The hypothesis that elimination of facultative and strict anaerobic microorganisms from the gastro-intestinal tract by antimicrobial drugs in the period of time around allogeneic bone marrow transplantation (BMT) prevents acute graft-versus-host disease (GVHD), was examined in a cohort of 112 children grafted between 1989 and 2002 for hematological malignancies. All patients received T-cell replete marrow from human leukocyte antigens (HLA) matched sibling donors under identical transplantation conditions. To eliminate microorganisms from the gastro-intestinal tract, total gastro-intestinal decontamination (GID) was applied by high doses of non-absorbable antimicrobial drugs while the graft recipient was maintained in strict protective isolation. About half of the children (51%) proved to be successfully decontaminated, and about half (49%) unsuccessfully. One recipient got acute GVHD in the first group and 8 in the second group (p = 0.013). The degree of success of total GID was decisive for the occurrence of acute GVHD, irrespective of the presence of other risk factors such as higher age of recipient and/or donor, female donor for male recipient and carriership or reactivation of herpesvirusesOur results demonstrate that successful total GID of the graft recipient prevents moderate to severe acute GVHD. We suppose that substantial translocation of gastro-intestinal microorganisms or parts of these, functioning as microbial-associated molecular patterns (MAMP's), triggering macrophages/dendritic cells via pattern recognizing receptors (PRR's) is prohibited. As a consequence the initiation and progression of an inflammatory process leading to acute GVHD is inhibited.

The infected and inflamed periodontium can act as a focus for systemic infection in neutropenic cancer patients. The incidence of these oral infections is unknown, but probably underestimated. Periodontal infections can easily be overlooked, primarily because symptoms of gingival inflammation may be minimal and the infection may be located in deeper parts of the periodontium. Assessment of a patient's periodontal condition before the onset of profound neutropenia is critical to the diagnosis and the management of these potentially life-threatening infections. This review article is aimed at informing supportive care providers of recent insights into the pathogenesis of periodontal diseases and the role of subgingival microorganisms, with the emphasis on these infections in cancer patients treated with high-dose chemotherapy. Furthermore, a multidisciplinary approach to the management of periodontal infections and the need for future research is discussed.

We assessed the activity and safety of liposomal nystatin, a broad-spectrum antifungal agent, for invasive aspergillosis in patients refractory to or intolerant of amphotericin B. Thirty-three patients were enrolled, received at least one dose of the study drug, and were evaluable for safety. Twenty-six patients had confirmed probable or definite aspergillosis and were fully eligible. Most patients had a hematological malignancy (53.8%) or hematopoietic stem cell transplantation (23.0%), were neutropenic (61.5%), and were refractory to previous amphotericin B (92.3%). The median duration of previous amphotericin B treatment was 16.5 days (range, 5 to 64 days). Aspergillosis was definite in 3 cases and probable in 23 cases. Liposomal nystatin was initiated at a dose of 4 mg/kg of body weight/day. Twenty-five patients were evaluable for response: a complete response was achieved for one patient, and a partial response was achieved for six. Thus, the overall response rate is 7 of 25 (28%; 95% confidence interval, 12 to 49%). Seventeen (68.0%) of the 25 evaluable patients died during therapy or within 1 month after the end of therapy. The primary cause of death was invasive aspergillosis for nine patients and underlying malignancy for eight patients. The most frequent side effects included chills, shivering, and fever, leading to discontinuation of therapy for two patients. Grade 1 decline in renal function was seen for 10 (30.3%) patients, and hypokalemia was seen for 13 (39.4%). We conclude that liposomal nystatin can be effective for salvage therapy of invasive aspergillosis. Infusion-related adverse events have been observed frequently.Mold infections continue to be an important cause of death for patients with leukemia, allogeneic hematopoietic stem cell transplantation, and advanced stages of malignancy. The mortality rate of invasive aspergillosis (IA) ranges from 40 to 90% depending on the degree of underlying immune suppression and the institution of early therapy (5,16).Until the recent approval of voriconazole, standard treatment of IA consisted of intravenous amphotericin B given at doses of at least 1 mg/kg of body weight/day (11, 24). Amphotericin B is associated with considerable toxicity and frequent treatment failure, particularly in the case of advanced disease and prolonged neutropenia. The liposomal formulation of amphotericin B has allowed the administration of more than fivefold doses of the drug with considerable improvement in the safety profile (15,25).The liposomal encapsulation technique can, however, be extended to other antifungal agents that were previously excluded for treatment of systemic fungal infections due to the lack of a well-tolerated intravenous formulation. Nystatin is a naturally occurring product of Streptomyces noursei that has been used as a topical fungicidal drug since the 1950s. It is active against Candida, Cryptococcus, Histoplasma, Blastomyces, and Aspergillus spp. and has a spectrum of antifungal activity similar to that of amphotericin B (1,4,13,22).Early attempt...

Mice made monocytopenic with etoposide or both granulocytopenic and monocytopenic with cyclophosphamide were infected in a thigh muscle with 3 x 10(6) CFU of Staphylococcus aureus; 1 h later erythromycin or roxithromycin was administered, and 4 h after that the number of CFU per thigh was determined. In vitro as well as in vivo, the maximal effect of both antibiotics was only bacteriostatic. Monocytopenia did not diminish the efficacy of either erythromycin or roxithromycin in vivo, whereas the combination of granulocytopenia and monocytopenia markedly decreased the efficacy of both drugs: a 4-fold dose increase was necessary to obtain the same final number of CFU at the site of infection as in the controls. It is concluded that granulocytes contributed substantially to antibiotic efficacy against S. aureus in this short-term infection model.

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