256. Role of an Older Tetracycline for Treatment of Multidrug-resistant Acinetobacter spp. Infections: Understanding the Enhanced Potency of Minocycline!
Session: Poster Abstract Session: Diagnostic Microbiology; Antimicrobial Sensitivities
Thursday, October 3, 2013
Room: The Moscone Center: Poster Hall C
  • IDWEEK 2013 Minocycline 256.pdf (111.1 kB)
  • Background: An intravenous formulation of minocycline (MINO) has recently become available for clinical use. In contrast to numerous older tetracyclines, MINO has high measurable activity against Acinetobacter spp. (ACB). To quantify MINO activity against contemporary (2007-2011) isolates; and its potential therapeutic role, a collection of 5,478 ACB were analyzed compared to tetracycline (TETR), doxycycline (DOXY) and numerous other agents.

    Methods: ACB collections (year 2007-2011) from the USA (760 strains), Europe (EU; 1,196), Latin America (LATAM; 1,498) and Asia-Pacific (APAC; 2,024) were susceptibility (S) tested using reference CLSI broth microdilution methods and CLSI/USA-FDA breakpoints (BPs). Cross-S calculations using TETR as a surrogate marker for MINO- and DOXY-S were also applied (target accuracy at >95%).

    Results: Activity of tetracyclines rank MINO (MIC50/90, 1/8 g/ml) > DOXY (MIC50/90, 2/>8 g/ml) > TETR (MIC50/90, >8/>8 g/ml). MINO inhibited 64.3, 79.1 and 90.9% of ACB at ≤2, ≤4 (CLSI/USA-FDA BP), and ≤8 g/ml, respectively; 19-49% greater than other class agents. MINO and tigecycline had comparable inhibition rates (46-48%) at ≤0.5 g/ml. MINO coverage of ACB strains was higher (% ≤4 g/ml) in LATAM (MIC50, 0.5 g/ml; 91.7%) > APAC=USA (MIC50, 1-2 g/ml; 75.1-75.3%) > EU (MIC50, 2 g/ml; 72.5%). DOXY and TETR only inhibited (≤4 g/ml) 30.2 to 59.6% of all ACB. The most potent agents tested were colistin (MIC90, 1 g/ml) and polymyxin B (MIC90, 0.5 g/ml), all other S rates ranged from only 17.7% (piperacillin/tazobactam [P/T]) to 39.4% (imipenem [IMP]); see Table. Finally, TETR used as a surrogate to predict S to DOXY and MINO using a ≤4 g/ml BP was highly accurate (99.76% [MINO] and 99.70% [DOXY]), but those results grossly underestimated the potential MINO use against ACB isolates (Table).

    Conclusion: Current surveillance data identifies MINO as a strong candidate for infections caused by ACB among USA-FDA-approved agents; and coverages (% S) potentially ranging from 64.3-90.9% (≤2 to ≤8 g/ml) as dictated by ECOFF values and CLSI/USA-FDA BPs. MINO should be considered for intravenous treatment of serious ACB infections; but guided by direct MINO testing, not surrogate TETR marker S results.

    Ronald Jones, MD1, Matthew Stilwell2, Olga Lomovskaya3 and Michael Dudley, PharmD3, (1)JMI Laboratories Inc, North Liberty, IA, (2)Jmi Laboratories Inc, North Liberty, IA, (3)Rempex Pharmaceuticals, Inc, San Diego, CA


    R. Jones, Rempex Pharmaceuticals: Grant Investigator, Grant recipient

    M. Stilwell, Rempex Pharmaceuticals: Grant Investigator, Grant recipient

    O. Lomovskaya, Rempex Pharmaceuticals: Employee, Salary

    M. Dudley, Rempex Pharmaceuticals: Employee, Salary

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