A prospective study of real-time panfungal PCR for the early diagnosis of invasive fungal infection in haemato-oncology patients.

A blinded prospective study was performed to determine whether screening of whole blood using a real-time, panfungal polymerase chain reaction (PCR) technique could predict the development of invasive fungal infection (IFI) in immunocompromised haemato-oncology patients. In all, 78 patients (125 treatment episodes) were screened twice weekly by real-time panfungal PCR using LightCyclertrade mark technology. IFI was documented in 19 treatment episodes (five proven, three probable and 11 possible), and in 12, PCR was sequentially positive. PCR positivity occurred in: 4/5 proven; 2/3 probable; 6/11 possible; and 29/106 with no IFI. In 8/12 with IFI and sequentially positive PCR results, PCR positivity occurred before (median 19.5 days) and in 4/12 (median 10.5 days) after the initiation of empirical antifungal therapy. Based on sequential positive results for proven/probable IFI sensitivity, specificity, positive predictive value and negative predictive value were 75, 70, 15 and 98%, respectively. Real-time panfungal PCR is a sensitive tool for the early diagnosis of IFI in immunocompromised haemato-oncology patients. It may be most useful as a screening method in high-risk patients, either to direct early pre-emptive antifungal therapy or to determine when empirical antifungal therapy can be withheld in patients with antibiotic--resistant neutropenic fever. However, these strategies require further assessment in comparative clinical trials.

Successful haemopoietic stem cell transplantation does not correct mannan-binding lectin deficiency.

It has been reported that in allogeneic stem cell transplantation, the mannan-binding lectin (MBL) status of the donor has prognostic value for the recipient. Two MBL-deficient patients, with coexisting haematological malignancy, were identified who were treated with bone marrow from donors with normal MBL concentrations. Although both patients engrafted successfully and remain in complete remission, neither seroconverted to the MBL sufficiency status of his donor over a follow-up period exceeding 2 years. This does not support the concept of MBL replacement by stem cell therapy, and does not provide an explanation for high MBL concentrations in stem cell donors protecting recipients from post transplant infections.

No strong relationship between mannan binding lectin or plasma ficolins and chemotherapy-related infections.

Chemotherapy causes neutropenia and an increased susceptibility to infection. Recent reports indicate that mannan-binding lectin (MBL) insufficiency is associated with an increased duration of febrile neutropenia and incidence of serious infections following chemotherapy for haematological malignancies. We aimed to confirm or refute this finding and to extend the investigation to the plasma ficolins, P35 (L-ficolin) and the Hakata antigen (H-ficolin). MBL, L-ficolin and H-ficolin were measured in 128 patients with haematological malignancies treated by chemotherapy alone or combined with bone marrow transplantation. Protein concentrations were related to clinical data retrieved from medical records. MBL concentrations were elevated compared with healthy controls in patients who received chemotherapy, while L-ficolin concentrations were decreased and H-ficolin levels were unchanged. There was no correlation between MBL, L-ficolin or H-ficolin concentration and febrile neutropenia expressed as the proportion of neutropenic periods in which patients experienced fever, and there was no relation between abnormally low (deficiency) levels of MBL, L-ficolin or H-ficolin and febrile neutropenia so expressed. Patients with MBL < or =0.1 microg/ml had significantly more major infections than no infections within the follow-up period (P<0.05), but overall most patients had signs or symptoms of minor infections irrespective of MBL concentration. Neither L-ficolin nor H-ficolin deficiencies were associated with infections individually, in combination or in combination with MBL deficiency. MBL, L-ficolin and H-ficolin, independently or in combination, did not have a major influence on susceptibility to infection in these patients rendered neutropenic by chemotherapy. These results cast doubt on the potential value of MBL replacement therapy in this clinical context.

Interaction between hormone replacement therapy preparations and oral anticoagulant therapy.

There is limited information regarding the interaction of hormone replacement therapy (HRT) and oral anticoagulants. Following the acute over-anticoagulation of two women shortly after the initiation of tibolone, we have undertaken a retrospective review of anticoagulated women to determine if the dose of oral anticoagulants and quality of anticoagulant control are affected by the introduction of HRT. We demonstrate that acute over-anticoagulation consistently occurs following the commencement of tibolone and requires anticoagulant dose modification to re-establish target international normalised ratio (INR). In contrast, non-tibolone HRT preparations do not consistently alter anticoagulant control or dose requirements.