Endimiani Andrea, Brigante Gioconda, Bettaccini Alessia A, Luzzaro Francesco, Grossi Paolo, Toniolo Antonio Q
Laboratory of Microbiology and Virology, University of Insubria and Ospedale di Circolo e Fondazione Macchi, Varese, Italy.
BMC Infect Dis. 2005 Nov 24;5:106. doi: 10.1186/1471-2334-5-106.
Streptococcus pneumoniae is the leading cause of community-acquired pneumonia (CAP). High global incidence of macrolide and penicillin resistance has been reported, whereas fluoroquinolone resistance is uncommon. Current guidelines for suspected CAP in patients with co-morbidity factors and recent antibiotic therapy recommend initial empiric therapy using one fluoroquinolone or one macrolide associated to other drugs (amoxicillin, amoxicillin/clavulanate, broad-spectrum cephalosporins). Resistance to fluoroquinolones is determined by efflux mechanisms and/or mutations in the parC and parE genes coding for topoisomerase IV and/or gyrA and gyrB genes coding for DNA gyrase. No clinical cases due to fluoroquinolone-resistant S. pneumoniae strains have been yet reported from Italy.
A 72-year-old patient with long history of chronic obstructive pulmonary disease and multiple fluoroquinolone treatments for recurrent lower respiratory tract infections developed fever, increased sputum production, and dyspnea. He was treated with oral levofloxacin (500 mg bid). Three days later, because of acute respiratory insufficiency, the patient was hospitalized. Levofloxacin treatment was supplemented with piperacillin/tazobactam. Microbiological tests detected a S. pneumoniae strain intermediate to penicillin (MIC, 1 mg/L) and resistant to macrolides (MIC >256 mg/L) and fluoroquinolones (MIC >32 mg/L). Point mutations were detected in gyrA (Ser81-Phe), parE (Ile460-Val), and parC gene (Ser79-Phe; Lys137-Asn). Complete clinical response followed treatment with piperacillin/tazobactam.
This is the first Italian case of community-acquired pneumonia due to a fluoroquinolone-resistant S. pneumoniae isolate where treatment failure of levofloxacin was documented. Molecular analysis showed a group of mutations that have not yet been reported from Italy and has been detected only twice in Europe. Treatment with piperacillin/tazobactam appears an effective means to inhibit fluoroquinolone-resistant strains of S. pneumoniae causing community-acquired pneumonia in seriously ill patients.
肺炎链球菌是社区获得性肺炎（CAP）的主要病因。据报道，大环内酯类和青霉素耐药在全球的发生率较高，而氟喹诺酮类耐药并不常见。目前针对合并症因素及近期接受过抗生素治疗的疑似CAP患者的指南推荐，初始经验性治疗采用一种氟喹诺酮类药物或一种大环内酯类药物联合其他药物（阿莫西林、阿莫西林/克拉维酸、广谱头孢菌素）。对氟喹诺酮类药物的耐药性由外排机制和/或编码拓扑异构酶IV的parC和parE基因及/或编码DNA旋转酶的gyrA和gyrB基因的突变所决定。意大利尚未报告过由耐氟喹诺酮类肺炎链球菌菌株引起的临床病例。
一名72岁男性患者，有慢性阻塞性肺疾病病史，因复发性下呼吸道感染多次接受氟喹诺酮类药物治疗，此次出现发热、痰液增多和呼吸困难。给予口服左氧氟沙星（500mg，每日两次）治疗。三天后，因急性呼吸功能不全入院。左氧氟沙星治疗基础上加用哌拉西林/他唑巴坦。微生物学检测发现一株肺炎链球菌，对青霉素中介（MIC，1mg/L），对大环内酯类耐药（MIC>256mg/L），对氟喹诺酮类耐药（MIC>32mg/L）。在gyrA（Ser81-Phe）、parE（Ile460-Val）和parC基因（Ser79-Phe；Lys137-Asn）检测到点突变。使用哌拉西林/他唑巴坦治疗后临床症状完全缓解。
这是意大利首例由耐氟喹诺酮类肺炎链球菌分离株引起的社区获得性肺炎病例，记录了左氧氟沙星治疗失败的情况。分子分析显示了一组在意大利尚未报告过、在欧洲仅被检测到两次的突变。对于重症患者中引起社区获得性肺炎的耐氟喹诺酮类肺炎链球菌菌株，哌拉西林/他唑巴坦治疗似乎是一种有效的治疗手段。
