Peritonitis

Please note that this page is currently being revised to reflect the ISPD Peritoneal dialysis-related infections recommendations: 2010 Update. 

The below should be considered background information only.

Peritonitis has always been an important complication of PD.  Modern systems have significantly reduced its incidence to typical rates of 0.5 episodes/year or less.  Contributing factors to the reduction of peritonitis are:

• Improved connectology
• Flush-before-fill (disconnect systems)
• Automated peritoneal dialysis

Peritonitis was one of the principal causes of PD technique failure in the 1980’s, but now it is by far superseded by inadequate dialysis.  The peritonitis rates have markedly dropped for CAPD during the last decade with the use of disconnect systems, while that of APD has remained relatively stable.  Nonetheless, lower peritonitis rates for APD are still being reported by the vast majority of investigators when compared to CAPD.

The International Society of Peritoneal Dialysis (ISPD) has published guidelines/recommendations for peritoneal dialysis-related infections since 1996.  The latest update was published in 2005¹².  Click here for ISPD Guidelines. 

In addition, we provide alternate algorithms taking into consideration the ISPD recommendations, but intended to simplify therapy once a decision has been made to use or avoid vancomycin.  Click here for Peritonitis Treatment Algorithms, Table 1 and Table 2

Arguments against abandoning vancomycin and aminoglycosides as empiric treatment of peritonitis and adopting first and third generation cephalosporins

The cure rate for vancomycin and cefazolin have been reported to be equally effective by some^13,14, but not by most^15-17.  Flanigan and Lim¹⁵ compared the initial efficacy of continuous vancomycin and cefazolin in a prospective randomized trial and reported the initial cure rate of vancomycin to be significantly better (84 vs 67%; p = 0.01). Furthermore, the rates of hospitalization, superinfection and relapse were also significantly lower for vancomycin.  Vancomycin was significantly better for both Staphylococcus aureus and for coagulase-negative staphylococcus (CoNS).  Others have also reported lower overall cure rates for cefazolin when compared to vancomycin^16,17.

There is concern about the use of cefazolin due to its lack of efficacy against methicillin resistant organisms, most commonly CoNS.  CoNS are responsible for 15 to 43% of peritonitis episodes and the frequency of resistance to cefazolin ranges from 39 to 88%^18-23.  Methicillin resistance is no longer confined to CoNS organisms.  Over recent years several centers have reported increasing numbers of coagulase positive staphylococci (S. aureus) to be methicillin resistant²³.  Based on this, it may be considered inappropriate to use a regimen that is ineffective in over 20% of all peritonitis episodes and that will delay therapy until the results of cultures and sensitivities become available.  Thus, it is imperative to consider the center’s experience and incidence of methicillin resistant organisms in order to make a responsible choice of empiric therapy. 

Let us now consider the problem with vancomycin resistance.  The incidence of vancomycin-resistant enterococci (VRE) is over 20% in certain locations and VRE are responsible for a significant proportion of peritonitis episodes in other locations^24-26.  Vancomycin—resistant CoNS peritonitis have also been reported^27,28.  More importantly, while not yet reported to cause peritonitis, vancomycin-intermediately sensitive S. aureus (VISA) have been recently identified^29-32. The emergence of these resistance organisms emphasize that vancomycin must not be used indiscriminately.  To this effect, the user is referred to the CDC guidelines for the prevention and spread of vancomycin resistance³³.  These guidelines caution against the use of vancomycin for routine prophylaxis, but does not discourage the responsible use of this antibiotic for empiric therapy of patients when the prevalence of methicillin resistance is substantial.

The use of many antibiotics aside from vancomycin has been associated with the development of VRE infections.  Foremost among them are third generation cephalosporins^24,34.  Some authorities feel that the excessive use of cephalosporins is the driver for the increase in enterococcal infections and their by-product, VRE^18,35.  Actually, the development of VRE has been reported to have been associated with a higher use of cephalosporins (93%) preceding the infection than vancomycin (56%)³⁶. Conversely, other studies suggest that reducing the use cephalosporins may affect the rate of development of  VRE infection²⁵, while reducing the use of vancomycin may not accomplish the same results³⁴. 

A vast body of literature documents the development of ceftazidime-resistant Enterobacteriae  as well as other bacteria, including Klebsiella^37-41.  This resistance results from point mutations within genes that encode widely prevalent and transferable plasmid-mediated enzymes^13,38.  These mutations confer bacteria the ability to hydrolyze cephalosporins and make them resistant to cefazidime and other antibiotics, including penicillins and beta-lactamase inhibitors.      

The aforementioned arguments, based on an extensive body of literature, raise significant concerns regarding the abandonment of vancomycin and aminoglycosides as empiric therapy for peritonitis in peritoneal dialysis.  Despite the remarkable reduction in the rate of peritonitis during the past decade, this complication remains a serious cause of morbidity and technique failure.

What should we do: use cephalosporins only or revert to the use of vancomycin and aminoglycosides for empiric therapy of peritonitis?

This is a complex issue that cannot be delegated to an algorithm.  It requires physician input, based on his knowledge of the specific patient, local epidemiology and quality of the microbiologic facilities in the community.  The frequent previous use of antibiotics in a particular patient and the type of organisms responsible for previous infections should be considered in the selection of therapy.  Recurrent peritonitis should raise the possibilities of inadequate dosing, resistance to previous antibiotics or undiagnosed secondary organisms.  The presence of VRE, methicillin resistant CoNS and coagulase positive staphylococcus or VISA in the community raises another set of questions that should increase the level of suspicion and aggressiveness of treatment.  The ability of the patient to self-administer continuous antibiotic therapy at home and the availability of antibiotics in some regions of the world are also practical considerations in the selection of therapy.  Finally, we should stress the importance of specific therapy based on susceptibility profiles.  Of course, by the time these become available empiric therapy is under way.

References:

1. de Fijter CWH, Oe LP, Nauta JJ, van der MJ, Verbrugh HA, Verhoef J, Donker AJ. Clinical efficacy and morbidity associated with continuous cyclic compared with continuous ambulatory peritoneal dialysis. Ann Intern Med 120:264-271, 1994
2. Gahrmani N, Gorban-Brennan N, Kliger AS, Finkelstein FO. Infection rates in end-stage renal disease patients treated with CCPD and CAPD using the UltraBagTM system.  Adv Perit Dial 11:164-166, 1995
3. Viglino G, Gandolfo C, Virga G, Cavalli PL. Role of automated peritoneal dialysis within a peritoneal dialysis program.  Adv Perit Dial 11:134-138, 1995
4.  Diaz-Buxo JA. Continuous ambulatory and continuous cycling peritoneal dialysis. In: Ronco C (ed). Peritoneal Dialysis. Milano: Wichtig Editore, 1986: 257-264
5. Troidle L, Gorban-Brennan N, Kliger AS, Finkelstein FO. Continuous cycler therapy, manual peritoneal dialysis therapy, and peritonitis. Adv Perit Dial 14:137-141, 1998
6. Locatelli A, Marcos G, Gomez M, Alvarez S, DeBenedetti L.  Comparing peritonitis in continuous ambulatory peritoneal dialysis patients versus automated peritoneal dialysis patients. Adv Perit Dial 15:193-196, 1999
7. Rodríguez-Carmona A, Fontán MP, Falcón TG, Rivera CF, Valdés F. A comparative analysis on the incidence of peritonitis and exit-site infection in CAPD and automated peritoneal dialysis. Perit Dial Int 19:253-258, 1999
8. Perez-Fontan M, Rodríguez-Carmona A, García-Falcón T, Fernández-Rivera C, Valdés F. Incidence of peritonitis (P) and exit site infection (ESI) in CAPD and automated PD (APD).  A comparative study. Perit Dial Int 19(Suppl 1):S35, 1999
9. Bro S, Bjorner J, Tofte-Jensen P, Klem S, Almtoft B, Danielsen H, Meincke M, Friedberg M, Feldt-Rasmussen B. A prospective, randomized multicenter study comparing APD and CAPD treatment. Perit Dial Int 19:526-533, 1999
10. Huang JW, Hung K-Y, Yen CJ, Wu KD, Tsai TJ. Comparison of infectious complications in peritoneal dialysis patients using either a twin-bag system or automated peritoneal dialysis. Nephrol Dial Transplant 16:604-607, 2001
11. Oo TN, Roberts TL, Collins AJ. A comparison of peritonitis rates from the United States Renal Data System database: CAPD versus continuous cycling peritoneal dialysis patients. Am J Kidney Dis 45:372-380, 2005
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15. Flanigan MJ, Lim VS.  Initial treatment of dialysis associated peritonitis: A controlled trial of vancomycin versus cefazolin.  Perit Dial Int 11:31-37, 1991
16. Gucek A, Bren AF, Lindic J, et al.  Is monotherapy with cefazolin or ofloxacin an adequate treatment for peritonitis in CAPD patients? Adv Perit Dial 10:144-146, 1994
17. Alves FR, Dantas RC. Is the treatment of beta lactam sensitive infections without vancomycin possible?  Perit Dial Int 17(Suppl 1): S27, 1997 (Abstract)
18. Teitelbaum I.  Vancomycin for the initial therapy of peritonitis: Don’t throw out the baby with the bathwater.  Perit Dial Int 21:235-238, 2001
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21. Sandoe JAT,  Gokal R, Struthers JK. Vancomycin-resistant enterococci and empirical vancomycin for CAPD peritonitis. Perit Dial Int 17: 617-618, 1997
22. Onozato ML, Caramori JCT, Barretti P. Initial treatment of CAPD peritonitis:  Poor response with association of cefazolin and amikacin. Perit Dial Int 19: 88-89, 1999
23. Mason NA, Zhang T, Messana J.  Methicillin resistance patterns associated with peritonitis in a university-based peritoneal dialysis center. Perit Dial Int 19:483-486, 1999
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29. Hiramatsu K, Aritaka N, Hanaki H, et al.  Dissemination in Japanese hospitals of strains of Staphylococcus aureus heterogeneously resistant to vancomycin.  Lancet  350:1679-1673, 1997
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32. Rotun SS, McMath V, Schoonmaker DJ, et al. Staphylococcus aureus with reduced susceptibility to vancomycin isolated from a patient with fatal bacteremia.  Emerg Infect Dis 5:147-149, 1999
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34. Morris JG, Shay DK, Hebden JN, et al.  Enterococci resistance of multiple antimicrobial agents, including vancomycin: Establishment of endemicity in a university medical center,  Ann Intern Med 123:250-259, 1995
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37. Ballow CH, Shcentag JJ. Trends in antibiotic utilization and bacterial resistance.  Report of the National Nosocomial Resistance Surveillance Group.  Diagn Microbio Infect Dis 15(Suppl 2):37S-42S, 1992
38. Rice LB.  Successful interventions for Gram-negative resistance to extended spectrum beta-lactam antibiotics.  Pharmacotherapy 19(8 Pt 2):120S-128S and 133S-137S, 1999
39. Landman D, Chockalingam M, Quale JM.  Reduction in the incidence of methicillin-resistant Staphylococcus aureus and ceftazidime-resistant Klebsiella pneumonia following changes in a hospital antibiotic formulary.  Clin Infect Dis 28:1062-1066, 1999
40. Mebis J, Goosens H, Bruyneel P, et al.  Decreasing antibiotic resistance of Enterobacteriaceae by introducing a new antibiotic combination therapy for neutropenic fever patients.  Leukemia 12:1627-1629, 1998
41. Meyer KS, Urban C, Eagan JA, et al.  Nosocomial outbreaks of Klebsiella infection resistant to late-generation cephalosporins.  Ann Intern Med 119:353-358, 1993