Antibiotics and False-positive Aspergillus galactomannan assay

Q: 54 years old post lung transplant patient is admitted to ICU with respiratory failure and found to have aspergillosis. Due to severe septic shock, the patient is also started on broad-spectrum antibiotics along with anti-fungal. Which of the following antibiotics may give false positive results of the gаlаϲtοmaոոaո enzyme immunoassay (EIA) when concomitantly administrated with anti-fungal?

A) Piperacillin-tazobactam

B) Levofloxacin

C) Trimethoprim-sulfamethoxazole

D) Clindamycin

E) Vancomycin

Answer: A

Gаlаϲtοmаոոan is a polysaccharide and is a significant constituent of Aspergillus cell walls. The gаlаϲtοmаոnаn EIA is reported as optical density (OD). FDA suggests a threshold OD index of 0.5, which means an OD index ≥0.5 is considered positive.

Most of these patients are usually very sick and get covered with broad-spectrum antibiotics besides anti-fungal. There have been case reports where intravenous piperacillin-tazobactam may cause false positive results due to the presence of gаlаϲtοmаոnan (or a cross-reactive antigen) in the antibiotic formulation. The risk of a false positive result persists for about 5 days after discontinuing the antibiotic. However, it appears that risk has been reduced with the change in formulations.

Similar reports have been published with one of the formulations of intravenous amoxicillin-clavulanate.

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References:

1. Mennink-Kersten MA, Donnelly JP, Verweij PE. Detection of circulating galactomannan for the diagnosis and management of invasive aspergillosis. Lancet Infect Dis 2004; 4:349.

2. Walsh TJ, Shoham S, Petraitiene R, et al. Detection of galactomannan antigenemia in patients receiving piperacillin-tazobactam and correlations between in vitro, in vivo, and clinical properties of the drug-antigen interaction. J Clin Microbiol 2004; 42:4744.

3. Vergidis P, Razonable RR, Wheat LJ, et al. Reduction in false-positive Aspergillus serum galactomannan enzyme immunoassay results associated with use of piperacillin-tazobactam in the United States. J Clin Microbiol 2014; 52:2199.

4.Mattei D, Rapezzi D, Mordini N, et al. False-positive Aspergillus galactomannan enzyme-linked immunosorbent assay results in vivo during amoxicillin-clavulanic acid treatment. J Clin Microbiol 2004; 42:5362.