Hanage William P, Huang Susan S, Lipsitch Marc, Bishop Cynthia J, Godoy Daniel, Pelton Stephen I, Goldstein Richard, Huot Heather, Finkelstein Jonathan A
Department of Infectious Disease Epidemiology, Imperial College, London, UK.
J Infect Dis. 2007 Feb 1;195(3):347-52. doi: 10.1086/510249. Epub 2006 Dec 27.
In response to the selective pressure of pneumococcal conjugate vaccine, increased asymptomatic carriage of antibiotic-nonsusceptible nonvaccine serotypes (NVTs) has been observed. Possible mechanisms include de novo acquisition of resistance, serotype switching, introduction of new clones, and expansion of existing clones.
To investigate the process of increased antibiotic nonsusceptibility among replacing serotypes, we applied multilocus sequence typing to samples of 126 and 222 pneumococci collected in 2001 and 2004, respectively, from the nasopharynges of children <7 years of age in 16 Massachusetts communities.
We found no evidence of penicillin resistance due to either serotype switching or de novo acquisition. Nonetheless, resistance increased through the expansion of previously recognized clones of NVTs, particularly in serotypes 19A, 15A, and 35B. In 19A, several unrelated clones increased in frequency, whereas, in the other 2 serotypes, single resistant lineages were responsible for the increased prevalence of resistant strains.
The decreased prevalence of antibiotic resistance with the introduction of heptavalent pneumococcal conjugate vaccine is likely to be partially eroded over time as vaccine-included serotypes are replaced by resistant clones of NVTs. The clinical significance of this will depend on the pathogenic potential of replacing clones to cause local (e.g., otitis media) or invasive disease.
为应对肺炎球菌结合疫苗的选择性压力,已观察到抗生素不敏感非疫苗血清型(NVTs)的无症状携带率增加。可能的机制包括耐药性的重新获得、血清型转换、新克隆的引入以及现有克隆的扩增。
为研究替代血清型中抗生素不敏感性增加的过程,我们对分别于2001年和2004年从马萨诸塞州16个社区7岁以下儿童鼻咽部采集的126株和222株肺炎球菌样本进行多位点序列分型。
我们没有发现因血清型转换或重新获得而导致青霉素耐药的证据。尽管如此,耐药性通过NVTs先前已识别克隆的扩增而增加,特别是在19A、15A和35B血清型中。在19A血清型中,几个不相关的克隆频率增加,而在其他两种血清型中,单一耐药谱系导致耐药菌株的患病率增加。
随着七价肺炎球菌结合疫苗的引入,抗生素耐药率的降低可能会随着时间的推移而部分受到侵蚀,因为疫苗包含的血清型被NVTs的耐药克隆所取代。这一情况的临床意义将取决于替代克隆引起局部(如中耳炎)或侵袭性疾病的致病潜力。