Impact of minocycline, polymyxin B, meropenem, and amikacin on growth-prevention of Acinetobacter baumannii with various biofilm-forming capabilities

BACKGROUND: Acinetobacter baumannii is a clinically challenging pathogen with biofilm (BF)- forming capabilities, making eradication difficult. The objective of this study was to compare in vitro activity of minocycline, polymyxin B, meropenem, and amikacin and evaluate the effectiveness in preventing BF formation utilizing previously validated methodology. METHODS: Minimum inhibitory concentrations (MIC) were performed on all isolates in duplicate using CLSI standards. Tryptic soy broth plus 1% dextrose (TSB+D1%) was used to quantify BF formation of 12 clinically unique and diverse strains of A. baumannii. Biofilm prevention concentration (BPC) was defined as the concentration of drug where no biofilm attachment was observed, as determined by optical density (OD). BPC was determined by evaluating increasing concentrations of antibiotic in TSB+D1% for 48 hours. BF was quantified by measuring OD of each well at 570nm via spectrophotometer. Previously described BF adherence categories were utilized to define BF strength (OD(570) > 2 = strong; OD(570) 1–2 = moderate; OD(570) >0.5 <1 = weak; OD(570) ≤ 0.5 = none). RESULTS: Twelve clinical isolates were evaluated with a full range of BF formation capabilities. Prevention of BF formation was observed at concentrations below the MIC by 2.57 ± 4.12-fold for minocycline, 5.57 ± 8.97-fold for polymyxin B, 5.77 ± 17.56-fold for meropenem, and 0.72 ± 0.35-fold for amikacin. Minocycline prevented BF formation at or below the MIC for 75% of isolates tested vs. 67% for polymyxin B, 33% for meropenem, and 33% for amikacin. Free drug concentrations at the end of a dosing interval, derived from pharmacokinetic data, imply that BF would be prevented for 75% of minocycline-exposed isolates vs. 58.3% polymyxin B-, 8.3% meropenem-, and 8.3% amikacin- exposed isolates. CONCLUSION: Minocycline, polymyxin B and meropenem prevented BF formation at clinically relevant concentrations. Prompt antimicrobial administration may be critical to prevent attachment of pathogen. BF production increased or remained unchanged in the presence of amikacin. Due to toxicity concerns and variation in resistance patterns, minocycline is a viable treatment option against A. baumannii. Additional studies are warranted. DISCLOSURES: K. LaPlante, Merck: Grant Investigator, Grant recipient. Pfizer: Grant Investigator, Grant recipient. Cempra: Scientific Advisor, Consulting fee. The Medicines Company: Grant Investigator, Grant recipient. Allergan: Scientific Advisor, Consulting fee. Bard/ Davol: Scientific Advisor, Consulting fee. Ocean Spray: Grant Investigator and Scientific Advisor, Consulting fee and Grant recipient. Zavante: Scientific Advisor, Consulting fee. Achaogen: Scientific Advisor, Consulting fee.