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1.
Medicine (Baltimore) ; 99(2): e18696, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914071

RESUMO

RATIONALE: Severe alcoholic hepatitis (AH) has a very high mortality rate. Current guidelines recommend oral corticosteroids as first-line agents in individuals with severe AH to reduce short-term mortality. However, systemic corticosteroids have serious adverse effects. In individuals with AH, infection, which is one of the complications of steroid use, can result in serious outcomes, such as acute-on-chronic liver failure. Pneumocystis pneumonia (PCP) is a life-threatening opportunistic infection which may occur when high-dose corticosteroids are prescribed for more than 1 month. Therefore, when high-dose corticosteroids are used, providing PCP prophylaxis is warranted. Although trimethoprim-sulfamethoxazole (TMP-SMX) is the drug of choice for the prophylaxis of PCP, its hepatotoxicity limits its use in patients with severe AH who are on high-dose corticosteroids. Moreover, there is a lack of consensus on which drugs should be used for PCP prophylaxis in individuals with severe AH who are on glucocorticoid treatment. Herein, we report a case of a 43-year-old male with fatal PCP that occurred after the use of corticosteroids for severe AH. PATIENT CONCERNS: A 43-year-old alcoholic man presented with a hematoma on his right leg. His liver function was poor, and he was he was diagnosed with severe AH and treated with oral corticosteroids for 26 days. After glucocorticoid treatment, he developed a productive cough. DIAGNOSES: A sputum PCR test was positive for Pneumocystis jirovecii. INTERVENTIONS: He was initially treated with TMP-SMX and required artificial ventilation. OUTCOMES: He developed disseminated intravascular coagulation and multi-organ failure, and died 10 days after starting TMP-SMX. LESSONS: To date, prevention of PCP in individuals with severe AH who are on corticosteroids has been overlooked. This case illustrates the need for prophylaxis of PCP in individuals with severe AH taking corticosteroids.


Assuntos
Hepatite Alcoólica/complicações , Hepatite Alcoólica/tratamento farmacológico , Metilprednisolona/uso terapêutico , Pneumonia por Pneumocystis/etiologia , Adulto , Humanos , Masculino , Metilprednisolona/efeitos adversos , Infecções Oportunistas , Pneumocystis carinii , Pneumonia por Pneumocystis/tratamento farmacológico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico
2.
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
5.
Clin Immunol ; 200: 16-18, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30630113

RESUMO

Severe combined immunodeficiency (SCID) can be caused by deleterious mutations in DCLRE1C, leading to deficient non-homologous end joining by compromising the function of the Artemis protein. This impairs the process of V(D)J recombination of the T- and B-cell receptors and typically results in radiosensitive T-, B-, NK+ SCID presenting during the first months of life. We present a case of a 3-year-old girl with two novel compound heterozygous variants in DCLRE1C (c.58G>C and c.374A>C) that were associated with marked reduced numbers of peripheral T- and B-cells and undetectable total serum IgG. Despite the severe laboratory phenotype, the patient had a normal development, albeit failure to thrive (-2.5 to -3 SD), during her first years of life including day-care attendance at preschool for 1.5 years. After being diagnosed with pneumonia the clinical picture of SCID was recognized and the girl successfully underwent hematopoietic stem-cell transplantation.


Assuntos
Agamaglobulinemia/genética , Proteínas de Ligação a DNA/genética , Endonucleases/genética , Imunodeficiência Combinada Severa/genética , Agamaglobulinemia/complicações , Agamaglobulinemia/imunologia , Pré-Escolar , Feminino , Heterozigoto , Humanos , Mutação , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/etiologia , Imunodeficiência Combinada Severa/complicações , Imunodeficiência Combinada Severa/diagnóstico , Imunodeficiência Combinada Severa/imunologia
6.
Mod Rheumatol ; 29(1): 31-40, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29718746

RESUMO

Methotrexate (MTX), the anchor drug in the current treatment strategy for rheumatoid arthritis (RA), was first approved for treatment of RA in Japan in 1999 at the recommended dose of 6-8 mg/week; it was approved as first-line drug with the maximum dose of 16 mg/week in February 2011. However, more than half of Japanese patients with RA are unable to tolerate a dose of 16 mg/week of MTX. Moreover, some serious adverse events during the treatment with MTX, such as pneumocystis pneumonia (PCP) and lymphoproliferative disorders (LPD) have been observed much more frequently in Japan than in other countries. Therefore, this article, an abridged English translation summarizing the 2016 update of the Japan College of Rheumatology (JCR) guideline for the use of MTX in Japanese patients with RA, is not intended to be valid for global use; however, it is helpful for the Japanese community of rheumatology and its understanding might be useful to the global community of rheumatology.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Transtornos Linfoproliferativos , Metotrexato , Pneumonia por Pneumocystis , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Artrite Reumatoide/epidemiologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Japão/epidemiologia , Transtornos Linfoproliferativos/epidemiologia , Transtornos Linfoproliferativos/etiologia , Transtornos Linfoproliferativos/prevenção & controle , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Pneumonia por Pneumocystis/epidemiologia , Pneumonia por Pneumocystis/etiologia , Pneumonia por Pneumocystis/prevenção & controle , Risco Ajustado/métodos , Resultado do Tratamento
7.
Mod Rheumatol ; 29(4): 656-661, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29972334

RESUMO

Objective: Pneumocystis pneumonia (PCP) is a serious complication in patients with rheumatic diseases who are receiving immunosuppressive therapy. These patients have a higher mortality from PCP than those with human immunodeficiency virus. We examined factors associated with poor prognosis in patients with rheumatic diseases and evaluated PCP treatment in this population. Methods: This retrospective, single-center, observational cohort study included 31 patients with rheumatic diseases who were admitted to Juntendo University Hospital for PCP treatment from June 2006 to December 2017. The primary outcome was non-disease-specific mortality at discharge. Results: The median age at PCP diagnosis was 64 years. The survival rate was 61.3% (19/31). Twelve patients died, in all cases due to respiratory failure due to PCP. Among variables at PCP diagnosis and those related to PCP treatment, the presence of coexisting pulmonary diseases and greater glucocorticoid dose at PCP diagnosis were associated with higher mortality. The mortality related to biological agents for PCP was low. Rapid tapering of glucocorticoids improved survivability. Conclusion: In the treatment of PCP in patients with rheumatic diseases, rapid tapering of glucocorticoids was associated with a higher survival rate than the use of conventional therapy.


Assuntos
Glucocorticoides/uso terapêutico , Pneumonia por Pneumocystis/tratamento farmacológico , Doenças Reumáticas/complicações , Adulto , Idoso , Feminino , Glucocorticoides/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia por Pneumocystis/etiologia , Resultado do Tratamento
9.
Parasitol Res ; 118(1): 181-189, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30392033

RESUMO

Pneumocystis jirovecii is an opportunistic fungus occurring in human lungs. The group at highest risk consists of HIV-infected and non-HIV-infected immunosuppressed individuals. In these patients, P. jirovecii infection may lead to Pneumocystis pneumonia; it may, however, persist also in an asymptomatic form. This study aimed to determine the prevalence of P. jirovecii and potential risk factors for infection in a group of renal transplant recipients and to characterize the genetic diversity of this fungus in the studied population. Sputum specimens from 72 patients were tested for presence of P. jirovecii using immunofluorescence microscopy, as well as nested PCR targeting the mtLSU rRNA gene. Genotyping involving analysis of four loci-mtLSU rRNA, CYB, DHPS, and SOD-was used to characterize the diversity of the detected organisms. Pneumocystis DNA was detected in eight (11.11%) patients. It has been shown that low eosinophil count and dual immunosuppressive treatment combining prednisone and calcineurin inhibitors are potential risk factors for colonization. Analysis of genotype distribution showed an association of the wild-type genotype of mtLSU rRNA with lower average age of patients and shorter time after kidney transplantation. Furthermore, CYB 2 genotype was detected only in patients with the ongoing prophylaxis regimen. In conclusion, renal transplant recipients are at risk of Pneumocystis colonization even a long time after transplantation. The present preliminary study identifies specific polymorphisms that appear to be correlated with certain patient characteristics and highlights the need for deeper investigation of these associations in renal transplant recipients.


Assuntos
Transplante de Rim/efeitos adversos , Pneumocystis carinii/isolamento & purificação , Pneumonia por Pneumocystis/microbiologia , Complicações Pós-Operatórias/microbiologia , Adulto , Idoso , Feminino , Variação Genética , Genótipo , Humanos , Hospedeiro Imunocomprometido , Pulmão/microbiologia , Masculino , Pessoa de Meia-Idade , Pneumocystis carinii/classificação , Pneumocystis carinii/genética , Pneumonia por Pneumocystis/etiologia , Pneumonia por Pneumocystis/imunologia , Reação em Cadeia da Polimerase , Complicações Pós-Operatórias/imunologia , Prevalência , Transplantados/estatística & dados numéricos , Adulto Jovem
10.
BMC Nephrol ; 19(1): 332, 2018 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-30463516

RESUMO

BACKGROUND: The goal of this study was to identify predictors for development of Pneumocystis jirovecii pneumonia (PJP) in kidney and simultaneous kidney and pancreas transplant recipients in the present era of universal primary prophylaxis. METHODS: We reviewed adult recipients of kidney transplant or simultaneous pancreas and kidney transplant at the University of Wisconsin between January 1, 1994 and December 31, 2016. Patients diagnosed with PJP during this time frame were included. Controls were randomly selected from among those whose post-transplant course was not complicated by PJP, matched on time since transplant through incidence density sampling with a 3:1 ratio. RESULTS: 28 (0.45%) of 6270 recipients developed PJP between 1994 and 2016. Median time since transplant was 4.6 years (interquartile range (IQR): 1.4-9.6 years). Affected recipients were older, had more HLA mismatches, and were more likely to have had BK viremia, CMV viremia and invasive fungal infections than matched controls. CMV viremia remained the only significant risk factor in multivariate analysis, and was a strong predictor (OR 6.27; p = 0.002). Ninety percent of the cases with prior CMV viremia had been diagnosed in the year preceding the diagnosis of PJP; among these, median time from diagnosis of CMV to diagnosis of PJP was 3.4 months (IQR: 1.74-11.5 months) and median peak CMV viral load prior to diagnosis of PJP was 3684.5 IU/mL (IQR: 1034-93,300 IU/mL). Additionally, 88.9% of patients with CMV in the preceding year had active infection at time of PJP diagnosis. Patient and graft survival were significantly worse at 2 years in recipients with PJP than our control group (42.4% vs. 88.5, and 37.9% vs. 79.9%; p < 0.001). CONCLUSIONS: Despite the low overall incidence of PJP in the era of universal prophylaxis, outcomes are poor. We suggest extending or re-initiating PJP prophylaxis for at least 6 months in the setting of CMV viremia due to the relatively low risk of therapy and potential significant impact on disease prevention.


Assuntos
Transplante de Rim/efeitos adversos , Transplante de Pâncreas/efeitos adversos , Pneumonia por Pneumocystis/diagnóstico , Profilaxia Pós-Exposição/métodos , Complicações Pós-Operatórias/diagnóstico , Transplantados , Adulto , Feminino , Seguimentos , Humanos , Transplante de Rim/tendências , Masculino , Pessoa de Meia-Idade , Transplante de Pâncreas/tendências , Pneumonia por Pneumocystis/etiologia , Pneumonia por Pneumocystis/prevenção & controle , Profilaxia Pós-Exposição/tendências , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Fatores de Risco
11.
Clin Transplant ; 32(8): e13339, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29956379

RESUMO

A growing number of publications have reported the outbreaks of post-transplant pneumocystis pneumonia (PJP). In most studies, the onset of PJP was beyond 6-12 months of prophylaxis. Cytomegalovirus (CMV) infection and allograft rejection have been repeatedly reported as probable risk factors for post-transplant PJP. In this systematic review and meta-analysis, we determined the pooled effect estimates of these 2 variables as risk factors. Data sources included PUBMED, MEDLINE-OVID, EMBASE-OVID, Cochrane Library, Networked Digital Library of Theses and Dissertations, World Health Organization, and Web of Science. We excluded publications related to hematopoietic stem cell transplantation (HSCT) or Human Immunodeficiency Virus (HIV) patients. Eventually, 15 studies remained for the final stage of screening. Cytomegalovirus infection (OR: 3.30, CI 95%: 2.07-5.26, I2 : 57%, P = 0.006) and allograft rejection (OR:2.36, CI95%: 1.54-3.62, I2: 45.5%, P = 0.05) significantly increased the risk of post-transplant PJP. Extended prophylaxis targeting recipients with allograft rejection or CMV infection may reduce the risk of PJP.


Assuntos
Infecções por Citomegalovirus/microbiologia , Citomegalovirus/isolamento & purificação , Rejeição de Enxerto/etiologia , Transplante de Órgãos/efeitos adversos , Pneumonia por Pneumocystis/etiologia , Infecções por Citomegalovirus/complicações , Rejeição de Enxerto/patologia , Humanos , Pneumonia por Pneumocystis/patologia , Fatores de Risco , Transplantados
12.
Front Immunol ; 9: 1118, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29887863

RESUMO

Introduction: Pneumocystis pneumonia (PCP) remains a severe complication with high mortality in immunocompromised patients. It has been well accepted that CD4+ T cells play a major role in controlling Pneumocystis infection. Th9 cells were the main source of IL-9 with multifaced roles depending on specific diseases. It is unclear whether IL-9/Th9 contributes to the immune response against PCP. The current study aims to explore the role of IL-9 and the effect of IL-9 on Th17 cells in murine model of PCP. Materials and methods: Mice were intratracheally injected with 1 × 106Pneumocystis organisms to establish the murine model of Pneumocystis infection. Pneumocystis burden was detected by TaqMan real-time PCR. Using IL-9-deficient (IL-9-/-) mice, flow cytometry, real-time PCR and enzyme-linked immunosorbent assay (ELISA) were conducted to investigate the immune function related to Th17 response in defense against Pneumocystis infection. Results: Reduced Pneumocystis burden was observed in lungs in IL-9-/- mice compared with WT mice at 3-week postinfection. IL-9-/-mice exhibited stronger Th17 immune responses than WT PCP mice through flow cytometer and real-time PCR. ELISA revealed higher levels of IL-17 and IL-23 in bronchoalveolar lavage fluid from IL-9-/- mice than WT mice. And IL-9 deficiency promoted Th17 differentiation from CD4+ naive T cells. IL-17A neutralization increased Pneumocystis burden in IL-9-/- mice. Conclusion: Although similar basic clearance of Pneumocystis organisms was achieved in both WT and IL-9-/- PCP mice, IL-9 deficiency could lower Pneumocystis organism burden and promote pulmonary Th17 cells response in the early stage of infection.


Assuntos
Suscetibilidade a Doenças , Interleucina-9/deficiência , Pneumocystis/imunologia , Pneumonia por Pneumocystis/etiologia , Células Th17/imunologia , Células Th17/metabolismo , Animais , Apoptose , Biomarcadores , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Modelos Animais de Doenças , Imunofenotipagem , Interleucina-17/metabolismo , Masculino , Camundongos , Camundongos Knockout , Neutrófilos/imunologia , Neutrófilos/metabolismo , Pneumocystis/genética , Pneumonia por Pneumocystis/microbiologia , Pneumonia por Pneumocystis/patologia
14.
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.
Clin Infect Dis ; 67(6): 913-919, 2018 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-29514207

RESUMO

Background: Although trimethoprim-sulfamethoxazole is the more efficient drug for prophylactic and curative treatment of pneumocystosis, atovaquone is considered a second-line prophylactic treatment in immunocompromised patients. Variations in atovaquone absorption and mutant fungi selection after atovaquone exposure have been associated with atovaquone prophylactic failure. We report here a Pneumocystis jirovecii cytochrome b (cyt b) mutation (A144V) associated with such prophylactic failure during a pneumocystosis outbreak among heart transplant recipients. Methods: Analyses of clinical data, serum drug dosage, and molecular modeling of the P. jirovecii Rieske-cyt b complex were performed to investigate these prophylactic failures. Results: The cyt b A144V mutation was detected in all infected, heart transplant recipient patients exposed to atovaquone prophylaxis but in none of 11 other immunocompromised, infected control patients not treated with atovaquone. Serum atovaquone concentrations associated with these prophylactic failures were similar than those found in noninfected exposed control patients under a similar prophylactic regimen. Computational modeling of the P. jirovecii Rieske-cyt b complex and in silico mutagenesis indicated that the cyt b A144V mutation might alter the volume of the atovaquone-binding pocket, which could decrease atovaquone binding. Conclusions: These data suggest that the cyt b A144V mutation confers diminished sensitivity to atovaquone, resulting in spread of Pneumocystis pneumonia among heart transplant recipients submitted to atovaquone prophylaxis. Potential selection and interhuman transmission of resistant P. jirovecii strain during atovaquone prophylactic treatment has to be considered and could limit its extended large-scale use in immucompromised patients.


Assuntos
Antifúngicos/farmacologia , Atovaquona/farmacologia , Citocromos b/genética , Transplante de Coração , Pneumocystis carinii/genética , Pneumonia por Pneumocystis/etiologia , Adulto , Idoso , Simulação por Computador , Surtos de Doenças , Feminino , Proteínas Fúngicas/genética , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Modelos Moleculares , Mutação , Pneumocystis carinii/efeitos dos fármacos , Pneumocystis carinii/enzimologia , Transplantados , Falha de Tratamento
18.
Clin Exp Rheumatol ; 36(3): 490-493, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29533748

RESUMO

OBJECTIVES: Guidelines for preventing Pneumocystis pneumonia (PCP) in HIV patients are based on CD4 below 200/mm3. Such cut-off value is suggested to guide prophylaxis in non-HIV conditions (NHIV) especially in autoimmune and inflammatory diseases (AD). We aimed to determine if CD4 could be used to guide PCP prophylaxis in AD. METHODS: CD4 and lymphocyte-count were retrospectively studied in patients diagnosed with PCP between January 2013 and February 2016. RESULTS: 129 patients were included. The median CD4-count was 302/mm3 in AD, which was significantly higher than in HIV patients (19/mm3; p<0.0001). Fifty percent (n=10) of AD patients had CD4 counts greater than 300/mm3. CONCLUSIONS: Prophylaxis for PCP cannot rely solely on CD4-count in NHIV patients especially in AD.


Assuntos
Doenças Autoimunes/tratamento farmacológico , Linfócitos T CD4-Positivos/imunologia , Infecções por HIV/terapia , Imunossupressores/efeitos adversos , Linfopenia/tratamento farmacológico , Pneumonia por Pneumocystis/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/imunologia , Doenças Autoimunes/complicações , Doenças Autoimunes/imunologia , Contagem de Linfócito CD4 , Crioglobulinemia/complicações , Crioglobulinemia/tratamento farmacológico , Crioglobulinemia/imunologia , Dermatomiosite/complicações , Dermatomiosite/tratamento farmacológico , Dermatomiosite/imunologia , Gerenciamento Clínico , Feminino , Arterite de Células Gigantes/complicações , Arterite de Células Gigantes/tratamento farmacológico , Arterite de Células Gigantes/imunologia , Infecções por HIV/complicações , Hepatite Autoimune/complicações , Hepatite Autoimune/tratamento farmacológico , Hepatite Autoimune/imunologia , Humanos , Hospedeiro Imunocomprometido , Linfopenia/etiologia , Linfopenia/imunologia , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/imunologia , Neoplasias/terapia , Transplante de Órgãos , Pneumonia por Pneumocystis/etiologia , Pneumonia por Pneumocystis/imunologia , Guias de Prática Clínica como Assunto , Estudos Retrospectivos
19.
J Artif Organs ; 21(3): 371-373, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29574652

RESUMO

Patients with immunosuppression from human immunodeficiency virus (HIV) have been traditionally considered poor candidates for extracorporeal membrane oxygenation (ECMO) because of high in-hospital mortality and poor long-term survival. Highly active antiretroviral therapy (HAART) has improved survival rates in compliant HIV patients and reversible severe respiratory failure may warrant ECMO in this group. Immune reconstitution inflammatory syndrome (IRIS) involves excessive inflammatory response to a pathogen with paradoxical clinical deterioration following HAART initiation and may present as severe respiratory failure. Patients with IRIS supported on ECMO have been infrequently reported in literature. We report two HIV-positive patients who developed acute respiratory distress syndrome from IRIS necessitating successful veno-venous ECMO as salvage therapy.


Assuntos
Oxigenação por Membrana Extracorpórea , Infecções por HIV/complicações , Reconstituição Imune , Pneumonia por Pneumocystis/terapia , Adulto , Infecções por HIV/imunologia , Humanos , Masculino , Pneumonia por Pneumocystis/etiologia , Pneumonia por Pneumocystis/imunologia , Insuficiência Respiratória , Resultado do Tratamento
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