Performance of the galactomannan antigen detection test in the diagnosis of invasive aspergillosis in children with cancer or undergoing haemopoietic stem cell transplantation.

Serum galactomannan (GM) antigen detection is not recommended for defining invasive aspergillosis (IA) in children undergoing aggressive chemotherapy or allogeneic haemopoietic stem cell transplantation (HSCT). The ability of the GM test to identify IA in children was retrospectively evaluated in a cohort of children. Test performance was evaluated on samples that were collected during 195 periods at risk of IA. Proven IA was diagnosed in seven periods, all with positive GM test results (true positives, 4%), and possible IA was diagnosed in 15 periods, all with negative GM test results (false negatives, 8%). The test result was positive with negative microbiological, histological and clinical features in three periods (false positives, 1%), and in 170 periods it was negative with negative microbiological, histological and clinical features (true negatives, 87%). The sensitivity was 0.32 and the specificity was 0.98; the positive predictive value was 0.70 and the negative predictive value was 0.92. The efficiency of the test was 0.91, the positive likelihood ratio was 18.3, and the negative likelihood ratio was 1.4. The probability of missing an IA because of a negative test result was 0.03. Test performance proved to be better during at-risk periods following chemotherapy than in periods following allogeneic HSCT. The GM assay is useful for identifying periods of IA in children undergoing aggressive chemotherapy or allogeneic HSCT.

Kinetics of galactomannan in surgical patients receiving perioperative piperacillin/tazobactam prophylaxis.

OBJECTIVES: The association between piperacillin/tazobactam and the positivity of the galactomannan (GM) detection ELISA test is well described. Little information is available about the kinetics of GM in patients treated with piperacillin/tazobactam. The present study aimed at clarifying the baseline interaction between piperacillin/tazobactam and GM in patients receiving this drug. PATIENTS AND METHODS: Seven patients undergoing abdominal surgery received perioperative prophylaxis with piperacillin/tazobactam. Each patient received three doses of 4.5 g of the drug, administered at 8 h intervals (one before and two after surgery). Three patients received antibiotic batches with 'medium' (GM-index = 1.782) and four patients received antibiotic batches with 'high' (GM-index = 6.665) GM content. Serum samples for GM evaluation were collected before drug infusion and at times +1, +3, +6 and +8 h after the first and third infusions. RESULTS: GM levels increased after infusion, in particular when batches with 'high' GM content were used. Moreover, a non-statistically significant increase between the first dose and the third dose was observed. All samples taken >6 h after administration were negative (GM-index < 0.2), both with the 'medium' and the 'high' GM content batches. CONCLUSIONS: The low content of GM 8 h after piperacillin/tazobactam infusion suggests that in non-neutropenic cancer patients with solid tumours receiving up to three doses of piperacillin/tazobactam, serum sampling for GM detection should be performed immediately before the next piperacillin/tazobactam administration.

Caspofungin associated with liposomal amphotericin B or voriconazole for treatment of refractory fungal pneumonia in children with acute leukaemia or undergoing allogeneic bone marrow transplant.

Caspofungin, in association with other antifungal drugs, was administered as rescue therapy in two cases of documented and one case of possible invasive fungal infection in children with acute leukaemia or undergoing allogeneic bone marrow transplant. The combined therapy was well-tolerated and seemed to be effective in all three patients. A combination antifungal therapy including caspofungin could represent an effective therapy for children with invasive mycoses refractory to single-agent antifungal therapy.

Antifungal prophylaxis with azole derivatives.

In recent years, several reports have underlined the increasing role of fungal infections as a cause of morbidity and mortality in hospitalised patients. For this reason, and also in light of the high mortality rate associated with these infections, chemoprophylaxis has been advocated by several authors. The available evidence suggests that both fluconazole and itraconazole are able to decrease candida colonisation and infection, when compared with placebo or with nonabsorbable antifungals. Data seem also to suggest that a decrease in fungus-related mortality can be achieved with prophylaxis, although with little effect on overall mortality, probably because of the importance of severe underlying diseases. Itraconazole proved to be effective in the prevention of fungal infections, including invasive aspergillosis, although with increased incidence of side-effects, often leading to treatment discontinuation. The other side of the coin is that antifungal prophylaxis might have untoward effects, such as the selection of triazole-resistant Candida strains or the induction of resistance. In addition, some authors have suggested that the use of triazoles might modulate the pattern of infecting organisms in cancer patients, increasing the risk of both aspergillosis and bacteremia. In conclusion, antifungal prophylaxis with triazole antifungals should be used with caution, only in patients at high risk for invasive fungal infections. These include allogeneic bone marrow transplant patients (especially those with mismatched or unrelated donors), acute myeloid leukaemia patients treated with high-dose cytarabine (C-ara), very-low-birth-weight infants, patients with chronic granulomatous disease, and high-risk surgical and intensive-care unit patients.

Antigen detection in the diagnosis and management of a patient with probable cerebral aspergillosis treated with voriconazole.

This report describes the diagnosis and management of a 16-year-old boy who developed neurological signs and symptoms suggestive of cerebral aspergillosis following a haploidentical bone marrow transplant. A new sandwich enzyme-linked immunosorbent assay (ELISA) for the detection of Aspergillus galactomannan circulating antigens (Platelia Aspergillus, Sanofi Diagnostic Pasteur, France) was used on serum and cerebrospinal fluid to obtain a presumptive diagnosis and to monitor the course of the disease. Having failed conventional therapy with amphotericin B, the patient received compassionate treatment with voriconazole for a period of 37 days. High levels of voriconazole were observed in both serum and cerebrospinal fluid (CSF), with a trend toward accumulation. After 7 days a marked improvement in the patient's neurological symptoms was noted, and ELISA data indicated a corresponding decrease in Aspergillus galactomannan levels in both serum and CSF. Voriconazole was well tolerated, with only transient increases in ALT/AST recorded during therapy. Although the patient survived the acute Aspergillus infection, he subsequently died of an unrelated infection.

Comparison of an enzyme immunoassay and a latex agglutination system for the diagnosis of invasive aspergillosis in bone marrow transplant recipients.

The performance of two Aspergillus antigenemia systems, the sandwich enzyme-linked immunosorbent assay (ELISA), Platelia Aspergillus test, and the latex agglutination (LA), Pastorex Aspergillus test, in the diagnosis of invasive aspergillosis were compared by testing 364 serum samples from 22 bone marrow transplant (BMT) recipients. Sensitivity and specificity for the ELISA test were 60% and 82% respectively, vs 40% and 94% for the LA test. In the two patients found positive with both methods, the ELISA test became positive earlier than the LA test or remained positive after the LA test had become negative. These results encourage further evaluation of the Platelia Aspergillus test, to assess its role in the management of invasive aspergillosis in BMT patients.

Antifungal treatment in patients with cancer.

Invasive fungal infections are one of the leading causes of morbidity and mortality in cancer patients. Amphotericin B deoxycholate is still considered the gold standard of antifungal therapy, although the new triazoles (itraconazole and, especially, fluconazole) have shown to be able to replace amphotericin B for some therapeutic indications. The new lipid formulations of amphotericin B have disclosed new therapeutic perspectives, especially in patients with severe renal failure and documented, infections. At this time, indications, contraindications and limitation of the various drugs in the antifungal armamentarium are still partially unclear. Antifungal prophylaxis with fluconazole may be indicated in high-risk patients, although the duration of such prophylaxis should be limited as much as possible, in order to prevent selection of resistant strains and acquired resistance. Empirical antifungal therapy is used extremely widely (maybe, too widely) in many cancer centres, despite being based on limited clinical data. For this indication, fluconazole may also be effective in patients not receiving fluconazole prophylaxis, in whom Aspergillus infection is unlikely.