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Antibiotic treatment choices for SBP

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) .

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Antibiotic treatment choices for SBP

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  1. Treviso 8 Giugno 2009 Antibiotic treatment choices for SBP P. Angeli Dept.ofClinical and Experimental Medicine Universityof Padova

  2. 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 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.

  3. 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.

  4. Infections in cirrhosis Prevalence of multiresistance to cefotaxime or amoxicillin/clavulanic acid in 224 patients with cirrhosis and bacterial infections (%) P < 0.001 P < 0.001 P < 0.05 P = N.S. J.G. Acevedo et. al. 2009 EASL Meeting

  5. Infections in cirrhosis Main multiresistant bacteria isolated in 224 patients with cirrhosis and bacterial infections (number of cases) P < 0.001 J.G. Acevedo et. al. 2009 EASL Meeting

  6. Infections in cirrhosis Risk factors for SBP due to extended-spectrum β-lactamase- producing Escherichia Coli and Klebsiella species (ESBL-EK) Kyoung-Ho Song et al. BMC Infect. Dis. 2009 ; 9 : 41 (Epub ahead of print)

  7. Infections in cirrhosis Resolution of bacterial infections with cefotaxime or amoxicillin/clavulanic acid in 224 patients with cirrhosis and bacterial infections (%) P < 0.001 P < 0.001 P < 0.005 P = 0.05 J.G. Acevedo et. al. 2009 EASL Meeting

  8. Infections in cirrhosis Mortality rate of spontaneous bacterial peritonitis and bacteremia by types of bacteria (%) P < 0.001 B. Campillo et al. Clin. Infect. Dis. 2002 ; 35 : 1-10.

  9. Infections in cirrhosis Resistances to antibiotic therapy in in 169 inpatients with cirrhosis and bacterial infections Preliminary unpublished data of an Italian multicenter study

  10. Infections in cirrhosis Thirty day-mortality rate of spontaneous bacterial peritonitis by types of bacteria P < 0.05 SBP due to non ESBL-EK SBP due to ESBL-EK 5 10 15 20 25 days Kyoung-Ho Song et al. BMC Infect. Dis. 2009 ; 9 : 41 (Epub ahead of print)

  11. Infections in cirrhosis Mortality in cirrhotic patients with ascites and SBP who failed to respond to the common first line therapies (%) P < 0.001 A. Umgelter, et al. Infection 2009 ; (Epub ahead of print)

  12. Infections in cirrhosis Thirty day mortality in cirrhotic patients with SBP according to the efficacy of initial antibiotic therapy (%) P < 0.001 Kyoung-Ho Song et al. BMC Infect. Dis. 2009 ; 9 : 41 (Epub ahead of print)

  13. 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.

  14. 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

  15. Infections in cirrhosis Pharmacokinetics and pahrmacodynamics of carbapenemes in peritoneal fluid K. Ikawa, et al. J. Infect. Chemother. 2008 ; 14 : 330-332.

  16. Infections in cirrhosis Pharmacokinetics of teicoplanin in patients udergoing continuous ambulatory peritoneal dialysis D. Stamadiatis, et al. Perit. Dial. Int. 2003 ; 23 : 127-131.

  17. Infections in cirrhosis Pharmacokinetics of daptomycin in patients udergoing continuous ambulatory peritoneal dialysis D. Stamadiatis, et al. Perit. Dial. Int. 2003 ; 23 : 127-131.

  18. Infections in cirrhosis Failure of antibiotic treatment of spontaneous bacterial peritonitis (SBP) P. Angeli, et al. Aliment. Pharmacol. Ther. 2006 ; 23 : 75-84.

  19. Infections in cirrhosis Mean cost of treatment per patient with spontaneous bacterial peritonitis (€) * = P < 0.001 * * * P. Angeli, et al. Aliment. Pharmacol. Ther. 2006 ; 23 : 75-84.

  20. Infections in cirrhosis Main multiresistant bacteria isolated in 169 inpatients with cirrhosis and bacterial infections Microrganisms E.Coli Pseudomonas sp . Klebsiella sp. Enterococci Staph aureus 46 3 7 27 7 ESBL-producers 17 - 4 Resistance 34 (76 %) 2 (66%) 4 (57%) 18 (66%) 5 (71%) Quinolones 29 1 3 16 4 Cephalosporins 23 2 3 - - Carbapenems 1 2 - 4 3 Meticillin- - 5 Vancomicina 1 - Preliminary unpublished data of an Italian multicenter study

  21. Infections in cirrhosis Resolution of bacterial infections with cefotaxime or amoxicillin/clavulanic acid in 224 patients with cirrhosis and bacterial infections (%) P < 0.001 P < 0.001 P < 0.005 P = 0.05 J.G. Acevedo et. al. 2009 EASL Meeting

  22. Infections in cirrhosis Geographic distribution of Escherichia Coli strains with a reduced susceptibility to ciprofloxacin in community-acquired UTI in Europe S. Cagnacci et al. J. Clin. Microb. 2008 ; 46 : 2605-2612.

  23. 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 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.

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