Colonización por pneumocystis jirovecii en pacientes en tratamiento con anti-tnf-alfa
- Autores: Isabel Martín Garrido
- Directores de la Tesis: Enrique J. Calderón (dir. tes.), José Manuel Varela Aguilar (dir. tes.), FJ Medrano (dir. tes.)
- Lectura: En la Universidad de Sevilla ( España ) en 2016
- Idioma: español
- Número de páginas: 100
- Tribunal Calificador de la Tesis: José Antonio Girón González (presid.), Antonio Grilo-Reina (secret.), Miguel Angel Muniain Ezcurra (voc.), Antonio Lorenzo Peñuelas (voc.), Francisco Vaz de Carvalho Esteves (voc.)
- Materias:
- Enlaces
- Tesis en acceso abierto en: Idus
- Resumen
BRIEF SUMMARY OF DOCTORAL THESIS Tittle: Pneumocystis jirovecii colonization in patients in treatment with anti-TNF drugs Authors: Conferring a doctor's degree: Isabel Martín Garrido Directors: Enrique Calderón Sandubete MD, PhD. José Manuel Varela Aguilar MD, PhD. Francisco Javier Medrano Ortega MD, PhD.
Tutor: Proffesor José Ricardo Villar Ortiz Introduction: Pneumocystis pneumonia (PcP) is an important opportunistic infection, with high mortality rate, not only in patients with acquired immunodeficiency syndrome (AIDS), but also in patients with autoimmune systemic disease, hematological or solid malignancies, transplant recipients or tumors, among others. There exists data that support the idea of which the colonization by P. jirovecii constitutes a risk for development of PCP in subjects submitted to some type of immunosuppression. Tumor necrosis factor alpha (TNF¿) is a pro-inflammatory cytokine that plays a fundamentally role in the control of the Pneumocystis jirovecii infection, for it, It is possible that the effect of the anti-TNF drugs, on having disabled the action of this cytokine, could favor the colonization by P. jirovecii or as PcP's later development in the patients who receive this type of treatments. It could be interesting to know P. jirovecii colonization state in order to know whose patients could receive effective chemoprophylaxis as in tuberculosis infection. Nowadays there is not sufficient information about the frequency of P. jirovecii colonization in patient in treatment with anti-TNF drugs.
Objectives: The aims of our study were to obtain information about the colonization by P. jirovecii among patients with systemic diseases treated with different anti TNF drugs and if there were differences rates of colonization by drug or underlying disease. Likewise to know the epidemiological characteristics and the potential risk factors for colonization by P. jirovecii in these patients.
Design: we examined oropharingeal washes collected from 195 patients with different autoimmune systemic diseases, rheumatoid arthritis (AR), ankylosing spondylitis (EA), psoriatic arthritis (APS) or psoriasis (PS), using a real-time polymerase chain reaction assay that employs specific primers from a portion of the mitochondrial large-subunit rRNA gene of P. jirovecii. One hundred and thirty two patients were under treatment with anti-TNF¿ drugs, 62 infliximab, 30 adalimumab and 40 etanercept. Sixty three patients without anti-TNF¿ treatment were included as controls. All they fulfilled all the inclusion criteria and they did not have reasons for exclusion.
Results: Prevalence of Pneumocystis jirovecii colonization in patients with autoimmune systemic diseases in our study has been high at 21%; and in patients receiving anti-TNF drugs was 20.5% with no statistically significant differences between patients who received these drugs and those who did not. There was a higher rate of colonization among the group of patients under treatment with infliximab (29%) compared to etanercept group (15%) and adalimumab group (10%) although no statistically significant differences. However, we found that colonized individuals increased as the length of treatment with infliximab increased (adjusted OR for every week 1.010, 95% CI 1.004 ¿1.016, p = 0.001). The risk factor associated more strongly to the fact of colonization in the patients studied has been the concomitant use of methotrexate (adjusted OR: 2.386, 95% CI: 1.081-5.266; p = 0.031). We found a relationship, although weaker, with the use of steroids (adjusted OR: 1.894, 95% CI: 0.872-4.111, p = 0.106) and with older patients (adjusted OR: 1.01, 95% CI: 0.983-1.039, p = 0.451). We have not found significant relationship between different studied diseases (AR, APS, PS or EA) smoking or if they had chronic underlying pulmonary disease or previous use of sulfonamides.
Conclusions: The overall prevalence of Pneumocystis jirovecii colonization in patients with systemic diseases in our study has been high at 21%; and in particular among patients receiving anti-TNF drugs was 20.5%, with no statistically significant differences between patients who received these drugs and those who do not. There is a higher rate of colonization among the group of patients receiving infliximab compared to other groups, although no statistically significant differences. However, we found that colonized individuals increased as the length of treatment with infliximab increased. Likewise, we have not found significant differences in colonization by studied diseases: rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis or psoriasis. The risk factor associated more strongly to the fact of colonization in the patients studied has been the concomitant use of methotrexate. We found a relationship, although weaker, with the use of steroids and with older patients. We have not found significant relationship between smoking or if they had chronic underlying pulmonary disease or previous use of sulfonamides.
