title: In vitro activity of levofloxacin against planktonic and biofilm Stenotrophomonas maltophilia lifestyles under conditions relevant to pulmonary infection in cystic fibrosis, and relationship with SmeDEF multidrug efflux pump expression.
abstract: The activity of levofloxacin against planktonic and biofilm Stenotrophomonas maltophilia cells and the role played by the multidrug efflux pump SmeDEF were evaluated under conditions relevant to the cystic fibrosis (CF) lung. MIC, MBC and MBEC of levofloxacin were assessed, against five CF strains, under 'standard' (CLSI-recommended) and 'CF-like' (pH 6.8, 5% CO2, in a synthetic CF sputum) conditions. Levofloxacin was tested against biofilms at concentrations (10, 50 and 100 μg mL(-1)) corresponding to achievable serum levels and sputum levels by aerosolisation. smeD expression was evaluated, under both conditions, in planktonic and biofilm cells by RT-PCR. The bactericidal effect of levofloxacin was decreased, in three out of five strains tested, under 'CF-like' conditions (MBC: 2-4 vs 8-16 μg mL(-1), under 'standard' and 'CF-like' conditions, respectively). Biofilm was intrinsically resistant to levofloxacin, regardless of conditions tested (MBECs ≥ 100 μg mL(-1) for all strains). Only under 'CF-like' conditions, smeD expression increased during planktonic-to-biofilm transition, and in biofilm cells compared to stationary planktonic cells. Our findings confirmed that S. maltophilia biofilm is intrinsically resistant to therapeutic concentrations of levofloxacin. Under conditions relevant to CF, smeD overexpression could contribute to levofloxacin resistance. Further studies are warranted to define the clinical relevance of our findings.
authors.affiliation: Department of Medical, Oral and Biotechnological Sciences, 'G. d'Annunzio' University of Chieti-Pescara, Chieti, Via dei Vestini 31, 66100 Italy Laboratory of Clinical Microbiology, Center of Excellence on Aging and Translational Medicine (CeSI-MeT), 'G. d'Annunzio' University of Chieti-Pescara, Via Luigi Polacchi, 66100 Chieti, Italy.
authors.forename: Arianna
authors.initials: A
authors.lastname: Pompilio
authors.affiliation: Department of Medical, Oral and Biotechnological Sciences, 'G. d'Annunzio' University of Chieti-Pescara, Chieti, Via dei Vestini 31, 66100 Italy Laboratory of Clinical Microbiology, Center of Excellence on Aging and Translational Medicine (CeSI-MeT), 'G. d'Annunzio' University of Chieti-Pescara, Via Luigi Polacchi, 66100 Chieti, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Crocetta
authors.affiliation: Laboratory of Clinical Microbiology, Center of Excellence on Aging and Translational Medicine (CeSI-MeT), 'G. d'Annunzio' University of Chieti-Pescara, Via Luigi Polacchi, 66100 Chieti, Italy Department of Pharmacy, 'G. d'Annunzio' University of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Verginelli
authors.affiliation: Department of Medical, Oral and Biotechnological Sciences, 'G. d'Annunzio' University of Chieti-Pescara, Chieti, Via dei Vestini 31, 66100 Italy Laboratory of Clinical Microbiology, Center of Excellence on Aging and Translational Medicine (CeSI-MeT), 'G. d'Annunzio' University of Chieti-Pescara, Via Luigi Polacchi, 66100 Chieti, Italy gdibonaventura@unich.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Di Bonaventura
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D003550:Cystic Fibrosis / Q000150:complications; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D019450:Genes, MDR; D016905:Gram-Negative Bacterial Infections / Q000209:etiology / Q000382:microbiology; D006801:Humans; D064704:Levofloxacin / Q000494:pharmacology*; D018410:Pneumonia, Bacterial / Q000209:etiology / Q000382:microbiology; D020615:Stenotrophomonas maltophilia / Q000187:drug effects* / Q000502:physiology*
chemical_list: D000900:Anti-Bacterial Agents; D064704:Levofloxacin
keywords: biofilm; cystic fibrosis; levofloxacin; lung infection; multidrug efflux pump; Stenotrophomonas maltophilia