Intraperitoneal Administration Of Antibiotics Research Articles

Clinical-experimental justification of the method of prevention and treatment of appendicular pylephlebitis

Taking into account the pathogenesis peculiarities of appendicular pylephlebitis, the risk group includes patients with a retrocecal location of the appendix, gangrenous and perforating appendicitis, the course of which was complicated by peritonitis or abscess. The purpose of our clinical-experimental study was to justify the method of pathogenetic treatment of acute appendicular pylephlebitis based on an experimental model of portal hypertension. Acute experiments were performed on male Wistar rats and outbred dogs. Clinical studies were prospectively-retrospective. In addition to traditional methods of treatment, we used the developed technique of draining the retroperitoneal space and introducing antibacterial compositions in a complex with a 10% dimethylsulfoxide (DMSO) solution was used. On the basis of experimental data, it was established that a 10% solution of DMSO complexed with a dye, when injected transperitoneally in the ileocecal angle area, preferentially penetrates the lymphatic and portal systems, even in conditions of portal hypertension. This is explained by the peculiarities of the anatomical structure. The use of the method of intraperitoneal administration of antibiotics in combination with DMSO is pathogenetically justified in patients with appendicular pylephlebitis, as it achieves local sanitation of the immediate source and primary ways of spreading the infection. Implementation of the developed method of prevention and treatment of acute pylephlebitis of appendicular genesis as part of improved treatment tactics allows to improve treatment results by likely reducing the frequency of postoperative complications from 18.7% to 2.7% (χ2 = 20.02, 95% CI 9.25-23.8) and the duration of hospitalization from 22.8 days to 8.5 days.

Intraperitoneally Administered Vancomycin in Patients with Peritoneal Dialysis-Associated Peritonitis: Population Pharmacokinetics and Dosing Implications.

Peritonitis is a limiting complication of peritoneal dialysis, which is treated by intraperitoneal administration of antibiotics. Various dosing strategies are recommended for intraperitoneally administered vancomycin, which leads to large differences in intraperitoneal vancomycin exposure. Based on data from therapeutic drug monitoring, we developed the first-ever population pharmacokinetic model for intraperitoneally administered vancomycin to evaluate intraperitoneal and plasma exposure after dosing schedules recommended by the International Society for Peritoneal Dialysis. According to our model, currently recommended dosing schedules lead to possible underdosing of a large proportion of patients. To prevent this, we suggest avoiding intermittent intraperitoneal vancomycin administration, and for the continuous dosing regimen, we suggest a loading dose of 20 mg/kg followed by maintenance doses of 50 mg/L in each dwell to improve the intraperitoneal exposure. Vancomycin plasma level measurement on the fifth day of treatment with subsequent dose adjustment would prevent it from reaching toxic levels in the few patients who are susceptible to overdose.

Specifičnost antibiotske terapije kod pacijenata sa hroničnom insuficijencijom bubrega

Chronic kidney diseases cause disruption of kidney function, but also of other organs which affects both the pharmacodynamics and the pharmacokinetics of many drugs. Prescribing drugs to patients with chronic kidney disease requires knowledge of changes in absorption, distribution, metabolism and excretion of drugs and their metabolites. Avoiding nephrotoxic drugs is the most important principle that we must follow in patients with chronic kidney disease. If administration of nephrotoxic drugs is necessary, regular control of glomerular filtration rate, serum electrolyte concentration, and serum drug concentration is required if possible. The dosing of drugs in patients with chronic renal insufficiency is very delicate, both when determining the initial dose and during the maintenance dose, so it is necessary to adjust the doses for each patient individually, depending on the degree of kidney damage. For most drugs, there are recommendations from the Agency for Drugs and Medical Devices of the Republic of Serbia on how to correct the dose of the drug in chronic kidney failure. If such a recommendation does not exist, general rules are used: the maintenance dose can be adapted to kidney function by reducing the dose, extending the intervals in which the unchanged dose of the drug is administered, or a combination of these two methods. In patients with chronic kidney damage, the infection accelerates the progression towards the terminal stage, when it is necessary to apply one of the methods to replace kidney function. The infection should be treated with appropriate doses of antibiotics and/or antifungals and for a sufficient period of time. Likewise, in dialysis patients, there are various causes of infections that must also be adequately treated in order not to compromise the dialysis method or endanger the patient's life. There are recommendations for the use of antibiotics and antimycotics in these cases, which should be applied and adjusted to the individual patient. In intensive care units, in hemodynamically unstable patients with sepsis and acute chronic kidney failure, instead of intermittent hemodialysis, the following methods can be used: prolonged intermittent hemodialysis (PID) and continuous procedures - continuous venovenous hemodialysis (CVVHD), continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodiafiltration (CVVHDF). The dosage of antibiotics in these patients is specific and adjusted to the individual patient and his kidney function. Peritoneal dialysis patients in the terminal phase of chronic kidney failure are at risk of developing peritonitis. The guides describe which antibiotics are used to start the treatment of peritonitis and how the antibiotics are then adjusted, according to the causative agent, after the dialysate culture is obtained. Treatment of peritonitis is mainly by intraperitoneal administration of antibiotics, but it is also possible with oral or parenteral antibiotics, i.e. their combination. The guidelines describe the initial and maintenance doses of antibiotics and antifungals. If treatment is not started on time, the dialysis method may be compromised and the patient may die. If fungi are isolated by culture, the treatment of the patient with peritoneal dialysis is stopped and the dialysis catheter is removed, and the treatment is continued with the administration of antibiotics intravenously.

Something Odd and Something New: A Case of Shewanella putrefaciens Peritonitis and Bacteremia Treated with Intraperitoneal Cefepime

Shewanella spp. is a Gram-negative rod that is normally found in the marine environment and rarely causes illness in humans. Since the late 1970s, cases of Shewanella spp. infection have been described in the literature with a wide array of clinical syndromes and was found to be commonly seen in patients with predisposing conditions. We report a case of a 73 year old woman with end-stage renal disease on peritoneal dialysis who presented with a 3 day history of abdominal pain and was found to have Shewanella putrefaciens peritonitis complicated by bacteremia. She was treated in a novel and successful way by administration of intraperitoneal cefepime. This was further validated by adequate cefepime blood concentrations after drawing a cefepime serum level on day 8 of treatment. To the best of our knowledge, intraperitoneal antibiotic administration to treat both bacterial peritonitis and bacteremia has not been reported in the literature. This treatment approach could potentially be a good precedent for peritoneal dialysis patients needing antibiotics as a less invasive option for antibiotic administration.

Peritoneal Dialysis Guidelines 2019 Part 2: Main Text (Position paper of the\xa0Japanese Society for Dialysis Therapy)

BackgroundThis article is a duplicated publication from the Japanese version of “2019 JSDT Guidelines for Peritoneal Dialysis” with permission from the Japanese Society for Dialysis Therapy (JSDT). This clinical practice guideline (CPG) was developed primarily by the Working Group on Revision of Peritoneal Dialysis (PD) Guidelines of the Japanese Society for Dialysis Therapy. Recently, the definition and creation process for CPGs have become far more rigorous; traditional methods and formats no longer adhere to current standards. To improve the reliability of international transmission of our findings, CPGs are created in compliance with the methodologies developed by the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) working group. Part 2 of this PD guideline is the first CPG developed by our society that conforms to the GRADE approach.MethodsDetailed processes were created in accordance with the Cochrane handbook and the GRADE approach developed by the GRADE working group.ResultsClinical question (CQ)1: Is the use of renin-angiotensin system inhibitors (RAS inhibitors), such as angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB), effective in PD patients?Recommendation: We suggest the usage of RAS inhibitors (ACEI and ARB) in PD patients (GRADE 2C).CQ2: Icodextrin or glucose solution: which is more useful as a dialysate among patients with PD?Recommendation: We suggest using icodextrin when managing body fluids in PD patients (GRADE 2C).CQ3: Is it better to apply or not apply mupirocin/gentamicin ointment to the exit site?Recommendation: We suggest not applying mupirocin/gentamicin ointment to the exit sites of PD patients (GRADE 2C).CQ4: Which surgical approach is more desirable when a PD catheter is placed, open surgery or laparoscopic surgery?No recommendation.CQ5: Which administration route of antibiotics is better in PD patients with peritonitis, intravenous or intraperitoneal?Recommendation: We suggest intraperitoneal administration of antibiotics in PD patients with peritonitis (GRADE 2C).Note: The National Insurance does not currently cover intraperitoneal administration.CQ6: Is peritoneal dialysis or hemodialysis better as the first renal replacement therapy in diabetic patients?No recommendation.ConclusionsIn the future, we suggest that society members construct their own evidence to answer CQs not brought up in this guideline, and thereby show the achievements of Japan worldwide.

Stability of ceftolozane and tazobactam in different peritoneal dialysis solutions.

Peritonitis is a common and serious complication of peritoneal dialysis (PD). PD-associated peritonitis (PDAP) caused by Pseudomonas is usually resistant to most antibiotics, resulting in high failure rates. Ceftolozane/tazobactam (C/T) has been shown to be effective in treating urinary tract and intra-abdominal infections caused by beta-lactam resistant Pseudomonas and other gram-negative bacteria. Given its favourable adverse effects profile, it has a potential role in the treatment of PDAP caused by Pseudomonas species resistant to other antibiotics. Intraperitoneal administration of antibiotics admixed with PD solutions for the treatment of PDAP is associated with superior outcomes. However, there is a lack of published data on the stability of C/T in PD solutions. Therefore, this study investigated the physical and chemical stability of C/T in commonly used PD solutions at different temperatures. A total of 27 PD bags (3 PD bags for each type of PD solution including Dianeal®, Extraneal®, Balance® and Physioneal® PD bags) containing C/T were prepared and stored at 25°C for 6 h, followed by 4°C for 168 h and then 37°C for 12 h. An aliquot from each PD bag was withdrawn, and the concentration of C/T before (0 h) and after predefined time points was determined using a stability-indicating high-performance liquid chromatography assay. Samples were also assessed for pH, colour change and particulate matter immediately after preparation and on each day of analysis. C/T retained more than 97% of their initial concentration when stored at 25°C for 6 h followed by storage at 4°C for 168 h and then at 37°C for 12 h. Particle formation was not detected at any time under the tested storage conditions. The pH and colour remained essentially unchanged throughout the study. These results provide a platform for clinical studies to determine the safety and therapeutic efficacy of intraperitoneal C/T for the treatment of PDAP caused by resistant Pseudomonas species.

Compatibility of aztreonam in four commercial peritoneal dialysis fluids

The preferable route for treatment of peritoneal dialysis related peritonitis remains the intraperitoneal administration of antibiotics admixed to peritoneal dialysis fluids. It is important to know whether the administered drug is compatible with the PD fluids and its container. In the present study the compatibility of aztreonam with four commercial PDFs at storing temperatures and duration representative for storing conditions in the clinical settings was investigated. Aztreonam concentrations were determined using high-performance liquid chromatography. The antimicrobial activity of aztreonam was evaluated using an E. coli diffusion disk inhibition assay and P. aeruginosa time-kill curves. In Extraneal evaluated at 6 °C, 25 °C and 37 °C aztreonam was stable over the whole study period of 14 days and 24 hours, respectively. In Physioneal and Nutrineal aztreonam was stable at 6 °C for up to 14 days. Antimicrobial activity was retained in all PD fluids over the whole study period. Aztreonam remained stable and was compatible with the PD fluids, particularly with Extraneal or Nutrineal, and no compensatory dose adjustment is needed when stored for up to 14 days at refrigeration temperature before use.

Compatibility of ciprofloxacin with commercial peritoneal dialysis solutions

Intraperitoneal administration of antibiotics together with peritoneal dialysis fluids (PDFs) remains the preferable route for treatment of peritoneal dialysis-related peritonitis. For home based therapy, antibiotic-containing PDFs are stored for up to two weeks and warmed up to body-temperature before administration. The present study investigated the compatibility of ciprofloxacin with five commercial PDFs at refrigeration-temperature, room-temperature and body-temperature. Ciprofloxacin concentrations were determined using high-performance liquid chromatography. Drug-diluent stability was evaluated by measurement of pH-values and visual inspection at each sampling point. The antimicrobial activity of ciprofloxacin was assessed by an E. coli disk diffusion method. Ciprofloxacin was stable at refrigeration-temperature and body-temperature in all PDFs evaluated over the whole study period of 14 days and 24 hours, respectively. At room-temperature, in contrast, ciprofloxacin demonstrated only limited stability in particular when tested in mixed Physioneal. Except for Physioneal 1.36%, no relevant drug adsorption was observed and the antimicrobial activity of ciprofloxacin was found to be preserved in each PDF at each storage condition investigated. Intraperitoneal ciprofloxacin might be used for inpatient and home based therapy of peritoneal dialysis-related peritonitis and no compensatory dose adjustment is needed when stored for up to two weeks at refrigeration-temperature before use.

Influence of different peritoneal dialysis fluids on the in vitro activity of fosfomycin against Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa

Peritonitis is still the main infectious complication among patients on peritoneal dialysis. For treatment of peritoneal dialysis-related peritonitis, the intraperitoneal administration of antibiotics admixed to peritoneal dialysis fluids (PDFs) should be preferred. However, the influence of diverse PDFs on the activity of frequently used antibiotics has been investigated insufficiently. Thus, the present study set out to investigate the in vitro activity of fosfomycin against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis, and Staphylococcus aureus in commercially available PDFs. Time-kill curves in four different PDFs (Dianeal®, Extraneal®, Nutrineal®, and Physioneal®) were performed over 24 h with two different concentrations of fosfomycin (150 and 400 mg/L) and without antibiotics as control. Cation-adjusted Mueller Hinton broth (CA-MHB) was used as a comparator solution. In blank PDFs, bacterial growth of each organism evaluated was reduced when compared to CA-MHB. For S. aureus in blank Physioneal®, a reduction under the limit of detection was observed within 24 h. The activity of fosfomycin was reduced in all PDFs when compared to CA-MHB except for P. aeruginosa in Nutrineal® where the activity of fosfomycin was increased when investigated at 400 mg/L. Against E.coli, bactericidal activity was demonstrated in Extraneal®, Nutrineal®, and Physioneal®. Fosfomycin resistance (MIC > 1024 mg/L) was observed for P. aeruginosa in CA-MHB at both concentrations and in Nutrineal® at 150 mg/L. Fosfomycin is active in PDFs particularly against the frequently isolated enterobacterium E. coli. The choice of the respective PDF considerably influences the microbiological outcome in vitro. Further studies are warranted to investigate the clinical relevance of these findings.

Compatibility of fosfomycin with different commercial peritoneal dialysis solutions

For treatment of peritoneal dialysis-related peritonitis, intraperitoneal administration of antibiotics remains the preferable route. For home-based therapy, patients are commonly supplied with peritoneal dialysis fluids already containing antimicrobial agents. The present study set out to investigate the compatibility of fosfomycin with different peritoneal dialysis fluids, namely, Extraneal®, Nutrineal®, Physioneal® 1.36% and Physioneal® 2.27%, under varying storage conditions. The peritoneal dialysis fluid bags including 4 g fosfomycin were stored over 14 days at refrigeration temperature (6°C) and room temperature (25°C) and over 24 h at body temperature (37°C). Drug concentrations over time were determined by using high-performance liquid chromatography coupled to a mass spectrometer. In addition, drug activity was assessed by a disk diffusion method, diluent stability by visual inspection and drug adsorption by comparison of the measured and calculated concentrations. Blank peritoneal dialysis fluids and deionized water were used as comparator solutions. Fosfomycin was stable in all peritoneal dialysis fluids and at each storage condition investigated over the whole study period. The remaining drug concentrations ranged between 94% and 104% of the respective initial concentrations. No significant drug adsorption was observed for any peritoneal dialysis fluid at any storage condition. No relevant reduction of antimicrobial activity was observed. Fosfomycin is compatible with Extraneal®, Nutrineal® and Physioneal® for up to two weeks at refrigeration or room temperature and may be used for home-based therapy. No dose adjustment is needed due to adsorption or degradation.

Intraperitoneal Vancomycin Plus Either Oral Moxifloxacin or Intraperitoneal Ceftazidime for the Treatment of Peritoneal Dialysis−Related Peritonitis: A Randomized Controlled Pilot Study

Intraperitoneal administration of antibiotics is recommended as a first treatment for managing peritoneal dialysis (PD)-related peritonitis. However, the efficacy of oral administration of quinolones has not been well studied. Randomized controlled pilot study. 80 eligible patients with PD-related peritonitis from Peking University First Hospital (40 in each arm). Intraperitoneal vancomycin, 1g, every 5 days plus oral moxifloxacin, 400mg, every day (treatment group) versus intraperitoneal vancomycin, 1g, every 5 days plus intraperitoneal ceftazidime, 1g, every day (control group). The primary end point was complete resolution of peritonitis, and secondary end points were primary or secondary treatment failure. PD effluent white blood cell count. Baseline demographic and clinical characteristics of the 2 groups were comparable. There were 24 and 22 Gram-positive organisms, 6 and 7 Gram-negative organisms, 9 and 10 culture-negative samples, and 1 and 1 fungal sample in the treatment and control groups, respectively. Complete resolution of peritonitis was achieved in 78% and 80% of cases in the treatment and control groups, respectively (OR, 0.86; 95% CI, 0.30-2.52; P=0.8). There were 3 and 1 cases of relapse in the treatment and control groups, respectively. Primary and secondary treatment failure rates were not significantly different (33% vs 20% and 10% vs 13%, respectively). In each group, there was 1 peritonitis-related death and 6 transfers to hemodialysis therapy. During the 3-month follow-up period, 7 and 3 successive episodes of peritonitis occurred in the treatment and control groups, respectively. Only 2 adverse drug reactions (mild nausea and mild rash, respectively) were observed in the 2 groups. Sample size was relatively small and the eligibility ratio was low. Also, the number of peritonitis episodes was low, limiting the power to detect a difference between groups. This pilot study suggests that intraperitoneal vancomycin with oral moxifloxacin is a safe, well-tolerated, practical, and effective first-line treatment for PD-related peritonitis. Larger adequately powered clinical trials are warranted.

The influence of different peritoneal dialysis fluids on the in vitro activity of ampicillin, daptomycin, and linezolid against Enterococcus faecalis.

Intraperitoneal administration of antibiotics is recommended for the treatment of peritoneal dialysis-related peritonitis. However, little data are available on a possible interference between peritoneal dialysis fluids and the activity of antimicrobial agents. Thus, the present in vitro study set out to investigate the influence of different peritoneal dialysis fluids on the antimicrobial activity of ampicillin, linezolid, and daptomycin against Enterococcus faecalis. Time-kill curves in four different peritoneal dialysis fluids were performed over 24h with four different concentrations (1 × MIC, 4 × MIC, 8 × MIC, 30 × MIC) of each antibiotic evaluated. Cation-adjusted Mueller-Hinton broth was used as the comparator solution. All four peritoneal dialysis fluids evaluated had a bacteriostatic effect on the growth of Enterococcus faecalis. Compared to the cation-adjusted Mueller-Hinton broth comparator solution, the antimicrobial activity of all antibiotics tested was reduced. For ampicillin and linezolid, no activity was found in any peritoneal dialysis fluid, regardless of the concentration. Daptomycin demonstrated dose-dependent activity in all peritoneal dialysis fluids. Bactericidal activity was observed at the highest concentrations evaluated in Dianeal® PDG4 and Extraneal®, but not in concentrations lower than 30 × MIC and not in Nutrineal® PD4 and Physioneal® 40. The antimicrobial activity of ampicillin and linezolid is limited in peritoneal dialysis fluids in vitro. Daptomycin is highly effective in peritoneal dialysis fluids and might, thus, serve as an important treatment option in peritoneal dialysis-related peritonitis. Further studies are needed to evaluate the clinical impact of the present findings.

Pharmacokinetics of Intraperitoneal Gentamicin in Peritoneal Dialysis Patients with Peritonitis (GIPD Study)

Peritonitis is a major infectious complication in peritoneal dialysis patients, and intraperitoneal antibiotic administration is preferred to ensure maximal antibiotic concentrations at the site of infection. This study aimed to describe the plasma and infection site pharmacokinetics of intraperitoneal gentamicin in patients with peritonitis. This prospective pharmacokinetic study of intraperitoneal gentamicin was conducted in peritoneal dialysis patients presenting to hospital with clinically defined signs and symptoms of peritonitis. Twenty-four patients were administered a 0.6-mg/kg dose of intraperitoneal gentamicin, which was allowed to dwell for 6 hours. Serial blood and dialysate samples were collected for 24 hours after the first dose. Gentamicin concentrations in plasma and dialysate were measured using a validated assay. The median percentage of the dose absorbed into the systemic circulation was 76% (interquartile range=69%-82%) and significantly different between patients with low average, high average, and high peritoneal membrane transporter status (P=0.03). The calculated pharmacokinetic parameters were plasma terminal elimination half-life of 24.7 (20.4-29.9) hours, terminal volume of distribution of 0.30 (0.20-0.36) L/kg, observed peak plasma concentration of 3.1 (2.4-3.4) mg/L, and observed trough plasma concentration of 1.9 (1.4-2.2) mg/L. The peak gentamicin concentration in dialysate was at least eight times the minimum inhibitory concentration of the likely pathogens. The high systemic absorption of gentamicin in patients with peritonitis and prolonged plasma elimination half-life may lead to drug accumulation in the systemic circulation, increasing the risk of toxicity.

Stability of Cefazolin Sodium in Four Heparinized and Non-Heparinized Dialysate Solutions at 38°C

Intraperitoneal administration of antibiotics is often required in the treatment of peritoneal dialysis-associated peritonitis. Extended use and heating may affect drug stability. The objective of our study was to determine the stability of cefazolin sodium (125 mg/L and 500 mg/L) in heparinized and non-heparinized dextrosecontaining peritoneal dialysis solution (Dianeal PD-2; Baxter Healthcare, Deerfield, Illinois, USA) containing 1.5%, 2.5%, or 4.25% dextrose, or 7.5% icodextrin, the new colloid formulation (Extraneal; Baxter), at 38 degrees C for 4 days. Three poly-vinyl chloride containers of each dialysis fluid were stored at 38 degrees C for 4 days. Samples were taken after the bags were mixed and allowed to stand for 2 minutes. Two 500-microL samples were collected from each bag at hours 0, 12, 24, 36, 48, 60, 72, 84, and 96. Samples were then analyzed by high-performance liquid chromatography (HPLC) in our laboratory. In order to establish the stability-indicating nature of the method, drugs 1.0 mg/mL, vehicles, and their mixtures were subjected to a forced degradation. This is done by acid (2.0 mol/L HCl) and base (2.0 mol/L NaOH) hydrolysis, oxidation (H(2)O(2) 0.3%), and heat at 80 degrees C. Samples were analyzed every 30 minutes until approximately 25% of the drug's peak disappeared. The drug was considered stable if its concentration exceeded 90% of the original. For all Dianeal PD-2 peritoneal dialysis solution containing 1.5%, 2.5%, and 4.25% dextrose, cefazolin sodium was considered stable at 38 degrees C for 60 hours at low cefazolin concentrations (125 mg/L), both with and without heparin, and for 48 hours at high cefazolin concentrations (500 mg/L). Cefazolin sodium was considered stable at 38 degrees C in icodextrin for 48 hours at low cefazolin concentrations in heparinized and non-heparinized solutions, and at high concentrations only in non-heparinized dialysate, not in heparinized dialysate. Cefazolin sodium was considered stable at 38 degrees C in icodextrin for 60 hours at high concentrations when heparinized. Cefazolin sodium was stable in all four nonheparinized dialysate fluids for at least 48 hours at 38 degrees C. In heparinized icodextrin dialysate, high concentrations of cefazolin sodium were not stable for extended periods of time. Extended use and heating of dialysate containing cefazolin may adversely affect patient outcome.

Recurrent Infection and Catheter Loss in Patients on Continuous Ambulatory Peritoneal Dialysis

To elucidate the factors leading to catheter loss from recurrent infection in patients on continuous ambulatory peritoneal dialysis (CAPD). All catheters removed from patients were prospectively examined for infection. CAPD unit in large tertiary-care general hospital. Sixty-five consecutive patients undergoing catheter removal for whatever cause; 20 catheters rejected because of desiccation or contamination in transit. None. Micro-organisms linked to catheter removal; their locations on removed catheters. Of 45 catheters removed between January 1994 and August 1995, 26 were infected: 13/26 infections were caused by Staphylococcus aureus and 7/26 by Pseudomonas aeruginosa. In only one case was S. epidermidis associated with catheter removal. The most striking finding was that the inner cuff harbored large numbers of the infecting organisms, even when antibiotics had eradicated them from the peritoneal cavity and exit site, where present, and the catheter lumen. The importance of S. aureus and Ps. aeruginosa rather than S. epidermidis in catheter loss due to relapsing infection is confirmed. Persistence of the causative organisms in the inner cuff is a likely explanation for relapse after treatment, and might be due to the predominantly intraperitoneal administration of antibiotics. A clinical trial of the effect on catheter retention of empirical use of systemic or oral agents that give high tissue levels and are active against intracellular micro-organisms, along with recommended intraperitoneal regimens, is indicated.

Imbalance between intraperitoneal coagulation and fibrinolysis during peritonitis of CAPD patients: the role of mesothelial cells

We compared peritoneal dialysis effluents from 18 CAPD patients who had not suffered from peritonitis during the last 6 months (group 1) with the effluents from five patients with acute peritonitis (group 2), measuring activation markers of coagulation and fibrinolysis. These markers included prothrombin fragment F1 + 2 (F1 + 2), thrombin-antithrombin III complex (TAT), fibrin monomer (FM), and fibrin degradation products (FbDP). In the dialysate of group 1 we found remarkably high levels of F1 + 2, TAT and FM concomitant with a high concentration of FbDP, indicating a high rate of intraperitoneal fibrin turnover. The balance between peritoneal generation and degradation of fibrin was disturbed in untreated patients of group 2, who had significantly higher levels of coagulation markers and a higher ratio between FM and FbDP. Seven days after treatment with intraperitoneal administration of antibiotics and heparin, F1 + 2, TAT, FM and FbDP decreased significantly. To evaluate the role of mesothelial cells (MC) in the high peritoneal fibrin turnover we investigated the expression of tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA), plasminogen activator inhibitor type-1 (PAI-1), and tissue factor in cultured human peritoneal MC under basal conditions and after exposure to tumour necrosis factor alpha (TNF alpha), interleukin-1 alpha (IL-1 alpha), or bacterial lipopolysaccharide (LPS). The exposure of MC to TNF alpha or to a lesser extent IL-1 alpha or LPS reduced their fibrinolytic activity by decreasing t-PA production and increasing PAI-1 synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug Therapy in Patients Undergoing Continuous Ambulatory Peritoneal Dialysis

Continuous ambulatory peritoneal dialysis (CAPD) is an accepted alternative to haemodialysis in the treatment of end-stage renal failure. The frequently used intraperitoneal administration of antibiotics to treat peritonitis and the possible role of CAPD in the elimination of drugs has stimulated pharmacokinetic research in this field. The 2 principal results derived from these studies are: (1) the elimination capacity of CAPD for drugs given systemically or orally is very low, and (2) drugs administered intraperitoneally rapidly enter the circulation, a significant amount of drug being absorbed from the peritoneal cavity. This pharmacokinetic behavior is easily understood considering some basic and simple pharmacokinetic principles: the higher the volume of distribution of a substance, the lower will be the percentage of drug present in the peritoneal cavity. Thus, a prerequisite for rapid drug elimination by CAPD is a low body volume of distribution of a particular drug. Only in such a case will the drug diffuse into the peritoneal space to a significant extent. For dosing regimens in CAPD patients, the fraction of the dose eliminated by the peritoneal route should be known or estimated. This fraction depends on the relation of the peritoneal clearance to the total body clearance, and on the protein binding of the drug. The low flow rate of the peritoneal effluent (approximately 10 L/day = 7 ml/min) appears to be the most important limiting factor for the low extraction capacity of CAPD. The list of drugs that have been found to be significantly eliminated by CAPD is short: particular mention should be made of the aminoglycosides and some cephalosporins. The data on the peritoneal elimination of vancomycin are inconsistent. Although the intravenous and oral routes have been successfully used for the treatment of peritonitis, the time course of antibiotic concentrations in the peritoneal space appears to favour the peritoneal route of drug administration. During peritonitis, intraperitoneally administered drugs enter the circulation more rapidly and completely, due to the increased permeability of the peritoneal membrane. As long as the dialysate outflow rate and protein binding of the drug are not extensively altered by peritoneal inflammation, however, the extraction capacity of CAPD appears to remain low.

Peritonealdialyse bei hämolytisch-urämischem Syndrom nach Ileozökalresektion wegen Invagination bei postoperativer Peritonitis

A 3-year-old girl is reported on who underwent laparotomy for ileocaecal intussusception elsewhere one week following severe gastroenteritis. Immediately after surgery, she developed haemolytic-uraemic syndrome with haemolytic anaemia, thrombocytopenia, increase of urea and creatinine and anuria as well as subsequent peritonitis, enterocolitis and sepsis. Following relaparotomy with establishment of ileostomy, peritoneal dialysis for several days was carried out for treatment of the haemolytic-uraemic syndrome. This case demonstrates that the haemolytic-uraemic syndrome can be treated effectively by peritoneal dialysis despite fresh bowel anastomoses, and that simultaneously occurring peritonitis can be managed by intraperitoneal administration of antibiotics via dialysis fluid.

Vancomycin pharmacokinetics in continuous ambulatory peritoneal dialysis patients with peritonitis.

Peritonitis has proven to be the major deterrent to the further growth of continuous ambulatory peritoneal dialysis (CAPD) as a treatment strategy for end-stage renal disease. The correct treatment of peritonitis remains unsettled as evidenced by the presence of advocates for oral, intravenous or intraperitoneal antibiotic administration. This study examines the pharmacokinetic parameters of intravenous vancomycin when employed in the therapy of peritonitis. One gram of intravenous vancomycin was administered during 7 episodes of peritonitis in 5 patients. Plasma and end-of-dwell dialysate levels were maintained above the minimum inhibitory concentration for Staphylococcus aureus and S. epidermidis for 7 days following this single dose of vancomycin. These data establish the existence of sustained intraperitoneal entry of intravenous vancomycin during peritonitis and raise for speculation its use as the sole therapy in most episodes of gram-positive peritonitis.

Cephalexin for the oral treatment of CAPD peritonitis.

Sixteen episodes of peritonitis in 13 patients undergoing continuous ambulatory peritoneal dialysis (CAPD) were treated with oral cephalexin given at each 6-hourly dialysate exchange. Serial measurements of the antibiotic concentration in serum and dialysate were made in seven cases. Cephalexin levels increased rapidly and by 12 h exceeded 27 mg/l in serum and 20 mg/l in dialysate. Dialysate levels considerably exceeded the minimum bactericidal concentration for organisms considered cephalexin-sensitive and in patients with these the clinical response was usually good. Although dialysate concentrations sometimes reached the minimum inhibitory concentration for organisms considered cephalexin-resistant the clinical response in patients from whom resistant bacteria were cultured was unsatisfactory. Intra-peritoneal antibiotic administration would seem unnecessary in many CAPD patients with peritonitis.