Antibiotic treatment choices for SBP

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


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


(%)

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


(number of cases)

P < 0.001


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)

0

20

40

60

80

100



P < 0.001

Resolution of bacterial infections with cefotaxime or amoxicillin/clavulanic acid in 224 patients with cirrhosis and



(%)


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


B. Campillo et al. Clin. Infect. Dis. 2002 ; 35 : 1-10.

(%)

P < 0.001


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



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


(%)

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


(%)


P < 0.001

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.

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

Pharmacokinetics and pahrmacodynamics of carbapenemes in peritoneal fluid


K. Ikawa, et al. J. Infect. Chemother. 2008 ; 14 : 330-332.

Pharmacokinetics of teicoplanin in patients udergoing continuous ambulatory peritoneal dialysis


D. Stamadiatis, et al. Perit. Dial. Int. 2003 ; 23 : 127-131.

Pharmacokinetics of daptomycin in patients udergoing continuous ambulatory peritoneal dialysis


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.


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.


* = 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


0

20

40

60

80

100



P < 0.001

Resolution of bacterial infections with cefotaxime or amoxicillin/clavulanic acid in 224 patients with cirrhosis and



(%)


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


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)


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.

Antibiotic treatment choices for SBP

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