Treatment Of Peritonitis In Peritoneal Dialysis Research Articles

The Association Between Serum Vancomycin Level and Clinical Outcome in Patients With Peritoneal Dialysis Associated Peritonitis

Intraperitoneal (IP) vancomycin is often first-line empiric therapy and then maintenance therapy for peritoneal dialysis (PD) peritonitis. However, how vancomycin serum levels correlate with clinical outcomes remains unclear. We conducted a retrospective single-center adult cohort study of 98 patients with PD peritonitis treated with IP vancomycin between January 2016 and May 2022. The association between nadir vancomycin level and cure was evaluated in a logistic regression model, first unadjusted and then adjusted for age, sex, weight, glomerular filtration rate (GFR), and total number of days on PD. Vancomycin was assessed both as a continuous exposure (per 1 mg/l increase) and as a categorical exposure (<15 mg/l vs.≥15 mg/l). A receiver operating characteristic curve (ROC) was created to explore nadir vancomycin level thresholds in an attempt to identify an optimal target level during treatment. Of the patients, 81% achieved cure, and patients with nadir vancomycin level≥15 mg/l were 7.5 times more likely to experience cure compared to those with a nadir level<15 mg/l (odds ratio [OR] 7.58, 95% confidence interval [CI] 1.71-33.57, P= 0.008). Weight, GFR, days on PD, sex, and age were not independently associated with outcome. The vancomycin level with the greatest discriminatory capacity for cure on the ROC analysis was 14.4 mg/l. Increasing IP vancomycin serum levels are associated with increased odds of cure; and maintaining vancomycin serum levels above 14-15 mg/l throughout the course of PD peritonitis treatment is likely to improve clinical outcomes.

Effect of different dialysis duration on the prognosis of peritoneal dialysis-associated peritonitis: a single-center, retrospective study

Background Peritoneal dialysis (PD)-associated peritonitis is a serious complication observed in peritoneal dialysis patients. Herein, we investigated the clinical characteristics and treatment outcomes of PD peritonitis in patients with different PD durations. Methods All peritonitis episodes from January 2007 to December 2020 at Peking University People’s hospital PD center were retrospectively analyzed and divided into the long-dialysis duration (≥60 months, LDD) and short-dialysis duration (<60 months, SDD) groups. Clinical characteristics and outcomes were compared between these groups. The risk factors for treatment failure were analyzed using a logistic regression model. Results During 14 years, 156 patients had 267 peritonitis episodes. There were 83 (31.1%) peritonitis episodes in the LDD group and 184 (68.9%) in the SDD group. No statistical difference was noted in peritonitis causes and the composition of causative pathogens between the two groups. The hospitalization, treatment failure, and transfer-to-hemodialysis rates, and peritonitis-related mortality were significantly higher in the LDD group than in the SDD group (all p < .05). Logistic regression analysis revealed that PD duration was an independent risk factor for PD-associated hospitalization, treatment failure and peritonitis-related death (p < .05). The receiver operating characteristic curve analysis results showed that when the cutoff value of PD duration was 5.5 years, the sensitivity of predicting PD peritonitis treatment failure was 51.1%, specificity was 78.8%, and the area under the curve was 0.679 (95% confidence interval: 0.594–0.765, p < .001). Conclusions PD duration is an independent risk factor for poor prognosis in PD peritonitis. Careful and active attention should be paid to the prevention of peritonitis in PD patients with long PD duration.

Relapsing and refractory peritoneal dialysis peritonitis caused by Corynebacterium amycolatum

BackgroundPeritonitis is an important complication and cause of morbidity in patients undergoing peritoneal dialysis (PD). Corynebacterium species, often considered skin and mucosal contaminants, are a rare cause of PD-associated peritonitis and have been acknowledged in published guidelines for the diagnosis and treatment of PD peritonitis only over the last decade.Case-Diagnosis/TreatmentWe present two children with difficult-to-treat episodes of PD peritonitis due to Corynebacterium amycolatum. Episodes were associated with fever, abdominal pain and cloudy dialysate, high dialysate polymorphonuclear leukocyte counts, and elevated serum C-reactive protein and procalcitonin concentrations. Symptoms persisted beyond 5 days in 4 of 5 peritonitis episodes, and peritonitis relapsed despite in vitro sensitivity of the bacterial isolates to guideline-recommended antibiotics. C. amycolatum was cultured from the PD catheter tip despite 4 weeks of intraperitoneal glycopeptide therapy and clinical peritonitis resolution suggestive of efficient biofilm formation. Our systematic literature search identified three previous (adult) case descriptions of C. amycolatum peritonitis, all with repeat episodes by the same organism. The incidence of C. amycolatum as a cause of PD peritonitis has not yet been established but is likely underreported due to challenges in species differentiation.ConclusionsC. amycolatum is a rarely identified cause of refractory and/or relapsing PD peritonitis. Species differentiation of non-diphtheriae Corynebacterium isolates is critical, and prolonged antibiotic treatment, preferably with a glycopeptide antibiotic, is recommended, with a low threshold for PD catheter change or removal in case of repeat peritonitis.

Association of Peritonitis With Cardiovascular Mortality Over Time in the Peritoneal Dialysis Population: An Australia and New Zealand Dialysis and Transplant Registry Study

Though peritonitis is associated with increased mortality in patients receiving peritoneal dialysis (PD), its association with cardiovascular mortality remains uncertain. The study participants included adult patients (≥18 years old) commencing PD in Australia (from October 2003 to December 2019) using the Australia and New Zealand Dialysis and Transplant (ANZDATA) registry. Association between peritonitis and cardiovascular mortality was evaluated using Cox proportional hazards analysis and competing risks analysis. Associations between peritonitis rates between different eras and cardiovascular mortality were also compared using Jointpoint regression model to determine the time point when a significant change in peritonitis trend occurred to define the era for cardiovascular mortality. Subgroup analysis dividing the groups into 0, 1 and≥2 episodes of peritonitis and sensitivity analysis censoring at 90 days post-transfer to hemodialysis (HD) were performed. The study included 9699 incident PD patients. The overall peritonitis rate was 0.37 episodes per patient-year and declined by 4.7% (95% confidence interval [CI] 3.6-5.8%) during the study period. Peritonitis was associated with increased cardiovascular mortality risk (subdistribution hazard ratio [SHR] 1.53, 95% CI 1.39-1.69, P< 0.001) with increasing peritonitis episodes associated with higher risk (1 episode of peritonitis SHR 1.41, 95%CI 1.24-1.61;≥2 episodes of peritonitis SHR 1.69, 95% CI 1.47-1.93, P< 0.001). Patients who commenced PD between 2012 and 2019 had a lower risk of cardiovascular mortality (SHR 0.60, 95% CI 0.50-0.72, P< 0.001), compared to patients who commenced between 2003 and 2011. Results were consistent in the sensitivity analysis. Peritonitis is independently associated with an increased risk of cardiovascular mortality, and the association is episode-dependent. Prevention and adequate treatment of PD peritonitis may improve cardiovascular outcomes among patients receiving PD.

Longer antibiotic durations for treating peritoneal dialysis-associated peritonitis: helpful or harmful?

Relapsing, recurrent or repeat peritonitis is a devastating complication for peritoneal dialysis (PD) patients and is usually associated with poor outcomes including prolonged hospitalization, catheter removal, hemodialysis transfer and even death. Despite its critical importance and frequent occurrence, there is limited available evidence to facilitate evidence-informed treatment of PD peritonitis. This editorial comments on the findings and limitations of a randomized controlled study published in this journal, which reported that extending antibiotic treatment duration for an additional week beyond that recommended by the International Society for PD did not reduce the risk of relapsing, recurrent or repeat peritonitis, and may have increased the risk of repeat peritonitis. These results are explored in the context of the existing literature and recommendations for practice and research are provided.

Loosening of the mesothelial barrier as an early therapeutic target to preserve peritoneal function in peritoneal dialysis.

Phenotype transition of peritoneal mesothelial cells (MCs) including the epithelial-to-mesenchymal transition (EMT) is regarded as an early mechanism of peritoneal dysfunction and fibrosis in peritoneal dialysis (PD), producing pro-inflammatory and pro-fibrotic milieu in the intra-peritoneal cavity. Loosening of intercellular tight adhesion between adjacent MCs as an initial process of EMT creates the environment where mesothelium and submesothelial tissue are more vulnerable to the composition of bio-incompatible dialysates, reactive oxygen species, and inflammatory cytokines. In addition, down-regulation of epithelial cell markers such as E-cadherin facilitates de novo acquisition of mesenchymal phenotypes in MCs and production of extracellular matrices. Major mechanisms underlying the EMT of MCs include induction of oxidative stress, pro-inflammatory cytokines, endoplasmic reticulum stress and activation of the local renin-angiotensin system. Another mechanism of peritoneal EMT is mitigation of intrinsic defense mechanisms such as the peritoneal antioxidant system and anti-fibrotic peptide production in the peritoneal cavity. In addition to use of less bio-incompatible dialysates and optimum treatment of peritonitis in PD, therapies to prevent or alleviate peritoneal EMT have demonstrated a favorable effect on peritoneal function and structure, suggesting that EMT can be an early interventional target to preserve peritoneal integrity.

Incidence and clinical features of patients with peritoneal dialysis peritonitis complicated by bacteremia.

The standard treatment of peritoneal dialysis peritonitis (PD peritonitis) is intraperitoneal antibiotic therapy. In patients with PD peritonitis complicated by bacteremia, intraperitoneal antibiotics combined with elective removal of the infected intraperitoneal catheter may be inadequate.We collected data of all patients with PD peritonitis admitted to Chi-Mei Medical Center during a 4-year period. We reviewed the medical records of the study cohort and collected their in-hospital details. Patients with positive blood culture results were assigned to the bacteremia group, whereas those with negative blood culture results were assigned to the peritonitis-only group.We discovered that 11.0% of patients with PD peritonitis had bacteremia complications, and immunocompromised comorbidities were more common in the bacteremia group than in the peritonitis-only group (66.7% vs 37.2%, P = .022). Additionally, the bacteremia group exhibited higher temperatures, greater respiratory rates, and lower serum sodium levels than the peritonitis-only group (temperature, 37.7 vs 37.2 °C, P = .014; respiratory rate, 19.1 vs 17.9 rate/min, P = .008; serum sodium level, 130.3 vs 132.7 mEq/L, P = .031). No mortality was found in patients with PD peritonitis complicated by bacteremia after intravenous and intraperitoneal antibiotic therapy.More than 1 in 10 patients with PD peritonitis was complicated by bacteremia, which resulted in extensive systemic derangements. Patients with immunocompromised comorbidities carried a higher risk of developing bacteremia, resulting in prolonged hospital stays. Combination of intraperitoneal and intravenous antibiotics therapies achieved fair prognoses in patients with PD peritonitis complicated by bacteremia.

Pharmacokinetics of Intravenous Amikacin in Intermittent Hemodialysis: Treatment of Peritoneal Dialysis Peritonitis Caused by Nontuberculous Mycobacterium (NTM)

Pharmacokinetics of Intravenous Amikacin in Intermittent Hemodialysis: Treatment of Peritoneal Dialysis Peritonitis Caused by Nontuberculous Mycobacterium (NTM)

Peritonitis in peritoneal dialysis patients in Japan: a 2013 retrospective questionnaire survey of Japanese Society for Peritoneal Dialysis member institutions

Peritonitis is the main cause of withdrawal from peritoneal dialysis (PD) therapy in Japan. The precise extent of PD-associated peritonitis in Japan has not been investigated since 2005; we aimed to clarify the recent incidence and prognosis of PD peritonitis. The 248 institutional members of the Japanese Society for Peritoneal Dialysis were surveyed by questionnaire regarding peritonitis episodes during January 1 to December 31, 2013. Replies from 114 members were received regarding 3042 PD patients, including 516 peritonitis patients, covering a total observation period of 31,686 patient months. The incidence of peritonitis in this study was 0.195 episodes per year. Detailed data on 544 peritonitis episodes in 466 patients was obtained. The causes, in ranked order, were unknown reason, contamination at peritoneal fluid exchange, and extension of intra-abdominal cavity infection. Effluent culture methods included using a blood culture bottle (50.9 %), large-volume culture (culturing sediment after centrifuging effluent) (31.7 %), and direct culture of effluent using a culture dish (12.7 %). The rank order of microbes identified in peritoneal effluent cultures was culture-negative, Streptococcus sp. and Staphylococcus aureus. Empiric therapy with two kinds of antibiotics was administered to 406 cases (75.2 %), most commonly cefazolin + ceftazidime. Antibiotic administration methods included intraperitoneal (51.4 %), intravenous (46.4 %), and oral (2.2 %). After a peritonitis episode, 461 patients (84.7 %) continued PD therapy, 80 (14.7 %) withdrew from PD treatment, and 6 (1.1 %) died. Prognosis among patients grouped by antibiotic administration method was statistically significantly different; in the oral administration group, the rates of mortality and catheter replacement were higher. Logistic regression analysis showed that catheter exit-site infection and frequency of past peritonitis episodes were independent factors associated with PD treatment withdrawal. Although the overall incidence of PD peritonitis in Japan was relatively low, several areas for future improvement were identified: unknown reason and culture-negative were the most frequently cited causes of peritonitis; 1.1 % of patients died, and 13.6 % discontinued PD therapy. Improvements in effluent culture techniques, antibiotic administration methods, etiology determination, and patient education could help. A more effective protocol must be established to further improve the treatment of PD peritonitis in Japan.

Systemic Toxicity of Intraperitoneal Vancomycin.

Intraperitoneal vancomycin is used for empiric treatment of peritoneal dialysis peritonitis. It is dosed intermittently and a high systemic concentration is often achieved. Despite this, there are very few reports of systemic toxicity from intraperitoneal vancomycin. We report the course of a patient who developed a drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome after three weeks of intraperitoneal vancomycin. We review the literature and conclude that this is the first ever reported case of DRESS syndrome from intraperitoneal vancomycin.

Effects of a Statewide Protocol for the Management of Peritoneal Dialysis-Related Peritonitis on Microbial Profiles and Antimicrobial Susceptibilities: A Retrospective Five-Year Review.

♦ Peritonitis is a major complication of peritoneal dialysis (PD) and is associated with significant morbidity and mortality. Early empirical antibiotic therapy is recommended, with the choice of agents guided by local resistance patterns. As routine use of specific antimicrobial agents can drive resistance, regular assessment of causative organisms and their susceptibility to empirical therapy is essential. ♦ We conducted a retrospective review of all PD peritonitis cases and positive PD fluid cultures obtained over a 5-year period in Western Australia following the introduction of a statewide protocol for the initial management of PD peritonitis with intraperitoneal vancomycin and gentamicin. ♦ The incidence of PD peritonitis decreased from 1 in 16 patient months (0.75/year at risk) to 1 in 29 patient months (0.41/year at risk) over the 5 years. There were 1,319 culture-positive samples and 1,069 unique isolates identified. Gram-positive bacteria accounted for 69.9% of positive cultures, with vancomycin resistance averaging 2% over the study period. Gram-negative bacteria accounted for 25.4% of positive cultures, with gentamicin resistance identified in an average of 8% of organisms. No increase in antimicrobial resistance to vancomycin or gentamicin occurred over the 5 years and there was no change in the proportion of gram-positive (69.9%), gram-negative (25.4%) or fungal (4.4%) organisms causing PD peritonitis. ♦ Over time, the peritonitis rates have dramatically improved although the profile of causative organisms remains similar. Empirical treatment of PD peritonitis with intraperitoneal vancomycin and gentamicin remains efficacious, with high levels of susceptibility and no evidence that the introduction of this statewide empirical PD peritonitis treatment protocol is driving resistance to these agents.

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.

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

BackgroundThe choice of antimicrobials for initial treatment of peritoneal dialysis (PD)-related peritonitis is crucial for a favorable outcome. There is no consensus about the best therapy; few prospective controlled studies have been published, and the only published systematic reviews did not report superiority of any class of antimicrobials. The objective of this review was to analyze the results of PD peritonitis treatment in adult patients by employing a new methodology, the proportional meta-analysis.MethodsA review of the literature was conducted. There was no language restriction. Studies were obtained from MEDLINE, EMBASE, and LILACS. The inclusion criteria were: (a) case series and RCTs with the number of reported patients in each study greater than five, (b) use of any antibiotic therapy for initial treatment (e.g., cefazolin plus gentamicin or vancomycin plus gentamicin), for Gram-positive (e.g., vancomycin or a first generation cephalosporin), or for Gram-negative rods (e.g., gentamicin, ceftazidime, and fluoroquinolone), (c) patients with PD-related peritonitis, and (d) studies specifying the rates of resolution. A proportional meta-analysis was performed on outcomes using a random-effects model, and the pooled resolution rates were calculated.ResultsA total of 64 studies (32 for initial treatment and negative culture, 28 reporting treatment for Gram-positive rods and 24 reporting treatment for Gram-negative rods) and 21 RCTs met all inclusion criteria (14 for initial treatment and negative culture, 8 reporting treatment for Gram-positive rods and 8 reporting treatment for Gram-negative rods). The pooled resolution rate of ceftazidime plus glycopeptide as initial treatment (pooled proportion = 86% [95% CI 0.82–0.89]) was significantly higher than first generation cephalosporin plus aminoglycosides (pooled proportion = 66% [95% CI 0.57–0.75]) and significantly higher than glycopeptides plus aminoglycosides (pooled proportion = 75% [95% CI 0.69–0.80]. Other comparisons of regimens used for either initial treatment, treatment for Gram-positive rods or Gram-negative rods did not show statistically significant differences.ConclusionWe showed that the association of a glycopeptide plus ceftazidime is superior to other regimens for initial treatment of PD peritonitis. This result should be carefully analyzed and does not exclude the necessity of monitoring the local microbiologic profile in each dialysis center to choice the initial therapeutic protocol.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2334-14-445) contains supplementary material, which is available to authorized users.

Cephazolin and Gentamicin Are Stable in Lactate-Buffered Fresenius Peritoneal Dialysate for Seven Days at Room Temperature

Peritoneal dialysis (PD) peritonitis is a common complication of PD and is associated with significant morbidity and mortality (1). Treatment involves intraperitoneal delivery of antibiotics, which, for this condition, is superior to the intravenous route (2). Outpatient treatment involves loading antibiotics into bags of dialysate, which are then self-administered. However, some patients are unable to load the antibiotics themselves and therefore rely on pre-loaded bags provided to them by health care staff. Treatment for PD peritonitis is usually required for no less than 14 days, and it is desirable to pre-load at least several days’ worth of bags for convenient outpatient therapy (3). That pre-loading in turn depends on the stability of the required antibiotic in solution under conditions of home storage. However, relevant data on antibiotic stability is limited to just some of the available PD solutions and containers (4-7). Guidelines, such as those published by the International Society for Peritoneal Dialysis provide information about the stability and compatibility of various antibiotics in peritoneal dialysate, although they note the limited data for specific PD solutions and suggest the need for further study (3). It has also been suggested by others that data obtained from experiments in one solution or system cannot be extrapolated to another (4). A commonly used PD system is the polyvinyl chloride twin-bagged lactate-buffered glucose-based solution from Fresenius (ANDY-Plus/Disc: Fresenius Medical Care, Bad Homburg, Germany). The stability of antibiotics in this system has not been widely studied and cannot be confirmed by the manufacturer. The aim of the present study was therefore to assess the stability of cephazolin and gentamicin in that dialysate under conditions that simulate up to 7 days of home storage, to ensure effective and convenient use for outpatient treatment of PD peritonitis.

Nafcillin-Induced Bullous Skin Eruption with Granulocytopenia in a Patient with End-Stage Renal Disease

Nafcillin is an antibiotic used for infections due to penicillin-resistant Staphylococcus aureus. In general, the adverse reactions to nafcillin have not been frequent and serious. We report here a new type of adverse reaction to nafcillin in a patient with end-stage renal disease in whom nafcillin caused the unexpected complication of bullous drug eruption and subseqent neutropenia. Three weeks after the start of intravenous nafcillin for the treatment of peritoneal dialysis peritonitis, the patient developed blisters on his right ankle. These became progressive and widespread, with bullae affecting most of the body surface. In addition, neutropenia developed three days after the appearance of bullous skin lesions. Spontaneous recovery of skin lesions and neutropenia was observed after the withdrawal of naficillin. When treating patients with chronic renal failure, physicians should be aware of these rare but potentially severe adverse reactions.

Treatment of Peritoneal Dialysis–Associated Peritonitis: A Systematic Review of Randomized Controlled Trials

Peritonitis frequently complicates peritoneal dialysis. Appropriate treatment is essential to reduce adverse outcomes. Available trial evidence about peritoneal dialysis peritonitis treatment was evaluated. The Cochrane CENTRAL Registry (2005 issue), MEDLINE (1966 to February 2006), EMBASE (1985 to February 2006), and reference lists were searched to identify randomized trials of treatments for patients with peritoneal dialysis peritonitis. Trials of antibiotics (comparisons of routes, agents, and dosing regimens), fibrinolytic agents, peritoneal lavage, and intraperitoneal immunoglobulin. Treatment failure, relapse, catheter removal, microbiological eradication, hospitalization, all-cause mortality, and adverse reactions. 36 eligible trials were identified: 30 trials (1,800 patients) of antibiotics; 4 trials (229 patients) of urokinase; 1 trial of peritoneal lavage (36 patients); and 1 trial of intraperitoneal immunoglobulin (24 patients). No superior antimicrobial class was identified. In particular, glycopeptides and first-generation cephalosporins were equivalent (3 trials, 387 patients; relative risk [RR], 1.84; 95% confidence interval [CI], 0.95 to 3.58). Simultaneous catheter removal/replacement was superior to urokinase at decreasing treatment failures (1 trial, 37 patients; RR, 2.35; 95% CI, 1.13 to 4.91). Continuous and intermittent intraperitoneal antibiotic dosing were equivalent regarding treatment failure (4 trials, 338 patients; RR, 0.69; 95% CI, 0.37 to 1.30) and relapse (4 trials, 324 patients; RR, 0.93; 95% CI, 0.63 to 1.39). One trial showed superiority of intraperitoneal antibiotics over intravenous therapy. The method quality of trials generally was suboptimal and outcome definitions were inconsistent. Small patient numbers led to inadequate power to show an effect. Interventions, such as optimal duration of antibiotic therapy, were not evaluated. Trials did not identify superior antibiotic regimens. Intermittent and continuous antibiotic dosing are equivalent treatment strategies.

Single UK centre experience on the treatment of PD peritonitis--antibiotic levels and outcomes

There are few studies of the pharmacokinetics of vancomycin and gentamicin in peritoneal dialysis (PD) patients and the influence of antibiotic concentrations on treatment outcome. Concerns about resistance to ceftazidime and potential of aminoglycoside toxicity make the choice of empiric antibiotic difficult. We retrospectively collected data from 613 patients on PD between 1 June 2002 and 31 December 2005. During this time, we adopted a protocol that minimized aminoglycoside exposure to patients with residual renal function and carefully monitored serum antibiotic concentrations. There were no statistical differences in mean day-5 vancomycin concentrations for continuous ambulatory peritoneal dialysis (CAPD) vs automated peritoneal dialysis (APD) and for anuric vs not-anuric patients. However, low levels (<12 mg/l) were recorded for 12.8% CAPD and 15% APD patients. These remained low at day 10 in 16% patients (25% if not anuric) despite incremental dosing. Vancomycin concentration did not predict cure or relapse of Gram-positive or culture-negative peritonitis. Gentamicin concentration (>2 mg/l in >50% patients) did not predict outcome of Gram-negative and culture-negative peritonitis. Moreover, cure rates were the same irrespective of whether gentamicin was continued for 14 days or was switched to ceftazidime after 5 days. We have confirmed that the International Society for Peritoneal Dialysis (ISPD) dosing guideline for vancomycin in CAPD and APD patients produces adequate serum concentrations of the antibiotics in the vast majority. However, large incremental dosing of vancomycin is needed if day-5 levels are low; especially for not-anuric patients. Whilst evidence of gentamicin toxicity in PD remains controversial, ISPD dosing regimen resulted in high levels for >50% patients. High gentamicin concentrations did not correlate with treatment success, but switching gentamicin to ceftazidime at day 5 appeared safe and limited aminoglycoside exposure. Increasing vancomycin and gentamicin concentrations do not appear to improve cure rates and alternative strategies (such as combination treatment) should be considered for future research.

Three-year analysis of microbial aetiology and antimicrobial susceptibilities of PD peritonitis

The first-line antibiotic treatment of peritoneal dialysis (PD) peritonitis has to cover the most common causative microorganisms. Our aim was to analyse antimicrobial sensitivities of different empirical protocols for initial therapy of PD peritonitis. We analysed the aetiological microorganisms of PD peritonitis and their antimicrobial sensitivities during a 36-month period. Clinical characteristics of the cases were recorded. Altogether 86 PD peritonitides were diagnosed during the study period. In 58 cases, microbial cultures were positive with 72 different causative agents. 28 cases (33%) were culture-negative. Over-representation of icodextrin users was noted among the culture-negative cases. Staphylococcus aureus was the most frequent causative agent, often leading to severe course of illness. Of antimicrobial protocols for initial treatment of peritonitis tested in vitro, the combination of a first-generation cephalosporin and an aminoglycoside was superior to the combination of a first-generation cephalosporin and ceftazidime as well as to fluoroquinolone monotherapy but similar to the combination of vancomycin and ceftazidime. Based on antimicrobial sensitivities we continue using an aminoglycoside in the empirical treatment of PD peritonitis. In the present material, users of icodextrin PD fluid were over-represented among patients with culture-negative peritonitis.

Efficacy of a non‐vancomycin‐based peritoneal dialysis peritonitis protocol

Peritonitis has a significant impact upon morbidity and mortality of peritoneal dialysis (PD) patients. Gram-positive organisms account for the majority of infections and vancomycin is a cost effective broad-spectrum antimicrobial treatment for PD peritonitis, but this may lead to the emergence of multiple antibiotic-resistant organisms. The purpose of the present paper was to evaluate the efficacy of a non-vancomycin-based protocol comprising cephazolin and gentamicin, which was introduced in the present PD population as empirical treatment for peritonitis. The study involved 82 peritonitis episodes over a 4-year period in 58 patients, excluding those with previous methicillin-resistant staphylococcal peritonitis. With cephazolin and gentamicin there was no apparent difference in response or relapse rates in comparison to reported studies using vancomycin-based first-line therapy protocols. We advocate initial treatment of PD peritonitis with non-vancomycin-based therapy given similar efficacy and the potential for reduction of resistant organisms.

Cefazolin plus Ceftazidime versus Imipenem / Cilastatin Monotherapy for Treatment of Capd Peritonitis — a Randomized Controlled Trial

Peritonitis is a serious complication of peritoneal dialysis (PD). We studied the efficacy of imipenem/cilastatin monotherapy in the treatment of PD-related peritonitis. We performed an open-label, randomized control study comparing imipenem/cilastatin monotherapy (treatment group) versus cefazolin plus ceftazidime (control group) in the treatment of PD peritonitis. The result was further compared to a historic group treated with cefazolin plus netilmycin. Outcome measures were primary response rate at day 10 and complete cure rate. We enrolled 51 patients in the treatment group, 51 in the control group, and identified 96 in the historic group. The primary response rate to the assigned antibiotics was 49.0%, 51.0%, and 49.0% for the treatment, control, and historic groups, respectively (p = 0.97). The primary response rate allowing for change in antibiotic was 82.4%, 90.2%, and 82.3%, respectively, for the three groups (p = 0.41). The complete cure rate was 72.5%, 80.4%, and 82.3%, respectively (p = 0.60). Tenckhoff catheter removal was needed in 6 cases in the treatment group, 6 cases in the control group, and 13 cases in the historic group (p = 0.90). We concluded that monotherapy of imipenem/cilastatin has similar efficacy compared to the two standard regimens of cefazolin plus ceftazidime or netilmycin in the treatment of PD peritonitis.