Predictive factors of outcome following staphylococcal peritonitis in continuous ambulatory peritoneal dialysis

Background and aims: Staphylococcus epidermidis and other coagulase-negative staphylococci (CoNS) are the most common agents of continuous ambulatory peritoneal dialysis (CAPD) peritonitis. Episodes caused by Staphylococcus aureus evolve with a high method failure rate while CoNS peritonitis is generally benign. The purpose of this study was to compare episodes of peritonitis caused by CoNS species and S. aureus to evaluate the microbiological and host factors that affect outcome. Material and methods: Microbiological and clinical data were retrospectively studied from 86 new episodes of peritonitis caused by staphylococci species between January 1996 and December 2000 in a university dialysis center. The influence of microbiological and host factors (age, sex, diabetes, use of vancomycin, exchange system and treatment time on CAPD) was analyzed by logistic regression model. The clinical outcome was classified into two results (resolution and non-resolution). Results: the odds of peritonitis resolution were not influenced by host factors. Oxacillin susceptibility was present in 30 of 35 S. aureus lineages and 22 of 51 CoNS (p = 0.001). There were 32 of 52 (61.5%) episodes caused by oxacillin-susceptible and 20 of 34 (58.8%) by oxacillin-resistant lineages resolved (p = 0.9713). of the 35 cases caused by S. aureus, 17 (48.6%) resolved and among 51 CoNS episodes 40 (78.4%) resolved. Resolution odds were 7.1 times higher for S. epidermidis than S. aureus (p = 0.0278), while other CoNS had 7.6 times higher odds resolution than S. epidermidis cases (p = 0.052). Episodes caused by S. haemolyticus had similar resolution odds to S. epidermidis (p = 0.859). Conclusions: S. aureus etiology is an independent factor associated with peritonitis non-resolution in CAPD, while S. epidermidis and S. haemolyticus have a lower resolution rate than other CoNS. Possibly the aggressive nature of these agents, particularly S. aureus, can be explained by their recognized pathogenic factors, more than antibiotic resistance.

Inflammation-induced modulation of cellular galectin-1 and-3 expression in a model of rat peritonitis

Objective and design: To investigate the effect of galectin-1 (Gal-1) and -3 (Gal-3) on leukocyte migration and analyze the expression of both galectins in inflammatory cells using a model of rat peritonitis.Material or Subjects: Sprague-Dawley rats (n = 4 per group).Treatment: Peritonitis was induced in animals through intraperitoneal injection of carrageenin (1.5 mg/kg) and rat mesenteries were analyzed at different time points (0, 4, 24 and 48h). For pharmacological treatment, rats received intravenous injection of Gal-1 or -3 (3 mu g/kg) followed by carrageenin.Methods: Western blotting and immunoelectron microscopy analysis. Statistical analysis was performed using ANOVA followed by Bonferroni test.Results: Pharmacological treatment with Gal-1, but not Gal-3, inhibited (similar to 50%) leukocyte recruitment into the peritoneal cavity at 4h time-point. In this early phase, immunogold staining of mesenteries showed a diminished Gal-3 expression in degranulated mast cells and Gal-1 in transmigrated neutrophils (similar to 20% reduction compared to intravascular cells). In the later phases (24 and 48 h), leukocyte turnover was associated with augmented Gal-1 expression in neutrophils and macrophages and Gal-3 in mast cells and macrophages.Conclusions: These results point to a balanced expression of cell-associated-Gal-1/Gal-3 and might impact on the development of new therapeutic strategies for inflammatory diseases.

Factors contributing to the differences in peritonitis rates between centers and regions

Despite improvements in connectology, peritoneal dialysis (PD) - associated peritonitis contributes significantly to morbidity and modality failure in patients maintained on PD therapy. A broad spectrum of organisms -gram-positive, gram-negative, fungal, anaerobic - are involved in this complication. In addition, a significant percentage of episodes involve polymicrobial and culture-negative infection. Technological advances are being developed to minimize the incidence of access-related complications such as peritonitis. Many traditional factors such as exit-site infection and poor technique have been already identified. In the present review, we discuss the geographic, patient selection, and clinical issues that can affect peritonitis rates in different areas of the world and in different centers in the same area.

PARTICIPATION OF MACROPHAGES IN CHLORAMPHENICOL-POTENTIATED CARRAGEENAN-INDUCED PERITONITIS IN RATS

1. We investigated the possible potentiating effect of chloramphenicol succinate (30 mg/kg, every 12 h for 4 days, ip) on the response of polymorphonuclear neutrophils to carrageenin (150 mug, ip) or dextran (100 mug, ip) in the peritoneal cavity of male Wistar rats (180-230 g; N = 12 in each group).2. Chloramphenicol potentiated the cell migration induced by carrageenin (35%) but not that induced by dextran. Previous macrophage depletion in the peritoneal cavity by washing with sterile saline abolished the cell response, whereas a previous thioglycollate-induced increase in macrophage numbers enhanced the potentiating effect (60%).3. These results suggest that the potentiating effect on polymorphonuclear neutrophil migration induced by chloramphenicol may be related to chemotactic factors released by macrophages.

The diagnostic value of Gram stain for initial identification of the etiologic agent of peritonitis in CAPD patients

Objective: To evaluate the effectiveness of the Gram stain in the initial diagnosis of the etiologic agent of peritonitis in continuous ambulatory peritoneal dialysis (CAPD). Design: Retrospective study analyzing the sensitivity (S), specificity (SS), positive predictive value (+PV), and negative predictive value (-PV) of the Gram stain relating to the results of cultures in 149 episodes of peritonitis in CAPD. The data were analyzed in two studies. In the first, only the cases with detection of a single agent by Gram stain were taken (Study 1). In the second, only the cases with two agents in Gram stain were evaluated (Study 2). Setting: Dialysis Unit and Laboratory of Microbiology of a tertiary medical center. Patients: Sixty-three patients on regular CAPD who presented one or more episodes of peritonitis from May 1992 to May 1995. Results: The positivity of Gram stain was 93.2% and the sensitivity was 95.7%. The values of S, SS, +PV, and -PV were respectively: 94.9%, 53.5%, 68.3%, and 90.9% for gram-positive cocci and 83.3%, 98.8%, 95.2%, and 95.6% for gram-negative bacilli. The association of gram-positive cocci plus gram-negative bacilli were predictive of growth of both in 6.8%, growth of gram-positive cocci in 13.7%, and growth of gram-negative bacilli in 72.5%. Conclusions: The Gram stain is a method of great value in the initial diagnosis of the etiologic agent of peritonitis in CAPD, especially for gram-negative bacilli.

Spatial and temporal profiles for anti-inflammatory gene expression in leukocytes during a resolving model of peritonitis

The recent appreciation of the role played by endogenous counterregulatory mechanisms in controlling the outcome of the host inflammatory response requires specific analysis of their spatial and temporal profiles. In this study, we have focused on the glucocorticoid-regulated anti-inflammatory mediator annexin 1. Induction of peritonitis in wild-type mice rapidly (4 h) produced the expected signs of inflammation, including marked activation of resident cells (e.g., mast cells), migration of blood-borne leukocytes, mirrored by blood neutrophilia. These changes subsided after 48-96 h. In annexin 1null mice, the peritonitis response was exaggerated (∼40% at 4 h), with increased granulocyte migration and cytokine production. In blood leukocytes, annexin 1 gene expression was activated at 4, but not 24, h postzymosan, whereas protein levels were increased ai both time points. Locally, endothelial and mast cell annexin 1 gene expression was not detectable in basal conditions, whereas it was switched on during the inflammatory response. The significance of annexin 1 system plasticity in the anti-inflammatory properties of dexamethasone was assessed. Clear induction of annexin 1 gene in response to dexamethasone treatment was evident in the circulating and migrated leukocytes, and in connective tissue mast cells; this was associated with the steroid failure to inhibit leukocyte trafficking, cytokine synthesis, and mast cell degranulation in the annexin 1null mouse. In conclusion, understanding how inflammation is brought under control will help clarify the complex interplay between pro- and anti-inflammatory pathways operating during the host response to injury and infection. Copyright © 2006 by The American Association of Immunologists, Inc.

Risk of peritonitis during peritoneal dialysis in carriers of Staphylococcus aureus and coagulase-negative staphylococci

The presence of Staphylococcus aureus in the nasal cavities and pericatheter skin of peritoneal dialysis patients put them at high risk of developing peritonitis. However, it is not clear whether the presence of coagulase-negative staphylococci (CNS) in the nasal passages and skin of patients is related to subsequent occurrence of peritoneal infection. The aim of the present study was to verify the relationship between endogenous sources of S. aureus and CNS and occurrence of peritonitis in patients undergoing peritoneal dialysis. Thirty-two patients on peritoneal hemodialysis were observed for 18 months. Staphylococcus species present in their nasal passage, pericatheter skin and peritoneal effluent were identified and compared based on drug susceptibility tests and dendrograms, which were drawn to better visualize the similarity among strains from extraperitoneal sites as well as their involvement in the causes of infection. Out of 288 Staphylococcus strains isolated, 155 (53.8%) were detected in the nasal cavity, 122 (42.4%) on the skin, and 11 (3.8%) in the peritoneal effluent of patients who developed peritonitis during the study. The most frequent Staphylococcus species were CNS (78.1%), compared with S. aureus (21.9%). Among CNS, S. epidermidis was predominant (64.4%), followed by S. warneri (15.1%), S. haemolyticus (10.7%), and other species (9.8%). Seven (64%) out of 11 cases of peritonitis analyzed presented similar strains. The same strain was isolated from different sites in two (66%) out of three S. aureus infection cases. In the six cases of S. epidermidis peritonitis, the species that caused infection was also found in the normal flora. From these, two cases (33%) presented highly similar strains and in three cases (50%), it was difficult to group strains as to similarity. Patients colonized with multidrug-resistant S. epidermidis strains were more predisposed to infection. Results demonstrated that an endogenous source of S. epidermidis could cause peritonitis in peritoneal dialysis patients, similarly to what has been observed with S. aureus.

NOVEL PREDICTORS OF PERITONITIS-RELATED OUTCOMES IN THE BRAZPD COHORT

Introduction: Peritonitis remains the main cause of peritoneal dialysis (PD) technique failure worldwide, despite significant reductions in infection rates observed over the past decades. Several studies have described risk factors for peritonitis, technique failure and mortality. However, there are scarce data regarding predictors of complications during and after a peritonitis episode. The aim of our study was to analyze predictors of peritonitis-related outcome in the Brazilian Peritoneal Dialysis study (BRAZPD) cohort.Methods: All adult incident patients recruited in the BRAZPD Study between December 2004 and October 2007, who remained at least 90 days on PD and presented their first peritonitis episode (n = 474 patients) were included in the study. The endpoints analyzed were non-resolution, death due to a peritonitis episode and long-term technique survival after a peritonitis episode.Results: In the multivariable regression, non-resolution was independently associated with older age (odds ratio (OR) 1.02; p < 0.01), collagenosis as the primary renal disease (OR 4.6; p < 0.05) and Pseudomonas spp as etiological agent (OR 2.9; p < 0.05). Patients who were transferred from APD to CAPD during peritonitis therapy presented a higher risk of non-response (OR 2.5; p < 0.05). The only factor associated with death during a peritonitis episode was older age (OR 1.04; p < 0.05). Exposure to vancomycin and male gender were the independent predictors of long-term technique failure (OR 2.2; p < 0.01).Conclusion: Apart from confirming previous observations of the negative impact of older age and Pseudomonas spp peritonitis on outcomes, we observed that collagenosis may negatively impact response to treatment and exposure to vancomycin may possibly reduce long-term technique survival. It is important to emphasize that the association of vancomycin with technique failure does not prove causality. These findings shed light on new factors predicting outcome when peritonitis is diagnosed.

Peritoneal Dialysis-Related Peritonitis due to Coagulase-Negative Staphylococcus: A Review of 115 Cases in a Brazilian Center

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Efficacy of antibiotic therapy for peritoneal dialysis-associated peritonitis: a proportional meta-analysis

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Impact of patient training patterns on peritonitis rates in a large national cohort study

Background. Ideal training methods that could ensure best peritoneal dialysis (PD) outcome have not been defined in previous reports. The aim of the present study was to evaluate the impact of training characteristics on peritonitis rates in a large Brazilian cohort.Methods. Incident patients with valid data on training recruited in the Brazilian Peritoneal Dialysis Multicenter Study (BRAZPD II) from January 2008 to January 2011 were included. Peritonitis was diagnosed according to International Society for Peritoneal Dialysis guidelines; incidence rate of peritonitis (episodes/patient-months) and time to the first peritonitis were used as end points.Results. Two thousand two hundred and forty-three adult patients were included in the analysis: 59 +/- 16 years old, 51.8% female, 64.7% with <= 4 years of education. The median training time was 15 h (IQI 10-20 h). Patients were followed for a median of 11.2 months (range 3-36.5). The overall peritonitis rate was 0.29 per year at risk (1 episode/41 patient-months). The mean number of hours of training per day was 1.8 +/- 2.4. Less than 1 h of training/day was associated with higher incidence rate when compared with the intervals of 1-2 h/day (P = 0.03) and > 2 h/day (P = 0.02). Patients who received a cumulative training of > 15 h had significantly lower incidence of peritonitis compared with < 15 h (0.26 per year at risk versus 0.32 per year at risk, P = 0.01). The presence of a caregiver and the number of people trained were not significantly associated with peritonitis incidence rate. Training in the immediate 10 days after implantation of the catheter was associated with the highest peritonitis rate (0.32 per year), compared with training prior to catheter implantation (0.28 per year) or > 10 days after implantation (0.23 per year). More experienced centers had a lower risk for the first peritonitis (P = 0.003).Conclusions. This is the first study to analyze the association between training characteristics and outcomes in a large cohort of PD patients. Low training time (particularly < 15 h), smaller center size and the timing of training in relation to catheter implantation were associated with a higher incidence of peritonitis. These results support the recommendation of a minimum amount of training hours to reduce peritonitis incidence regardless of the number of hours trained per day.

Evidence-based medicine: an update on treatments for peritoneal dialysis-related peritonitis

Peritonitis continues to be a major complication of peritoneal dialysis (PD), and adequate treatment is crucial for a favorable outcome. There is no consensus regarding the optimal therapeutic regimen, and few prospective controlled studies have been published. The objective of this manuscript is to review the results of PD peritonitis treatment reported in narrative reviews, systematic reviews, and proportional meta-analyses. Two narrative reviews, the only existing systematic review and its update published between 1991 and 2014 were included. In addition, we reported the results of a proportional meta-analysis published by our group. Results from systematic reviews of randomized control trials (RCT) and quasi-RCT were not able to identify any optimal antimicrobial treatment, but glycopeptide regimens were more likely to achieve a complete cure than a first generation cephalosporin. Compared to urokinase, simultaneous catheter removal and replacement resulted in better outcomes. Continuous and intermittent IP antibiotic use had similar outcomes. Intraperitoneal antibiotics were superior to intravenous antibiotics in reducing treatment failure. In the proportional meta-analysis of RCTs and the case series, the resolution rate (86%) of ceftazidime plus glycopeptide as initial treatment was significantly higher than first generation cephalosporin plus aminoglycosides (66%) and glycopeptides plus aminoglycosides (75%). Other comparisons of regimens used for either initial treatment or treatment of gram-positive rods or gram-negative rods did not show statistically significant differences. The superiority of a combination of a glycopeptide and a third generation cephalosporin was also reported by a narrative review study published in 1991, which reported an 88% resolution rate.

Effect of treatment delay on disease severity and need for resuscitation in porcine fecal peritonitis

Objective: Early treatment in sepsis may improve outcome. The aim of this study was to evaluate how the delay in starting resuscitation influences the severity of sepsis and the treatment needed to achieve hemodynamic stability. Design: Prospective, randomized, controlled experimental study. Setting: Experimental laboratory in a university hospital. Subjects: Thirty-two anesthetized and mechanically ventilated pigs. Interventions: Pigs were randomly assigned (n = 8 per group) to a nonseptic control group or one of three groups in which fecal peritonitis (peritoneal instillation of 2 g/kg autologous feces) was induced, and a 48-hr period of protocolized resuscitation started 6 (Delta T-6 hrs), 12 (Delta T-12 hrs), or 24 (Delta T-24 hrs) hrs later. The aim of this study was to evaluate the impact of delays in resuscitation on disease severity, need for resuscitation, and the development of sepsis-associated organ and mitochondrial dysfunction. Measurements and Main Results: Any delay in starting resuscitation was associated with progressive signs of hypovolemia and increased plasma levels of interleukin-6 and tumor necrosis factor-alpha prior to resuscitation. Delaying resuscitation increased cumulative net fluid balances (2.1 +/- 0.5 mL/kg/hr, 2.8 +/- 0.7 mL/kg/hr, and 3.2 +/- 1.5 mL/kg/hr, respectively, for groups.T-6 hrs, Delta T-12 hrs, and.T-24 hrs; p < .01) and norepinephrine requirements during the 48-hr resuscitation protocol (0.02 +/- 0.04 mu g/kg/min, 0.06 +/- 0.09 mu g/kg/min, and 0.13 +/- 0.15 mu g/kg/min; p = .059), decreased maximal brain mitochondrial complex II respiration (p = .048), and tended to increase mortality (p = .08). Muscle tissue adenosine triphosphate decreased in all groups (p < .01), with lowest values at the end in groups Delta T-12 hrs and.T-24 hrs. Conclusions: Increasing the delay between sepsis initiation and resuscitation increases disease severity, need for resuscitation, and sepsis-associated brain mitochondrial dysfunction. Our results support the concept of a critical window of opportunity in sepsis resuscitation. (Crit Care Med 2012; 40:2841-2849)