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1.
Sci Rep ; 11(1): 9226, 2021 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-33927297

RESUMO

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.


Assuntos
Líquido da Lavagem Broncoalveolar/química , L-Lactato Desidrogenase/sangue , Pneumocystis carinii/isolamento & purificação , Pneumonia por Pneumocystis/diagnóstico , Proteoglicanas/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Pneumonia por Pneumocystis/sangue , Pneumonia por Pneumocystis/imunologia , Pneumonia por Pneumocystis/microbiologia , Estudos Retrospectivos , Adulto Jovem
2.
Ann Hematol ; 100(2): 321-336, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33079221

RESUMO

To ensure the safety of high-dose chemotherapy and autologous stem cell transplantation (HDC/ASCT), evidence-based recommendations on infectious complications after HDC/ASCT are given. This guideline not only focuses on patients with haematological malignancies but also addresses the specifics of HDC/ASCT patients with solid tumours or autoimmune disorders. In addition to HBV and HCV, HEV screening is nowadays mandatory prior to ASCT. For patients with HBs antigen and/or anti-HBc antibody positivity, HBV nucleic acid testing is strongly recommended for 6 months after HDC/ASCT or for the duration of a respective maintenance therapy. Prevention of VZV reactivation by vaccination is strongly recommended. Cotrimoxazole for the prevention of Pneumocystis jirovecii is supported. Invasive fungal diseases are less frequent after HDC/ASCT, therefore, primary systemic antifungal prophylaxis is not recommended. Data do not support a benefit of protective room ventilation e.g. HEPA filtration. Thus, AGIHO only supports this technique with marginal strength. Fluoroquinolone prophylaxis is recommended to prevent bacterial infections, although a survival advantage has not been demonstrated.


Assuntos
Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Hepacivirus/metabolismo , Vírus da Hepatite B/metabolismo , Hepatite B/prevenção & controle , Hepatite C/prevenção & controle , Pneumocystis carinii/metabolismo , Pneumonia por Pneumocystis/prevenção & controle , Alemanha , Hematologia , Hepatite B/sangue , Anticorpos Anti-Hepatite B/sangue , Hepatite C/sangue , Humanos , Oncologia , Pneumonia por Pneumocystis/sangue , Guias de Prática Clínica como Assunto , RNA Viral/sangue , Sociedades Médicas , Transplante Autólogo , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico
3.
PLoS One ; 15(7): e0236095, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32726358

RESUMO

The Fungitell assay (FA) and the Wako ß-glucan test (GT) are employed to measure the serum/plasma 1,3-ß-D-glucan (BDG), a well-known invasive fungal disease biomarker. Data to convincingly and/or sufficiently support the GT as a valuable alternative to the FA are yet limited. In this study, we evaluated the FA and the GT to diagnose invasive aspergillosis (IA), invasive candidiasis (IC), and Pneumocystis jirovecii pneumonia (PJP). The FA and GT performances were compared in sera of patients with IA (n = 40), IC (n = 78), and PJP (n = 17) with respect to sera of control patients (n = 187). Using the manufacturer's cutoff values of 80 pg/mL and 11 pg/mL, the sensitivity and specificity for IA diagnosis were 92.5% and 99.5% for the FA and 60.0% and 99.5% for the GT, respectively; for IC diagnosis were 100.0% and 97.3% for the FA and 91.0% and 99.5% for the GT, respectively; for PJP diagnosis were 100.0% and 97.3% for the FA and 88.2% and 99.5% for the GT, respectively. When an optimized cutoff value of 7.0 pg/mL for the GT was used, the sensitivity and specificity were 80.0% and 97.3% for IA diagnosis, 98.7% and 97.3% for IC diagnosis, and 94.1% and 97.3% for PJP diagnosis, respectively. At the 7.0-pg/mL GT cutoff, the agreement between the assays remained and/or became excellent for IA (95.1%), IC (97.3%), and PJP (96.5%), respectively. In conclusion, we show that the GT performed as well as the FA only with a lowered cutoff value for positivity. Further studies are expected to establish the equivalence of the two BDG assays.


Assuntos
Aspergilose/diagnóstico , Candidíase Invasiva/diagnóstico , Testes Diagnósticos de Rotina/métodos , Pneumonia por Pneumocystis/diagnóstico , beta-Glucanas/análise , Adulto , Idoso , Aspergilose/sangue , Aspergilose/microbiologia , Aspergillus/imunologia , Aspergillus/isolamento & purificação , Candida albicans/imunologia , Candida albicans/isolamento & purificação , Candidíase Invasiva/sangue , Candidíase Invasiva/microbiologia , Testes Diagnósticos de Rotina/classificação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumocystis carinii/imunologia , Pneumocystis carinii/isolamento & purificação , Pneumonia por Pneumocystis/sangue , Pneumonia por Pneumocystis/microbiologia , Curva ROC
4.
Clin Microbiol Infect ; 26(9): 1137-1143, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32479781

RESUMO

BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) can be a life-threatening opportunistic infection in immunocompromised hosts. The diagnosis can be challenging, often requiring semi-invasive respiratory sampling. The serum 1,3-ß-D-glucan (BDG) assay has been proposed as a minimally invasive test for the presumptive diagnosis of PJP. METHOD: We carried out a systematic review and meta-analysis using articles in the English language published between January 1960 and September 2019. We estimated the pooled sensitivity and specificity of BDG testing using a bivariate random effects approach and compared test performance in human immunodeficiency virus (HIV) and non-HIV subgroups with meta-regression. Data from the pooled sensitivity and specificity were transformed to generate pre- and post-test probability curves. RESULTS: Twenty-three studies were included. The pooled sensitivity and specificity of serum BDG testing for PJP were 91% (95%CI 87-94%) and 79% (95%CI 72-84%) respectively. The sensitivity in patients with HIV was better than in patients without (94%, 95%CI 91-96%) versus 86% (95%CI 78-91%) (p 0.02), with comparable specificity (83%, 95%CI 69-92% versus 83%, 95%CI 72-90%) (p 0.10). A negative BDG was only associated with a low post-test probability of PJP (≤5%) when the pre-test probability was low to intermediate (≤20% in non-HIV and ≤50% in HIV). CONCLUSIONS: Among patients with a higher likelihood of PJP, the pooled sensitivity of BDG is insufficient to exclude infection. Similarly, for most cases, the pooled specificity is inadequate to diagnose PJP. Understanding the performance of BDG in the population being investigated is therefore essential to optimal clinical decision-making.


Assuntos
Pneumocystis carinii/metabolismo , Pneumonia por Pneumocystis/diagnóstico , Testes Sorológicos/métodos , beta-Glucanas/sangue , Humanos , Pneumocystis carinii/química , Pneumonia por Pneumocystis/sangue , Sensibilidade e Especificidade
5.
Eur J Clin Microbiol Infect Dis ; 39(11): 2205-2209, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32557324

RESUMO

Interest in the detection of specific anti-Pneumocystis jirovecii antibodies has emerged as less-invasive alternative diagnostic approaches. Here is presented the performance of an ELISA based on a recombinant synthetic multi-epitope kexin 1 (Kex1) antigen of P. jirovecii, previously developed. Results showed that IgM anti-Kex1 levels were found significantly increased in patients with Pneumocystis pneumonia (PcP) compared with non-PcP cases (p < 0.001), allowing a diagnostic performance of PcP with a 70.8% sensitivity and a 75.0% specificity. These results suggest that this Kex1-based ELISA is a promising tool toward the serodiagnosis of PcP when the standard methods are difficult to perform.


Assuntos
Anticorpos Antifúngicos/imunologia , Pneumocystis carinii/imunologia , Pneumonia por Pneumocystis/microbiologia , Área Sob a Curva , Ensaio de Imunoadsorção Enzimática , Humanos , Pneumonia por Pneumocystis/sangue , Pró-Proteína Convertases/química , Pró-Proteína Convertases/imunologia , Estudos Retrospectivos , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/imunologia , Sensibilidade e Especificidade
6.
Radiol Oncol ; 54(2): 221-226, 2020 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-32463392

RESUMO

Background Pneumocystis jirovecii pneumonia (PCP) is a common and potentially fatal opportunistic infection in immunocompromised non-HIV individuals. There are problems with clinical and diagnostic protocols for PCP that lack sensitivity and specificity. We designed a retrospective study to compared several methods that were used in diagnostics of PCP. Patients and methods One hundred and eight immunocompromised individuals with typical clinical picture for PCP and suspicious radiological findings were included in the study. Serum samples were taken to measure the values of (1→3)-ß-D-glucan (Fungitell, Associates of Cape Cod, USA). Lower respiratory tract samples were obtained to perform direct immunofluorescence (DIF, MERIFLUOR® Pneumocystis, Meridian, USA) stain and real-time PCR (qPCR). Results Fifty-four (50%) of the 108 patients in our study had (1→3)-ß-D-glucan > 500 pg/ml. Patients that had (1→3)-ß-D-glucan concentrations < 400 pg/ml in serum, had mean threshold cycles (Ct) 35.43 ± 3.32 versus those that had (1→3)-ß-D-glucan concentrations >400 pg/mL and mean Ct of 28.97 ± 5.27 (P < 0.001). If we detected P. jirovecii with DIF and qPCR than PCP was proven. If the concentration of (1→3)-ß-D-glucan was higher than 400 pg/ml and Ct of qPCR was below 28.97 ± 5.27 than we have been able be certain that P. jirovecii caused pneumonia (odds ratio [OR] 2.31, 95% confidence interval [CI] 1.62-3.27, P < 0.001). Conclusions Measurement of (1→3)-ß-D-glucan or qPCR alone could not be used to diagnose PCP. Diagnostic cut-off value for (1→3)-ß-D-glucan > 400pg/ml and qPCR below 30 Ct, allow us to conclude that patient has PCP. If the values of (1→3)-ß-D-glucan are < 400 pg/ml and qPCR is above 35 Ct than colonization with P. jirovecii is more possible than PCP.


Assuntos
Hospedeiro Imunocomprometido , Pneumocystis carinii , Pneumonia por Pneumocystis/diagnóstico , Proteoglicanas/sangue , Biomarcadores/sangue , Intervalos de Confiança , Técnica Direta de Fluorescência para Anticorpo , Infecções por HIV , Humanos , Pessoa de Meia-Idade , Razão de Chances , Pneumocystis carinii/química , Pneumocystis carinii/genética , Pneumonia por Pneumocystis/sangue , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Valores de Referência , Estudos Retrospectivos
8.
Sci Rep ; 9(1): 12508, 2019 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-31467367

RESUMO

A few cases of hypercalcemia related to Pneumocystis jirovecii pneumonia (PJP) have previously been described, supposedly associated with an 1α-hydroxylase enzyme-dependent mechanism. The prevalence and significance of hypercalcemia in PJP remain unclear, especially in kidney transplant recipients (KTR) who frequently display hypercalcemia via persisting hyperparathyroidism. We here retrospectively identified all microbiologically-proven PJP in adult KTR from 2005 to 2017 in the Lille University Hospital, and studied the mineral and bone metabolism parameters during the peri-infectious period. Clinical features of PJP-patients were analyzed according to their serum calcium level. Hypercalcemia (12.6 ± 1.6 mg/dl) was observed in 37% (18/49) of PJP-patients and regressed concomitantly to specific anti-infectious treatment in all cases. No other cause of hypercalcemia was identified. In hypercalcemic patients, serum levels of 1,25-dihydroxyvitamin D were high at the time of PJP-diagnosis and decreased after anti-infectious treatment (124 ± 62 versus 28 ± 23 pg/mL, p = 0.006) while PTH serum levels followed an inverse curve (35 ± 34 versus 137 ± 99 pg/mL, p = 0.009), suggesting together a granuloma-mediated mechanism. Febrile dyspnea was less frequent in hypercalcemic PJP-patients compared to non-hypercalcemic (29 versus 67%). In summary, hypercalcemia seems common during PJP in KTR. Unexplained hypercalcemia could thus lead to specific investigations in this particular population, even in the absence of infectious or respiratory symptoms.


Assuntos
Hipercalcemia/etiologia , Transplante de Rim/efeitos adversos , Pneumonia por Pneumocystis/etiologia , Idoso , Cálcio/sangue , Feminino , Humanos , Hipercalcemia/sangue , Masculino , Pessoa de Meia-Idade , Pneumocystis carinii/fisiologia , Pneumonia por Pneumocystis/sangue , Pneumonia por Pneumocystis/microbiologia , Estudos Retrospectivos , Vitamina D/análogos & derivados , Vitamina D/sangue
9.
J Clin Microbiol ; 58(1)2019 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-31434728

RESUMO

INTRODUCTIONDespite the widespread use of prophylactic antibiotics in high-risk individuals, Pneumocystis jirovecii remains an important cause of pneumonia in immunocompromised patients. During the peak of the AIDS epidemic, many hospitals and outpatient clinics were very proficient at collecting induced sputum specimens for the diagnosis of Pneumocystis jirovecii pneumonia (PJP). With the dramatic reduction in the occurrence PJP in the current era of highly effective antiretroviral therapy, many centers no longer collect induced sputum samples. Thus, the diagnosis of PJP requires bronchoalveolar lavage (BAL) specimens or a decision to treat the patient empirically without a definitive diagnosis. Sputum or BAL specimens are tested for P. jirovecii using special stains or molecular assays, which require highly trained staff that may not be available with a rapid turnaround time. Given the invasive nature of collecting BAL specimens and the expertise needed for interpreting PJP test results, there is interest in using serum 1,3-ß-d-glucan (BDG) testing for the diagnosis of PJP. In this point-counterpoint, Luis Ostrosky-Zeichner and Gabriela Corsi-Vasquez discuss the pro view of using BDG testing for the diagnosis of PJP, while Paul E. Sax and Edward F. Pilkington III present the con view of using BDG testing for the diagnosis of PJP.


Assuntos
Biomarcadores , Pneumocystis carinii , Pneumonia por Pneumocystis/sangue , Pneumonia por Pneumocystis/diagnóstico , beta-Glucanas/sangue , Feminino , Humanos , Masculino , Pneumonia por Pneumocystis/microbiologia
10.
Int J Infect Dis ; 88: 141-148, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31442630

RESUMO

OBJECTIVES: The aim of this study was to investigate the efficacy of combination therapy of caspofungin and TMP/SMZ (trimethoprim/sulfamethoxazole) in moderate to severe pneumocystis jirovecii pneumonia (PJP) in patients without human immunodeficiency virus infection (HIV) and the relationship between therapeutic effect and plasma (1, 3) Beta-d-Glucan (BDG) levels. METHODS: We retrospectively reviewed HIV-negative patients with PJP diagnosed in our department, who were treated with combination therapy of caspofungin and TMP/SMZ or monotherapy of TMP/SMZ during a six and a half year period. RESULTS: A total of 126 moderate to severe PJP patients were enrolled in the study. In the multivariate analysis, low lymphocyte counts, high serum lactate dehydrogenase levels at the diagnosis of PJP and progression to shock were significant risk factors for death. In all patients, there was no significant difference in risk of death at 3 months. In the group of BDG≥800pg/m, patients receiving combination therapy was associated with a significantly decreased risk of death at 3 months, whereas in the group of BDG<800pg/ml, there were no statistically significant difference in survival rate between the two treatment regimens. CONCLUSION: High initial plasma (1, 3) Beta-d-Glucan concentration may be a predictor of satisfactory caspofungin response to HIV-negative patients with PJP. Based on our findings, we suggest the choice of combination therapy with caspofungin and TMP/SMZ as the initial treatment when BDG≥800pg/ml in moderate to severe HIV-negative patients with PJP.


Assuntos
Antifúngicos/uso terapêutico , Caspofungina/administração & dosagem , Pneumonia por Pneumocystis/tratamento farmacológico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , beta-Glucanas/sangue , Adulto , Monitoramento de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumocystis carinii/efeitos dos fármacos , Pneumocystis carinii/fisiologia , Pneumonia por Pneumocystis/sangue , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/mortalidade , Estudos Retrospectivos , Fatores de Risco
11.
BMC Infect Dis ; 19(1): 658, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31337356

RESUMO

BACKGROUND: Pneumocystis jirovecii pneumonia (PCP) is one of the most common HIV-related opportunistic infections. The diagnosis of PCP is based on analyses from respiratory tract specimens which may require the invasive procedure of a diagnostic bronchoscopy. The objective of this study was to evaluate the diagnostic potential of Pneumocystis jirovecii PCR in serum combined with the 1,3-ß-D-glucan (betaglucan) test for the diagnosis of PCP in HIV-infected patients. METHODS: This was a retrospective case-control study including serum samples from 26 HIV-infected patients with PCP collected within 5 days prior to the start of PCP treatment, 21 HIV-infected control subjects matched by blood CD4+ cell counts, and 18 blood donors. The serum samples were analyzed for Pneumocystis jirovecii PCR and betaglucan. The reference standard for PCP was based on previously described microbiological and clinical criteria. RESULTS: All patients with PCP had detectabe Pneumocystis jirovecii DNA in serum yielding a sensitivity for the Pneumocystis jirovecii PCR assay in serum of 100%. All blood donors had negative Pneumocystis PCR in serum. The specificity when testing HIV-infected patients was 71%, but with a PCR Cycle threshold (Ct) value of 34 as cut-off the specificity was 90%. At a putative pretest probaility of 20%, the negative and positive predictive value for the Pneumocystis PCR assay in serum was 0.99 and 0.71, respectively. Betaglucan with cut-off level 200 pg/ml combined with a positive Pneumocystis jirovecii PCR result had sensitivity and specificity of 92 and 90%, respectively. The concentration of Pneumocystis jirovecii DNA in serum samples, expressed by the PCR Ct values, correlated inversely to the betaglucan levels in serum. CONCLUSION: In this case-control study including 70% of all HIV-infected patients with PCP treated at Sahlgrenska University Hospital during a time period of 13 years, Pneumocystis PCR analysis on serum samples had a very high sensitivity and negative predictive value for the diagnosis of PCP in HIV-infected patients. A serum-based diagnostic procedure either based on Pneumocystis jirovecii PCR alone or in combination with betaglucan analysis may thus be feasible and would facilitate the care of HIV-infected patients with suspected PCP.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Pneumocystis carinii/genética , Pneumonia por Pneumocystis/microbiologia , beta-Glucanas/sangue , Adolescente , Adulto , Idoso , Doadores de Sangue , Estudos de Casos e Controles , DNA Fúngico/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumocystis carinii/patogenicidade , Pneumonia por Pneumocystis/sangue , Reação em Cadeia da Polimerase , Estudos Retrospectivos , Sensibilidade e Especificidade
12.
BMC Infect Dis ; 19(1): 525, 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31200652

RESUMO

BACKGROUND: As technology progresses, several highly sensitive human immunodeficiency virus (HIV) screening kits are being researched and developed to quickly and efficiently identify serum HIV antibodies within the non-window period. In individuals who are HIV-seronegative, HIV infections that are not within a window period are rare. In such cases, all antibody detection methods will fail, and misdiagnosing these patients will have catastrophic consequences. CASE PRESENTATION: A 22-year-old male Chinese patient with diffuse exudative lesions in both lungs and initial symptoms of cough and dyspnoea was diagnosed with Pneumocystis jirovecii pneumonia (PJP) by aetiological examination, and the patient's plasma CD4+ T-cell count was extremely low. In China, PJP is prevalent in HIV-infected individuals. Pneumocystis jirovecii (P. jirovecii) has a high colonisation rate in patients with HIV infections. This patient was naturally suspected of being an HIV patient; however, serum HIV antibody tests were negative using both an enzyme-linked immunosorbent assay (ELISA) and a latex agglutination assay, and HIV was not detected by western blotting. Subsequently, the plasma HIV viral load was found to be extremely high on two repeated plasma HIV RNA tests, thus confirming HIV-seronegative acquired immunodeficiency syndrome (AIDS) in this patient. With administration of effective anti-P. jirovecii treatment and highly active antiretroviral therapy (HAART) after diagnosis, the patient's disease condition was rapidly controlled. CONCLUSION: This is the second reported case in China of an HIV-seronegative AIDS patient. Such cases are also rare worldwide. Although HIV-seronegative HIV infections are rare, AIDS should be considered in immunodeficient patients with opportunistic infections, even if the test results are HIV-seronegative. Plasma HIV RNA testing is important for such patients.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/sangue , Síndrome de Imunodeficiência Adquirida/sangue , Pneumonia por Pneumocystis/complicações , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/patologia , Infecções Oportunistas Relacionadas com a AIDS/virologia , Síndrome de Imunodeficiência Adquirida/complicações , Síndrome de Imunodeficiência Adquirida/patologia , Síndrome de Imunodeficiência Adquirida/virologia , Antibacterianos/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Humanos , Masculino , Pneumocystis carinii/isolamento & purificação , Pneumonia por Pneumocystis/sangue , Pneumonia por Pneumocystis/tratamento farmacológico , Pneumonia por Pneumocystis/patologia , RNA Viral/sangue , Resultado do Tratamento , Adulto Jovem
13.
J Infect Chemother ; 25(12): 936-942, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31186197

RESUMO

BACKGROUND: For patients with non-human immunodeficiency virus (HIV) Pneumocystis pneumonia (PCP), data are limited on serial changes in serum biomarkers and the correlations with clinical outcomes. OBJECTIVE: This study evaluated serial change in serum biomarkers and clinical outcomes of non-HIV PCP. METHODS: We retrospectively reviewed data from 63 patients treated for non-HIV PCP at Toho University Omori Medical Center. The patients were classified as survivors and nonsurvivors on the basis of 60-day PCP mortality. The groups were compared for clinical course and levels of serum biomarkers (ß-D glucan, Krebs von den Lungen-6 antigen [KL-6], and surfactant protein-D [SP-D]), which were measured at baseline, and 7 days and 14 days after starting treatment. In addition, serial changes in serum biomarkers were analyzed in survivors and nonsurvivors. RESULTS: There were 14 PCP nonsurvivors and 49 survivors. Biomarker values were not different between groups at baseline. At 7 and 14 days after starting treatment, the proportions of patients with elevated ß-D glucan and KL-6 did not significantly differ between groups; however, the proportion of patients with elevated SP-D was significantly lower among survivors than among nonsurvivors (57.1% vs. 100%, p = 0.009; 30% vs. 100%, p < 0.001; respectively). SP-D on day 14 was significantly lower than that at baseline among survivors (99.6 [61.0-190.3] vs. 156 [100.8-283.5]; p = 0.045) but significantly higher among nonsurvivors (974 [744.5-1565] vs. 317 [211-448]; p = 0.03). CONCLUSION: Serum SP-D value continues to increase after failure of treatment for non-HIV PCP and may thus be associated with outcomes for non-HIV PCP patients.


Assuntos
Antibacterianos/uso terapêutico , Hospedeiro Imunocomprometido , Pneumocystis carinii/isolamento & purificação , Pneumonia por Pneumocystis/terapia , Sobreviventes/estatística & dados numéricos , Idoso , Biomarcadores/sangue , Terapia Combinada/métodos , Feminino , Glucocorticoides/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Mucina-1/sangue , Mucina-1/imunologia , Oxigenoterapia , Pneumonia por Pneumocystis/sangue , Pneumonia por Pneumocystis/microbiologia , Pneumonia por Pneumocystis/mortalidade , Proteína D Associada a Surfactante Pulmonar/sangue , Proteína D Associada a Surfactante Pulmonar/imunologia , Estudos Retrospectivos , Falha de Tratamento , Combinação Trimetoprima e Sulfametoxazol , beta-Glucanas/sangue , beta-Glucanas/imunologia
14.
PLoS One ; 14(3): e0214324, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30908547

RESUMO

OBJECTIVE: Pneumocystis pneumonia (PCP) is one of the most common opportunistic infections. In systemic autoimmune disease patients receiving immunosuppressive treatments, low lymphocyte count, old age and coexisting lung disease have been known as risk factors for the occurrence of PCP. However, factors relevant to prognosis of PCP have not been fully studied. METHODS: A total of 95 sequential patients who developed PCP during immunosuppressive treatment for systemic autoimmune diseases was identified from five Japanese centres. We retrospectively assessed baseline characteristics, immunosuppressive treatment prior to the onset of PCP, treatment for PCP and survival. Univariate and multivariate analyses were performed to identify prognostic factors. RESULTS: Forty-two deaths (44.2%) were observed in this study. Age at the diagnosis of PCP was higher in non-survivors than in survivors (74 years vs. 64 years, p = 0.008). Non-survivors more frequently had lung involvement than did survivors (47.6% vs. 13.2%, p<0.001). Median lymphocyte count at the diagnosis of PCP was lower in non-survivors than in survivors (499/µl vs. 874/µl, p = 0.002). Multivariate analysis identified lower lymphocyte count, older age and coexisting lung disease at the diagnosis of PCP as independent risk factors for death. Those risk factors for death were similar to the known risk factors for the occurrence of PCP. CONCLUSION: Although PCP can occur even in patients without these risk factors, our data demonstrate that the overall prognosis of PCP in such patients is good. Given that the standard prophylactic treatment against PCP has safety issues, the risk-stratified use of prophylactic treatment may be advisable.


Assuntos
Doenças Autoimunes/tratamento farmacológico , Imunossupressores/uso terapêutico , Pneumopatias/diagnóstico , Infecções Oportunistas/diagnóstico , Pneumonia por Pneumocystis/diagnóstico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Doenças Autoimunes/complicações , Doenças Autoimunes/mortalidade , Feminino , Humanos , Japão , Pneumopatias/sangue , Pneumopatias/mortalidade , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/sangue , Infecções Oportunistas/mortalidade , Pneumonia por Pneumocystis/sangue , Pneumonia por Pneumocystis/mortalidade , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida
16.
J Clin Microbiol ; 57(6)2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30918045

RESUMO

Measuring serum beta-d-glucan (BDG) is a useful tool for supporting a quantitative PCR (qPCR)-based diagnosis of suspected Pneumocystis pneumonia (PCP) with bronchoalveolar lavage (BAL) fluid. Since the 2000s, the Fungitell assay was the only BDG assay which was FDA cleared and Conformité Européenne (CE) marked. However, the Wako ß-glucan test was also recently CE marked and commercialized. We analyzed archived sera from 116 PCP cases (who were considered to have PCP based on compatible clinical and radiological findings plus a BAL fluid qPCR threshold cycle value of ≤28) and 114 controls (those with a BAL fluid qPCR threshold cycle value of >45 and no invasive fungal infection) using the Fungitell and Wako assays in parallel and assessed their diagnostic performance using the manufacturer's proposed cutoffs of 80 pg/ml and 11 pg/ml, respectively. We found the Wako assay to be more specific (0.98 versus 0.87, P < 0.001) and the Fungitell assay to be more sensitive (0.78 versus 0.85, P = 0.039) at the proposed cutoffs. Overall performance, as determined by the area under the receiver operating characteristic curve, was similar for both assays. We determined a new Wako assay cutoff (3.616 pg/ml) to match the sensitivity of the Fungitell assay (0.88 at a cutoff of ≥60 pg/ml). Using this newly proposed cutoff, the specificity of the Wako assay was significantly better than that of the Fungitell assay (0.89 versus 0.82, P = 0.011). In conclusion, the Wako assay performed excellently compared to the Fungitell assay for the diagnosis of presumed PCP based on qPCR. In addition, contrary to the Fungitell assay, the Wako assay allows for single-sample testing with lower inter- and intrarun variability. Finally, we propose an optimized cutoff for the Wako assay to reliably exclude PCP.


Assuntos
Técnicas de Diagnóstico Molecular/métodos , Técnicas de Diagnóstico Molecular/normas , Pneumonia por Pneumocystis/sangue , Pneumonia por Pneumocystis/diagnóstico , beta-Glucanas/sangue , Biomarcadores , Estudos de Casos e Controles , Humanos , Pneumocystis carinii/classificação , Pneumocystis carinii/genética , Pneumonia por Pneumocystis/microbiologia , Curva ROC , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
18.
Med Mycol ; 57(6): 710-717, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30535059

RESUMO

1,3-ß-D-glucan (BG), a cell-wall component of most fungi including Pneumocystis (PC), is recommended by international guidelines for screening for pneumocystis pneumonia (PCP) in hematologic patients. We retrospectively validated the BG test in our tertiary university hospital. Forty-five patients (median age 53 years, 33% female) tested for PC by polymerase chain reaction (PCR) and/or immunoflourescence (IF)-microscopy with a stored blood sample within ±5 days of the PC test were tested by the Fungitell (cutoff <60 and >80 pg/ml). Cases had symptoms and radiology compatible with PCP and positive IF-microscopy (proven PCP, n = 8) or positive PCR (probable PCP, n = 10). Controls had no compatible symptoms/radiology and negative tests for PC on conventional testing (no PCP, n = 24), or positive PCR/IF-microscopy (colonized, n = 3). Median BG-levels were 1108 pg/ml (proven PCP), 612 pg/ml (probable PCP), 29 pg/ml (colonized), and 48 pg/ml (controls, P < 0.001). Compared to the PCP case/control classification, the BG test showed sensitivities of 83-89% and specificities of 64-74%, positive likelihood ratio (LR) of 3.2 and negative LR of 0.23 at recommended cutoff and moderate agreement between tests. Optimal cutoff was ≥73 pg/ml. In PCR-positive cases, the agreement between the BG test and IF-microscopy was 78-89% with fair/moderate agreement. Elevated BG levels were seen in controls with probable invasive fungal infections (n = 4), hemodialysis, bacterial infections and/or betalactams. To conclude, 11% of patients with PCP would be missed if the BG test had been used for diagnosing PCP. Specificity was moderate. Among PCR-positive patients, the BG test identified more cases than IF-microscopy. BG testing is potentially helpful but sensitivity is insufficient to exclude PCP.


Assuntos
Pneumonia por Pneumocystis/diagnóstico , Centros de Atenção Terciária , beta-Glucanas/sangue , Adolescente , Adulto , Idoso , Líquido da Lavagem Broncoalveolar/microbiologia , Criança , Pré-Escolar , Dinamarca , Feminino , Hospitais Universitários , Humanos , Lactente , Recém-Nascido , Infecções Fúngicas Invasivas/diagnóstico , Infecções Fúngicas Invasivas/microbiologia , Masculino , Pessoa de Meia-Idade , Pneumonia por Pneumocystis/sangue , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
20.
J Clin Microbiol ; 56(7)2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29720434

RESUMO

Currently, diagnosis of Pneumocystis jirovecii pneumonia (PJP) relies on analysis of lower respiratory specimens, either by microscopy or quantitative real-time PCR (qPCR). Thus, bronchoscopy is required, which is associated with increased risk of respiratory failure. We assessed the value of noninvasive serologic ß-d-glucan (BDG) testing for laboratory diagnosis of PJP using a newly available turbidimetric assay. We identified 73 cases of PJP with positive qPCR results from lower respiratory specimens for Pneumocystis and serology samples dating from 1 week before to 4 weeks after qPCR. In addition, 25 sera from controls with suspected PJP but specimens negative for Pneumocystis by qPCR were identified. Sera were tested with a turbidimetric BDG assay (Fujifilm Wako Chemicals Europe GmbH, Neuss, Germany), using an 11-pg/ml cutoff. Sensitivity and specificity were calculated based on qPCR test results as a reference. The turbidimetric BDG assay identified 63/73 patients with positive or slightly positive qPCR tests for an overall sensitivity of 86%; after exclusion of cases with only slightly positive qPCR results, sensitivity was 91%. No correlation between serum BDG levels and respiratory specimen DNA levels was found. Serologic BDG testing was negative in 25/25 controls with negative qPCR for a specificity of 100% using the predefined cutoff. In 22/25 samples (88%), no BDG was detected. Serologic BDG testing using the turbidimetric assay showed high sensitivity and specificity compared to qPCR of lower respiratory specimens for the diagnosis of PJP. Both turnover time and test performance will allow clinicians to delay or in some cases forego bronchoscopy.


Assuntos
Polissacarídeos Fúngicos/sangue , Imunoturbidimetria/normas , Pneumocystis , Pneumonia por Pneumocystis/diagnóstico , beta-Glucanas/sangue , Testes Diagnósticos de Rotina , Feminino , Alemanha , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Pneumonia por Pneumocystis/sangue , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Sensibilidade e Especificidade
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