Parallel evolution of linezolid-resistant Staphylococcus aureus in patients with cystic fibrosis

被引:0
作者
Pitcher, Nicholas J. [1 ]
Feder, Andries [2 ]
Bolden, Nicholas [3 ]
Zirbes, Christian F. [1 ]
Pamatmat, Anthony J. [1 ]
Boyken, Linda [4 ]
Hill, Jared J. [1 ]
Bartels, Alyssa R. [1 ]
Thurman, Andrew L. [5 ]
Reeb, Valerie C. [6 ]
Porterfield, Harry S. [7 ]
Moustafa, Ahmed M. [2 ,3 ]
Planet, Paul J. [2 ,3 ,8 ]
Fischer, Anthony J. [1 ]
机构
[1] Univ Iowa, Carver Coll Med, Stead Family Dept Pediat, Iowa City, IA 52242 USA
[2] Childrens Hosp Philadelphia, Philadelphia, PA USA
[3] Univ Penn, Perelman Sch Med, Philadelphia, PA USA
[4] Univ Iowa, Carver Coll Med, Dept Pathol, Iowa City, IA USA
[5] Univ Iowa, Carver Coll Med, Dept Internal Med, Iowa City, IA USA
[6] Univ Iowa, State Hyg Lab, Coralville, IA USA
[7] NIH, Clin Ctr, Bethesda, MD USA
[8] Amer Museum Nat Hist, Inst Comparat Genom, New York, NY USA
来源
MICROBIOLOGY SPECTRUM | 2023年
关键词
Staphylococcus aureus; linezolid; MRSA; ribosomal RNA; hypermutation;
D O I
暂无
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Linezolid is an antibiotic used to treat serious Staphylococcus aureus infections. Resistance to linezolid is considered rare but could emerge with repeated dosing. We recently reported widespread prescription of linezolid for a cohort of patients with cystic fibrosis (CF). The goals of this study were to determine the incidence of linezolid-resistant methicillin-resistant Staphylococcus aureus (MRSA) in CF and identify molecular mechanisms for linezolid resistance. We identified patients who cultured S. aureus resistant to linezolid with minimum inhibitory concentration (MIC) >4 at the University of Iowa CF Center between 2008 and 2018. We obtained isolates from these patients and retested susceptibility to linezolid using broth microdilution. We used whole genome sequencing to perform phylogenetic analysis of linezolid-resistant isolates and examine sequences for mutations or accessory genes that confer linezolid resistance. Between 2008 and 2018, 111 patients received linezolid, and 4 of these patients cultured linezolid-resistant S. aureus. We sequenced 11 resistant and 21 susceptible isolates from these 4 subjects. Phylogenetic analysis indicated that linezolid resistance developed in ST5 or ST105 backgrounds. Three individuals had linezolid-resistant S. aureus with a G2576T mutation in 23S rRNA. One of these subjects additionally had a mutS(-) mutL(-) hypermutating S. aureus that produced five resistant isolates with multiple ribosomal subunit mutations. In one subject, the genetic basis for linezolid resistance was unclear. We conclude that linezolid resistant S. aureus can occur through multiple genetic mechanisms in patients with repeated exposure to this antibiotic.
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页数:17
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