Youssef Souad, Rodriguez Gilhen, Rolston Kenneth V, Champlin Richard E, Raad Issam I, Safdar Amar
From Department of Infectious Diseases, Infection Control, and Employee Health (SY, GR, KVR, IIR, AS); and Department of Blood and Marrow Transplantation (REC), M. D. Anderson Cancer Center, Houston, Texas.
Medicine (Baltimore). 2007 Mar;86(2):69-77. doi: 10.1097/md.0b013e31803eb176.
Streptococcus pneumoniae infections can cause serious systemic disease in patients following hematopoietic stem cell transplantation (HSCT), and the response to pneumococcal vaccine is inadequate in most HSCT recipients. We evaluated the clinical spectrum of pneumococcal disease and vaccine-breakthrough infections in HSCT recipients at our cancer center in a retrospective analysis of all consecutive episodes of S. pneumoniae infection from 1989 through 2005. During the study period, 7888 patients underwent HSCT at our center; we identified 47 HSCT recipients with 54 S. pneumoniae infections. The overall incidence of S. pneumoniae infection was 7 per 1000 HSCTs. The incidence was higher in recipients of allogeneic grafts than in recipients of autologous grafts (9 vs. 5 per 1000 HSCTs, respectively; p <or= 0.012). Thirty-two of the 47 patients (68%) had leukemia or lymphoma; 24 patients (51%) had a malignancy that was in complete remission. Seventeen patients (36%) had graft-versus-host disease, which was chronic in 16. The 54 episodes of S. pneumoniae infection occurred 433 +/- 669 days after HSCT; 5 patients (11%) had multiple episodes. Four episodes of S. pneumoniae infection occurred within 100 days following transplantation (45 +/- 49 d); 2 of these were during the pre-engraftment period and 3 were nosocomial infections. All 50 late post-transplant episodes (93%), which occurred 473 +/- 671 days following transplantation, were community-acquired infections (p < 0.00016). Thirty-three episodes (61%) presented as bacteremic pneumonia, 10 (19%) as pneumonia, and 8 (15%) as uncomplicated S. pneumoniae bacteremia alone. Logistic regression analysis showed that patients receiving systemic corticosteroids had increased risk for bacteremic pneumonia (odds ratio [OR], 11.7; 95% confidence intervals [CI], 1.371-99.280; p <or= 0.025). Patients with lymphoma (OR, 6.101; 95% CI, 1.106-33.640; p <or= 0.04) were more likely to develop pneumonia alone. In 27 episodes (93%) among 29 in which S. pneumoniae susceptibility testing was performed, the patients received concordant antimicrobials. Among the 6 patients (13%) who died of S. pneumoniae infection, 4 had S. pneumoniae bacteremic pneumonia and only 1 had chronic GVHD. Admission to a critical care unit at the onset of infection (OR, 15.5; 95% CI, 2.116-113.541; p <or= 0.007) and each unit increase in APACHE II score increase the probability of death (OR, 1.9; 95% CI, 1.181-3.054; p <or= 0.008). All 5 (11%) patients who developed vaccine-breakthrough S. pneumoniae infection (546 +/- 732 d following vaccination) had pneumonia, and in 4 patients concurrent bacteremia also occurred. A serious S. pneumoniae infection in HSCT recipients occurred more commonly in patients with lymphoma and patients receiving high-dose systemic corticosteroid therapy. It is noteworthy that there were no cases of extrapulmonary organ infection in HSCT recipients who presented with S. pneumoniae infection at our institution.
肺炎链球菌感染可在造血干细胞移植(HSCT)患者中引发严重的全身性疾病,并且大多数HSCT受者对肺炎球菌疫苗的反应不足。我们通过对1989年至2005年期间所有连续性肺炎链球菌感染病例进行回顾性分析,评估了我们癌症中心HSCT受者中肺炎球菌疾病的临床谱和疫苗突破性感染情况。在研究期间,我们中心有7888例患者接受了HSCT;我们确定了47例发生54次肺炎链球菌感染的HSCT受者。肺炎链球菌感染的总体发生率为每1000例HSCT中有7例。异基因移植受者的感染发生率高于自体移植受者(分别为每1000例HSCT中有9例和5例;p≤0.012)。47例患者中有32例(68%)患有白血病或淋巴瘤;24例患者(51%)的恶性肿瘤处于完全缓解状态。17例患者(36%)发生了移植物抗宿主病,其中16例为慢性。54次肺炎链球菌感染发生在HSCT后433±669天;5例患者(11%)有多次感染发作。4次肺炎链球菌感染发生在移植后100天内(45±49天);其中2次发生在植入前期,3次为医院感染。所有50次移植后期感染发作(93%)发生在移植后473±671天,均为社区获得性感染(p<0.00016)。33次发作(61%)表现为菌血症性肺炎,10次(19%)为肺炎,8次(15%)仅为无并发症的肺炎链球菌菌血症。逻辑回归分析显示,接受全身性皮质类固醇治疗的患者发生菌血症性肺炎的风险增加(优势比[OR]为11.7;95%置信区间[CI]为1.371 - 99.280;p≤0.025)。淋巴瘤患者(OR为6.101;95%CI为1.106 - 33.640;p≤0.04)更易单独发生肺炎。在29次进行了肺炎链球菌药敏试验的发作中有此27次发作(93%),患者接受了与之相符的抗菌药物治疗。在6例死于肺炎链球菌感染的患者(13%)中,4例患有肺炎链球菌菌血症性肺炎且仅1例患有慢性移植物抗宿主病。感染发作时入住重症监护病房(OR为15.5;95%CI为2.116 - 113.541;p≤0.007)以及急性生理与慢性健康状况评分系统(APACHE II)评分每增加一个单位,死亡概率增加(OR为1.9;95%CI为1.181 - 3.054;p≤0.008)。所有5例(11%)发生疫苗突破性肺炎链球菌感染的患者(接种疫苗后546±732天)均患有肺炎,4例患者还并发了菌血症。HSCT受者中严重的肺炎链球菌感染在淋巴瘤患者和接受高剂量全身性皮质类固醇治疗的患者中更为常见。值得注意的是,在我们机构发生肺炎链球菌感染的HSCT受者中没有肺外器官感染病例。