In vitro activity of minocycline alone or in combination in multidrug-resistant Acinetobacter baumannii isolates

Abstract

Minocycline (MIN) usually shows good activity against Acinetobacter baumannii strains. The reintroduction to the market of intravenous MIN provides an additional agent to the limited options for the treatment of A. baumannii infections. The activity of MIN as a single agent and in combination with rifampicin (RIF), colistin (COL) or imipenem (IMI) was evaluated by means of killing curves and 24 h-time-kill curves in five A. baumannii isolates which were selected on the basis of different antimicrobial resistance profiles. MIN showed bacteriostatic activity in three isolates (26 or 166 MIC) and bactericidal activity in the other isolates (646 MIC). In isolates harbouring the tetB gene, the associations studied were always indifferent. However, in isolates not harbouring tetB, the use of MIN in combination showed a rapid synergistic effect (at 4 h) in four out of nine combinations (two with RIF and one each with IMI and COL). At 24 h, this effect was observed in six out of nine combinations (two in each association). MIN in combination with RIF, IMI and COL showed bactericidal synergy in most of the isolates which did not harbour the tetB gene, but the combinations were not synergistic in tetB-positive isolates.

Biology of Acinetobacter baumannii: Pathogenesis, Antibiotic Resistance Mechanisms, and Prospective Treatment Options

“…The TetB efflux pump is the main determinants of minocycline resistance (Vilacoba et al, 2013). Minocycline therapy combined with colistin is effective for treating minocycline-resistant A. baumannii infections (Yang et al, 2016), and minocycline therapy combined with rifampicin, colistin, or imipenem has a synergistic effect in most of isolates without the tetB gene, but combined therapies are not synergistic in isolates with the tetB gene (Rodriguez et al, 2015). …”

The Role of Minocycline in the Treatment of Nosocomial Infections Caused by Multidrug, Extensively Drug and Pandrug Resistant Acinetobacter baumannii: A Systematic Review of Clinical Evidence

“…Whether the administration of combinations occurred in more severe underlying infections or sicker patients and therefore resulted in lower success rates, or indeed, whether minocycline is more effective as a monotherapy, cannot be answered from this data. Many microbiological studies have reported the synergistic effects of minocycline when combined with other agents like rifampicin, imipenem, cefoperazone/sulbactam or colistin in in vitro experiments [42,43,44,45]. Similarly, in animal studies, combination regimens with rifampicin, amikacin or polymyxin B have also demonstrated promising results against experimental A. baumannii infections [46,47].…”

In Vitro Assessment of Combined Polymyxin B and Minocycline Therapy against Klebsiella pneumoniae Carbapenemase (KPC)-Producing K. pneumoniae

“…Previous studies have evaluated polymyxin (polymyxin B or colistin) in combination with minocycline against A. baumannii in both in vitro and in vivo models of infection with favorable results (17)(18)(19). Bowers et al (20) determined that subinhibitory concentrations of polymyxin B (0.5 mg/liter) could increase intracellular minocycline concentrations (2 and 8 mg/liter) and enhance minocycline's activity in static time-kill experiments against three clinical isolates and one laboratory isolate (20) with polymyxin B MICs of Ն2 mg/liter and minocycline MICs ranging between 0.25 and 16 mg/liter.…”

“…Minocycline inhibits bacterial protein synthesis and has favorable tissue penetrability due to its lipophilicity (16). Minocycline combined with colistin is synergistic against multidrugresistant (MDR) A. baumannii (17)(18)(19) based on the hypothesis that polymyxin disrupts outer membrane integrity to raise intracellular concentrations of minocycline in Gramnegative bacteria (20,21). The objective of this study was to evaluate the rate and extent of killing activity of polymyxin B and minocycline alone and in combination against KPC-2-producing K. pneumoniae isolates using static in vitro time-kill studies.…”