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1.
Rev Invest Clin ; 71(5): 311-320, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31599877

RESUMO

Background: Severe hypoxemic respiratory failure (SHRF) due to Pneumocystis jiroveci pneumonia (PJP) in AIDS patients represents the main cause of admission and mortality in respiratory intensive care units (RICUs) in low- and middle-income countries. Objective: The objective of this study was to develop a predictive scoring system to estimate the risk of mortality in HIV/AIDS patients with PJP and SHRF. Methods: We analyzed data of patients admitted to the RICU between January 2013 and January 2018 with a diagnosis of HIV infection and PJP. Multivariate logistic regression and Kaplan-Meier method were used in data analysis. The RICU and inhospital mortality were 25% and 26%, respectively. Multivariate analysis identified four independent predictors: body mass index, albumin, time to ICU admission, and days of vasopressor support. A predictive scoring system was derived and validated internally. The discrimination was 0.869 (95% confidence interval: 0.821-0.917) and calibration intercept (α) and slope (ß) were 0.03 and 0.99, respectively. The sensitivity was 47.2%, specificity was 84.6%, positive predictive value was 89.2%, and negative predictive value was 82.6%. Conclusions: This scoring system is a potentially useful tool to assist clinicians, in low- and medium-income countries, in estimating the RICU and inhospital mortality risk in patients with HIV/AIDS and SHRF caused by PJP.


Assuntos
Síndrome de Imunodeficiência Adquirida/mortalidade , Infecções por HIV/mortalidade , Pneumonia por Pneumocystis/mortalidade , Insuficiência Respiratória/mortalidade , Síndrome de Imunodeficiência Adquirida/complicações , Adulto , Estudos de Coortes , Feminino , Infecções por HIV/complicações , Mortalidade Hospitalar , Humanos , Hipóxia/etiologia , Hipóxia/mortalidade , Unidades de Terapia Intensiva , Masculino , Pneumonia por Pneumocystis/etiologia , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Insuficiência Respiratória/etiologia , Sensibilidade e Especificidade
2.
Respir Res ; 20(1): 213, 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31554510

RESUMO

BACKGROUND: The prevalence of pneumocystis pneumonia (PCP) and associated hypoxic respiratory failure is increasing in human immunodeficiency virus (HIV)-negative patients. However, no prior studies have evaluated the effect of early anti-PCP treatment on clinical outcomes in HIV-negative patient with severe PCP. Therefore, this study investigated the association between the time to anti-PCP treatment and the clinical outcomes in HIV-negative patients with PCP who presented with hypoxemic respiratory failure. METHODS: A retrospective observational study was performed involving 51 HIV-negative patients with PCP who presented in respiratory failure and were admitted to the intensive care unit between October 2005 and July 2018. A logistic regression model was used to adjust for potential confounding factors in the association between the time to anti-PCP treatment and in-hospital mortality. RESULTS: All patients were treated with appropriate anti-PCP treatment, primarily involving trimethoprim/sulfamethoxazole. The median time to anti-PCP treatment was 58.0 (28.0-97.8) hours. Thirty-one (60.8%) patients were treated empirically prior to confirmation of the microbiological diagnosis. However, the hospital mortality rates were not associated with increasing quartiles of time until anti-PCP treatment (P = 0.818, test for trend). In addition, hospital mortality of patients received early empiric treatment was not better than those of patients received definitive treatment after microbiologic diagnosis (48.4% vs. 40.0%, P = 0.765). In a multiple logistic regression model, the time to anti-PCP treatment was not associated with increased mortality. However, age (adjusted OR 1.07, 95% CI 1.01-1.14) and failure to initial treatment (adjusted OR 13.03, 95% CI 2.34-72.65) were independently associated with increased mortality. CONCLUSIONS: There was no association between the time to anti-PCP treatment and treatment outcomes in HIV-negative patients with PCP who presented in hypoxemic respiratory failure.


Assuntos
Soronegatividade para HIV , Pneumonia por Pneumocystis/terapia , Insuficiência Respiratória/fisiopatologia , Adulto , Fatores Etários , Idoso , Antibacterianos/uso terapêutico , Cuidados Críticos , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia por Pneumocystis/complicações , Pneumonia por Pneumocystis/mortalidade , Insuficiência Respiratória/terapia , Estudos Retrospectivos , Tempo para o Tratamento , Resultado do Tratamento , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico
3.
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
4.
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
5.
Biomed Res Int ; 2019: 6057028, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30906778

RESUMO

We aimed to develop and validate a predictive model to evaluate in-hospital mortality risk in HIV/AIDS patients with PCP in China. 1001 HIV/AIDS patients with PCP admitted in the Beijing Ditan hospital from August 2009 to January 2018 were included in this study. Multivariate Cox proportional hazard model was used to identify independent risk factors of death, and a predictive model was devised based on risk factors. The overall in-hospital mortality was 17.3%. The patients were randomly assigned into derivation cohort (801cases) and validation cohort (200 cases) in 8:2 ratio, respectively, in which in derivation cohort we found that 7 predictors, including LDH >350U/L, HR>130 times/min, room air PaO2 <70mmHg, later admission to ICU, Anemia (HGB≤90g/L), CD4<50cells/ul, and development of a pneumothorax, were associated with poor prognosis in HIV/AIDS patients with PCP and were included in the predictive model. The model had excellent discrimination with AUC of 0.904 and 0.921 in derivation and validation cohort, respectively. The predicted scores were divided into two groups to assess the in-hospital mortality risk: low-risk group (0-11 points with mortality with 2.15-12.77%) and high-risk group (12-21 points with mortality with 38.78%-81.63%). The cumulative mortality rate also indicated significant difference between two groups with Kaplan-Meier curve (p<0.001). A predictive model to evaluate mortality in HIV/AIDS patients with PCP was constructed based on routine laboratory and clinical parameters, which may be a simple tool for physicians to assess the prognosis in HIV/AIDS patients with PCP in China.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/mortalidade , Síndrome de Imunodeficiência Adquirida/mortalidade , HIV-1 , Mortalidade Hospitalar , Pneumonia por Pneumocystis/mortalidade , Infecções Oportunistas Relacionadas com a AIDS/terapia , Síndrome de Imunodeficiência Adquirida/terapia , Adulto , China/epidemiologia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia por Pneumocystis/terapia , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
6.
BMC Pulm Med ; 19(1): 47, 2019 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-30791907

RESUMO

BACKGROUND: In patients with non-HIV Pneumocystis jirovecii pneumonia (PjP), computed tomography imaging reveals ground grass opacities (GGO). Previous reports show that some patients with non-HIV PjP exhibit GGO with crazy paving. However, there have been no studies on the association between crazy paving GGO and non-HIV PjP clinical outcomes. Here, at the diagnosis of non-HIV PjP, we reviewed high-resolution computed tomography (HRCT) findings that included GGO types and evaluated the prognostic impact of crazy paving GGO on the clinical outcomes of non-HIV PjP immunocompromised patients. METHODS: We retrospectively reviewed the clinical information including the HRCT findings of patients diagnosed with non-HIV PjP from five institutions between 2006 and 2015. The GGO types included those with or without crazy paving. The associations between clinical factors such as HRCT findings and in-hospital mortality were assessed using the Cox regression model. RESULTS: Sixty-one patients were included in our study. Nineteen patients died at a hospital. All patients exhibited GGO on HRCT imaging at diagnosis of non-HIV PjP. The HRCT findings included crazy paving GGO (29 patients, 47.5%), consolidations (23 patients, 37.7%), bronchiectasis (14 patients, 23.0%), and centrilobular small nodules (30 patients, 49.2%). Cysts were not observed in any patient. Multivariate analysis revealed that crazy paving GGO and low serum albumin levels were independent risk factors for mortality. CONCLUSIONS: At the diagnosis of non-HIV PjP, patients with crazy paving GGO on HRCT imaging and low serum albumin levels may have a poor prognosis.


Assuntos
Mortalidade Hospitalar , Pulmão/diagnóstico por imagem , Pneumonia por Pneumocystis/diagnóstico por imagem , Corticosteroides/efeitos adversos , Idoso , Antineoplásicos/efeitos adversos , Doenças Autoimunes/imunologia , Estudos de Coortes , Doenças do Tecido Conjuntivo/imunologia , Feminino , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias/imunologia , Pneumonia por Pneumocystis/imunologia , Pneumonia por Pneumocystis/metabolismo , Pneumonia por Pneumocystis/mortalidade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Albumina Sérica/metabolismo , Tomografia Computadorizada por Raios X
7.
J Infect Chemother ; 25(4): 253-261, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30642768

RESUMO

OBJECTIVES: To evaluate the effectiveness and safety of lower-dose sulfamethoxazole/trimethoprim therapy (SMX/TMP) for Pneumocystis jirovecii pneumonia (PCP) in patients with systemic rheumatic diseases. METHODS: In this multicenter retrospective study, we compared effectiveness and safety of SMX/TMP for the treatment of PCP among patients divided into three groups according to the initial dosage of SMX/TMP: the low, ≤10 mg/kg/day; the intermediate, 10-15 mg/kg/day; and the high and conventional, 15-20 mg/kg/day for TMP dose. RESULTS: Eighty-one patients, including 22, 30, and 29 patients in the low-, the intermediate- and the high-dose group could be analyzed and the 30-day survival rate were 100%, 93.3%, and 96.7%, respectively (P = 0.28). There were significant dose-dependent increasing trends of severe adverse drug reactions (ADRs) for SMX/TMP that were graded as ≥3 according to the Common Terminology Criteria for Adverse Events. When stratified by presence of severe hypoxemia defined by alveolar-arterial O2 gradient ≥45 mmHg, the 30-day survival and treatment modification rate were similar among the three groups, but frequency of severe ADRs were significantly decreased in the low-dose group. The low-dose group was independently and negatively associated with treatment modification within 14 days and severe ADRs. CONCLUSIONS: Lower dose SMX/TMP therapy with ≤10 mg/kg/day for TMP was as effective as higher dose therapy for the treatment of PCP and associated with lower rates of treatment modification and severe ADRs in patients with systemic rheumatic diseases.


Assuntos
Antibacterianos/administração & dosagem , Infecções Oportunistas/tratamento farmacológico , Pneumonia por Pneumocystis/tratamento farmacológico , Doenças Reumáticas/complicações , Combinação Trimetoprima e Sulfametoxazol/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Humanos , Imunossupressão/efeitos adversos , Imunossupressão/métodos , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/complicações , Infecções Oportunistas/imunologia , Infecções Oportunistas/mortalidade , Pneumocystis carinii/isolamento & purificação , Pneumonia por Pneumocystis/complicações , Pneumonia por Pneumocystis/imunologia , Pneumonia por Pneumocystis/mortalidade , Estudos Retrospectivos , Doenças Reumáticas/tratamento farmacológico , Doenças Reumáticas/imunologia , Doenças Reumáticas/mortalidade , Taxa de Sobrevida , Resultado do Tratamento , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos
8.
J Neurooncol ; 142(1): 139-148, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30536197

RESUMO

PURPOSE: Acute respiratory failure (ARF) is common and potentially fatal in patients with primary malignant brain tumors (PMBT). However, few data are available regarding its precipitating factors and prognosis. We sought to: (1) compare the causes of ARF and the outcome between patients with PMBT and patients with other peripheral solid tumors (PST), (2) identify the factors influencing ICU survival in PMBT patients. METHODS: Two-center retrospective case-control study from March 1996 to May 2014. Primary central nervous system lymphomas were also included. RESULTS: Eighty-four patients with PMBT and 133 patients with PST were included. Acute infectious pneumonia was more frequent in PMBT than PST patients (77 vs. 36%, p < 0.001). Pulmonary embolism was also more frequent in PMBT patients (13% vs. 5%, p = 0.042), while cardiogenic pulmonary edema and acute-on-chronic respiratory failure were more frequent in PST patients (37 vs. 10%, p < 0.001). Among acute infectious pneumonia, Pneumocystis pneumonia and aspiration pneumonia were more frequent in PMBT patients (19 vs. 2%, p < 0.001 and 19 vs. 8%, p < 0.001, respectively). ICU mortality was similar between PMBT and PST patients (24% vs. 24%, p = 0.966). In multivariate analysis, cancer progression (OR 7.25 95% CI 1.13-46.45, p = 0.034), need for intubation (OR 7.01 95% CI 1.29-38.54, p = 0.022), were independently associated with ICU mortality in PMBT patients. CONCLUSIONS: The cause of ARF in patients with PMBT differs significantly than those with PST and up to 50% may have been prevented. Mortality did not differ between the two groups. These results suggest that PMBT alone is not a relevant criterion for ICU recusal.


Assuntos
Neoplasias Encefálicas/complicações , Pneumonia Aspirativa/complicações , Pneumonia por Pneumocystis/complicações , Insuficiência Respiratória/etiologia , Idoso , Neoplasias Encefálicas/mortalidade , Estudos de Casos e Controles , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Pneumonia Aspirativa/mortalidade , Pneumonia por Pneumocystis/mortalidade , Prognóstico , Insuficiência Respiratória/mortalidade , Estudos Retrospectivos , Taxa de Sobrevida
9.
Int J Infect Dis ; 79: 109-115, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30529109

RESUMO

OBJECTIVES: A mortality rate of non-human immunodeficiency virus-infected pneumocystis pneumonia (non-HIV PCP) is 30-60%. But the effectiveness of adjunctive corticosteroids with trimethoprim-sulfamethoxazole has been unclear, and we examined whether it lowered risk of mortality in non-HIV PCP. METHODS: We did an observational study of adult non-HIV PCP patients from April 2010 through March 2016, using Japanese nationwide healthcare records of the Diagnostic Procedure Combination database (DPC). The risk was estimated by the time-dependent Cox regression analyses with inverse probability weights. RESULT: 1299 eligible non-HIV PCP patients were identified. 737 patients were severe respiratory status (partial pressure of oxygen in arterial blood [PaO2] ≤60mm Hg) and 562 were moderate (PaO2 >60mm Hg) at hospital admission. Among patients with severe respiratory status, the adjunctive corticosteroids was associated with lower risk of 60-day mortality (HR 0.71; 95% confidence interval [CI], 0.55-0.91), and significantly decreased mortality rates (24.7% vs 36.6%, P=0.006). In contrast, no significant differences were observed in the risk of 60-day mortality (HR 1.17; 95% CI, 0.73-1.86) and the mortality rate (10.9% vs 9.1%, P=0.516) among patients with moderate respiratory status. CONCLUSION: The adjunctive corticosteroids were associated with lower risk of 60-day mortality in severe non-HIV PCP patients.


Assuntos
Corticosteroides/uso terapêutico , Pneumonia por Pneumocystis/tratamento farmacológico , Pneumonia por Pneumocystis/mortalidade , Adulto , Idoso , Feminino , Infecções por HIV , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico
10.
Crit Care ; 22(1): 307, 2018 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-30454031

RESUMO

BACKGROUND: Despite modern intensive care with standardized strategies against acute respiratory distress syndrome (ARDS), Pneumocystis pneumonia (PcP) remains a life-threatening disease with a high mortality rate. Here, we analyzed a large mixed cohort of immunocompromised patients with PcP, with regard to clinical course and treatment, and aimed at identifying predictors of outcome. METHODS: This was a single-center retrospective analysis in a tertiary care institution across 17 years. Diagnosis of PcP required typical clinical features and microbiological confirmation of Pneumocystis jirovecii. Epidemiological, clinical, laboratory and outcome data were collected from patient records. RESULTS: A total of 52,364 specimens from 7504 patients were sent for microbiological assessment (3653 with clinical suspicion of Pneumocystis pneumonia). PcP was confirmed in 240 patients, about half of them HIV positive (52%). The remaining subjects were either solid organ transplant recipients (16.3%) or suffered from malignancy (15.8%) or autoimmune diseases (11.7%). Of note, 95% of patients with PcP were not receiving chemoprophylaxis. Overall in-hospital mortality was 25.4%, increasing to 58% if ICU admission was required. Multivariable regression identified lactate dehydrogenase (LDH) as predictor of in-hospital mortality (adjusted OR 1.17 (95% CI 1.09-1.27), p < 0.0001). Mortality in LDH quartiles increased from 8% to 49%, and a cutoff value of 495 U/L predicted mortality with sensitivity and specificity of 70%. With regard to treatment, 40% of patients received trimethoprim-sulfamethoxazole at doses that were lower than recommended, and these patients had a higher mortality risk (HR 1.80 (95% CI 1.10-3.44), p = 0.02). CONCLUSIONS: PcP remains a life-threatening disease among immunocompromised patients. About half of patients with PcP do not have HIV infection. Initial LDH values might serve as a stratifying tool to identify those patients at high risk of death among patients with HIV and without HIV infection.


Assuntos
Hospedeiro Imunocomprometido , Pneumonia por Pneumocystis/complicações , Adulto , Área Sob a Curva , Estudos de Coortes , Feminino , Infecções por HIV/complicações , Infecções por HIV/fisiopatologia , Mortalidade Hospitalar , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Razão de Chances , Pneumocystis carinii/patogenicidade , Pneumonia por Pneumocystis/mortalidade , Modelos de Riscos Proporcionais , Curva ROC , Análise de Regressão , Estudos Retrospectivos , Resultado do Tratamento
11.
PLoS One ; 13(10): e0206231, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30359436

RESUMO

BACKGROUND: Pneumocystis jirovecii pneumonia (PCP) is often fatal in human immunodeficiency (HIV)-negative patients and typically presents with respiratory insufficiency. Predicting treatment failure is challenging. This study aimed to identify prognostic factors and examine PCP polymerase chain reaction (PCR)-negative conversion in non-HIV PCP patients with respiratory failure. METHOD: We retrospectively enrolled 81 non-HIV patients diagnosed with and treated for PCP with respiratory failure in the intensive care unit at a tertiary hospital over a 3-year period. PCP was diagnosed via nested PCR-mediated detection of Pneumocystis jirovecii in induced sputum samples, endotracheal aspirates, and bronchoalveolar lavage fluids. PCP PCR was performed weekly to check for negative conversion. RESULTS: The overall survival rate was 35.8%. Seventy-four patients (91.3%) required mechanical ventilation, and 6 (7.4%) required high-flow nasal oxygen treatment. The PCP PCR-negative conversion rate was 70.5% (survivors, 97%; non-survivors, 63.5%); the median time to conversion was 10 (7.0-14.0) days. On univariate analysis, the APACHE II score (p < 0.001), renal failure requiring renal replacement therapy (p = 0.04), PCP PCR-negative conversion (p = 0.003), and the PaO2/FiO2 ratio (first 24 hours) (p < 0.001) significantly correlated with mortality. On multivariate analysis, PCP PCR-negative conversion (hazard ratio, 0.433; 95% confidence interval, 0.203-0.928; p = 0.031) and the PaO2/FiO2 ratio (first 24 hours) (hazard ratio, 0.988; 95% confidence interval, 0.983-0.993; p < 0.001) independently predicted prognosis. CONCLUSIONS: Determination of PCP PCR-negative conversion and PaO2/FiO2 ratios may help physicians predict treatment failure and mortality in non-HIV PCP patients with respiratory failure.


Assuntos
Pneumocystis carinii/genética , Pneumonia por Pneumocystis/complicações , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/microbiologia , Síndrome do Desconforto Respiratório do Adulto/complicações , Síndrome do Desconforto Respiratório do Adulto/diagnóstico , Idoso , Feminino , Conversão Gênica , HIV , Soronegatividade para HIV/fisiologia , Humanos , Hospedeiro Imunocomprometido , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Pneumocystis carinii/isolamento & purificação , Pneumonia por Pneumocystis/mortalidade , Reação em Cadeia da Polimerase , Prognóstico , Síndrome do Desconforto Respiratório do Adulto/microbiologia , Síndrome do Desconforto Respiratório do Adulto/mortalidade , Estudos Retrospectivos , Análise de Sobrevida
12.
Clin Respir J ; 12(11): 2590-2597, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30244544

RESUMO

INTRODUCTION: Impact of Cytomegalovirus (CMV) co-infection pneumonia in non-HIV patients with Pneumocystis jirovecii pneumonia (PCP) is unclear. OBJECTIVES: The aim of our study was to determine whether CMV co-infection is associated with an increased risk of mortality. METHODS: Our study was conducted at Ege University Hospital, Turkey. We used molecular assays to diagnose Pneumocystis jirovecii in respiratory samples, and CMV in both respiratory and blood samples. We compared morbidity and mortality stratified by CMV co-infection status. RESULTS: Between 2009 and 2015, 43 patients (mean age: 56.7 ± 15.3 years) were diagnosed with PCP. Only 3 of 43 patients had received PCP prophylaxis. We microbiologically confirmed CMV co-infection in 28 of 43 (65.1%) patients. Acute respiratory distress syndrome (ARDS) and requirement of mechanical ventilation were more common in the CMV co-infection group (P = .019 and P = .031 respectively), and duration of intensive care unit was also longer (P = .006). In univariate analyses, mortality at 30 days was higher in the CMV co-infection group as compared to the group with PCP alone (78.6% and 46.7% respectively; P = .046). In multivariate analyses, mortality was independently associated only with the presence of ARDS [OR: 6.22 95% CI 1.3-29.32] and the association with CMV co-infection was no longer significant [OR: 2.6 95% CI 0.49-13.72, P = .257]. CONCLUSION: The risk of mortality appears to be increased in the setting of CMV and PCP co-infection in HIV-uninfected immunocompromised patients. PCP prophylaxis use was lower than expected, suggesting low physician awareness of the risks of PCP in this population.


Assuntos
Coinfecção/complicações , Infecções por Citomegalovirus/epidemiologia , Hospedeiro Imunocomprometido/imunologia , Pneumonia por Pneumocystis/epidemiologia , Adulto , Idoso , Conscientização , Coinfecção/mortalidade , Coinfecção/prevenção & controle , Citomegalovirus/genética , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/mortalidade , Infecções por Citomegalovirus/virologia , Feminino , HIV/classificação , Humanos , Masculino , Pessoa de Meia-Idade , Pneumocystis carinii/genética , Pneumocystis carinii/isolamento & purificação , Pneumonia por Pneumocystis/microbiologia , Pneumonia por Pneumocystis/mortalidade , Respiração Artificial/métodos , Síndrome do Desconforto Respiratório do Adulto , Estudos Retrospectivos , Turquia/epidemiologia , Carga Viral
13.
Ann Hematol ; 97(12): 2373-2380, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30030570

RESUMO

Patients with non-Hodgkin's lymphoma (NHL) receiving rituximab-containing chemotherapy are at risk of developing respiratory complications, but comprehensive information on these complications and their impact on survival is lacking. We performed a retrospective cohort analysis on 123 NHL patients who received rituximab-containing chemotherapy between 2009 and 2016 in order to describe the incidence, etiologies and effect on survival of respiratory complications defined by new or worsening respiratory symptoms requiring diagnostic work-up or hospitalization. Thirty patients (24%) developed respiratory complications during a follow-up time of 825 (555-1338) days after chemotherapy. They had a higher prevalence of congestive heart failure and lung or pleural involvement at diagnosis as compared to patients who did not develop complications. Overall, 58 episodes of pulmonary complications were observed after median (interquartile) times from the first and last rituximab doses of 205 (75-580) days and 27 (14-163) days respectively. Infectious etiologies accounted for 75% of the respiratory complications, followed by heart failure exacerbation, lymphomatous involvement, and ARDS. Two Pneumocystis jirovecii pneumonias were observed, and no complication was ascribed to rituximab toxicity. Respiratory complications required ICU admission in 19 cases (33%) and invasive mechanical ventilation in 14 cases (24%). Using a time-dependent Cox regression analysis, we observed that the occurrence of respiratory complications was associated with a 170% increase in death hazard (hazard ratio 2.65, 95% CI 1.60-4.40, p = 0.001). In conclusion, respiratory complications in NHL patients receiving chemotherapy are relatively frequent, severe, and mostly infectious and are associated with increased mortality.


Assuntos
Linfoma não Hodgkin/tratamento farmacológico , Pneumocystis carinii , Pneumonia por Pneumocystis/induzido quimicamente , Rituximab/efeitos adversos , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pneumonia por Pneumocystis/mortalidade , Pneumonia por Pneumocystis/patologia , Pneumonia por Pneumocystis/fisiopatologia , Estudos Retrospectivos , Rituximab/administração & dosagem , Taxa de Sobrevida
14.
Pharmacol Res ; 134: 61-67, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29890253

RESUMO

Pneumocystis jirovecii pneumonia (PJP) is an opportunistic infection diagnosed in immunocompromized patients. After solid organ transplantation, early infection has decreased as a result of effective prophylaxis, but late infections and even outbreaks caused by interpatient transmission of pneumocystis by air are present in the SOT community. Different risk factors for PJP have been described and several indications for PJP prophylaxis have to be considered by clinicians in patients even years after transplantation. Diagnosis of PJP is confirmed by microscopy and immunofluorescence staining of bronchial fluid but PCR as well as serum ß-D-Glucan analysis have become increasingly valuable diagnostic tools. Treatment of choice is Trimethoprim/sulfamethoxazole and early treatment improves prognosis. However, mortality of PJP in solid organ transplant patients is still high and many aspects including the optimal management of immunosuppression during PJP treatment require further investigations.


Assuntos
Antifúngicos/administração & dosagem , Infecções Oportunistas/tratamento farmacológico , Transplante de Órgãos/efeitos adversos , Pneumocystis carinii/efeitos dos fármacos , Pneumonia por Pneumocystis/tratamento farmacológico , Antifúngicos/efeitos adversos , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Infecções Oportunistas/imunologia , Infecções Oportunistas/microbiologia , Infecções Oportunistas/mortalidade , Transplante de Órgãos/mortalidade , Pneumocystis carinii/imunologia , Pneumocystis carinii/patogenicidade , Pneumonia por Pneumocystis/imunologia , Pneumonia por Pneumocystis/microbiologia , Pneumonia por Pneumocystis/mortalidade , Guias de Prática Clínica como Assunto , Fatores de Risco , Resultado do Tratamento
15.
Clin Rheumatol ; 37(7): 1991-1996, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29808456

RESUMO

Immunosuppression in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is complicated by increasing risk of infections including opportunistic infections like Pneumocystis jirovecii pneumonia (PJP). Available evidence on risk factors and indications for prophylaxis in AAV is derived from PJP occurring early in the course of AAV. In this retrospective study, we characterized the profile of PJP in patients with AAV. PJP cases were identified retrospectively based on positive polymerase chain reaction test from electronic record followed by confirmation from medical records over a 10-year period. AAV patients without PJP over the same period were used as control group. Sixteen PJP+AAV+ were identified; in 14 of them, we were able to confirm they received PJP prophylaxis during induction therapy, while in two cases, data were missing. The onset of the infection was after 6 months from AAV diagnosis in 80% of cases. Escalations in immunosuppression prior to PJP were observed in six cases within 3 months prior to PJP onset. Overall mortality was 12.5%. By univariate analysis, renal involvement at AAV diagnosis was associated with PJP. These results indicate that PJP is not limited to the first 6 months following AAV diagnosis. Late-onset infection can occur in context of augmented immunotherapy, particularly with concurrent lymphopenia. Other risk factors that can independently predict late-onset PJP remain to be identified.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Infecções Oportunistas/etiologia , Pneumocystis carinii , Pneumonia por Pneumocystis/etiologia , Proteínas Adaptadoras de Transdução de Sinal , Idade de Início , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Feminino , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/mortalidade , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/mortalidade , Estudos Retrospectivos
16.
Transpl Infect Dis ; 20(3): e12876, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29512868

RESUMO

BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) affected 5%-15% of solid organ transplant (SOT) recipients prior to universal prophylaxis, classically with trimethoprim-sulfamethoxazole (TMP-SMX). Guidelines generally recommend 6-12 months of prophylaxis post-SOT, yet optimal duration and robust PJP risk stratification have not been established. METHODS: A retrospective, single-center, case-control study of PJP among SOT recipients from January 1998 to December 2013 was conducted. Cases had positive PJ direct fluorescent antibody assay of respiratory specimens. Controls were matched 4:1 by nearest date of SOT. Univariate testing and multivariate logistic regressions were performed. RESULTS: Fifteen cases were identified among 5505 SOT recipients (0.27% rate) and analyzed vs 60 controls. PJP occurred on average 6.1 years (range 0.9-13.8) post-SOT; no case was receiving PJP prophylaxis at diagnosis. Most were treated with reduced immunosuppression and TMP-SMX plus steroids (80%). Six patients (40%) required critical care; 3 (20%) died. There were no significant demographic differences, though cases tended to be older at SOT (54 vs 48 years, P = .1). In univariate analysis, prior viral infection was more common among cases (67% vs 37%, P = .08). Lower absolute lymphocyte count (ALC) at diagnosis date was strongly associated with PJP (400 vs 1230 × 106  cells/µL, P < .001); odds of infection were high with ALC ≤ 500 × 106 cells (OR 18.7, P < .01). CONCLUSION: Pneumocystis jirovecii pneumonia is a rare, late complication of SOT with significant morbidity and mortality. Severe lymphopenia may be useful in identifying SOT recipients who warrant continued or reinstated PJP prophylaxis.


Assuntos
Linfopenia/etiologia , Transplante de Órgãos/efeitos adversos , Pneumonia por Pneumocystis/imunologia , Adolescente , Adulto , Idoso , Antibacterianos/administração & dosagem , Estudos de Casos e Controles , Feminino , Humanos , Hospedeiro Imunocomprometido , Imunossupressão/efeitos adversos , Transplante de Rim/efeitos adversos , Modelos Logísticos , Linfopenia/microbiologia , Masculino , Pessoa de Meia-Idade , Pneumocystis carinii/efeitos dos fármacos , Pneumocystis carinii/imunologia , Pneumocystis carinii/isolamento & purificação , Pneumonia por Pneumocystis/etiologia , Pneumonia por Pneumocystis/microbiologia , Pneumonia por Pneumocystis/mortalidade , Profilaxia Pré-Exposição , Estudos Retrospectivos , Combinação Trimetoprima e Sulfametoxazol/administração & dosagem , Adulto Jovem
17.
J Int AIDS Soc ; 21(1)2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29334197

RESUMO

INTRODUCTION: HIV-1 infection leads to chronic inflammation and to an increased risk of non-AIDS mortality. Our objective was to determine whether AIDS-defining events (ADEs) were associated with increased overall and cause-specific non-AIDS related mortality after antiretroviral therapy (ART) initiation. METHODS: We included HIV treatment-naïve adults from the Antiretroviral Therapy Cohort Collaboration (ART-CC) who initiated ART from 1996 to 2014. Causes of death were assigned using the Coding Causes of Death in HIV (CoDe) protocol. The adjusted hazard ratio (aHR) for overall and cause-specific non-AIDS mortality among those with an ADE (all ADEs, tuberculosis (TB), Pneumocystis jiroveci pneumonia (PJP), and non-Hodgkin's lymphoma (NHL)) compared to those without an ADE was estimated using a marginal structural model. RESULTS: The adjusted hazard of overall non-AIDS mortality was higher among those with any ADE compared to those without any ADE (aHR 2.21, 95% confidence interval (CI) 2.00 to 2.43). The adjusted hazard of each of the cause-specific non-AIDS related deaths were higher among those with any ADE compared to those without, except metabolic deaths (malignancy aHR 2.59 (95% CI 2.13 to 3.14), accident/suicide/overdose aHR 1.37 (95% CI 1.05 to 1.79), cardiovascular aHR 1.95 (95% CI 1.54 to 2.48), infection aHR (95% CI 1.68 to 2.81), hepatic aHR 2.09 (95% CI 1.61 to 2.72), respiratory aHR 4.28 (95% CI 2.67 to 6.88), renal aHR 5.81 (95% CI 2.69 to 12.56) and central nervous aHR 1.53 (95% CI 1.18 to 5.44)). The risk of overall and cause-specific non-AIDS mortality differed depending on the specific ADE of interest (TB, PJP, NHL). CONCLUSIONS: In this large multi-centre cohort collaboration with standardized assignment of causes of death, non-AIDS mortality was twice as high among patients with an ADE compared to without an ADE. However, non-AIDS related mortality after an ADE depended on the ADE of interest. Although there may be unmeasured confounders, these findings suggest that a common pathway may be independently driving both ADEs and NADE mortality. While prevention of ADEs may reduce subsequent death due to NADEs following ART initiation, modification of risk factors for NADE mortality remains important after ADE survival.


Assuntos
Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Fármacos Anti-HIV/uso terapêutico , Síndrome de Imunodeficiência Adquirida/complicações , Adulto , Estudos de Coortes , Feminino , Humanos , Linfoma não Hodgkin/mortalidade , Masculino , Pessoa de Meia-Idade , Pneumonia por Pneumocystis/mortalidade , Tuberculose/mortalidade
18.
J Microbiol Immunol Infect ; 51(6): 810-820, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28779879

RESUMO

BACKGROUND/PURPOSE: The efficacy of low-dose trimethoprim-sulfamethoxazole (TMP-SMX) may be acceptable for the treatment of pneumocystis pneumonia (PCP) in non-human immunodeficiency virus (HIV)-infected patients, with a low incidence of adverse reactions. This study is aimed to evaluate the efficacy and safety of such a regimen for the treatment of non-HIV PCP. METHODS: We retrospectively enrolled 24 consecutive patients diagnosed with non-HIV PCP who were treated with low-dose TMP-SMX (TMP, 4-10 mg/kg/day; SMX, 20-50 mg/kg/day). Data of the conventional-dose treatment were used as reference. The primary endpoints were the 30- and 180-day survival rates from the day of treatment, and secondary endpoints were the incidence of each adverse reaction and dropout rate from the initial TMP-SMX regimen. The survival rate was estimated using the Kaplan-Meier method with 95% confidence interval (CI). RESULTS: The median age of patients was 72 years (54.2% men), and connective tissue disease was the most frequent underlying disease (66.7%) in the low-dose group. The 30- and 180-day survival rates were 95.8% (95% CI: 88.2-100.0%) and 91.0% (95% CI: 79.9%-100.0%), respectively, in the low-dose group and 69.0% (95% CI: 54.0%-88.0%) and 51.5% (95% CI: 36.1%-73.4%), respectively, in the conventional-dose group. The total adverse reaction rate was 58.3% in the low-dose group and 72.4% in the conventional-dose group. A total of 75.0% of patients in the low-dose group and 31.0% in the conventional-dose group completed treatment with the initial regimen. CONCLUSION: Low-dose TMP-SMX may be a treatment option for patients with non-HIV PCP.


Assuntos
Antibacterianos/administração & dosagem , Hospedeiro Imunocomprometido , Pneumonia por Pneumocystis/tratamento farmacológico , Combinação Trimetoprima e Sulfametoxazol/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Cálculos da Dosagem de Medicamento , Feminino , Humanos , Japão , Masculino , Pneumonia por Pneumocystis/mortalidade , Estudos Retrospectivos , Segurança , Taxa de Sobrevida , Resultado do Tratamento , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos
19.
J Infect Dev Ctries ; 12(10): 824-834, 2018 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-32004150

RESUMO

INTRODUCTION: Pneumocystis jirovecii (PJ) pneumonia (PJP) is an important opportunistic infection affecting various types of immunocompromised patients and is associated with an increased risk of mortality. PJ is a unique fungal pathogen which is increasingly common and maybe associated with a higher mortality rate in patients without AIDS. We present the characteristics of PJP, diagnosis, and treatment outcomes between AIDS and non-AIDS patients. METHODOLOGY: We conducted a review of studies of AIDS and non-AIDS patients with PJP using PubMed to search for studies until December 2017. RESULTS: The annual incidence of AIDS-PJP decreased from 13.4 to 3.3 per 1000 person-years in industrialized countries, while the incidence of non-AIDS-PJP varied widely. Both groups had similar clinical manifestations and radiological features, but the non-AIDS-PJP group potentially had a more fulminant course, more diffuse ground glass opacities, and fewer cystic lesions. The mortality rate decreased in the AIDS-PJP group after the advent of antiretroviral therapy; however, the mortality rate remained high in both groups. A laboratory diagnosis was usually nonspecific; CD4+ T-cell < 200 cells/mL or < 14% favored AIDS-PJP. Serum 1,3-ß-D-glucan (BDG) had a high diagnostic odds ratio. Combining BDG and lactic dehydrogenase improved the diagnosis of AIDS-PJP. Histopathological staining and polymerase chain reactions could not discriminate infection from colonization when the result was positive. The use of antibiotics, prophylaxis, and adjunctive corticosteroids was controversial. CONCLUSIONS: Early diagnosis and treatment can be achieved through vigilance, thereby improving the survival rate for PJP in immunocompromised patients.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS , Hospedeiro Imunocomprometido , Pneumocystis carinii , Pneumonia por Pneumocystis , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Infecções Oportunistas Relacionadas com a AIDS/mortalidade , Infecções Oportunistas Relacionadas com a AIDS/terapia , Estudos de Casos e Controles , Diagnóstico Precoce , Humanos , Pneumocystis carinii/isolamento & purificação , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/imunologia , Pneumonia por Pneumocystis/mortalidade , Pneumonia por Pneumocystis/terapia , Taxa de Sobrevida
20.
Artigo em Inglês | MEDLINE | ID: mdl-28893787

RESUMO

The dose of trimethoprim-sulfamethoxazole (TMP-SMX) for the treatment of Pneumocystis pneumonia (PCP) in patients without human immunodeficiency virus (HIV) infection has not been verified. The aim of this study was to investigate the efficacy and toxicity of a low-dose TMP-SMX regimen in such patients. A retrospective study was conducted in four hospitals. We reviewed the medical records of patients with PCP but not HIV (non-HIV-PCP) who were treated with TMP-SMX between 2003 and 2016. The patients were divided into conventional-dose (TMP, 15 to 20 mg/kg/day) and low-dose (TMP, <15 mg/kg/day) groups after patients who received high-dose (TMP, >20 mg/kg/day) treatment were excluded. Grouping was done according to a correction dose, which was based on renal function. Eighty-two patients had non-HIV-PCP. The numbers of patients who received high-, conventional-, and low-dose treatments were 5, 36, and 41, respectively. Kaplan-Meier analysis for death associated with PCP showed no statistically significant difference in survival rates between the conventional- and low-dose groups. Ninety-day cause-specific mortality rates were 25.0% and 19.5% in the conventional-dose and low-dose groups (P = 0.76), respectively. Adverse events that were graded as ≥3 according to the Common Terminology Criteria for Adverse Events (version 4.0) (National Cancer Institute, 2010) were 41.7% and 17.1% in the conventional-dose and low-dose groups (P = 0.02), respectively. Moreover, vomiting (P = 0.03) and a decrease in platelet count (P = 0.03) occurred more frequently in the conventional-dose group. Treatment of non-HIV-PCP with low-dose or conventional-dose TMP-SMX produces comparable survival rates; however, the low-dose regimen is better tolerated and associated with fewer adverse effects.


Assuntos
Pneumocystis carinii/efeitos dos fármacos , Pneumonia por Pneumocystis/tratamento farmacológico , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Idoso , Feminino , Humanos , Masculino , Pneumonia por Pneumocystis/mortalidade , Pneumonia por Pneumocystis/parasitologia , Estudos Retrospectivos , Taxa de Sobrevida
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