Gonococcal Peritonitis in a Patient Treated With Continuous Ambulatory Peritoneal Dialysis (CAPD)

Gonococcal Peritonitis in a Patient Treated With Continuous Ambulatory Peritoneal Dialysis (CAPO) Allan B. Wolfson,MD, Irving Nachamkin, DrPH, Irwin Singer, MD, FACp, Charlene M. Moffitt, RN, and Alicia M. Buchan, RN • We report a case of gonococcal peritonitis in a sexually active female on continuous ambulatory peritoneal dialysis. The presumed route of entry into the peritoneal cavity was via the Fallopian tube. The episode responded rapidly to a standard antibiotic treatment protocol. Some episodes of culture-negative peritonitis may be caused by genital tract organisms which are not cultured by routine methods. © 1985 by the National Kidney Foundation, Inc. INDEX WORDS: Peritonitis; chronic ambulatory peritoneal dialysis; Neisseria gonorrhoeae.

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NFECTIOUS PERITONITIS is the most common complication of continuous ambulatory peritoneal dialysis (CAPD). The most common offending organisms are staphylococci (S epidermidis and S au reus ), accounting for 65 % to 75 % of the cases, and enteric gram-negative organisms, accounting for 15 % to 25 %. H Simultaneous catheter tunnel or exit site infections mayor may not be present. In recent years several unusual organisms have been reported to cause peritonitis in this patient population, including Serratia sp, Pasteurella sp, Fusarium sp, Aspergillus sp, Pityrosporum ovale, Rhodotorula sp, and Nocardia asteroides. We report a case of gonococcal peritonitis in a patient treated with CAPD, a most unlikely presentation for this "venereal" disease. CASE REPORT A 17-year-old black female was admitted to the CAPD program at the Hospital of the University of Pennsylvania in July 1983. She was discovered to be hypertensive in 1982 and a diagnosis of focal glomerulosclerosis was made by renal biopsy in January 1983. She progressed to end-stage renal disease (ESRD) with a blood urea nitrogen concentration of 98 mg/dL and a serum creatinine concentration of 13.6 mg/dL by June 1983. The patient was sexually active and underwent therapeutic abortions in February 1982, and February 1983. She had two "heavy" menstrual periods in June 1983 and one in January 1984, but no others; a small amount of blood appeared in the dialysis tubing on one occasion in August 1983. She remained sexually active after entering the CAPD program and had no gynecological complaints. CAPD was uneventful for the first three months of treatment, although there were problems with compliance. An exit-site infection with Group A streptococcus and gram-negative rods (Acinetobacter calcoaceticus, Enterobacter cloacae, and Citrobacter freundii) was successfully treated with a 12-day course of 80 mg trimethoprim/400 mg sulfamethoxazole twice daily. A routine gynecologic outpatient visit in September 1983, re-

vealed no abnormalities on pelvic examination. Cervical and vaginal swab cultures were negative. On January 9, 1984, the patient presented to the CAPD clinic with cramping lower abdominal pain, an oral temperature of 10 I. 8 of, and cloudy peritoneal dialysate. The patient denied nausea and vomiting, and had no gynecologic complaints. Normal bowel sounds were present, and there was no localized abdominal tenderness. The exit site was not tender and appeared normal; there was no evidence of a tunnel infection. There were no joint pains or skin lesions. A pelvic examination was not performed. The cloudy peritoneal dialysate contained 14,800 white blood cells (WBC) (70% neutrophils, 2 % lymphocytes, 28% monocytes) and no red cells (RBC)/mm 3 • Gram stain and India ink preparations revealed no organisms. Cultures of the peritoneal dialysate were obtained (see Microbiology). The patient was treated according to the standard peritonitis protocol: a loading base of 1.0 g cefazolin was given intravenously, and she was instructed to add cefazolin in a dose of 125 mg/L to each peritoneal dialysis exchange. She responded well to therapy after 48 hours, with decreased abdominal pain and an oral temperature of 98.8 oF. However, the peritoneal dialysate remained cloudy and contained 1000 WBC/mm 3 (84 % neutrophils); Gram stain was again negative. Oxidase-positive gram-negative diplococci were isolated 48 hours after obtaining the initial peritoneal dialysate, and subsequently were identified as Neisseria gonorrhoeae. A Rapid Plasma Reagin (RPR) test for syphilis was negative. Repeat dialysate Gram stain and cultures as well as cervical cultures obtained on January 17 failed to reveal gonococci. The peritoneal dialysate contained 350 WBC/mm 3 Because a scanty growth of a coagulase-negative Staphylococcus, sensitive to cephalosporins, was identified in the dialysate, cefazolin From the Department of Medicine and Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia. Address reprint requests to Allan B. Wolfson, MD, Emergency Services Department, Ground Floor Silverstein, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104. © 1985 by the National Kidney Foundation, Inc. 0272-6386/85/0604-0011 $03.00/0

American Journal of Kidney Diseases, Vol VI, No 4, October 1985

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WOLFSON ET AL

258 therapy was continued for a total of 18 days. A repeat dialysate analysis after therapy revealed clear fluid containing < 50 WBC/mm 3 (100% mononuclear cells); Gram stain and culture revealed no organisms.

MICROBIOLOGY

Peritoneal dialysate was submitted to the Clinical Microbiology Laboratory in a dual blood culture bottle system (Tryptic Soy Broth/Thio Broth; Difco Laboratories, Detroit, MI), of which the tryptic soy broth (TSB) bottle was transiently vented. After 48 hours of incubation at 37 DC, a blind subculture to sheep blood agar was made from each bottle. A gram-negative oxidasepositive diplococcus grew from the TSB bottle. The isolate grew well on sheep blood agar, chocolate agar, and selective Thayer-Martin chocolate agar. Although gonococci do not generally grow on ordinary media,4 occasional strains have been isolated on blood agar plates. Identification was based on standard criteria 5: the organism was gram-negative and oxidasepositive, and in cysteine tryptic agar utilized glucose but not maltose, sucrose or lactose. The isolate did not produce beta-Iactamase using the chromogenic cephalosporin assay. 6 An isolate submitted to the Neisseria Research Laboratory at the University of Washington (Seattle, WA; J .S. Knapp) was confirmed to be N gonorrhoeae. Auxotyping studies 7 revealed the organism to require proline (Pro -), a finding previously reported in organisms causing either disseminated or uncomplicated infection. 7.8 Serogrouping with monoclonal antibodies by coagglutination testing 9.10 revealed this organism to be a member of the WII serogroup (serovar IB-9), an uncommon strain which has been isolated in the United States and elsewhere and is thought to have originated in the Far East (l.S. Knapp: Personal communication, February 2, 1984). DISCUSSION

In the long term, recurrent peritonitis is the most serious complication of CAPD. Gram-positive cutaneous organisms, predominantly Staphylococcus, and gram-negative enteric organisms are most commonly implicated, and presumably gain access to the peritoneal cavity by inadvertent contamination of the catheter or by direct invasion from an infected catheter tunnel or exit site. Polymicrobial infection implies contamination by intestinal or genitourinary flora, and suggests communication between one of these organ systems and the peri to-

neal cavity. 1112 In some cases of clinical peritonitis (WBC > lOO/mm3; neutrophils > 50%) no organism is found by Gram stain or culture, but the episode clears with standard antimicrobial therapy. Possible causes for apparently "sterile" peritonitis include: infection with slow-growing or fastidious organisms; partially treated infection due to previous antibiotic administration; inadequate processing or culturing techniques; and noninfectious causes. The recent introduction of improved culturing techniques has apparently decreased the incidence of "sterile" peritonitis. I - 3 In this paper we report a case of bacterial peritonitis due to N gonorrhoeae in a sexually active female CAPD patient. Since no external route of infection was demonstrated in our patient, the presumed route of entry into the peritoneal cavity was via the Fallopian tube. Such a connection clearly may be present, as demonstrated by retrograde menstruation reported by Blumenkrantz et aP3 in women on CAPD. These patients did not have clinical peritonitis and did not have salpingitis. Retrograde menstruation may occur in all normal women and may account for the frequent clinical onset of pelvic inflammatory disease around the time of the menses. 14.15 The appearance of blood in the dialysis tubing in our patient in August 1983 might have represented retrograde menstruation. Gonococcal peritonitis secondary to salpingitis or pelvic abscess, though not common, is well recognized in the nonCAPD population. 15.16 The leakage of peritoneal fluid into the vagina in CAPD patients is also evidence of an open pathway, and there have been several reports of peritonitis due to vaginal flora (including Candida sp) in such cases. 12 17-20 The peritoneal origin of the vaginal fluid was inferred from its high glucose concentration and/or by the appearance in the vagina of methylene blue instilled intraperitoneally. In several patients the communication was demonstrated by hysterosalpingography or by direct visualization at laparotomy,12.17.19.20 and in these cases the fallopian tubes appeared to be anatomically abnormal or damaged. Bilateral tubal ligation stopped the leakage and prevented further episodes of peritonitis. Direct communication via a peritoneo-vaginal fistula has been observed in one case. 21 The fistula was attributed to erosion produced by the Tenckhoff catheter; the Fallopian tubes were demonstrated to be closed. One case of CAPD-related peritonitis due to Gardnerella va-

GONOCOCCAL PERITONITIS IN CAPO

ginalis has been reported. 22 The route of infection was not determined but presumably was via the Fallopian tube. Peritonitis in CAPD patients could also in theory result from bacteremia with seeding of the dialysis fluid in the peritoneal cavity. Although uncommon, our isolate has been associated with disseminated gonococcal infections. 7 . 8 However, our patient had no evidence of septicemia or disseminated gonococcal infection at any time in her course. Recommended treatment schedules for gonococcal infection do not include first-generation cephalosporins such as cefazolin,2324 although prior to the advent of the newer cephalosporins there had been some experience with their use. 16 Although treatment with cefazolin was successful in our case, probably because of the extremely high steady-state serum and peritoneal fluid levels produced by our standard peritonitis protocol,25.26 the treatment of choice of CAPD-associated gonococcal peritonitis is unknown. Penicillin has been shown to lose approximately 25 % of its antimicrobial activity when stored in the acid peritoneal dialysate medium (pH approximately 5.2) for 24 hours at room temperature,26 but in vivo the dialysate reaches neutral pH within 30 to 60 minutesY The fate of penicillin when exposed to acid dialysate at body temperature for the first 30 to 60 minutes of dialysis is not clear. Intraperitoneal penicillin may be effective treatment for this type of peritonitis, but to our knowledge no clinical information about such therapy is available. Ampicillin has been shown to be stable in peritoneal dialysate and would appear to be another reasonable choice for treatment,29 as would the thirdgeneration cephalosporin cefotaxime. 24 .29 Meticulous culturing techniques may be needed to isolate unusual or fastidious peritoneal pathogens and to decrease the incidence of culturenegative ("sterile") peritonitis in CAPD patients. 23.22 Blood culture bottle techniques, such as the dual system used in the present case, do not permit the use of concentration procedures which increase the yield of positive cultures when organisms are present in low numbers. In addition, blood culture media usually contain sodium polyanethol sulfonate, an anticoagulant that may inhibit the growth of certain organisms, including gonococci. 30.31 At present we recommend that a 50-mL syringe of peritoneal dialysate be sent directly to the labo-

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ratory for centrifugation and the concentrated material cultured on both aerobic and anaerobic media. Recently a new technique has been recommended in which growth medium is injected into an entire bag of peritoneal dialysate for incubation, with subsequent subculture onto other media. 32 The identification of several female genital tract organisms as causes of CAPD-associated peritonitis suggests that some episodes of culturenegative peritonitis may be due to genital tract organisms which are not cultured by routine methods. For example, chlamydia has been incriminated as a cause of salpingitis and associated peritonitis ,33.34 although we are unaware of any reports of these fastidious organisms causing CAPD-related peritonitis. We suggest that clinicians caring for CAPD patients be alert to the possibility of "venereal" disease in CAPD patients, particularly to the possibility that female genital tract organisms may cause peritonitis in sexually active females. These organisms may require special techniques to be identified, and may be a cause of culture-negative "sterile" peritonitis if such techniques are not used. ACKNOWLEDGMENT The authors thank Dr Joan S. Knapp, Neisseria Reference Laboratory, University of Washington, for performing auxotyping and serotyping on our isolate. We would also like to express our appreciation to Patricia Laird for her expert secretarial assistance.

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260 atypical Neisseria gonorrhoeae from disseminated and localized infections. Infect Immun 13:1510-1516,1976 9. Lewis JS, Martin JE: Evaluation of the Phadebact gonococcus test, a coagglutination procedure for confirmation of Neisseria gonorrhoeae. J Clin Microbiol 11: 153-156, 1980 10. Sandstrom EG, Knapp JS, Buchanan TB: Serology of Neisseria gonorrhoeae: W-antigen serogrouping by coagglutination and protein I serogrouping by enzyme-linked immunosorbent assay both detect protein I antigens. Infect Immun 35:229-239, 1982 II. O'Connor J, MacCormick DE: Mixed organism peritonitis complicating continuous ambulatory peritoneal dialysis. New Zealand Med J 95:811-812, 1982 12. Swartz RD, Campbell DA, Stone D, et al: Recurrent polymicrobial peritonitis from a gynecologic source as a complication of CAPD. Perit Dial Bull 3:32-33, 1983 13. Blumenkrantz MJ, Gallagher N, Bashore RA, et al: Retrograde menstruation in women undergoing chronic peritoneal dialysis. Obstet Gynecol 57:667-670, 1981 14. Eschenbach DA: Pelvic inflammatory disease, in Isselbacher KS, Adams RD, Braunwald E, et al (eds): Harrison's Principles of Internal Medicine (ed 9), Update III. New York, McGraw-Hili, 1981, pp 67-81 15. Douglas GW: Infections of the reproductive tract, in Danforth DN (ed): Textbook of Obstetrics and Gynecology (ed 2). New York, Harper & Row, 1971, pp 862-879. 16. Sparling PF: Neisseria gonorrhoeae, in Mandell GL, Douglas RG Jr, Bennett JE (eds): Principles and Practice of Infectious Diseases. New York, Wiley, 1979, pp 1655-1666 17. Alexander SR, Tank ES: Surgical aspects of continuous ambulatory peritoneal dialysis in infants, children and adolescents. J Urol 127:501-504, 1982 18. Vas S: Discussion on microbiological aspects of peritonitis. Perit Dial Bull l(supp):SI4-S16, 1981 19. Coward RA, Gokal R, Wise M, et al: Peritonitis associated with vaginal leakage of dialysis fluid in continuous ambulatory peritoneal dialysis. Br Med J (Clin Res) 284: 1529, 1982 20. Wright CA, Moran J, Silk D: Is peritoneal-vaginal fistula the main cause of fungal peritonitis in female CAPD patients? Perit Dial Bull 4:51, 1984 (letter) 21. Diaz-Buxo JA, Burgess P, Walker PJ: Peritoneovaginal fistula-unusual complication of peritoneal dialysis. Perit Dial Bull 3:142-143, 1983

WOLFSON ET AL 22. DePaepe M, Lameire N, Claeys G, et al: Gardnerella vagina lis (Hemophilus vagina/is), an unusual cause of peritonitis in CAPD. Clin Exper Dial & Apheresis 6: 197-204, 1982 23. Centers for Disease Control: Sexually transmitted diseases treatment guidelines 1982. Morbidity and Mortality Weekly Report 31:37S-42S, 1982 24. Med Lett Drugs Ther, 26:5-10, 1984 25. Neu HC, Meropol NJ, Fu KP: Antibacterial activity of ceftriaxone (Ro 13-9904), a beta-Iactamase-stable cephalosporin. Antimicrob Agents Chemother 19:414-423, 1981 26. Turck M: Cephalosporins and related beta-Iactam antibiotics, in Isselbacher KS, Adams RD, Braunwald E, et al (eds): Harrison's Principles of Internal Medicine (ed 9), Update I. New York, McGraw-Hill, 1981, pp 231-244 27. Sewell DL, Golper TA: Stability of antimicrobial agents in peritoneal dialysate. Antimicrob Agents Chemother 21:528529, 1982 28. Duwe AK, Vas SI, Weatherhead JW: Effects of the composition of peritoneal dialysis fluid on chemilumine~cence, phagocytosis, and bactericidal activity in vitro. Infect Immun 33:130-135,1981 29. Sewell DL, Golper TA, Brown SD, et al: Stability of single and combination antimicrobial agents in various peritoneal dialysates in the presence of insulin and heparin. Am J Kidney Dis 3:209-212, 1983 30. Staneck JL, Vincent S: Inhibition of Neisseria gonorrhoeae by sodium polyanethol sulfonate. J Clin Microbiol 13:463-467, 1981 31. Eng J: Effect of sodium polyanethol sulfonate in blood cultures. J Clin Microbiol 1:119-123, 1975 32. Dawson MS, Harford AM, Garner BK, et al: A new culture technique for the recovery of micro-organisms from CAPD patients with peritonitis. Ann Meet, Am Soc Microbiol 1984, C-244, P 277 (abstract) 33. Eschenbach DA, Buchanan TM, Pollock HM, et al: Polymicrobial etiology of acute pelvic inflammatory disease. N Engl J Med 293:166-171,1975 34. Muller-Schoop J\V, Wang SF, Muziger J, et al: Chlamydia trachomatis as possible cause of peritonitis and perihepatitis in young women. Br Med J (Clin Res) I: 1022-1024, 1978