Chen Derrick, Cunningham Scott A, Cole Nicolynn C, Kohner Peggy C, Mandrekar Jayawant N, Patel Robin
Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin, USA.
Division of Clinical Microbiology, Mayo Clinic, Rochester, Minnesota, USA.
Antimicrob Agents Chemother. 2017 Mar 24;61(4). doi: 10.1128/AAC.02530-16. Print 2017 Apr.
Failure to eradicate infection is often a result of antimicrobial resistance, which for clarithromycin is typically mediated by specific point mutations in the 23S rRNA gene. The purpose of this study was to define current patterns of antimicrobial susceptibility in isolates derived primarily from the United States and to survey them for the presence of point mutations in the 23S rRNA gene and assess the ability of these mutations to predict phenotypic clarithromycin susceptibility. Antimicrobial susceptibility testing was performed using agar dilution on 413 isolates submitted to Mayo Medical Laboratories for susceptibility testing. For a subset of these isolates, a 150-bp segment of the 23S rRNA gene was sequenced. A total of 1,970 MICs were reported over the 4-year study period. The rate of clarithromycin resistance was high (70.4%), and elevated MICs were frequently observed for metronidazole (82.4% of isolates had an MIC of >8 μg/ml) and ciprofloxacin (53.5% of isolates had an MIC of >1 μg/ml). A total of 111 archived isolates underwent 23S rRNA gene sequencing; we found 95% concordance between genotypes and phenotypes ( = 0.9802). Resistance to clarithromycin was most commonly due to an A2143G mutation (82%), followed by A2142G (14%) and A2142C (4%) mutations. Clinical isolates derived primarily from the United States demonstrated a high rate of clarithromycin resistance and elevated metronidazole and ciprofloxacin MICs. The relative distribution of point mutations at positions 2143 and 2142 in the 23S rRNA gene in clarithromycin-resistant was similar to that reported from other parts of the world; these mutations predict phenotypic resistance to clarithromycin.
未能根除感染通常是抗菌药物耐药性导致的结果，对于克拉霉素而言，耐药性通常由23S rRNA基因中的特定点突变介导。本研究的目的是确定主要来自美国的分离株中当前的抗菌药物敏感性模式，并检测它们23S rRNA基因中的点突变情况，评估这些突变预测克拉霉素表型敏感性的能力。使用琼脂稀释法对提交至梅奥医学实验室进行敏感性检测的413株分离株进行抗菌药物敏感性试验。对这些分离株的一个子集，对23S rRNA基因的150 bp片段进行测序。在4年的研究期间共报告了1970个最低抑菌浓度（MIC）。克拉霉素耐药率很高（70.4%），甲硝唑（82.4%的分离株MIC>8 μg/ml）和环丙沙星（53.5%的分离株MIC>1 μg/ml）的MIC经常升高。共对111株存档分离株进行了23S rRNA基因测序；我们发现基因型和表型之间的一致性为95%（κ = 0.9802）。对克拉霉素的耐药最常见的原因是A2143G突变（82%），其次是A2142G（14%）和A2142C（4%）突变。主要来自美国的临床分离株显示出较高的克拉霉素耐药率以及升高的甲硝唑和环丙沙星MIC。克拉霉素耐药分离株中23S rRNA基因2143和2142位点的点突变相对分布与世界其他地区报道的相似；这些突变可预测对克拉霉素的表型耐药性。
