Division of Rheumatology, Department of Pediatrics, Seattle Children's Hospital, University of Washington School of Medicine.
Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia.
J Pediatric Infect Dis Soc. 2018 Dec 3;7(4):283-289. doi: 10.1093/jpids/pix052.
Antimicrobial prophylaxis is indicated to prevent Pneumocystis jirovecii pneumonia (PJP) in profoundly immunosuppressed children. The incidence of PJP infection in children with chronic glucocorticoid exposure is unknown, and PJP prophylaxis has been associated with adverse events. We hypothesized that PJP infection is rare in children without human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), cancer, or a transplant history who are using chronic glucocorticoids and that those exposed to PJP prophylaxis are more likely to experience a cutaneous hypersensitivity reaction or myelosuppression than unexposed patients.
This study involved a retrospective cohort from the Clinformatics Data Mart Database (OptumInsight, Eden Prairie, MN). We identified patients ≤18 years of age who received at least 2 prescriptions for a systemic glucocorticoid within a 60-day period and excluded patients with a history of PJP infection, an oncologic diagnosis, transplant, or HIV/AIDS. PJP prophylaxis exposure was identified by using national drug codes. Cutaneous hypersensitivity reaction or myelosuppression was identified by using International Classification of Diseases, 9th Revision (ICD-9), codes. We used a discrete time-failure model to examine the association between exposure and outcome.
We identified 119399 children on glucocorticoids, 10% of whom received PJP prophylaxis. The incidences of PJP were 0.61 and 0.53 per 10000 patient-years in children exposed and those unexposed to PJP prophylaxis, respectively. In a multivariable model, trimethoprim-sulfamethoxazole was associated with cutaneous hypersensitivity reaction (odds ratio, 3.20; 95% confidence interval, 2.62-3.92) and myelosuppression (odds ratio, 1.85; 95% confidence interval, 1.56-2.20).
PJP infection was rare in children using glucocorticoids chronically, and PJP prophylaxis-associated cutaneous hypersensitivity reactions and myelosuppression are more common. The use of PJP chemoprophylaxis in children without HIV/AIDS, cancer, or a transplant history who are taking glucocorticoids chronically should be considered carefully.
抗微生物预防被用于预防严重免疫抑制儿童的卡氏肺孢子虫肺炎（PJP）。在接受慢性糖皮质激素暴露的儿童中，PJP 感染的发生率尚不清楚，且 PJP 预防与不良反应相关。我们假设，在没有人类免疫缺陷病毒（HIV）/获得性免疫缺陷综合征（AIDS）、癌症或移植史且正在使用慢性糖皮质激素的儿童中，PJP 感染较为罕见，且暴露于 PJP 预防的患者比未暴露的患者更有可能发生皮肤过敏反应或骨髓抑制。
本研究为来自 Clinformatics Data Mart 数据库（OptumInsight，Eden Prairie，MN）的回顾性队列研究。我们纳入了在 60 天内至少接受 2 次全身糖皮质激素处方的≤18 岁患者，并排除了有 PJP 感染、肿瘤诊断、移植或 HIV/AIDS 病史的患者。通过国家药物代码识别 PJP 预防暴露。通过国际疾病分类，第 9 版（ICD-9）代码识别皮肤过敏反应或骨髓抑制。我们使用离散时间失效模型来检查暴露与结局之间的关联。
我们确定了 119399 名使用糖皮质激素的儿童，其中 10%接受了 PJP 预防。暴露于和未暴露于 PJP 预防的儿童的 PJP 发生率分别为每 10000 患者-年 0.61 例和 0.53 例。在多变量模型中，甲氧苄啶-磺胺甲恶唑与皮肤过敏反应相关（比值比，3.20；95%置信区间，2.62-3.92）和骨髓抑制相关（比值比，1.85；95%置信区间，1.56-2.20）。
在长期使用糖皮质激素的儿童中，PJP 感染较为罕见，且与 PJP 预防相关的皮肤过敏反应和骨髓抑制更为常见。在没有 HIV/AIDS、癌症或移植史且正在长期接受糖皮质激素治疗的儿童中，应慎重考虑使用 PJP 化学预防。
