antibiotic treatment choices for sbp
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Treviso 8 Giugno 2009. Antibiotic treatment choices for SBP. P. Angeli D ept. of Clinical and Experimental Medicine Universit y of Pad ova. Infections in cirrhosis. Treatment of spontaneous bacterial peritonitis (SBP) . - PowerPoint PPT PresentationTRANSCRIPT
Antibiotic treatment choices for SBP
Treviso 8 Giugno 2009
P. AngeliDept. of Clinical and Experimental Medicine University of Padova
• 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 cost-effective 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 (SBP)
In 1990s cefotaxime or other third generation cephalosporins wereinvestigated more extensively in the treatment of SBP on the basis oftwo 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.
Treatment of spontaneous bacterial peritonitis
Infections in cirrhosis
A. Rimola, et al. J. Hepatol. 2000 ; 32 : 142-153.
0
20
40
60
80
100
SPB UTI Cellulitis Pneumoniae
nosocomial community-acquired
P < 0.001
Prevalence of multiresistance to cefotaxime or amoxicillin/clavulanic acid in 224 patients with cirrhosis and
bacterial infections
Infections in cirrhosis
(%)
J.G. Acevedo et. al. 2009 EASL Meeting
P < 0.001 P < 0.05 P = N.S.
0
10
20
30
40
50
Enterobacteria producingbetalactamase
Pseudomonas aeruginosa Meticillin-resistant Staphylococcusaureus
Enterococcus faecium
Main multiresistant bacteria isolated in 224 patients with cirrhosis and bacterial infections
Infections in cirrhosis
(number of cases)
P < 0.001
J.G. Acevedo et. al. 2009 EASL Meeting
Risk factors for SBP due to extended-spectrum β-lactamase- producing Escherichia Coli and Klebsiella species (ESBL-EK)
Infections in cirrhosis
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)
0
20
40
60
80
100
SPB UTI Cellulitis Pneumoniae
nosocomial community-acquired
P < 0.001
Resolution of bacterial infections with cefotaxime or amoxicillin/clavulanic acid in 224 patients with cirrhosis and
bacterial infections
Infections in cirrhosis
(%)
J.G. Acevedo et. al. 2009 EASL Meeting
P < 0.001 P < 0.005 P = 0.05
0
25
50
75
100
MSSA Meticcillin-resistantStaphyl. Aureus
Coagulase negativeStaphylococci sp.
Enterobacteriaceae
Mortality rate of spontaneous bacterial peritonitis and bacteremia by types of bacteria
Infections in cirrhosis
B. Campillo et al. Clin. Infect. Dis. 2002 ; 35 : 1-10.
(%)
P < 0.001
Infections in cirrhosis
0
10
20
30
40
50
Resistances to antibiotic therapy in in 169 inpatients with cirrhosis and bacterial infections
Preliminary unpublished data of an Italian multicenter study
Thirty day-mortality rate of spontaneous bacterial peritonitis by types of bacteria
Infections in cirrhosis
Kyoung-Ho Song et al. BMC Infect. Dis. 2009 ; 9 : 41 (Epub ahead of print)
0
20
40
60
80
100
5
P < 0.05
15 days2010 25
SBP due to non ESBL-EK
SBP due to ESBL-EK
0
20
40
60
80
100
No need to change therapy Need to change of therapy
A. Umgelter, et al. Infection 2009 ; (Epub ahead of print)
Mortality in cirrhotic patients with ascites and SBP who failed to respond to the common first line therapies
Infections in cirrhosis
(%)
P < 0.001
0
20
40
60
80
100
Uneffective therapy Effective therapy
Thirty day mortality in cirrhotic patients with SBP according to the efficacy of initial antibiotic therapy
Infections in cirrhosis
(%)
Kyoung-Ho Song et al. BMC Infect. Dis. 2009 ; 9 : 41 (Epub ahead of print)
P < 0.001
Treatment of nosocomial spontaneous bacterial peritonitis: proposal for consensus (1)
Infections in cirrhosis
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.
Factors in the selection of antibiotics for enpirical therapy
Infections in cirrhosis
• 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
Pharmacokinetics and pahrmacodynamics of carbapenemes in peritoneal fluid
Infections in cirrhosis
K. Ikawa, et al. J. Infect. Chemother. 2008 ; 14 : 330-332.
Pharmacokinetics of teicoplanin in patients udergoing continuous ambulatory peritoneal dialysis
Infections in cirrhosis
D. Stamadiatis, et al. Perit. Dial. Int. 2003 ; 23 : 127-131.
Pharmacokinetics of daptomycin in patients udergoing continuous ambulatory peritoneal dialysis
Infections in cirrhosis
D. Stamadiatis, et al. Perit. Dial. Int. 2003 ; 23 : 127-131.
Failure of antibiotic treatment of spontaneous bacterial peritonitis (SBP)
P. Angeli, et al. Aliment. Pharmacol. Ther. 2006 ; 23 : 75-84.
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.
Infections in cirrhosis
0
1000
2000
3000
4000
5000
Ceftazidime Ciprofloxacin
Cost of antibiotic Cost of hospital stay Total
Mean cost of treatment per patient with spontaneous bacterial peritonitis
P. Angeli, et al. Aliment. Pharmacol. Ther. 2006 ; 23 : 75-84.
Infections in cirrhosis
* = P < 0.001
*
*
*
(€)
Microrganisms E.Coli Pseudomonas sp. Klebsiella sp. Enterococci Staph aureus46 3 7 27 7
ESBL-producers 17 - 4
Resistance 34 (76 %) 2 (66%) 4 (57%) 18 (66%) 5 (71%)Quinolones 29 1 3 16 4Cephalosporins 23 2 3 - -Carbapenems 1 2 - 4 3
Meticillin- - 5Vancomicina 1 -
Preliminary unpublished data of an Italian multicenter study
Main multiresistant bacteria isolated in 169 inpatients with cirrhosis and bacterial infections
Infections in cirrhosis
0
20
40
60
80
100
SPB UTI Cellulitis Pneumoniae
nosocomial community-acquired
P < 0.001
Resolution of bacterial infections with cefotaxime or amoxicillin/clavulanic acid in 224 patients with cirrhosis and
bacterial infections
Infections in cirrhosis
(%)
J.G. Acevedo et. al. 2009 EASL Meeting
P < 0.001 P < 0.005 P = 0.05
Geographic distribution of Escherichia Coli strains with a reduced susceptibility to ciprofloxacin in community-acquired UTI in Europe
Infections in cirrhosis
0
10
20
30
40
50
Russia Italy Spain Poland Hungary Germany France Austria
S. Cagnacci et al. J. Clin. Microb. 2008 ; 46 : 2605-2612.
Treatment of community-acquired spontaneous bacterial peritonitis (SBP): proposal for consensus (2)
Infections in cirrhosis
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 community-acquired SBP but only in patients who are not on prophylaxis with norfloxacin and only in countries with low prevalence of quinolone-resistance E. coli.