Cystic Fibrosis Centre, Department of Paediatric Respiratory Medicine, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrech, The Netherlands.
Clin Microbiol Infect. 2012 Jun;18(6):567-74. doi: 10.1111/j.1469-0691.2011.03627.x. Epub 2011 Aug 29.
Despite intensive eradication therapy, some CF patients with early Pseudomonas aeruginosa infection rapidly develop a chronic infection. To elucidate factors associated with this persistence, bacterial characteristics of early P. aeruginosa isolates were analysed that were either eradicated rapidly or persisted despite multiple antimicrobial treatments. Eighty-six early infection episodes were studied. First P. aeruginosa isolates from patients with eradication (36) or persistent infection (16) were included; isolates from patients with intermittent infection (34) were omitted from the study. Virulence assays, antimicrobial resistance, cytotoxicity and mutation frequencies were analysed in vitro. P. aeruginosa was genotyped by SNP-array. Transcriptomic profiles of two eradicated and two persistent strains were compared. Nineteen per cent of patients developed persistent infection; 42% achieved eradication. Secretion of virulence factors and mutation frequencies were highly variable among both eradicated and persistent isolates and were not different between the groups. Cytotoxicity was present in 57% of eradicated vs. 100% of persistent isolates (p <0.01). None of the isolates were resistant to antibiotics. The isolates were genotypically highly diverse. Multivariate analysis showed that in vitro determined bacterial characteristics could not predict persistence after first P. aeruginosa infection. Preliminary transcriptomic data showed increased expression of some genes related to a metabolic pathway. The early onset of chronic infection was not associated with (in vitro determined) bacterial characteristics only. Although the persistent isolates were more often cytotoxic, for the individual patient it was not possible to predict the risk of persistence based on bacterial characteristics. Unknown factors such as host-pathogen and pathogen-pathogen interactions should be further explored.
尽管进行了强化清除治疗，但一些早期铜绿假单胞菌感染的 CF 患者仍迅速发展为慢性感染。为了阐明与这种持续性相关的因素，分析了快速清除或尽管多次抗菌治疗仍持续存在的早期铜绿假单胞菌分离株的细菌特征。研究了 86 例早期感染发作。纳入了快速清除（36 例）或持续感染（16 例）患者的首次铜绿假单胞菌分离株；从间歇性感染患者（34 例）中分离的分离株被排除在研究之外。在体外分析了毒力测定、抗生素耐药性、细胞毒性和突变频率。通过 SNP 芯片对铜绿假单胞菌进行基因分型。比较了两种清除和两种持续的菌株的转录组谱。19%的患者发生持续感染；42%的患者清除。在清除和持续分离株中，毒力因子的分泌和突变频率均高度可变，两组之间无差异。清除组的细胞毒性为 57%，而持续组为 100%（p<0.01）。没有分离株对抗生素有耐药性。分离株的基因型高度多样化。多变量分析表明，体外确定的细菌特征不能预测首次铜绿假单胞菌感染后的持续性。初步转录组数据显示，一些与代谢途径相关的基因表达增加。慢性感染的早期发作不仅与（体外确定的）细菌特征有关。尽管持续分离株的细胞毒性更高，但对于个体患者而言，基于细菌特征预测持续性的风险是不可能的。宿主-病原体和病原体-病原体相互作用等未知因素应进一步探讨。
