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口服米诺环素作为异基因造血细胞移植后凝固酶阴性葡萄球菌所致非复杂性静脉通路装置相关血流感染的全身治疗方法。

Oral minocycline as systemic therapy for uncomplicated venous access device-related bloodstream infection with coagulase-negative staphylococci after allogeneic hematopoietic cell transplantation.

作者信息

Bayoudh Firas, Giot Jean-Baptiste, Descy Julie, Fontaine Corentin, Hayette Marie-Pierre, Baron Frédéric, Willems Evelyne, Beguin Yves, Frippiat Frédéric, Servais Sophie

机构信息

Department of Clinical Hematology, University Hospital of Liège, CHU Sart-Tilman, 4000 Liège, Belgium.

Department of Infectious Disease, University Hospital of Liège, CHU Sart-Tilman, 4000 Liège, Belgium.

出版信息

Curr Res Transl Med. 2024 Mar;72(1):103422. doi: 10.1016/j.retram.2023.103422. Epub 2023 Oct 16.

Abstract

BACKGROUND

Venous access device-related bloodstream infection (VAD-BSI) with coagulase-negative staphylococci (CoNS) is a common complication after allogeneic hematopoietic cell transplantation (alloHCT). Standard systemic antimicrobial therapy for uncomplicated VAD-BSI with methicillin-resistant CoNS consists of intravenous (IV) vancomycin (vanco). This requires hospitalization, needs new competent venous access, exposes patients to potential toxicity (mainly renal) and increases the risk of commensal flora dysbiosis with selection of vanco-resistant enterococci. Combined with VAD management (removal or antibiotic locks), oral minocycline (mino) has been evaluated as an alternative systemic therapy for the treatment of uncomplicated VAD-BSIs with CoNS at our center, primarily when the reference treatment with IV vanco was not possible (renal failure or allergy) or when hospitalization was refused by patients. Here, we retrospectively report our single center experience with this mino-based approach.

PATIENTS AND METHODS

From January 2012 to December 2020, 24 uncomplicated VAD-BSIs with CoNS in 23 alloHCT patients were treated with oral mino as systemic antibiotic therapy in combination with VAD management. VAD were implantable ports (n = 17), tunneled catheter (n = 1) or PIC-lines (n = 6). Staphylococci were S. epidermidis (n = 21) or S. haemolyticus (n = 3). Mino was administered with a loading dose of 200 mg followed by 100 mg BID for 7-14 days. For 8 VAD-BSIs, patients were initially treated with IV vanco for the first 1-3 days followed by oral mino, while 16 VAD-BSIs were treated with oral mino as the sole antimicrobial agent for systemic therapy. VAD management consisted of catheter removal (for tunneled catheters and PIC-lines, n = 7) or antibiotic locks with vanco (n = 15) or gentamicin (n = 2) administered at least 3 times a week for 14 days (for ports).

RESULTS

Overall, clearance of bacteremia (as assessed by negativity for the same CoNS of surveillance peripheral blood cultures drawn between day+ 3 and +30 after initiation of systemic therapy) was achieved in all but 1 patient (with port) who had persistent bacteremia at day +9. No complication such as suppurative thrombophlebitis, endocarditis, distant foci of infection or BSI-related death was observed in any patient during the 3-month period after initiation of treatment. Regarding the 17 port-BSI cases for which VAD conservative strategy was attempted, failure of 3-month VAD preservation was documented in 7/17 cases and 3-month recurrence of VAD-BSI was observed in 3/17 cases (with 1 patient with cellulitis). Treatment with mino was well tolerated except for a mild skin rash in one patient.

CONCLUSION

Further prospective studies are needed to evaluate efficacy and safety of this approach.

摘要

背景

凝固酶阴性葡萄球菌(CoNS)所致的静脉通路装置相关血流感染(VAD-BSI)是异基因造血细胞移植(alloHCT)后的常见并发症。对于由耐甲氧西林CoNS引起的非复杂性VAD-BSI,标准的全身抗菌治疗是静脉注射(IV)万古霉素(vanco)。这需要住院治疗,需要新的合适静脉通路,使患者面临潜在毒性(主要是肾脏毒性),并增加共生菌群失调的风险以及耐万古霉素肠球菌的选择风险。结合VAD管理(拔除或抗生素封管),口服米诺环素(mino)已在我们中心被评估为治疗由CoNS引起的非复杂性VAD-BSI的替代全身治疗方法,主要用于无法进行IV vanco标准治疗的情况(肾衰竭或过敏)或患者拒绝住院时。在此,我们回顾性报告我们单中心采用这种基于米诺环素方法的经验。

患者和方法

从2012年1月至2020年12月,23例alloHCT患者发生的24例由CoNS引起的非复杂性VAD-BSI接受了口服米诺环素作为全身抗生素治疗并结合VAD管理。VAD为植入式端口(n = 17)、隧道式导管(n = 1)或外周静脉留置针(PIC-line,n = 6)。葡萄球菌为表皮葡萄球菌(n = 21)或溶血葡萄球菌(n = 3)。米诺环素的给药方案为首剂200 mg,随后100 mg每日两次,共7 - 14天。对于8例VAD-BSI患者,最初1 - 3天先用IV vanco治疗,随后改为口服米诺环素,而16例VAD-BSI患者仅用口服米诺环素作为全身治疗的抗菌药物。VAD管理包括拔除导管(用于隧道式导管和PIC-line,n = 7)或用vanco(n = 15)或庆大霉素(n = 2)进行抗生素封管,至少每周3次,持续14天(用于端口)。

结果

总体而言,除1例(植入端口)患者在第9天仍有持续性菌血症外,所有患者均实现了菌血症清除(通过在全身治疗开始后第3天至第30天采集的监测外周血培养中相同CoNS呈阴性来评估)。在治疗开始后的3个月内,任何患者均未观察到诸如化脓性血栓性静脉炎、心内膜炎、远处感染灶或BSI相关死亡等并发症。对于尝试采用VAD保守策略的17例端口相关BSI病例,17例中有7例记录了3个月VAD保留失败,17例中有3例观察到VAD-BSI的3个月复发(其中1例患者发生蜂窝织炎)。除1例患者出现轻度皮疹外,米诺环素治疗耐受性良好。

结论

需要进一步的前瞻性研究来评估这种方法的疗效和安全性。

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