Emergence and Spread in French Hospitals of Methicillin-Resistant Staphylococcus aureus with Increasing Susceptibility to Gentamicin and Other Antibiotics

Oxacillin (methicillin) resistance in methicillin-resistant Staphylococcus aureus (MRSA) is associated with an increased incidence of resistance to other antibiotics, which has increased since it was first reported in 1969. In 1992 a new phenotype of MRSA arose in France; this was characterized by a heterogeneous expression of resistance to oxacillin and susceptibility to various antibiotics, including gentamicin but also tetracycline, minocycline, lincomycin, pristinamycin, co-trimoxazole, rifampin, and fusidic acid. In French hospitals a longitudinal nationwide surveillance of antibiotic resistance in S. aureus has allowed for the detection of changes in antibiotic susceptibility profiles. Seven French clinical laboratories (six from the mainland and one from the West Indies) reported the results of susceptibility testing of 57,347 S. aureus strains isolated in their institutes between 1992 and 1998. Over a 7-year period the incidence of isolation of gentamicin-susceptible MRSA (GS-MRSA) strains has steadily increased to represent, in 1998, 46.8 to 94.4% of the MRSA strains, irrespective of the overall incidence of MRSA. Two predominant types recognized by pulsed-field gel electrophoresis (PFGE) accounted for the majority of the GS-MRSA in different mainland hospitals, both differing from the predominant type observed in the French West Indies. Some GS-MRSA and gentamicin-resistant MRSA (GR-MRSA) strains had closely related PFGE profiles, and hybridization studies confirmed the lack in GS-MRSA of the aac6′-aph2" gene, which confers resistance to all aminoglycosides, with conservation of the ant4′ gene, which confers resistance to kanamycin, tobramycin, and amikacin. Thus, it is likely that certain GS-MRSA strains could have emerged from GR-MRSA strains by excision or deletion of the aac6′-aph2" gene.

耐甲氧西林金黄色葡萄球菌（methicillin-resistant Staphylococcus aureus, MRSA）对苯唑西林（oxacillin，又称甲氧西林）的耐药性，往往伴随其他抗菌药物耐药发生率的升高，该现象自1969年首次被报道以来呈上升趋势。1992年法国出现了一种新型MRSA表型：该表型以对苯唑西林的异质性耐药，以及对庆大霉素、四环素、米诺环素、林可霉素、普那霉素、复方新诺明、利福平、夫西地酸等多种抗菌药物的易感为特征。法国全国范围内开展的金黄色葡萄球菌耐药性纵向监测项目，得以捕捉抗菌药物敏感性谱的变化。1992至1998年间，法国7家临床实验室（6家位于本土，1家位于西印度群岛）上报了其机构内分离的57347株金黄色葡萄球菌的药敏试验结果。在7年监测周期内，庆大霉素敏感型MRSA（gentamicin-susceptible MRSA, GS-MRSA）的分离率稳步上升，至1998年时，无论MRSA整体流行率如何，GS-MRSA已占MRSA分离株的46.8%至94.4%。脉冲场凝胶电泳（pulsed-field gel electrophoresis, PFGE）分型显示，法国本土多家医院的多数GS-MRSA菌株归属于两种优势基因型，这两种基因型均与法属西印度群岛的优势流行基因型存在差异。部分GS-MRSA与庆大霉素耐药型MRSA（gentamicin-resistant MRSA, GR-MRSA）菌株的PFGE图谱高度相似；杂交实验证实，GS-MRSA菌株缺失了介导所有氨基糖苷类耐药的aac6′-aph2"基因，但保留了介导卡那霉素、妥布霉素和阿米卡星耐药的ant4′基因。据此推测，部分GS-MRSA菌株可能由GR-MRSA菌株通过切除或缺失aac6′-aph2"基因演化而来。