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Meconium stimulates a pro-inflammatory response in peritoneal macrophages: implications for meconium peritonitis.

BACKGROUND/PURPOSE: Although meconium peritonitis is a rare condition, the mortality rate can be as high as 40%. Meconium peritonitis is a result of intestinal perforation in utero, which leads to dense inflammation in the peritoneal cavity. The fetus has relatively immature peritoneal defense mechanisms, so the cause of this dense inflammation is unclear. The peritoneal macrophage is a key cell in the peritoneal inflammatory response in adults. The purpose of this investigation was to determine if sterile meconium had a direct stimulatory effect on the peritoneal macrophage. METHODS: Peritoneal macrophages were harvested from adult C3H/HEN mice. The cells were placed in microtiter wells at 10(5) cells per well. Sterile human meconium was diluted in media and placed in the wells at varying concentrations for 8 hours. Lipopolysaccharide (LPS) (10 microg/mL) served as a positive control. Supernatants were harvested and assayed for tumor necrosis factor alpha (TNF-alpha) using a commercial ELISA kit. Separate cells were assayed for TNF-alpha message using polymerase chain reaction (PCR). In another series of experiments, procoagulant activity (PCA) was determined on freeze-thawed cells using a two-stage amidolytic assay. To test for the role of protein kinase C (PKC) in the PCA response H7, a PKC inhibitor, was used as well. RESULTS: Meconium stimulation resulted in a significant increase in TNF-alpha compared with negative controls with a peak at 0.1% meconium (121 pg/mL v 11 pg/mL, P<.05). There was a significant increase in PCA, with a 10-fold increase with 1% meconium compared with controls (P<.05). This response was limited to less than 5% by PKC inhibition. CONCLUSIONS: Sterile meconium results in a marked proinflammatory response in the peritoneal macrophage with elevations of both PCA and TNF-alpha. The TNF response is likely mediated at a pretranscriptional level because there is a marked increase in TNF mRNA. These data suggest that the PCA response is regulated by a PKC mechanism similar to LPS. Stimulation of the peritoneal macrophage by meconium is a possible cause of the marked inflammation seen in meconium peritonitis.

Animals↗

Peritonitis in continuous ambulatory peritoneal dialysis: impact of a compulsory switch from a standard to a Y-connector system in a single North American Center.

One hundred one continuous ambulatory peritoneal dialysis (CAPD) patients from a single North American center were analyzed in a retrospective and cross-over study for peritonitis rates using a standard system (Travenol System II) or a Y-shaped disconnect-disinfectant system (Travenol O-set). Twenty-one of 34 patients using the standard set (group I) had 53 episodes of peritonitis in 508 patient-months or one episode per 9.6 patient-months. Nine of 17 patients switching from the standard to the disconnect-disinfectant system (group II) experienced 22 episodes of peritonitis in 275 patient-months or one episode per 12.5 patient-months on the standard set, while six patients had 10 episodes of peritonitis in 275 patient-months or one episode per 27.5 patient-months on the disconnect-disinfectant system (P less than 0.04). Twenty-eight of 67 new CAPD patients starting on the disconnect-disinfectant system (group III) had 37 episodes of peritonitis in 1,086 patient-months or one episode per 29.4 patient-months (P less than 0.01 v group I). Exit-site infections (ESI) occurred in 35.3% of patients using the standard set versus 34.3% of those using the O-set. The presence of an ESI was not associated with a higher risk of peritonitis, but modified the bacteriological profile of subsequent peritonitis episodes in patients using the O-set, favoring the organisms isolated from the exit site. Decreases in peritonitis rates with the O-set were due to a reduction of peritonitis episodes secondary to most bacterial agents and not only to skin organisms. Diabetics using intraperitoneal insulin had similar peritonitis and ESI rates as nondiabetics.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Acute changes in peritoneal morphology and transport properties with infectious peritonitis and mechanical injury.

Peritoneal clearance studies were performed in rats undergoing acute peritoneal dialysis. Some of these animals were then exposed to laparotomy and mechanical drying of the peritoneum. Peritoneal clearance studies were repeated at intervals up to 11 days. Another group of rats was placed on daily peritoneal dialysis and allowed to spontaneously develop peritonitis which was not treated. These rats underwent peritoneal transport studies at differing durations of infection. In all groups, animals were sacrificed at the time of the last transport studies for morphological assessment of the peritoneum by light microscopy, scanning electron microscopy, and transmission electron microscopy. The results showed similar decreases in drainage volume and increases in glucose absorption and protein losses with both infection and drying. Both types of injury resulted in extensive mesothelial structural changes. While drying caused mainly denudation of the mesothelial surface, infectious peritonitis was associated with separation of mesothelial cells, and the appearance of numerous white blood cells between and on mesothelial cells. Exposure to peritoneal dialysis alone had no obvious effects on anatomy. Although changes in the peritoneal microcirculation and deeper structures cannot be excluded as contributing to peritoneal transport alterations, the findings suggest that alterations of mesothelium might explain some of the changes in peritoneal transport properties under the conditions of these studies.

Acute Disease↗

Analysis of microbiological trends in peritoneal dialysis-related peritonitis from 1991 to 1998.

The microbial cause of peritoneal dialysis-related peritonitis is an important determinant of clinical outcome and the basis of widely used treatment guidelines. Five hundred forty-six cases of peritonitis in 374 patients from 1991 to 1998 were analyzed. The rate of peritonitis declined significantly from 1.37 episodes/patient-year in 1991 to 0.55 episode/patient-year in 1998 (P = 0.02). The rate of Gram-positive peritonitis decreased significantly from 0.75 to 0.28 episode/patient-year during the same period (P = 0.02). Conversely, the occurrence of Gram-negative peritonitis remained constant at approximately 0.16 episode/patient-year (P = 0.28). Staphylococcus epidermidis and Staphylococcus aureus were the most common causes of peritonitis, isolated in 27.8% and 19.3% of the culture-positive cases, respectively. A distinct decrease in peritonitis caused by S epidermidis was observed, with 0.40 episode/patient-year in 1991 compared with 0.11 to 0.20 episode/patient-year during subsequent years. The rate of infections caused by S aureus decreased significantly over time from a high of 0.21 episode/patient-year in 1992 to a low of 0.04 episode/patient-year in 1998 (P = 0.01). Pseudomonas aeruginosa, Escherichia coli, and KLEBSIELLA: species were the most common causes of Gram-negative peritonitis, identified in 7.1%, 6.8%, and 5.2% of culture-positive cases, respectively. The most dramatic increase in antibiotic resistance was seen among S epidermidis. From 1991 and 1992 to 1997 and 1998, resistance to ciprofloxacin increased from 5.4% to 47.8% (P = 0.003), and resistance to methicillin increased from 18.9% to 73.9% (P = 0.03). Our study showed significant trends in the causative pathogens of peritoneal dialysis-related peritonitis and dramatic increases in antibiotic resistance. These data support further study and warrant reevaluation of current treatment practices.

Case-Control Studies↗

Peritonitis in peritoneal dialysis patients after renal transplantation.

BACKGROUND: The occurrence of peritonitis in peritoneal dialysis patients after renal transplantation during immunosuppression might increase morbidity and mortality. Hence the timing of catheter removal is still controversial. The associated risk factors of this complication have not been analyzed. METHODS: We analyzed, retrospectively, the incidence of peritonitis within 90 days after transplantation, its associated morbidity and mortality, as well as risk factors. From 1980 until March 1995, 238 consecutive kidney transplants in peritoneal dialysis patients were performed. Univariate and multivariated logistic regression analysis were used to identify risk factors for the development of peritonitis. RESULTS: 232 cases (141 men, 91 women) were available for analysis. In 191 patients, the catheter was removed with a mean interval after transplantation of 122 days (range 0-573). Thirty peritonitis episodes with predominantly Staphylococcus aureus (10/30) or gram-negative bacteria (12/30) were observed. Independent risk factors before transplantation were the total number of peritonitis episodes (P<10(-5)), previous peritonitis with S. aureus bacteria (P<10(-5)), and male sex (P<0.004). Risk factors after transplantation were technical surgical problems (P<10(-5)), more than two rejection episodes (P<0.02), permanent graft nonfunction (P<0.026), and urinary leakage (P<0.035). CONCLUSIONS: Transplantation without simultaneous peritoneal catheter removal is feasible. However, this increases the risk of peritonitis after transplantation. Early catheter removal should be considered seriously in those patients at risk. When peritonitis develops, antibiotic treatment should be directed against gram-positive as well as gram-negative bacteria until culture results are available.

Adult↗

The clinical course of peritoneal dialysis-related peritonitis caused by Corynebacterium species.

BACKGROUND: Corynebacterium species are part of the normal skin flora. The incidence of nosocomial infections caused by Corynebacterium species have increased substantially over the past two decades. However, the clinical course of Corynebacterium peritonitis complicating peritoneal dialysis remains unclear. METHOD: We reviewed all the Corynebacterium peritonitis in our dialysis unit from 1995 to 2002. During this period, there were 1485 episodes of peritonitis recorded; 27 (1.8%) of which were caused by Corynebacterium species. RESULTS: The underlying renal diagnosis and prevalence of comorbid conditions of the 27 patients were similar to our whole dialysis population. The bacteria isolated were resistant to penicillin in 8 cases (29.6%). Three cases (11.1%) had concomitant exit-site infection. The overall primary response rate was 74.1%; the complete cure rate was 37.0%. Episodes that received vancomycin as initial antibiotic had a marginally higher primary response rate (9 in 10 vs 11 in 17 episodes, P = 0.2) and complete cure rates (7 in 10 vs 3 in 17 episodes, P = 0.12) than the episodes that received cephalosporins, although neither of the differences was statistically significant. Thirteen cases (48.1%) had recurrent peritonitis after antibiotic therapy, 8 of which had the recurrent episode at least 30 days after stopping antibiotics (median 54 days, range 43-60 days). Eight recurrent cases (61.5%) were successfully cured by another 3 week course of intra-peritoneal vancomycin. CONCLUSIONS: Recurrent Corynebacterium peritonitis is common after a 2 week course of antibiotics. Recurrent Corynebacterium peritonitis may be delayed up to 2 months after the antibiotic is stopped. Recurrent peritonitis can usually be cured with a 3 week course of intra-peritoneal vancomycin, which is probably the preferred antibiotic regimen for Corynebacterium peritonitis.

Anti-Bacterial Agents↗

Characterization of human peritoneal dendritic cell precursors and their involvement in peritonitis.

Scattered evidence suggests that the human peritoneal cavity contains cells of the dendritic cell (DC) lineage but their characterization is missing. Here, we report that the peritoneal cavity of normal subjects and of stable patients on peritoneal dialysis (PD) contains a population of CD14(+) cells that can differentiate into DCs or macrophages. Within this pool, we characterized a CD14(+)CD4(+) cell subset (2.2% of the peritoneal cells) fulfilling the definition of myeloid DC precursors or pre-DC1 cells. These cells expressed high levels of HLA-DR, CD13, CD33, and CD86, and low levels of CD40, CD80, CD83, CD123, CD209, TLR-2 and TLR-4. These cells retained CD14 expression until late stages of differentiation, despite concomitant up-regulation of DC-SIGN (CD209), CD1a, CD80 and CD40. Peritoneal pre-DC1 cells had endocytic capacity that was down-regulated upon LPS/IFN-gamma stimulation, were more potent allo-stimulators than peritoneal CD14(+)CD4(-/lo) cells and monocyte-derived macrophages, and induced Th1 cytokine responses. More importantly, the number of peritoneal pre-DC1 cells increased during PD-associated peritonitis, with a different profile for Gram positive and Gram negative peritonitis, suggesting that these cells participate in the induction of peritoneal adaptive immune responses, and may be responsible for the bias towards Th1 responses during peritonitis.

Adult↗

Higher rate and earlier peritonitis in Aboriginal patients compared to non-Aboriginal patients with end-stage renal failure maintained on peritoneal dialysis in Australia: analysis of ANZDATA.

BACKGROUND: Aboriginal patients maintained on peritoneal dialysis (PD) have a higher rate of technique failure than any other racial group in Australia. Peritonitis accounts for the bulk of these technique failures, but it is uncertain whether the increased risk of peritonitis in Aboriginal patients was independent of associated comorbid conditions, such as diabetes mellitus. METHODS: Using data collected by the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA), peritonitis rates and time to first peritonitis were compared between Aboriginal (n = 238) and non-Aboriginal patients (n = 2924) commencing PD in Australia between 1 April 1999 and 31 March 2003. RESULTS: Aboriginal PD patients were younger, and had a higher incidence of diabetes than their non-Aboriginal counterparts. Mean peritonitis rates were significantly higher among Aboriginal (1.15 episodes/year; 95% confidence interval (CI): 1.03-1.28) than non-Aboriginal patients (0.60 episodes/year; 95% CI: 0.57-0.62, P < 0.05). Using multivariate negative binomial regression, independent predictors of higher peritonitis rates include Aboriginal racial origin (adjusted odds ratio 1.78; 95% CI: 1.45-2.19), obesity, age and absence of a recorded dialysate : plasma creatinine ratio (D/P creatinine) measurement. Aboriginal racial origin was also associated with a shorter median time to first peritonitis (9.9 vs 19.3 months, P < 0.05), which remained statistically significant in a multivariate Cox proportional hazards model (adjusted hazard ratio 1.76; 95% CI: 1.47-2.11, P < 0.05). CONCLUSION: Aboriginal and obese PD patients have a higher rate of peritonitis and a shorter time to first peritonitis, independent of demographic and comorbid factors. Further investigation of the causes of increased peritonitis risk in Aboriginal patients is needed.

Adolescent↗

Course of C-reactive protein during continuous peritoneal dialysis-associated peritonitis.

OBJECTIVE: C-reactive protein (CRP) levels increase during peritonitis. Little is known about the extent and duration of CRP elevation. PATIENTS AND METHODS: Patients on continuous peritoneal dialysis (CPD) therapy had a baseline CRP value at the start of the study. CRP values were determined at 48 h, 2 weeks and 4 weeks after an episode of peritonitis developed in the 13 months after the study started. RESULTS: The demographic values and comorbid diseases of the patients developing and not developing peritonitis were not significantly different. Patients who developed peritonitis had a mean +/- SD CRP value of 15.0 +/- 11.1 mg/L compared with 15.7 +/- 9.9 mg/L in patients without peritonitis. The CRP value rose to 118.35 +/- 96.86 mg/L at 48 h, and decreased to 34.5 +/- 43.6 mg/L at 2 weeks and to 30.1 +/- 39.7 mg/L at 4 weeks after the onset of peritonitis. All types of peritonitis were associated with a significant increase in CRP at 48 h. Nine patients had CRP elevations above baseline at 4 weeks; seven patients had active medical issues. CONCLUSION: CRP values become significantly elevated during peritonitis. Most patients have a decrease in the CRP values toward baseline values at 4 weeks following the onset of peritonitis while 20% of patients had continued elevations. The significance of the elevations is unclear. Given the associations of CRP with cardiovascular mortality in both uremic and non-uremic patients and the association of peritonitis with mortality, the role of this inflammatory marker deserves further evaluation.

Adult↗

What is the actual incidence of peritonitis in maintenance peritoneal dialysis? A prospective study.

Generally, the incidence of peritonitis in maintenance peritoneal dialysis programs is calculated as a percentage of the total number of treatments or as the number of episodes per patient-months. Both statistical methods give the wrong impression that peritonitis is seldom observed. However, peritonitis is still the major and unsolved challenge to successful long-term peritoneal dialysis. The lack of a standard and homogeneous definition of peritonitis is another critical point that prevents a rational interpretation of the published experiences. In the present study, dialysate cell counts of greater than 1,100 cells/mm3 were assumed to be the first sign of peritoneal infection. As long as more signs and symptoms are required for recognizing peritonitis (fever, abdominal pains, positive cultures), the statistical probability of making such a diagnosis shows the characteristics of a Poisson distribution. It is concluded that in long-term peritoneal dialysis, the currently used statistical methodology for evaluation of the incidence of peritonitis, including the clinical definition of this complication, is misleading. Dialysate cell counts appear to be the more sensitive sign for early diagnosis of peritonitis.

Adult↗

Effect of prolonged subcutaneous implantation of peritoneal catheter on peritonitis rate during CAPD: a prospective randomized study.

We conducted a prospective randomized controlled study to confirm our earlier observation that prolonged subcutaneous implantation of peritoneal catheter reduced peritonitis rate when compared to retrospective data from patients with catheters placed by conventional access technique. A total of 60 patients were randomized into two groups: 30 patients had catheters left implanted subcutaneously for 6 weeks (I) and the other 30 patients had catheters inserted by conventional technique and had 6 weeks of break-in period (C). Subgroups of 15 patients each with new and conventional techniques used Y-connector (IY, CY) and remaining patients used standard spikes (IS, CS). Mean age was 47.7 years (range 16-71); 61.0% were male and 44.1% diabetics. Peritonitis, exit site infection, simultaneous peritonitis and exit site infection, and complication related to Staphylococcus or Pseudomonas infections were observed for up to 2 years in each patient after initiation of bag exchange or until termination of CAPD by transfer to hemodialysis or by death. Total duration of observation was 493.2 patient-months for new access technique and 409.6 patient-months for conventional technique. Patients in IY group had the lowest incidence of peritonitis (1/14.9 patient-months) and exit site infection (1/16.8 patient-months) among four subgroups. Peritonitis rate in IY was significantly lower compared to CY or CS. The total peritonitis-free period in those patients who did not experience peritonitis during the observation period was also significantly longer in IY (120 patient-months) than in CY (26 patient-months), IS (10.6 patient-months), or CS (10.4 patient-months). Simultaneous peritonitis and exit site infection was observed in none of IY group but 3 episodes in CY, 4 episodes in IS, and 3 episodes in CS. The rates of complications related to Staphylococcus aureus and Pseudomonas infections were also significantly lower in IY than in CY, IS, or CS. Technique survival did not differ between the two groups. The present results confirm our previous observation that the new access technique reduces the incidence of peritonitis probably by reducing infection via periluminal route. The Y-connector system further reduces peritonitis rate by reducing infection via intraluminal route.

Adolescent↗

Peritoneal dialysis complicated by Bipolaris hawaiiensis peritonitis: successful therapy with catheter removal and oral itraconazol without the use of amphotericin-B.

Fungi classified in the genera Bipolaris are an uncommon source of infection in human diseases. It is also a rare source of peritonitis in peritoneal dialysis (PD) patients. All cases of Bipolaris peritonitis reported in the United States have occurred in the southern states. This form of peritonitis appears to have a good prognosis, with cure achieved only after removal of the peritoneal dialysis catheter and antifungal therapy. Systemic or intraperitoneal amphotericin-B with or without oral ketoconazole has been used in all previously reported cases. However, the role of antifungal therapy is unclear. We report a case of Bipolaris hawaiiensis peritonitis in a 73-year-old female on continuous cyclic peritoneal dialysis (CCPD) for 10 months who presented with a nonfunctioning peritoneal catheter. The catheter had characteristic dark gray particles, each composing a fungal ball within the lumen of the catheter. Microscopic examination confirmed the organism attached to the inner wall of the catheter. The patient achieved cure without using either amphotericin-B or ketoconazole. She was treated with removal of the catheter and a 2-week course of oral itraconazole 100 mg twice daily. A new catheter was placed after 1 month and the patient continued to do well on CCPD 12 months later with no evidence of recurrent infection. We conclude that (1) itraconazole can effect cure following removal of the catheter without using amphotericin-B or ketoconazole; (2) peritoneal dialysis can be safely reinstituted after itraconazole therapy for this uncommon fungal infection, and (3) itraconazole therapy allows for out-patient treatment of B. hawaiiensis peritonitis in peritoneal dialysis patients.

Administration, Oral↗

Simple peritoneal sclerosis and sclerosing peritonitis: related or distinct entities?

AIM: The etiopathogenesis of sclerosing peritonitis is still debated, with some sustaining that it is a rare form of progression of simple peritoneal sclerosis and others that it is a primitive form. The aim of the present research was to clarify this question. MATERIAL AND METHODS: 438 peritoneal biopsies from 253 patients were re-examined. 174 were obtained prior to peritoneal dialysis and 224 after various periods of dialysis. Forty biopsies were from peritoneal dialysis patients who developed sclerosing peritonitis. Peritoneal morphology was studied for signs of transition from simple sclerosis to sclerosing peritonitis. RESULTS: Evidence was found sustaining the hypothesis that simple sclerosis to sclerosing peritonitis patients have distinct pathologies. CONCLUSIONS: The results confirm previous observations, excluding the existence of any type of relation between simple peritoneal sclerosis to sclerosing peritonitis.

Basement Membrane↗

[Peritoneal sclerosis in children under treatment with peritoneal dialysis].

Peritoneal dialysis(PD) is an established method of dialysis for children at the end stage of renal failure. Among several problems associated with PD, peritoneal sclerosis is one of the most serious complications. We examined four children on PD who were diagnosed as having peritoneal sclerosis in 1997 and 1998. Three of these cases were switched to hemodialysis(HD) and one is now undergoing a switch from PD to HD. Although all of the four patients had a history of bacterial peritonitis, they had been maintained in a fairly good condition on PD. The mean duration of PD was 9 years(4-14 years). All cases were anuric and had been maintained on PD without any problems of peritoneal function. From these observations, we should consider peritoneal sclerosis even in patients with a good clinical condition during the long-term period of PD. We recommend serial peritoneal biopsies, at least at the time of peritoneal catheter changes, to check for peritoneal sclerosis. The patients who are diagnosed as having sclerotic thickening of the peritoneal membrane should be switched from PD to HD to prevent the occurrence of life-threatening peritoneal sclerosis.

Adolescent↗

Comparison of vancomycin versus cefazolin as initial therapy for peritonitis in peritoneal dialysis patients.

The incidence of peritonitis ranges from 1 episode every 24 patient treatment months to 1 episode every 60 patient treatment months [Keane WF, et al. ISPD Guidelines/Recommendations. Adult peritoneal dialysis-related peritonitis treatment recommendations: 2000 update. Perit Dial Int 2000; 20:396-411.]. Gram-positive organisms account for over 80% of continuous ambulatory peritoneal dialysis (PD)-associated peritonitis. Recent fear of vancomycin-resistant enterococci (VRE) has prompted suggestions of limiting vancomycin use. Fifty-one episodes of peritonitis in 30 patients studied over 2 years were evaluated. Cloudiness of the PD fluid and/or abdominal pain were considered suggestive of peritonitis and were confirmed by cell count and culture. Baseline cell count, Gram stain, and cultures were obtained, with periodic follow-up. Patients were randomized to receive either vancomycin 1 g/L intraperitoneally (IP) as loading dose, repeated on day 5 or day 8, depending on residual renal function, for 2 weeks, or cefazolin 1 g in the first PD bag and continued with 125 mg/L every exchange for 2 or 3 weeks, depending on culture results. All patients also received gentamicin 40 mg IP every day until the culture results were available. A similar randomized trial comparing vancomycin and cefazolin in the past used a lower concentration of cefazolin 50 mg/L [Flanigan MJ, Lim VS. Initial treatment of dialysis associated peritonitis: a controlled trial of vancomycin versus cefazolin. Perit Dial /nt 1991; 11:31-7.]. Peritoneal dialysate fluid cultures revealed 31(60.7%) gram-positive organisms, 7(13.7%) gram-negative organisms, and 2 (3.9%) cultured yeast; 11 (21.5%) cultures yielded no growth. The incidence of peritonitis at our center was 1 episode every 42 patient treatment months. No case of VRE was noted. There was no statistical difference in clinical response or relapse rate for the two protocols. It was the authors' and nurses' observation that patient compliance and satisfaction was better with vancomycin, and the cost per treatment was 23% less than cefazolin. Based on these data we believe vancomycin should still be considered for first-line treatment of PD-associated peritonitis.

Adult↗

Cytokines and peritonitis in continuous ambulatory peritoneal dialysis: immunodeviation and immunodeficiency.

Cytokines are soluble mediators of the immune system, which regulate the immune response to antigenic stimuli. In continuous ambulatory peritoneal dialysis (CAPD) patients with peritonitis, an inflammatory process occurs, but the patterns of cytokine secretion have not yet been clarified. We compared the characteristics of the intracellular production of cytokines and looked for the immunophenotypes T helper 1 (TH1), T helper 2 (TH2), and T helper 0 (TH0) in CAPD patients with and without peritonitis. Our descriptive, prospective study was carried out in the dialysis unit of the San José University Hospital, a tertiary health care center in Popayán, southwest Colombia. We obtained 28 peripheral blood samples from CAPD patients (8 with peritonitis and 20 without peritonitis) and processed them by flow cytometry for intracellular detection of cytokines. The peritonitis diagnosis was made based using established clinical and laboratory criteria. We measured the general clinical characteristics and percentage of intracellular production of interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-12 (IL-12), tumor necrosis factor alpha (TNF alpha), interleukin-4 (IL-4), and interferon-gamma (INF-gamma) in T lymphocytes. Diabetic nephropathy and chronic glomerulonephritis were the most frequent primary pathologies in both groups of patients. The patients on CAPD without peritonitis expressed high levels of CD69 and the pro-inflammatory cytokines IL-1, IL-6, IL-12, TNF alpha, and IL-4, indicating in vivo immune activation similar to the group with peritonitis. In the group without peritonitis, 95% of samples displayed immunodeviation TH2. Just 5% of samples approached TH0, producing IFN-gamma. After mitogen activation, 45% of the samples stayed in TH2; 55% approached TH0. Patients with peritonitis produced high levels of IL-4 and little IFN-gamma, which indicates immunodeviation TH2 in 75% of samples; 25% approached TH0. When cells were stimulated by ionomicin and phorbol 12-myristate 13-acetate (PMA), more IFN-gamma appeared and high levels of IL-4 persisted in 75% of the samples, which looked like intent to correct the TH2 immunodeviation toward TH0. Patients on CAPD with and without peritonitis showed immune activation per se and high production of pro-inflammatory cytokines accompanied by a strong pattern of cytokine TH2 and a deficiency of IFN-gamma production, suggesting heavy immunodeviation TH2 and immunodeficiency TH1 (owing to the deficit of IFN-gamma). Finally, with in vitro immune stimulation, the TH2 pattern tried to approach TH0.

CD4-CD8 Ratio↗

A 12-month review of peritoneal dialysis-related peritonitis in Western Australia: is empiric vancomycin still indicated for some patients?

BACKGROUND: The International Society for Peritoneal Dialysis (ISPD) guidelines recommend empiric therapy with cefazolin and ceftazidime for peritoneal dialysis (PD)-related peritonitis. Empiric cefazolin therapy may have diminishing efficacy because of emerging methicillin resistance in gram-positive bacteria (GPB). Western Australia also has large numbers of Aboriginal and isolated regional patients, where giving these antimicrobials can be impractical. OBJECTIVES: To evaluate, based on local antimicrobial resistance patterns, the feasibility of following ISPD guidelines in Western Australia and to identify any subgroups of PD peritonitis patients that may benefit from alternative empiric intraperitoneal antibiotics (e.g., vancomycin). STUDY DESIGN: Retrospective study of all PD peritonitis episodes in Western Australia from 1 February 2000 to 31 January 2001. SETTING: Three adult tertiary referral university hospitals and their PD patients in metropolitan Perth and regional Western Australia. PATIENTS: All adults on PD in Western Australia. MAIN OUTCOME MEASURE: Isolates and antibiograms were analyzed versus patient characteristics, including race and patient demographics. RESULTS: 293 patients (28% Aborigines, 32% regional patients) received PD. 145 episodes of PD peritonitis occurred during the study. The overall PD peritonitis rate was 1 episode/16 patient months, with Aborigines having 1 episode/10.5 patient months versus non-Aborigines having 1 episode/17 patient months (p < 0.001). 36% of isolates from PD peritonitis episodes were resistant to cefazolin or ceftazidime. 22% were methicillin-resistant GPB (MR-GPB) [18% coagulase-negative staphylococci (CoNS), 1.6% MR Staphylococcus aureus]; 2.5% were multidrug-resistant gram-negative bacteria (MDR-GNB); 5.7% were polymicrobial (MR-GPB and/or MDR-GNB); and 5.7% were fungal. 63% of CoNS were methicillin resistant. Non-Aboriginal patients yielded MR-GPB in 22% of isolates versus 23% in Aborigines (p = 0.9). Six of seven cases of fungal peritonitis occurred in Aboriginal patients (p < 0.001). CONCLUSIONS: In our study population the ISPD guidelines were appropriate for 64% of patients with PD peritonitis. We could not identify specific patient subgroups where empiric cefazolin use could be more effective. High proportions of MR-GPB PD peritonitis episodes, along with local factors, make empiric cefazolin unsuitable for many regional PD patients in Western Australia.

Adult↗

Severe peritoneal mononucleosis associated with icodextrin use in continuous ambulatory peritoneal dialysis.

Icodextrin is a glucose polymer obtained from starch hydrolysis. It is used as an osmotic agent at 7.5% for peritoneal dialysis (PD). Its use in PD has been associated with several side effects separate from the one reported here, the most frequent being sterile peritonitis. Recently, three mechanisms have been proposed to explain the occurrence of sterile peritonitis: allergy to dextrin, production of anti-dextran antibodies, and impurities introduced during manufacture. Here, we report a peritoneal mononucleosis outbreak that is highly suggestive of being a consequence of the last-mentioned mechanism. During the period December 2001 to May 2002, a group of 8 Spanish hospitals whose individual PD programs regularly share information and activity reported 29 cases of sterile peritonitis associated with icodextrin use in continuous ambulatory peritoneal dialysis (CAPD) patients [mean age: 60.7 +/- 14.47 years; 8 women (27.59%), 21 men (72.41%); mean time on PD: 25.21 +/- 35.31 months; mean time on icodextrin: 15.17 +/- 11.03 months]. Of the 29 patients, 51.8% showed no symptoms. The remainder presented with mild abdominal discomfort and anorexia. Only 2 patients showed general malaise, severe nausea, fever, and abdominal pain. The initial white cell count in peritoneal effluent was 512 +/- 386 cells/mL (45.0% +/- 28% neutrophils, 44.92% +/- 32.6% mono-nuclear cells, 7.75% +/- 12% eosinophils). In 5 of the patients, we performed an immunophenotype (CD14) study, demonstrating the monocyte nature of 60%-80% (mean: 70.6%) of the cells. Microbiology cultures were always negative. A rechallenge with the same batches of PD fluid was tried. In 100% of the patients, the clinical and cellular patterns relapsed. No short-term changes in peritoneal function have been observed. The manufacturer informed us that the icodextrin was contaminated with a peptidoglycan. In this sterile peritonitis outbreak with a simultaneous, similar clinical presentation in a group of patients treated with icodextrin solution (presumably contaminated with peptidoglycan), clinical outcome was, for the most part, mild-to-moderate. Symptoms disappeared immediately after icodextrin withdrawal and relapsed after rechallenge with the relevant fluid batches. Monocyte cell counts predominated during the episode. Although we cannot rule out an allergic cause, the massive peritoneal mononuclear cell recruitment suggests a particular mechanism. This is a new mechanism for peritoneal cell recruitment in PD.

Adult↗