PERITONITIS IN CAPD: RELAPSE OR REINFECTION?

PERITONITIS IN CAPD: RELAPSE OR REINFECTION?

238 tested in rats three bacteristatic antibiotics for the prevention of endocarditis due to 3 different S. viridans strains, with ID90 as challenge i...

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238 tested in rats three bacteristatic antibiotics for the prevention of endocarditis due to 3 different S. viridans strains, with ID90 as challenge inoculum. We used doses that produced serum levels similar to those reached in men after the usual oral dose (i.e., doxycycline 200 mg, erythromycin 500 mg, and clindamycin 450 mg). Only clindamycin was successful against all 3 strains. Erythromycin used against a strain of S. intermedius in rats,8 and a strain of S. sanguis in rabbits,9 was protective only at doses that resulted in serum levels far above those achieved after the usual 500 mg oral dose in man. We realise that the Working Party could not agree on the relevance to man of animal experiments. However, they recommended "bactericidal" antibiotics, probably because experiments in rabbits had suggested that killing was a mechanism of prophylaxis. Our in vitro studies on the successful prophylaxis achieved with amoxycillin in vivo challenge this mode of action. A single dose of amoxycillin seems adequate for patients at low risk, but other antibiotics, including bacteristatic ones, might be just as effective and at doses that are lower and, possibly, cheaper. We have concerns about other recommendations. For patients at high risk, will a single dose of a combination of amoxycillin and gentamicin really be more effective than amoxycillin alone; this combination was not more effective in animals. The doubts applies particularly to patients with prosthetic heart valves undergoing a dental procedure. There is experimental evidence that a foreign body increases considerably the sensitivity of sterile vegetations to infection from Escherichia co/iIo and from S. intermedius (unpublished) and that the presence of a foreign body diminishes a thousand-fold the efficacy of antibiotics for the prophylaxis of endocarditis. 11 For patients with prosthetic heart valves, we follow recommendations of the American Heart AssociationI2 of multiple doses regimens that give long lasting serum levels and a chance for killing the bacteria. We would caution against the extensive use of erythromycin as a "second choice" antibiotic because this antibiotic is only partly successful in animals, and prophylactic failures have been described in man. 13 The dose recommended by the Working Party is higher than the one usually prescribed, and might therefore be as effective as low doses of clindamycin. We do agree with the Working Party’s last recommendation-that patients at risk must carry with them a warning to the dentist. We have seen too many cases of endocarditis after dental procedures in patients known to be at risk but not given prophylaxis.

Division of Infectious Diseases, Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland

M. P. GLAUSER P. FRANCIOLI P. MEYLAN PH. MOREILLON E. HERAÏEF

PERITONITIS IN CAPD: RELAPSE OR REINFECTION?

SIR,-The major limitation on continuous ambulatory peritoneal dialysis (CAPD) is recurrent peritonitis. Dr Gokal and colleagues (Dec. 18, p. 1488) describe recurrences which, even with extended courses of antibiotics, occurred in 21% of episodes in the last year 8. Glauser MP, Francioli P. Successful prophylaxis of experimental streptococcal endocarditis with bacteriostatic antibiotics. J Infect Dis 1982; 146: 806-10. 9. Pelletier LL, Durack DT, Petersdorf MG. Chemotherapy of experimental streptococcal endocarditis IV: Further observations on prophylaxis. J Clin Invest 1975; 56: 319-30. 10. Heraïef E, Glauser MP, Freedman LR. Natural history of aortic valve endocarditis in rats. Infect Immun 1982; 37: 127-31 11. Heraïef E, Glauser MP, Freedman LR. Vancomycin prophylaxis of streptococcal endocarditis in the rat. In: Nelson JD, Grassi C, eds. Current chemotherapy and infectious diseases Proceedings of the 11th International Congress of Chemotherapy and the 19th Interscience Conference on Antimicrobial Agents and Chemotherapy. Washington: American Society of Microbiology, 1980, 911-13. 12. American Heart Association Committee on Rheumatic Fever and Bacterial endocarditis: Prevention of bacterial endocarditis. Circulation 1977; 56: 139A-143A. 13.

Eng MHK, Wolff M, Smith SM. Failure of erythromycin endocarditis. Arch Intern Med 1982; 142: 1958-59.

episodes of peritonitis (A) and from start of CAPD episode (B). Solid bars 1st to 2nd episode; broken bars 2nd, 3rd, and subsequent episodes. Intervals between to 1st

=

=

reported by them. They chose an interval of 10 days from the end of antibiotic therapy as the criterion for "recurrent" infection. Can relapse and reinfection be distinguished in terms of intervals between episodes? This is important to the estimation of the success rate of antibiotic therapy and to the consideration of preventive measures.

We have reviewed our experience of peritonitis in CAPD, having with a 3 week latency in a patient whose catheter was "locked off" after renal transplantation. We have treated thirty-one patients for 329 patient-months. Peritonitis was diagnosed by criteria identical to those ofGokal et al. and others.1 Initial treatment was cefuroxime 1 -5gintravenously followed by 200 mg/1 added to four exchanges of fluid daily. This was continued for 10 days if cultures indicated sensitive organisms or no growth was recorded. For resistant organisms gentamicin or vancomycin were introduced. Nineteen patients have had one or more episodes of peritonitis. Eleven patients have had more than one with a mean interval between episodes of 2-6±2-7months (range 1 week to 10.55 months). This contrasts with a mean time from starting CAPD to the first episode of peritonitis of 5-2±3’0months (range 1-14-55 months) for all nineteen patients (p<0-05) (figure). The two patients with the longest intervals between first and second episodes (7 and 10,5 months) had unusually prolonged initial antibiotic courses (of 4 or more weeks). If these two patients are excluded from the analysis the mean interval between episodes falls to 1-8±1’ 18 months (range 1 week to 5 months) and the comparison becomes more significant (p<0 01). The interval to a second episode (figure), when effluent had cleared throughout the course of treatment, showed no clear pattern. Recurrence was irrespective of the last antibiotic used. Ten patients have been on CAPD for a mean of 8±4 months (range 2-15 months) without infection. No differences were apparent between spike (220 patient-months) and luer lock (109 patient-months) systems. The clustering of first, second, and subsequent episodes would, in most instances, have been thought due to reinfection. This is implausible, however, since after an episode of peritonitis patients were re-motivated and re-educated in technique and their equipment was checked. We suspect, not reinfection, but relapse caused by inadequate treatment of the first episode. Intraperitoneal cefuroxime2 was used in all nineteen initial episodes of peritonitis and in eight of the subsequent episodes where it was thought that previous infection had responded. If treatment failure is defined as recurrence during treatment or within 6 weeks of the antibiotic course the failure rate for cefuroxime was 33% for culture-negative peritonitis and 60% for identified sensitive organisms. This would be reason enough to change antibiotic policy. seen a recurrence

1. in preventing bacterial

2.

Golper TA, Bennett WM, Jones SR. Peritonitis associated dialysis. Dialysis Transplant 1978; 7: 1173. Editorial. Ambulatory peritonitis. Lancet 1982; i: 1104-05.

with chronic

peritoneal

239

experience of relapse because if relapse is common published peritonitis rates will reflect treatment failure rather than technical failure. This could have considerable implications for patient management, especially with regard to Other units should indicate their

catheter replacement at an early stage, and certainly before patients declared unsuitable for CAPD. Removal of the catheter is a step already considered essential in fungal peritonitis.3In vitro experiments have demonstrated colonisation of intravenous catheters by staphylococci which then produce a protective covering of "slime"4and scanning electron microscopy of CAPD catheters has shown bacterial persistence in fibrin deposits.5 These findings may explain a tendency to relapse in

were

coagulase-negative

peritonitis. The duration of antibiotic

therapy may

well have

to

be further

extended.

on

We conclude that there is

no

need for routine folic acid

supplements in patients on haemodialysis or CAPD, provided they are eating an adequate mixed diet, which is the policy in most renal units nowadays. Department of Nephrology, Christchurch Hospital, Christchurch,

C. P. SWAINSON

New Zealand Medical Renal Unit,

We thank Dr A. M. Davison whose

Department of Renal Medicine. St James’s University Hospital, Leeds LS9 7TF

study period the mean Hb of the patients remaining haemodialysis and those patients who transferred to CAPD was unchanged, while in patients starting CAPD the mean Hb rose (p<0’02) (see table). There were no changes in MCV. Mean plasma folate (see table) and red cell folate values were normal at the end of the study, with no differences between the groups. At the end of the

patients

are

included in these data.

E. J. WILL D. J. READ B. KINGSWOOD

Royal Infirmary, Edinburgh EH3 9YW

R. J. WINNEY

HOW RELIABLE, IN TERMS OF ONCOGENIC DEVELOPMENT, ARE FUNCTIONAL MARKERS OF

COLORECTAL CANCER? DO DIALYSIS PATIENTS NEED EXTRA FOLATE?

SIR,-Patients on regular haemodialysis usually receive folic acid supplements because of loss of this water-soluble vitamin across the dialysis membraneand as a hangover from the old days of protein restriction. Folic acid loss during dialysis is equivalent to a daily loss only slightly greater than urinary excretion in normal subjects, and a retrospective study found no evidence of folate deficiency in patients who had been on haemodialysis without folate supplements for an average of 2 yearsWe wish to briefly report the results of withdrawal of folic acid supplements in a small group of patients on regular dialysis for chronic renal failure. Twelve patients, aged 34-69 years (mean 56), were studied. Nine had been on haemodialysis for at least a year and had been taking folic acid 5 mg, vitamin C 200 mg, ferrous iron 160 mg, and ’Aneurin-Co Forte’ two tablets daily. The folic acid supplement was withdrawn. Six patients continued haemodialysis and three were

changed to continuous ambulatory peritoneal dialysis (CAPD). The other three patients started CAPD without previous haemodialysis; they had never received folic acid supplements. All patients took aluminium hydroxide (’Aludrox’) 10-20 ml daily before meals. Haemoglobin (Hb) and mean corpuscular volume (MCV) were measured monthly on a Coulter counter, and serum and red cell folate concentrations were measured by radioimmunoassay at entry and at 6 and 12 months. No patient received a blood transfusion in the 3 months before withdrawal of folic acid or during the study

period. 3. Khanna R, Oreopoulos DG, Vas S, et al. Fungal peritonitis in patients undergoing chronic intermittent or continuous ambulatory peritoneal dialysis. Proc EDTA 1980; 17: 291-96. 4. Peters G, Locci R, Pulverer G. Adherence and growth of coagulase negative staphylococci on surfaces of intravenous catheters. J Inf Dis 1982; 146: 479-82. 5. Schuenemann B, Schwartz P, Mergerian H, et al. Fibrin coating of the peritoneal catheter as a cause of recurrent peritonitis. In: Gahl GM, Kessel M, Nolph KD, eds. Advances in peritoneal dialysis. Amsterdam: Excerpta Medica, 1981: 296-98. I Johns DG, Sperti S, Burgen A. The metabolism of titrated folic acid in man. J Clin Invest 1961; 40: 1684-95. 2. Cunningham J, Sharman VL, Goodwin FJ, Marsh FP. Do patients receiving haemodialysis need folic acid supplements? Br Med J 1981; 282: 1582. HAEMOGLOBIN AND SERUM FOLATE VALUES

SiR,—DrJass (Jan. 1/8, p. 28) presents an interesting hypothesis about the development ofcolorectal carcinoma. Two separate sets of putative factors are assumed to be necessary: those leading to cytological and architectural atypia of tubular adenomas combined with those producing functional changes as disclosed inmetaplastic polyps. Such functional changes, common to carcinomas and metaplastic polyps, include increased expression of carcinoembryonic antigen (CEA) and absence of cytoplasmic secretory IgA. In our opinion, however, these changes are not necessarily indicators of oncogenic development. Like Jass we have shown that metaplastic polyps are strongly positive for CEA, whereas secretory component and epithelial IgA are much reduced compared with normal colonic epithelium.’ Nevertheless, the same pattern was found for these makers in reactive hyperplasia in ulcerative colitis,2 and in the reactively altered transitional mucosa adjacent to carcinomas.3 The functional changes must in these cases be considered as epiphenomena. Moreover, in ulcerative colitis with dysplasia, and in adenomas with marked dysplasia, CEA expression was not significantly increased compared with that in normal colonic mucosa.l2 Our studies contradict the reports of Isaacson and Le Vann4and Isaacson5and we were, in addition, unable to support Isaacson’sclaim that absence of secretory component is a conclusive marker of dysplasia in ulcerative colitis. It is difficult to reconcile the hypothesis of Jass with what is known about the two functional epithelial markers, CEA and secretory IgA. Increased expression of CEA and reduced epithelial uptake of IgA in hyperplastic polyps may reflect a certain proliferative activity unrelated to oncogenesis. This does not exclude the possibility that occasional mutant clones may emerge and give rise to rare carcinomas in hyperplastic polyps, as observed by us and others. Department of Paediatrics and Institute of Pathology, Rikshospitalet, Oslo 1, Norway

T. O. ROGNUM P. BRANDTZAEG

1. Rognum TO, Fausa O, Brandtzaeg P. Immunohistochemical evaluation of carinoembryonic antigen, secretory component, and epithelial IgA in tubular and villous large-bowel adenomas with different grades of dysplasia. Scand J Gastroenterol 1982; 17: 341-48.

Rognum TO, Elgjo K, Fausa O, Brandtzaeg P. Immunohistochemical evaluation of carcinoembryonic antigen, secretory component, and epithelial IgA in ulcerative colitis with dysplasia. Gut 1982; 23: 123-33. 3. Rognum TO, Elgjo K, Brandtzaeg P, Oerjasaeter H, Bergan A. Plasma CEA levels and immunohistochemical patterns of epithelial marker antigens in patients with large bowel carcinoma. J Clin Pathol 1982; 35: 922-33. 4. Isaacson P, Le Vann HP. The demonstration of carcinoembryonic antigen in colorectal carcinoma and colonic polyps using an immunoperoxidase technique. Cancer 1976; 2.

38: 1348-56. 5. Isaacson P. Tissue demonstration of carcinoembryonic colitis Gut 1976; 17: 561-67. 6 Isaacson P. Immunoperoxidase study of the secretory

colonic

neoplasia. J Clin Pathol 1982; 35: 14-25.

antigen (CEA)

in ulcerative

immunoglobulin system

in