Bacteriostatic and bactericidal activity of levofloxacin against clinical isolates from cystic fibrosis patients

Abstract

Chronic microbial colonisation of the major airwaysleading to debilitating exacerbation of pulmonary infectionis the major cause of morbidity and mortality in patientswith cystic fibrosis. The microbial pathogens mostcommonly reported include Staphylococcus aureus, Hae-mophilus influenzae, Pseudomonas aeruginosa and Bur-kholderia cepacia. Aggressive antibiotic therapy with anincreasing number of antimicrobial agents has undoubt-edly contributed to the control of infections due to S.aureus and H. influenzae. In contrast, P. aeruginosastrains, mainly the mucoid alginate-producing variants, areseldom eradicated [1, 2].Levofloxacin is a new fluoroquinolone with a broadantibacterial spectrum encompassing gram-positive (e.g.Streptococcus pneumoniae and S. aureus) and gram-negative (e.g. Enterobacteriaceae and P. aeruginosa)bacteria [3]. Levofloxacin reaches lung concentrationshigher than other currently available fluoroquinolones andcan be administered once daily [4]. Recently, the in vitroand in vivo clinical efficacy of levofloxacin against P.aeruginosa infections was reviewed [4], and levofloxacinseems suitable for the treatment of respiratory infections incystic fibrosis patients. We report here the results of acomparative in vitro study in which levofloxacin and otherantimicrobial agents were tested against cystic fibrosisisolates collected at our hospital.Eighty strains isolated from consecutive respiratoryspecimens of cystic fibrosis patients collected betweenMarch and July 2000 were studied: 20 mucoid P.aeruginosa, 20 non-mucoid P. aeruginosa,20S. aureus,ten B. cepacia, ten H. influenzae. Care was taken toexclude isolates from replicate cultures of the samepatients, and the numbers of isolates of each specieswere chosen according to isolation frequency. All of the B.cepacia strains belonged to genomovar III. Referencestrains from the American Type Culture Collection(ATCC) were used as controls. Minimum inhibitoryconcentrations of levofloxacin, ciprofloxacin, piperacil-lin/tazobactam, ceftazidime, meropenem, and tobramycinwere determined using the E test (AB Biodisk, Solna,Sweden) according to the manufacturer’s instructions. Thebreakpoints for susceptibility, intermediate susceptibilityand resistance of all drugs, including levofloxacin, weredetermined according to the guidelines of the NationalCommittee of Clinical Laboratory Standards [5]. Oxacillinresistance in S. aureus was tested using Mueller–Hintonbroth with NaCl according to National Committee ofClinical Laboratory Standards’ guidelines [5].Killing curves were performed for five P. aeruginosa (2slime-producing) clinical isolates and the control strain P.aeruginosa ATCC 27853 in Mueller–Hinton broth (DifcoLaboratories, Detroit, MI, USA) at a starting cell densityof approximately 10