Centre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux, Paris, France.
Antimicrob Agents Chemother. 2011 Feb;55(2):775-81. doi: 10.1128/AAC.00861-10. Epub 2010 Dec 6.
Clarithromycin was the drug of choice for Mycobacterium abscessus infections until inducible resistance due to erm(41) was described. Because M. abscessus was split into M. abscessus sensu stricto, Mycobacterium massiliense, and Mycobacterium bolletii, we looked for erm(41) in the three species and determined their clarithromycin susceptibility levels. Ninety strains were included: 87 clinical strains from cystic fibrosis patients (61%) and others (39%), representing 43 M. abscessus, 30 M. massiliense, and 14 M. bolletii strains identified on a molecular basis, and 3 reference strains. Clarithromycin and azithromycin MICs were determined by broth microdilution and Etest with a 14-day incubation period. Mutations in rrl (23S rRNA gene) known to confer acquired clarithromycin resistance were also sought. erm(41) was detected in all strains but with two deletions in all M. massiliense strains. These strains were indeed susceptible to clarithromycin (MIC(90) of 1 μg/ml) except for four strains with rrl mutations. M. abscessus strains harbored an intact erm(41) but had a T/C polymorphism at the 28th nucleotide: T28 strains (Trp10 codon) demonstrated inducible clarithromycin resistance (MIC(90) of >16 μg/ml), while C28 strains (Arg10) were susceptible (MIC(90) of 2 μg/ml) except for two strains with rrl mutations. M. bolletii strains had erm(41) sequences similar to the sequence of the T28 M. abscessus group, associated with inducible clarithromycin resistance (MIC(90) of >16 μg/ml). erm(41) sequences appeared species specific within the M. abscessus group and were fully concordant with clarithromycin susceptibility when erm(41) sequencing was associated with detection of rrl mutations. Clarithromycin-resistant strains, including the six rrl mutants, were more often isolated in cystic fibrosis patients, but this was not significantly associated with a previous treatment.
克拉霉素曾是治疗脓肿分枝杆菌感染的首选药物，直到发现 erm(41)诱导耐药性。由于脓肿分枝杆菌被分为脓肿分枝杆菌、马萨诸塞分枝杆菌和博莱氏分枝杆菌，我们在这三种细菌中寻找 erm(41)并确定它们对克拉霉素的敏感性。共纳入 90 株菌：61%为囊性纤维化患者的临床株（87 株），39%为其他株，代表 43 株脓肿分枝杆菌、30 株马萨诸塞分枝杆菌和 14 株博莱氏分枝杆菌，这些菌株均基于分子生物学方法鉴定，还有 3 株参考株。通过肉汤微量稀释法和含 14 天孵育期的 Etest 法测定克拉霉素和阿奇霉素的 MIC。还寻找了已知导致获得性克拉霉素耐药的 rrl（23S rRNA 基因）突变。所有菌株均检测到 erm(41)，但所有马萨诸塞分枝杆菌菌株均存在 erm(41)缺失。这些菌株对克拉霉素均敏感（MIC90 为 1 μg/ml），除 4 株具有 rrl 突变的菌株外。脓肿分枝杆菌菌株含有完整的 erm(41)，但在第 28 个核苷酸处存在 T/C 多态性：T28 株（Trp10 密码子）表现出诱导性克拉霉素耐药（MIC90>16 μg/ml），而 C28 株（Arg10）敏感（MIC90 为 2 μg/ml），除 2 株具有 rrl 突变的菌株外。博莱氏分枝杆菌菌株的 erm(41)序列与 T28 脓肿分枝杆菌组的序列相似，与诱导性克拉霉素耐药相关（MIC90>16 μg/ml）。在脓肿分枝杆菌组内，erm(41)序列具有种特异性，当与 rrl 突变检测相结合时，erm(41)序列与克拉霉素敏感性完全一致。包括 6 株 rrl 突变株在内的克拉霉素耐药株在囊性纤维化患者中更常分离到，但这与既往治疗无显著相关性。
