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Effects of intraperitoneal antibiotics on human peritoneal mesothelial cell growth
1Department of Internal Medicine, National Taiwan University, Taipei, ROC.
Abstract:
Peritonitis is one of the most frequent complications of continuous ambulatory peritoneal dialysis (CAPD). Necrosis and exfoliation of the mesothelial cell layer of the peritoneum develop during the acute phase of peritonitis. Agents that hamper regeneration of mesothelial cells will cause delayed recovery of the peritoneal surface, which results in continuous exposure of underlying stem cells to the stimulation of growth factors and possibly leads to peritoneal fibrosis syndrome. The aim of the present study is to determine the effects of several intraperitoneal antibiotics on human peritoneal mesothelial cell (HPMC) growth at their usual loading and maintenance doses. HPMCs were isolated from human omenta. Proliferation of HPMC was evaluated by modified methyltetrazolium assay and cell membrane integrity was assessed by lactate dehydrogenase method. The results showed that most cephalosporins exert an inhibitory, even toxic, effect on HPMCs at their loading doses. Cephalothin, cephradine, cefamandole, cefoxitin, cefuroxime and cefoperazone inhibited HPMC proliferation at their maintenance doses. Vancomycin, clindamycin, aztreonam, piperacillin, imipenem, tobramycin and ceftriaxone have no effect in their usual intraperitoneal doses. From the viewpoint of peritoneal protection, not only drug sensitivity of the causative microorganisms but also effects of antibiotics on HPMC regeneration should be considered when selecting antibiotics for CAPD peritonitis.
Insights
Certain cephalosporin antibiotics can inhibit human peritoneal mesothelial cell growth, potentially delaying recovery from peritonitis. Antibiotic selection for continuous ambulatory peritoneal dialysis (CAPD) peritonitis should consider effects on mesothelial cell regeneration.
Area of Science:
- Nephrology
- Cell Biology
- Pharmacology
Background:
- Peritonitis is a common complication of continuous ambulatory peritoneal dialysis (CAPD).
- Mesothelial cell damage during peritonitis can lead to peritoneal fibrosis syndrome if regeneration is impaired.
- Understanding antibiotic effects on mesothelial cells is crucial for managing CAPD peritonitis.
Purpose of the Study:
- To evaluate the impact of intraperitoneal antibiotics on human peritoneal mesothelial cell (HPMC) proliferation.
- To assess the toxicity of commonly used antibiotics in CAPD peritonitis treatment.
Main Methods:
- Human peritoneal mesothelial cells (HPMCs) were isolated from omenta.
- HPMC proliferation was measured using a modified methyltetrazolium assay.
- Cell membrane integrity was assessed via lactate dehydrogenase (LDH) release.
Main Results:
- Most cephalosporins showed inhibitory or toxic effects on HPMCs at loading doses.
- Several cephalosporins (cephalothin, cephradine, cefamandole, cefoxitin, cefuroxime, cefoperazone) inhibited HPMC proliferation at maintenance doses.
- Vancomycin, clindamycin, aztreonam, piperacillin, imipenem, tobramycin, and ceftriaxone did not affect HPMC proliferation at standard intraperitoneal doses.
Conclusions:
- Antibiotic choice for CAPD peritonitis requires consideration of both antimicrobial efficacy and potential toxicity to HPMCs.
- Some cephalosporins may impede peritoneal healing, necessitating careful selection to avoid long-term complications.