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七价肺炎球菌结合疫苗时代的耐抗生素肺炎链球菌:多社区样本中携带情况的预测因素

Antibiotic-resistant Streptococcus pneumoniae in the heptavalent pneumococcal conjugate vaccine era: predictors of carriage in a multicommunity sample.

作者信息

Finkelstein Jonathan A, Huang Susan S, Daniel James, Rifas-Shiman Sheryl L, Kleinman Ken, Goldmann Donald, Pelton Stephen I, DeMaria Alfred, Platt Richard

机构信息

Department of Ambulatory Care and Prevention, Harvard Medical School/HPHC, Boston, Massachusetts 02215, USA.

出版信息

Pediatrics. 2003 Oct;112(4):862-9. doi: 10.1542/peds.112.4.862.

Abstract

OBJECTIVE

Despite immunization with heptavalent pneumococcal conjugate vaccine (PCV7), the rising prevalence of antibiotic resistance makes Streptococcus pneumoniae a continuing threat to child health. Data on carriage of resistant organisms by healthy children in communities in which immunization with PCV7 has been implemented will help to define and decrease these risks further.

METHODS

Children who were <7 years old, resided in a study community, and presented for routine well care or a "sick" visit between March 13 and May 11, 2001, at 31 primary care practices in 16 geographically distinct Massachusetts communities were studied. Consenting parents provided demographic information and data on potential risk factors for carriage of S pneumoniae and of penicillin-nonsusceptible S pneumoniae (PNSP). S pneumoniae isolates from nasopharyngeal specimens were tested for resistance to commonly used antibiotics including penicillin, ceftriaxone, erythromycin, and trimethoprim/sulfamethoxazole. Isolates were serotyped and grouped into PCV7-included serotypes, potentially cross-reactive serotypes (ie, an organism of a serogroup included in the vaccine), or non-PCV7 serotypes. Diagnosis on the day of collection, history of recent antibiotic use, and history of PCV7 immunization were obtained by chart review. Separate bivariate and multivariate analyses were performed to identify correlates of colonization with S pneumoniae and colonization with PNSP, accounting for clustering within communities.

RESULTS

S pneumoniae was isolated from the nasopharynx of 190 (26%) of the 742 children studied. Of the 166 tested, 33% were nonsusceptible to penicillin, with 14% showing intermediate susceptibility (minimum inhibitory concentration [MIC] 0.12-1.0) and 19% fully resistant (MIC > or =2). Nonsusceptibility to other antibiotics was common, including ceftriaxone (14%), erythromycin (22%), and trimethoprim/sulfa (31%); 20% of S pneumoniae isolates were not susceptible to > or =3 antibiotics. Thirty-six percent of isolates were of serotypes covered by PCV7; 30% were of PCV7 serogroups and potentially cross-reactive, but not 1 of the 7 included serotypes; and 34% were unrelated to PCV7 serogroups. Nonsusceptibility to penicillin was more common in PCV7-included strains (45%) and potentially cross-reactive strains (51%) than in non-PCV7 serotypes (8%). Risk factors for PNSP colonization included child care attendance (odds ratio [OR]: 3.9; 95% confidence interval [CI]: 2.3-6.5), current respiratory tract infection (OR: 4.7; 95% CI: 2.5-8.6), and recent antibiotic use (OR: 1.7; 95% CI: 1.0-2.8). PCV7 immunization was associated with decreased carriage of PCV7-included serotypes but not with an overall decrease in S pneumoniae colonization or with a decline in PNSP colonization.

CONCLUSIONS

In this multicommunity sample, pneumococcal antibiotic resistance was common and was most frequently found in PCV7-included and PCV7 serogroup strains. The long-term impact of PCV7 immunization will be partially determined by the protection that it affords against invasive infection with potentially cross-reactive serotypes, as well as the virulence and future resistance patterns of unrelated serotypes.

摘要

目的

尽管使用了七价肺炎球菌结合疫苗(PCV7)进行免疫接种,但抗生素耐药性的日益普遍使肺炎链球菌继续对儿童健康构成威胁。关于已实施PCV7免疫接种的社区中健康儿童携带耐药菌的数据,将有助于进一步明确并降低这些风险。

方法

对2001年3月13日至5月11日期间在马萨诸塞州16个地理位置不同的社区的31家初级保健机构就诊的742名7岁以下儿童进行了研究,这些儿童居住在研究社区,前来进行常规健康检查或“患病”就诊。同意参与的家长提供了人口统计学信息以及关于肺炎链球菌和青霉素不敏感肺炎链球菌(PNSP)携带的潜在风险因素的数据。对从鼻咽标本中分离出的肺炎链球菌菌株进行常用抗生素耐药性检测,包括青霉素、头孢曲松、红霉素和甲氧苄啶/磺胺甲恶唑。对分离菌株进行血清分型,并分为PCV7包含的血清型、潜在交叉反应血清型(即疫苗中包含的血清群中的一种微生物)或非PCV7血清型。通过病历审查获取采集当天的诊断、近期抗生素使用史和PCV7免疫接种史。进行了单独的双变量和多变量分析,以确定肺炎链球菌定植和PNSP定植的相关因素,同时考虑社区内的聚集情况。

结果

在所研究的742名儿童中,有190名(26%)从鼻咽中分离出肺炎链球菌。在166株检测菌株中,33%对青霉素不敏感,其中14%表现为中度敏感(最低抑菌浓度[MIC]为0.12 - 1.0),19%完全耐药(MIC≥2)。对其他抗生素不敏感的情况也很常见,包括头孢曲松(14%)、红霉素(22%)和甲氧苄啶/磺胺(31%);20%的肺炎链球菌分离株对≥3种抗生素不敏感。36%的分离株属于PCV7覆盖的血清型;30%属于PCV7血清群且可能交叉反应,但不是7种包含血清型中的任何一种;34%与PCV7血清群无关。在PCV7包含的菌株(45%)和潜在交叉反应菌株(51%)中,对青霉素不敏感的情况比非PCV7血清型(8%)更常见。PNSP定植的风险因素包括入托(优势比[OR]:3.9;95%置信区间[CI]:2.3 - 6.5)、当前呼吸道感染(OR:4.7;95% CI:2.5 - 8.6)和近期抗生素使用(OR:1.7;95% CI:1.0 - 2.8)。PCV7免疫接种与PCV7包含血清型的携带率降低有关,但与肺炎链球菌定植的总体减少或PNSP定植的下降无关。

结论

在这个多社区样本中,肺炎球菌抗生素耐药性很常见,且最常出现在PCV7包含的菌株和PCV7血清群菌株中。PCV7免疫接种的长期影响将部分取决于它对潜在交叉反应血清型侵袭性感染的保护作用,以及无关血清型的毒力和未来耐药模式。

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