Clinical treatment and management of invasive fungal disease in recipients of solid organ transplantation / 器官移植

With widespread application of solid organ transplantation (SOT), the incidence of postoperative invasive fungal disease (IFD) in SOT recipients has been increased year by year. In recent years, the awareness of preventive antifungal therapy for SOT recipients has been gradually strengthened. However, the problem of fungal resistance has also emerged, leading to unsatisfactory efficacy of original standardized antifungal regimens. Drug-drug interaction and hepatorenal toxicity induced by drugs are also challenges facing clinicians. In this article, the characteristics of drug-drug interaction and hepatorenal toxicity among triazole, echinocandin and polyene antifungal drugs and immunosuppressants were reviewed, and postoperative preventive strategies for IFD in different types of SOT recipients and treatment strategies for IFD caused by infection of different pathogens were summarized, aiming to provide reference for physicians in organ transplantation and related disciplines.

Of “Cotton Balls” and “Owl’s eyes”

@#Report of a 3-month old girl child who died due to multi-systemic infection of cytomegalovirus (CMV) involving the lungs, liver and kidneys along with pneumocystis jiroveci pneumonia (PJP). The mother of the child tested positive for CMV IgG and HIV with a very low CD4 count (160/ µl). Co-infection of cytomegalovirus and pneumocystis jiroveci always occurs in the setting of immunocompromise. Congenital CMV infection is transmitted through the placenta, especially during the first trimester and causes severe multi-systemic disease whereas perinatal infection is acquired during childbirth/ breastfeeding where the babies have maternal protective antibodies leading to much milder or asymptomatic infection. PJP is more common in infancy and presents as hypoxic pneumonia. CMV causes cyto-nucleomegaly and classic “owl’s eye” inclusions on histology while PJP presents with characteristic fluffy “cotton ball” alveolar exudates.

A multivariate prognostic score for predicting mortality of acquired immunodeficiency syndrome patients with Hypoxemic Respiratory Failure and Pneumocystis Jiroveci Pneumonia

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 (β) 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.

The Safety Profiles of Biological Drugs for Rheumatoid Arthritis / 薬剤疫学

To identify the most frequently reported preferred terms （PTs） in the cases of rheumatoid arthritis （RA） patients treated with immunosuppressive biological drugs as suspected drugs, we analyzed the cases in the Japanese Adverse Drug Event Report （JADER） database. We found that pneumonia, interstitial lung disease, Pneumocystis jiroveci pneumonia （PCP), cellulitis, sepsis, and herpes zoster were the most frequently reported PTs. We obtained the reporting odds ratio （ROR） and the time to onset of these six PTs and compared them in the cases reported for each immunosuppressant as a suspected drug. We focused on RA treatment, including five tumor necrosis factor （TNF） antagonists （infliximab, etanercept, adalimumab, golimumab, and certolizumab pegol). For pneumonia, interstitial lung disease and sepsis, no specific correlation was observed for each immunosuppressant for RA. In the case of PCP, the highest ROR was observed in the patients treated with infliximab. The time to onset of PCP in the infliximab-treated patients （median, 0.19 yr） was significantly shorter than the onset time in the patients treated with tocilizumab, an interleukin-6 receptor blocker that is another type of drug for RA（0.32 yr, p<0.01, Mann-Whitney test). The onset time in the patients treated with golimumab （0.24 yr） was also significantly shorter than the onset time for tocilizumab（p<0.05), but the ROR was not as high. These results suggested a correlation between PCP and infliximab. In the cases of cellulitis and herpes zoster, a similar correlation was observed with tocilizumab and certolizumab pegol, respectively. We should consider these results when patients have a respiratory disorder or skin/subcutaneous tissue disorder.

<b>The Safety Profiles of Biological Drugs for Rheumatoid Arthritis </b> / 薬剤疫学

<p>To identify the most frequently reported preferred terms （PTs） in the cases of rheumatoid arthritis （RA） patients treated with immunosuppressive biological drugs as suspected drugs, we analyzed the cases in the Japanese Adverse Drug Event Report （JADER） database. We found that pneumonia, interstitial lung disease, <i>Pneumocystis jiroveci</i> pneumonia （PCP), cellulitis, sepsis, and herpes zoster were the most frequently reported PTs. We obtained the reporting odds ratio （ROR） and the time to onset of these six PTs and compared them in the cases reported for each immunosuppressant as a suspected drug. We focused on RA treatment, including five tumor necrosis factor （TNF） antagonists （infliximab, etanercept, adalimumab, golimumab, and certolizumab pegol). For pneumonia, interstitial lung disease and sepsis, no specific correlation was observed for each immunosuppressant for RA. In the case of PCP, the highest ROR was observed in the patients treated with infliximab. The time to onset of PCP in the infliximab-treated patients （median, 0.19 yr） was significantly shorter than the onset time in the patients treated with tocilizumab, an interleukin-6 receptor blocker that is another type of drug for RA（0.32 yr, p<0.01, Mann-Whitney test). The onset time in the patients treated with golimumab （0.24 yr） was also significantly shorter than the onset time for tocilizumab（p<0.05), but the ROR was not as high. These results suggested a correlation between PCP and infliximab. In the cases of cellulitis and herpes zoster, a similar correlation was observed with tocilizumab and certolizumab pegol, respectively. We should consider these results when patients have a respiratory disorder or skin/subcutaneous tissue disorder.</p>