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[马尔马拉大学医院分离出的首例耐甲硝唑拟杆菌属菌种:多形拟杆菌]

[The first metronidazole-resistant Bacteroides species isolated at Marmara University Hospital: Bacteroides thetaiotaomicron].

作者信息

Toprak Ülger Nurver, Sayın Elvan, Soyad Ad, Dane Faysal, Söyletir Güner

机构信息

Marmara University Faculty of Medicine, Department of Medical Microbiology, Istanbul, Turkey.

出版信息

Mikrobiyol Bul. 2013 Oct;47(4):717-21. doi: 10.5578/mb.5064.

DOI:10.5578/mb.5064
PMID:24237441
Abstract

Bacteroides species, the predominant constituents of the human intestinal microbiota can cause serious intraabdominal and postoperative wound infections and bacteremia. Moreover, these bacteria are more resistant to antimicrobial agents than the other anaerobes. The limited number of the antimicrobials, such as carbapenems, beta-lactam/beta-lactamase inhibitors and nitroimidazoles are highly effective in eliminating Bacteroides. However, a few metronidazole-resistant isolates have been reported from several countries recently. The nim genes (nim A-G) are suggested to be responsible for the majority of the metronidazole resistance. Here, we describe a metronidazole-resistant Bacteroides thetaiotaomicron isolated from a blood culture. A gram-negative obligate anaerobic rod was isolated from the postoperative 5th day blood culture of a 62-year-old male patient with adenocarcinoma of the pancreas head. The strain was identified as B.thetaiotaomicron by using a combination of conventional tests and commercially available biochemical kits. Antimicrobial susceptibility testing was performed by agar dilution method. The resistance genes were investigated by means of PCR using specific primer pairs for nim gene. The purified PCR product was sequenced and analyzed by comparison of the consensus sequences with GenBank sequences. The MIC for metronidazole was 16 mg/L. Although the strain was intermediate according the CLSI criteria, it was resistant (> 4 mg/L) according to EUCAST criteria. The isolate was nim gene positive, and nucleotide sequencing of the PCR product shared 100% similarity with nimE gene (emb |AM042593.1 |). On the other hand the isolate was susceptible to carbapenems and sulbactam-ampicillin. Following administration of ampicillin-sulbactam, the patient's fever disappeared after 24 hours. The clinical condition improved considerably and he was discharged at day 8. The patient was followed up at the medical oncology clinic; however he died due to disease progression six months after surgery. Since anaerobic bacteremia is associated with high mortality rate, prompt diagnosis and proper management are critical. The studies on Bacteroides bacteremia have revealed adverse outcomes in patients receiving antibiotics to which the bacterium was resistant. In the present case, the metronidazole-resistant organism would be reported as susceptible according to CLSI breakpoint value and on account of this result the treatment might lead to clinical failure. Therefore EUCAST MIC values seem to be more rational in case of Bacteroides antibiotic susceptibility testing.

摘要

拟杆菌属是人类肠道微生物群的主要组成部分,可引起严重的腹腔内感染、术后伤口感染和菌血症。此外,这些细菌比其他厌氧菌对抗菌药物更具耐药性。有限的几种抗菌药物,如碳青霉烯类、β-内酰胺/β-内酰胺酶抑制剂和硝基咪唑类,对消除拟杆菌非常有效。然而,最近在几个国家都报道了一些对甲硝唑耐药的分离株。nim基因(nim A-G)被认为是导致大多数甲硝唑耐药的原因。在此,我们描述了一株从血培养中分离出的对甲硝唑耐药的嗜内脏拟杆菌。从一名62岁患有胰头腺癌男性患者术后第5天的血培养中分离出一株革兰氏阴性专性厌氧杆菌。通过传统试验和市售生化试剂盒相结合的方法,将该菌株鉴定为嗜内脏拟杆菌。采用琼脂稀释法进行药敏试验。使用针对nim基因的特异性引物对,通过PCR研究耐药基因。对纯化的PCR产物进行测序,并通过将共有序列与GenBank序列进行比较来分析。该菌株对甲硝唑的最低抑菌浓度(MIC)为16mg/L。虽然根据美国临床和实验室标准协会(CLSI)标准该菌株为中介型,但根据欧洲抗菌药物敏感性试验委员会(EUCAST)标准它是耐药的(>4mg/L)。该分离株nim基因呈阳性,PCR产物的核苷酸测序与nimE基因(登录号:emb |AM042593.1 |)有100%的相似性。另一方面,该分离株对碳青霉烯类和舒巴坦-氨苄西林敏感。给予氨苄西林-舒巴坦后,患者的发热在24小时后消退。临床状况明显改善,他在第8天出院。患者在医学肿瘤诊所接受随访;然而,他在手术后6个月因疾病进展而死亡。由于厌氧菌血症与高死亡率相关,及时诊断和适当处理至关重要。关于拟杆菌菌血症的研究表明,接受该细菌耐药的抗生素治疗的患者会出现不良后果。在本病例中,根据CLSI断点值,对甲硝唑耐药的菌株会被报告为敏感,基于此结果,治疗可能会导致临床失败。因此,在进行拟杆菌药敏试验时,EUCAST的MIC值似乎更合理。

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