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囊性纤维化患者中分枝杆菌感染的流行病学和相关大环内酯类药物的慢性使用。

Epidemiology of nontuberculous mycobacterial infections and associated chronic macrolide use among persons with cystic fibrosis.

机构信息

1 Epidemiology Unit and.

出版信息

Am J Respir Crit Care Med. 2013 Oct 1;188(7):807-12. doi: 10.1164/rccm.201307-1200OC.

Abstract

RATIONALE

Persons with cystic fibrosis (CF) are at high risk of nontuberculous mycobacterial (NTM) infection, with treatment requiring prolonged multidrug regimens that include macrolides. Although macrolides, specifically azithromycin, are used in the management of patients with CF with chronic Pseudomonas, macrolide-resistant NTM infections are of growing concern.

OBJECTIVES

To evaluate the relationship between chronic macrolide use and NTM infection among patients with CF included in the 2011 CF Patient Registry (CFPR).

METHODS

We performed a nested case-control study: incident NTM cases were persons aged more than 5 years with at least one positive culture for NTM in 2011. Controls were persons with negative cultures in 2010 and 2011.

MEASUREMENTS AND MAIN RESULTS

The 2011 CFPR included 27,112 patients; 5,403 (20%) were cultured for mycobacteria in 2010-2011 and met all inclusion criteria. Of these, 191 (4%) were NTM-positive in 2011 only (cases); 5,212 (96%) were NTM-negative in 2010 and 2011 (control subjects). Among the cases, 122 (64%) were culture-positive for Mycobacterium avium complex (MAC) and 69 (36%) for M. abscessus. Azithromycin use in 2010 was less frequently reported among MAC cases (57%; odds ratio = 0.7, P < 0.05) and M. abscessus cases (51%; odds ratio = 0.5, P < 0.01) than in control subjects (66%). Among adolescents and adults, patients with the greatest number of years on chronic macrolides were the least likely to develop incident NTM in 2011 (P < 0.01).

CONCLUSIONS

Patients with incident NTM infections from either MAC or M. abscessus were less likely to have had chronic azithromycin treatment in the past year. However, because macrolide monotherapy may lead to macrolide resistance, routine screening for NTM should be considered for persons with CF.

摘要

背景

囊性纤维化(CF)患者感染非结核分枝杆菌(NTM)的风险很高,治疗需要长期使用多种药物,包括大环内酯类药物。虽然大环内酯类药物,特别是阿奇霉素,用于治疗 CF 患者的慢性铜绿假单胞菌感染,但大环内酯类耐药 NTM 感染的问题越来越受到关注。

目的

评估纳入 2011 年 CF 患者登记处(CFPR)的 CF 患者慢性大环内酯类药物使用与 NTM 感染之间的关系。

方法

我们进行了一项巢式病例对照研究:新发病例为 2011 年至少有一次 NTM 阳性培养的年龄大于 5 岁的患者。对照为 2010 年和 2011 年培养阴性的患者。

测量和主要结果

2011 年 CFPR 共纳入 27112 例患者;2010-2011 年有 5403 例(20%)进行了分枝杆菌培养,且均符合所有纳入标准。其中,191 例(4%)仅在 2011 年为 NTM 阳性(病例);5212 例(96%)在 2010 年和 2011 年均为 NTM 阴性(对照)。在病例中,122 例(64%)为鸟分枝杆菌复合群(MAC)阳性,69 例(36%)为脓肿分枝杆菌阳性。MAC 病例(57%;比值比=0.7,P<0.05)和脓肿分枝杆菌病例(51%;比值比=0.5,P<0.01)的大环内酯类药物(阿奇霉素)使用报告率低于对照(66%)。在青少年和成人中,接受慢性大环内酯类药物治疗时间最长的患者在 2011 年发生新的 NTM 感染的可能性最小(P<0.01)。

结论

新发生 MAC 或脓肿分枝杆菌 NTM 感染的患者在过去一年中不太可能接受慢性阿奇霉素治疗。然而,由于大环内酯类药物单药治疗可能导致大环内酯类耐药,因此 CF 患者应常规筛查 NTM。

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