Purpose We studied whether the risk of central venous catheter (CVC) -related thrombosis increased after an episode of CVC-related infection in patients undergoing intensive chemotherapy. Secondly, we determined whether thrombosis can be predicted or excluded by CVC lock fluid surveillance cultures. Patients and Methods In a prospective setting, 105 consecutive patients were carefully examined for CVC-related infection and thrombosis. In all patients, microbial surveillance cultures of CVC lock fluid were taken every other day. All patients with clinical suspicion of CVC-related thrombosis underwent Doppler ultrasound or additional venography. Results The cumulative incidence of CVC-related infection was 24% (25 of 105 patients). Clinically manifest thrombosis occurred in 13 (12%) of 105 patients. In patients with CVC-related infection, the risk of thrombosis increased markedly in comparison to those without infection (relative risk, 17.6; 95% CI, 4.1 to 74.1). In patients having two or more positive subsequent CVC lock fluid cultures with identical micro-organisms, 71.4% developed thrombosis, as compared with 3.3% in patients with negative or a single positive culture. Conclusion The risk of clinically manifest thrombosis is increased after an episode of CVC-related infection in patients undergoing intensive chemotherapy. Surveillance culturing of CVC lock fluid may be clinically useful in estimating the risk for thrombosis and the instigation of focused early intervention.

To determine which patients are at high risk for disseminated fungal infection and should be given systemic prophylaxis, we studied the charts of 341 patients with malignant hematologic disorders who were admitted to our institution during 10 consecutive years. These patients represented 636 admissions; during these admissions, 60 invasive fungal infections occurred, with deaths in 44 cases. All patients who died of these infections either had persisting granulocytopenia and a poor prognosis for the underlying disease or suffered from chronic graft-vs.-host disease. Two of 58 patients who had no or low-level candidal colonization developed this infection (P < .001). Nine of the 10 patients with candidal infection had microbiologically proven bacteremia within the week preceding the candidal infection. After bone marrow transplantation, 8 of 10 patients with chronic graft-vs.-host disease vs. 2 of 36 without this disease (P < .001) developed fatal infection with Aspergillus species. The results of our study reveal that patients with high-level candidal colonization who were treated for microbiologically proven bacteremia and patients with chronic graft-vs.-host disease might benefit from systemic antifungal prophylaxis.

IntroductionTo reduce the risk of infections in neutropenic patients a combination of protective isolation and gut decontamination by oral administration of antibiotics is often used. [1][2][3][4] Since it has been shown that selective elimination of the major potentially pathogenic microorganisms from the digestive tract is as effective or even superior to total decontamination in preventing infections in neutropenic patients, 5-8 selective gut decontamination 9 or partial antibiotic decontamination 10 mainly directed against aerobic Gram-negative rods and fungi is usually applied. The various antibiotics used for selective decontamination can be divided into 2 main groups, those that are absorbed 11-13 after oral administration (eg, cotrimoxazole, quinolones) and those that are not absorbed 2-4 after oral administration (eg, polymyxin, colistin, aminoglycosides).Mobilized hematopoietic progenitor cells (HPCs) are increasingly used for hematopoietic recovery instead of bone marrow to allow rapid hematopoietic recovery after autologous and allogeneic transplantation. [14][15][16][17][18] An increasing number of different growth factors and chemokines such as granulocyte colony-stimulating factor (G-CSF), 19,20 granulocyte-macrophage colony-stimulating factor (GM-CSF), 19,21 stem cell factor (SCF), 22 flt3 ligand (FL), 23 interleukin-1 (IL-1), 24 26 and thrombopoietin 27 when either administered alone or in combination 28 are capable of mobilizing peripheral blood progenitor cells. In the clinical setting, the growth factor G-CSF has become the standard for autologous as well as allogeneic peripheral blood stem cell transplantation. [29][30][31] Although patients receiving selective gut decontamination or systemic antibiotic treatment while concurrently being treated with G-CSF are able to mobilize peripheral blood progenitor cells, little is known of the effect of antibiotics on the efficacy of mobilization.Endotoxins are ubiquitously present and constitute an important component of the normal intestinal flora and are known to induce HPC mobilization. [32][33][34] We therefore hypothesized that low levels of endotoxins passing through the intestinal mucosa into the blood may contribute to the levels of circulating HPCs. Here, we used a mouse model to study the effects of selective antibiotic decontamination on cytokine-induced stem cell mobilization. We found that the ability to mobilize in response to IL-8, G-CSF, or FL was significantly reduced in animals receiving endotoxin binding antibiotics or antibiotics that modulate the anaerobic flora. The mobilizing capacity was partially restored after adding endotoxins to the drinking water of decontaminated mice. These observations indicate that endotoxins are involved as cofactors in cytokineinduced hematopoietic stem cell mobilization. Supported by a grant from the Fund for Scientific Research FWO-Vlaanderen, the "Geconcerteerde Onderzoeks Acties" (GAO), and by the Dutch Cancer Society (NKB-RUL 99-2029).Reprints: Willem E. Fibbe, Department of Hematology, Lei...

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