铜绿假单胞菌感染性肺炎患者的病原菌特征和肺表面活性蛋白B基因多态性和疾病进展与抗菌疗效的关系

Characteristics of pathogens and the relationship between polymorphisms of lung surfactant protein B gene,disease progression and antimicrobial efficacy in patients with Pseudomonas aeruginosa infectious pneumonia

目的分析铜绿假单胞菌感染性肺炎患者的病原菌特征和肺表面活性蛋白B(surfactant protein B,SP–B)基因多态性和疾病进展与抗菌疗效的关系。方法回顾性分析2019年8月至2021年8月绍兴第二医院收治的102例肺炎患者的临床资料,根据是否感染铜绿假单胞菌(Pseudomonas aeruginosa,PA)分成PA组(n=36)和非PA组(n=66)。采用全自动微生物分析仪进行菌株鉴定,采用K–B纸片扩散法检测菌株对常用抗菌药的敏感性;实时聚合酶链式反应–限制性片段长度多态性法检测患者SP–B基因多态性。结果102例肺炎患者共检出PA36株(35.29%),其中耐碳青霉烯类铜绿假单胞菌(carbapenem–resistance Pseudomonas aeruginosa,CRPA)感染6例(16.67%),多重耐药铜绿假单胞菌(multi–drug resistance Pseudomonas aeruginosa,MDRPA)感染12例(33.33%),泛耐药铜绿假单胞菌(pan–drug resistance Pseudomonas aeruginosa,PDRPA)感染2例(5.56%),各年度PA感染率以及CRPA、MDRPA发生率比较,差异无统计学意义(P>0.05);全部36例(100.00%)PA感染患者对氨苄西林耐药,其次为阿莫西林(97.22%)和美罗培南(63.89%),36例PA感染患者对环丙沙星和妥布霉素敏感,敏感率分别为63.89%和61.11%;PA组SP–B 1580位点基因型TT、TC和CC的分布频数与非PA组比较,差异有统计学意义(P<0.05),等位基因T的频率明显低于非PA组,等位基因C的频率明显高于非PA组,差异均有统计学意义(P<0.05)。PA组SP–B 8714位点基因型GG、GC和CC的分布频数与非PA组比较,差异均无统计学意义(P>0.05),等位基因G的频率低于非PA组,差异无统计学意义(P>0.05)。SP–B 1580位点CC、CT和TT基因型肺功能水平差异均有统计学意义(P<0.05),TT基因型患者血氧分压(blood oxygen partial pressure,PaO_(2))、一氧化碳弥散值(diffusing capacity of the lungs for carbon monoxide,DLCO)和一秒钟用力呼气容积(forced expiratory volume in one second,FEV1)/用力肺活量(forced vital capacity,FVC)明显高于CT和TT基因型患者,FVC、FEV1明显低于CT和TT基因型患者,差异均有统计学意义(P<0.05)。结论PA主要对氨苄西林、阿莫西林和美罗培南等多种抗生素耐药,对环丙沙星和妥布霉素敏感,SP–B基因多态性与PA感染性肺炎患者肺损害程度具有相关性,临床可通过检测其表达水平评估患者疾病进展。

Objective To analyze the relationship between pathogen characteristics,lung surface active protein B(SP–B)gene polymorphism,disease progression and antimicrobial efficacy in patients with Pseudomonas aeruginosa(PA)infected pneumonia.Methods The clinical data of 102 patients with pneumonia admitted to Shaoxing Second Hospital from August 2019 to August 2021 were retrospectively analyzed,and they were divided into PA group(n=36)and non-PA group(n=66)according to whether they were infected with PA.Strains were identified by automatic microbiological analyzer,and the sensitivity of strains to commonly used antibacterial drugs was detected by K-B disk diffusion method.SP-B gene polymorphism was detected by real-time polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).Results A total of 36 pastrains(35.29%)were detected in 102 patients with pneumonia,among which 6 cases(16.67%)were infected with carbapenem-resistance Pseudomonas aeruginosa(CRPA).12 cases(33.33%)were infected with multi-drug resistance Pseudomonas aeruginosa(MDRPA).There were two cases of PAN-drug resistance Pseudomonas aeruginosa(PDRPA)infection(5.56%),and there were no significant differences in PA infection rate and incidence of CRPA and MDRPA among years(P>0.05).36 patients with PA infection were completely resistant to ampicillin,followed by amoxicillin(97.22%)and meropenem(63.89%).36 patients with PA infection were sensitive to ciprofloxacin and tobramycin(63.89%and 61.11%,respectively).The distribution frequency of TT,TC and CC of sp-B 1580 genotype in PA group was significantly different from that in non-PA group(P<0.05),and the frequency of allele T were significantly lower than those in non-PA group,while the frequency of allele C was significantly higher than that in non-PA group(P<0.05).The distribution frequency of GG,GC and CC of SP-B 8714 genotype in PA group were not significantly different from those in non-PA group(P>0.05),and the frequency of allele G was lower than that in non-PA group(P>0.05).Lung function levels of CC,CT and TT genotypes at SP-B 1580 were significantly different(P<0.05).Blood oxygen partial pressure(PaO_(2)),carbon monoxide dispersion value(DLCO)and forced expiratory volume in 1 second/forced vital capacity(FEV1/FVC)in TT genotypes were significantly higher than those in CT and TT genotypes.Forced vital capacity(FVC)and forced expiratory volume in one second(FEV1)were significantly lower than those in CT and TT genotypes(P<0.05).Conclusion PA is mainly resistant to ampicillin,amoxicillin,meropenem and other antibiotics,and sensitive to ciprofloxacin and tobramycin.SP-B gene polymorphism is correlated with lung damage in patients with PA infection pneumonia,and the disease progression of patients can be assessed by detecting its expression level.