Jean Baptiste, Crolle Maelys, Pollani Candice, Le Guilloux Adèle, Martin-Blondel Guillaume, Tattevin Pierre, Le Bot Audrey, Luque Paz David, Guérin François, Cattoir Vincent, Armand-Lefevre Laurence, Gueye Signara, Lescure François-Xavier, Duval Xavier, Massip Clémence, Delobel Pierre
Service des Maladies Infectieuses et Tropicales, Centre Hospitalier Universitaire (CHU) de Toulouse, Université Paul Sabatier Toulouse III, Toulouse, France.
Laboratoire de Bactériologie-Hygiène, CHU de Toulouse, Université Paul Sabatier Toulouse III, Toulouse, France.
JAMA Netw Open. 2024 Dec 2;7(12):e2451353. doi: 10.1001/jamanetworkopen.2024.51353.
Infective endocarditis (IE) caused by Staphylococcus aureus is associated with high mortality, approximately 20% to 30%, mostly in the first month, with no improvement in recent decades. Current opinion is that antistaphylococcal penicillin and cefazolin are equally effective in treating methicillin-susceptible S aureus (MSSA) IE, and both are recommended as possible first-line treatments. Most MSSA strains carry the β-lactamase blaZ gene, and some blaZ-positive strains exhibit an inoculum effect, meaning increased minimum inhibitory concentrations at high inoculum. This reduced susceptibility to an antibiotic at high bacterial inoculum may be particularly relevant in IE, where vegetations have very high bacterial densities.
To evaluate the association between phenotypic characteristics of S aureus isolates, β-lactam used, and outcome in patients with MSSA IE.
DESIGN, SETTINGS, AND PARTICIPANTS: This retrospective case series included MSSA cases treated at 3 French university hospitals between February 2016 and February 2022. The study included patients who had clinical isolates available and had definite or possible S aureus IE that involved native or prosthetic valves. Data were analyzed from July 2023 to June 2024.
MSSA isolates were tested for the presence of blaZ and for inoculum effects to cefazolin and oxacillin. The association between first-month mortality and the β-lactam used, the presence of blaZ, and the presence of an inoculum effect to the treatment received was evaluated.
This study included 216 patients with MSSA IE (median [IQR] age, 65 [49-73] years; 152 [70.4%] male) who were treated with antistaphylococcal penicillin (139 [64.4%]) or cefazolin (77 [35.6%]). One-month mortality of left-sided IE was 44 of 180 patients (24.4%), with no overall difference between patients treated with antistaphylococcal penicillin or cefazolin. However, 1-month mortality was higher in patients infected with blaZ-positive strains than with blaZ-negative strains (38 of 129 [29.5%] vs 6 of 51 [11.8%]; P = .01), and with strains with an inoculum effect to the β-lactam received than with strains without an inoculum effect (25 of 62 [40.3%] vs 13 of 67 [19.4%]; P = .005). On multivariable analysis, the presence of an inoculum effect was independently associated with first-month mortality (HR, 2.84; 95% CI, 1.28-6.30; P = .01).
In this case series of MSSA IE, the presence of an inoculum effect to the β-lactam received was a risk factor for death in the first month. Phenotyping MSSA isolates for inoculum effect may guide β-lactam choice and improve outcomes.
金黄色葡萄球菌引起的感染性心内膜炎（IE）死亡率较高，约为20%至30%，大多在第一个月内，近几十年来并无改善。目前观点认为，抗葡萄球菌青霉素和头孢唑林在治疗甲氧西林敏感金黄色葡萄球菌（MSSA）IE方面同样有效，二者均被推荐作为可能的一线治疗药物。大多数MSSA菌株携带β-内酰胺酶blaZ基因，一些blaZ阳性菌株表现出接种量效应，即在高接种量时最低抑菌浓度增加。在IE中，细菌接种量高时对抗生素敏感性降低这一情况可能尤为重要，因为赘生物处细菌密度非常高。
评估MSSA IE患者中金黄色葡萄球菌分离株的表型特征、使用的β-内酰胺类药物与预后之间的关联。
设计、地点和参与者：这项回顾性病例系列研究纳入了2016年2月至2022年2月期间在3家法国大学医院接受治疗的MSSA病例。研究包括有临床分离株且患有明确或可能的金黄色葡萄球菌IE（累及天然瓣膜或人工瓣膜）的患者。数据于2023年7月至2024年6月进行分析。
检测MSSA分离株中blaZ的存在情况以及对头孢唑林和苯唑西林的接种量效应。评估第一个月死亡率与使用的β-内酰胺类药物、blaZ的存在情况以及对所接受治疗的接种量效应之间的关联。
本研究纳入了216例MSSA IE患者（年龄中位数[四分位间距]为65[49 - 73]岁；152例[70.4%]为男性），他们接受了抗葡萄球菌青霉素治疗（n = 139[64.4%]）或头孢唑林治疗（n = 77[35.6%]）。左侧IE患者的1个月死亡率为180例中的44例（24.4%），接受抗葡萄球菌青霉素或头孢唑林治疗的患者总体上无差异。然而，感染blaZ阳性菌株的患者1个月死亡率高于blaZ阴性菌株患者（129例中的38例[29.5%]对51例中的6例[11.8%]；P = 0.01），对所接受β-内酰胺类药物有接种量效应的菌株感染患者的死亡率高于无接种量效应的菌株感染患者（62例中的25例[40.3%]对67例中的13例[19.4%]；P = 0.005）。多变量分析显示，接种量效应的存在与第一个月死亡率独立相关（风险比，2.84；95%置信区间，1.28 - 6.30；P = 0.01）。
在这个MSSA IE病例系列中，对所接受β-内酰胺类药物有接种量效应是第一个月死亡的危险因素。对MSSA分离株进行接种量效应表型分析可能有助于指导β-内酰胺类药物的选择并改善预后。
