Pneumocystis jirovecii en pacientes inmunocomprometidos con enfermedades reumáticas

ObjectivesTo develop EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in patients with autoimmune inflammatory rheumatic diseases (AIIRD).MethodsAn international Task Force (TF) (22 members/15 countries) formulated recommendations, supported by systematic literature review findings. Level of evidence and grade of recommendation were assigned for each recommendation. Level of agreement was provided anonymously by each TF member.ResultsFour overarching principles (OAP) and eight recommendations were developed. The OAPs highlight the need for infections to be discussed with patients and with other medical specialties, in accordance with national regulations. In addition to biologic/targeted synthetic disease-modifying antirheumatic drugs (DMARDs) for which screening for latent tuberculosis (TB) should be performed, screening could be considered also before conventional synthetic DMARDs, glucocorticoids and immunosuppressants. Interferon gamma release assay should be preferred over tuberculin skin test, where available. Hepatitis B (HBV) antiviral treatment should be guided by HBV status defined prior to starting antirheumatic drugs. All patients positive for hepatitis-C-RNA should be referred for antiviral treatment. Also, patients who are non-immune to varicella zoster virus should be informed about the availability of postexposure prophylaxis should they have contact with this pathogen. Prophylaxis againstPneumocystis jiroveciiseems to be beneficial in patients treated with daily doses >15–30 mg of prednisolone or equivalent for >2–4 weeks.ConclusionsThese recommendations provide guidance on the screening and prevention of chronic and opportunistic infections. Their adoption in clinical practice is recommended to standardise and optimise care to reduce the burden of opportunistic infections in people living with AIIRD.

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2022 EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in adults with autoimmune inflammatory rheumatic diseases

Fragoulis

Nikiphorou

Dey

et al. 2022

Ann Rheum Dis

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Clinical practice pattern of Pneumocystis pneumonia prophylaxis in systemic lupus erythematosus: a cross-sectional study from lupus registry of nationwide institutions (LUNA)

Onishi,

Sada,

Hayashi

et al. 2024

Arthritis Res Ther

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Background Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection in patients undergoing immunosuppressive therapy, such as glucocorticoid (GC) medication, for systemic autoimmune diseases like systemic lupus erythematosus (SLE). Despite the confirmed effectiveness of PCP prophylaxis, its clinical administration, especially in conjunction with GC dosage, remains unclear. We aimed to describe the clinical practice of PCP prophylaxis in association with SLE in Japan, evaluate the relationship between GC dosage and PCP prophylaxis, and explore the practice patterns associated with PCP prophylaxis. Methods This cross-sectional study used data from the Lupus Registry of Nationwide Institutions in Japan from 2016 to 2021 and included patients diagnosed with SLE. Using descriptive statistics, multivariate analysis, and decision tree analysis, we examined the prevalence of PCP prophylaxis and its association with the GC dosage. Results Out of 1,460 patients, 21% underwent PCP prophylaxis. The frequency of prophylaxis decreased with a decrease in GC dosage. After adjusting for confounders, logistic regression revealed the odds ratio of PCP prophylaxis increased with higher prednisolone (PSL) doses: 3.7 for 5 ≤ PSL < 7.5 mg, 5.2 for 7.5 ≤ PSL < 10 mg, 9.0 for 10 ≤ PSL < 20 mg, and 43.1 for PSL ≥ 20 mg, using PSL < 5 mg as the reference. Decision tree analysis indicated that a PSL dosage of < 11 mg/day and immunosuppressant use were key determinants of PCP prophylaxis. Conclusion This study provides valuable insights into PCP prophylaxis practices in patients with SLE in Japan, underscoring the importance of GC dosage and concomitant immunosuppressant use.

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Enantioselective Interactions of Anti-Infective 8-Aminoquinoline Therapeutics with Human Monoamine Oxidases A and B

et al. 2021

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8-Aminoquinolines (8-AQs) are an important class of anti-infective therapeutics. The monoamine oxidases (MAOs) play a key role in metabolism of 8-AQs. A major role for MAO-A in metabolism of primaquine (PQ), the prototypical 8-AQ antimalarial, has been demonstrated. These investigations were further extended to characterize the enantioselective interactions of PQ and NPC1161 (8-[(4-amino-1-methylbutyl) amino]-5-[3, 4-dichlorophenoxy]-6-methoxy-4-methylquinoline) with human MAO-A and -B. NPC1161B, the (R)-(−) enantiomer with outstanding potential for malaria radical cure, treatment of visceral leishmaniasis and pneumocystis pneumonia infections is poised for clinical development. PQ showed moderate inhibition of human MAO-A and -B. Racemic PQ and (R)-(−)-PQ both showed marginally greater (1.2- and 1.6-fold, respectively) inhibition of MAO-A as compared to MAO-B. However, (S)-(+)-PQ showed a reverse selectivity with greater inhibition of MAO-B than MAO-A. Racemic NPC1161 was a strong inhibitor of MAOs with 3.7-fold selectivity against MAO-B compared to MAO-A. The (S)-(+) enantiomer (NPC1161A) was a better inhibitor of MAO-A and -B compared to the (R)-(−) enantiomer (NPC1161B), with more than 10-fold selectivity for inhibition of MAO-B over MAO-A. The enantioselective interaction of NPC1161 and strong binding of NPC1161A with MAO-B was further confirmed by enzyme-inhibitor binding and computational docking analyses. Differential interactions of PQ and NPC1161 enantiomers with human MAOs may contribute to the enantioselective pharmacodynamics and toxicity of anti-infective 8-AQs therapeutics.

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Pneumocystis jirovecii en pacientes inmunocomprometidos con enfermedades reumáticas

Cited by 3 publications

References 56 publications

2022 EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in adults with autoimmune inflammatory rheumatic diseases

2022 EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in adults with autoimmune inflammatory rheumatic diseases

Clinical practice pattern of Pneumocystis pneumonia prophylaxis in systemic lupus erythematosus: a cross-sectional study from lupus registry of nationwide institutions (LUNA)

Enantioselective Interactions of Anti-Infective 8-Aminoquinoline Therapeutics with Human Monoamine Oxidases A and B

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