Peritoneal dialysis-related peritonitis and bacteremia caused by Fusarium verticillioides: a case report and literature review

Liu Ye, Sun Fuyun

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Chinese Journal of Nephrology ›› 2023, Vol. 39 ›› Issue (12) : 935-938. DOI: 10.3760/cma.j.cn441217-20230321-00329
Case Report

Peritoneal dialysis-related peritonitis and bacteremia caused by Fusarium verticillioides: a case report and literature review

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Abstract

Fusarium is a kind of conditional pathogenic fungus. There are few reports of peritonitis caused by Fusarium at home and abroad. This paper reports a case of Fusarium verticillioides peritonitis complicated with bacteremia and reviews relevant literature. The patient was admitted to the hospital due to fever and abdominal pain. After peritonitis was diagnosed, the initial treatment was vancomycin plus ceftazidime kept in the abdominal cavity every night for 3 days, but the effect was not good. The antibiotic was upgraded to vancomycin plus meropenem for 2 days, but still, there was no effect. Subsequently, Fusarium was found after ascites fluid culture, and the treatment regimen was changed to voriconazole antifungal therapy and hemodialysis. However, the patient developed a dialysis catheter-related infection. After the infection was cured, the fever was still repeated, and the infection indexes did not improve. Further, the pathogenic microorganism of whole blood infection was detected by high-throughput gene detection, and it was clinically confirmed as Fusarium verticillioides. At last, the patient recovered and was discharged from the hospital after treatment with voriconazole combined with amphotericin B. Fusarium is highly pathogenic, and it is hoped to attract more attention of clinicians.

Key words

Fusarium / Fusariosis / Peritonitis / Peritoneal dialysis / Fusarium verticillioides

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Liu Ye. , Sun Fuyun. Peritoneal dialysis-related peritonitis and bacteremia caused by Fusarium verticillioides: a case report and literature review[J]. Chinese Journal of Nephrology, 2023, 39(12): 935-938. DOI: 10.3760/cma.j.cn441217-20230321-00329.
镰刀菌(Fusarium)是一种透明丝状真菌,在环境中随处可见,是免疫功能低下患者临床常见的霉菌之一1。由于大多数抗真菌药物对镰刀菌的最低抑菌浓度较高,镰刀菌感染的治疗较为困难2。轮枝样镰刀菌(Fusarium verticillioides)感染在腹膜透析(peritoneal dialysis,PD)患者中更加罕见,国内外均未见报道。本文报道1例轮枝样镰刀菌所致PD相关性腹膜炎(PD-related peritonitis,PDRP)及菌血症的诊疗经过,并进行文献复习,以提高临床医师对PD患者镰刀菌感染的识别和诊治能力。
患者男性,18岁,主因“PD 40个月,发热、腹痛1 d”于2022年3月6日入院。于40个月前因“恶心呕吐4 d”就诊于本院,查血肌酐1 493 μmol/L,尿素55.3 mmol/L,血红蛋白56 g/L,双肾彩超提示双肾体积缩小,诊断为慢性肾小球肾炎、慢性肾脏病5期,开始规律行持续不卧床PD(continuous ambulatory PD,CAPD),未曾患PDRP,尿素清除指数(Kt/V)一直保持为1.75~1.90。目前透析处方为CAPD 2.5%×2 L×4次,全天留腹。1周前患者帮家里晾晒玉米,1 d前出现发热伴下腹痛,体温最高37.4 ℃,伴进食差。入院后患者腹痛明显,查白细胞13.68×109/L,中性粒细胞10.91×109/L,淋巴细胞1.26×109/L,血红蛋白129 g/L,降钙素原(PCT)0.8 μg/L,超敏C反应蛋白(Hs-CRP)88.12 mg/L。腹水常规:有核细胞27×106/L。生化全项:白蛋白35.8 g/L,肌酐919 μmol/L,尿素19.4 mmol/L,钾4.2 mmol/L。腹部CT:双肾缩小,腹盆腔积液。患者腹水有核细胞数正常,未提示腹膜炎。入院第2天患者腹透液浑浊,查腹水常规:有核细胞609×106/L,多形核细胞74.6%。诊断:慢性肾脏病5期;PD;PDRP。治疗上给予万古霉素联合头孢他啶入腹腔抗感染治疗。3 d后患者腹痛无好转,腹水有核细胞升至1 519×106/L,多形核细胞81.6%。将抗生素升级为万古霉素联合美罗培南入腹腔2 d,仍无效果。入院第5天腹水培养结果回报为镰刀菌。考虑为PD相关镰刀菌性腹膜炎,停PD,给予股静脉深静脉置管改为血液透析(HD),静脉给予伏立康唑抗真菌治疗,第7天拔除PD导管。拔除PD导管后患者腹痛明显好转,术后第2天患者HD后出现高热,体温最高39.4 ℃,血降钙素原(PCT)>100 μg/L,考虑HD导管相关感染菌血症,给予拔出股静脉临时置管,改为颈内静脉半永久置管,静脉使用万古霉素联合美罗培南抗感染治疗。术后第9天查感染指标明显下降,PCT 2.2 μg/L。但患者仍反复高热,体温最高39.2 ℃。反复留取血培养均为阴性。查半乳甘露聚糖(GM)试验阴性,内毒素阴性,1,3-β-D葡聚糖检测211.2 ng/L,仍考虑真菌感染,全血感染病原微生物高通量基因检测(PMseq-DNA)提示镰刀菌属轮枝样镰刀菌,确诊为侵袭性镰刀菌感染。治疗上单用伏立康唑效果不佳,联合两性霉素B抗感染治疗,1周后患者体温恢复正常,感染指标均逐步下降,见图1。患者转HD 1年余感染未复发,仍在随访中。
图1 感染指标趋势图
注:血白细胞单位:×109/L;血中性粒细胞单位:×109/L;血超敏C反应蛋白单位:×10 mg/L

Full size|PPT slide

讨论 镰刀菌属物种呈全球分布,约有十种与人类病原体有关,其中茄病镰刀菌(Fusarium solani)是最常见和最具毒性的(约占40%~60%),其他有尖孢镰刀菌(Fusarium oxysporum)(约20%)、藤仓镰刀菌(Fusarium fujikuroi3-5。镰刀菌真菌毒素包括三烯菌素、伏马菌素、串珠菌素和真菌雌激素玉米赤霉烯酮,这些毒素可以抑制体液和细胞免疫,并导致组织破裂。2005—2018年间,侵袭性镰刀菌病病例数量增加6。镰刀菌感染包括浅表性和局部侵袭性及深部或者播散性感染,在血液系统恶性肿瘤和造血干细胞移植患者中发病率较高7。PD患者感染轮枝样镰刀菌并不常见,检索PubMed,仅有6例PD患者镰刀菌性腹膜炎感染的报道(见表18-13;国内没有相关报道。
表1 腹膜透析相关镰刀菌性腹膜炎病例汇总
患者

年龄(岁)/

性别

透析龄 微生物 体征和症状

既往发生

腹膜炎次数

治疗

导管

拔除

导管

培养

预后
18 69/男 未报告 镰刀菌 引流缓慢

金黄色葡萄球菌感染

3次;粪肠球菌1次

两性霉素B 阳性 存活
29 10.5/男 23个月 镰刀菌 无症状 3次 两性霉素B(0.5 mg·kg-1·d-1) IV+ 两性霉素B(5.0 mg/L透析液)IP 阳性 存活
310 57/男 36个月 尖孢镰刀菌 无症状 0 两性霉素B(50 mg/d)IV 14 d 阳性 存活

411

56/女

29个月

镰刀菌属

无症状

未报告

伏立康唑第1天每12小时负荷剂量 6 mg/kg,随后每12小时4 mg/kg IV治疗2个月

未报告

存活

512

39/男

6个月

单隔镰刀菌

Fusarium dimerum

低热、腹痛

0

两性霉素B脂质体1.5 mg·kg-1·d-1

IV+氟胞嘧啶75 mg·kg-1·d-1IV 4 d后

停用氟胞嘧啶,继续使用两性霉素B

脂质体3 mg·kg-1·d-1 IV

阳性

存活

613 29/女 48个月 镰刀菌属

腹痛、恶心、

呕吐

表皮和粪肠球菌

腹膜炎史

泊沙康唑800 mg/d后改为600 mg/d

维持量,治疗3个月

阳性 存活
注:IV:静脉注射;IP:腹腔注射;PO:口服
镰刀菌性腹膜炎临床症状不典型,以上病例中仅有2例患者有腹痛症状,其余4例均无明显临床症状;1例继发于细菌性腹膜炎后(病例2);6例患者均局限于腹腔感染,无血行播散情况;5例患者透析龄平均为28.4个月;对PD充分性与镰刀菌的相关性均未进行探讨。轮枝样镰刀菌相关性腹膜炎未见报道,患者发病前晾晒玉米,首先出现低热及剧烈腹痛症状,入院后第2天出现腹透液浑浊确诊PDRP,可见轮枝样镰刀菌致病有潜伏期。通过对本例患者的诊疗过程分析可以得出,轮枝样镰刀菌可由局部腹腔感染播散至血液,致病性及侵袭性强,单用伏立康唑效果不佳。
由于镰刀菌属表现出多药耐药性,其中一些具有泛耐药性,因而镰刀菌感染治疗困难。两性霉素B、那他霉素和伏立康唑是有效的药物,可以联合使用。泊沙康唑已被用于抢救治疗14。另有研究显示,艾氟康唑是一种新型的三唑类药物,可能是治疗浅表镰刀菌感染的有前途的候选药物,但低于镰刀菌病的主要选择15。对于镰刀菌性腹膜炎的治疗,表1可见有2例单用两性霉素B静脉注射,1例使用两性霉素B静脉注射联合腹腔注射,1例使用两性霉素B静脉注射联合氟胞嘧啶静脉注射,1例使用伏立康唑静脉注射,1例口服泊沙康唑治疗。而本例患者伏立康唑单用效果不佳,联合两性霉素B静脉注射后患者症状很快好转。有研究显示,两性霉素B腹腔注射可引起严重的化学性腹膜炎,在电解质和(或)酸性溶液中易发生沉淀,若通过腹腔给药可能会失去抗真菌活性16。在PD患者腹腔给药的药代动力学研究中发现,两性霉素B很难从血液中渗透到腹腔中8,镰刀菌属对两性霉素B也有耐药的报道11。但从表1可见病例1和病例3均单用两性霉素B静脉注射,病例2为两性霉素B静脉注射联合腹腔给药,而腹腔给药仅1次并未提及不良反应,这3例患者均预后良好,故两性霉素B使用方法推荐以静脉注射为主。镰刀菌对于PD导管也有入侵,对病例1导管进行显微镜观察,可见真菌堵塞导管的孔隙,导致导管引流缓慢。这6例患者均拔除PD导管并联合抗真菌治疗,其中2例患者重新置管后继续行PD,所以对于镰刀菌性腹膜炎的治疗,建议在抗真菌治疗的同时尽快拔除PD导管,治疗效果好还有重返PD的可能。有研究显示,对血液系统肿瘤及脏器移植患者,镰刀菌感染病死率高,侵袭性镰刀菌病患者总病死率达50%,播散性镰刀菌病病死率达83%,主要死亡原因为败血症、中性粒细胞减少症和肺炎17。但由表1可见镰刀菌性腹膜炎患者,经积极治疗后均存活,考虑与PD患者感染后能及时发现腹透液浑浊,治疗方案选择得当有关。
目前对镰刀菌感染的研究很少,镰刀菌感染引起的PDRP的治疗方案尚无统一,国际PD协会也无相关用药剂量及疗程推荐。表1中4例患者虽使用两性霉素B治疗,但对于用药剂量、频率及累积量并无统一。本例患者采用两性霉素B静脉注射方式,治疗量20 mg,从5 mg/d起始剂量采用爬坡式给药4 d达治疗剂量,继续给予20 mg/72 h治疗,累积量1.5 g停药。对于镰刀菌感染抗真菌常用药,急需动物实验数据来更好地指导临床治疗。若遇到单药治疗效果不佳仍有发热症状患者,可使用PMseq-DNA方法较快获得病原学证据,以便调整治疗方案来挽救生命。

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