Carbapenem-Resistance in Gram-Negative Bacilli and Intravenous Minocycline: An Antimicrobial Stewardship Approach at the Detroit Medical Center

Abstract

In the era of carbapenem-resistance in Acinobacter baumannii and Enterobacteriaceae, there are limited treatment options for these pathogens. It is essential that clinicians fully assess all available therapeutic alternatives for these multidrug-resistant organisms. We herein describe the approach of the antimicrobial stewardship team at the Detroit Medical Center (DMC) for the evaluation and use of intravenous (IV) minocycline for the treatment of these resistant organisms, given potential advantages of IV minocycline over tigecycline and doxycycline. In vitro analyses at the DMC demonstrated good activity against A. baumannii (78% susceptibility), including 74% of carbapenem-resistant strains, but limited activity against our carbapenem-resistant K.pneumoniae (12% susceptibility.) Based in part on these results, IV minocycline was added to the formulary, primarily for the treatment of carbapenem-resistant A. baumannii. Early experience has been positive: 6/9 (67%) of patients who received IV minocycline had infections due to these organisms cured, including 6/7 (86%) who received doses of 200 mg twice daily.

Factores asociados a nefrotoxicidad por polimixina B en un hospital universitario de Neiva, Colombia. 2011-2015

“…No obstante, en la última década, ante el surgimiento y alta tasa de mortalidad en infecciones invasoras causadas por BGN-MR, polimixina B, en monoterapia o en combinación con otros antimicrobianos activos contra BGN-MR, permanece como el principal antimicrobiano usado para agentes de este tipo en nuestro medio 1,7,8 . Históricamente, la falla renal asociada al uso de polimixina B fluctúa entre 14 y 60% [8][9][10][11][12][13] .…”

Minocycline for the treatment of Acinetobacter spp. infection

“…While tigecycline shows excellent in vitro activity against CRAB, enthusiasm surrounding this agent has been tempered due to pharmacokinetic limitations of the drug, the development of resistance while on therapy, and its inability to demonstrate non-inferiority in the treatment of hospital-acquired and ventilator-associated pneumonia with suboptimal drug levels in the epithelial lining fluid being suggested as a possible cause for its poor performance. [4,5] Because infections due to CRAB are most commonly seen in the lungs, blood, and urine, the role of tigecycline in the treatment of these resistant pathogens remains unclear and its efficacy uncertain. [5] Minocycline has been proposed as a potential alternative to tigecycline given its pharmacokinetic advantage in the blood, where it achieved higher serum concentrations (2.1 to 6.6 µg/mL with the 200 mg IV dose) and its FDAapproved indication for treatment of infections due to Acinetobacter spp.…”

“…[4,5] Because infections due to CRAB are most commonly seen in the lungs, blood, and urine, the role of tigecycline in the treatment of these resistant pathogens remains unclear and its efficacy uncertain. [5] Minocycline has been proposed as a potential alternative to tigecycline given its pharmacokinetic advantage in the blood, where it achieved higher serum concentrations (2.1 to 6.6 µg/mL with the 200 mg IV dose) and its FDAapproved indication for treatment of infections due to Acinetobacter spp. as well as for urinary tract infections.…”

“…Additionally, with the availability of both IV and PO minocycline formulations, and the relatively high bioavailability of the oral formulation, the ability to switch from IV to PO routes with minocycline is attractive. [5] Minocycline being more lipophilic allows for increased tissue penetration with longer half-lives. The most common efflux pump mediating tetracycline resistance does not affect minocycline.…”

“…The most common efflux pump mediating tetracycline resistance does not affect minocycline. [5] Tigecycline was synthetically designed to overcome these efflux pumps and has activity if either TetA or TetB is present. Current literature suggests that the development of such resistance has been associated with the TetX gene and, perhaps most importantly for A. baumannii, the overexpression of various efflux pumps (AdeABC, AdeIJK, AdeFGH, AbeM, AdeDE).…”