
儿童金黄色葡萄球菌脓毒症抗生素治疗现状分析
李媛媛, 李沁原, 张光莉, 田小银, 陈大鹏, 罗征秀
中国当代儿科杂志 ›› 2019, Vol. 21 ›› Issue (4) : 387-392.
儿童金黄色葡萄球菌脓毒症抗生素治疗现状分析
Current status of antibiotic therapy for Staphylococcus aureus sepsis in children
目的 回顾性分析金黄色葡萄球菌脓毒症患儿经验性抗生素治疗现状,探讨治疗模式对其预后的影响。方法 将2014年1月至2017年8月收治的78例金黄色葡萄球菌脓毒症患儿,依据血培养报告金黄色葡萄球菌生长前经验性首选抗生素治疗类型分为碳青霉烯类治疗组(n=16)、β-内酰胺类治疗组(n=37)、万古霉素治疗组(n=15)、万古霉素+β-内酰胺类治疗组(n=10)。收集各组患儿的一般情况、基础疾病、急性生理功能与慢性健康状况评分系统Ⅱ(APACHE Ⅱ)、免疫抑制剂使用史、甲氧西林耐药性及预后资料,进行回顾性分析。采用logistic回归探讨经验性抗生素治疗方案对金黄色葡萄球菌脓毒症患儿临床疗效及预后的影响。结果 各组患儿一般情况、基础疾病、免疫抑制剂使用史、APACHE Ⅱ评分、院内感染、MRSA检出率比较差异无统计学意义(P > 0.05)。四组间脓毒性休克、院内死亡率比较差异有统计学意义(P < 0.05),其中碳青霉烯类治疗组脓毒性休克、院内死亡率均最高(分别为69%、50%)。多因素logistic回归分析结果提示,经验性抗生素治疗类型是金黄色葡萄球菌脓毒症患儿发生脓毒性休克和院内死亡的独立危险因素(P < 0.05);APACHE Ⅱ评分≥ 15是金黄色葡萄球菌脓毒症患儿发生脓毒性休克的独立危险因素(P < 0.05);与使用万古霉素治疗组相比,碳青霉烯类治疗组发生脓毒性休克和院内死亡的风险高(P < 0.05)。结论 不恰当的经验性使用抗生素治疗可能导致儿童金黄色葡萄球菌脓毒症预后不佳。临床疑诊金黄色葡萄球菌脓毒症患儿,不建议经验性使用碳青霉烯类抗菌药物治疗。
Objective To investigate the current status of empirical antibiotic therapy for children with Staphylococcus aureus sepsis and the effect of therapeutic paradigm on prognosis based on a retrospective analysis. Methods A total of 78 children with Staphylococcus aureus sepsis who were admitted from January 2014 to August 2017 were enrolled. According to the preferred empirical antibiotics before the detection of Staphylococcus aureus by blood culture, these children were divided into a carbapenem group with 16 children, a β-lactam group with 37 children, a vancomycin group with 15 children and a vancomycin+β-lactam group with 10 children. A retrospective analysis was performed for related clinical data including general status, underlying diseases, Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score, history of use of immunosuppressant, drug resistance to methicillin and prognosis. A logistic regression analysis was used to investigate the effect of empirical antibiotic therapy on the clinical outcome and prognosis of children with Staphylococcus aureus sepsis. Results There were no significant differences among these groups in general status, underlying diseases, history of use of immunosuppressant, APACHE Ⅱ score, nosocomial infection and detection rate of methicillin-resistant Staphylococcus aureus (P > 0.05). There were significant differences in the incidence rate of septic shock and in-hospital mortality among these four groups (P < 0.05). The carbapenem group had the highest incidence rate of septic shock and in-hospital mortality (69% and 50% respectively). The multivariate logistic regression analysis showed that empirical antibiotic therapy with different antibiotics had different risks for septic shock and in-hospital death in children with Staphylococcus aureus sepsis (P < 0.05), and that an APACHE Ⅱ score of ≥ 15 was an independent risk factor for septic shock in these children (P < 0.05). The carbapenem group had significantly higher risks of septic shock and in-hospital death than the vancomycin group (P < 0.05). Conclusions Inappropriate empirical use of antibiotics may lead to a poor prognosis in children with Staphylococcus aureus sepsis. Empirical use of carbapenems is not recommended for children suspected of Staphylococcus aureus sepsis.
Sepsis / Staphylococcus aureus / Antibiotic / Prognosis / Child
[1] Shankar-Hari M, Phillips GS, Levy ML. Developing a new definition and assessing new clinical criteria for septic shock:for the third international consensus definitions for sepsis and septic shock (sepsis-3)[J]. JAMA, 2016, 315(8):775-787.
[2] Wang Y, Sun B, Yue H, et al. An epidemiologic survey of pediatric sepsis in regional hospitals in China[J]. Pediatr Crit Care Med, 2014, 15(9):814-820.
[3] Ruth A, McCracken CE, Fortenberry JD, et al. Pediatric severe sepsis:current trends and outcomes from the Pediatric Health Information Systems database[J]. Pediatr Crit Care Med, 2014, 15(9):828-838.
[4] 魏泽庆, 沈萍, 陈云波, 等. Mohnarin 2011年度报告:血流感染细菌构成及耐药性[J]. 中华医院感染学杂志, 2012, 22(24):5497-5502.
[5] Schlapbach LJ, Straney L, Alexander J, et al. Mortality related to invasive infections, sepsis, and septic shock in critically ill children in Australia and New Zealand, 2002-13:a multicentre retrospective cohort study[J]. Lancet Infect Dis, 2015, 15(1):46-54.
[6] Ostrowski JA, MacLaren G, Alexander J, et al. The burden of invasive infections in critically ill indigenous children in Australia[J]. Med J Aust, 2017, 206(2):78-84.
[7] Verhoeven PO, Gagnaire J, Botelho-Nevers E, et al. Detection and clinical relevance of Staphylococcus aureus nasal carriage:an update[J]. Expert Rev Anti Infect Ther, 2014, 12(1):75-89.
[8] 李光辉, 朱德妹, 汪复, 等. 2012年中国CHINET血培养临床分离菌的分布及耐药性[J]. 中国感染与化疗杂志, 2014, 14(6):474-481.
[9] Kim CJ, Kim HB, Oh MD, et al. The burden of nosocomial staphylococcus aureus bloodstream infection in South Korea:a prospective hospital-based nationwide study[J]. BMC Infect Dis, 2014, 14:590.
[10] Tong SY, Davis JS, Eichenberger E, et al. Staphylococcus aureus infections:epidemiology, pathophysiology, clinical manifestations, and management[J]. Clin Microbiol Rev, 2015, 28(3):603-661.
[11] Felsenstein S, Bender JM, Sposto R, et al. Impact of a rapid blood culture assay for Gram-positive identification and detection of resistance markers in a pediatric hospital[J]. Arch Pathol Lab Med, 2016, 140(3):267-275.
[12] Jung N, Rieg S. Essentials in the management of S. aureus bloodstream infection[J]. Infection, 2018, 46(4):441-442.
[13] Dellinger RP, Levy MM, Rhodes A, et al. Surviving sepsis campaign:international guidelines for management of severe sepsis and septic shock:2012[J]. Intensive Care Med, 2013, 39(2):165-228.
[14] Zhang D, Micek ST, Kollef MH. Time to appropriate antibiotic therapy is an independent determinant of postinfection ICU and hospital lengths of stay in patients with sepsis[J]. Crit Care Med, 2015, 43(10):2133-2140.
[15] Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children:executive summary[J]. Clin Infect Dis, 2011, 52(3):285-292.
[16] Goldstein B, Giroir B, Randolph A. International pediatric sepsis consensus conference:definitions for sepsis and organ dysfunction in pediatrics[J]. Pediatr Crit Care Med, 2005, 6(1):2-8.
[17] Seymour CW, Liu VX, Iwashyna TJ, et al. Assessment of clinical criteria for sepsis:for the third international consensus definitions for sepsis and septic shock (sepsis-3)[J]. JAMA, 2016, 315(8):762-774.
[18] Weiss SL, Fitzgerald JC, Balamuth F, et al. Delayed antimicrobial therapy increases mortality and organ dysfunction duration in pediatric sepsis[J]. Crit Care Med, 2014, 42(11):2409-2417.
[19] Kumar A, Roberts D, Wood KE, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock[J]. Crit Care Med, 2006, 34(6):1589-1596.
[20] Paul M, Shani V, Muchtar E, et al. Systematic review and metaanalysis of the efficacy of appropriate empiric antibiotic therapy for sepsis[J]. Antimicrob Agents Chemother, 2010, 54(11):4851-4863.
[21] Ferrer R, Martin-Loeches I, Phillips G, et al. Empiric antibiotic treatment reduces mortality in severe sepsis and septic shock from the first hour:results from a guideline-based performance improvement program[J]. Crit Care Med, 2014, 42(8):1749-1755.
[22] Lodise TP, McKinnon PS. Clinical and economic impact of methicillin resistance in patients with Staphylococcus aureus bacteremia[J]. Diagn Microbiol Infect Dis, 2005, 52(2):113-122.
[23] 牛志民, 李艳红. 205例脓毒症患儿生存分析[J]. 临床儿科杂志, 2012, 30(1):18-21.
[24] 邱瑜, 胥志跃, 肖政辉, 等. PICU患儿脓毒症病原学分析及WHO推荐抗感染治疗应用现状[J]. 医学临床研究, 2014, 31(8):1611-1612.
[25] McConeghy KW, Bleasdale SC, Rodvold KA. The empirical combination of vancomycin and a β-lactam for Staphylococcal bacteremia[J]. Clin Infect Dis, 2013, 57(12):1760-1765.
[26] Schweizer ML, Furuno JP, Harris AD, et al. Empiric antibiotic therapy for Staphylococcus aureus bacteremia may not reduce in-hospital mortality:a retrospective cohort study[J]. PLoS One, 2010, 5(7):e11432.
[27] Marchaim D, Kaye KS, Fowler VG, et al. Case-control study to identify factors associated with mortality among patients with methicillin-resistant Staphylococcus aureus bacteraemia[J]. Clin Microbiol Infect, 2010, 16(6):747-752.
[28] 吴琳琳. 住院患儿金黄色葡萄球菌感染的临床研究[D]. 大连:大连医科大学, 2012.
[29] Carrara E, Pfeffer I, Zusman O, et al. Determinants of inappropriate empirical antibiotic treatment:systematic review and meta-analysis[J]. Int J Antimicrob Agents, 2018, 51(4):548-553.
[30] Gasch O, Camoez M, Dominguez MA, et al. Predictive factors for early mortality among patients with methicillin-resistant Staphylococcus aureus bacteraemia[J]. J Antimicrob Chemother, 2013, 68(6):1423-1430.
[31] Marquet K, Liesenborgs A, Bergs J, et al. Incidence and outcome of inappropriate in-hospital empiric antibiotics for severe infection:a systematic review and meta-analysis[J]. Crit Care, 2015, 19:63.
[32] Ibrahim EH, Sherman G, Ward S, et al. The influence of inadequate antimicrobial treatment of bloodstream infections on patient outcomes in the ICU setting[J]. Chest, 2000, 118(1):146-155.
[33] Arias-Ortiz PM, Calderón LD, Castillo JS, et al. Risk factors for methicillin-resistant Staphylococcus aureus bacteremia:a multicenter matched case-control study[J]. Biomedica, 2016, 36(4):612-619.
[34] Stryjewski ME, Szczech LA, Benjamin DK Jr, et al. Use of vancomycin or first-generation cephalosporins for the treatment of hemodialysis-dependent patients with methicillin-susceptible Staphylococcus aureus bacteremia[J]. Clin Infect Dis, 2007, 44(2):190-196.
[35] Stein GE, Wells EM. The importance of tissue penetration in achieving successful antimicrobial treatment of nosocomial pneumonia and complicated skin and soft-tissue infections caused by methicillin-resistant Staphylococcus aureus:vancomycin and linezolid[J]. Curr Med Res Opin, 2010, 26(3):571-588.
[36] Dilworth TJ, Ibrahim O, Hall P, et al. β-Lactams enhance vancomycin activity against methicillin-resistant Staphylococcus aureus bacteremia compared to vancomycin alone[J]. Antimicrob Agents Chemother, 2014, 58(1):102-109.
[37] Wong D, Wong T, Romney M, et al. Comparative effectiveness of β-lactam versus vancomycin empiric therapy in patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia[J]. Ann Clin Microbiol Antimicrob, 2016, 15:27.
[38] 艾宇航. 脓毒症的治疗[J]. 中国感染控制杂志, 2008, 7(5):293-296.
国家临床重点专科建设项目(2011-873)。