Intravenous minocycline in multidrug-resistant infections: a profile of its use in the USA with a focus on Acinetobacter infections

Abstract

Intravenous (IV) minocycline (Minocin Ò) is approved in the USA for use in patients with infections due to susceptible strains of many bacteria (e.g. Gram-positive and Gram-negative pathogens, including infections due to Acinetobacter spp.). Minocycline shows antibacterial activity against A. baumannii clinical isolates worldwide, and exhibits synergistic bactericidal activity against multidrug-resistant (MDR) and extensively drug-resistant (XDR) A. baumannii isolates when combined with other antibacterial agents. In retrospective studies, IV minocycline provided high rates of clinical success or improvement, and was generally well tolerated among patients with MDR or carbapenem-resistant A. baumannii infections. What is the rationale for reintroducing the IV formulation of minocycline? Minocycline (Minocin Ò) is a second-generation tetracycline that has been available since the 1960s [1, 2]. An older intravenous (IV) formulation of minocycline was voluntarily withdrawn from the US market in 2005 due to declining use [2], and was reintroduced in 2009 to address the increase in MDR infections due to susceptible strains of Gram-positive and-negative pathogens, including infections due to Acinetobacter spp. [2, 3]. A new IV formulation of minocycline was approved by the US FDA in 2015 [4]. Trends in Acinetobacter baumannii resistance among clinical isolates from US patients with respiratory and blood stream infections have shown that, after the withdrawal of IV minocycline, the rate of minocycline resistance decreased from 56.5% (2003-2005) to 30.5% (2009-2012), while resistance to other antibacterial agents (such as carbapenems and colistin) increased more than twofold [5]. Among A. baumannii isolates collected globally from integumentary sources in 2010-2014, the rate of minocycline resistance (6.6%) was lower than that of any other antibacterial agent tested (30.9-50.3%), and showed no significant change over the course of this time period [6]. These findings suggest a potential role for IV minocycline in treating patients with infections caused by A. baumannii and other susceptible Gram-positive and-negative bacteria. Why is it important to find antibacterials to treat A. baumannii? Acinetobacter spp. have recently emerged as a major cause of morbidity and mortality due to healthcare-associated infections, and are often multidrug-resistant (MDR) Adis evaluation of IV minocycline in susceptible infections Provides high rates of clinical success or improvement in patients with MDR or carbapenem-resistant Acinetobacter baumannii infections Demonstrates antibacterial activity against A. baumannii clinical isolates (including MDR and XDR strains) Exhibits synergistic bactericidal activity against A. baumannii isolates when combined with other antibacterials Generally well tolerated When used in combination with colistin, reduces the risk of colistinassociated nephrotoxicity relative to colistin alone IV intravenous, MDR multidrug resistant, XDR extensively drugresistant