International Journal of Antimicrobial Agents 27 (2006) 300–302 Emergence of linezolid-resistant Staphylococcus aureus during treatment of pulmonary infection in a patient with cystic fibrosis Ana C. Gales a,∗ , H´ elio S. Sader a,b , Soraya S. Andrade a , Larissa Lutz c , Ad˜ ao Machado c , Afonso L. Barth c a Laborat´ orio Alerta, Universidade Federal de S˜ ao Paulo, S˜ ao Paulo, Brazil b JMI Laboratories, North Liberty, IA, USA c Unidade de Microbiologia, Servi¸ co de Patologia Cl´ ınica, Hospital de Cl´ ınicas, Porto Alegre, RS, Brazil Received 22 August 2005; accepted 8 November 2005 Abstract We report the first linezolid-resistant Staphylococcus aureus strain isolated in Brazil. The strain was isolated from a 10-year-old female patient with cystic fibrosis (CF) who received repeated and prolonged courses of low-dose linezolid. The strain belonged to the Brazilian endemic methicillin-resistant S. aureus clone, and the G2576U mutation was identified in domain V of the 23S rRNA. Detection of this mechanism of resistance in a CF patient is very worrisome, as these patients may become a reservoir for further dissemination of resistant strains. Our findings emphasise the importance of optimal dosage of linezolid to prevent the emergence of resistance. © 2006 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. Keywords: Staphylococcus aureus; Linezolid; Drug resistance; Cystic fibrosis 1. Introduction Linezolid is the first member of the oxazolidinone class of antimicrobials approved for clinical use in 2000 [1]. Line- zolid is active against the vast majority of clinically important Gram-positive cocci, including multidrug-resistant Staphylo- coccus spp., Enterococcus spp. and streptococci [2]; acquired resistance is extremely rare. Linezolid inhibits the formation of the initiation complex formed with mRNA, fMet-tRNA and the 30S ribosomal subunit [3]. Mutations in the cen- tral loop of domain V of 23S rRNA have been associated with resistance to linezolid in several species [3–5]. To our knowledge, only four cases of linezolid-resistant Staphylo- coccus aureus have been reported previously and none of them involved cystic fibrosis (CF) patients [4–7]. ∗ Corresponding author. Present address: Rua Leandro Dupr´ et, 188, S˜ ao Paulo, SP 04025-010, Brazil. Tel.: +55 11 5081 2819; fax: +55 11 5571 5180. E-mail address: galesac@aol.com (A.C. Gales). 2. Case report A 10-year-old female with CF and recurrent methicillin- resistant S. aureus (MRSA) pulmonary infections was treated with linezolid for the first time in December 2000 owing to poor clinical response to glycopeptides, including continu- ous infusion of vancomycin. The patient received multiple courses of linezolid between December 2000 and July 2002. Linezolid regimens administered to the patient are described in Table 1. On 17 July 2002, she presented with clinical deterioration due to a new episode of lung infection after 55 days of continuous treatment. At that time, sputum was collected for bacteriological analysis and linezolid therapy was changed to vancomycin plus quinupristin/dalfopristin. An S. aureus strain (JMI-700) isolated from sputum cul- ture was categorised as resistant to linezolid by the disk diffusion method. Antimicrobial susceptibility testing was repeated using broth dilution methods as recommended by the Clinical and Laboratory Standards Institute [8]. Line- zolid resistance was also confirmed by agar dilution [8] and Etest (AB Biodisk, Solna, Sweden) methods. Owing to this 0924-8579/$ – see front matter © 2006 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. doi:10.1016/j.ijantimicag.2005.11.008