Treatment and outcome of CPD-associated peritonitis

CPD-associated peritonitis is a leading cause of morbidity and mortality for ESRD patients maintained on CPD therapy. The percentage of ESRD patients maintained on CPD therapy is declining. The reasons are unclear, but may be due to concerns about CPD-associated peritonitis. The incidence of CPD-associated peritonitis has decreased largely attributed to technical advances and the identification of risk factors including exit-site infection, colonization with Staphylococcus aureus and depression. The typical spectrum of organisms causing peritonitis include gram-positive organisms (67%), gram-negative organisms (28%), fungi (2.5%) or anaerobic organisms (2.5%). Culture-negative episodes do occur: up to 20% of the episodes of peritonitis in some series are culture-negative. The treatment of CPD associated peritonitis is rather standardized with current recommendations by the International Society of Peritoneal Dialysis universally adopted. Approximately 80% of the patients developing peritonitis will respond to antimicrobial therapy and remain on CPD therapy, while 10 to 15% of the patients require catheter removal and transfer to hemodialysis. Approximately 6% of the patients expire as a result of peritonitis. The outcome is different based on organism with gram-negative and fungal episodes having a worse outcome than gram-positive episodes. The development of CPD-associated peritonitis can be linked to traditional risk factors such as exit-site infection and poor technique. Bacterial biofilm has also been suggested as a cause of peritonitis. Our current antimicrobial protocols may not permit adequate dosing to penetrate the biofilm and be a reason for recurrent or repeat episodes of peritonitis. It is important that we improve our understanding of factors responsible for the development and outcome of CPD-associated peritonitis in order for this renal replacement therapy to remain a viable option for patients with ESRD

Unusual presentation of peritonitis with persistent clear aspirate: a case report

<p>Abstract</p> <p>Introduction</p> <p>Peritonitis is the most frequent complication of peritoneal dialysis. Diagnosis of peritonitis includes symptoms and signs of peritonitis with a cloudy aspirate of more than 100 WBC/ml, as well as positive cultures. Although sterile peritonitis has been reported in the literature, to the best of our knowledge this is the first report of an unusual presentation of peritonitis without any white blood cells in the peritoneal aspirate despite multiple positive peritoneal cultures.</p> <p>Case presentation</p> <p>An 82-year-old Caucasian man who had been on continuous cycling peritoneal dialysis for 12 years was admitted to our hospital with general malaise, loss of appetite, weight loss and somnolence. He did not describe abdominal pain or fever. Even though his peritoneal fluid was consistently negative for leukocytes and clear, he had peritonitis with different organisms consecutively.</p> <p>Conclusions</p> <p>Our case report shows that any patient on peritoneal dialysis presenting with evidence of infection (fever, peripheral leukocytosis) without an obvious cause should have aspirate cultures done even if the aspirate is clear and abdominal pain is absent. Our case report may change the initial work-up and management of these patients. We believe this report is of interest to general medicine and emergency room physicians as well as nephrologists.</p

The role of virulence factors in the outcome of staphylococcal peritonitis in CAPD patients

<p>Abstract</p> <p>Background</p> <p>Peritonitis continues to be the most frequent cause of peritoneal dialysis (PD) failure, with an important impact on patient mortality. Gram-positive cocci such as <it>Staphylococcus epidermidis</it>, other coagulase-negative staphylococci (CoNS), and <it>Staphylococcus aureus </it>are the most frequent etiological agents of PD-associated peritonitis worldwide. The objective of the present study was to compare peritonitis caused by <it>S. aureus </it>and CoNS and to evaluate the factors influencing outcome.</p> <p>Methods</p> <p>Records of 86 new episodes of staphylococcal peritonitis that occurred between 1996 and 2000 in the Dialysis unit of a single university hospital were studied (35 due to <it>S. aureus</it>, 24 to <it>S. epidermidis </it>and 27 to other CoNS). The production of slime, lipase, lecithinase, nuclease (DNAse), thermonuclease (TNAse), α- and β-hemolysin, enterotoxins (SEA, SEB, SEC, SED) and toxic shock syndrome toxin-1 (TSST-1) was studied in <it>S. aureus </it>and CoNS. Antimicrobial susceptibility was evaluated based on the minimal inhibitory concentration determined by the E-test. Outcome predictors were evaluated by two logistic regression models.</p> <p>Results</p> <p>The oxacillin susceptibility rate was 85.7% for <it>S. aureus</it>, 41.6% for <it>S. epidermidis</it>, and 51.8% for other CoNS (p = 0.001). Production of toxins and enzymes, except for enterotoxin A and α-hemolysin, was associated with <it>S. aureus </it>episodes (p < 0.001), whereas slime production was positive in 23.5% of CoNS and 8.6% of <it>S. aureus </it>strains (p = 0.0047). The first model did not include enzymes and toxins due to their association with <it>S. aureus</it>. The odds of resolution were 9.5 times higher for <it>S. epidermidis </it>than for <it>S. aureus </it>(p = 0.02) episodes, and were similar for <it>S. epidermidis </it>and other CoNS (p = 0.8). The resolution odds were 68 times higher for non-slime producers (p = 0.001) and were not influenced by oxacillin resistance among vancomycin-treated cases (p = 0.89). In the second model, the resolution rate was similar for <it>S. aureus </it>and <it>S. epidermidis </it>(p = 0.70), and slime (p = 0.001) and α-hemolysin (p = 0.04) production were independent predictors of non-resolution.</p> <p>Conclusion</p> <p>Bacterial species and virulence factors rather than antibiotic resistance influence the outcome of staphylococcal peritonitis.</p

Human neutrophil clearance of bacterial pathogens triggers anti-microbial gamma delta T cell responses in early infection

Human blood Vc9/Vd2 T cells, monocytes and neutrophils share a responsiveness toward inflammatory chemokines and are rapidly recruited to sites of infection. Studying their interaction in vitro and relating these findings to in vivo observations in patients may therefore provide crucial insight into inflammatory events. Our present data demonstrate that Vc9/Vd2 T cells provide potent survival signals resulting in neutrophil activation and the release of the neutrophil chemoattractant CXCL8 (IL-8). In turn, Vc9/Vd2 T cells readily respond to neutrophils harboring phagocytosed bacteria, as evidenced by expression of CD69, interferon (IFN)-c and tumor necrosis factor (TNF)-a. This response is dependent on the ability of these bacteria to produce the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), requires cell-cell contact of Vc9/Vd2 T cells with accessory monocytes through lymphocyte function-associated antigen-1 (LFA-1), and results in a TNF-a dependent proliferation of Vc9/Vd2 T cells. The antibiotic fosmidomycin, which targets the HMB-PP biosynthesis pathway, not only has a direct antibacterial effect on most HMB-PP producing bacteria but also possesses rapid anti-inflammatory properties by inhibiting cd T cell responses in vitro. Patients with acute peritoneal-dialysis (PD)-associated bacterial peritonitis – characterized by an excessive influx of neutrophils and monocytes into the peritoneal cavity – show a selective activation of local Vc9/Vd2 T cells by HMB-PP producing but not by HMB-PP deficient bacterial pathogens. The cd T celldriven perpetuation of inflammatory responses during acute peritonitis is associated with elevated peritoneal levels of cd T cells and TNF-a and detrimental clinical outcomes in infections caused by HMB-PP positive microorganisms. Taken together, our findings indicate a direct link between invading pathogens, neutrophils, monocytes and microbe-responsive cd T cells in early infection and suggest novel diagnostic and therapeutic approaches.Martin S. Davey, Chan-Yu Lin, Gareth W. Roberts, Sinéad Heuston, Amanda C. Brown, James A. Chess, Mark A. Toleman, Cormac G.M. Gahan, Colin Hill, Tanya Parish, John D. Williams, Simon J. Davies, David W. Johnson, Nicholas Topley, Bernhard Moser and Matthias Eber

Seeking Clarity within Cloudy Effluents: Differentiating Fungal from Bacterial Peritonitis in Peritoneal Dialysis Patients

Fungal peritonitis is a serious complication of peritoneal dialysis (PD) therapy with the majority of patients ceasing PD permanently. The aims of this study were to identify risk factors and clinical associations that may discriminate between fungal from bacterial peritonitis.We retrospectively identified episodes of fungal peritonitis from 2001-2010 in PD patients at Liverpool and Westmead Hospitals (Australia). Fungal peritonitis cases were matched in a 1:2 ratio with patients with bacterial peritonitis from each institution's dialysis registry, occurring closest in time to the fungal episode. Patient demographic, clinical and outcome data were obtained from the medical records.Thirty-nine episodes of fungal peritonitis (rate of 0.02 episodes per patient-year of dialysis) were matched with 78 episodes of bacterial peritonitis. Candida species were the commonest pathogens (35/39; 90% episodes) with Candida albicans (37%), Candida parapsilosis (32%) and Candida glabrata (13%) the most frequently isolated species. Compared to bacterial peritonitis, fungal peritonitis patients had received PD for significantly longer (1133 vs. 775 catheter-days; p = 0.016), were more likely to have had previous episodes of bacterial peritonitis (51% vs. 10%; p = 0.01), and to have received prior antibacterial therapy (51% vs. 10%; p = 0.01). Patients with fungal peritonitis were less likely to have fever and abdominal pain on presentation, but had higher rates of PD catheter removal (79% vs. 22%; p<0.005), and permanent transfer to haemodialysis (87% vs. 24%; p<0.005). Hospital length of stay was significantly longer in patients with fungal peritonitis (26.1 days vs. 12.6 days; p = 0.017), but the all-cause 30-day mortality rate was similar in both groups. Fluconazole was a suitable empiric antifungal agent; with no Candida resistance detected.Prompt recognition of clinical risk factors, initiation of antifungal therapy and removal of PD catheters are key considerations in optimising outcomes

Chronic kidney disease care delivered by US family medicine and internal medicine trainees: results from an online survey

BACKGROUND: Complications of chronic kidney disease (CKD) contribute to morbidity and mortality. Consequently, treatment guidelines have been developed to facilitate early detection and treatment. However, given the high prevalence of CKD, many patients with early CKD are seen by non-nephrologists, who need to be aware of CKD complications, screening methods and treatment goals in order to initiate timely therapy and referral. METHODS: We performed a web-based survey to assess perceptions and practice patterns in CKD care among 376 family medicine and internal medicine trainees in the United States. Questions were focused on the identification of CKD risk factors, screening for CKD and associated co-morbidities, as well as management of anemia and secondary hyperparathyroidism in patients with CKD. RESULTS: Our data show that CKD risk factors are not universally recognized, screening for CKD complications is not generally taken into consideration, and that the management of anemia and secondary hyperparathyroidism poses major diagnostic and therapeutic difficulties for trainees. CONCLUSION: Educational efforts are needed to raise awareness of clinical practice guidelines and recommendations for patients with CKD among future practitioners

Dialysis-associated peritonitis in children

Peritonitis remains a frequent complication of peritoneal dialysis in children and is the most common reason for technique failure. The microbiology is characterized by a predominance of Gram-positive organisms, with fungi responsible for less than 5% of episodes. Data collected by the International Pediatric Peritonitis Registry have revealed a worldwide variation in the bacterial etiology of peritonitis, as well as in the rate of culture-negative peritonitis. Risk factors for infection include young age, the absence of prophylactic antibiotics at catheter placement, spiking of dialysis bags, and the presence of a catheter exit-site or tunnel infection. Clinical symptoms at presentation are somewhat organism specific and can be objectively assessed with a Disease Severity Score. Whereas recommendations for empiric antibiotic therapy in children have been published by the International Society of Peritoneal Dialysis, epidemiologic data and antibiotic susceptibility data suggest that it may be desirable to take the patient- and center-specific history of microorganisms and their sensitivity patterns into account when prescribing initial therapy. The vast majority of patients are treated successfully and continue peritoneal dialysis, with the poorest outcome noted in patients with peritonitis secondary to Gram-negative organisms or fungi and in those with a relapsing infection

Characterization of a genus-specific chlamydial antigen

Chlamydia has been identified as a major human and animal pathogen worldwide. The development of effective treatments and methods of prevention of chlamydial disease relies on the understanding of the immunobiology of the organism. This dissertation describes the characterization of a genus-specific antigen isolated from the supernatants of infected cell cultures, termed the glycolipid exoantigen, or GLXA. Initial characterization studies compared GLXA to a class of known glycolipid antigens, the lipopolysaccharides, or LPSs. Results from SDS-PAGE, antibody binding profiles, Limulus ameobocyte lysate assays, and mitogenicity experiments indicated that GLXA differs from various known LPSs by all four parameters. Further characterization of GLXA biochemically and biologically was hindered by impure samples of antigen. Thus, experiments were carried out to determine the most efficient and effective purification method for purification of GLXA. Size fractionation coupled with nucleic acid digestion was effective in yielding pure GLXA samples when analyzed by PAGE, spectrophotometric scanning, enzyme digestion experiments and electron microscopy. A number of biochemical characteristics were then determined for GLXA. Results from these studies indicated that GLXA is a large molecular weight antigen and appears to exist as 10-50nm blebs that may aggregate with purification. In addition, antibody studies coupled with various biochemical treatments suggested that recognition of the relevant epitopes of GLXA are sensitive to environmental and biochemical conditions. Finally, the role of GLXA in infection and disease was investigated. GLXA samples (isolated in various manners) were not mitogenic or cytotoxic for murine splenocytes; however, GLXA isolated by hydrophobic/affinity chromatography exhibited an antiproliferative effect that was not attributable to cytotoxicity. Leukocytes from previously infected mice were not stimulated by GLXA preparations in vitro; however, further studies are necessary to determine the host response to GLXA during infection. GLXA was detectable in supernatants from primary cultures infected with various strains of Chlamydia, indicating an in vivo relevance for the antigen. Finally, pretreatment studies demonstrated that GLXA may play a role in infectivity of the organism. Results from this study strengthen the argument that GLXA is a relevant chlamydial antigen which may play a significant role in chlamydial infection and/or disease