Clinical Performance of (1,3) Beta-D Glucan for the Diagnosis of Pneumocystis Pneumonia (PCP) in Cancer Patients Tested With PCP Polymerase Chain Reaction.
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SUBMITTER: Morjaria S
PROVIDER: S-EPMC6763633 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundPneumocystis jirovecii pneumonia (PJP) is a life-threatening infection occurring in patients receiving bendamustine. The poorly defined incidence, particularly when utilizing polymerase chain reaction (PCR)-based diagnostic techniques, precipitates unclear prophylaxis recommendations. Our objective was to determine the cumulative incidence of PJP diagnosed by single copy target, non-nested PCR in patients receiving bendamustine.MethodsPatients were evaluated for PJP from initiation of bendamustine through 9 months after the last administration. The cumulative incidence of PJP was estimated using the Aalen-Johansen method. Cox proportional hazard models were used to demonstrate the strength of association between the independent variables and PJP risk.ResultsThis single-center, retrospective cohort included 486 adult patients receiving bendamustine from 1 January 2006 through 1 August 2019. Most patients received bendamustine-based combination therapy (n = 461, 94.9%), and 225 (46.3%) patients completed six cycles. Rituximab was the most common concurrent agent (n = 431, 88.7%). The cumulative incidence of PJP was 1.7% (95% CI 0.8%-3.3%, at maximum follow-up of 2.5 years), after the start of bendamustine (n = 8 PJP events overall). Prior stem cell transplant, prior chemotherapy within 1 year of bendamustine, and lack of concurrent chemotherapy were associated with the development of PJP in univariate analyses. Anti-Pneumocystis prophylaxis was not significantly associated with a reduction in PJP compared to no prophylaxis (HR 0.37, 95% CI (0.05, 3.04), p = 0.36).ConclusionsOur incidence of PJP below 3.5%, the conventional threshold for prophylaxis implementation, indicates routine anti-Pneumocystis prophylaxis may not be necessary in this population. Factors indicating a high-risk population for targeted prophylaxis require further investigation.
| S-EPMC8335812 | biostudies-literature
Project description:BackgroundPneumocystis jirovecii polymerase chain reaction (PCR) testing is a sensitive diagnostic tool but does not distinguish infection from colonization. Cycle threshold (CT) may correlate with fungal burden and could be considered in clinical decision making. Clinical use of PCR and significance of CT values have not previously been examined with the DiaSorin Molecular platform.MethodsRetrospective review of P jirovecii PCR, CT values and clinical data from 18 months in a multihospital academic health system. The diagnostic performance of PCR with respect to pathology and correlation of CT with severity were examined.ResultsNinety-nine of 1006 (9.8%) assays from 786 patients in 919 encounters were positive. Among 91 (9.9%) encounters in which P jirovecii pneumonia (PJP) was treated, 41 (45%) were influenced by positive PCR. Negative PCR influenced discontinuation of therapy in 35 cases. Sensitivity and specificity of PCR were 93% (95% CI, 68%-100%) and 94% (95% CI, 91%-96%) with respect to pathology. CT values from deep respiratory specimens were significantly different among treated patients (P = .04) and those with positive pathology results (P < .0001) compared to patients not treated and those with negative pathology, respectively, and was highly predictive of positive pathology results (area under the curve = 0.92). No significant difference was observed in comparisons based on indicators of disease severity.ConclusionsPneumocystis jirovecii PCR was a highly impactful tool in the diagnosis and management of PJP, and use of CT values may have value in the treatment decision process in select cases. Further investigation in a prospective manner is needed.
| S-EPMC8754379 | biostudies-literature
Project description:BACKGROUND:Pneumocystis pneumonia (PCP) is a disease affecting immunocompromised patients. PCP among these patients is associated with significant morbidity and mortality. OBJECTIVES:To assess the effectiveness of PCP prophylaxis among non-HIV immunocompromised patients; and to define the type of immunocompromised patient for whom evidence suggests a benefit for PCP prophylaxis. SEARCH METHODS:Electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 1), MEDLINE and EMBASE (to March 2014), LILACS (to March 2014), relevant conference proceedings; and references of identified trials. SELECTION CRITERIA:Randomised controlled trials (RCTs) or quasi-RCTs comparing prophylaxis with an antibiotic effective against PCP versus placebo, no intervention, or antibiotic(s) with no activity against PCP; and trials comparing different antibiotics effective against PCP among immunocompromised non-HIV patients. We only included trials in which Pneumocystis infections were available as an outcome. DATA COLLECTION AND ANALYSIS:Two review authors independently assessed risk of bias in each trial and extracted data from the included trials. We contacted authors of the included trials to obtain missing data. The primary outcome was documented PCP infections. Risk ratios (RR) with 95% confidence intervals (CI) were estimated and pooled using the random-effects model. MAIN RESULTS:Thirteen trials performed between the years 1974 and 2008 were included, involving 1412 patients. Four trials included 520 children with acute lymphoblastic leukemia and the remaining trials included adults with acute leukemia, solid organ transplantation or autologous bone marrow transplantation. Compared to no treatment or treatment with fluoroquinolones (inactive against Pneumocystis), there was an 85% reduction in the occurrence of PCP in patients receiving prophylaxis with trimethoprim/sulfamethoxazole, RR of 0.15 (95% CI 0.04 to 0.62; 10 trials, 1000 patients). The evidence was graded as moderate due to possible risk of bias. PCP-related mortality was also significantly reduced, RR of 0.17 (95% CI 0.03 to 0.94; nine trials, 886 patients) (low quality of evidence due to possible risk of bias and imprecision), but in trials comparing PCP prophylaxis against placebo or no treatment there was no significant effect on all-cause mortality (low quality of evidence due to imprecision). Occurrence of leukopenia or neutropenia and their duration were not reported consistently. No significant differences in overall adverse events or events requiring discontinuation were seen comparing trimethoprim/sulfamethoxazole to no treatment or placebo (four trials, 470 patients, moderate quality evidence). No differences between once daily versus thrice weekly trimethoprim/sulfamethoxazole were seen (two trials, 207 patients). AUTHORS' CONCLUSIONS:Given an event rate of 6.2% in the control groups of the included trials, prophylaxis for PCP using trimethoprim/sulfamethoxazole is highly effective among non-HIV immunocompromised patients, with a number needed to treat to prevent PCP of 19 patients (95% CI 17 to 42). Prophylaxis should be considered for patients with a similar baseline risk of PCP.
| S-EPMC6457644 | biostudies-literature
Project description:BackgroundDiagnosis of Pneumocystis jirovecii pneumonia (PCP) is challenging, particularly in developing countries. Highly sensitive diagnostic methods are costly, while less expensive methods often lack sensitivity or specificity. Cost-effectiveness comparisons of the various diagnostic options have not been presented.Methods and findingsWe compared cost-effectiveness, as measured by cost per life-years gained and proportion of patients successfully diagnosed and treated, of 33 PCP diagnostic options, involving combinations of specimen collection methods [oral washes, induced and expectorated sputum, and bronchoalveolar lavage (BAL)] and laboratory diagnostic procedures [various staining procedures or polymerase chain reactions (PCR)], or clinical diagnosis with chest x-ray alone. Our analyses were conducted from the perspective of the government payer among ambulatory, HIV-infected patients with symptoms of pneumonia presenting to HIV clinics and hospitals in South Africa. Costing data were obtained from the National Institutes of Communicable Diseases in South Africa. At 50% disease prevalence, diagnostic procedures involving expectorated sputum with any PCR method, or induced sputum with nested or real-time PCR, were all highly cost-effective, successfully treating 77-90% of patients at $26-51 per life-year gained. Procedures using BAL specimens were significantly more expensive without added benefit, successfully treating 68-90% of patients at costs of $189-232 per life-year gained. A relatively cost-effective diagnostic procedure that did not require PCR was Toluidine Blue O staining of induced sputum ($25 per life-year gained, successfully treating 68% of patients). Diagnosis using chest x-rays alone resulted in successful treatment of 77% of patients, though cost-effectiveness was reduced ($109 per life-year gained) compared with several molecular diagnostic options.ConclusionsFor diagnosis of PCP, use of PCR technologies, when combined with less-invasive patient specimens such as expectorated or induced sputum, represent more cost-effective options than any diagnostic procedure using BAL, or chest x-ray alone.
| S-EPMC3156114 | biostudies-literature
Project description:BackgroundNon-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.MethodsIn 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.ResultsA 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.ConclusionsThe 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.
| S-EPMC8628137 | biostudies-literature
Project description:According to the immunodepression status, the diagnosis of Pneumocystis jirovecii pneumonia (PjP) may be difficult. Molecular methods appear very sensitive, but they lack specificity because Pj DNA can be detected in Pneumocystis-colonized patients. The aim of this study was to evaluate the value of a serum ß-d-Glucan (BDG) assay for the diagnosis of PjP in a large cohort of HIV-negative and HIV-positive patients, either as a first-line diagnostic test for PjP or as a tool to distinguish between colonization and PjP in cases of low fungal load. Data of Pj qPCR performed on bronchopulmonary specimens over a 3-year period were retrieved retrospectively. For each result, we searched for a BDG serum assay performed within ±5 days. Among the 69 episodes that occurred in HIV-positive patients and the 609 episodes that occurred in immunocompromised HIV-negative patients, we find an equivalent sensitivity of BDG assays compared with molecular methods to diagnose probable/proven PjP, in a first-line strategy. Furthermore, BDG assay can be used confidently to distinguish between infected and colonized patients using a 80 pg/mL cut-off. Finally, it is necessary to search for causes of false positivity to increase BDG assay performance. BDG assay represents a valuable adjunctive tool to distinguish between colonization and infection.
| S-EPMC9318034 | biostudies-literature
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.
| S-EPMC8386019 | biostudies-literature
Project description:We evaluated the serum levels of (1-3)-beta-D-glucan (BG) and lactate dehydrogenase (LDH) as a tool to support pneumocystis pneumonia (PCP) diagnostic procedures in non-HIV patients. We retrospectively collected non-HIV (human immunodeficiency virus) patients presenting clinical features of PCP between April 1st, 2013, and December 31st, 2018. A total of 225 included patients were tested for Pneumocystis jirovecii by polymerase chain reaction (PCR) and methenamine silver staining. Based on different exclusion criteria, 179 cases were included in the BG group, and 196 cases were included in the LDH group. In each group, cases with positive immunofluorescence (IF) microscopy and PCR were considered proven PCP, while cases with only positive PCR were considered probable PCP. Fifty patients with negative IF and PCR results and proven to be non-PCP infection were chosen randomly as the control group. The cut-off levels of BG and LDH to distinguish non-PCP from probable PCP were 110 pg/mL and 296 U/L with 88% sensitivity and 86% specificity, and 66% sensitivity and 88% specificity, respectively. The cut-off levels of BG and LDH to distinguish non-PCP from proven PCP were 285.8 pg/mL and 379 U/L with 92% sensitivity and 96% specificity, and 85% sensitivity and 77% specificity, respectively. The cut-off levels of BG and LDH to distinguish non-PCP from proven/probable PCP were 144.1 pg/mL and 363 U/L with 90% sensitivity, 86% specificity and 80% sensitivity, 76% specificity respectively. BG and LDH are reliable indicators for detecting P. jirovecii infection in HIV-uninfected immunocompromised patients.
| S-EPMC8085008 | biostudies-literature
Project description:Background and aimDifferent polymerase chain reaction (PCR) techniques have and are still being used for the direct detection of Brucella DNA in serum samples of different animal species and humans without being validated or properly validated, resulting in discrepancies. Thus, this study aimed to evaluate the diagnostic performance of the TaqMan Real-Time-PCR (RT-PCR) targeting the bcsp31 gene versus conventional PCR for the accurate diagnosis of brucellosis at the genus level in cattle sera.Materials and methodsOne hundred and eighty-four serum samples were collected from bacteriologically positive and negative cows with ages ranging from 1 to 5 years old at some infected private farms in the Nile Delta under quarantine measures as well as brucellosis free farms. These samples were classified into four groups after serological diagnosis and investigated by TaqMan RT-PCR and conventional PCR targeting the IS711 gene for Brucella DNA detection. The diagnostic performance characteristics of both PCR techniques were estimated considering the bacteriological results as a gold standard.ResultsTaqMan RT-PCR revealed superiority over conventional PCR; it was able to detect Brucella DNA in 95% (67/70) and 89% (25/28) of the cattle sera samples belonging to Group 1 (serologically and bacteriologically positive) and Group 2 (serologically negative but bacteriologically positive), respectively. On evaluating the diagnostic performance, TaqMan RT-PCR showed superior diagnostic sensitivity (93.9%), diagnostic specificity (88.4%), performance index (182.3), almost perfect kappa agreement (0.825±0.042), strong positive correlation (r=0.826), high accuracy based on the receiver operating characteristic (ROC) curve, and area under the ROC curve (0.911) at p<0.05 and CI of 95%.ConclusionA cattle serum sample is not the metric of choice for targeting Brucella genomic DNA by conventional PCR. The time-saving and rapid TaqMan RT-PCR method revealed a better diagnostic performance in the detection of Brucella DNA in cattle sera. Such performance offered by TaqMan RT-PCR may be considered a step toward the possibility of using such technology in the direct differentiation between Brucella-infected and -vaccinated cattle immunized by smooth vaccines from cattle sera using primers specific for such vaccines.
| S-EPMC7896886 | biostudies-literature
Project description:BackgroundThe incidence of cytomegalovirus (CMV) pneumonia is increasing in patients diagnosed with hematologic malignancies. The utility of CMV-DNA viral load measurement has not been standardized, and viral cut-off values have not been established. This study was designed to investigate the utility of CMV quantitative real-time PCR (qRT-PCR) using bronchial washing fluid.MethodsWe retrospectively reviewed the microbiologic and pathologic results of bronchial washing fluid and biopsy specimens in addition to the patients' clinical characteristics.ResultsA total of 565 CMV qRT-PCR assays were performed using bronchial washing fluid from patients with hematologic malignancies. Among them, 101 were positive for CMV by qRT-PCR; of these, 24 were diagnosed with CMV pneumonia and 70 with CMV infection, and 7 were excluded due to a diagnosis of invasive pulmonary aspergillosis rather than viral pneumonia. The median CMV load determined by qPCR was 1.8 × 105 copies/mL (3.6 103-1.5 × 108) in CMV pneumonia patients and 3.0 × 103 copies/mL (5.0 × 102-1.1 × 105) in those diagnosed with CMV infection (P < 0.01). Using the ROC curve, the optimal inflection points were 18,900 copies/mL (137,970 IU/mL) in post-bone marrow transplantation (BMT) patients, 316,415 copies/mL (2,309,825 IU/mL) in no-BMT patients and 28,774 copies/mL (210,054 IU/mL) in all patients.ConclusionsThe CMV titers in bronchial washing fluid determined by qRT-PCR differed significantly between patients diagnosed with CMV pneumonia and those with CMV infection. The viral cut-off values in bronchial washing fluid were suggested for the diagnosis of CMV pneumonia, which were different depending on the BMT status.
| S-EPMC5503648 | biostudies-literature