Plasmalyte: No Longer a Culprit in Causing False-Positive Galactomannan Test Results

Abstract

dFalse-positive galactomannan (GM) results have been reported in patients treated with gluconate-containing solutions, such as Plasmalyte. The GM optical density index was tested on 33 distinct batches of Plasmalyte and was found to be negative in all of the batches, confirming that Plasmalyte is no longer a cause of false-positive GM results. Invasive aspergillosis is a serious infection associated with a high mortality rate in patients at risk, such as those receiving chemotherapy or undergoing allogeneic hematopoietic stem cell transplantation or those admitted in the intensive care unit (ICU). Galactomannan (GM), a fungal antigen produced by Aspergillus spp. during growth, is an important biomarker for early nonculture-based diagnosis of invasive aspergillosis in immunocompromised patients. Currently, positive serum testing on the GM enzyme immunoassay (Platelia Aspergillus; Bio-Rad, Marnes-La-Coquette, France) is one of the criteria for establishing the diagnosis of probable invasive aspergillosis in immunocompromised patients according to the European Organization for Research and Treatment of Cancer and Mycoses Study Group (EORTC/MSG) (1). For the last decade, GM testing has also been applied on bronchoalveolar lavage (BAL) fluid, especially in nonneutropenic ICU patients, as this has been shown to have good sensitivity and specificity in diagnosing invasive aspergillosis in patients without the classic immunocompromising risk factors (2).An important limiting factor for GM testing is the association with false-positive test results, which have been reported in patient serum or BAL fluid, if the patient is treated with generic piperacillin-tazobactam and amoxicillin clavulanate (3, 4). These antibiotics are produced by fermentation in Penicillium, which generates GM recognized by the monoclonal antibody used in the Platelia assay.Plasmalyte (Baxter, Lessines, Belgium) is a sterile, nonpyrogenic electrolyte solution that contains sodium chloride, potassium chloride, magnesium chloride, sodium acetate trihydrate, and bicarbonate ions with or without sodium gluconate. It is used for fluid resuscitation and hydration in severely ill patients. Fluid resuscitation in ICU patients has been a matter of debate during the last decade, with many studies investigating resuscitation efficacy in terms of hemodynamic and patient outcome versus potential adverse effects, such as kidney injury and the need for renal replacement therapy (5). Several studies suggested that balanced salt solutions, based on gluconate, acetate, or lactate should be used preferentially in order to avoid the side effects related to hyperchloremia and renal dysfunction associated with normal saline purely composed of chlorine salts (5). Since 2012, Plasmalyte, a balanced electrolyte solution, has been the default resuscitation fluid in our hospital, particularly in septic critically ill patients, as recommended by recent international consensus (6).In Belgium, only gluconate-containing Plasmalyte solutions are available (Plasmalyte A Viaflo and ...

False‐positive Candida and Aspergillus antigen testing in recipients of allogeneic haematopoietic cell transplantation due to administration of parenteral nutrition and fixed combinations of piperacillin‐tazobactam

“…False‐positive GM antigenemia is reported in haematological patients after allogeneic PBSCT due to gastrointestinal chronic GvHD . However, recent publications regarding GM in beta‐lactam antibiotics and sodium gluconate could not detect GM anymore . Furthermore, false‐positive GM EIA results due to TZP or PN infusion did not occur in our investigation which is consistent with the results of our previous in vitro study .…”

“…26 However, recent publications regarding GM in beta-lactam antibiotics and sodium gluconate could not detect GM anymore. [13][14][15][16][17][18]27,28 Furthermore, false-positive GM EIA results due to TZP or PN infusion did not occur in our investigation which is consistent with the results of our previous in vitro study. 7 In contrast, Recommendations to the handling of false positivity exist only for the GM EIA.…”

Plasma-Lyte 148: A clinical review

“…Positive test results in patients receiving PL 148 should therefore be interpreted cautiously and the galactomannan antigen should be confirmed by other diagnostic methods[4]. More recently however, Spriet et al[8] tested 33 distinct batches of PL 148 and reported that with contemporary sophisticated manufacturing processes, PL 148 does not result in false-positive galactomannan test results.…”

False positive bronchoalveolar lavage galactomannan: Effect of host and cut‐off value

“…Bronchoalveolar lavage galactomannan is more sensitive than serum GM in diagnosing probable or proven IA, likely due to a higher fungal burden in the airways than in the blood in IA, and increased secretion of GM in lung tissue . False positive BAL‐GM results occur in immunocompetent patients colonised with Aspergillus without clinical or radiographic evidence of IA, and potentially in patients receiving piperacillin‐tazobactam or gluconate‐containing solutions containing GM antigens; this is no longer a major concern due to changes in manufacturing . Occasionally, BAL‐GM may be positive in infections with other non‐ Aspergillus fungi .…”

“…7,10 False positive BAL-GM results occur in immunocompetent patients colonised with Aspergillus without clinical or radiographic evidence of IA, 11 and potentially in patients receiving piperacillin-tazobactam or gluconate-containing solutions containing GM antigens; this is no longer a major concern due to changes in manufacturing. [12][13][14] Occasionally, BAL-GM may be positive in infections with other non-Aspergillus fungi. 15 False negative results have been reported in patients receiving antifungal agents.…”