False positivity of the Aspergillus galactomannan Platelia ELISA because of piperacillin/tazobactam treatment: does it represent a clinical problem?

OBJECTIVES: False-positive results of the galactomannan (GM) ELISA caused by concurrent administration of piperacillin/tazobactam have been reported in patients with febrile neutropenia. PATIENTS AND METHODS: This prospective study investigated different sampling times in 30 patients receiving piperacillin/tazobactam for febrile neutropenia. RESULTS: Prior to the first piperacillin/tazobactam infusion, a median GM index of 0.2 [interquartile range (IQR) 0.1-0.3] was noted; in two patients (7%) the index was 0.5. Immediately after piperacillin/tazobactam infusion, the median index increased to 0.3 (IQR 0.2-0.4, P = 0.002) leading to 21% (7/30) false-positive results, if > or = 0.5 is assumed as the cut-off level. GM indices before the next piperacillin/tazobactam infusion were not increased (median 0.2, IQR 0.2-0.35, P > 0.05), but 10% (3/30) were still > or = 0.5. With a cut-off level of > 0.7, no false-positive results were noted at any sampling time point. CONCLUSIONS: We conclude that the clinical relevance of false-positive GM results during piperacillin/tazobactam treatment is small if samples are collected prior to infusion and if a cut-off level of > 0.7 is used.

An audit of efficacy and toxicity of teicoplanin versus vancomycin in febrile neutropenia: is the different toxicity profile clinically relevant?

BACKGROUND: Glycopeptides are often used for persistent fever in neutropenic patients. This study compares efficacy and toxicity of teicoplanin and vancomycin. PATIENTS AND METHODS: Hundred consecutive neutropenic patients with hematological malignancies and persistent fever after 72 h of first-line antibiotic therapy (91% piperacillin/tazobactam) were treated with teicoplanin (800 mg on day 1, then 400 mg/day)+piperacillin/tazobactam+gentamicin from 08/96 to 09/00 (group T) or with vancomycin (2 g/day)+meropenem+levofloxacin from 10/00 to 04/02 (group V). Success was defervescence (>or=7 days) in absence of any sign of continuing infection. Nephrotoxicity was monitored daily as increase in serum creatinine. RESULTS: Fifty patients were analyzed in each group. Efficacy was evaluated in patients with piperacillin/tazobactam as first-line therapy only. Treatment was successful in 76% in group T (n=42) and 59% in group V (n=49), p=0.118. Toxicity was evaluated in all patients. The median increase of creatinine was 11% (interquartile range 0%-30%) in group T and 17% (0%-74%) in group V, p=0.062. In patients who received concomitant amphotericin B (given for 7 days and 6 days, respectively, p=0.525), median creatinine increased from 0.9 mg/dl (0.8-1.1) to 1.2 mg/dl (0.9-1.5) in group T and from 0.9 mg/dl (0.8-1.08) to 1.55 mg/dl (1.33-2.23) in group V (p<0.001). This led to a doubling of creatinine in 2/23 (9%) patients of group T and in 9/16 (56%) patients of group V (p=0.003). A multivariate analysis revealed that concomitant use of amphotericin B (p<0.001) and treatment with vancomycin (p=0.002) were independently associated with nephrotoxicity. CONCLUSION: Teicoplanin and vancomycin were comparably effective in patients with neutropenia and persistent fever, but - if combined with amphotericin B - vancomycin was significantly more nephrotoxic than teicoplanin.

Change of procalcitonin predicts clinical outcome of febrile episodes in patients with hematological malignancies.

BACKGROUND: Procalcitonin (PCT) was widely investigated in febrile neutropenia as an indirect marker of infection. Many institutions also use PCT as a tool to monitor the course of a febrile episode because increases in PCT values during the febrile episode were associated with development of complications. However, to date, no study systematically evaluated the accuracy of decreasing PCT values in predicting favorable outcomes of a febrile episode. The aim of this study was to evaluate the changes in PCT values after resolution of fever with regard to their predictive value of stable defervescence. MATERIALS AND METHODS: PCT was studied prospectively in 94 febrile episodes of 35 patients with hematological malignancies. RESULTS: Sixty-seven episodes were associated with an increased level of PCT at the beginning. In these episodes, stable resolution of fever was significantly correlated with a decrease in PCT values. The best cut-off level to predict freedom from recurrence of fever for at least 5 days was <70% of the maximum PCT value on the second afebrile day. Out of 44 patient episodes with a subsequent decrease to <70%, only two patients had recurrent fever within the next 5 days, revealing a negative predictive value of 95%, p<0.001. CONCLUSION: Our study supports the value of PCT as a reliable tool to predict clinical outcome in febrile neutropenia.

Caspofungin treatment in severely ill, immunocompromised patients: a case-documentation study of 118 patients.

BACKGROUND: Caspofungin has shown efficacy in empirical antifungal therapy in neutropenic patients, refractory invasive Aspergillus infections and invasive candidiasis. Here we report the currently largest series of patients treated with caspofungin outside clinical trials. METHODS: Centres in Germany that were known to treat patients with invasive fungal infections were asked to fill out detailed questionnaires for all patients treated with caspofungin. No effort was made to influence the decision to use caspofungin. RESULTS: A total of 118 patients were evaluable (median age 48 years, interquartile range 38-58), out of which 41 (35%) suffered from acute leukaemia, 31 (26%) had allogeneic stem cell transplants, 16 (14%) lymphoma or myeloma, 8 (7%) autologous stem cell transplants and 22 (19%) other causes for immunosuppression. One hundred and six patients were evaluable for efficacy out of which 68 (64%) patients achieved a complete or partial remission. A total of 81 out of 115 (70%) patients were alive 30 days after the end of caspofungin therapy. Response rates were similar in proven (20/32, 63%) and probable (27/46, 59%) infections, in neutropenic patients (41/55, 75%) and in patients who were (44/70, 63%) or were not (24/36, 67%) refractory to antifungal pre-treatment. The response rate in mechanically ventilated patients was 29% (7/24). Caspofungin was well tolerated, even in 14 patients, who were concomitantly treated with ciclosporin A, no drug-related elevations of bilirubin, alanine aminotransferase or creatinine were found. CONCLUSIONS: This open case study of severely ill patients with invasive fungal infections demonstrates both excellent efficacy and very low toxicity of caspofungin.

MTX-induced white matter changes are associated with polymorphisms of methionine metabolism.

Methotrexate (MTX) is a folate antagonist inhibiting nucleic acid and methionine synthesis. Methionine is necessary for CNS myelination. In 42 patients with primary CNS lymphoma (PCNSL) treated with a systemic and intraventricular high-dose MTX-based polychemotherapy, the presence of a risk haplotype defined by polymorphisms influencing methionine metabolism referred a relative risk for CNS white matter changes of 4.7 (p = 0.001). The authors conclude that methionine metabolism influences MTX neurotoxicity.

[Acute central nervous symptoms in oncologic patients]. / Akute zentralnervöse Symptome.

Oncologic patients may suffer from acute central nervous system disorders either related to the disease itself or to its therapy. These disorders may present as a disturbance of consciousness, as mental changes, as focal neurological signs, as epileptic seizures or as a combination of these. Symptoms may be caused by cerebral metastases, hemorrhage, ischemia or infectious complication, by metabolic changes or by treatment sequealae. This article will focus on clinical presentation, diagnostic workup and possible therapy or prophylaxis of these complications.