant bacteria isolated in 169 inpatients
with cirrhosis and bacterial infections
Microrganisms
ESBL-producers
E.Coli
46
17
Resistance
Quinolones
Cephalosporins
Carbapenems
34 (76 %)
29
23
1
MeticillinVancomicina
Pseudomonas sp.
3
-
2 (66%)
1
2
2
Klebsiella sp.
7
4
4 (57%)
3
3
-
Enterococci Staph aureus
27
7
18 (66%)
16
4
1
Preliminary unpublished data of an Italian multicenter study
5 (71%)
4
3
5
-
Infections in cirrhosis
Resolution of bacterial infections with cefotaxime or
amoxicillin/clavulanic acid in 224 patients with cirrhosis and
bacterial infections
(%)
100
P < 0.001
P < 0.001
P < 0.005
P = 0.05
80
60
40
20
0
SPB
UTI
nosocomial
Cellulitis
Pneumoniae
community-acquired
J.G. Acevedo et. al. 2009 EASL Meeting
Infections in cirrhosis
Geographic distribution of Escherichia Coli strains with a reduced
susceptibility to ciprofloxacin in community-acquired UTI in Europe
50
40
30
20
10
0
Russia
Italy
Spain
Poland
Hungary
Germany
France
S. Cagnacci et al. J. Clin. Microb. 2008 ; 46 : 2605-2612.
Austria
Infections in cirrhosis
Treatment of community-acquired spontaneous bacterial
peritonitis (SBP): proposal for consensus (2)
Up to now, third generation cephalosporins or amoxicillin-clavulanic
acid can still be considered as the first-line empirical antibiotic
therapy in patients with cirrhosis and community-acquired SBP.
Quinolones may still be an alternative antibiotic choice in communityacquired SBP but only in patients who are not on prophylaxis with
norfloxacin and only in countries with low prevalence of quinoloneresistance E. coli.