Woods G M, Jorgensen J H, Waclawiw M A, Reid C, Wang W, Pegelow C H, Rogers Z R, Iyer R V, Holbrook C T, Kinney T R, Vichinsky E, DeBaun M R, Grossman N J, Thomas M D, Falletta J M
Department of Pediatrics, University of Texas Health Science Center at San Antonio.
J Pediatr Hematol Oncol. 1997 Jul-Aug;19(4):327-33. doi: 10.1097/00043426-199707000-00011.
To evaluate the consequences of prolonged prophylactic penicillin use on the rates of nasopharyngeal colonization with Streptococcus pneumoniae and the prevalence of resistant pneumococcal strains in children with sickle cell anemia.
Nasopharyngeal specimens were obtained from children with sickle cell anemia (Hb SS or Hb S beta degrees thalassemia) at 10 teaching hospitals throughout the United States. These patients were participating in a prospective, randomized, placebo-controlled trial in which they were prescribed prophylactic penicillin before their fifth birthday and were randomized to prophylactic penicillin or placebo after their fifth birthday (PROPS II). The specimens were cultured for S. pneumoniae, and isolates were analyzed for antimicrobial susceptibility to nine commonly prescribed antimicrobial agents.
Of the 226 patients observed, an average of 8.4 specimens were collected per patient. From 1,896 individual culture specimens, 5.5% of the specimens were positive for S. pneumoniae; 27% of patients had at least one positive culture. Nine percent of the study patients had at least one isolate of penicillin intermediate or resistant pneumococci. There was no significant difference in the percent of positive cultures for S. pneumoniae in those patients given penicillin prophylaxis after 5 years of age (4.1%) compared with those patients given placebo after 5 years of age (6.4%). Likewise, there was no significant difference (p = 0.298) in the percent of patients with at least one positive culture for S. pneumoniae in the group given prophylactic penicillin after 5 years of age (21.8%) compared with the group given placebo after 5 years of age (28.3%). There was no difference between the penicillin and placebo groups in the proportion of patients with penicillin intermediate or resistant pneumococci, but there was a trend toward increased carriage of multiply drug-resistant pneumococci in children > 5 years of age receiving prophylactic penicillin compared to children > 5 years of age receiving placebo. The increased colonization rate with multiply drug-resistant organisms of children > 5 years of age receiving penicillin prophylaxis is not statistically significant.
The potential for continued penicillin prophylaxis to contribute to the development of multiply resistant pneumococci should be considered before continuing penicillin prophylaxis in children with sickle cell anemia who are older than 5 years of age. Added to the published data from PROPS II, which demonstrated no apparent advantage to continue prophylaxis, the data support the conclusion that, for children with no history of invasive pneumococcal disease, consideration should be given to discontinue prophylactic penicillin after their fifth birthday.
评估长期预防性使用青霉素对镰状细胞贫血患儿肺炎链球菌鼻咽部定植率及耐药肺炎链球菌菌株流行率的影响。
从美国10家教学医院的镰状细胞贫血（血红蛋白SS型或血红蛋白Sβ0地中海贫血型）患儿中获取鼻咽部标本。这些患者参与了一项前瞻性、随机、安慰剂对照试验，试验中他们在5岁前被给予预防性青霉素，5岁后被随机分为接受预防性青霉素组或安慰剂组（PROPS II）。对标本进行肺炎链球菌培养，并对分离株进行9种常用抗菌药物的药敏分析。
在观察的226例患者中，平均每位患者采集8.4份标本。从1896份个体培养标本中，5.5%的标本肺炎链球菌呈阳性；27%的患者至少有一次培养阳性。9%的研究患者至少有一株青霉素中介或耐药肺炎链球菌。5岁后接受青霉素预防的患者中肺炎链球菌培养阳性率（4.1%）与5岁后接受安慰剂的患者（6.4%）相比无显著差异。同样，5岁后接受预防性青霉素组中至少有一次肺炎链球菌培养阳性的患者百分比（21.8%）与5岁后接受安慰剂组（28.3%）相比无显著差异（p = 0.298）。青霉素组和安慰剂组中青霉素中介或耐药肺炎链球菌患者的比例无差异，但与接受安慰剂的5岁以上儿童相比，接受预防性青霉素的5岁以上儿童多重耐药肺炎链球菌的携带率有增加趋势。接受青霉素预防的5岁以上儿童多重耐药菌定植率增加无统计学意义。
对于5岁以上的镰状细胞贫血患儿，在继续进行青霉素预防之前，应考虑持续预防性使用青霉素导致多重耐药肺炎链球菌产生的可能性。加上PROPS II公布的数据（该数据表明继续预防无明显优势），这些数据支持以下结论：对于无侵袭性肺炎链球菌疾病史的儿童，应考虑在其5岁生日后停止预防性使用青霉素。
