Dataset Information

Low cut-off value of serum (1,3)-beta-D-glucan for the diagnosis of Pneumocystis pneumonia in non-HIV patients: a retrospective cohort study.

ABSTRACT:

Background

Non-human immunodeficiency virus (HIV) Pneumocystis pneumonia (PCP) is a fulminant disease with an increasing incidence. The serum beta-D-glucan (BDG) assay is used as an adjunct to the diagnosis of PCP; however, the cut-off value for this assay is not well-defined, especially in the non-HIV PCP population. Therefore, we aimed to identify the assay cut-off value for this population.

Methods

In this retrospective observational study, we reviewed the medical records of all patients (≥ 18 years old) with clinical suspicion of PCP who underwent evaluation of respiratory tract specimens between December 2008 and June 2014 at Kameda Medical Center. We created a receiver operating characteristic curve and calculated the area under the curve to determine the cut-off value for evaluating the inspection accuracy of the BDG assay.

Results

A total of 173 patients were included in the study. Fifty patients showed positive results in specimen staining, loop-mediated isothermal amplification assay, and polymerase chain reaction test, while 123 patients showed negative results. The receiver operating characteristic analyses suggested that the BDG cut-off level was 8.5 pg/mL, with a sensitivity and specificity of 76% and 76%, respectively.

Conclusions

The Wako-BDG cut-off value for the diagnosis of non-HIV PCP is 8.5 pg/mL, which is lower than the classical cut-off value from previous studies. Clinicians should potentially consider this lower BDG cut-off value in the diagnosis and management of patients with non-HIV PCP.

Trial registration

The participants were retrospectively registered.

SUBMITTER: Taniguchi J

PROVIDER: S-EPMC8628137 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveThe current study evaluated the diagnostic performance of serum (1,3)-beta-D Glucan (BDG) in differentiating PJP from P. jirovecii-colonization in HIV-uninfected patients with P. jirovecii PCR-positive results.MethodsThis was a single-center retrospective study between 2019 and 2021. The diagnosis of PJP was based on the following criteria: detection of P. jirovecii in sputum or BAL specimen by qPCR or microscopy; Meet at least two of the three criteria: (1) have respiratory symptoms of cough and/or dyspnea, hypoxia; (2) typical radiological picture findings; (3) receiving a complete PJP treatment. After exclusion, the participants were divided into derivation and validation cohorts. The derivation cohort defined the cut-off value of serum BDG. Then, it was verified using the validation cohort.ResultsTwo hundred and thirteen HIV-uninfected patients were enrolled, with 159 PJP and 54 P. jirovecii-colonized patients. BDG had outstanding specificity, LR, and PPV for PJP in both the derivation (90.00%, 8.900, and 96.43%) and the validation (91.67%, 9.176, and 96.30%) cohorts at ≥ 117.7 pg/mL. However, it had lower sensitivity and NPV in the derivation cohort (89.01% and 72.97%), which was even lower in the validation cohort (76.47% and 57.89%). Of note, BDG ≥ 117.7 pg/mL has insufficient diagnostic efficacy for PJP in patients with lung cancer, interstitial lung disease (ILD) and nephrotic syndrome. And although lymphocytes, B cells, and CD4+ T cells in PJP patients were significantly lower than those in P. jirovecii-colonized patients, the number and proportion of peripheral blood lymphocytes did not affect the diagnostic efficacy of serum BDG.ConclusionsSerum BDG ≥ 117.7 pg/mL could effectively distinguish P. jirovecii-colonization from infection in qPCR-positive HIV-uninfected patients with infectious diseases, solid tumors (excluding lung cancer), autoimmune or inflammatory disorders, and hematological malignancies. Of note, for patients with lung cancer, ILD, and nephrotic diseases, PJP should be cautiously excluded at BDG < 117.7 pg/mL.

Project description:Background: Serum (1,3)-β-D-glucan (BG) testing is increasingly being used in the diagnostic armamentarium for invasive fungal diseases. Given its high sensitivity, some studies suggest that a negative BG result contributes to rule out a diagnosis of Pneumocystis pneumonia (PCP). However, recent reports described a suboptimal sensitivity in HIV-negative immunocompromised patients. In this study, we evaluated the performance of BG assay for PCP diagnosis in HIV-negative patients with diverse PCP risk factors. We also assessed the correlation between Pneumocystis jirovecii load in pulmonary samples and serum BG levels. Methods: We retrospectively included HIV-negative patients with microscopically proven PCP and for whom a BG result was available. We also enrolled patients colonized by Pneumocystis as control group. Colonized patients were matched with PCP patients based on their underlying condition that exposed to PCP. Pulmonary fungal loads were determined by an in-house real-time PCR, and BG levels were measured by using the Fungitell® kit (Associates of Cape Cod, Inc.). Results: Thirty-nine patients were included in each of the two groups. Thirty-four of 39 PCP patients and one of 39 colonized patient had a positive BG test, resulting in a sensitivity of 0.87 (95% CI: 0.73-0.94), a specificity of 0.97 (95% CI: 0.87-0.99), a positive predictive value of 0.97 (95% CI: 0.85-0.99), and a negative predictive value of 0.88 (95% CI: 0.75-0.95) for BG assay. Nonetheless, median BG level differed according to the underlying condition. Among the PCP group, the lowest median level of 211 pg/ml was observed in patients with hematological malignancy (HM) and differed significantly from that observed either in solid organ transplants (3,473 pg/ml) or in patients with autoimmune or inflammatory disorder (3,480 pg/ml). Indeed, the sensitivity of BG assay was estimated at 0.64 (95% CI: 0.35-0.85) in HM patients and was lower than the one observed in the whole PCP group. Furthermore, BG level and fungal burden correlated poorly among all PCP patients. Conclusion: BG is not a reliable biomarker for ruling out PCP in HIV-negative patients with HM. Interpretation of a negative BG result should take into account, but not be limited to, the underlying condition predisposing to PCP.