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Peritonitis: Empiric Treatment -- Should we follow the ISPD Guidelines?
Jose A. Diaz-Buxo, MD, FACP |
Based on the emergence of vancomycin resistance, the International Society of Peritoneal Dialysis (ISPD) first recommended in 1996, and later reiterated in 2000, recommendations for the empiric treatment of peritonitis in adult patients (1,2). These guidelines recommended a first generation cephalosporin (cefazolin or cephalothin) to substitute vancomycin and a third generation cephalosporin (ceftazidime) or an aminoglycoside to cover Gram negative organisms. The elimination or reduction of vancomycin and aminoglycosides as empiric therapy for peritonitis also was intended to reduce ototoxicity and nephrotoxicity, another noble consideration. The actions of the ISPD Ad Hoc Advisory Committee for Peritonitis Management were based on evidence (whenever available) and expert consensus and left the final selection of antibiotics to the best judgement of the practicing physician (3). Several recent editorials and letters to the ISPD have revisited the guidelines and offered important criticism to be considered in the final determination of empiric therapy for peritonitis (4-6). The following discussion is intended to emphasize the complexity of the issues at hand and to offer an alternative to the ISPD guidelines according to the specific circumstances affecting the patient, geographic location and local bacterial flora and physician choice.
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, (6,7) but not by most.8-10 Flanigan and Lim (8) 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 (9,10).
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% (4,5,11-14). 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 resistant (14) 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 (15-17). Vancomycin—resistant CoNS peritonitis have also been reported (18,19). More importantly, while not yet reported to cause peritonitis, vancomycin-intermediately sensitive S. aureus (VISA) have been recently identified (20-23). 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 resistance (24). 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 (15,25). Some authorities feel that the excessive use of cephalosporins is the driver for the increase in enterococcal infections and their by-product, VRE (4,26). 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%) (27). Conversely, other studies suggest that reducing the use cephalosporins may affect the rate of development of VRE infection,(16) while reducing the use of vancomycin may not accomplish the same results (25).
A vast body of literature documents the development of ceftazidime-resistant Enterobacteriae as well as other bacteria, including Klebsiella (28-31). This resistance results from point mutations within genes that encode widely prevalent and transferable plasmid-mediated enzymes (6,29). 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 not allow any set of guidelines or recommendations to supercede susceptibility results. Both the ISPD Ad Hoc Committee and the various critics to their recommendations stress the importance of specific therapy based on susceptibility profiles. Of course, by the time these become available empiric therapy is under way.
Editorial Note: This article first appeared in the PDServe Connection newsletter Vol 6, No 2, 2002.
PDServe™ has developed comprehensive algorithms for the treatment of peritonitis and exit site infections in PD patients based on the ISPD guidelines and other current literature on this topic. To view these, please visit the "All about PD" and click on "Peritonitis and other infectious complications", the "Peritonitis Treatment Algorithms"
References
1 - Keane WF, Alexander SR, Bailie GR, et al. Peritoneal dialysis-related peritonitis treatment recommendations: 1996 update. Perit Dial Int 16:557-573, 1996
2 - Keane WF, Bailie GR, Boeschoten E, et al. ISPD Guidelines / Recommendations. Perit Dial Int 20:396-411, 2000
3- Vas S. Dr. Vas Replies (Letter to the Editor) Perit Dial Int 21:320-321, 2001.
4- Teitelbaum !. Vancomycin for the initial therapy of peritonitis: Don't throw out the baby with the bathwater. Perit Dial Int 21:235-238, 2001
5- Hockensmith ML, Madinger NE, Teitelbaum I. Concerns regarding recommendations for the treatment of CAPD peritonitis. Perit Dial Int 21:317-319, 2001
6- Korzets Z, Lang R. On the recent recommendations of the Ad Hoc Advisory Committee on the Peritonitis Management – Or should ceftazidime be used as initial empiric therapy? Perit Dial Int 21:319-320, 2001
7- Kent JR, Almond MK. A survey of CAPD peritonitis management and outcomes in north and south Thames NHS regions (U.K.): Support of the ISPD Guidelines Perit Dial Int 20: 301-305, 2000
8- Flanigan MJ, Lim VS. Initial treatment of dialysis associated peritonitis: A controlled trial of vancomycin versus cefazolin. Perit Dial Int 11:31-37, 1991
9- 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
10- Alves FR, Dantas RC. Is the treatment of beta lactam sensitive infections without vancomycin possible? Perit Dial Int 17(Suppl 1):S27, 1997 (Abstract)
11- Vas S, Bargman JM, Oreopoulos DG. Treatment in PD patients of peritonitis caused by Gram-positive organisms with single daily dose of antibiotics. Perit Dial Int 17:91-94, 1997
12- Sandoe JAT, Gokal R, Struthers JK. Vancomycin-resistant enterococci and empirical vancomycin for CAPD peritonitis. Perit Dial Int 17:617-618, 1997
13- 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
14- 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
15- Perl TA. The threat of vancomycin resistance. Am J Med 106(5A):26S-37D, 1999
16- Murray BE. Drug therapy: Vancomycin-resistant enterococcal infections. N Engl J Med 342:710-721, 2000
17- Troidle L, Kliger AS, Gorban-Brennan N, et al. Nine episodes of CPD-associated peritonitis with vancomycin resistant enterococci. Kidney Int 50:1368-1372, 1996
18- Schwalbe RS, Spapleton Jt, Gilligan PH. Emergence of vancomycin resistance in coagulase-negative staphylococci. N Engl J Med 316:927-931, 1987
19- Sanyal D, Johnson AP, George RC, et al. Peritonitis due to vancomycin-resistant Staphylococcus epidermidis. Lancet 337:54, 1991
20- 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
21- Smith TL, Pearson TL, Wilcox KR, et al. Emergence of vancomycin-resistance in Staphylococcus aureus. N Engl J Med 340:493-501, 1999
22- Sieradzki K, Roberts RB, Haber SW, Tomasz A. The development of vancomycin resistance in a patient with methicillin-resistant Staphylococcus aureus infection. N Engl J Med 340:517-523, 1999
23- 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
24- Hospital Infection Control Practices Advisory Committee. Recommendations for preventing the spread of vancomycin resistance. Infect Control Hosp Epidemiol 16:105-13, 1995
25- 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
26- Barlett JG, Bradley SF, Herwaldt LA, et al. A roundtable discussion of antibiotic resistance: Putting the lessons to work. Am J Med 106(5A):48S-52S, 1999
27- Uttley AHC, George RC, Naidoo J, et al. High-level vancomycin-resistant enterococci causing hospital infections. Epdemio Infect 103:173-181, 1989
28- 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
29- 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
30- 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
31- 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
32- 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
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Last modified Monday, July 25, 2005
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