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[儿童肺炎链球菌分离株中pbp2B、ermB、ermA/B、mefA基因与对青霉素和红霉素耐药性的关系]

[Relation of pbp2B, ermB, ermA/B, mefA genes with resistance to penicillin and erythromycin among Streptococcus pneumoniae isolates from children].

作者信息

Ding Yun-fang, Zhang Jian-hua, Mi Zu-huang, Tao Yun-zhen, Qin Ling

机构信息

Department of Medical Laboratory, The Children's Hospital Affiliated to Suzhou University, Suzhou 215003, China.

出版信息

Zhonghua Er Ke Za Zhi. 2005 May;43(5):364-7.

Abstract

OBJECTIVE

To investigate the relation of pbp2B, ermB, ermA/B and mefA genes to penicillin and erythromycin resistance among isolated Streptococcus pneumoniae (Sp) in children.

METHODS

Twenty-six strains of Sp were collected from September 2002 to April 2003 at the Children Hospital of Suzhou University. (1) Twenty-six pneumococcal isolates were obtained from respiratory tract secretions of children with respiratory diseases. (2) Susceptibility of the isolates to penicillin, cefuroxime, ceftriaxone, cefotaxime and erythromycin was determined by E-test. (3) The genes pbp2B, ermB, ermA/B and mefA of the isolates were detected with PCR. (4) The PCR product of pbp2B gene was sequenced. (5) DNA sequences of pbp2B of pneumococcal isolates were compared with those of SpR6 [penicillin sensitive (www.ncbi.nlm.gov/nucleotide, NC-003098)].

RESULTS

Among the 26 isolates studied, pbp2B gene mutation was found in 15(58%) isolates, all were point mutation of A, B, C and D genotypes which were seen in 11(73%), 2(13%), 1(7%) and 1(7%), respectively. The numbers of isolates susceptible to penicillin, cefuroxime, ceftriaxone and cefotaxime were 9(82%), 10(91%), 11(100%) and 11(100%), of 11 non-mutation isolates;numbers of isolates resistant to penicillin, cefuroxime, ceftriaxone, and cefotaxime were 13(87%), 11(73%), 1(7%) and 1(7%) out of 15 isolates with mutation.ErmB, ermA/B, mefA and erm/mef genes were positive in 9(35%), 16(62%), 7(27%) and 21(81%)isolates. MIC of erythromycin was 2 to > 256 mg/L among pneumococcal isolates with erm/mef genes.

CONCLUSION

Among antibiotic resistant pneumococcal isolates in the area, the main basis of penicillin resistance was the mutation of pbp2B genes. Genotype A mutation had the highest rate among the isolates with mutation and manifested as resistance to penicillin and cefuroxime. Expression of either all or any of the ermA, ermB and mef genes led to erythromycin resistance. Antibiotics resistant Sp strains in this area are forming a challenge to efficacy of penicillin and erythromycin.

摘要

目的

探讨儿童分离肺炎链球菌(Sp)中pbp2B、ermB、ermA/B和mefA基因与青霉素及红霉素耐药性的关系。

方法

2002年9月至2003年4月从苏州大学儿童医院收集26株Sp。(1)从呼吸道疾病患儿的呼吸道分泌物中获得26株肺炎球菌分离株。(2)采用E-test法测定分离株对青霉素、头孢呋辛、头孢曲松、头孢噻肟和红霉素的敏感性。(3)采用PCR法检测分离株的pbp2B、ermB、ermA/B和mefA基因。(4)对pbp2B基因的PCR产物进行测序。(5)将肺炎球菌分离株pbp2B的DNA序列与SpR6[青霉素敏感株(www.ncbi.nlm.gov/nucleotide,NC-003098)]的序列进行比较。

结果

在所研究的26株分离株中,15株(58%)分离株发现pbp2B基因突变,均为A、B、C和D基因型的点突变,分别见于11株(73%)、2株(13%)、1株(7%)和1株(7%)。11株非突变分离株中对青霉素、头孢呋辛、头孢曲松和头孢噻肟敏感的分离株数分别为9株(82%)、10株(91%)、11株(100%)和11株(100%);15株突变分离株中对青霉素、头孢呋辛、头孢曲松和头孢噻肟耐药的分离株数分别为13株(87%)、11株(73%)、1株(7%)和1株(7%)。ermB、ermA/B、mefA和erm/mef基因在9株(35%)、16株(62%)、7株(27%)和21株(81%)分离株中呈阳性。在携带erm/mef基因的肺炎球菌分离株中,红霉素的MIC为2至>256mg/L。

结论

该地区抗生素耐药肺炎球菌分离株中,青霉素耐药的主要原因是pbp2B基因突变。基因型A突变在突变分离株中发生率最高,表现为对青霉素和头孢呋辛耐药。ermA、ermB和mef基因全部或任何一个的表达导致红霉素耐药。该地区抗生素耐药Sp菌株对青霉素和红霉素的疗效构成挑战。

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