Serum Galactomannan Detection In The Diagnosis Of Invasive Aspergillosis And The Influence Of Commonly Used Antibiotics To It

PART I THE VALUE OF SERUM GALACTOMANNAN DETECTION IN THE DIAGNOSIS OF INVASIVE ASPERGILLOSISOBJECTIVE: To explore the sensitivity and specificity of galactomannan test in the diagnosis of invasive aspergillosis of hematological malignancies. And compare the two different index cutoffs of the test.METHODS:28 inpatients of hematology department in Qilu hospital were selected according to the host factors of invasive fungus infection diagnosis standards of patients with hematologic disease/cancer of China.19 other inpatients without host factors and healthy volunteer are also selected as control. The level of the serum galactomannan was detected by Platelia Aspergillus test. At the same time,the clinical,pathological,laboratory manifestation,images and treatment effect were also collected.RESULTS: According to the invasive fungus infection diagnosis standards of patients with hematologic disease/cancer,the people involved in the experiment can be classified as proven, probable, possible and non-fungus infection.Taking the reagent given serum GM index ≥1.5 as index cutoff and the proven+probable patients as fungus-infection patients, the test's sensitivity is 75%, specificity is 89.2%, positive predictive value is 69.2% and negative predictive value is91.7%. 9 GM test positive patients were treated with itraconazole,5 patients got obvious remission, 4 patients got progress remission, their CT imaging and laboratory tests were also remitted, GM Index obviously decreased.The time needed of GM Index switched into negative (<1.5) after effective treatment was 3.86 days.Taking the reagent index cutoff and the proven+probable+ possible patients as fungus infection patients, the test's sensitivity is 37.9%, specificity is 90.0%, positive predictive value is 84.6% and negative predictive value is 50.0%,the test's sensitivity become obviously low. US FDA recommends the index cutoff of the test is GM index ≥0.5,taking this index cutoff, the test's sensitivity is 75.9%, specificity is 90.0%, positive predictive value is 91.7% and negative predictive value is 72.0%.Considering the possible patients, we can find out that using the FDA cutoff has an obviously higher sensitivity compared to the reagent cutoff, positive predictive value and negative predictive value are also improved,but specificity remains the same.CONCLUSIONS: Serum galactomannan detection in the diagnosis of invasive aspergillosis by enzyme-linked immunosorbent assay has a high sensitivity and specificity.After effective treatment ,the serum GM index decreases obviously,which is important to the diagnosis and effect judgement.In order to elevate the sensitivity of the test ,specially to the possible fungus-infection patients,the index cutoff can be decreased from 1.5 to 0.5,the sensitivity can be increased markedly,but the specificity decrease is unconspicuous. PART II THE INFLUENCE OF COMMONLY USED ANTIBIOTICS TO THE SERUM GALACTOMANNAN DETECTION BY ELISAOBJECTIVE:To determine the influence of commonly used antibioticses to the detection of serum galactomannan by ELISA.METHODS: we selected the representative types from 5 major classes of antibiotics (beta-lactams, fluoroquinolones, aminoglycosides, glycopeptides and macrolides) commonly used in our hospital. Galactomannan antigen was detected in vitro to those antibiotics by Platelia Aspergillus test, and it was also detected in the patients without the host factors of invasive fungus infection who had received those antibiotics treatment for some days.The antibiotics that showed a positive results got further investigation. The results were judgede by reagent given cutoff.RESULTS: On the in vitro antibiotics tests, ampicillin solution GM index was 0.907,which wasn't reach the intermediate positive but was markedly higher than other antibiotics. Piperacillin-tazobactam solution GM index was 1.124,which reached the intermediate positive. Averagely, 2.8 patients without the host factors of invasive fungus infection received those antibiotics ,the duration of treatment was 3-11 days,the patients serum GM tests showed ampicillin and piperacillin-tazobactam treatment got intermediat positive and positive results,their GM index was 1.194±0.354 and 1.430 ±0.482, but all the other antibiotics showed negative results.In the further clinical investigation of the two antibiotics, the patients given ampicillin showed 3/7 intermediat positive results; and those given piperacillin-tazobactam showed 4/9 positive results. 6 patients from those GM tested intermediat positive or positive got follow-up,none of them developped into invasive aspergillosis.CONCLUSIONS: The use of Piperacillin-tazobactam 4.5g Bid could get positive results of serum GM index,and Ampicillin 5g Bid could get intermediate positive results,which should be noticed in the diagnosis of invasive aspergillosis.But the other tested antibiotics didn't show similar results in in vitro and in vivo tests.