title: Are intracellularly penetrating antibiotics warranted in CAPD-related peritonitis?
abstract: Survival and growth of bacteria within peritoneal macrophages has been implicated as causes of recurrences and relapses of Staphylococcus epidermidis peritonitis. We compared the effect of cephradine--known not to penetrate into peritoneal macrophages--with that of clindamycin--known to concentrate in phagocytes--on the intracellular killing of S. epidermidis by human peritoneal macrophages. Clindamycine (q.i.d. 300 mg) or cephradine (q.i.d. 250 mg) was taken orally for one day in a randomized cross-over setting by 8 stable CAPD patients. On both days peritoneal macrophages were isolated from the overnight effluents and their capacity to phagocytize and kill S. epidermidis was measured. Phagocytes isolated from and incubated in effluents containing clindamycin, showed better bacterial uptake (32 vs 17%, p less than 0.01) and killing (70 vs 42%, p less than 0.01) compared to cephradine. Moreover, clindamycin prevented S. epidermidis to multiply intracellularly (-0.33 decrease in log colony forming units (cfu)/ml after 18 h). In sharp contrast, phagocytes incubated with cephradine allowed S. epidermidis to increase over 18 h (+1.48 increase in log cfu/ml; p less than 0.01 compared to clindamycin). We conclude that antibiotics with the ability to suppress intracellular bacterial growth may provide a more optimal treatment of CAPD-related peritonitis.
authors.affiliation: Department of Internal Medicine, Free University Hospital, Amsterdam, The Netherlands.
authors.forename: C W
authors.initials: CW
authors.lastname: de Fijter
authors.forename: H A
authors.initials: HA
authors.lastname: Verbrugh
authors.forename: H C
authors.initials: HC
authors.lastname: Heezius
authors.forename: H
authors.initials: H
authors.lastname: van Bronswijk
authors.forename: J
authors.initials: J
authors.lastname: van der Meulen
authors.forename: P L
authors.initials: PL
authors.lastname: Oe
authors.forename: A J
authors.initials: AJ
authors.lastname: Donker
authors.forename: J
authors.initials: J
authors.lastname: Verhoef
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D002515:Cephradine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002981:Clindamycin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003176:Complement C3 / Q000032:analysis; D015314:Dialysis Solutions; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D066298:In Vitro Techniques; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology / Q000502:physiology; D008875:Middle Aged; D009000:Monocytes / Q000502:physiology; D009895:Opsonin Proteins / Q000502:physiology; D010529:Peritoneal Cavity / Q000166:cytology; D010531:Peritoneal Dialysis, Continuous Ambulatory / Q000009:adverse effects*; D010538:Peritonitis / Q000188:drug therapy* / Q000209:etiology / Q000382:microbiology; D010587:Phagocytosis / Q000187:drug effects; D013212:Staphylococcus epidermidis / Q000254:growth & development / Q000502:physiology
chemical_list: D003176:Complement C3; D015314:Dialysis Solutions; D007074:Immunoglobulin G; D009895:Opsonin Proteins; D002981:Clindamycin; D002515:Cephradine