Assessing the risk of false positive serum galactomannan among patients receiving piperacillin/tazobactam for febrile neutropenia

&NA; Galactomannan (GM) assay is commonly used as an early diagnostic tool for invasive fungal infection (IFI) in high‐risk hematology patients. False positivity is frequently observed in GM with the use of piperacillin/tazobactam. The usage of generic drugs over the original brand has a significant cost advantage. The aim of this study was to assess the performance of GM test among patients receiving original and generic piperacillin/tazobactam formulations. The study included 85 adult patients; 62.4% were male with hematological malignancy currently receiving piperacillin/tazobactam. The study group was divided into two groups: patients receiving original and generic piperacillin/tazobactam. Serum GM index was positive in one of 35 patients receiving original piperacillin/tazobactam, whereas it was positive in 46 out of 50 patients receiving generic piperacillin/tazobactam (P < .001). However, the patients receiving generic piperacillin/tazobactam underwent computed tomography (CT) scans more frequently than those receiving original piperacillin/tazobactam (P = .047). In addition, in vitro analysis of GM was performed in two generics and one original piperacillin/tazobactam vials. One generic piperacillin/tazobactam vial included high GM level. False positivity of serum GM with generic formulations of piperacillin/tazobactam is still an ongoing issue in hematology patients. A high rate of serum GM index false positivity may unexpectedly lead to a higher rate of CT scan. Selected piperacillin/tazobactam vials in each batch should be checked for GM to identify a false positivity of GM before purchase.

[1]  Kihyun Kim,et al.  Multiple myeloma as a major cause of false-positive galactomannan tests in adult patients with cancer. , 2016, The Journal of infection.

[2]  C. Pfeiffer,et al.  Diagnosis of Invasive Aspergillosis: Use of the Galactomannan Assay , 2015, Current Treatment Options in Infectious Diseases.

[3]  C. Jung,et al.  Generic piperacillin/tazobactam is not associated with galactomannan false-positivity in adult patients with cancer: a case–control study , 2015, European Journal of Clinical Microbiology & Infectious Diseases.

[4]  A. Caliendo,et al.  Reduction in False-Positive Aspergillus Serum Galactomannan Enzyme Immunoassay Results Associated with Use of Piperacillin-Tazobactam in the United States , 2014, Journal of Clinical Microbiology.

[5]  P. Tattevin,et al.  Efficacy and quality of antibacterial generic products approved for human use: a systematic review. , 2014, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[6]  G. Metan The interaction between piperacillin–tazobactam and Aspergillus galactomannan antigenemia assay: is the story over? , 2013, Infection.

[7]  J. Wingard,et al.  Diagnostic methods for invasive fungal diseases in patients with hematologic malignancies , 2012, Expert review of hematology.

[8]  C. Viscoli,et al.  Piperacillin/tazobactam (Tazocin™) seems to be no longer responsible for false-positive results of the galactomannan assay. , 2012, The Journal of antimicrobial chemotherapy.

[9]  K. Donhuijsen,et al.  Diagnosis of invasive fungal infections in hematology and oncology--guidelines from the Infectious Diseases Working Party in Haematology and Oncology of the German Society for Haematology and Oncology (AGIHO). , 2012, Annals of oncology : official journal of the European Society for Medical Oncology.

[10]  P. Rousselot,et al.  False positive galactomannan Platelia due to piperacillin-tazobactam. , 2012, Medecine et maladies infectieuses.

[11]  A. Thiébaut,et al.  European guidelines for antifungal management in leukemia and hematopoietic stem cell transplant recipients: summary of the ECIL 3—2009 Update , 2011, Bone Marrow Transplantation.

[12]  A. Koç,et al.  The interaction between piperacillin/tazobactam and assays for Aspergillus galactomannan and 1,3-beta-d-glucan in patients without risk factors for invasive fungal infections , 2010, Infection.

[13]  V. Aquino,et al.  Galactomannan detection from piperacillin-tazobactam brands available in the Brazilian market. , 2009, The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases.

[14]  A. Vekhoff,et al.  Empirical versus preemptive antifungal therapy for high-risk, febrile, neutropenic patients: a randomized, controlled trial. , 2009, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[15]  Patricia Muñoz,et al.  Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. , 2008, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[16]  H. Nakasone,et al.  False-positive Aspergillus galactomannan antigenaemia after haematopoietic stem cell transplantation. , 2007, The Journal of antimicrobial chemotherapy.

[17]  P. Verweij,et al.  Issues with galactomannan testing. , 2006, Medical mycology.

[18]  J. Fine,et al.  Diagnosis of invasive aspergillosis using a galactomannan assay: a meta-analysis. , 2006, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[19]  R. Porcher,et al.  Occurrence and Kinetics of False-Positive Aspergillus Galactomannan Test Results following Treatment with β-Lactam Antibiotics in Patients with Hematological Disorders , 2006, Journal of Clinical Microbiology.

[20]  C. Viscoli,et al.  Galactomannan in Piperacillin-Tazobactam: How Much and to What Extent? , 2005, Antimicrobial Agents and Chemotherapy.

[21]  Nina Singh,et al.  Aspergillus Infections in Transplant Recipients , 2005, Clinical Microbiology Reviews.

[22]  S. Ogawa,et al.  Prospective Comparison of the Diagnostic Potential of Real-Time PCR, Double-Sandwich Enzyme-Linked Immunosorbent Assay for Galactomannan, and a (1→3)-β-d-Glucan Test in Weekly Screening for Invasive Aspergillosis in Patients with Hematological Disorders , 2004, Journal of Clinical Microbiology.

[23]  Nina Singh,et al.  Reactivity of Platelia Aspergillus Galactomannan Antigen with Piperacillin-Tazobactam: Clinical Implications Based on Achievable Concentrations in Serum , 2004, Antimicrobial Agents and Chemotherapy.

[24]  P. Bruzzi,et al.  False-positive galactomannan platelia Aspergillus test results for patients receiving piperacillin-tazobactam. , 2004, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[25]  R. Tauxe,et al.  Lack of Evidence That False-Positive Aspergillus Galactomannan Antigen Test Results Are Due to Treatment with Piperacillin- Tazobactam , 2004 .