Chong Yong Pil, Park Su-Jin, Kim Hee Sueng, Kim Eun Sil, Kim Mi-Na, Park Ki-Ho, Kim Sung-Han, Lee Sang-Oh, Choi Sang-Ho, Jeong Jin-Yong, Woo Jun Hee, Kim Yang Soo
From the Department of Infectious Diseases (YPC, KHP, SHK, SOL, SHC, JHW, YSK) and Department of Laboratory Medicine (MNK), Asan Medical Center, University of Ulsan College of Medicine, Center for Antimicrobial Resistance and Microbial Genetics (SJP, HSK, ESK, JYJ, YSK), Seoul, Republic of Korea.
Medicine (Baltimore). 2013 Mar;92(2):98-108. doi: 10.1097/MD.0b013e318289ff1e.
Persistent Staphylococcus aureus bacteremia (SAB) that fails to respond to appropriate antibiotic therapy is associated with poor outcomes. Comprehensive prospective studies on risk factors and outcomes of persistent bacteremia are limited. We investigated outcomes and risk factors encompassing clinical, pharmacokinetic, microbiologic, and genotypic characteristics associated with persistent bacteremia using a case-control study nested in a prospective cohort of patients with SAB at a tertiary-care hospital from August 2008 through September 2010. We compared the clinical characteristics, management, and outcomes of patients with persistent bacteremia (≥7 d) with controls with resolving bacteremia (<3 d). To detect associations between microbiologic and genotypic characteristics of methicillin-resistant S. aureus (MRSA) isolates and persistent bacteremia, we determined the heteroresistance phenotype, SCCmec type, agr genotype and functionality, multilocus sequence typing, and presence of 41 virulence genes. Our cohort consisted of 483 patients; 76 (15.7%) had persistent bacteremia, 212 (43.5%) had resolving bacteremia. In the multivariate analysis, independent risk factors associated with persistent bacteremia were community-onset bacteremia (odds ratio [OR], 2.91; 95% confidence interval [CI], 1.24-6.87), bone and joint infection (OR, 5.26; 95% CI, 1.45-19.03), central venous catheter-related infection (OR, 3.36; 95% CI, 1.47-7.65), metastatic infection (OR, 36.22; 95% CI, 12.71-103.23), and methicillin resistance (OR, 16.99; 95% CI, 5.53-52.15). For patients with eradicable foci, delay (>3 d) in the removal of the infection focus was significantly associated with persistent bacteremia (OR, 2.18; 95% CI, 1.05-4.55). There were no significant associations of persistent bacteremia with high vancomycin minimal inhibitory concentration, vancomycin heteroresistance, and microbiologic/genotypic characteristics of MRSA isolates. However, initial vancomycin trough level <15 mg/L was an independent risk factor for persistent MRSA bacteremia (OR, 4.25; 95% CI, 1.51-11.96) in the multivariate analysis. Clinical outcomes were significantly worse for patients with persistent bacteremia. Relapse of bacteremia and attributable mortality within 12 weeks after SAB were significantly higher in patients with persistent bacteremia than in those with resolving bacteremia (9.2% [7/76] vs. 2.4% [5/212], p = 0.02 and 21.1% [16/76] vs. 9.4% [20/212], p = 0.009, respectively). In conclusion, patients with SAB should be given early aggressive treatment strategies, including early source control and maintenance of a vancomycin trough level ≥15 mg/L, to reduce the risk of persistent bacteremia.
对适当抗生素治疗无反应的持续性金黄色葡萄球菌菌血症（SAB）与不良预后相关。关于持续性菌血症的危险因素和预后的全面前瞻性研究有限。我们通过一项巢式病例对照研究，调查了2008年8月至2010年9月在一家三级护理医院的SAB前瞻性队列患者中，与持续性菌血症相关的临床、药代动力学、微生物学和基因型特征的预后及危险因素。我们比较了持续性菌血症（≥7天）患者与菌血症缓解（<3天）对照患者的临床特征、治疗及预后。为检测耐甲氧西林金黄色葡萄球菌（MRSA）分离株的微生物学和基因型特征与持续性菌血症之间的关联，我们确定了异质性耐药表型、SCCmec类型、agr基因型和功能、多位点序列分型以及41个毒力基因的存在情况。我们的队列包括483例患者；76例（15.7%）有持续性菌血症，212例（43.5%）有菌血症缓解。在多变量分析中，与持续性菌血症相关的独立危险因素包括社区获得性菌血症（比值比[OR]，2.91；95%置信区间[CI]，1.24 - 6.87）、骨和关节感染（OR，5.26；95% CI，1.45 - 19.03）、中心静脉导管相关感染（OR，- 3.36；95% CI，1.47 - 7.65）、转移性感染（OR，36.22；95% CI，12.71 - 103.23）和耐甲氧西林（OR，16.99；95% CI, 5.53 - 52.15）。对于有可根除病灶的患者，感染灶清除延迟（>3天）与持续性菌血症显著相关（OR，2.18；95% CI，1.05 - 4.55）。持续性菌血症与万古霉素最低抑菌浓度高、万古霉素异质性耐药以及MRSA分离株的微生物学/基因型特征无显著关联。然而，在多变量分析中，初始万古霉素谷浓度<15 mg/L是持续性MRSA菌血症的独立危险因素（OR，4.25；95% CI，1.51 - 11.96）。持续性菌血症患者的临床结局明显更差。SAB后12周内菌血症复发率和归因死亡率在持续性菌血症患者中显著高于菌血症缓解患者（分别为9.2%[7/76]对2.4%[5/212]，p = 0.02；21.1%[16/76]对9.4%[20/212]，p = 0.009）。总之，SAB患者应尽早给予积极的治疗策略，包括早期源头控制和维持万古霉素谷浓度≥15 mg/L，以降低持续性菌血症的风险。
