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Are intracellularly penetrating antibiotics warranted in CAPD-related peritonitis?
C W de Fijter1, H A Verbrugh, H C Heezius
1Department of Internal Medicine, Free University Hospital, Amsterdam, The Netherlands.
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.
Insights
Clindamycin enhances bacterial killing by peritoneal macrophages in patients with Staphylococcus epidermidis peritonitis. This antibiotic effectively inhibits bacterial growth within cells, unlike cephradine, suggesting better treatment outcomes.
Area of Science:
- Infectious Diseases
- Pharmacology
- Immunology
Background:
- Bacterial survival within macrophages contributes to recurrent Staphylococcus epidermidis peritonitis.
- Understanding antibiotic effects on intracellular bacterial killing is crucial for effective treatment.
Purpose of the Study:
- To compare the efficacy of clindamycin and cephradine in killing intracellular Staphylococcus epidermidis.
- To evaluate the impact of antibiotic penetration into peritoneal macrophages on treatment outcomes.
Main Methods:
- A randomized cross-over study involving 8 Continuous Ambulatory Peritoneal Dialysis (CAPD) patients.
- Peritoneal macrophages were isolated and their phagocytic and bactericidal capacity against S. epidermidis was measured after one-day oral administration of clindamycin or cephradine.
Main Results:
- Clindamycin significantly improved bacterial uptake (32% vs 17%) and killing (70% vs 42%) by macrophages compared to cephradine.
- Clindamycin inhibited intracellular bacterial multiplication, while cephradine allowed bacterial growth within macrophages.
Conclusions:
- Antibiotics concentrating within phagocytes, like clindamycin, offer superior intracellular killing of S. epidermidis.
- Targeting intracellular bacterial growth with appropriate antibiotics may optimize the treatment of CAPD-related peritonitis.