PD-associated peritonitis
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Infekce zůstávají důležitým problémem, s nímž se prakticky potýkají všechny obory medicíny. Nejinak je tomu u peritoneální dialýzy (PD), kde je prevence a léčba peritonitidy klíčovou součástí péče. Doporučení zabývající se tímto tématem vydává již od roku 1983 Mezinárodní společnost pro peritoneální dialýzu (ISPD). V letošním roce byla publikována jejich další aktualizovaná verze, která nám přináší některé novinky. Byly definovány nové kategorie peritonitid (asociované s PD katétrem, enterální, pre-PD peritonitida). Byl aktualizován a zpřísněn požadavek na maximální incidenci peritonitid (0,4 epizody na rok léčby). Je kladen vyšší důraz na vypuštění dialyzátu před invazivními gastroenterologickými a gynekologickými vyšetřeními. Dalšími preventivními opatřeními je korekce hypokalemie a neužívání antagonistů H2-receptorů. Pokud jde o empirickou antibiotickou léčbu, je novinkou možnost užívat monoterapii cefepimem. K terapii aminoglykosidy je pak doporučováno rutinně přidávat N-acetylcystein k prevenci ototoxicity. Novinky jsou i v přístupu k refrakterní peritonitidě, peritonitidě způsobené Corynebacterii a dalšími agens. Publikovaná doporučení poskytují cenný soubor aktuálních odpovědí na problémy, s nimiž se v běžné praxi často setkáváme.
Infections remain an important problem facing virtually all medical disciplines. This is no different with peritoneal dialysis (PD), where the prevention and treatment of peritonitis is a key part of care. The International Society for Peritoneal Dialysis (ISPD) has been issuing recommendations on this subject since 1983. This year, their next updated version was published, which brings us some news. New categories of peritonitis (associated with PD catheter, enteral, pre-PD peritonitis) have been defined. The requirement for a maximum peritonitis rate has been updated and tightened (0.4 episodes per year of treatment). There is a greater emphasis on PD fluid drainage before invasive gastroenterological and gynecological examinations. Other preventive measures are the correction of hypokalaemia and the avoidance of H2-receptor antagonists. In empirical antibiotic treatment, the possibility of using cefepime monotherapy is a novelty. It is recommended to add N-acetylcysteine routinely to aminoglycoside therapy to prevent ototoxicity. There are also new approaches to refractory peritonitis, peritonitis caused by Corynebacteria and other agents. The published recommendations provide a valuable set of answers to the problems we often encounter in common practice.
Peritonitida je častou a závažnou komplikací peritoneální dialýzy. Dvě třetiny infekcí jsou vyvolány grampozitivními bakteriemi, které pronikají do dutiny peritoneální cestou peritoneálního katétru. Infekce způsobené gramnegativními bakteriemi s výjimkou pseudomonádové vznikají přestupem infekce stěnou střevní. Peritonitidy se léčí antibiotiky podávanými intraperitoneálně do vaků a peritoneální dialýza se nepřerušuje. Cílem léčby je nejen vyléčení infekce, ale i ochrana peritonea. Bakterie Staphylococcus aureus, St. epidermidis a další koaguláza negativní stafylokoky, Pseudomonas aeruginosa a n některé gramnegativní bakterie mají schopnost na povrchu katétru vytvářet biofilm. Bakterie jsou pak chráněny vůči účinku antibiotik a mohou vyvolávat opakované infekce a relapsy. Peritonitidy způsobené těmito bakteriemi jsou pak indikací k odstranění peritoneálního katétru. Opakované, ale vzácné infekce vyvolává Micrococcus sp. a Corynebacterium sp. Některé infekce peritonea vznikají po předchozí antibiotické léčbě přerůstáním bakterií ve střevě a přestupem stěnou střevní na peritoneum. Jedná se o mykotické infekce, infekce vyvolané Lactobacillem sp., nebo infekce vyvolané kmeny. Enterococcus faecium. nebo E. fecalis. Tyto infekce jsou pak také důvodem k odstranění peritoneálního katétru. Streptokokové infekce většinou vznikají hematogenním přenosem při odontogenní nebo kožní infekci. Infekce vyvolané Streptococcus agalactiae souvisí s infekcí vaginální stěny a přestupem do dutiny peritoneální cestou pohlavních orgánů. Polymikrobiální peritonitida je indikací k okamžitému odstranění peritoneálního katétru a revizi dutiny peritoneální. Léčba peritonitid musí být okamžitá, antibiotikum je voleno podle místní rezistence, 1. volbou je obvykle kombinace cefalosporin 1. generace a aminoglykosid. Vancomycin je rezervním antibiotikem a neměl by být použit jako lék 1. volby při neznámé etiologii. Katétr má být odstraněn, pokud se stav nelepší a antibiotické léčba je neúčinná do 72 hodin od prvních příznaků infekce. Důležitá je prevence peritonitid. Výuka pacientů a personálu v provádění výměn dialyzačního roztoku je základní podmínkou dobře fungující peritoneální dialýzy.
Peritonitis is a frequent and serious complication of peritoneal dialysis. Two-thirds of infections are caused by Gram-positive organisms and are often related to a catheter infection. Infections caused by Gram-negative bacterias - with the exception of Pseudomonas infections - may originate from the bowel. Peritonitis is treated with antibiotics given to the bags, administered intraperiton eally. The goal of treatment is not only to treat infection, but also to protect the peritoneum. Staphylococcus aureus , St. epidermidis and other coagulase-negative staphylococci, Pseudomonas aeruginosa and some Gram-negative bacterias have the capacity to create biofilms on the catheter surface. Bacterias are then protected against the effect of antibiotics and can cause recurrent infect ions and relapses. Reinfections and relapsing peritonitis are the indications for removal of the peritoneal catheter. Repeated but r are infections are caused by Micrococcus sp. and Corynebacterium sp. Some of peritoneal infections occur after antibiotic treatment due to bacterial overgrowth in the gut and intestinal wall segment to the peritoneum. Those are: fungal infections, infections caus ed by Lactobacillus sp. , or infections caused by strains of Enterococcus faecium or E. fecalis . These infections often need removal of the peritoneal catheter. Streptococcal infections are often associated with odontogenic hematogenous transmission or skin infection . Infections caused by Streptococcus agalactiae relate to vaginal walls infections and transfer to the peritoneal cavity through the genitals. Polymicrobial peritonitis is an indication for immediate removal of the peritoneal catheter and revision of the perit oneal cavity. Peritonitis treatment must be started immediately. The ISPD recommends specific selection of empirical therapy dependent on loc al history of sensitivities of organisms. Gram-positive organisms may be covered by cephalosporin of the first generation. Vancomy cin can be used as a reserve antibiotics, and should not be used as the first choice in unknown etiology. Gram – negative organisms must be treated by the third generation cephalosporin or an aminoglycoside. Catheter removal is indicated in the refractory peritoni tis, defined as a failure of the antibiotics treatment of peritonitis after 5 days. Reducing risk of PD - related infections should be a primary goal of every PD program. Education of patients and also the staff in implamenting the exchange of dialysis solution is the bas ic condition for a well-functioning peritoneal dialysis.
- MeSH
- antibakteriální látky * MeSH
- Bacteria * klasifikace patogenita MeSH
- biofilmy MeSH
- Corynebacterium MeSH
- Enterococcus MeSH
- grampozitivní bakterie * MeSH
- infekce spojené se zdravotní péčí MeSH
- Lactobacillus MeSH
- lidé MeSH
- peritoneální dialýza MeSH
- peritonitida * etiologie farmakoterapie MeSH
- Pseudomonas MeSH
- rizikové faktory MeSH
- stafylokokové infekce MeSH
- zaváděcí katétry * škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Encapsulating peritoneal sclerosis (EPS) is a rare life-threatening complication associated with peritoneal dialysis (PD). EPS is characterized by progressive fibrosis and sclerosis of the peritoneum, with the formation of a membrane and tethering of loops of the small intestine resulting in intestinal obstruction. It is very rare in children. We present a case of a 16-year-old adolescent boy who developed EPS seven years after being placed on continuous ambulatory peritoneal dialysis (CAPD) complicated by several episodes of bacterial peritonitis. The diagnosis was based on clinical, radiological, intraoperative and histopathological findings. The patient was successfully treated with surgical enterolysis. During a 7-year follow-up, there have been no further episodes of small bowel obstruction documented. He still continues to be on regular hemodialysis and is awaiting a deceased donor kidney transplant. EPS is a long-term complication of peritoneal dialysis and is typically seen in adults. Rare cases may be seen in the pediatric population and require an appropriate surgical approach that is effective and lifesaving for these patients.
- MeSH
- dítě MeSH
- dospělí MeSH
- kontinuální ambulantní peritoneální dialýza * škodlivé účinky MeSH
- lidé MeSH
- mladiství MeSH
- peritoneální dialýza * škodlivé účinky MeSH
- peritoneální fibróza * diagnóza etiologie patologie MeSH
- peritoneum patologie MeSH
- peritonitida * diagnóza etiologie patologie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
BACKGROUND: The unphysiological composition of peritoneal dialysis (PD) fluids induces progressive peritoneal fibrosis, hypervascularization and vasculopathy. Information on these alterations after kidney transplantation (KTx) is scant. METHODS: Parietal peritoneal tissues were obtained from 81 pediatric patients with chronic kidney disease stage 5 (CKD5), 72 children on PD with low glucose degradation product (GDP) PD fluids, and from 20 children 4-8 weeks after KTx and preceding low-GDP PD. Tissues were analyzed by digital histomorphometry and quantitative immunohistochemistry. RESULTS: While chronic PD was associated with peritoneal hypervascularization, after KTx vascularization was comparable to CKD5 level. Submesothelial CD45 counts were 40% lower compared with PD, and in multivariable analyses independently associated with microvessel density. In contrast, peritoneal mesothelial denudation, submesothelial thickness and fibrin abundance, number of activated, submesothelial fibroblasts and of mesothelial-mesenchymal transitioned cells were similar after KTx. Diffuse peritoneal podoplanin positivity was present in 40% of the transplanted patients. In subgroups matched for age, PD vintage, dialytic glucose exposure and peritonitis incidence, submesothelial hypoxia-inducible factor 1-alpha abundance and angiopoietin 1/2 ratio were lower after KTx, reflecting vessel maturation, while arteriolar and microvessel p16 and cleaved Casp3 were higher. Submesothelial mast cell count and interleukin-6 were lower, whereas transforming growth factor-beta induced pSMAD2/3 was similar as compared with children on PD. CONCLUSIONS: Peritoneal membrane damage induced with chronic administration of low-GDP PD fluids was less severe after KTx. While peritoneal microvessel density, primarily defining PD transport and ultrafiltration capacity, was normal after KTx and peritoneal inflammation less pronounced, diffuse podoplanin positivity and profibrotic activity were prevalent.
- MeSH
- chronické selhání ledvin * chirurgie metabolismus MeSH
- dialýza ledvin MeSH
- dialyzační roztoky metabolismus MeSH
- dítě MeSH
- glukosa metabolismus MeSH
- lidé MeSH
- peritoneální dialýza * škodlivé účinky MeSH
- peritoneum metabolismus MeSH
- peritonitida * metabolismus MeSH
- transplantace ledvin * škodlivé účinky MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The impact of peritoneal dialysis (PD) associated peritonitis on peritoneal membrane integrity is incompletely understood. Children are particularly suited to address this question, since they are largely devoid of preexisting tissue damage and life-style related alterations. Within the International Peritoneal Biobank, 85 standardized parietal peritoneal tissue samples were obtained from 82 children on neutral pH PD fluids with low glucose degradation product (GDP) content. 37 patients had a history of peritonitis and 16 of the 37 had two or more episodes. Time interval between tissue sampling and the last peritonitis episode was 9 (4, 36) weeks. Tissue specimen underwent digital imaging and molecular analyses. Patients with and without peritonitis were on PD for 21.0 (12.0, 36.0) and 12.8 (7.3, 27.0) months (p = 0.053), respectively. They did not differ in anthropometric or histomorphometric parameters [mesothelial coverage, submesothelial fibrosis, blood, and lymphatic vascularization, leukocyte, macrophage and activated fibroblast counts, epithelial-mesenchymal transition (EMT), podoplanin positivity and vasculopathy]. VEGF and TGF-ß induced pSMAD abundance were similar. Similar findings were also obtained after matching for age and PD vintage and a subgroup analysis according to time since last peritonitis (<3, <6, >6 months). In patients with more than 24 months of PD vintage, submesothelial thickness, vessel number per mmm section length and ASMA fibroblast positivity were higher in patients with peritonitis history; only the difference in ASMA positivity persisted in multivariable analyses. While PD duration and EMT were independently associated with submesothelial thickness, and glucose exposure and EMT with peritoneal vessel density in the combined groups, submesothelial thickness was independently associated with EMT in the peritonitis free patients, and with duration of PD in patients with previous peritonitis. This detailed analysis of the peritoneal membrane in pediatric patients on PD with neutral pH, low GDP fluids, does not support the notion of a consistent long-term impact of peritonitis episodes on peritoneal membrane ultrastructure, on inflammatory and fibrotic cell activity and EMT. Peritoneal alterations are mainly driven by PD duration, dialytic glucose exposure, and associated EMT.
- Publikační typ
- časopisecké články MeSH
- MeSH
- diferenciální diagnóza MeSH
- difuzní idiopatická skeletální hyperostóza diagnóza farmakoterapie MeSH
- familiární středomořská horečka diagnóza etiologie farmakoterapie klasifikace MeSH
- inhibitory kontrolních bodů farmakologie škodlivé účinky MeSH
- komplikace diabetu diagnóza metabolismus MeSH
- lidé MeSH
- metabolické nemoci kostí diagnóza farmakoterapie klasifikace MeSH
- osteonekróza diagnóza etiologie farmakoterapie MeSH
- revmatické nemoci * diagnóza farmakoterapie klasifikace MeSH
- sarkoidóza diagnostické zobrazování diagnóza farmakoterapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
BACKGROUND: Platinum-resistant ovarian cancer patients have a poor prognosis and few treatment options are available. Preclinical and clinical data demonstrated that the combination of poly-ADP ribose polymerase inhibitors with immune checkpoint inhibitors could have a synergistic antitumor activity in this setting of patients. PRIMARY OBJECTIVE: The primary objective is to assess the efficacy of niraparib plus dostarlimab compared with chemotherapy in recurrent ovarian cancer patients not suitable for platinum treatment. STUDY HYPOTHESIS: This trial will assess the hypothesis that niraparib plus dostarlimab therapy is effective to increase overall survival, progression-free survival, and time to first subsequent therapy respect to chemotherapy alone, with an acceptable toxicity profile. TRIAL DESIGN: This is a phase III, multicenter trial, where recurrent ovarian cancer patients not eligible for platinum re-treatment will be randomized 1:1 to receive niraparib plus dostarlimab vs physician's choice chemotherapy until disease progression, intolerable toxicity, or withdrawal of patient consent. The study will be performed according to European Network for Gynaecological Oncological Trial groups (ENGOT) model B and patients will be recruited from 40 sites across MITO, CEEGOG, GINECO, HeCOG, MANGO, and NOGGO groups. MAJOR INCLUSION/EXCLUSION CRITERIA: Eligible patients must have recurrent epithelial ovarian cancer not eligible for platinum retreatment. Patients who received previous treatment with poly-ADP ribose polymerase inhibitors and/or immune checkpoint inhibitors will be eligible. No more than two prior lines of treatment are allowed. PRIMARY ENDPOINT: The primary endpoint is overall survival defined as the time from the randomization to the date of death by any cause. SAMPLE SIZE: 427 patients will be randomized. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: June 2024 TRIAL REGISTRATION NUMBER: NCT04679064.
- MeSH
- chemorezistence MeSH
- humanizované monoklonální protilátky aplikace a dávkování MeSH
- indazoly aplikace a dávkování MeSH
- inhibitory kontrolních bodů aplikace a dávkování MeSH
- lidé MeSH
- lokální recidiva nádoru farmakoterapie MeSH
- nádory vaječníků farmakoterapie MeSH
- PARP inhibitory aplikace a dávkování MeSH
- peritoneální nádory farmakoterapie MeSH
- piperidiny aplikace a dávkování MeSH
- protokoly protinádorové kombinované chemoterapie aplikace a dávkování MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
INTRODUCTION: Gram-negative peritonitis (GNP) is associated with significant morbidity in children receiving long-term peritoneal dialysis (PD) and current treatment recommendations are based on limited data. METHODS: Analysis of 379 GNP episodes in 308 children (median age 6.9 years, interquartile range [IQR]: 3.0-13.6) from 45 centers in 28 countries reported to the International Pediatric Peritoneal Dialysis Network registry between 2011 and 2023. RESULTS: Overall, 74% of episodes responded well to empiric therapy and full functional recovery (FFR) was achieved in 82% of cases. In vitro bacterial susceptibility to empiric antibiotics and lack of severe abdominal pain at onset were associated with a good initial response. Risk factors for failure to achieve FFR included severe abdominal pain at onset and at 60 to 72 hours from treatment initiation (odds ratio [OR]: 3.81, 95% confidence interval [CI]: 2.01-7.2 and OR: 3.94, 95% CI: 1.06-14.67, respectively), Pseudomonas spp. etiology (OR: 1.73, 95% CI: 1.71-4.21]) and in vitro bacterial resistance to empiric antibiotics (OR: 2.40, 95% CI: 1.21-4.79); the risk was lower with the use of monotherapy as definitive treatment (OR: 0.40, 95% CI: 0.21-0.77). Multivariate analysis showed no benefit of dual antibiotic therapy for treatment of Pseudomonas peritonitis after adjustment for age, presenting symptomatology, 60 to 72-hour treatment response, and treatment duration. Monotherapy with cefazolin in susceptible Enterobacterales peritonitis resulted in a similar FFR rate (91% vs. 93%) as treatment with ceftazidime or cefepime monotherapy. CONCLUSION: Detailed microbiological assessment, consisting of patient-specific and center-specific antimicrobial susceptibility data, should guide empiric treatment. Treatment "deescalation" with the use of monotherapy and narrow spectrum antibiotics according to susceptibility data is not associated with inferior outcomes and should be advocated in the context of emerging bacterial resistance.
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Pleural or pericardial effusions secondary to pleuro-peritoneal fistula (PPF) and pericardio-peritoneal fistula (PcPF) are rare but serious complications of peritoneal dialysis (PD). METHODS: We conducted a 10-year survey across all participating centres in the European Paediatric Dialysis Working Group to review the incidence, diagnostic techniques, therapeutic options and outcome of children on chronic PD with PPF and/or PcPF. RESULTS: Of 1506 children on PD there were ten cases (8 of PPF, 1 each of PcPF and PPF + PcPF), with a prevalence of 0.66%. The median age at presentation was 1.5 [inter-quartile range (IQR) 0.4-2.4] years, and nine children were <3 years. The time on PD before onset of symptoms was 4.3 (IQR 1.3-19.8) months. Eight children had herniae and seven had abdominal surgery in the preceding 4 weeks. Symptoms at presentation were respiratory distress, reduced ultrafiltration and tachycardia. PD was stopped in all children; three were managed conservatively and thoracocentesis was performed in seven (with pleurodesis in 3). PD was restarted in only three children, in two of them with success. CONCLUSION: In conclusion, PPF and PcPF are rare in children on chronic PD, but are associated with significant morbidity, requiring a change of dialysis modality in all cases. Risk factors for PPF development include age of <3 years, herniae and recent abdominal surgery.
- MeSH
- ascitická tekutina patologie MeSH
- chronické selhání ledvin terapie MeSH
- dítě MeSH
- incidence MeSH
- kojenec MeSH
- lidé MeSH
- perikardiální efuze epidemiologie etiologie MeSH
- peritoneální dialýza škodlivé účinky MeSH
- píštěle epidemiologie etiologie MeSH
- pleurální výpotek epidemiologie etiologie MeSH
- předškolní dítě MeSH
- prevalence MeSH
- průzkumy a dotazníky MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Evropa MeSH
Permanent irritation of the peritoneum during peritoneal dialysis (PD) treatment leads to local chronic inflammation and subsequently activation of processes driving fibrogenesis in the long-term. The aim of the study was to compare the peritoneal effluent transcriptome of 20 patients treated less and 13 patients treated more than 2 years using microarray analysis. An increased expression of genes associated with an immune response was observed in long-term treated patients with well preserved peritoneal function, when compared to patients treated less than 2 years. From 100 genes highly expressed in long-term patients, a significant up-regulation of six was found by RT-qPCR: LY9 (lymphocyte antigen 9), TNSFR4 (tumor necrosis factor receptor superfamily, member 4), CD 79A (CD79a molecule), CCR7 (chemokine C-C receptor 7), CEACAM1 (carcinoembryonic antigen-related cell adhesion molecule 1) and IL2RA (interleukin 2 receptor alpha chain). Furthermore, the effluent cell population was analysed. A positive relationship between the number of granulocytes and NK cells on one hand, and duration of PD treatment on the other, was shown. We conclude, that the mechanisms of adaptive immunity promoting T helper 2 cells response are activated in the long-term before functional alterations develop. It consequently might trigger the fibrosis promoting processes.
- MeSH
- adaptivní imunita genetika MeSH
- ascitická tekutina imunologie metabolismus MeSH
- časové faktory MeSH
- fibróza MeSH
- kontinuální ambulantní peritoneální dialýza škodlivé účinky MeSH
- lidé MeSH
- nádory ledvin terapie MeSH
- peritoneální dialýza škodlivé účinky MeSH
- peritoneum imunologie metabolismus patologie MeSH
- regulace genové exprese MeSH
- stanovení celkové genové exprese MeSH
- transkriptom MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH