In vitro effectiveness of colistin, tigecycline and levofloxacin alone and combined with clarithromycin and/or heparin as lock solutions against embedded Acinetobacter baumannii strains

Objectives: To determine the in vitro stability and efficacy of colistin, tigecycline and levofloxacin alone or in combination with clarithromycin and/or heparin as lock solutions against biofilm-embedded Acinetobacter baumannii strains. Methods: Candidate antibiotics (colistin, tigecycline and levofloxacin) were investigated in vitro, either alone or in combination with clarithromycin and/or heparin in solution. The efficacy of antibiotic lock solutions was tested in an in vitro catheter biofilm model against A. baumannii isolated from catheter-related bacteraemia. Results: Candidate antibiotics at 400x MICs combined with clarithromycin (200 mg/mL) and/or heparin (1000 U/mL) were compatible. Colistin, tigecycline and levofloxacin and their combinations with clarithromycin demonstrated bactericidal activity against the biofilm-embedded A. baumannii strains. Compared with other antibiotics alone, the lock solution including only colistin was the best agent to eradicate A. baumannii embedded in the catheter model. When tested antibiotics were used in combination with clarithromycin, the combinations were significantly more effective and more rapid in reducing the live cell number or eliminating A. baumannii colonization in biofilms than each of the antibiotics alone. Conclusions: Catheter lock solutions containing colistin may have the most promise for treating or preventing biofilm-producing catheter infections caused by A. baumannii. Clarithromycin was ultimately effective with the studied antibiotics to reduce live cell number or eradicate A. baumannii colonization in biofilms and could serve as an antibiotic enhancer. Our in vitro model findings now warrant clinical trials to investigate their real role in the management of catheter-related bacteraemia.